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  • 1. Aeinehband, Shahin
    et al.
    Brenner, Philip
    Stahl, Sara
    Bhat, Maria
    Fidock, Mark D.
    Khademi, Mohsen
    Olsson, Tomas
    Engberg, Goran
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Erhardt, Sophie
    Piehl, Fredrik
    Cerebrospinal fluid kynurenines in multiple sclerosis: relation to disease course and neurocognitive symptoms2016Inngår i: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 51, s. 47-55Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 2.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Karolinska Inst, Dept Clin Neurosci Psychiat, Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
    Cholesterol and CSF 5-HIAA in attempted suicide2010Inngår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 125, nr 1-3, s. 388-92Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 3.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
    Cholesterol and the "Cycle of Violence" in attempted suicide2014Inngår i: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 215, nr 3, s. 646-50Artikkel i tidsskrift (Fagfellevurdert)
    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".

  • 4.
    Asellus, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nordström, Peter
    Nordström, Anna-Lena
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Neuroscience, Karolinska Institutet, R5, Karolinska University Hospital/Solna, Stockholm, Sweden.
    CSF Apolipoprotein E in attempted suicide2018Inngår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 225, s. 246-249Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 5. Asellus, Peter
    et al.
    Nordström, Peter
    Nordström, Anna-Lena
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, R5, Karolinska University Hospital/Solna.
    Plasma apolipoprotein E and severity of suicidal behaviour2016Inngår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 190, s. 137-142Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 6.
    Bendix, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Neuroscience / Centre for Psychiatry Research & Stockholm Health Care Services, Stockholm County Council, Karolinska Institutet, Stockholm, Sweden.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wihlbäck, Anna-Carin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Ahokas, Antti
    Mehiläinen Clinic, Helsinki, Finland .
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 findings2019Inngår i: Neurology, psychiatry and brain research, ISSN 0941-9500, Vol. 34, s. 50-57Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 7.
    Bendix, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Uvnas-Moberg, Kerstin
    Petersson, Maria
    Asberg, Marie
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap. 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 controls2016Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 71, s. 26-26Artikkel i tidsskrift (Annet vitenskapelig)
  • 8.
    Bendix, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Uvnas-Moberg, Kerstin
    Petersson, Maria
    Gustavsson, Petter
    Svanborg, Par
    Asberg, Marie
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Plasma oxytocin and personality traits in psychiatric outpatients2015Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 57, s. 102-110Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 9.
    Bendix, Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Uvnäs-Moberg, Kerstin
    Petersson, Maria
    Kaldo, Viktor
    Åsberg, Marie
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Insulin and glucagon in plasma and cerebrospinal fluid in suicide attempters and healthy controls2017Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 81, s. 1-7Artikkel i tidsskrift (Fagfellevurdert)
    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. 

  • 10.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 skills2013Inngår i: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 13, s. 336-Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 11. Bihlar Muld, Berit
    et al.
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Bölte, Sven
    Hirvikoski, Tatja
    Long-term outcomes of pharmacologically treated versus non-treated adults with ADHD and substance use disorder: a naturalistic study2015Inngår i: Journal of Substance Abuse Treatment, ISSN 0740-5472, E-ISSN 1873-6483, Vol. 51, s. 82-90Artikkel i tidsskrift (Fagfellevurdert)
    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.

    Fulltekst (pdf)
    fulltext
  • 12. Bjureberg, Johan
    et al.
    Ohlis, Anna
    Ljotsson, Brjann
    D'Onofrio, Brian M.
    Hedman-Lagerlöf, Erik
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 register2019Inngår i: Journal of Child Psychology and Psychiatry and Allied Disciplines, ISSN 0021-9630, E-ISSN 1469-7610, Vol. 60, nr 3, s. 295-304Artikkel i tidsskrift (Fagfellevurdert)
    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.

    Fulltekst (pdf)
    fulltext
  • 13. Bjureberg, Johan
    et al.
    Sahlin, Hanna
    Hedman-Lagerlöf, Erik
    Gratz, Kim L.
    Tull, Matthew T.
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 version2018Inngår i: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 18, artikkel-id 326Artikkel i tidsskrift (Fagfellevurdert)
    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.

