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  • 1.
    Adebahr, Roberth
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Anova, Karolinska University Hospital, Stockholm, Sweden.
    Zamore Söderström, Elin
    Arver, Stefan
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Healthcare Services, Stockholm County Council, Stockholm, Sweden.
    Görts Öberg, Katarina
    Reaching Men and Women at Risk of Committing Sexual Offences: Findings From the National Swedish Telephone Helpline PrevenTell2021In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 18, no 9, p. 1571-1581Article in journal (Refereed)
    Abstract [en]

    Background: In 2012 the Swedish Helpline project PrevenTell, targeting men and women with self-identified out-of-control and paraphilic sexual behavior, was launched by ANOVA, Karolinska University Hospital. The overall purpose was to reach the target group and via a telephone-contact encourage further on-site assessment and treatment.

    Aim: To describe men and women contacting PrevenTell during the first 7 years by delineate sexuality-related risk-factors for sexual violence, gender differences, and age-and gender-preferences when reporting a pedophilic interest.

    Method: A 52-item semi-structured telephone interview was conducted by experts in sexual medicine with individuals who contacted the helpline. The interview covered sociodemographic characteristics, problematic sexual behavior(s), and mental health and based on the information reported, interventions included recommending an appointment at ANOVA, supporting other appropriate healthcare, or motivation of individuals still ambivalent to treatment.

    Results: Data collection took place between March 2012 and October 2019. A total of 1573 respondents in the main target group (1454 men and 119 women) gave informed consent for participation. Compulsive sexual behavior was reported by 69% of respondents and 56% described at least one paraphilic interest. The prevalence of concomitant compulsive sexual behavior and a paraphilic interest was high, varying between 65% and 83%. Significant gender differences were found in socioeconomic and mental health variables, in which women showed fewer positive and stable life factors compared to men. A sexual preference for minors was reported by 24% of respondents. In this group, 63% reported use of child sexual exploitation material and 15% committed child sexual abuse. Respondents were offered anonymity, however 55% disclosed their identity and were enrolled for further assessment and treatment at ANOVA.

    Clinical Implications: The result of this study is of substantial relevance when developing secondary preventive initiatives targeting sexual violence in the community.

    Strengths and Limitations: This is the first study to present data from a national helpline targeting both men and women with a wide range of self-identified problematic sexual behaviors. Limitations include the lack of diagnostic confirmation on-site, hence, presented data provides only an indication of clinical conditions. Furthermore, the main objective of the interview was to motivate participants to seek further treatment, sometimes necessary to prioritize this over adherence to the semi-structured questionnaire, explaining the relatively high absence rate in some variables.

    Conclusion: Men and women at risk of committing sexual crimes can be reached through a national helpline service and motivated to undergo further assessment and treatment.

  • 2.
    Andersson, Peter
    et al.
    Department of Clinical Neuroscience/Psychology, Karolinska Institute, Stockholm, Sweden; Center for Clinical Research Dalarna, Uppsala University, Falun, Sweden.
    Jamshidi, Esmail
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Ekman, Carl-Johan
    Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden; Stockholm Health Care Services, Karolinska University Hospital, Region Stockholm, Sweden.
    Tedroff, Kristina
    Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital.
    Björkander, Jonnie
    Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Sjögren, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Lundberg, Johan
    Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden; Stockholm Health Care Services, Karolinska University Hospital, Region Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden; Stockholm Health Care Services, Karolinska University Hospital, Region Stockholm, Sweden.
    Boström, Adrian Desai E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden; Stockholm Health Care Services, Karolinska University Hospital, Region Stockholm, Sweden; Department of Women's and Children's Health/Neuropediatrics, Karolinska Institute, Stockholm, Sweden.
    Anorexia nervosa with comorbid severe depression: a systematic scoping review of brain stimulation treatments2023In: Journal of ECT, ISSN 1095-0680, E-ISSN 1533-4112, Vol. 39, no 4, p. 227-234Article in journal (Refereed)
    Abstract [en]

    Major depressive disorder (MDD) is highly prevalent in individuals with anorexia nervosa (AN) and is a predictor of greater clinical severity. However, there is a limited amount of evidence supporting the use of psychotropic medications for its management. A systematic scoping review was conducted to assess the current literature on brain stimulation treatments for AN with comorbid MDD, with a specific focus on MDD treatment response and weight restoration. This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the PubMed, PsycInfo, and MEDLINE databases were searched until July 2022 using specific key words related to AN and brain stimulation treatments. A total of 373 citations were identified, and 49 treatment studies that met the inclusion criteria were included in the review. The initial evidence suggests that electroconvulsive therapy, repetitive transcranial magnetic stimulation, and deep-brain stimulation may be effective in managing comorbid MDD in AN. Emerging evidence suggests that transcranial direct current stimulation may have a positive effect on body mass index in individuals with severe to extreme AN. However, there is a need for the development of better measurement techniques for assessing the severity of depression in the context of AN. Controlled trials that are adequately designed to account for these limitations are highly warranted for deep-brain stimulation, electroconvulsive therapy, and repetitive transcranial magnetic stimulation and hold promise for providing clinically meaningful results.

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  • 3.
    Andersson, Peter
    et al.
    Department of Clinical Neuroscience/Psychology, Karolinska Institute, Stockholm, Sweden; Centre for Clinical Research Dalarna, Uppsala University, Falun, Sweden.
    Jamshidi, Esmail
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Ekman, Carl-Johan
    Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden.
    Tedroff, Kristina
    Department of Women's and Children's Health/Neuropediatrics, Karolinska Institutet, Stockholm, Sweden.
    Björkander, Jonnie
    Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Sjögren, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Lundberg, Johan
    Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden.
    Boström, Adrian Desai E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health/Neuropediatrics, Karolinska Institutet, Stockholm, Sweden.
    Mapping length of inpatient treatment duration and year-wise relapse rates in eating disordered populations in a well-defined Western-European healthcare region across 1998–20202023In: International Journal of Methods in Psychiatric Research, ISSN 1049-8931, E-ISSN 1557-0657, Vol. 32, no 4, article id e1960Article in journal (Refereed)
    Abstract [en]

    Objectives: Updated international guideline recommendations for AN inpatient care rely on expert opinions/observational evidence and promote extended inpatient stays, warranting investigation using higher-level ecological evidence.

    Methods: The study was conducted according to Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Data encompassing 13,885 ED inpatients (5336 adolescents and 8549 adults) was retrieved from Swedish public health registries. Variables analyzed included (1) ED inpatient care opportunities, (2) unique number of ED inpatients and (3) mean length of ED-related inpatient stays in age groups 15–19 and 20–88+, across 1998–2020.

    Results: Mean length of inpatient stays was inversely correlated to relapse to ED-related inpatient care within the same year (p < 0.001, R-squaredadj = 0.5216 and p < 0.00001, R-squaredadj = 0.5090, in the 15–19 and 20–88+ age groups, respectively), independent of number of ED inpatients treated within a year in both age groups. Extending mean adolescent inpatient duration from 35 to 45 days was associated with a ∼30% reduction in the year-wise relapse rate.

    Conclusions: Mean length of ED-related inpatient treatment stays was associated with reduced relapses to inpatient care within the same year, which could be interpreted as support for recommendations to include a stabilization phase in inpatient ED treatment.

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  • 4.
    Andersson, Peter
    et al.
    Department of Clinical Neuroscience/Psychology, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Dalarna, Uppsala University, Uppsala, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden.
    Jarbin, Håkan
    Section of Child and Adolescent Psychiatry, Department of Clinical Sciences, Lund University, Lund, Sweden; Child and Adolescent Psychiatry, Region Halland, Halmstad, Sweden.
    Lundberg, Johan
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Desai Boström, Adrian E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Association of Bipolar Disorder Diagnosis With Suicide Mortality Rates in Adolescents in Sweden2023In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 80, no 8, p. 796-802Article in journal (Refereed)
    Abstract [en]

    Importance: The association of early diagnosis and management of bipolar disorder with adolescent suicide mortality (ASM) is unknown.

    Objective: To assess regional associations between ASM and bipolar disorder diagnosis frequencies.

    Design, Setting, and Participants: This cross-sectional study investigated the association between annual regional ASM and bipolar disorder diagnosis rates in Swedish adolescents aged 15 to 19 years in January 1, 2008, through December 31, 2021. Aggregated data without exclusions reported at the regional level encompassed 585 suicide deaths, constituting 588 unique observations (ie, 21 regions, 14 years, 2 sexes).

    Exposures: Bipolar disorder diagnosis frequencies and lithium dispensation rates were designated as fixed-effects variables (interaction term in the case of males). An interaction term between psychiatric care affiliation rates and the proportion of psychiatric visits to inpatient and outpatient clinics constituted independent fixed-effects variables. Region and year comprised random intercept effect modifiers. Variables were population adjusted and corrected for heterogeneity in reporting standards.

    Main Outcomes and Measures: The main outcomes were sex-stratified, regional, and annual ASM rates in adolescents aged 15 to 19 years per 100 000 inhabitants as analyzed using generalized linear mixed-effects models.

    Results: Female adolescents were diagnosed with bipolar disorder almost 3 times more often than male adolescents (mean [SD], 149.0 [19.6] vs 55.3 [6.1] per 100 000 inhabitants, respectively). Median regional prevalence rates of bipolar disorder varied over the national median by a factor of 0.46 to 2.61 and 0.00 to 1.82 in females and males, respectively. Bipolar disorder diagnosis rates were inversely associated with male ASM (β = -0.00429; SE, 0.002; 95% CI, -0.0081 to -0.0004; P = .03) independent of lithium treatment and psychiatric care affiliation rates. This association was replicated by β-binomial models of a dichotomized quartile 4 ASM variable (odds ratio, 0.630; 95% CI, 0.457-0.869; P = .005), and both models were robust after adjusting for annual regional diagnosis rates of major depressive disorder and schizophrenia. No such association was observed in females.

    Conclusions and Relevance: In this cross-sectional study, lower suicide death rates in adolescent males was robustly associated with regional diagnosis rates of bipolar disorder at an estimated magnitude of approximately 4.7% of the mean national suicide death rate. The associations could be due to treatment efficacy, early diagnosis and management, or other factors not accounted for.

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  • 5.
    Andersson, Peter
    et al.
    Department of Clinical Neuroscience/Psychology, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research, Uppsala University, Falun, Sweden.
    Lundberg, Johan
    Stockholm Health Care Services, Region Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden.
    Jarbin, Håkan
    Child and Adolescent Psychiatry, Region Halland, Sweden; Department of Clinical Sciences Lund, Section of Child and Adolescent Psychiatry, Lund University, Lund, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden.
    Boström, Adrian Desai E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Stockholm Health Care Services, Region Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden.
    Inverse association of anti-inflammatory prescription fills and suicide-related mortality in young adults: Evidence from a nationwide study of Swedish regions, 2006–20212023In: Brain, Behavior, and Immunity - Health, E-ISSN 2666-3546, Vol. 31, article id 100665Article in journal (Refereed)
    Abstract [en]

    Background: This cross-sectional study examined nationwide real-world associations between anti-inflammatory agent fills and suicide-related death rates in 20–24-year-olds across the 21 Swedish regions during 2006–2021.

    Methods: Nationwide Swedish registers were used to compare regional year-wise suicide-related mortality (SRM) and dispensations for anti-inflammatory agents (ATC-code: M01) in 20–24-year-olds. Dispensations for paracetamol (ATC-code: N02BE01) was applied as a control variable. Associations between regional year-wise SRM and dispensation rates were analyzed by sex-stratified zero-inflated generalized linear mixed effect models (GLMM). Dispensation rates of paracetamol and inflammatory agents were designated as independent fixed effects variables, and year and region constituted random-intercept effects.

