Umeå University's logo

umu.sePublications
Change search
Refine search result
123 1 - 50 of 136
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 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. Aeinehband, Shahin
    et al.
    Brenner, Philip
    Stahl, Sara
    Bhat, Maria
    Fidock, Mark D.
    Khademi, Mohsen
    Olsson, Tomas
    Engberg, Goran
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Erhardt, Sophie
    Piehl, Fredrik
    Cerebrospinal fluid kynurenines in multiple sclerosis: relation to disease course and neurocognitive symptoms2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 51, p. 47-55Article in journal (Refereed)
    Abstract [en]

    Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system, with a high rate of neurocognitive symptoms for which the molecular background is still uncertain. There is accumulating evidence for dysregulation of the kynurenine pathway (KP) in different psychiatric and neurodegenerative conditions. We here report the first comprehensive analysis of cerebrospinal fluid (CSF) kynurenine metabolites in MS patients of different disease stages and in relation to neurocognitive symptoms. Levels of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) were determined with liquid chromatography mass spectrometry in cell-free CSF. At the group level MS patients (cohort 1; n = 71) did not differ in absolute levels of TRP, KYN, KYNA or QUIN as compared to non-inflammatory neurological disease controls (n = 20). Stratification of patients into different disease courses revealed that both absolute QUIN levels and the QUIN/KYN ratio were increased in relapsing-remitting MS (RRMS) patients in relapse. Interestingly, secondary progressive MS (SPMS) displayed a trend for lower TRP and KYNA, while primary progressive (PPMS) patients displayed increased levels of all metabolites, similar to a group of inflammatory neurological disease controls (n = 13). In the second cohort (n = 48), MS patients with active disease and short disease duration were prospectively evaluated for neuropsychiatric symptoms. In a supervised multivariate analysis using orthogonal projection to latent structures (OPLS-DA) depressed patients displayed higher KYNA/TRP and KYN/TRP ratios, mainly due to low TRP levels. Still, this model had low predictive value and could not completely separate the clinically depressed patients from the non-depressed MS patients. No correlation was evident for other neurocognitive measures. Taken together these results demonstrate that clinical disease activity and differences in disease courses are reflected by changes in KP metabolites. Increased QUIN levels of RRMS patients in relapse and generally decreased levels of TRP in SPMS may relate to neurotoxicity and failure of remyelination, respectively. In contrast, PPMS patients displayed a more divergent pattern more resembling inflammatory conditions such as systemic lupus erythematosus. The pattern of KP metabolites in RRMS patients could not predict neurocognitive symptoms.

  • 3.
    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.

    Download full text (pdf)
    fulltext
  • 4.
    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.

    Download full text (pdf)
    fulltext
  • 5.
    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.

    Download full text (pdf)
    fulltext
  • 6.
    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.

    Download full text (pdf)
    fulltext
  • 7.
    Asellus, Peter
    et al.
    Karolinska Inst, Dept Clin Neurosci Psychiat, Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
    Nordström, P
    Karolinska Inst, Dept Clin Neurosci Psychiat, Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Karolinska Inst, Dept Clin Neurosci Psychiat, Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
    Cholesterol and CSF 5-HIAA in attempted suicide2010In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 125, no 1-3, p. 388-92Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Low serum cholesterol has been linked to suicide and violent behaviour. The same kind of associations has been reported regarding low levels of 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and suicidal behaviour. The hypothesis of the link between serum cholesterol and suicide incorporate serotonin. It proposes that low cholesterol is related to altered serotonergic neurotransmission. A correlation between CSF 5-HIAA and serum cholesterol has been shown in animal studies, but has not been found in humans.

    AIM: To study the interrelationship between serum cholesterol and CSF 5-HIAA in suicide attempters. Since both cholesterol and CSF 5-HIAA are associated with suicide and violent suicide attempts, we also investigated the correlation with suicide, violent suicide attempt method, suicide intent, hopelessness and depression severity.

    METHODS: Serum total cholesterol and CSF 5-HIAA were measured in 42 medication free suicide attempters. Patients were assessed with Becks's Hopelessness scale (BHS), Suicide Intent Scale (SIS) and Montgomery-Asberg depression rating scale (MADRS) and followed-up for causes of death.

    RESULTS: Serum total cholesterol and CSF 5-HIAA showed a significant positive correlation adjusted for age, body mass index and substance abuse diagnosis. Cholesterol and CSF 5-HIAA levels did not differ between violent and non-violent suicide attempters or between suicide completers and survivors.

    CONCLUSIONS: These findings indicate that the serotonergic system may be connected to serum cholesterol in patients with a recent suicide attempt.

  • 8.
    Asellus, Peter
    et al.
    Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    Nordström, Peter
    Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    Nordström, Anna-Lena
    Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    Cholesterol and the "Cycle of Violence" in attempted suicide2014In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 215, no 3, p. 646-50Article in journal (Refereed)
    Abstract [en]

    An association between low levels of serum cholesterol and violent or suicidal behaviour has frequently been reported. However the role of serum cholesterol in the cycle of violence (Widom, 1989) has not been studied. The aim of this study was to investigate association between exposure to violence during childhood and used adult violence in suicide attempters with low and high serum cholesterol levels. 81 suicide attempters were assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behaviour in childhood (between 6 and 14 years of age) and during adult life (15 years or older). We used median split to dichotomise groups below and above median serum cholesterol. In patients with serum cholesterol below median, the correlation between exposure to violence as a child and used adult violence was significant (rho=0.52, p=0.002), while in patients with serum cholesterol above median, the correlation between exposure to violence as a child and expressed violent behaviour as an adult was not significant (rho=0.25, p=0.2). Comorbid substance abuse predicted violent behaviour as an adult only in patients with serum cholesterol above median. Serum cholesterol may modify the effect of the "Cycle of Violence".