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  • 14. Bjureberg, Johan
    et al.
    Sahlin, Hanna
    Hellner, Clara
    Hedman-Lagerlof, Erik
    Gratz, Kim L.
    Bjarehed, Jonas
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 study2017Inngår i: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 17, artikkel-id 411Artikkel i tidsskrift (Fagfellevurdert)
    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.

    Fulltekst (pdf)
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  • 15. 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?2015Inngår i: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 15, artikkel-id 286Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 16. Bostrom, Adrian E.
    et al.
    Chatzittofis, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 genes2019Inngår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308Artikkel i tidsskrift (Fagfellevurdert)
    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,p(FDR) = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, p(FDR) = 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.

    Fulltekst (pdf)
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  • 17. Brenner, P.
    et al.
    Burkill, S.
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 study2016Inngår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 23, nr 8, s. 1329-1336Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 18. Brenner, P.
    et al.
    Burkill, S.
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap. 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 study2015Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, s. 23-24Artikkel i tidsskrift (Annet vitenskapelig)
  • 19.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 study2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 8, s. e104165-Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 20. Brenner, Philip
    et al.
    Granqvist, Mathias
    Königsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Al Nimer, Faiez
    Piehl, Fredrik
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 immunomarkers2018Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 89, s. 53-58Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 21. Brenner, Philip
    et al.
    Mittendorfer-Rutz, Ellenor
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 controls2016Inngår i: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 51, nr 7, s. 1047-1054Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 22. Budhiraja, Meenal
    et al.
    Pereira, Joana B.
    Lindner, Philip
    Westman, Eric
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 152019Inngår i: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 289, s. 37-44Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 23. 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/adolescence2017Inngår i: Cognitive, Affective, & Behavioral Neuroscience, ISSN 1530-7026, E-ISSN 1531-135X, Vol. 17, nr 4, s. 869-885Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 24.
    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 psychosis2013Inngår i: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 205, nr 1-2, s. 165-7Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 25.
    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 psychosis2010Inngår i: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 64, nr 1, s. 68-72Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 26.
    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 psychosis2011Inngår i: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 65, nr 2, s. 101-5Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 27.
    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 schizophrenia2010Inngår i: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 10, nr 7, s. 1153-64Artikkel, forskningsoversikt (Fagfellevurdert)
    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.

  • 28.
    Chatzittofis, A.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Boström, A.
    Öberg, K.
    Flanagan, J.
    Schioth, H.
    Arver, S.
    Jokinen, J.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Testosterone, luteinizing hormone levels and methylation status in men with hypersexual disorders2019Inngår i: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, s. S135-S135Artikkel i tidsskrift (Annet vitenskapelig)
  • 29. Chatzittofis, Andreas
    et al.
    Arver, Stefan
    Öberg, Katarina
    Hallberg, Jonas
    Nordström, Peter
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    HPA axis dysregulation in men with hypersexual disorder2016Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 63, s. 247-253Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 30. Chatzittofis, Andreas
    et al.
    Arver, Stefan
    Öberg, Katarina
    Hallberg, Jonas
    Nordström, Peter
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    HPA axis dysregulation in patients with hypersexual disorder2015Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 61, s. 53-53Artikkel i tidsskrift (Annet vitenskapelig)
  • 31.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 attempters2013Inngår i: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 23, nr 10, s. 1280-7Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 32.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 revictimization2014Inngår i: Neuro - endocrinology letters, ISSN 0172-780X, Vol. 35, nr 3, s. 213-217Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 33. Chatzittofis, Andreas
    et al.
    Savard, Josephine
    Arver, Stefan
    Görts Öberg, Katarina
    Hallberg, Jonas
    Nordström, Peter
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men2017Inngår i: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 6, nr 2, s. 187-193Artikkel i tidsskrift (Fagfellevurdert)
    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.