    Results: Acetic acid derivatives and related substances (M01AB) and propionic acid derivates (M01A3) accounted for ∼71% of measured dispensation fills for anti-inflammatory agents. Diclofenac fills constituted ∼98% of the former category, whereas dispensations for Ibuprofen (∼21%), Naproxen (∼62%) and Ketoprofen (∼13%) constituted the most prescribed agents in the latter category. Regional yearly dispensation rates of anti-inflammatory agents in 20–24-year-old females were inversely associated with female SRM (β = −0.095, p = 0.0393, 95% CI -0.186, −0.005) – independent of paracetamol rates, which were unassociated to SRM (p = 0.2094). Results were confirmed in validation analyses for anti-inflammatory agents (OR = 0.7232, p = 0.0354, 95% CI [OR] 0.5347, 0.9781). No association was demonstrated in males (p = 0.833).

    Conclusion: Anti-inflammatory agent dispensation rates were independently associated to lower suicide-related death rates in female 20-24-year-olds. This adds to growing evidence implicating inflammatory processes in mental disorders, warranting trials focusing on the suicide preventative potential of anti-inflammatories in young adults.

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  • 6.
    Bendix, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Wihlbäck, Anna-Carin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Ahokas, Antti
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Allopregnanolone and progesterone in estradiol treated severe postpartum affective disorder2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 107, p. 68-68Article in journal (Other academic)
  • 7.
    Bendix, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience / Centre for Psychiatry Research & Stockholm Health Care Services, Stockholm County Council, Karolinska Institutet, Stockholm, Sweden.
    Bixo, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Wihlbäck, Anna-Carin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Ahokas, Antti
    Mehiläinen Clinic, Helsinki, Finland .
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience / Centre for Psychiatry Research & Stockholm Health Care Services, Stockholm County Council, Karolinska Institutet, Stockholm, Sweden.
    Allopregnanolone and progesterone in estradiol treated severe postpartum depression and psychosis: Preliminary findings2019In: Neurology, psychiatry and brain research, ISSN 0941-9500, Vol. 34, p. 50-57Article in journal (Refereed)
    Abstract [en]

    Background: Postpartum affective disorders may be associated with dysregulation of gonadal steroids. We investigated peripheral levels of allopregnanolone and progesterone in a combined group of women with postpartum onset of severe depression and/or psychosis who, as previously reported, responded with rapid symptom remission during sublingual estradiol treatment. The aim was to assess differences in allopregnanolone and progesterone between patients and healthy controls at baseline, and hormonal changes during estradiol treatment and symptom remission in patients.

    Methods: Allopregnanolone and progesterone in serum were analyzed with radioimmunoassay before and four weeks after initiation of sublingual estradiol treatment in ten women with postpartum depression and four women with postpartum psychosis (ICD-10). Twenty-eight healthy postpartum controls were included for baseline comparison.

    Results: Allopregnanolone declined significantly during estradiol treatment while there was a trend for lower baseline allopregnanolone levels in patients compared with healthy postpartum controls. The ratio between allopregnanolone and progesterone was significantly lower in patients compared with controls and it remained unchanged after clinical recovery.

    Limitations: This study is a secondary analysis of two estradiol treatment studies based on availability of samples for the analysis of allopregnanolone. Healthy controls were assessed earlier after delivery. Data on potential confounders (somatic health, breastfeeding, other medication) were not available.

    Conclusions: These preliminary findings suggest that clinical recovery of severe postpartum depression and psychosis during estradiol treatment does not seem to depend on increasing levels of allopregnanolone. Differences in progesterone metabolism may constitute a risk factor for severe postnatal affective dysregulation.

  • 8.
    Bendix, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Uvnäs-Moberg, Kerstin
    Petersson, Maria
    Kaldo, Viktor
    Åsberg, Marie
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Insulin and glucagon in plasma and cerebrospinal fluid in suicide attempters and healthy controls2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 81, p. 1-7Article in journal (Refereed)
    Abstract [en]

    Mental disorders and related behaviors such as suicidality and violence have been associated to dysregulation of e g carbohydrate metabolism. We hypothesized that patients after suicide attempt, compared to healthy controls, would have higher insulin and lower glucagon levels in plasma and cerebrospinal fluid and that these changes would be associated to violent behavior. Twenty-eight medication-free patients (10 women, 18 men), hospitalized after suicide attempt, and 19 healthy controls (7 women, 12 men) were recruited with the aim to study risk factors for suicidal behavior. Psychological/psychiatric assessment was performed with SCID I and II or the SCID interview for healthy volunteers respectively, the Karolinska Interpersonal Violence Scale (KIVS) for assessment of lifetime violence expression behavior, the Montgomery-Asberg-Depression-Scale (MADRS) and the Comprehensive Psychological Rating Scale (CPRS) for symptomatic assessment of depression and appetite. Fasting levels of insulin and glucagon were measured in plasma (P) and cerebrospinal fluid (CSF). Suicide attempters had higher insulin- and lower glucagon-levels in plasma- and CSF compared to controls. Except for P-glucagon these associations remained significant after adjusting for age and/or BMI. Patients reported significantly more expressed interpersonal violence compared to healthy volunteers. Expressed violence was significantly positively correlated with P- and CSF-insulin and showed a significant negative correlation with P-glucagon in study participants. These findings confirm and extend prior reports that higher insulin and lower glucagon levels in plasma and cerebrospinal fluid are associated with suicidal behavior pointing towards a potential autonomic dysregulation in the control of insulin and glucagon secretion in suicidal patients. 

  • 9. Bjureberg, Johan
    et al.
    Ohlis, Anna
    Ljotsson, Brjann
    D'Onofrio, Brian M.
    Hedman-Lagerlöf, Erik
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Sahlin, Hanna
    Lichtenstein, Paul
    Cederlöf, Martin
    Hellner, Clara
    Adolescent self-harm with and without suicidality: cross-sectional and longitudinal analyses of a Swedish regional register2019In: Journal of Child Psychology and Psychiatry, ISSN 0021-9630, E-ISSN 1469-7610, Vol. 60, no 3, p. 295-304Article in journal (Refereed)
    Abstract [en]

    Background: Self-harm is common and there is a need for studies that investigate the relevance of this behavior in clinical samples to inform risk assessment and treatment. The objectives in the current studies were to compare clinical and psychosocial correlates and subsequent adverse outcomes in youth who present to child and adolescent mental health services (CAMHS) with self-harm only (SH), self-harm with suicidality (SH+SU), with those without any indication of SH or SH+SU.

    Methods: We conducted a case-control study and a longitudinal cohort study using data from a regional clinical care register, and Swedish national registers. The case-control study included all patients (5-17 years) between 2011 and 2015 (N = 25,161). SH and SH+SU cases were compared with controls (patients without SH) regarding a range of correlates. The longitudinal study included former CAMHS patients (N = 6,120) who were followed for a median time of 2.8 years after termination of CAMHS contact regarding outcomes such as clinical care consumption, social welfare recipiency, and crime conviction.

    Results: In the case-control study, both the SH and SH+SU groups received more clinical care, had lower global functioning, and higher odds of having mental disorders compared to controls. In most comparisons, the SH+SU group had more problems than the SH group. In the longitudinal study, the same pattern emerged for most outcomes; for example, the adjusted hazard ratio for recurrent care due to self-harm was 23.1 (95% confidence interval [CI], 17.0-31.4) in the SH+SU group compared to 3.9 (95% CI, 2.3-6.7) in the SH group.

    Conclusions: Adolescent patients presenting with self-harm have higher risks for adverse outcomes than patients without self-harm. Suicidality in addition to self-harm is associated with more severe outcomes, importantly recurrent episodes of care for self-harm.

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  • 10. Bostrom, Adrian E.
    et al.
    Chatzittofis, Andreas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Ciuculete, Diana-Maria
    Flanagan, John N.
    Krattinger, Regina
    Bandstein, Marcus
    Mwinyi, Jessica
    Kullak-Ublick, Gerd A.
    Oberg, Katarina Gorts
    Arver, Stefan
    Schioth, Helgi B.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling: A DNA methylation analysis of miRNA genes2020In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 15, no 1-2, p. 145-160Article in journal (Refereed)
    Abstract [en]

    Hypersexual disorder (HD) was proposed as a diagnosis in the DSM-5 and the classification ‘Compulsive Sexual Behavior Disorder’ is now presented as an impulse-control disorder in ICD-11. HD incorporates several pathophysiological mechanisms; including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. No previous study investigated HD in a methylation analysis limited to microRNA (miRNA) associated CpG-sites. The genome wide methylation pattern was measured in whole blood from 60 subjects with HD and 33 healthy volunteers using the Illumina EPIC BeadChip. 8,852 miRNA associated CpG-sites were investigated in multiple linear regression analyses of methylation M-values to a binary independent variable of disease state (HD or healthy volunteer), adjusting for optimally determined covariates. Expression levels of candidate miRNAs were investigated in the same individuals for differential expression analysis. Candidate methylation loci were further studied for an association with alcohol dependence in an independent cohort of 107 subjects. Two CpG-sites were borderline significant in HD – cg18222192 (MIR708)(p < 10E-05,pFDR = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, pFDR = 5.81E-02). MIR4456 was significantly lower expressed in HD in both univariate (p < 0.0001) and multivariate (p < 0.05) analyses. Cg01299774 methylation levels were inversely correlated with expression levels of MIR4456 (p < 0.01) and were also differentially methylated in alcohol dependence (p = 0.026). Gene target prediction and pathway analysis revealed that MIR4456 putatively targets genes preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signalling pathway. In summary, our study implicates a potential contribution of MIR4456 in the pathophysiology of HD by putatively influencing oxytocin signalling.

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  • 11.
    Boström, Adrian Desai E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Women's and Children's Health/Neuropediatrics, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Peter
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Centre for Clinical Research Dalarna, Uppsala University, Falun, Sweden.
    Chatzittofis, Andreas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Medical School, University of Cyprus, Nicosia, Cyprus.
    Savard, Josephine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Rask-Andersen, Mathias
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Öberg, Katarina G.
    Anova, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Arver, Stefan
    Anova, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    HPA-axis dysregulation is not associated with accelerated epigenetic aging in patients with hypersexual disorder2022In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 141, article id 105765Article in journal (Refereed)
    Abstract [en]

    Background: Hypersexual disorder (HD) - a nonparaphilic sexual desire disorder with impulsivity component - was evaluated for inclusion as a diagnosis in the DSM-5 and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the ICD-11. Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity is believed to affect cellular senescence and has been implicated in HD. No previous study investigated HD or HPA-axis dysregulation in relation to measures of epigenetic age (EA) acceleration.

    Methods: This study reports on a case-control study set-up from a well-characterized cohort, contrasting EA predictors in relation to 60 HD patients and 33 healthy volunteers (HV) and 19 mixed HD/HV exhibiting dexamethasone suppression test (DST) non-suppression to 73 mixed HD/HV DST controls. The genome-wide methylation pattern was measured in whole blood from 94 subjects using the Illumina Infinium Methylation EPIC BeadChip and preprocessed according to specialized protocols suitable for epigenetic age estimation. The online DNAm Age Calculator (https://dnamage.genetics.ucla.edu/) was implemented to retrieve various EA predictors, which were compared between the in-silico generated subgroups.

    Results: Quality control analyses indicated strong correlations between the EA measure DNA methylation GrimAge (DNAm GrimAge – the EA clock most reliably associated with mortality risk) and chronological age in all sub-groups. The study was adequately powered to detect differences of 2.5 and 3.0 years in DNAm GrimAge minus age in relation to both HD and HPA-axis dysregulation, respectively. Baseline DNAm GrimAge exceeded chronological age by 2.8 years on average across all samples. No EA acceleration marker was associated with HD or DST suppression status (p > 0.05).

    Conclusion: EA acceleration markers shown to be strongly predictive of physiological dysregulation and mortality-risk, are not related to HD or DST non-suppression status (measured after 0.5 mg dexamethasone). The independency of HPA-axis dysregulation to EA acceleration does not support the biological relevance of this dosage-regimen when applied to patients with HD. These findings do not support the notion of accelerated cellular senescence in HD. Studies stratifying DST non-suppressors according to established dosage-regimens in somatic settings are needed to fully elucidate the putative contribution of HPA-axis dysregulation to EA.