  • 9.
    Asellus, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nordström, Peter
    Nordström, Anna-Lena
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, R5, Karolinska University Hospital/Solna, Stockholm, Sweden.
    CSF Apolipoprotein E in attempted suicide2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 225, p. 246-249Article in journal (Refereed)
    Abstract [en]

    Background: Cholesterol and cholesterol metabolism, involved in continued neural plasticity, has been associated to suicide and suicidal behavior. Apolipoprotein E (ApoE) plays an important role in the cholesterol metabolism. The purpose of this study was to investigate whether ApoE in cerebrospinal fluid was related to severity of suicidal behavior as measured by number of earlier suicide attempts, reversibility/interruptabilty and violent method of suicide attempt. Methods: CSF ApoE and 5-hydroxyindolacetic acid (5-HIAA) were measured in 42 medication free suicide attempters. Earlier suicide attempts and the reversibility of suicide attempt method were assessed with the Suicide Intent Scale (SIS) and the Freeman Scale. Suicide attempts were classified according to violence of method. Results: CSF ApoE levels significantly negatively correlated to the scores on Freeman Reversibility and there was a trend for lower CSF ApoE levels in suicide attempters using a violent method. Patients with at least one earlier suicide attempt (repeaters) showed a trend for higher CSF ApoE levels compared to suicide attempters debuting with suicidal behavior at inclusion in the study. The correlation between CSF ApoE and 5-HIAA was not significant. Limitations: The main limitations to this study were a relatively small sample size and lack of a healthy control group. Conclusion: Irreversible suicide attempts, representing a high risk for completed suicide, may be associated with lower level of ApoE in CSF.

  • 10. Asellus, Peter
    et al.
    Nordström, Peter
    Nordström, Anna-Lena
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, R5, Karolinska University Hospital/Solna.
    Plasma apolipoprotein E and severity of suicidal behaviour2016In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 190, p. 137-142Article in journal (Refereed)
    Abstract [en]

    There is evidence for association between low cholesterol levels and suicidal behaviour. Since apolipoprotein E (ApoE) is involved in the cholesterol metabolism in both the periphery and in the central nervous system; it may be of particular interest in the neurobiology of suicidal behaviour. Furthermore, hypothalamic-pituitary-adrenal (HPA) axis function, one of the main biological systems implicated in both suicidal behaviour and early-life adversity, affect ApoE levels. Very few studies have assessed plasma ApoE in relation to suicidal behaviour. The purpose of this study was to investigate levels of ApoE in plasma in relation to the severity of suicidal behaviour and life-time adversity in the form of exposure to interpersonal violence in suicide attempters. A total of 100 suicide attempters (67 women and 33 men) were enroled in the study. Information on earlier suicide attempts and age at onset of suicidal behaviour was gathered using the Karolinska Suicide History Interview. The Karolinska Interpersonal Violence Scale was used to assess exposure to interpersonal violence. Plasma ApoE was measured by immunonephelometry according to accredited routines. Patients with at least one earlier suicide attempt had significantly higher ApoE levels compared to suicide attempters debuting with suicidal behaviour at inclusion in the study. A higher number of earlier suicide attempts was significantly correlated with higher plasma ApoE levels. Age at onset was significantly negatively correlated with ApoE after adjusting for age. ApoE showed a significant positive correlation with exposure to interpersonal violence as a child in male suicide attempters. Our findings indicate that ApoE may be related to stress and trauma and the temporal severity of suicidal behaviour.

  • 11.
    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.

  • 12.
    Bendix, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Uvnas-Moberg, Kerstin
    Petersson, Maria
    Asberg, Marie
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Higher insulin and lower glucagon levels in plasma and cerebrospinal fluid in suicide attempters compared to healthy controls2016In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 71, p. 26-26Article in journal (Other academic)
  • 13.
    Bendix, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Uvnas-Moberg, Kerstin
    Petersson, Maria
    Gustavsson, Petter
    Svanborg, Par
    Asberg, Marie
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Plasma oxytocin and personality traits in psychiatric outpatients2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 57, p. 102-110Article in journal (Refereed)
    Abstract [en]

    The oxytocin system is regarded as being of relevance for social interaction. In spite of this, very few studies have investigated the relationship between oxytocin and personality traits in clinical psychiatric populations. We assessed the relationship between personality traits and plasma oxytocin levels in a population of 101 medication-free psychiatric outpatients (men = 37, women = 64). We used the Karolinska Scale of Personality (KSP) and diagnostic and symptomatic testing. Plasma oxytocin levels were analysed with a specific radioimmunoassay at inclusion and after one month for testing of stability. Plasma oxytocin levels were stable over time and did not differ between patients with or without personality disorders, nor were they related to severity of depressive or anxiety symptoms. The KSP factors Impulsiveness and Negative Emotionality were significant independent predictors of plasma oxytocin. A subscale analysis of these personality factors showed significant positive correlations between baseline plasma oxytocin and the KSP subscales monotony avoidance and psychic anxiety. The significant association between the KSP factor Impulsiveness and oxytocin levels observed at baseline was observed also one month later in men. These findings suggest that personality traits such as Impulsiveness and Negative emotionality which are linked to social functioning in several psychiatric disorders seem to be associated with endogenous plasma oxytocin levels. These variations in oxytocin levels might have an impact on social sensitivity or social motivation with possible gender differences.

  • 14.
    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 Neuroscience/Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Corrigendum to "Insulin and glucagon in plasma and cerebrospinal fluid in suicide attempters and healthy controls" [Psychoneuroendocrinology 81 (2017) 1-7]2018In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 94, article id 168Article in journal (Refereed)
  • 15.
    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. 