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  • 34. Ehlert, Ulrike
    et al.
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 life2019Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 107, s. 67-67Artikkel i tidsskrift (Annet vitenskapelig)
  • 35. Forsell, Erik
    et al.
    Bendix, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    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 universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. 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 trial2017Inngår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 221, s. 56-64Artikkel i tidsskrift (Fagfellevurdert)
    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.

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  • 36. Haglund, Axel
    et al.
    Lindh, Asa U.
    Lysell, Henrik
    Renberg, Ellinor Salander
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Waern, Margda
    Runeson, Bo
    Interpersonal violence and the prediction of short-term risk of repeat suicide attempt2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikkel-id 36892Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this multi-center cohort study, suicide attempters presenting to hospital (N = 355, 63% women) were interviewed using the Karolinska Interpersonal Violence Scale (KIVS) and followed-up by medical record review. Main outcome was non-fatal or fatal repeat suicide attempt within six months. Also, repeat attempt using a violent method was used as an additional outcome in separate analyses. Data were analyzed for the total group and for men and women separately. Repeat attempts were observed within six months in 78 persons (22%) and 21 (6%) of these used a violent method. KIVS total score of 6 or more was associated with repeat suicide attempt within six months (OR = 1.81, CI 1.08-3.02) and predicted new attempts with a sensitivity of 62% and a specificity of 53%. A three-fold increase in odds ratio was observed for repeat attempt using a violent method (OR = 3.40, CI 1.22-9.49). An association between exposure to violence in adulthood and violent reattempt was seen in women (OR = 1.38, CI 1.06-1.82). The overall conclusions are that information about interpersonal violence may help predict short-term risk for repeat suicide attempt, and that structured assessment of interpersonal violence may be of value in risk assessment after attempted suicide.

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  • 37. Haglund, Axel
    et al.
    Tidemalm, Dag
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Långström, Niklas
    Lichtenstein, Paul
    Fazel, Seena
    Runeson, Bo
    Suicide after release from prison: a population-based cohort study from Sweden2014Inngår i: Journal of Clinical Psychiatry, ISSN 0160-6689, E-ISSN 1555-2101, Vol. 75, nr 10, s. 1047-53Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Released prisoners have high suicide rates compared with the general population, but little is known about risk factors and possible causal pathways. We conducted a population-based cohort study to investigate rates and risk factors for suicide in people previously imprisoned.

    METHOD: We identified individuals released from prison in Sweden between January 1, 2005, and December 31, 2009, through linkage of national population-based registers. Released prisoners were followed from the day of release until death, emigration, new incarceration, or December 31, 2009. Survival analyses were conducted to compare incidence rates and psychiatric morbidity with nonconvicted population controls matched on gender and year of birth.

    RESULTS: We identified 38,995 releases among 26,985 prisoners (7.6% female) during 2005-2009. Overall, 127 suicides occurred, accounting for 14% of all deaths after release (n = 920). The mean suicide rate was 204 per 100,000 person-years, yielding an incidence rate ratio of 18.2 (95% CI, 13.9-23.8) compared with general population controls. Previous substance use disorder (hazard ratio [HR] = 2.1; 95% CI, 1.4-3.2), suicide attempt (HR = 2.5; 95% CI, 1.7-3.7), and being born in Sweden versus abroad (HR = 2.1; 95% CI, 1.2-3.6) were independent risk factors for suicide after release.

    CONCLUSIONS: Released prisoners are at high suicide risk and have a slightly different pattern of psychiatric risk factors for suicide compared with the general population. Results suggest appropriate allocation of resources to facilitate transition to life outside prison and increased attention to prisoners with both a previous suicide attempt and substance use disorder.