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  • 12.
    Boström, Adrian Desai E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden.
    Andersson, Peter
    Department of Clinical Neuroscience/Psychology, Karolinska Institute, Stockholm, Sweden; Centre for Clinical Research Dalarna, Uppsala University, Falun, Sweden.
    Jamshidi, Esmail
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Wilczek, Alexander
    Department of Clinical Sciences, Karolinska Institutet at Danderyd Hospital, Stockholm, Sweden.
    Nilsonne, Åsa
    Department of Clinical Sciences, Karolinska Institutet at Danderyd Hospital, Stockholm, Sweden.
    Rask-Andersen, Mathias
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Åsberg, Marie
    Department of Clinical Sciences, Karolinska Institutet at Danderyd Hospital, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden.
    Accelerated epigenetic aging in women with emotionally unstable personality disorder and a history of suicide attempts2023In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, no 1, article id 66Article in journal (Refereed)
    Abstract [en]

    Emotional unstable personality disorder (EUPD; previously borderline personality disorder, BPD) is associated with excess natural-cause mortality, comorbid medical conditions, poor health habits and stress related epigenomic alterations. Previous studies demonstrated that GrimAge – a state-of-the-art epigenetic age (EA) estimator – strongly predicts mortality risk and physiological dysregulation. Herein, we utilize the GrimAge algorithm to investigate whether women with EUPD and a history of recent suicide attempts exhibit EA acceleration (EAA) in comparison to healthy controls. Genome-wide methylation patterns were measured using the Illumina Infinum Methylation Epic BeadChip in whole blood from 97 EUPD patients and 32 healthy controls. The control group was significantly older (p < 0.0001) and reported lesser exposure to violent behavior in both youth and adulthood (p < 0.0001). Groups were otherwise comparable regarding gender, BMI, or tobacco usage (p > 0.05). EA estimator DNAmGrimAge exceeded chronological age by 8.8 and 2.3 years in the EUPD and control group, respectively. Similarly, EAA marker AgeAccelGrim was substantially higher in EUPD subjects when compared to controls, in both univariate and multivariate analyzes (p < 0.00001). Tobacco usage conferred substantial within-group effects on the EA-chronological age difference, i.e., 10.74 years (SD = 4.19) compared to 6.00 years (SD = 3.10) in the non-user EUPD group (p < 0.00001). Notably, past alcohol and substance abuse, use of psychotropic medications, global assessment of functioning, self-reported exposure to violent behavior in youth and adulthood, later completed suicide (N = 8) and age at first suicide attempt did not predict EAA in the EUPD group (p > 0.05). These results underscore the importance of addressing medical health conditions along with low-cost preventative interventions aimed at improving somatic health outcomes in EUPD, such as efforts to support cessation of tobacco use. The independency of GrimAge to other EA algorithms in this group of severely impaired EUPD patients, suggest it may have unique characteristics to evaluate risk of adverse health outcomes in context of psychiatric disorders.

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  • 13.
    Boström, Adrian Desai E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Women's and Children's Health/Neuropediatrics, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, SE-171 76, Stockholm, Sweden. adrian.desai.bostrom@ki.se.
    Andersson, Peter
    Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research, Uppsala University, Dalarna, Falun, Sweden.
    Rask-Andersen, Mathias
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Jarbin, Håkan
    Department of Clinical Sciences Lund, Section of Child and Adolescent Psychiatry, Lund University, Lund, Sweden; Child and Adolescent Psychiatry, Region Halland, Halland, Sweden.
    Lundberg, Johan
    Stockholm Health Care Services, Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
    Regional clozapine, ECT and lithium usage inversely associated with excess suicide rates in male adolescents2023In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 1281Article in journal (Refereed)
    Abstract [en]

    Advanced psychiatric treatments remain uncertain in preventing suicide among adolescents. Across the 21 Swedish regions, using nationwide registers between 2016-2020, we found negative correlation between adolescent excess suicide mortality (AESM) and regional frequencies of clozapine, ECT, and lithium (CEL) usage among adolescents (β = -0.613, p = 0.0003, 95% CI: -0.338, -0.889) and males (β = -0.404, p = 0.009, 95% CI: -0.130, -0.678). No correlation was found among females (p = 0.197). Highest CEL usage among male adolescents was seen in regions with lowest quartile (Q1) AESM (W = 74, p = 0.012). Regional CEL treatment frequency in 15-19-year-olds was related to lower AESM in males, reflecting potential treatment efficacy, treatment compliance or better-quality mental health care. Suicide prevention may benefit from early recognition and CEL treatment for severe mental illness in male adolescents. The results indicate association but further research, using independent samples and both prospective and observational methodologies, is needed to confirm causality.

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  • 14.
    Boström, Adrian Desai E.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health/Neuropediatrics, Karolinska Institutet, Stockholm, Sweden.
    Jamshidi, Esmail
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Manu, Diana-Maria
    Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden.
    Kular, Lara
    Department of Clinical Neruoscience/Neuro, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Schiöth, Helgi B.
    Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden.
    Åsberg, Marie
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Epigenetic changes in the CYP2D6 gene are related to severity of suicide attempt: A cross-sectional study of suicide attempters2023In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 160, p. 217-224Article in journal (Refereed)
    Abstract [en]

    Background: The ability to accurately estimate risk of suicide deaths on an individual level remains elusive.

    Methods: This study reports on a case-control study set-up from a well-characterized cohort of 88 predominantly female suicide attempters (SA), stratified into low- (n = 57) and high-risk groups (n = 31) based on reports of later death by suicide, as well as degree of intent-to-die and lethality of SA method. We perform an unbiased analysis of 12,930 whole-blood derived CpG-sites (Illumina Infinium EPIC BeadChip) previously demonstrated to be more conciliable with brain-derived variations. The candidate site was validated by pyrosequencing. External replication was performed in (1) relation to age at index suicide attempt in 97 women with emotionally unstable personality disorder (whole-blood) and (2) death by suicide in a mixed group of 183 prefrontal-cortex (PFC) derived samples who died by suicide or from non-psychiatric etiologies.

    Results: CYP2D6-coupled CpG-site cg07016288 was hypomethylated in severe suicidal behavior (p < 10E-06). Results were validated by pyrosequencing (p < 0.01). Replication analyses demonstrate hypomethylation of cg07016288 in relation to age at index SA in females (p < 0.05) and hypermethylation in PFC of male suicide completers (p < 0.05). Limitations: Genotyping of CYP2D6 was not performed and CpG-site associations to gene expression were not explored.

    Conclusions: CYP2D6-coupled epigenetic markers are hypomethylated in females in dependency of features known to confer increased risk of suicide deaths and hypermethylated in PFC of male suicide completers. Further elucidating the role of CYP2D6 in severe suicidality or suicide deaths hold promise to deduce clinically meaningful results.

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  • 15. Budhiraja, Meenal
    et al.
    Pereira, Joana B.
    Lindner, Philip
    Westman, Eric
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institute, Psychiatry Building R5:00, Karolinska, University Hospital, Stockholm 171 76, Sweden.
    Savic, Ivanka
    Tiihonen, Jari
    Hodgins, Sheilagh
    Cortical structure abnormalities in females with conduct disorder prior to age 152019In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 289, p. 37-44Article in journal (Refereed)
    Abstract [en]

    Among females, conduct disorder (CD) before age 15 is associated with multiple adverse outcomes in adulthood. The few existing structural neuroimaging studies of females with CD report abnormalities of gray matter volumes. The present study compared cortical thickness and surface area of young women with childhood/adolescent CD and healthy women to determine whether cortical abnormalities were present in adulthood and whether they were related to prior CD. Structural brain images from 31 women with CD and 25 healthy women were analyzed using FreeSurfer. Group differences between cortical thickness and surface area were assessed using cluster-wise corrections with Monte Carlo simulations. Women with prior CD, relative to healthy women, showed: (1) reduced cortical thickness in left fusiform gyrus extending up to entorhinal cortex and lingual gyrus; (2) reduced surface area in right superior parietal cortex; (3) increased surface area in left superior temporal gyrus, and right precentral gyrus. These differences remained significant after adjusting for past comorbid disorders, current symptoms of anxiety and depression, current substance use as well as maltreatment. The study suggests that among females, CD prior to age 15 is associated with cortical structure abnormalities in brain regions involved in emotion processing and social interaction.

  • 16.
    Chatzittofis, A.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Boström, A.
    Öberg, K.
    Flanagan, J.
    Schioth, H.
    Arver, S.
    Jokinen, J.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Testosterone, luteinizing hormone levels and methylation status in men with hypersexual disorders2019In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, p. S135-S135Article in journal (Other academic)
  • 17.
    Chatzittofis, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Medical School, University of Cyprus, Nicosia, Cyprus.
    Boström, Adrian Desai E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Neuropaediatric Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Ciuculete, Diana M.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Öberg, Katarina Görts
    Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
    Arver, Stefan
    Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
    Schiöth, Helgi B.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden; Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russian Federation.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    HPA axis dysregulation is associated with differential methylation of CpG-sites in related genes2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 20134Article in journal (Refereed)
    Abstract [en]

    DNA methylation shifts in Hypothalamic–pituitary–adrenal (HPA) axis related genes is reported in psychiatric disorders including hypersexual disorder. This study, comprising 20 dexamethasone suppression test (DST) non-suppressors and 73 controls, examined the association between the HPA axis dysregulation, shifts in DNA methylation of HPA axis related genes and importantly, gene expression. Individuals with cortisol level ≥ 138 nmol/l, after the low dose (0.5 mg) dexamethasone suppression test (DST) were classified as non-suppressors. Genome-wide methylation pattern, measured in whole blood using the EPIC BeadChip, investigated CpG sites located within 2000 bp of the transcriptional start site of key HPA axis genes, i.e.: CRH, CRHBP, CRHR-1, CRHR-2, FKBP5 and NR3C1. Regression models including DNA methylation M-values and the binary outcome (DST non-suppression status) were performed. Gene transcripts with an abundance of differentially methylated CpG sites were identified with binomial tests. Pearson correlations and robust linear regressions were performed between CpG methylation and gene expression in two independent cohorts. Six of 76 CpG sites were significantly hypermethylated in DST non-suppressors (nominal P < 0.05), associated with genes CRH, CRHR1, CRHR2, FKBP5 and NR3C1. NR3C1 transcript AJ877169 showed statistically significant abundance of probes differentially methylated by DST non-suppression status and correlated with DST cortisol levels. Further, methylation levels of cg07733851 and cg27122725 were positively correlated with gene expression levels of the NR3C1 gene. Methylation levels of cg08636224 (FKBP5) correlated with baseline cortisol and gene expression. Our findings revealed that DNA methylation shifts are involved in the altered mechanism of the HPA axis suggesting that new epigenetic targets should be considered behind psychiatric disorders.

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  • 18.
    Chatzittofis, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Medical School, University of Cyprus, Palaios Dromos Lefkosias Lemesou No.215/6 2029 Aglantzia, Nicosia, Cyprus.
    Boström, Adrian Desai E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Neuropaediatric Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Savard, Josephine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Öberg, Katarina Görts
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Arver, Stefan
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Neurochemical and Hormonal Contributors to Compulsive Sexual Behavior Disorder2022In: Current Addiction Reports, E-ISSN 2196-2952, Vol. 9, p. 23-31Article, review/survey (Refereed)
    Abstract [en]

    Purpose of Review: Compulsive sexual behavior disorder has been recently included in the 11th revision of the International Classification of Diseases (ICD-11), and the possible contribution of neurochemical and hormonal factors have been reported. However, relatively little is known concerning the neurobiology underlying this disorder. The aim of this article is to review and discuss published findings in the area.

    Recent Findings: Evidence suggests that the neuroendocrine systems are involved in the pathophysiology of compulsive sexual behavior. The hypothalamus-pituitary adrenal axis, the hypothalamus-pituitary–gonadal axis, and the oxytocinergic system have been implicated.

    Summary: Further studies are needed to elucidate the exact involvement of neuroendocrine and hormonal systems in compulsive sexual behavior disorder. Prospective longitudinal studies are particularly needed, especially those considering co-occurring psychiatric disorders and obtaining hormonal assessments in experimental circumstances with appropriate control groups.