  • 16.
    Bihlar Muld, Berit
    et al.
    SiS LVM Inst Horno, Enköping, Sweden. Karolinska Inst, Dept Womens & Childrens Hlth, Pediat Neuropsychiat Unit, Ctr Neurodev Disorders,Karolinska Inst KIND, SE-11330 Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Karolinska Inst, Dept Clin Neurosci, SE-11330 Stockholm, Sweden.
    Bölte, Sven
    Karolinska Inst, Dept Womens & Childrens Hlth, Pediat Neuropsychiat Unit, Ctr Neurodev Disorders,Karolinska Inst KIND, SE-11330 Stockholm, Sweden.
    Hirvikoski, Tatja
    Karolinska Inst, Dept Womens & Childrens Hlth, Pediat Neuropsychiat Unit, Ctr Neurodev Disorders,Karolinska Inst KIND, SE-11330 Stockholm, Sweden.
    Attention deficit/hyperactivity disorders with co-existing substance use disorder is characterized by early antisocial behaviour and poor cognitive skills2013In: BMC Psychiatry, E-ISSN 1471-244X, Vol. 13, p. 336-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) is associated with an increased risk of co-existing substance abuse. The Swedish legislation on compulsory healthcare can be applied to persons with severe substance abuse who can be treated involuntarily during a period of six months. This context enables a reliable clinical assessment of ADHD in individuals with severe substance use disorder (SUD).

    METHODS: In the context of compulsory care for individuals with severe SUD, male patients were assessed for ADHD, co-morbid psychiatric symptoms, psychosocial background, treatment history, and cognition. The data from the ADHD/SUD group (n = 60) was compared with data from (1) a group of individuals with severe substance abuse without known ADHD (SUD group, n = 120), as well as (2) a group with ADHD from an outpatient psychiatric clinic (ADHD/Psych group, n = 107).

    RESULTS: Compared to the general SUD group in compulsory care, the ADHD/SUD group had already been significantly more often in compulsory care during childhood or adolescence, as well as imprisoned more often as adults. The most common preferred abused substance in the ADHD/SUD group was stimulant drugs, while alcohol and benzodiazepine abuse was more usual in the general SUD group. Compared to the ADHD/Psych group, the ADHD/SUD group reported more ADHD symptoms during childhood and performed poorer on all tests of general intellectual ability and executive functions.

    CONCLUSIONS: The clinical characteristics of the ADHD/SUD group differed from those of both the SUD group and the ADHD/Psych group in several respects, indicating that ADHD in combination with SUD is a particularly disabling condition. The combination of severe substance abuse, poor general cognitive ability, severe psychosocial problems, including indications of antisocial behaviour, and other co-existing psychiatric conditions should be considered in treatment planning for adults with ADHD and SUD.

  • 17. Bihlar Muld, Berit
    et al.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bölte, Sven
    Hirvikoski, Tatja
    Long-term outcomes of pharmacologically treated versus non-treated adults with ADHD and substance use disorder: a naturalistic study2015In: Journal of Substance Abuse Treatment, ISSN 0740-5472, E-ISSN 1873-6483, Vol. 51, p. 82-90Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: The pharmacological treatment of individuals with attention deficit hyperactivity disorder (ADHD) and severe substance use disorder (SUD) is controversial, and few studies have examined the long-term psychosocial outcome of these treatments. Our aim was to investigate whether pharmacological treatment was associated with improved long-term psychosocial outcomes.

    METHODS: The present naturalistic study consisted of a long-term follow-up of 60 male patients with ADHD and comorbid severe SUD; all participants had received compulsory inpatient treatment due to severe substance abuse. The average interval between inpatient discharge and follow-up was 18.4months. Thirty patients had received pharmacological treatment for ADHD, and 30 patients were pharmacologically untreated. The groups were compared with respect to mortality and psychosocial outcomes operationalized as substance abuse status, ongoing voluntary rehabilitation, current housing situation and employment status.

    RESULTS: The groups were comparable with regard to the demographic and background characteristics. Overall, mortality was high; 8.3% of the participants had deceased at follow-up (one in the pharmacologically treated group and four in the untreated group; the between-group difference was not significant). The group that received pharmacological treatment for ADHD exhibited fewer substance abuse relapses, received more frequently voluntary treatments in accordance with a rehabilitation plan, required less frequent compulsory care, were more frequently accommodated in supportive housing or a rehabilitation center, and displayed a higher employment rate than the non-treated group.

    CONCLUSIONS: The recommendations for the close clinical monitoring of high-risk populations and the prevention of misuse and drug diversion were fulfilled in the structured environment of compulsory care for the treated group. Pharmacological treatment of ADHD in individuals with severe SUD may decrease the risk of relapse and increase these patients' ability to follow a non-pharmacological rehabilitation plan, thereby improving their long-term outcomes.

    Download full text (pdf)
    fulltext
  • 18. 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.

    Download full text (pdf)
    fulltext
  • 19. Bjureberg, Johan
    et al.
    Sahlin, Hanna
    Hedman-Lagerlöf, Erik
    Gratz, Kim L.
    Tull, Matthew T.
    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, Norra stationsgatan 69, SE-11364 Stockholm, Sweden.
    Hellner, Clara
    Ljótsson, Brjánn
    Extending research on Emotion Regulation Individual Therapy for Adolescents (ERITA) with nonsuicidal self-injury disorder: open pilot trial and mediation analysis of a novel online version2018In: BMC Psychiatry, E-ISSN 1471-244X, Vol. 18, article id 326Article in journal (Refereed)
    Abstract [en]

    Background: Nonsuicidal self-injury (NSSI) is common among adolescents and associated with negative outcomes. However, treatments developed specifically for NSSI and the proposed NSSI disorder (NSSID) are scarce, and access to empirically supported treatments for NSSI in many areas is limited. Online treatments carry the potential to increase the availability of evidence-based treatments. Emotion regulation individual therapy for adolescents (ERITA) has shown promise in the treatment of adolescents with NSSID.

    Method: The present study examined the feasibility, acceptability, and utility of an online version of ERITA. Twenty-five adolescents (aged 13-17) with NSSID and their parents were included in an uncontrolled open trial. Self-report and clinician-rated assessments of outcomes such as NSSI, self-destructive behaviors, emotion dysregulation, and global functioning were administered at pre-treatment, post-treatment, 3- and 6- month follow-up. Measures of NSSI, self-destructive behaviors, and emotion dysregulation were also assessed weekly during treatment.