  • 38. Hallberg, Jonas
    et al.
    Kaldo, Viktor
    Arver, Stefan
    Dhejne, Cecilia
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Oberg, Katarina Gorts
    A Randomized Controlled Study of Group-Administered Cognitive Behavioral Therapy for Hypersexual Disorder in Men2019Inngår i: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 16, nr 5, s. 733-745Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

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

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

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

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

  • 39.
    Hirvikoski, T
    et al.
    Karolinska Inst, Dept Mol Med, Stockholm, Sweden.
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Personality traits in attempted and completed suicide2012Inngår i: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 27, nr 7, s. 536-41Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Though widely used in clinical and biological studies, no investigation of the factor structure of the Karolinska Scales of Personality (KSP) has been performed in suicide attempters. There are very few studies of personality traits in suicide completers. The aim of the present study was to assess the factor structure of KSP in suicide attempters. A secondary aim was to examine whether the factor structure of the KSP was related to gender and/or to violent method of the suicide attempt or to suicide completion.

    METHOD: The factor structure of the KSP was analysed in data from 165 suicide attempters from the Suicide Prevention Clinic at the Karolinska University Hospital using principal component analysis and orthogonal varimax rotation for the factor extraction. The effect of gender and (1) used method in the suicide attempt (violent versus nonviolent), and (2) later completed suicide on the factors was assessed in two separate series of the two-way ANOVAs.

    RESULT: A four-factor solution appeared: (1) Neuroticism, (2) Nonconformity, (3) Psychoticism and (4) Extraversion. Men who later completed suicide reported more Extroversion than male survivors.

    CONCLUSION: The obtained factor structure is comparable to a previous factor structure in a group of twins from the population-based Swedish Twin Registry indicating that no specific personality structure characterized the current sample. Differences in personality traits between suicide completers and survivors indicate that these groups may have some distinct characteristics.

  • 40. Hirvikoski, T.
    et al.
    Lindstrom, T.
    Carlsson, J.
    Waaler, E.
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of clinical neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Bolte, S.
    Psychoeducational groups for adults with ADHD and their significant others (PEGASUS): A pragmatic multicenter and randomized controlled trial2017Inngår i: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 44, s. 141-152Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To examine the feasibility, efficacy, and effectiveness of PEGASUS, a group-based structured psychoeducation for adults with ADHD and their significant others.

    Method: A pragmatic parallel group add-on design multicenter randomized controlled trial was conducted, comparing an 8-session treatment with PEGASUS (allocated n = 97; 48 with ADHD and 49 with significant others) to treatment as usual (TAU, allocated n = 82; 39 with ADHD and 43 significant others). Participants (individuals with ADHD and significant others) were recruited from five psychiatric outpatient departments and block randomized to PEGASUS or TAU. Knowledge about ADHD was measured using the ADHD 20 scale pre- and post-intervention and served as primary outcome.

    Results: Knowledge about ADHD (d = 0.97 [95% CI: 0.61–1.31]) increased following PEGASUS participation compared to TAU. Improvements were also observed in secondary outcomes e.g. global life satisfaction (d = 0.25 [95% CI: from –0.09 to 0.59]). Overall treatment satisfaction was good. Over 90% of the participants completed the program. Post-intervention data was obtained from n = 89 in PEGASUS group and n = 70 in TAU group and analyses were conducted per protocol. No important adverse effects or side effects were observed.

    Conclusions: Group-based structured psychoeducation PEGASUS for adults with ADHD and their significant others is a feasible, efficacious, and effective treatment option to increase ADHD knowledge and general life satisfaction in psychiatric outpatient care.