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  • 19.
    Chatzittofis, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Medical School, University of Cyprus, Nicosia, Cyprus.
    Boström, Adrian E.
    Öberg, Katarina Görts
    Flanagan, John N.
    Schiöth, Helgi B.
    Arver, Stefan
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska nstitutet,Karolinska University Hospital, Stockholm, Sweden.
    Normal Testosterone but Higher Luteinizing Hormone Plasma Levels in Men With Hypersexual Disorder2020In: Sexual Medicine, E-ISSN 2050-1161, Vol. 8, no 2, p. 243-250Article in journal (Refereed)
    Abstract [en]

    Introduction: Hypersexual disorder as suggested to be included in the Diagnostic and Statistical Manual of Mental Disorders-5 integrates aspects of sexual desire deregulation, impulsivity, and compulsivity. However, it is unknown how it affects gonadal activity and the function of the hypothalamus-pituitary-gonadal (HPG) axis.

    Aim: The aim of this study was to investigate testosterone and luteinizing hormone (LH) levels in hypersexual men compared with healthy controls. Furthermore, we investigated associations between epigenetic markers and hormone levels.

    Methods: Basal morning plasma levels of testosterone, LH, and sex hormone-binding globulin (SHBG) were assessed in 67 hypersexual men (mean age: 39.2 years) compared with 39 age-matched healthy controls (mean age: 37.5 years). The Sexual Compulsivity Scale and the Hypersexual Disorder: Current Assessment Scale were used for assessing hypersexual behavior, the Montgomery-Asberg Depression Scale-self rating was used for depression severity, and the Childhood Trauma Questionnaire (CTQ) was used for assessing history of childhood adversity. The genome-wide methylation pattern of more than 850 K CpG sites was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip. CpG sites located within 2,000 bp of the transcriptional start site of hypothalamus pituitary adrenal (HPA) and HPG axis-coupled genes were included.

    Main Outcome Measures: Testosterone and LH plasma levels in association with clinical rating and a secondary outcome was the epigenetic profile of HPA and HPG axis-coupled CpG sites with testosterone and LH levels.

    Results: LH plasma levels were significantly higher in patients with hypersexual disorder than in healthy volunteers. No significant differences in plasma testosterone, follicle stimulating hormone, prolactin, and SHBG levels were found between the groups. There were no significant associations between DNA methylation of HPA and HPG axis-coupled genes and plasma testosterone or LH levels after multiple testing corrections.

    Conclusions: Subtle dysregulation of the HPG axis, with increased LH plasma levels but no difference in testosterone levels may be present in hypersexual men.

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  • 20. Chen, Qi
    et al.
    Zhang-James, Yanli
    Barnett, Eric J.
    Lichtenstein, Paul
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    D'Onofrio, Brian M.
    Faraone, Stephen, V
    Larsson, Henrik
    Fazel, Seena
    Predicting suicide attempt or suicide death following a visit to psychiatric specialty care: A machine learning study using Swedish national registry data2020In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 17, no 11, article id e1003416Article in journal (Refereed)
    Abstract [en]

    Background: Suicide is a major public health concern globally. Accurately predicting suicidal behavior remains challenging. This study aimed to use machine learning approaches to examine the potential of the Swedish national registry data for prediction of suicidal behavior.

    Methods and findings: The study sample consisted of 541,300 inpatient and outpatient visits by 126,205 Sweden-born patients (54% female and 46% male) aged 18 to 39 (mean age at the visit: 27.3) years to psychiatric specialty care in Sweden between January 1, 2011 and December 31, 2012. The most common psychiatric diagnoses at the visit were anxiety disorders (20.0%), major depressive disorder (16.9%), and substance use disorders (13.6%). A total of 425 candidate predictors covering demographic characteristics, socioeconomic status (SES), electronic medical records, criminality, as well as family history of disease and crime were extracted from the Swedish registry data. The sample was randomly split into an 80% training set containing 433,024 visits and a 20% test set containing 108,276 visits. Models were trained separately for suicide attempt/death within 90 and 30 days following a visit using multiple machine learning algorithms. Model discrimination and calibration were both evaluated. Among all eligible visits, 3.5% (18,682) were followed by a suicide attempt/death within 90 days and 1.7% (9,099) within 30 days. The final models were based on ensemble learning that combined predictions from elastic net penalized logistic regression, random forest, gradient boosting, and a neural network. The area under the receiver operating characteristic (ROC) curves (AUCs) on the test set were 0.88 (95% confidence interval [CI] = 0.87-0.89) and 0.89 (95% CI = 0.88-0.90) for the outcome within 90 days and 30 days, respectively, both being significantly better than chance (i.e., AUC = 0.50) (p < 0.01). Sensitivity, specificity, and predictive values were reported at different risk thresholds. A limitation of our study is that our models have not yet been externally validated, and thus, the generalizability of the models to other populations remains unknown.

    Conclusions: By combining the ensemble method of multiple machine learning algorithms and high-quality data solely from the Swedish registers, we developed prognostic models to predict short-term suicide attempt/death with good discrimination and calibration. Whether novel predictors can improve predictive performance requires further investigation. Author summary Why was this study done? Suicidal behavior is overrepresented in people with mental illness and contributes to the substantial public health burden of psychiatric conditions. Accurately predicting suicidal behavior has long been challenging. The potential of applying machine learning to linked national datasets to predict suicidal behavior remains unknown. What did the researchers do and find? We identified a sample of 541,300 inpatient and outpatient visits to psychiatric specialty care in Sweden during 2011 and 2012. The sample was then divided into a training dataset and a test dataset. We first trained prediction models separately for suicide attempt/death within 90 days and 30 days following a visit to psychiatric specialty care, using 4 different machine learning algorithms. We then used an ensemble method to combine the performance of the trained models with the intention to achieve an overall performance superior than each individual model. The final model based on the ensemble method achieved the best predictive performance. This model was applied to test dataset and showed good model discrimination and calibration for both the 90-day and 30-day outcomes. What do these findings mean? Our findings suggest that combining machine learning with registry data has the potential to accurately predict short-term suicidal behavior. An approach combining 4 machine learning methods showed an overall predictive performance slightly better than each individual model.

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  • 21. Ehlert, Ulrike
    et al.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Stockholm Cty Council, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden; Stockholm Cty Council, Stockholm Hlth Care Serv, Stockholm, Sweden; Karolinska Inst, Stockholm, Sweden.
    Sexual steroids during the course of female life2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 107, p. 67-67Article in journal (Other academic)
  • 22.
    Flanagan, John
    et al.
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Chatzittofis, Andreas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Medical School, University of Cyprus, Nicosia, Cyprus.
    Boström, Adrian Desai E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Neuropaediatric Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Hallberg, Jonas
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Öberg, Katarina Görts
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Arver, Stefan
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    High plasma oxytocin levels in men with hypersexual disorder2022In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 107, no 5, p. e1816-e1822Article in journal (Refereed)
    Abstract [en]

    Context: Hypersexual disorder (HD) involves excessive, persistent sexual behaviors related to various mood states and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the 11th revision of the International Classification of Diseases. Although the neurobiology behind the disorder is not clear, some studies suggest dysregulated hypothalamic-pituitary-adrenal axis. Oxytocin acts as counterregulatory neuroendocrine hormone to cortisol and is also involved in sexual behavior.

    Objective: We hypothesized that oxytocin may play a role in the pathophysiology of HD with compensatory actions to cortisol.

    Design: Longitudinal.

    Setting: ANOVA clinic (Karolinska University Hospital).

    Patients or other participants: 64 males with HD and 38 age-matched healthy volunteers.

    Main Outcome Measures: Plasma oxytocin levels, measured with radioimmunoassay; Hypersexual Disorder Screening Inventory; and Hypersexual Disorder: Current Assessment Scale for assessing hypersexual symptoms.

    Interventions: A patient subgroup (n=30) completed the manual-based group-administered cognitive-behavioral therapy (CBT) program for HD, and posttreatment oxytocin levels were measured.

    Results: Hypersexual men (n=64) exhibited significantly higher oxytocin plasma levels (mean±SD: 31.0±9.9 pM) compared with healthy volunteers (16.9±3.9 pM; P<0.001). There were significant positive correlations between oxytocin levels and the rating scales measuring hypersexual behavior. Patients who completed CBT treatment (n=30) had a significant reduction of oxytocin plasma levels from pretreatment (30.5±10.1 pM) to posttreatment (20.2±8.0 pM; P<0.001).

    Conclusions: The results suggest that the hyperactive oxytocinergic system in hypersexual men may be a compensatory mechanism to attenuate hyperactive stress.

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  • 23.
    Geale, Kirk
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Quantify Research, Stockholm, Sweden.
    Henriksson, Martin
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Association of Skin Psoriasis and Somatic Comorbidity With the Development of Psychiatric Illness in a Nationwide Swedish Study2020In: JAMA dermatology, ISSN 2168-6068, E-ISSN 2168-6084, Vol. 156, no 7, p. 795-804Article in journal (Refereed)
    Abstract [en]

    Importance: Psoriasis is a complex systemic disease with skin involvement, somatic comorbidity, and psychiatric illness (PI). Although this view of psoriasis is widely accepted, potential synergies within this triad of symptoms have not been adequately investigated.

    Objectives: To investigate the independent association of skin psoriasis and somatic comorbidity with the development of PI and to assess whether skin psoriasis and somatic comorbidity act synergistically to produce a risk of PI that is greater than the additive associations.

    Design, Setting, and Participants: Participants were enrolled between January 2005 and December 2010, in this retrospective matched case-control study using secondary (ie, administrative), population-based registry data from Swedish patients in routine clinical care. The dates of analysis were March 2017 to December 2019. Participants were patients with skin psoriasis and control participants without psoriasis matched on age, sex, and municipality, who were all free of preexisting PI.

    Exposures: Presence of skin psoriasis and somatic comorbidity (captured through the Charlson Comorbidity Index and the Elixhauser Comorbidity Index).

    Main Outcomes and Measures: Risk of PI onset (composite of depression, anxiety, and suicidality) is shown using Kaplan-Meier curves stratified by the presence of skin psoriasis and somatic comorbidity. Adjusted associations of skin psoriasis and somatic comorbidity with the development of PI were analyzed using Cox proportional hazards regression models, including interactions to assess synergistic associations. The 3 components of PI were also assessed individually.a

    Results: A total of 93 239 patients with skin psoriasis (mean [SD] age, 54 [17] years; 47 475 men [51%]) and 1 387 495 control participants (mean [SD] age, 54 [16] years; 702 332 men [51%]) were included in the study. As expected, patients with skin psoriasis were more likely to have somatic comorbidity and PI than control participants. Compared with those without skin psoriasis or somatic comorbidity, patients with psoriasis without somatic comorbidity had a 1.32 times higher risk of PI onset (hazard ratio [HR], 1.32; 95% CI, 1.27-1.36; P < .001), whereas patients with psoriasis with somatic comorbidity had a 2.56 times higher risk of PI onset (HR, 2.56; 95% CI, 2.46-2.66; P < .001). No synergistic associations of skin psoriasis and somatic comorbidity with the development of PI were found (HR, 0.93; 95% CI, 0.81-1.04; P = .21).

    Conclusions and Relevance: This study found that somatic comorbidity appeared to alter PI onset even more than skin psoriasis. The observed association of skin psoriasis and somatic comorbidity with the development of PI reinforces the need for proactive, holistic treatment of patients with psoriasis.

  • 24.
    Görts, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Savard, Josephine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Görts-Öberg, Katarina
    Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Dhejne, Cecilia
    Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Arver, Stefan
    Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Ingvar, Martin
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Abé, Christoph
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 5Quantify Research, Stockholm, Sweden.
    Structural brain differences related to compulsive sexual behavior disorder2023In: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 12, no 1, p. 278-287Article in journal (Refereed)
    Abstract [en]

    Background and aims: Compulsive sexual behavior disorder (CSBD) has been included as an impulse control disorder in the International Classification of Diseases (ICD-11). However, the neurobiological mechanisms underlying CSBD remain largely unknown, and given previous indications of addiction-like mechanisms at play, the aim of the present study was to investigate if CSBD is associated with structural brain differences in regions involved in reward processing.