    Results: Ratings of treatment credibility, expectancy, and satisfaction were acceptable, and the therapeutic alliance and treatment completion rate (96%) were high. Adolescent participation in the treatment was associated with a statistically significant increase in past-month NSSI abstinence (p = .007), large-sized improvements in past-month NSSI frequency (55% reduction, 95% confidence interval [CI]: 29, 72; Cohen's d = 0.88, 95% CI: 0.73, 1.06) and global functioning (d = 1.01, 95% CI: 0.77, 1.32), and medium-sized improvements in emotion dysregulation (d = 0.75, 95% CI: 0.59, 0.90) and NSSI versatility (d = 0.63, 95% CI: 0.54, 0.77) from pre- to post-treatment. These improvements were further strengthened at 3-month follow-up and maintained at 6-month follow-up. The online therapist-guided parent program was associated with small-to large-sized (ds = 0.47-1.22) improvements in adaptive parent behaviors, and these improvements were maintained or further improved upon at 6-month follow-up. Moreover, in line with the theoretical model underlying ERITA, change in emotion dysregulation mediated changes in both NSSI frequency and self-destructive behaviors over the course of treatment.

    Conclusions: Together, results suggest that online ERITA is an acceptable, feasible, and promising low-intensity treatment for adolescents with NSSID. The results of this open trial must be replicated in controlled studies.

    Download full text (pdf)
    fulltext
  • 20. Bjureberg, Johan
    et al.
    Sahlin, Hanna
    Hellner, Clara
    Hedman-Lagerlof, Erik
    Gratz, Kim L.
    Bjarehed, 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, Norra Stationsgatan 69, SE-11364 Stockholm, Sweden.
    Tull, Matthew T.
    Ljotsson, Brjann
    Emotion regulation individual therapy for adolescents with nonsuicidal self-injury disorder: a feasibility study2017In: BMC Psychiatry, E-ISSN 1471-244X, Vol. 17, article id 411Article in journal (Refereed)
    Abstract [en]

    Background: Nonsuicidal self-injury (NSSI) is a serious health risk behavior that forms the basis of a tentative diagnosis in DSM-5, NSSI Disorder (NSSID). To date, established treatments specific to NSSI or NSSID are scarce. As a first step in evaluating the feasibility, acceptability, and utility of a novel treatment for adolescents with NSSID, we conducted an open trial of emotion regulation individual therapy for adolescents (ERITA): a 12-week, behavioral treatment aimed at directly targeting both NSSI and its proposed underlying mechanism of emotion regulation difficulties.

    Methods: Seventeen girls (aged 13–17; mean = 15.31) with NSSID were enrolled in a study adopting an uncontrolled open trial design with self-report and clinician-rated assessments of NSSI and other self-destructive behaviors, emotion regulation difficulties, borderline personality features, and global functioning administered at pre-treatment, post-treatment, and 6-month follow-up. Measures of NSSI and emotion regulation difficulties were also administered weekly during treatment.

    Results: Ratings of treatment credibility and expectancy and the treatment completion rate (88%) were satisfactory, and both therapeutic alliance and treatment attendance were strong. Intent-to-treat analyses revealed significant improvements associated with large effect sizes in past-month NSSI frequency, emotion regulation difficulties, self-destructive behaviors, and global functioning, as well as a medium effect size in past-month NSSI versatility, from pre- to post-treatment. Further, all of these improvements were either maintained or further improved upon at 6-month follow-up. Finally, change in emotion regulation difficulties mediated improvements in NSSI over the course of treatment.

    Conclusions: Results suggest the acceptability, feasibility, and utility of this treatment for adolescents with NSSID.

    Download full text (pdf)
    fulltext
  • 21. Björkenstam, Charlotte
    et al.
    Tinghög, Petter
    Brenner, Philip
    Mittendorfer-Rutz, Ellenor
    Hillert, Jan
    Jokinen, Jussi
    Alexanderson, Kristina
    Is disability pension a risk indicator for future need of psychiatric healthcare or suicidal behavior among MS patients: a nationwide register study in Sweden?2015In: BMC Psychiatry, E-ISSN 1471-244X, Vol. 15, article id 286Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mental disorders and suicidal behavior are common in patients with multiple sclerosis (MS), they also carry a higher risk of disability pension (DP). Our aim was to investigate if DP and other factors are associated with psychiatric disorders and suicidal behavior among MS patients, and whether DP is a stronger risk indicator among certain groups.

    METHOD: A prospective population-based cohort study with six-year follow-up (2005-2010), including 11 346 MS patients who in 2004 were aged 16-64 and lived in Sweden. Incidence rate ratios (IRR) with 95 % confidence intervals (CI) were calculated.

    RESULTS: MS patients on DP had a modestly higher risk of requiring psychiatric healthcare, IRR: 1.36 (95 % CI: 1.18-1.58). MS patients with previous psychiatric healthcare had a higher IRR for both psychiatric healthcare and suicidal behavior; 2.32 (2.18-2.47) and 1.91 (1.59-2.30), respectively. DP moderated the association between sex and psychiatric healthcare, where women on DP displayed higher risk than men, X(2) 4.74 (p = 0.03).

    CONCLUSION: The findings suggest that losing one's role in work life aggravates rather than alleviates the burden of MS, as MS patients on DP seem to have a higher need for psychiatric healthcare, especially among women; which calls for extra awareness among clinicians.

  • 22. 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.

    Download full text (pdf)
    fulltext
  • 23.
    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.

    Download full text (pdf)
    fulltext
  • 24.
    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.

    Download full text (pdf)
    fulltext
  • 25.
    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.

    Download full text (pdf)
    fulltext
  • 26.
    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.