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  • 41. Hirvikoski, T
    et al.
    Waaler, E
    Lindström, T
    Bölte, S
    Jokinen, Jussi
    Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
    Cognitive behavior therapy-based psychoeducational groups for adults with ADHD and their significant others (PEGASUS): an open clinical feasibility trial2015Inngår i: ADHD Attention Deficit and Hyperactivity Disorders, ISSN 1866-6116, E-ISSN 1866-6647, Vol. 7, nr 1, s. 89-99Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this pilot study was to investigate the feasibility and effectiveness of a new psychoeducative intervention program (PEGASUS) for adults with ADHD and their significant others in a psychiatric outpatient context. At three outpatient psychiatric clinics, adults with ADHD and their significant others took part in PEGASUS, a psychoeducational program based on theories from cognitive behavioral therapy, neuropsychology, and cross-disciplinary evidence regarding ADHD. In total, 108 adults were allocated to treatment (51 with ADHD and their 57 significant others). Feasibility was evaluated regarding suitability of the intervention at a psychiatric outpatient clinic and treatment completion. Preliminary efficacy was evaluated per protocol from baseline to post-intervention (n = 41 adults with ADHD and 40 significant others). In a feasibility analysis, the intervention was judged to be a suitable treatment option for 94.5 % of all individuals with a primary diagnosis of ADHD at an outpatient psychiatric clinic. In total, 43 out of 51 allocated individuals with ADHD (84.3 %) completed the intervention. The corresponding figures for their significant others were 42 out of 57 (73.7 %). Knowledge about ADHD increased, and both the quality of relationships and psychological well-being improved from baseline to post-intervention in all participants. The significant others reported a reduction in the subjective burden of care, such as worry and guilt. The objective burden of care (such as financial problems) did not change. The findings support the potential value of psychoeducation for adults with ADHD and their significant others. An ongoing randomized controlled trial will generate further evidence concerning the PEGASUS program.

  • 42. Isung, J
    et al.
    Aeinehband, S
    Mobarrez, F
    Mårtensson, B
    Nordström, P
    Asberg, M
    Piehl, F
    Jokinen, Jussi
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Low vascular endothelial growth factor and interleukin-8 in cerebrospinal fluid of suicide attempters2012Inngår i: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 2, s. e196-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A dysregulated immune system influencing pathways for cytokine regulation and growth factor expression is implicated in the pathophysiology of several neuropsychiatric disorders. Here, we analyzed cerebrospinal fluid (CSF) cytokines and growth factors with an ultra-sensitive immunoassay system in 43 medication-free suicide attempters and 20 healthy male volunteers. CSF vascular endothelial growth factor (VEGF) and CSF interleukin-8 (IL-8) levels were significantly lower in suicide attempters compared with healthy controls. Further, CSF VEGF showed a significant negative correlation with depression severity. CSF IL-6 levels did not differ between suicide attempters and healthy controls. Low CSF levels of VEGF may represent a lack of trophic support to neurons and downregulation of neurogenesis in the hippocampus reflecting more severe depressive states. IL-8 has also been reported as important in neuroprotection as well as having chemokine activity in the innate immune response. The results support a role for an impaired innate immunity and dysregulation of neuroprotection in the pathophysiology of depression and suicidal behavior.

  • 43. Isung, J
    et al.
    Aeinehband, S
    Mobarrez, F
    Nordström, P
    Runeson, B
    Asberg, M
    Piehl, F
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    High interleukin-6 and impulsivity: determining the role of endophenotypes in attempted suicide2014Inngår i: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 4, nr e470Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dysregulation of inflammation has been associated with depression and, more recently, with suicidal behaviors. The reports regarding the relationship between interleukin-6 (IL-6) and suicide attempts are inconsistent. Personality traits such as impulsivity and aggression are considered endophenotypes and important factors that underlie suicidal behaviors. The aim of the current study was to assess whether plasma and cerebrospinal fluid (CSF) levels of IL-6 are associated with personality traits among suicide attempters. We assessed the relationships among personality traits, IL-6 and violent suicide attempts. The plasma and CSF levels of IL-6 were measured in suicide attempters (plasma=58, CSF=39) using antibody-based immunoassay systems. Personality domains were assessed using the Karolinska Scale of Personality (KSP). IL-6 levels in plasma and CSF were used to predict personality domains via regression models. Plasma IL-6 was significantly and positively correlated with extraversion as well as the KSP subscales impulsivity and monotony avoidance. CSF IL-6 was positively correlated with monotony avoidance. Violent suicide attempts tended to be associated with high plasma IL-6 levels. Plasma and CSF levels of IL-6 were not significantly associated with each other. These results indicate that impulsivity and the choice of a violent suicide attempt method might be related to higher levels of IL-6 in individuals who attempt suicide. The neuroinflammation hypothesis of suicidal behavior on the basis of elevated IL-6 levels might be partly explained by the positive association between IL-6 and impulsivity, which is a key element of the suicidal phenotype.