    Methods: We analyzed structural MRI data of 22 male CSBD patients (mean = 38.7 years, SD = 11.7) and 20 matched healthy controls (HC; mean = 37.6 years, SD = 8.5). Main outcome measures were regional cortical thickness and surface area. We also tested for case-control differences in subcortical structures and the effects of demographic and clinical variables, such as CSBD symptom severity, on neuroimaging outcomes. Moreover, we explored case-control differences in regions outside our hypothesis including white matter.

    Results: CSBD patients had significantly lower cortical surface area in right posterior cingulate cortex than HC. We found negative correlations between right posterior cingulate area and CSBD symptoms scores. There were no group differences in subcortical volume.

    Conclusions: Our findings suggest that CSBD is associated with structural brain differences, which contributes to a better understanding of CSBD and encourages further clarifications of the neurobiological mechanisms underlying the disorder.

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  • 25. Hallberg, Jonas
    et al.
    Kaldo, Viktor
    Arver, Stefan
    Dhejne, Cecilia
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Oberg, Katarina Gorts
    A Randomized Controlled Study of Group-Administered Cognitive Behavioral Therapy for Hypersexual Disorder in Men2019In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 16, no 5, p. 733-745Article in journal (Refereed)
    Abstract [en]

    Background: Hypersexual disorder (HD) is defined as a condition in which the individual loses control over engagement in sexual behaviors, leading to distress and negative effects on key life areas. Cognitive behavioral therapy (CBT) has been proven to reduce symptoms of hypersexual behavior; however, no randomized controlled study of CBT interventions for HD has been reported previously.

    Aim: To investigate the efficacy of group-administered CBT for HD.

    Methods: Male participants (n = 137) diagnosed with HD, were randomized between 7 weeks of group-administered CBT (n = 70) and a waitlist control receiving the intervention after 8 weeks (n = 67). Measurements were administered at pre-, mid-, and posttreatment, with follow-up after 3 and 6 months.

    Outcomes: The primary outcome was the Hypersexual Disorder: Current Assessment Scale (HD:CAS), and secondary outcomes were the Sexual Compulsivity Scale (SCS) and measures of depression (Montgomery–Åsberg Depression Rating Scale (MADRS-S), psychological distress (Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), and treatment satisfaction (CSQ-8).

    Results: A significantly greater decrease in HD symptoms and sexual compulsivity, as well as significantly greater improvements in psychiatric well-being, were found for the treatment condition compared with the waitlist. These effects remained stable at 3 and 6 months after treatment.

    Clinical Implications: CBT can ameliorate HD symptoms and psychiatric distress, suggesting that the CBT program may serve as a first-line treatment in clinical settings.

    Strengths & Limitations: This is the first randomized controlled study evaluating the efficacy of a CBT program in a rather large sample of HD-specific diagnosed men. The long-term treatment effects are vague due to the low response rate on follow-up measurements, and the efficacy of this program for hypersexual women remains unknown.

    Conclusion: This study supports the efficacy of a group-administered CBT program as a treatment option for HD; however, future studies should include women, comprise dismantling analysis of the constituting interventions, and evaluate other treatment formats, for example, administration via the Internet.

  • 26. Hallberg, Jonas
    et al.
    Kaldo, Viktor
    Arver, Stefan
    Dhejne, Cecilia
    Piwowar, Marta
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm Sweden & Stockholm Healthcare Services, Stockholm County Council, Stockholm, Sweden.
    Oberg, Katarina Gorts
    Internet-Administered Cognitive Behavioral Therapy for Hypersexual Disorder, With or Without Paraphilia(s) or Paraphilic Disorder(s) in Men: A Pilot Study2020In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 17, no 10, p. 2039-2054Article in journal (Refereed)
    Abstract [en]

    Background: Hypersexual disorder (HD) is a condition in which the individual experiences loss of control over engagement in sexual behaviors, leading to negative effects on various areas of life. Paraphilias often present concomitantly with HD, and although cognitive behavioral therapy (CBT) has been proven to reduce engagement in hypersexual behavior, no studies have investigated the effects of Internet-administered CBT (ICBT) on HD, with or without paraphilia(s) or paraphilic disorder(s).

    Aim: To investigate the effects of Internet-administered CBT on HD, with or without paraphilia(s) or paraphilic disorder(s).

    Methods: Male participants (n = 36) evaluated positive according to the proposed diagnostic HD criteria, with or without paraphilia(s) or paraphilic disorder(s), received 12 weeks of ICBT. Measures were administered weekly over the treatment period, with an additional follow-up measurement 3 months after completion of treatment. An assessment interview was performed 2 weeks after treatment.

    Outcomes: The primary outcome was the Hypersexual Behavior Inventory (HBI-19), and secondary outcomes were the Hypersexual Disorder: Current Assessment Scale (HD:CAS), the Sexual Compulsivity Scale (SCS), as well as a tentative composite of 6 Severity Self-rating Measures, for Paraphilic Disorders and depression (Montgomery-Åsberg Depression Rating Scale [MADRS-S]), psychological distress (Clinical Outcomes in Routine Evaluation Outcome Measure [CORE-OM]), and treatment satisfaction (CSQ-8).

    Results: Large, significant decreases in HD symptoms and sexual compulsivity were found, as well as moderate improvements in psychiatric well-being and paraphilic symptoms. These effects remained stable 3 months after treatment.

    Clinical Implications: ICBT can ameliorate HD symptoms, psychiatric distress, and paraphilic symptoms, which suggests that the ICBT for HD, with or without paraphilia(s) or paraphilic disorder(s), may constitute a valuable addition of treatment options in clinical settings.

    Strengths and Limitations: This is the first study evaluating the efficacy of ICBT on a sample of men suffering from HD. In addition, a proportion of the sample reported concomitant paraphilic interests and disorders, thus mirroring an everyday clinical practice in the field of sexual medicine. No control group was assigned, and some of the outcome measures are still to be validated. The long-term effects of ICBT and its efficacy in hypersexual women are unknown.

    Conclusions: This study gives support for ICBT as an effective treatment option for HD. Future evaluations of the treatment program should include women and larger samples in randomized controlled procedures and investigate the long-term effects.

  • 27.
    Hirvikoski, Tatja
    et al.
    Pediatric Neuropsychiatry Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Habilitation and Health, Region Stockholm, Stockholm, Sweden; Center for Psychiatry Research, Region Stockholm, Stockholm, Sweden; Center for Neurodevelopmental Disorders at Karolinska Institutet (KIND), CAP Research Center, Stockholm, Sweden.
    Lajic, S.
    Pediatric Endocrinology Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Jokinen, Jussi
    Center for Psychiatry Research, Region Stockholm, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Renhorn, E.
    Pediatric Neuropsychiatry Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Habilitation and Health, Region Stockholm, Stockholm, Sweden.
    Trillingsgaard, A.
    Department of Psychology, University of Aarhus, Aarhus, Denmark.
    Kadesjö, B.
    Gillberg Neuropsychiatry Centre, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Sahlgrenska University Hospital, Gothenburg, Sweden.
    Gillberg, C.
    Gillberg Neuropsychiatry Centre, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Sahlgrenska University Hospital, Gothenburg, Sweden.
    Borg, J.
    Center for Psychiatry Research, Region Stockholm, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Using the five to fifteen-collateral informant questionnaire for retrospective assessment of childhood symptoms in adults with and without autism or ADHD2021In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 30, no 9, p. 1367-1381Article in journal (Refereed)
    Abstract [en]

    Due to lack of previous studies, we aimed at evaluating the use of the Five to Fifteen (FTF) questionnaire in adults with neurodevelopmental disorders (NDD) and in controls without NDD. The NDD group consisted of adults with autism spectrum disorder ASD (n = 183) or attention-deficit/hyperactivity disorder (ADHD) (n = 174) without intellectual disability, recruited from a tertiary outpatient clinic. A web survey was used to collect data from general population adult control group without NDD (n = 738). The participants were retrospectively rated by their parents regarding childhood symptoms, using five to fifteen-collateral informant questionnaire (FTF-CIQ). Adults with NDD had higher FTF-CIQ domain and subdomain scores than controls, and displayed similar test profiles as children with corresponding diagnosis in previous studies. Based on the FTF-CIQ domain scores, 84.2% of the study participants (93% of the controls; 64% of the adults with NDD) were correctly classified in a logistic regression analysis. Likewise, Receiver Operating Characteristic (ROC) curve analysis on FTF-CIQ total sum score indicated that a cut-off value of 20.50 correctly classified 90% of the controls and 67% of the clinical cases, whilst a cut-off value of 30.50 correctly classified 84% of the controls and 77% of the clinical cases. The factor analysis revealed three underlying components: learning difficulties, cognitive and executive functions; social skills and emotional/behavioural symptoms; as well as motor and perceptual skills. Whilst not designed as a diagnostic instrument, the FTF-CIQ may be useful for providing information on childhood symptoms and associated difficulties in individuals assessed for NDD as adults.

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  • 28. Isung, Josef
    et al.
    Granqvist, Mathias
    Trepci, Ada
    Huang, Jesse
    Schwieler, Lilly
    Kierkegaard, Marie
    Erhardt, Sophie
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Piehl, Fredrik
    Differential effects on blood and cerebrospinal fluid immune protein markers and kynurenine pathway metabolites from aerobic physical exercise in healthy subjects2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 1669Article in journal (Refereed)
    Abstract [en]

    Mounting evidence shows that physical exercise modulates systemic inflammation. However, its effect on cerebrospinal fluid (CSF) immune-marker profiles in man are largely unknown. We here report a study on healthy subjects (n=27, males=12, mean age 28.7, range 22-52) allocated to either an acute exercise setting over four consecutive days, or a training intervention over 4 weeks. Paired plasma and CSF samples collected at baseline, after 7 days of exercise abstention, and the day after completion of the exercise interventions, were analyzed for protein inflammation markers using a multiplex proximity extension assay and neurotransmitters and kynurenine pathway (KP) metabolites using liquid chromatography, respectively. Routine cell counts, and albumin, immunoglobulin G and neurofilament light chain concentrations in CSF remained unchanged in both paradigms, while several inflammatory proteins became upregulated after acute exercise. However, only changes in three CSF (vascular endothelial growth factor-A, interleukin-7 and matrix metalloproteinase-10) and 12 plasma proteins reached significance levels after adjustment for multiple comparisons and exclusion of less stable proteins. Similarly, KP metabolites only changed among participants after acute exercise, while neurotransmitter levels, except for increased CSF serine, remained stable. Both in plasma and CSF changes in KP metabolites and inflammatory proteins correlated, suggesting that these processes are functionally linked. These findings suggest that acute aerobic physical exercise affects immune markers and KP metabolites systemically and in the CSF.

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  • 29.
    Jamshidi, Esmail
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Boström, Adrian Desai E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Wilczek, Alexander
    Department of Clinical Sciences, Karolinska Institutet at Danderyd Hospital, Stockholm, Sweden.
    Nilsonne, Åsa
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Åsberg, Marie
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Increased methylation of brain-derived neurotrophic factor (BDNF) is related to emotionally unstable personality disorder and severity of suicide attempt in women2023In: Cells, E-ISSN 2073-4409, Vol. 12, no 3, article id 350Article in journal (Refereed)
    Abstract [en]

    Brain-derived neurotrophic factor (BDNF) has previously been associated with the pathogenesis of both emotionally unstable personality disorder (EUPD) and suicidal behavior. No study has yet investigated BDNF-associated epigenetic alterations in a group of severely impaired EUPD and suicidal patients. The discovery cohort consisted of 97 women with emotionally unstable personality disorder (EUPD) with at least two serious suicide attempts (SAs) and 32 healthy female controls. The genome-wide methylation pattern was measured by the Illumina EPIC BeadChip and analyzed by robust linear regression models to investigate mean BDNF methylation levels in a targeted analysis conditioned upon severity of suicide attempt. The validation cohort encompassed 60 female suicide attempters, stratified into low- (n = 45) and high-risk groups (n = 15) based on degree of intent-to-die and lethality of SA method, and occurrence of death-by-suicide at follow-up. Mean BDNF methylation levels exhibited increased methylation in relation to EUPD (p = 0.0159, percentage mean group difference ~3.8%). Similarly, this locus was confirmed as higher-methylated in an independent cohort of females with severe suicidal behavior (p = 0.0300). Results were independent of age and BMI. This is the first study to reveal emerging evidence of epigenetic dysregulation of BDNF with dependence on features known to confer increased risk of suicide deaths (lethality of suicide-attempt method and presence of EUPD diagnosis with history of recent SAs). Further studies investigating epigenetic and genetic effects of BDNF on severe suicidal behavior and EUPD are needed to further elucidate the role of epigenetic regulatory mechanisms and neurotrophic factors in relation to suicide and EUPD, and hold potential to result in novel treatment methods.