    Download full text (pdf)
    fulltext
  • 27. Brenner, P.
    et al.
    Burkill, S.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm.
    Hillert, J.
    Bahmanyar, S.
    Montgomery, S.
    Multiple sclerosis and risk of attempted and completed suicide - a cohort study2016In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 23, no 8, p. 1329-1336Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Patients with multiple sclerosis (MS) are known to have an elevated suicide risk, but attempted suicide is incompletely investigated. The relation between education level and suicidality has not been investigated in MS patients. Our objective was to estimate attempted suicide and completed suicide risks amongst MS patients.

    Methods: A total of 29 617 Swedish MS patients were identified through the Swedish Patient Register and matched with 296 164 people without MS from the general population. Cox regression analysis estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of MS with attempted and completed suicide, with adjustment for age, sex, education and calendar period.

    Results: The adjusted HR for attempted suicide amongst MS patients is 2.18 (95% CI 1.97-2.43) compared with the general population cohort. For completed suicide the HR is 1.87 (95% CI 1.53-2.30). In both groups women are at higher risk of attempting suicide, whilst men are at higher risk of completing suicide. Education level is inversely associated with completed suicide amongst the non-MS cohort (0.68, 0.51-0.91), but not amongst MS patients (1.10, 0.60-2.04).

    Conclusion: Multiple sclerosis patients are at higher risk of both attempted and completed suicide. No evidence was found of an inverse association between educational level and risk of completed suicide amongst MS patients.

  • 28. Brenner, P.
    et al.
    Burkill, S.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Moore, A.
    Geissbuehler, Y.
    Hillert, J.
    Bahmanyar, S.
    Montgomery, S.
    Multiple sclerosis and risk of completed and attempted suicide - a national cohort study2015In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, p. 23-24Article in journal (Other academic)
  • 29.
    Brenner, Philip
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Alexanderson, Kristina
    Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden .
    Björkenstam, Charlotte
    Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden .
    Hillert, Jan
    Division of Neuro, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Mittendorfer-Rutz, Ellenor
    Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Tinghög, Petter
    Division of Insurance Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Psychiatric diagnoses, medication and risk for disability pension in multiple sclerosis patients: a population-based register study2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 8, p. e104165-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Psychiatric comorbidity is common among multiple sclerosis (MS) patients. The majority of MS patients of working ages are on disability pension. The aims of this study were to chart the prevalences of psychiatric diagnoses and medications among MS patients of working ages, and to investigate their association with the risk for future disability pension.

    METHODS: This nationwide, population-based prospective cohort study includes 10,750 MS patients and 5,553,141 non-MS individuals who in 2005 were aged 17-64 years. Psychiatric diagnoses and medications were identified using nationwide registers. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated adjusting for socio-demographics. Furthermore, a survival analysis with five-year follow-up was performed among the 4,571 MS patients not on disability pension in 2005, with psychiatric diagnoses and medication as risk factors, and disability pension as the outcome.

    RESULTS: Among MS patients, 35% had been prescribed psychiatric medication compared to 10% of non-MS individuals, adjusted OR 3.72 (95% CI 3.57 to 3.88). Ten percent of MS patients had received a psychiatric diagnosis, compared to 5.7% of non-MS individuals, OR 1.82 (95% CI 1.71 to 1.94). Serotonin reuptake inhibitors (SSRIs), were the most commonly prescribed drugs (17%) among MS patients, while depression (4.8%) was the most common psychiatric diagnosis. In the survival analysis, MS patients with any psychiatric diagnosis had a hazard ratio (HR) of 1.83 (95% CI 1.53 to 2.18) for disability pension compared to other MS patients. MS patients with any psychiatric drug prescription had a HR for disability pension of 2.09 (95% CI 1.84 to 2.33).

    CONCLUSION: Psychiatric diagnoses and medications are common among MS patients and adversely affect risk for disability pension. This highlights the importance of correct diagnosis and management of psychiatric comorbidity, in a clinical as well as in a societal perspective.

  • 30. Brenner, Philip
    et al.
    Granqvist, Mathias
    Königsson, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Al Nimer, Faiez
    Piehl, Fredrik
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Depression and fatigue in multiple sclerosis: Relation to exposure to violence and cerebrospinal fluid immunomarkers2018In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 89, p. 53-58Article in journal (Refereed)
    Abstract [en]

    Multiple sclerosis (MS) is a neuroinflammatory condition characterized by chronic dysregulation of immune responses leading to repeated episodes of inflammation in the central nervous system. Depression and fatigue are common among MS patients, even in early disease phases, and the disease course can be negatively affected by stressful events. IL-6 and IL-8 have been associated with depression and stressful life events in non-MS patients. The aim of this study was to examine the relationships between depression, fatigue, and exposure to violence, with IL-6 and IL-8 levels in the cerebrospinal fluid (CSF) of MS patients. Levels of IL-6 and -8 were analyzed in the CSF of 47 patients with relapsing-remitting MS. Correlations between IL-6 and IL-8 levels and self-rated depression and fatigue symptoms, as well as clinician-rated history of being exposed to interpersonal violence, were analyzed with correction for age, sex and MS disability status. IL-6 correlated significantly (p < 0.05) with depressive symptoms (adjusted Spearman’s ρ = 0.39), fatigue (ρ = 0.39), and exposure to violence in adult life (ρ = 0.35). Depression correlated with both fatigue and being exposed to violence. Associations were not present among patients exposed to disease modifying drugs. In exploratory analyses, the relationship between exposure to violence and IL-6 was non-significant when controlled for depression. Further research should focus on replication of these results, as well as exploring the impact of stressful life events on immune regulation and the clinical characteristics and prognosis of MS patients.