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  • 44. Isung, Josef
    et al.
    Mobarrez, Fariborz
    Nordström, Peter
    Asberg, Marie
    Jokinen, Jussi
    Karolinska Inst, Dept Clin Neurosci, SE-17176 Stockholm, Sweden.
    Low plasma vascular endothelial growth factor (VEGF) associated with completed suicide2012Inngår i: World Journal of Biological Psychiatry, ISSN 1562-2975, E-ISSN 1814-1412, Vol. 13, nr 6, s. 468-73Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Immunological differences have previously been associated with depression and suicidal behaviour. Several cytokines have been identified as potentially important in understanding the pathophysiology of mood disorders and suicidality. Here we aimed to identify new inflammatory biomarkers for suicide prediction.

    METHODS: Plasma concentrations of interleukin (IL) 1-a , IL1-b, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFNG), tumor necrosis factor-a (TNF-a), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) were measured in 58 suicide attempters with a high throughput automated biochip immunoassay system. Patients were evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Suicide Intent Scale (SIS). All patients were followed up for cause of death.

    RESULTS: We found significantly lower levels of VEGF in the seven patients who upon a mean follow-up of 13 years were found to have completed suicide. VEGF also showed a trend for negative correlation with the planning subscale of SIS. A trend could be shown for lower IL-2 and for higher IFNG levels in suicide victims.

    CONCLUSIONS: Our study provides further support for a role of inflammation in the pathophysiology of suicidality. VEGF may be related with suicide risk.

  • 45.
    Jokinen, Jussi
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Methylation of the HPA axis related genes in men with hypersexual disorder2017Inngår i: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 41, s. S849-S850Artikkel i tidsskrift (Annet vitenskapelig)
  • 46.
    Jokinen, Jussi
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Bostrom, Adrian
    Asberg, Marie
    Schioth, Helgi
    Severity of Suicide Attempt is Associated With Epigenetic and Transcriptional Changes in the CYP2D6 Gene2018Inngår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, nr 9, s. S373-S374Artikkel i tidsskrift (Annet vitenskapelig)
  • 47.
    Jokinen, Jussi
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Bostrom, Adrian E.
    Chatzittofis, Andreas
    Ciuculete, Diana M.
    Oberg, Katarina Gorts
    Flanagan, John N.
    Arver, Stefan
    Schioth, Helgi B.
    Methylation of HPA axis related genes in men with hypersexual disorder2017Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, s. 67-73Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, and proposed as a diagnosis in the DSM 5, shares some overlapping features with substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. In this study, comprising 67 HD male patients and 39 male healthy volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality. The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip, measuring the methylation state of over 850 K CpG sites. Prior to analysis, the global DNA methylation pattern was pre-processed according to standard protocols and adjusted for white blood cell type heterogeneity. We included CpG sites located within 2000 bp of the transcriptional start site of the following HPA-axis coupled genes: Corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor I (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FKBP5 and the glucocorticoid receptor (NR3C1). We performed multiple linear regression models of methylation M-values to a categorical variable of hypersexuality, adjusting for depression, dexamethasone non-suppression status, Childhood Trauma Questionnaire total score and plasma levels of TNF-alpha and IL-6. Of 76 tested individual CpG sites, four were nominally significant (p<0.05), associated with the genes CRH, CRHR2 and NR3C1. Cg23409074-located 48 bp upstream of the transcription start site of the CRH gene - was significantly hypomethylated in hypersexual patients after corrections for multiple testing using the FDR-method. Methylation levels of cg23409074 were positively correlated with gene expression of the CRH gene in an independent cohort of 11 healthy male subjects. The methylation levels at the identified CRH site, cg23409074, were significantly correlated between blood and four different brain regions. CRH is an important integrator of neuroendocrine stress responses in the brain, with a key role in the addiction processes. Our results show epigenetic changes in the CRH gene related to hypersexual disorder in men. (C) 2017 Elsevier Ltd. All rights reserved.

  • 48.
    Jokinen, Jussi
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Neuroscience/Center for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
    Bostrom, Adrian E.
    Dadfar, Ali
    Ciuculete, Diana M.
    Chatzittofis, Andreas
    Asberg, Marie
    Schioth, Helgi B.
    Epigenetic changes in the CRH gene are related to severity of suicide attempt and a general psychiatric risk score in adolescents2018Inngår i: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 27, s. 123-133Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study, comprising 88 suicide attempters, was to identify hypothalamic-pituitary-adrenal (HPA) -axis coupled CpG-sites showing methylation shifts linked to severity of the suicide attempt. Candidate methylation loci were further investigated as risk loci for a general psychiatric risk score in two cohorts of adolescents (cohort 1 and 2). The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip. Subjects were stratified into high-risk and low-risk groups based on the severity of the suicidal behavior. We included CpG sites located within 2000 basepairs away from transcriptional start site of the following HPA-axis coupled genes: corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor 1 (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FK506-binding protein 51 (FKBP5) and the glucocorticoid receptor (NR3C1). Themethylation state of two corticotropin releasing hormone (CRH)-associated CpG siteswere significantly hypomethylated in the high-risk group of suicide attempters (n=31) (cg19035496 and cg23409074) (p < 0.001). Adolescent cohort 1 and 2 consisted of 129 and 93 subjects, respectively, and were stratified by the in silico generated DAWBA measurements of a general psychiatric risk score into high-risk group (>similar to 50% risk) or controls. In adolescent cohort 2, cg19035496 was hypermethylated in subjects with a high general psychiatric risk score. Our results show epigenetic changes in the CRH gene related to severity of suicide attempt in adults and a general psychiatric risk score in adolescents. 

    Fulltekst (pdf)
    fulltext
  • 49.
    Jokinen, Jussi
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Boström, Adrian
    Chatzittofis, Andreas
    Görts Öberg, Katarina
    Flanagan, John N.
    Arver, Stefan
    Schiöth, Helgi
    Methylation of the HPA axis related genes in men with hypersexual disorder2017Inngår i: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 6, s. 23-23Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, was proposed as a diagnosis in the DSM 5. Some overlapping features between HD and substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function have been reported. In this study, comprising 67 male patients diagnosed with HD and 39 healthy male volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality. Methods: The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip, measuring the methylation state of over 850 K CpG sites. Prior to analysis, the global DNA methylation pattern was pre-processed according to standard protocols and adjusted for white blood cell type heterogeneity. We included CpG sites located within 2000 bp of the transcriptional start site of the following HPAaxis coupled genes: Corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor 1 (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FKBP5 and the glucocorticoid receptor (NR3C1). We performed multiple linear regression models of methylation M-values to a categorical variable of hypersexuality, adjusting for depression, DST non-suppression status, Childhood Trauma Questionnaire total score and plasma levels of TNF-alpha and IL-6. Results: 76 individual CpG sites were tested, and four of these were nominally significant (p < 0.05), associated with the genes CRH, CRHR2 and NR3C1. Cg23409074 – located 48 bp upstream of the TSS of the CRH gene – was significantly hypomethylated in hypersexual patients after corrections for multiple testing using the FDR-method. Methylation levels of cg23409074 were positively correlated with gene expression of the CRH gene in an independent cohort of 11 healthy male subjects. Conclusions: CRH is an important integrator of neuroendocrine stress responses in the brain, modulating behavior and the autonomic nervous system. Our results show epigenetic changes in CRH gene related to hypersexual disorder in men.

  • 50.
    Jokinen, Jussi
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Boström, Adrian
    Åsberg, Marie
    Schioth, Helgi
    Epigenetic and Transcriptional Changes in the CYP2D6 Gene are Related to Severity of Suicide Attempt2017Inngår i: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 42, s. S156-S156Artikkel i tidsskrift (Annet vitenskapelig)
123 1 - 50 of 103
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