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  • 30.
    Jokinen, Jussi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychology, Karolinska Institute, Stockholm, Sweden.
    Andersson, Peter
    Department of Clinical Neuroscience/Psychology, Karolinska Institute, Stockholm, Sweden; Centre for Clinical Research Dalarna, Uppsala University, Falun, Sweden.
    Chatzittofis, Andreas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Medical School, University of Cyprus, Nicosia, Cyprus.
    Savard, Josephine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Rask-Andersen, Mathias
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Åsberg, Marie
    Department of Clinical Neuroscience/Psychology, Karolinska Institute, Stockholm, Sweden.
    Boström, Adrian Desai E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Women’s and Children’s Health/Neuropediatrics, Karolinska Institutet, Stockholm, Sweden.
    Accelerated epigenetic aging in suicide attempters uninfluenced by high intent-to-die and choice of lethal methods2022In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, no 1, article id 224Article in journal (Refereed)
    Abstract [en]

    Suicide attempts (SA) are associated with excess non-suicidal mortality, putatively mediated in part by premature cellular senescence. Epigenetic age (EA) estimators of biological age have been previously demonstrated to strongly predict physiological dysregulation and mortality risk. Herein, we investigate if violent SA with high intent-to-die is predictive of epigenetics-derived estimates of biological aging. The genome-wide methylation pattern was measured using the Illumina Infinium Methylation EPIC BeadChip in whole blood of 88 suicide attempters. Subjects were stratified into two groups based on the putative risk of later committed suicide (low- [n = 58] and high-risk [n = 30]) in dependency of SA method (violent or non-violent) and/or intent-to-die (high/low). Estimators of intrinsic and extrinsic EA acceleration, one marker optimized to predict physiological dysregulation (DNAmPhenoAge/AgeAccelPheno) and one optimized to predict lifespan (DNAmGrimAge/AgeAccelGrim) were investigated for associations to severity of SA, by univariate and multivariate analyses. The study was adequately powered to detect differences of 2.2 years in AgeAccelGrim in relation to SA severity. Baseline DNAmGrimAge exceeded chronological age by 7.3 years on average across all samples, conferring a mean 24.6% increase in relation to actual age. No individual EA acceleration marker was differentiated by suicidal risk group (p > 0.1). Thus, SA per se but not severity of SA is related to EA, implicating that excess non-suicidal mortality in SA is unrelated to risk of committed suicide. Preventative healthcare efforts aimed at curtailing excess mortality after SA may benefit from acting equally powerful to recognize somatic comorbidities irrespective of the severity inherent in the act itself.

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  • 31.
    Jokinen, Jussi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Flanagan, John
    Chatzittofis, Andreas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Öberg, Katarina
    Arver, Stefan
    High Plasma Oxytocin Levels in Men With Hypersexual Disorder2019In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 44, p. 114-114Article in journal (Other academic)
    Abstract [en]

    Background: Hypersexual disorder (HD) integrating pathophysiological aspects such as sexual desire deregulation, sexual addiction, impulsivity and compulsivity was suggested as a diagnosis for the DSM-5. "Compulsive Sexual Behavior Disorder" is now presented as an impulse-control disorder in ICD-11. Recent studies showed dysregulated HPA axis in men with HD. Oxytocin (OXT) affects the function of the HPA axis; no studies have assessed OXT levels in patients with HD. Whether a CBT treatment for HD symptoms has an effect on OXT levels has not been investigated.

    Methods: We examined plasma OXT levels in 64 male patients with HD and 38 male age-matched healthy volunteers. Further, we examined correlations between plasma OXT levels and dimensional symptoms of HD using the rating scales measuring hypersexual behaviour: Hypersexual disorder screening inventory (HDSI) and the Sexual Compulsive scale (SCS). A part of the patients (N = 30) completed the manual-based group-administered CBT program for HD and had a secondary measurement of OXT at post-treatment. OXT was measured with Radioimmunoassay (RIA).

    Results: Patients with HD had significantly higher OXT (Mean 31.0 ± SD 9.9 pM) levels compared to healthy volunteers (Mean 16.9 ± SD 3.9 pM) (p < 0.001). There were significant positive correlations between OXT levels and the rating scales measuring hypersexual behaviour (Spearman rhos between HDSI r = 0.649, p < 0.001 and SCS r = 0.629, p < 0.001) in the study participants combined. Patients who completed CBT treatment had significant reduction of OXT levels from pre-treatment (30.5 ± 10.1pM) to post-treatment (20.2 ± 8.0pM) (p < 0.001). Patients with HD had a significant positive correlation of their changes in HD:CAS with plasma oxytocin level before and after CBT(r = 0.388, p value= 0.0344).

    Conclusions: The results suggest hyperactive oxytonergic system in male patients with hypersexual disorder which may be a compensatory mechanism to attenuate hyperactive stress system. A successful CBT group therapy may have effect on hyperactive oxytonergic system.

  • 32.
    Jokinen, Jussi
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Ljung, Rickard
    Socialmedicinare, Institutet för miljömedicin, Karolinska institutet, Sweden.
    Unga som gjort självmordsförsök har kraftigt förkortad livslängd2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, article id EYDZArticle in journal (Other academic)
  • 33.
    Kauppila, Joonas H.
    et al.
    Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Surgery Research Unit, Medical Research Center Oulu, University of Oulu, Oulu University Hospital, Oulu, Finland.
    Santoni, Giola
    Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Tao, Wenjing
    Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Lynge, Elsebeth
    Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Tryggvadóttir, Laufey
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Icelandic Cancer Registry, Icelandic Cancer Society, Reykjavik, Iceland.
    Ness-Jensen, Eivind
    Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Faculty of Medicine, Laeknagardur, University of Iceland, Reykjavik, Iceland; Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
    Pukkala, Eero
    Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland; Faculty of Social Sciences, Tampere University, Tampere, Finland.
    Von Euler-Chelpin, My
    Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Lagergren, Jesper
    Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; School of Cancer and Pharmaceutical Sciences, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
    Risk Factors for Suicide After Bariatric Surgery in a Population-based Nationwide Study in Five Nordic Countries2022In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 275, no 2, p. E410-E414Article in journal (Refereed)
    Abstract [en]

    Objective:To identify risk factors for suicide after bariatric surgery.

    Summary background data:Bariatric surgery reduces obesity-related mortality. However, it is for unclear reasons is associated with an increased risk of suicide.

    Methods:This population-based cohort study included patients having undergone bariatric surgery in 1982 to 2012 in any of the 5 Nordic countries, with follow-up through 2012. Eleven potential risk factors of suicide (sex, age, comorbidity, surgery type, surgical approach, calendar year of surgery, history of depression or anxiety, psychosis, schizophrenia, mania, or bipolar disorder, personality disorder, substance use, and number of previously documented psychiatric diagnoses) were analyzed using Cox regression.

    Results:Of 49,977 bariatric surgery patients, 98 (0.2%) committed suicide during follow-up. Women had a decreased risk of suicide compared to men (hazard ratio [HR] = 0.48, 95% confidence interval [CI] 0.33-0.77), although age and comorbidity did not influence this risk. Compared to gastric bypass, other types of bariatric surgery had lower risk of suicide (HR = 0.44, 95%CI 0.27-0.99). There was no difference in suicide risk between laparoscopic and open surgical approach. A history of depression or anxiety (HR = 6.87, 95%CI 3.97-11.90); mania, bipolar disorder, psychosis, or schizophrenia (HR = 2.70, 95%CI 1.14-6.37); and substance use (HR = 2.28, 95%CI 1.08-4.80), increased the risk of suicide. More of the above psychiatric diagnoses increased the risk of suicide (HR = 22.59, 95%CI 12.96-39.38 for ≥2 compared to 0 diagnoses).

    Conclusions:Although the risk of suicide is low, psychiatric disorders, male sex, and gastric bypass procedure seem to increase the risk of suicide after bariatric surgery, indicating a role for tailored preoperative psychiatric evaluation and postoperative surveillance.

  • 34.
    Landgren, Valdemar
    et al.
    Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Savard, Josephine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Anova, Karolinska University Hospital, Stockholm, Sweden.
    Dhejne, Cecilia
    Anova, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Arver, Stefan
    Anova, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Seto, Michael C.
    Royal Ottawa Health Care Group, ON, Ottawa, Canada.
    Rahm, Christoffer
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Pharmacological Treatment for Pedophilic Disorder and Compulsive Sexual Behavior Disorder: A Review2022In: Drugs, ISSN 0012-6667, E-ISSN 1179-1950, Vol. 82, p. 663-681Article, review/survey (Refereed)
    Abstract [en]

    Guidelines for the pharmacological treatment of paraphilic disorders have historically been based on data from forensic settings and on risk levels for sexual crime. However, emerging treatment options are being evaluated for individuals experiencing distress because of their sexual urges and preferences, targeting both paraphilic disorders such as pedophilic disorder (PeD) and the new diagnosis of compulsive sexual behavior disorder (CSBD) included in the International Classification of Diseases, 11th Revision (ICD-11). As in other mental disorders, this may enable individualized pharmacological treatment plans, taking into account components of sexuality (e.g. high libido, compulsivity, anxiety-driven/sex as coping), medical and psychiatric comorbidity, adverse effects and patient preferences. In order to expand on previous reviews, we conducted a literature search focusing on randomized controlled trials of pharmacological treatment for persons likely to have PeD or CSBD. Our search was not restricted to studies involving forensic or criminal samples. Twelve studies conducted between 1974 and 2021 were identified regardless of setting (outpatient or inpatient), with only one study conducted during the last decade. Of a total of 213 participants included in these studies, 122 (57%) were likely to have PeD, 34 (16%) were likely to have a CSBD, and the remainder had unspecified paraphilias (40, 21%) or sexual offense (17, 8%) as the treatment indication. The diagnostic procedure for PeD and/or CSBD, as well as comorbid psychiatric symptoms, has been described in seven studies. The studies provide some empirical evidence that testosterone-lowering drugs reduce sexual activity for patients with PeD or CSBD, but the body of evidence is meager. There is a need for studies using larger samples, specific criteria for inclusion, longer follow-up periods, and standardized outcome measures with adherence to international reporting guidelines.

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  • 35.
    Liberg, Benny
    et al.
    Department of Clinical Neuroscience, Osher Center, Karolinska Institutet, Stockholm, Sweden.
    Görts-Öberg, Katarina
    Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Huddinge, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Savard, Josephine
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Karolinska University Hospital, Stockholm, Sweden.
    Dhejne, Cecilia
    Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Huddinge, Sweden.
    Arver, Stefan
    Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Huddinge, Sweden.
    Fuss, Johannes
    Institute of Forensic Psychiatry and Sex Research, Center for Translational Neuro- and Behavioral Sciences, University of Duisburg-Essen, Essen, Germany.
    Ingvar, Martin
    Department of Clinical Neuroscience, Osher Center, Karolinska Institutet, Stockholm, Sweden.
    Abé, Christoph
    Department of Clinical Neuroscience, Osher Center, Karolinska Institutet, Stockholm, Sweden; Quantify Research, Stockholm, Sweden.
    Neural and behavioral correlates of sexual stimuli anticipation point to addiction-like mechanisms in compulsive sexual behavior disorder2022In: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 11, no 2, p. 520-532Article in journal (Refereed)
    Abstract [en]

    Background and aims: Compulsive sexual behavior disorder (CSBD) is characterized by persistent patterns of failure to control sexual impulses resulting in repetitive sexual behavior, pursued despite adverse consequences. Despite previous indications of addiction-like mechanisms and the recent impulse-control disorder classification in the International Classification of Diseases (ICD-11), the neurobiological processes underlying CSBD are unknown.