  • 31. Brenner, Philip
    et al.
    Mittendorfer-Rutz, Ellenor
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, Center for Psychiatry Research, Karolinska Universitetssjukhuset R5:00, 171 77 Stockholm, Sweden.
    Alexanderson, Kristina
    Hillert, Jan
    Tinghog, Petter
    Prescribed psychiatric medication among multiple sclerosis patients before and after disability pension: a register study with matched controls2016In: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 51, no 7, p. 1047-1054Article in journal (Refereed)
    Abstract [en]

    Many multiple sclerosis (MS) patients of working ages have psychiatric comorbidity, and 60 % are on disability pension (DP). It is unknown how DP is associated with MS patients' mental health. The objective of this study was to investigate the association between prescriptions of psychiatric medication and time before and after receiving full-time DP in MS patients compared with matched controls. Nationwide Swedish registers were used to identify 3836 MS patients who were granted DP in 2000-2012 and 19,180 DP controls matched on socio-demographic variables by propensity scores. Patients and controls were organized in groups by year granted DP. Adjusted odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated for being prescribed selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, or sleeping agents in 2006. Both patients and controls, who were not yet on DP in the study year of 2006, had lower OR compared with those who were granted DP in the same year. The OR increased when being closer to DP. MS patients, who had been granted DP 5-6 years earlier, had a higher risk for prescription of benzodiazepines (OR 1.72; 95 % CI 1.16-2.57) than controls (OR 1.14; 95 % CI 1.14-1.18). These patients also had a higher risk for SSRI prescription when compared directly with controls (OR 1.76; 95 % CI 1.44-2.15). MS patients have substantially higher odds ratios for being prescribed psychiatric drugs after DP than other disability pensioners. Further research on the association of DP with the mental health of MS patients is warranted.

  • 32. 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.

  • 33. Budhiraja, Meenal
    et al.
    Savic, Ivanka
    Lindner, Philip
    Jokinen, Jussi
    Tiihonen, Jari
    Hodgins, Sheilagh
    Brain structure abnormalities in young women who presented conduct disorder in childhood/adolescence2017In: Cognitive, Affective, & Behavioral Neuroscience, ISSN 1530-7026, E-ISSN 1531-135X, Vol. 17, no 4, p. 869-885Article in journal (Refereed)
    Abstract [en]

    The phenotype and genotype of antisocial behavior among females are different from those among males. Previous studies have documented structural brain alterations in males with antisocial behavior, yet little is known about the neural correlates of female antisocial behavior. The present study examined young women who had presented conduct disorder (CDW) prior to age 15 to determine whether brain abnormalities are present in adulthood and whether the observed abnormalities are associated with comorbid disorders or maltreatment that typically characterize this population. Using magnetic resonance imaging and voxel-based morphometry, we compared gray matter volumes (GMV) of 31 women who presented CD by midadolescence and 25 healthy women (HW), age, on average, 23 years. Participants completed structured, validated interviews to diagnose mental disorders, and validated questionnaires to document physical and sexual abuse. Relative to HW, CDW presented increased GMV in the left superior temporal gyrus that was associated with past alcohol and drug dependence, current use of alcohol and drugs, and current anxiety and depression symptoms and maltreatment. Additionally, CDW displayed reduced GMV in lingual gyrus, hippocampus, and anterior cingulate cortex that was associated with past comorbid disorders, current alcohol and drugs use, current anxiety and depression symptoms, and maltreatment. The CDW also presented reduced total GMV that was associated with past comorbid disorders and current anxiety/depression symptoms. Alterations of brain structure were observed among young adult females with prior CD, relative to HW, all of which were associated with internalizing and externalizing disorders and maltreatment that typically accompany CD.

  • 34.
    Carlborg, Andreas
    et al.
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden.
    Jokinen, Jussi
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden.
    Jönsson, Erik G
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden.
    Erhardt, Sophie
    Department of Physiology and Pharmacology, Karolinska Insitutet, Stockholm, Sweden.
    Nordström, Peter
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden.
    CSF kynurenic acid and suicide risk in schizophrenia spectrum psychosis2013In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 205, no 1-2, p. 165-7Article in journal (Refereed)
    Abstract [en]

    Relationships between concentrations of cerebrospinal fluid (CSF) kynurenic acid (KYNA) and suicidal behavior were evaluated in 59 patients with psychosis after 22 years of follow-up. Three patients died from suicide and nine patients had a history of attempted suicide. Patients with attempted suicide had significantly lower concentrations of CSF KYNA.

  • 35.
    Carlborg, Andreas
    et al.
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, Solna, Sweden.
    Jokinen, Jussi
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, Solna, Sweden.
    Nordström, Anna-Lena
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, Solna, Sweden.
    Jönsson, Erik G
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, Solna, Sweden.
    Nordström, Peter
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, Solna, Sweden.
    Attempted suicide predicts suicide risk in schizophrenia spectrum psychosis2010In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 64, no 1, p. 68-72Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: People with schizophrenia have an increased risk of suicide and attempted suicide is suggested to be an important risk factor.

    AIM: Our objective was to assess the cumulative survival, predictive values and odds ratios of attempted suicide for suicide in a long-term cohort of patients with schizophrenia spectrum psychosis with and without previous attempted suicide.

    METHOD: Inpatients (n=224) hospitalized with schizophrenia spectrum psychosis were followed for a mean of 25 years. All patients were followed up for causes of death. Information on suicide attempt before the end of the observation period was retrieved from medical records.

    RESULTS: Eight percent died by suicide during the follow-up. Eighteen percent of suicide attempters died by suicide. Two percent of non-attempters died by suicide. There was a strong association between previous suicide attempt and suicide in men and women. Odds ratio for attempters vs. non-attempters was 10. Suicide risk was almost three times higher in male than female suicide attempters.

    CONCLUSION: Previous attempted suicide is an important risk factor for suicide in both men and women with schizophrenia spectrum psychosis, particularly in male suicide attempters. The suicide risk remains high over a long period. Continuous assessment of risk factors and appropriate treatment are crucial for this patient group to prevent suicide.

  • 36.
    Carlborg, Andreas
    et al.
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, Solna, Sweden.
    Jokinen, Jussi
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, Solna, Sweden.
    Nordström, Anna-Lena
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, Solna, Sweden.
    Jönsson, Erik G
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, Solna, Sweden.
    Nordström, Peter
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, Solna, Sweden.
    Early death and CSF monoamine metabolites in schizophrenia spectrum psychosis2011In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 65, no 2, p. 101-5Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Patients with schizophrenia have higher rates of mortality than the general population. Lower concentrations of the cerebrospinal fluid (CSF) monoamine metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) have been associated with suicidal, aggressive and impulsive behavior. Mortality has been suggested as a measure of impulsivity and a relationship between early death and lower concentrations of CSF monoamine metabolites has been reported but the studies are few with short periods of follow-up and small numbers.

    AIM: The objective of this study was to investigate a relationship between early death and concentrations of CSF 5-HIAA and HVA.

    METHODS: Three hundred and eighty-five inpatients with schizophrenia spectrum psychosis were lumbar punctured in a standardized manner and followed for a median of 26 years. Patients were searched to identify those who had died. Causes of death were obtained from the Causes of Death Register.

    RESULTS: During the time of follow-up, 97 patients died. Schizophrenia spectrum psychosis patients died at an earlier age from both natural and unnatural causes of death. No significant associations were found between CSF 5-HIAA and HVA concentrations and non-suicidal death. Attempted suicide was not a risk factor for non-suicidal death at younger age.

    CONCLUSION: Patients with schizophrenia spectrum psychosis die at an earlier age from both natural and unnatural causes of death. Attempted suicide is not a risk factor for non-suicidal death at younger age. Low concentrations of CSF HVA and 5-HIAA were not a risk factor for non-suicidal death at younger age in schizophrenia spectrum psychosis.

  • 37.
    Carlborg, Andreas
    et al.
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, S-17176 Stockholm, Sweden.
    Winnerbäck, Kajsa
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, S-17176 Stockholm, Sweden.
    Jönsson, Erik G
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, S-17176 Stockholm, Sweden.
    Jokinen, Jussi
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, S-17176 Stockholm, Sweden.
    Nordström, Peter
    Karolinska Inst, Dept Clin Neurosci, Karolinska Univ Hosp, S-17176 Stockholm, Sweden.
    Suicide in schizophrenia2010In: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 10, no 7, p. 1153-64Article, review/survey (Refereed)
    Abstract [en]

    Schizophrenia is a disorder with an estimated suicide risk of 4-5%. Many factors are involved in the suicidal process, some of which are different from those in the general population. Clinical risk factors include attempted suicide, depression, male gender, substance abuse and hopelessness. Biosocial factors, such as a high intelligence quotient and high level of premorbid function, have also been associated with an increased risk of suicide in patients with schizophrenia. Suicide risk is especially high during the first year after diagnosis. Many of the suicides occur during hospital admission or soon after discharge. Management of suicide risk includes both medical treatment and psychosocial interventions. Still, risk factors are crude; efforts to predict individual suicides have not proved useful and more research is needed.

  • 38.
    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)
  • 39. Chatzittofis, Andreas
    et al.
    Arver, Stefan
    Öberg, Katarina
    Hallberg, Jonas
    Nordström, Peter
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    HPA axis dysregulation in men with hypersexual disorder2016In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 63, p. 247-253Article in journal (Refereed)
    Abstract [en]

    Hypersexual disorder integrating pathophysiological aspects such as sexual desire deregulation, sexual addiction, impulsivity and compulsivity was suggested as a diagnosis for the DSM-5. However, little is known about the neurobiology behind this disorder. A dysregulation of the hypothalamic pituitary adrenal (HPA) axis has been shown in psychiatric disorders but has not been investigated in hypersexual disorder. The aim of this study was to investigate the function of the HPA axis in hypersexual disorder. The study includes 67 male patients with hypersexual disorder and 39 healthy male volunteers. Basal morning plasma levels of cortisol and ACTH were assessed and low dose (0.5 mg) dexamethasone suppression test was performed with cortisol and ACTH measured post dexamethasone administration. Non-suppression status was defined with DST-cortisol levels >= 138 nmol/l. The Sexual Compulsive scale (SCS), Hypersexual disorder current assessment scale (HD:CAS), Montgomery-Asberg Depression Scale-self rating (MADRS-S) and Childhood trauma questionnaire (CTQ), were used for assessing hypersexual behavior, depression severity and early life adversity. Patients with hypersexual disorder were significantly more often DST non-suppressors and had significantly higher DST-ACTH levels compared to healthy volunteers. The patients reported significantly more childhood trauma and depression symptoms compared to healthy volunteers. CTQ scores showed a significant negative correlation with DST-ACTH whereas SCS and HD:CAS scores showed a negative correlation with baseline cortisol in patients. The diagnosis of hypersexual disorder was significantly associated DST non-suppression and higher plasma DST-ACTH even when adjusted for childhood trauma. The results suggest HPA axis dysregulation in male patients with hypersexual disorder.

  • 40. Chatzittofis, Andreas
    et al.
    Arver, Stefan
    Öberg, Katarina
    Hallberg, Jonas
    Nordström, Peter
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    HPA axis dysregulation in patients with hypersexual disorder2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 61, p. 53-53Article in journal (Other academic)
  • 41.
    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.

    Download full text (pdf)
    fulltext
  • 42.
    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.

    Download full text (pdf)
    fulltext
  • 43.
    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.