    Methods: We designed and applied a behavioral paradigm aimed at disentangling processes related to anticipation and viewing of erotic stimuli. In 22 male CSBD patients (age: M = 38.7, SD = 11.7) and 20 healthy male controls (HC, age: M = 37.6, SD = 8.5), we measured behavioral responses and neural activity during functional magnetic resonance imaging (fMRI). The main outcomes were response time differences between erotic and non-erotic trials and ventral striatum (VS) activity during anticipation of visual stimuli. We related these outcomes with each other, to CSBD diagnosis, and symptom severity.

    Results: We found robust case-control differences on behavioral level, where CSBD patients showed larger response time differences between erotic and non-erotic trials than HC. The task induced reliable main activations within each group. While we did not observe significant group differences in VS activity, VS activity during anticipation correlated with response time differences and self-ratings for anticipation of erotic stimuli.

    Discussion and Conclusions: Our results support the validity and applicability of the developed task and suggest that CSBD is associated with altered behavioral correlates of anticipation, which were associated with ventral striatum activity during anticipation of erotic stimuli. This supports the idea that addiction-like mechanisms play a role in CSBD.

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  • 36. Lindh, Åsa U.
    et al.
    Dahlin, Marie
    Beckman, Karin
    Strömsten, Lotta M. J.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Wiktorsson, Stefan
    Salander Renberg, Ellinor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Waern, Margda
    Runeson, Bo
    A Comparison of Suicide Risk Scales in Predicting Repeat Suicide Attempt and Suicide: A Clinical Cohort Study2019In: Journal of Clinical Psychiatry, ISSN 0160-6689, E-ISSN 1555-2101, Vol. 80, no 6, article id 18m12707Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare the predictive accuracy of the Suicide Intent Scale (SIS), the Suicide Assessment Scale (SUAS), the Karolinska Interpersonal Violence Scale (KIVS), and the Columbia-Suicide Severity Rating Scale (C-SSRS) for suicide attempts and suicides within 3 and 12 months of an episode of self-harm.

    METHODS: This prospective multicenter cohort study included patients (N = 804) aged 18-95 years with a recent episode of self-harm assessed in psychiatric emergency settings from April 2012 to April 2016. Suicide attempts and suicides were identified in medical records and in the National Cause of Death Register. Receiver operating characteristic curves were constructed, and accuracy statistics were calculated. A sensitivity of at least 80% combined with a specificity of at least 50% were considered minimally acceptable.

    RESULTS: At least 1 suicide attempt was recorded for 216 participants during follow-up, and 19 participants died by suicide. The SUAS and C-SSRS were better than chance in classifying the 114 suicide attempts occurring within the first 3 months; a C-SSRS score ≥ 27 yielded a sensitivity/specificity of 79.8%/51.5% (P < .001). During 1-year follow-up, the SUAS and C-SSRS also performed better than chance, but no cutoff on either instrument gave a sensitivity/specificity of ≥ 80%/≥ 50%. The SIS was the only instrument that could classify suicides correctly. At 3 months, the area under the curve (AUC) was 0.94 (95% CI, 0.89-0.99), and a score ≥ 21 predicted suicide with a sensitivity/specificity of 100%/81.9%, based on only 4 suicides. At 1-year follow-up, the AUC was 0.74 (95% CI, 0.61-0.87), and a score ≥ 17 predicted suicide with a sensitivity/specificity of 72.2%/57.9%.

    CONCLUSIONS: Instruments that predicted nonfatal repeat suicide attempts did not predict suicide and vice versa. With the possible exception of the prediction of suicide by the SIS in a short time frame, the specificity of these instruments was low, giving them a limited relevance in the prediction of suicidal behaviors.

  • 37. Lindner, Philip
    et al.
    Flodin, Pär
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; .
    Budhiraja, Meenal
    Savic, Ivanka
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Tiihonen, Jari
    Hodgins, Sheilagh
    Associations of Psychopathic Traits With Local and Global Brain Network Topology in Young Adult Women2018In: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, ISSN 2451-9022, Vol. 3, no 12, p. 1003-1012Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Psychopathic traits vary dimensionally in the population and are associated with multiple negative outcomes. The impaired integration theory (IIT) proposes that psychopathic traits are associated with abnormal neural network topology, such that disturbed integration of neural networks results in a self-perpetuating impairment in rapid integration and learning from multiple components of information. The IIT is based on findings from male offenders presenting high scores on all psychopathic traits. The present study investigated whether IIT predictions of topology abnormalities were associated with psychopathic traits, measured dimensionally, in young adult women with subsyndromal scores.

    METHODS: Seventy-three women, with an average age of 25 years, were assessed using the Psychopathy Checklist-Revised and completed resting-state magnetic resonance imaging. Preprocessed time series from 90 anatomical regions were extracted to form connectivity matrices and used to calculate network topology based on graph theory. Correlations between total psychopathy and factor scores with both the raw connectivity matrix and global and local graph theory measures were computed.

    RESULTS: Total psychopathy scores and behavioral factor scores were related to connectivity between several pairs of regions, primarily limbic/paralimbic. Psychopathic traits were not associated with global topology measures. Topology abnormalities, robust across network formation thresholds, were found in nodes of the default mode network and in hubs connecting several resting-state networks.

    CONCLUSIONS: IIT predictions of abnormal topology of hubs and default mode network nodes with dimensionally measured psychopathic traits were confirmed in a sample of young women. Regional abnormalities, accompanied by preserved global topology, may underlie context-specific abnormal information processing and integration.

  • 38. Pahnke, Johan
    et al.
    Hirvikoski, Tatja
    Bjureberg, Johan
    Bölte, Sven
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bohman, Benjamin
    Lundgren, Tobias
    Acceptance and commitment therapy for autistic adults: An open pilot study in a psychiatric outpatient context2019In: Journal of Contextual Behavioral Science, ISSN 2212-1447, Vol. 13, p. 34-41Article in journal (Refereed)
    Abstract [en]

    Highlights:

    Feasibility and credibility of the NeuroACT protocol was high.

    Symptoms of stress and depression were significantly reduced.

    Cognitive defusion and psychological flexibility significantly increased.

    Quality of life and social functioning were significantly improved.

  • 39.
    Pahnke, Johan
    et al.
    Karolinska Institutet and Region Stockholm, Sweden.
    Jansson-Fröjmark, Markus
    Karolinska Institutet and Region Stockholm, Sweden.
    Andersson, Gerhard
    Karolinska Institutet and Region Stockholm, Sweden; Linköping University, Sweden.
    Bjureberg, Johan
    Karolinska Institutet and Region Stockholm, Sweden; Stanford University, United States.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bohman, Benjamin
    Karolinska Institutet and Region Stockholm, Sweden.
    Lundgren, Tobias
    Karolinska Institutet and Region Stockholm, Sweden.
    Acceptance and commitment therapy for autistic adults: a randomized controlled pilot study in a psychiatric outpatient setting2023In: Autism, ISSN 1362-3613, E-ISSN 1461-7005, Vol. 27, no 5, p. 1461-1476Article in journal (Refereed)
    Abstract [en]

    Autistic adults are at risk of stress-related psychiatric disorders and reduced life quality due to social, cognitive, and perceptual challenges. Mental health interventions adapted to autistic adults are scarce. Acceptance and commitment therapy has preliminarily indicated health benefits in autistic adults, although it has not been robustly evaluated. Overall, 39 adults (21 males; 21–72 years) with autism spectrum disorder and normal intellectual ability (IQ M = 108.5; SD = 13.5) were randomized to 14 weeks of adapted acceptance and commitment therapy group treatment (NeuroACT) or treatment as usual. The intervention was feasible. Perceived stress and quality of life (primary outcomes), alongside psychological inflexibility, cognitive fusion, cognitive and behavioral avoidance, and autistic mannerism were statistically significantly improved in NeuroACT compared with treatment as usual (d = 0.70–0.90). Clinically significant changes in perceived stress and quality of life were in favor of NeuroACT. Between-group altered depression, anxiety, sleep problems, one quality of life measure, functional impairment, social aspects of autism, and executive difficulties were statistically non-significant. Dropout was slightly higher in NeuroACT. NeuroACT may be a promising treatment for autistic adults with co-existing stress and reduced quality of life. More extensive studies are warranted to evaluate NeuroACT further. 

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  • 40.
    Rajalin, Mia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Stockholm, Stockholm County Council, Stockholm, Sweden.
    Hirvikoski, Tatja
    Salander Renberg, Ellinor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Åsberg, Marie
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Stockholm, Stockholm County Council, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Exposure to Early Life Adversity and Interpersonal Functioning in Attempted Suicide2020In: Frontiers in Psychiatry, E-ISSN 1664-0640, Vol. 11, article id 552514Article in journal (Refereed)
    Abstract [en]

    Background: Early life adversity (ELA) may lead to an increased risk for mental health problems including suicidal behavior. ELA alters biological stress systems that affect behavior and control within the individual that in turn will affect interpersonal behavior. Strained relations and interpersonal conflicts leading to rejection and isolation have been shown to be factors for suicidal behavior. Difficulties in interpersonal relationships are a common reason for seeking help in psychiatric care. In the present study, we examined relationship between different types of interpersonal problems and adverse childhood experiences in patients with a recent suicide attempt.

    Method: The study included 181 recent suicide attempters. We assessed early life adversity and specific interpersonal problems by using the Karolinska Interpersonal Violence Scale and the Inventory of Interpersonal problems respectively.

    Results: Suicide attempters with high levels of early life adversity expressed a more socially avoidant, non-assertive, and exploitable personal style even after adjustment for comorbidities with personality disorder and substance use disorder.

    Conclusions: Patients with a recent suicide attempt with high levels of early life adversity tend to isolate themselves, of being introvert, and having difficulties to open up and confide in others. They report low self-confidence and self-esteem and problems with feeling and expressing anger. These behaviors complicate interaction with others and make establishment of solid relationships more difficult. In regards to detection of suicidal communication and treatment of suicidal patients, this may lead to misinterpretations and difficulties to fully benefit from treatment given or for professionals to provide the appropriate treatment. Clinicians should closely investigate the presence of early life adversity in suicidal patients and pay attention to their personal style and their difficulties in interpersonal exchange.

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  • 41. Sahlin, Hanna
    et al.
    Bjureberg, Johan
    Gratz, Kim L.
    Tull, Matthew T.
    Hedman-Lagerlöf, Erik
    Bjärehed, Jonas
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Lundh, Lars-Gunnar
    Hellner, Clara
    Ljotsson, Brjann
    Predictors of improvement in an open-trial multisite evaluation of emotion regulation group therapy2019In: Cognitive Behaviour Therapy, ISSN 1650-6073, E-ISSN 1651-2316, Vol. 48, no 4, p. 322-336Article in journal (Refereed)
    Abstract [en]

    Emotion regulation group therapy (ERGT) is a novel treatment specifically targeting deliberate non-suicidal self-harm (DSH) in individuals with borderline personality disorder (BPD). Identifying robust predictors of positive response to ERGT could aid clinicians in treatment selection; however, to date, only one such study has been conducted. Thus, we aimed to replicate previously identified predictors of treatment response to ERGT by investigating demographic, clinical, and diagnostic predictors in 95 women with BPD or subclinical BPD who had participated in an open-trial evaluation of ERGT. Outcomes evaluated were frequency of DSH and emotion dysregulation. Assessments were conducted at pretreatment, post-treatment, and 6-month follow-up. Multilevel mixed linear models and multilevel negative binomial generalized estimated equations were used to identify significant interactions between the predictors and outcomes.

    We found that greater pretreatment DSH frequency was associated with greater improvements in DSH during treatment (b = 0.998, SE = 0.00, p = 0.03) and follow-up (b = 0.997, SE = 0.00, p < 0.01) and that greater BPD severity was associated with greater improvements in DSH during treatment (b = 0.84, SE = 0.06, p = 0.02) and in emotion dysregulation at follow-up (b = −3.05, SE = 1.47, p = 0.04). Co-occurring disorders were associated with poorer treatment response during follow-up. Results were generally consistent with a previous study of the predictors of response to ERGT. The findings provide further support for the utility of this treatment across a range of BPD patients, including patients with severe DSH and BPD.

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  • 42.
    Savard, Josephine
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Görts Öberg, Katarina
    Chatzittofis, Andreas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Dhejne, Cecilia
    Arver, Stefan
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    A Feasibility Study of Naltrexone Treatment for Compulsive Sexual Behavior Disorder2020In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 87, no 9, p. S354-S354Article in journal (Other academic)
  • 43.
    Savard, Josephine
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Anova, Karolinska University Hospital, Stockholm, Sweden.
    Görts Öberg, Katarina
    Chatzittofis, Andreas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Medical School, University of Cyprus, Nicosia, Cyprus.
    Dhejne, Cecilia
    Arver, Stefan
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Naltrexone in Compulsive Sexual Behavior Disorder: A Feasibility Study of Twenty Men2020In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 17, no 8, p. 1544-1552Article in journal (Refereed)
    Abstract [en]

    Background: Compulsive sexual behavior disorder (CSBD) is a common disorder affecting different areas of life, although studies focusing on pharmacological treatment are sparse.

    Aim: To investigate whether the opioid receptor antagonist naltrexone is feasible and tolerable and can provide symptom reduction in CSBD.

    Methods: Twenty men aged 27-60 years (mean = 38.8 years, standard deviation = 10.3) with CSBD seeking treatment in an outpatient nonforensic clinic received four weeks of naltrexone 25-50 mg. Measurements were made before, during, and four weeks after treatment.

    Outcomes: The self-assessment Hypersexual Disorder: Current Assessment Scale (HD: CAS) score was the primary outcome measure, and secondary outcomes were the Hypersexual Behavior Inventory (HBI) score, reported adverse effects, adherence to treatment, and dropouts.

    Results: There was significant decrease on both HD: CAS and HBI scores during treatment with naltrexone. Even though some of the effects remained after treatment, the increased scores on HD: CAS indicated worsening of CSBD symptoms. The most reported side effects were fatigue (55%), nausea (30%), vertigo (30%), and abdominal pain (30%). However, there were no serious adverse effects leading to discontinuation of naltrexone.

    Clinical Implications: Despite side effects being common, naltrexone seems to be feasible in the treatment of CSBD.

    Strengths & Limitations: Being the first nonforensic prospective trial on naltrexone in CSBD, this study provides novel insights on a pharmacological intervention. However, owing to the small sample size and the lack of a control group, conclusions of effectiveness should be interpreted with caution.

    Conclusion: Naltrexone is feasible and tolerable and may reduce symptoms of CSBD; nevertheless, future studies should ensure a randomized controlled procedure to evaluate possible effectiveness.

  • 44.
    Savard, Josephine
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Anova Clinic, Karolinska University Hospital, Stockholm, Sweden.
    Görts Öberg, Katarina
    Anova Clinic, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Dhejne, Cecilia
    Anova Clinic, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A randomised controlled trial of fluoxetine versus naltrexone in compulsive sexual behaviour disorder: presentation of the study protocol2022In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 6, article id e051756Article in journal (Refereed)
    Abstract [en]

    Background: Compulsive sexual behaviour disorder is a new disorder in the International Classification of Diseases (ICD-11), and is associated with negative consequences in different areas of life. Evidence for pharmacological treatment of compulsive sexual behaviour disorder is weak and treatment options are limited. This proposed study will be the largest and the first randomised controlled trial comparing the efficacy and tolerability of two active drugs in compulsive sexual behaviour disorder.

    Methods and analysis: Eighty adult participants with compulsive sexual behaviour disorder according to ICD-11 will be randomised to receive either naltrexone 25-50 mg or fluoxetine 20-40 mg for 8 weeks, followed by 6 weeks without treatment. The study will be conducted in a subspecialised outpatient sexual medicine unit at Karolinska University Hospital, Stockholm, Sweden. The study is financed by grants and entirely independent of the manufacturers. Exclusion criteria include severe psychiatric or psychical illness, changes to concurrent medication and non-compatible factors contraindicating the use of either drug. The primary outcome measure is the Hypersexual Disorder: Current Assessment Scale (HD: CAS), and tolerability will be assessed by the Udvalg for Kliniske Undersogelser side effect rating scale (UKU), drug accountability, adherence to treatment and drop-out rate. Participants will complete questionnaires at regular intervals, with the main endpoint for efficacy after 8 weeks (end of treatment) and after 14 weeks (follow-up). Blood chemistry will be repeatedly collected as a safety precaution and for research purposes. The results will be analysed using an appropriate analysis of variance model or a mixed model, depending on the distribution of HD: CAS and the extent of missing data.

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  • 45.
    Savard, Josephine
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Görts Öberg, Katarina
    Dhejne, Cecilia
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    A Randomized Controlled Trial of Fluoxetine Versus Naltrexone in Compulsive Sexual Behavior Disorder: Presentation of the Study ProtocolManuscript (preprint) (Other academic)
  • 46.
    Savard, Josephine
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. ANOVA, Karolinska University Hospital, Stockholm, Sweden.
    Hirvikoski, Tatja
    Görts Öberg, Katarina
    Dhejne, Cecilia
    Rahm, Christoffer
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Impulsivity in Compulsive Sexual Behavior Disorder and Pedophilic Disorder2021In: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 10, no 3, p. 839-847Article in journal (Refereed)
    Abstract [en]

    Background and aims: Impulsivity is regarded as a risk factor for sexual crime reoffending, and a suggested core feature in Compulsive Sexual Behavior Disorder. The aim of this study was to explore clinical (e.g. neurodevelopmental disorders), behavioral and neurocognitive dimensions of impulsivity in disorders of problematic sexuality, and the possible correlation between sexual compulsivity and impulsivity.

    Methods: Men with Compulsive Sexual Behavior Disorder (n = 20), and Pedophilic Disorder (n = 55), enrolled in two separate drug trials in a specialized Swedish sexual medicine outpatient clinic, as well as healthy male controls (n = 57) were assessed with the Hypersexual Behavior Inventory (HBI) for sexual compulsivity, and with the Barratt Impulsiveness Scale (BIS) and Connors' Continuous Performance Test-II (CPT-II) for impulsivity. Psychiatric comorbidity information was extracted from interviews and patient case files.

    Results: Approximately a quarter of the clinical groups had Attention-Deficit/Hyperactivity Disorder (ADHD) or Autism Spectrum Disorder. Both clinical groups reported more compulsive sexuality (r = 0.73-0.75) and attentional impulsivity (r = 0.36-0.38) than controls (P < 0.05). Based on results on univariate correlation analysis, BIS attentional score, ADHD, and Commissions T-score from CPT-II were entered in a multiple linear regression model, which accounted for 15% of the variance in HBI score (P < 0.0001). BIS attentional score was the only independent positive predictor of HBI (P = 0.001).

    Discussion: Self-rated attentional impulsivity is an important associated factor of compulsive sexuality, even after controlling for ADHD. Psychiatric comorbidity and compulsive sexuality are common in Pedophilic Disorder.

    Conclusion: Neurodevelopmental disorders and attentional impulsivity - including suitable interventions - should be further investigated in both disorders.

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  • 47.
    Sokolov, Aleksandr V.
    et al.
    Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden.
    Manu, Diana-Maria
    Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden.
    Nordberg, Didi O. T.
    Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden.
    Boström, Adrian Desai E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Women’s and Children’s Health/Neuropediatrics, Karolinska Institutet, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Schiöth, Helgi B.
    Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden.
    Methylation in MAD1L1 is associated with the severity of suicide attempt and phenotypes of depression2023In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 15, no 1, article id 1Article in journal (Refereed)
    Abstract [en]

    Depression is a multifactorial disorder representing a significant public health burden. Previous studies have linked multiple single nucleotide polymorphisms with depressive phenotypes and suicidal behavior. MAD1L1 is a mitosis metaphase checkpoint protein that has been linked to depression in GWAS. Using a longitudinal EWAS approach in an adolescent cohort at two time points (n = 216 and n = 154), we identified differentially methylated sites that were associated with depression-related genetic variants in MAD1L1. Three methylation loci (cg02825527, cg18302629, and cg19624444) were consistently hypomethylated in the minor allele carriers, being cross-dependent on several SNPs. We further investigated whether DNA methylation at these CpGs is associated with depressive psychiatric phenotypes in independent cohorts. The first site (cg02825527) was hypomethylated in blood (exp(β) = 84.521, p value ~ 0.003) in participants with severe suicide attempts (n = 88). The same locus showed increased methylation in glial cells (exp(β) = 0.041, p value ~ 0.004) in the validation cohort, involving 29 depressed patients and 29 controls, and showed a trend for association with suicide (n = 40, p value ~ 0.089) and trend for association with depression treatment (n = 377, p value ~ 0.075). The second CpG (cg18302629) was significantly hypomethylated in depressed participants (exp(β) = 56.374, p value ~ 0.023) in glial cells, but did not show associations in the discovery cohorts. The last methylation site (cg19624444) was hypomethylated in the whole blood of severe suicide attempters; however, this association was at the borderline for statistical significance (p value ~ 0.061). This locus, however, showed a strong association with depression treatment in the validation cohort (exp(β) = 2.237, p value ~ 0.003) with 377 participants. The direction of associations between psychiatric phenotypes appeared to be different in the whole blood in comparison with brain samples for cg02825527 and cg19624444. The association analysis between methylation at cg18302629 and cg19624444 and MAD1L1 transcript levels in CD14+ cells shows a potential link between methylation at these CpGs and MAD1L1 expression. This study suggests evidence that methylation at MAD1L1 is important for psychiatric health as supported by several independent cohorts.

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  • 48. Stenbacka, Marlene
    et al.
    Moberg, Tomas
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet,Stockholm, Sweden.
    Adolescent criminality: multiple adverse health outcomes and mortality pattern in Swedish men2019In: BMC Public Health, E-ISSN 1471-2458, Vol. 19, article id 400Article in journal (Refereed)
    Abstract [en]

    Background: To investigate the impact of adolescent violent and non-violent criminality and subsequent risk of morbidity and mortality in adulthood in a large Swedish cohort of young men conscripted for military service in 1969/70.

    Methods: The cohort consisted of 49,398 18-year-old Swedish conscripts followed up for morbidity and mortality up to the age of 55 years in Swedish national registers. Information about convictions for crime before conscription was obtained from national crime registers. Data from a survey at conscription were scrutinized to get information on potential confounders.

    Results: Hospitalization due to alcohol and drug related diagnoses and attempted suicide were significantly more evident in the violent group compared to non-violent criminals and non-criminals. More than one fifth (21.13%) of the young violent offenders, 12.90% of the non-violent offenders and 4.96% of the non-criminals had died during the follow-up period. In Cox proportional multivariate analyses, young violent offenders had twice the hazard (HR = 4.29) of all-cause mortality than the non-violent offenders (HR = 2.16) during the follow-up period. Alcohol and drug related mortality, suicide and fatal accidents were most evident in both violent and non-violent offenders.

    Conclusions: Men with adolescent criminality received more inpatient care due to alcohol and drug related diagnoses and attempted suicide as adults. Mortality due to unnatural causes, alcohol, and drug related diagnoses, suicide and accidents was most evident in violent offenders, while these causes of death were much lower in non-criminals. Men with adolescent criminality are a high-risk group for multiple adverse health outcomes and for early death. Efforts for detection of substance use and psychiatric disorders in this group is important for the prevention work in both local- and community levels as well as national prevention programs.

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