    Download full text (pdf)
    fulltext
  • 44.
    Chatzittofis, Andreas
    et al.
    Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    Nordström, Peter
    Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    Hellström, Christer
    Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    Arver, Stefan
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Sweden.
    Åsberg, Marie
    Department of Clinical Sciences, Karolinska Institutet, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    CSF 5-HIAA, cortisol and DHEAS levels in suicide attempters2013In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 23, no 10, p. 1280-7Article in journal (Refereed)
    Abstract [en]

    The serotonin system and the hypothalamic-pituitary-adrenal (HPA) axis are involved in the biological vulnerability to suicidal behaviour. Altered levels of dehydroepiandrosterone (DHEA) and its sulphate ester DHEAS have been reported in neuropsychiatric conditions. The aim of this study was to investigate CSF levels of 5-Hydroxyindoleacetic acid (5-HIAA) and CSF and plasma levels of cortisol and DHEAS in 28 medication free suicide attempters and 19 healthy volunteers. Another aim was to investigate the relationship between neuroendocrine measures and childhood trauma in suicide attempters. As the study design includes a longitudinal part, we investigated whether CSF cortisol, 5-HIAA or DHEAS would predict subsequent suicide. We hypothesized higher cortisol levels in suicide attempters and lower CSF 5-HIAA levels and higher cortisol levels in suicide victims. Suicide attempters had higher CSF and plasma cortisol levels compared to healthy volunteers. Male suicide attempters had higher CSF DHEAS levels and female suicide attempters had lower CSF 5-HIAA levels compared to male and female healthy volunteers respectively. Exposure to interpersonal violence as a child showed a negative correlation with CSF cortisol/DHEAS ratio adjusted for age, gender and depression severity in a regression analysis. Suicide victims tended to have low CSF 5-HIAA and high CSF cortisol. Abused suicide victims had higher CSF cortisol compared to suicide victims with low exposure to interpersonal violence as a child. The results underlie the important role of the serotonergic system and HPA axis in suicidal behaviour and suggest that CSF DHEAS may be elevated in male suicide attempters.

  • 45.
    Chatzittofis, Andreas
    et al.
    Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    Nordström, Peter
    Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    Uvnäs-Moberg, Kerstin
    Department of Animal Environment and Health, Swedish University of Agriculture, Skara, Sweden.
    Åsberg, Marie
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    CSF and plasma oxytocin levels in suicide attempters, the role of childhood trauma and revictimization2014In: Neuro - endocrinology letters, ISSN 0172-780X, Vol. 35, no 3, p. 213-217Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Some studies have reported an inverse relationship between childhood adversity and oxytocin levels. The purpose of this study was to assess the relationship between CSF and plasma oxytocin levels and lifetime trauma history in suicide attempters. We hypothesised lower CSF and plasma oxytocin levels in suicide attempters with high exposure to interpersonal violence and negative childhood emotional climate.

    METHODS: 28 medication free suicide attempters participated in the study. CSF and plasma morning basal levels of oxytocin were assessed with specific radio-immunoassays. The Karolinska Interpersonal Violence Scale (KIVS) was used to elicit lifetime trauma history and revictimization status and the childhood emotional climate factor was derived from the socialization subscale of the Karolinska Scales of Personality.

    RESULTS: Correlations between exposure to interpersonal violence as a child and as an adult and CSF and plasma oxytocin levels were not significant. Revictimized suicide attempters had significantly lower plasma oxytocin levels and more negative childhood emotional climate compared to non-revictimized suicide attempters.

    CONCLUSIONS: Our results indicate a complex relationship between life time trauma and the oxytocin system.

  • 46. Chatzittofis, Andreas
    et al.
    Savard, Josephine
    Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Arver, Stefan
    Görts Öberg, Katarina
    Hallberg, Jonas
    Nordström, Peter
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men2017In: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 6, no 2, p. 187-193Article in journal (Refereed)
    Abstract [en]

    Background and aims: There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods: This case-control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire-Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery-Asberg Depression Rating Scale - Self-rating. Results: Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion: Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion: Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men.

    Download full text (pdf)
    fulltext
  • 47. 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.

    Download full text (pdf)
    fulltext
  • 48. 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)
  • 49.
    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.

    Download full text (pdf)
    fulltext
  • 50. Forsell, Erik
    et al.
    Bendix, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Holländare, Fredrik
    Szymanska von Schultz, Barbara
    Nasiell, Josefine
    Blomdahl-Wetterholm, Margareta
    Eriksson, Caroline
    Kvarned, Sara
    Lindau van der Linden, Johanna
    Söderberg, Elin
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Sweden.
    Wide, Katarina
    Kaldo, Viktor
    Internet delivered cognitive behavior therapy for antenatal depression: A randomised controlled trial2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 221, p. 56-64Article in journal (Refereed)
    Abstract [en]

    Major depression occurs in 5-10% of pregnancies and is associated with many negative effects for mother and child, yet treatment options are scarce. To our knowledge, this is the first published randomised controlled trial on Internet delivered Cognitive Behavior Therapy (ICBT) for this group.

    Objective: To test the efficacy of a pregnancy adapted version of an existing 10-week ICBT-program for depression as well as assessing acceptability and adherence.

    Design: Randomised controlled trial.

    Setting: Online and telephone.

    Population or sample: Self-referred pregnant women (gestational week 10-28 at intake) currently suffering from major depressive disorder.

    Methods: 42 pregnant women (gestational week 12-28) with major depression were randomised to either treatment as usual (TAU) provided at their antenatal clinic or to ICBT as an add-on to usual care.

    Main outcome measures: The primary outcome was depressive symptoms measured with the Montgomery-Asberg depression rating scale-self report (MADRS-S). The Edinburgh Postnatal Depression Scale and measures of anxiety and sleep were used. Credibility, satisfaction, adherence and utilization were also assessed.

    Results: The ICBT group had significantly lower levels of depressive symptoms post treatment (p < 0.001, Hedges g = 1.21) and were more likely to be responders (i.e. achieve a statistically reliable improvement) (RR = 0.36; p = 0.004). Measures of treatment credibility, satisfaction, utilization, and adherence were comparable to implemented ICBT for depression.

    Limitations: Small sample size and no long-term evaluation.

    Conclusion: Pregnancy adapted ICBT for antenatal depression is feasible, acceptable and efficacious. These results need to be replicated in larger trials to validate these promising findings.

    Download full text (pdf)
    fulltext
123 1 - 50 of 136
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf