Anorexia Nervosa With Comorbid Severe Depression: A Systematic Scoping Review of Brain Stimulation Treatments.

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

Risk Factors for Suicide After Bariatric Surgery in a Population-based Nationwide Study in Five Nordic Countries.

OBJECTIVE: To identify risk factors for suicide after bariatric surgery. SUMMARY BACKGROUND DATA: Bariatric surgery reduces obesity-related mortality. However, it is for unclear reasons is associated with an increased risk of suicide. METHODS: This population-based cohort study included patients having undergone bariatric surgery in 1982 to 2012 in any of the 5 Nordic countries, with follow-up through 2012. Eleven potential risk factors of suicide (sex, age, comorbidity, surgery type, surgical approach, calendar year of surgery, history of depression or anxiety, psychosis, schizophrenia, mania, or bipolar disorder, personality disorder, substance use, and number of previously documented psychiatric diagnoses) were analyzed using Cox regression. RESULTS: Of 49,977 bariatric surgery patients, 98 (0.2%) committed suicide during follow-up. Women had a decreased risk of suicide compared to men (hazard ratio [HR] = 0.48, 95% confidence interval [CI] 0.33-0.77), although age and comorbidity did not influence this risk. Compared to gastric bypass, other types of bariatric surgery had lower risk of suicide (HR = 0.44, 95%CI 0.27-0.99). There was no difference in suicide risk between laparoscopic and open surgical approach. A history of depression or anxiety (HR = 6.87, 95%CI 3.97-11.90); mania, bipolar disorder, psychosis, or schizophrenia (HR = 2.70, 95%CI 1.14-6.37); and substance use (HR = 2.28, 95%CI 1.08-4.80), increased the risk of suicide. More of the above psychiatric diagnoses increased the risk of suicide (HR = 22.59, 95%CI 12.96-39.38 for ≥2 compared to 0 diagnoses). CONCLUSIONS: Although the risk of suicide is low, psychiatric disorders, male sex, and gastric bypass procedure seem to increase the risk of suicide after bariatric surgery, indicating a role for tailored preoperative psychiatric evaluation and postoperative surveillance.

Reaching Men and Women at Risk of Committing Sexual Offences - Findings From the National Swedish Telephone Helpline PrevenTell.

BACKGROUND: In 2012 the Swedish Helpline project PrevenTell, targeting men and women with self-identified out-of-control and paraphilic sexual behavior, was launched by ANOVA, Karolinska University Hospital. The overall purpose was to reach the target group and via a telephone-contact encourage further on-site assessment and treatment. AIM: To describe men and women contacting PrevenTell during the first 7 years by delineate sexuality-related risk-factors for sexual violence, gender differences, and age- and gender-preferences when reporting a pedophilic interest. METHOD: A 52-item semi-structured telephone interview was conducted by experts in sexual medicine with individuals who contacted the helpline. The interview covered sociodemographic characteristics, problematic sexual behavior(s), and mental health and based on the information reported, interventions included recommending an appointment at ANOVA, supporting other appropriate healthcare, or motivation of individuals still ambivalent to treatment. RESULTS: Data collection took place between March 2012 and October 2019. A total of 1573 respondents in the main target group (1454 men and 119 women) gave informed consent for participation. Compulsive sexual behavior was reported by 69% of respondents and 56% described at least one paraphilic interest. The prevalence of concomitant compulsive sexual behavior and a paraphilic interest was high, varying between 65% and 83%. Significant gender differences were found in socioeconomic and mental health variables, in which women showed fewer positive and stable life factors compared to men. A sexual preference for minors was reported by 24% of respondents. In this group, 63% reported use of child sexual exploitation material and 15% committed child sexual abuse. Respondents were offered anonymity, however 55% disclosed their identity and were enrolled for further assessment and treatment at ANOVA. CLINICAL IMPLICATIONS: The result of this study is of substantial relevance when developing secondary preventive initiatives targeting sexual violence in the community. STRENGTHS AND LIMITATIONS: This is the first study to present data from a national helpline targeting both men and women with a wide range of self-identified problematic sexual behaviors. Limitations include the lack of diagnostic confirmation on-site, hence, presented data provides only an indication of clinical conditions. Furthermore, the main objective of the interview was to motivate participants to seek further treatment, sometimes necessary to prioritize this over adherence to the semi-structured questionnaire, explaining the relatively high absence rate in some variables. CONCLUSION: Men and women at risk of committing sexual crimes can be reached through a national helpline service and motivated to undergo further assessment and treatment. Adebahr R, Söderström EZ, Arver S, et al. Reaching Men and Women at Risk of Committing Sexual Offences - Findings From the National Swedish Telephone Helpline PrevenTell. J Sex Med 2021;18:1571-1581.

Multitasking in Driving as Optimal Adaptation Under Uncertainty.

OBJECTIVE: The objective was to better understand how people adapt multitasking behavior when circumstances in driving change and how safe versus unsafe behaviors emerge. BACKGROUND: Multitasking strategies in driving adapt to changes in the task environment, but the cognitive mechanisms of this adaptation are not well known. Missing is a unifying account to explain the joint contribution of task constraints, goals, cognitive capabilities, and beliefs about the driving environment. METHOD: We model the driver's decision to deploy visual attention as a stochastic sequential decision-making problem and propose hierarchical reinforcement learning as a computationally tractable solution to it. The supervisory level deploys attention based on per-task value estimates, which incorporate beliefs about risk. Model simulations are compared against human data collected in a driving simulator. RESULTS: Human data show adaptation to the attentional demands of ongoing tasks, as measured in lane deviation and in-car gaze deployment. The predictions of our model fit the human data on these metrics. CONCLUSION: Multitasking strategies can be understood as optimal adaptation under uncertainty, wherein the driver adapts to cognitive constraints and the task environment's uncertainties, aiming to maximize the expected long-term utility. Safe and unsafe behaviors emerge as the driver has to arbitrate between conflicting goals and manage uncertainty about them. APPLICATION: Simulations can inform studies of conditions that are likely to give rise to unsafe driving behavior.

Predicting suicide attempt or suicide death following a visit to psychiatric specialty care: A machine learning study using Swedish national registry data.

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

Internet-Administered Cognitive Behavioral Therapy for Hypersexual Disorder, With or Without Paraphilia(s) or Paraphilic Disorder(s) in Men: A Pilot Study.

BACKGROUND: Hypersexual disorder (HD) is a condition in which the individual experiences loss of control over engagement in sexual behaviors, leading to negative effects on various areas of life. Paraphilias often present concomitantly with HD, and although cognitive behavioral therapy (CBT) has been proven to reduce engagement in hypersexual behavior, no studies have investigated the effects of Internet-administered CBT (ICBT) on HD, with or without paraphilia(s) or paraphilic disorder(s). AIM: To investigate the effects of Internet-administered CBT on HD, with or without paraphilia(s) or paraphilic disorder(s). METHODS: Male participants (n = 36) evaluated positive according to the proposed diagnostic HD criteria, with or without paraphilia(s) or paraphilic disorder(s), received 12 weeks of ICBT. Measures were administered weekly over the treatment period, with an additional follow-up measurement 3 months after completion of treatment. An assessment interview was performed 2 weeks after treatment. OUTCOMES: The primary outcome was the Hypersexual Behavior Inventory (HBI-19), and secondary outcomes were the Hypersexual Disorder: Current Assessment Scale (HD:CAS), the Sexual Compulsivity Scale (SCS), as well as a tentative composite of 6 Severity Self-rating Measures, for Paraphilic Disorders and depression (Montgomery-Åsberg Depression Rating Scale [MADRS-S]), psychological distress (Clinical Outcomes in Routine Evaluation Outcome Measure [CORE-OM]), and treatment satisfaction (CSQ-8). RESULTS: Large, significant decreases in HD symptoms and sexual compulsivity were found, as well as moderate improvements in psychiatric well-being and paraphilic symptoms. These effects remained stable 3 months after treatment. CLINICAL IMPLICATIONS: ICBT can ameliorate HD symptoms, psychiatric distress, and paraphilic symptoms, which suggests that the ICBT for HD, with or without paraphilia(s) or paraphilic disorder(s), may constitute a valuable addition of treatment options in clinical settings. STRENGTHS AND LIMITATIONS: This is the first study evaluating the efficacy of ICBT on a sample of men suffering from HD. In addition, a proportion of the sample reported concomitant paraphilic interests and disorders, thus mirroring an everyday clinical practice in the field of sexual medicine. No control group was assigned, and some of the outcome measures are still to be validated. The long-term effects of ICBT and its efficacy in hypersexual women are unknown. CONCLUSIONS: This study gives support for ICBT as an effective treatment option for HD. Future evaluations of the treatment program should include women and larger samples in randomized controlled procedures and investigate the long-term effects. Hallberg J, Kaldo V, Arver S, et al. Internet-Administered Cognitive Behavioral Therapy for Hypersexual Disorder, With or Without Paraphilia(s) or Paraphilic Disorder(s) in Men: A Pilot Study. J Sex Med 2020;17:2039-2054.

Naltrexone in Compulsive Sexual Behavior Disorder: A Feasibility Study of Twenty Men.

BACKGROUND: Compulsive sexual behavior disorder (CSBD) is a common disorder affecting different areas of life, although studies focusing on pharmacological treatment are sparse. AIM: To investigate whether the opioid receptor antagonist naltrexone is feasible and tolerable and can provide symptom reduction in CSBD. METHODS: Twenty men aged 27-60 years (mean = 38.8 years, standard deviation = 10.3) with CSBD seeking treatment in an outpatient nonforensic clinic received four weeks of naltrexone 25-50 mg. Measurements were made before, during, and four weeks after treatment. OUTCOMES: The self-assessment Hypersexual Disorder: Current Assessment Scale (HD: CAS) score was the primary outcome measure, and secondary outcomes were the Hypersexual Behavior Inventory (HBI) score, reported adverse effects, adherence to treatment, and dropouts. RESULTS: There was significant decrease on both HD: CAS and HBI scores during treatment with naltrexone. Even though some of the effects remained after treatment, the increased scores on HD: CAS indicated worsening of CSBD symptoms. The most reported side effects were fatigue (55%), nausea (30%), vertigo (30%), and abdominal pain (30%). However, there were no serious adverse effects leading to discontinuation of naltrexone. CLINICAL IMPLICATIONS: Despite side effects being common, naltrexone seems to be feasible in the treatment of CSBD. STRENGTHS & LIMITATIONS: Being the first nonforensic prospective trial on naltrexone in CSBD, this study provides novel insights on a pharmacological intervention. However, owing to the small sample size and the lack of a control group, conclusions of effectiveness should be interpreted with caution. CONCLUSION: Naltrexone is feasible and tolerable and may reduce symptoms of CSBD; nevertheless, future studies should ensure a randomized controlled procedure to evaluate possible effectiveness. Savard J, Öberg KG, Chatzittofis A, et al. Naltrexone in Compulsive Sexual Behavior Disorder: A Feasibility Study of Twenty Men. J Sex Med 2020;17:1544-1552.

Adolescent self-harm with and without suicidality: cross-sectional and longitudinal analyses of a Swedish regional register.

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.

A Randomized Controlled Study of Group-Administered Cognitive Behavioral Therapy for Hypersexual Disorder in Men.

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. Hallberg J, Kaldo V, Arver S, et al. A Randomized Controlled Study of Group-Administered Cognitive Behavioral Therapy for Hypersexual Disorder in Men. J Sex Med 2019;16:733-745.

Adolescent criminality: multiple adverse health outcomes and mortality pattern in Swedish men.

BACKGROUND: To investigate the impact of adolescent violent and non-violent criminality and subsequent risk of morbidity and mortality in adulthood in a large Swedish cohort of young men conscripted for military service in 1969/70. METHODS: The cohort consisted of 49,398 18-year-old Swedish conscripts followed up for morbidity and mortality up to the age of 55 years in Swedish national registers. Information about convictions for crime before conscription was obtained from national crime registers. Data from a survey at conscription were scrutinized to get information on potential confounders. RESULTS: Hospitalization due to alcohol and drug related diagnoses and attempted suicide were significantly more evident in the violent group compared to non-violent criminals and non-criminals. More than one fifth (21.13%) of the young violent offenders, 12.90% of the non-violent offenders and 4.96% of the non-criminals had died during the follow-up period. In Cox proportional multivariate analyses, young violent offenders had twice the hazard (HR = 4.29) of all-cause mortality than the non-violent offenders (HR = 2.16) during the follow-up period. Alcohol and drug related mortality, suicide and fatal accidents were most evident in both violent and non-violent offenders. CONCLUSIONS: Men with adolescent criminality received more inpatient care due to alcohol and drug related diagnoses and attempted suicide as adults. Mortality due to unnatural causes, alcohol, and drug related diagnoses, suicide and accidents was most evident in violent offenders, while these causes of death were much lower in non-criminals. Men with adolescent criminality are a high-risk group for multiple adverse health outcomes and for early death. Efforts for detection of substance use and psychiatric disorders in this group is important for the prevention work in both local- and community levels as well as national prevention programs.

Predictors of improvement in an open-trial multisite evaluation of emotion regulation group therapy.

Emotion regulation group therapy (ERGT) is a novel treatment specifically targeting deliberate non-suicidal self-harm (DSH) in individuals with borderline personality disorder (BPD). Identifying robust predictors of positive response to ERGT could aid clinicians in treatment selection; however, to date, only one such study has been conducted. Thus, we aimed to replicate previously identified predictors of treatment response to ERGT by investigating demographic, clinical, and diagnostic predictors in 95 women with BPD or subclinical BPD who had participated in an open-trial evaluation of ERGT. Outcomes evaluated were frequency of DSH and emotion dysregulation. Assessments were conducted at pretreatment, post-treatment, and 6-month follow-up. Multilevel mixed linear models and multilevel negative binomial generalized estimated equations were used to identify significant interactions between the predictors and outcomes. We found that greater pretreatment DSH frequency was associated with greater improvements in DSH during treatment (b = 0.998, SE = 0.00, p = 0.03) and follow-up (b = 0.997, SE = 0.00, p < 0.01) and that greater BPD severity was associated with greater improvements in DSH during treatment (b = 0.84, SE = 0.06, p = 0.02) and in emotion dysregulation at follow-up (b = -3.05, SE = 1.47, p = 0.04). Co-occurring disorders were associated with poorer treatment response during follow-up. Results were generally consistent with a previous study of the predictors of response to ERGT. The findings provide further support for the utility of this treatment across a range of BPD patients, including patients with severe DSH and BPD.

Trajectories of antidepressant medication use in individuals before and after being granted disability pension due to common mental disorders- a nationwide register-based study.

BACKGROUND: Early retirement caused by disability pension (DP) due to common mental disorders (CMDs) is frequent in European countries. Inadequate treatment, e.g., suboptimal antidepressant (AD) medication before DP can be crucial in such DP. This explorative study aimed to disentangle trajectories of AD based on defined daily dose (DDD) before and after granted DP, and to characterize the trajectories by socio-demographics and medical factors. METHODS: All 4642 individuals in Sweden aged 19-64 with incident DP due to CMD in 2009-2010 were included. Trajectories of annual DDDs of AD were analysed over a 6-year period by a group-based trajectory method. Associations between socio-demographic or medical factors and different trajectories were estimated by chi2-test and multinomial logistic regression. RESULTS: Five trajectories of ADs were identified. Three groups, comprising 34%, 34%, and 21% of the cohort, had constant AD levels before and after DP with mean annual DDDs of 29, 234, and 580, respectively. Two groups, each including 6% of the cohort, had increasing levels of DDDs, levelling off at around 1150 and 785 DDDs after DP. Particularly age, outpatient care due to mental diagnoses and DP diagnoses were significantly associated with different trajectories (p < 0.05). All the groups had a larger proportion of older individuals (> 50%, 45-64 years), except for the 'increasing low' group, where younger individuals were in majority (> 60%, 18-44 years), who more frequently exited labour market due to 'anxiety disorders', with lower education and more specialised healthcare before DP than the other groups. CONCLUSION: The heterogeneity among the five trajectory groups was partly explained by age, the severity of the mental disorder and the DP diagnoses. DDDs of ADs, though on different levels, varied marginally before and after granted DP in the majority. Moreover, AD levels were very low in one third of the individuals. Early identification and focus on the 'increasing low' group might be important in order to identify individuals at risk for further increase in annual DDDs of ADs even after granted DP, and might also contribute in prevention of DP. Further detailed research regarding different groups is warranted.

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 version.

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. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02697019 ). Registered 2 March 2016.

Brain structure abnormalities in young women who presented conduct disorder in childhood/adolescence.

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.

Emotion regulation individual therapy for adolescents with nonsuicidal self-injury disorder: a feasibility study.

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. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02326012, December 22, 2014, retrospectively registered).

Cerebrospinal fluid kynurenines in multiple sclerosis; relation to disease course and neurocognitive symptoms.

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.

Prescribed psychiatric medication among multiple sclerosis patients before and after disability pension: a register study with matched controls.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Suicide attempt and future risk of cancer: a nationwide cohort study in Sweden.

PURPOSE: Little is known about cancer incidence among patients with a history of suicide attempt. Suicide attempters have lower levels of oxytocin, a hormone related to lactation, stress, social functioning, and well-being, and recent research indicates influence on carcinogenesis. We hypothesized that the low oxytocin levels among suicide attempters results in an increased risk of cancer in general and in organs with oxytocin receptors in particular. METHODS: A nationwide cohort study of patients aged 15 years or older with hospitalization for self-inflicted injury or attempted suicide was identified from the Swedish patient register in 1968-2011. The cancer outcomes were identified from the Swedish cancer register. Cancer risk in suicide attempters was compared with the risk in the background population of the corresponding age, sex, and calendar period by calculating standardized incidence ratios (SIRs) with 95 % confidence intervals (95 % CI). RESULTS: The 186,627 patients (83,637 men and 102,990 women) hospitalized for self-inflicted injury or attempted suicide contributed with 2.6 million person-years at risk. The SIR for all cancer was 1.3 (95 % CI 1.27-1.33) in men and 1.25 (1.22-1.28) in women. For cancers in organs rich in oxytocin receptors (uterus, breast, and brain), the corresponding SIRs were 1.02 (0.87-1.19) and 1.13 (1.09-1.17), respectively. There was a particularly increased risk of cancers related to alcohol and tobacco in both sexes. CONCLUSION: Patients attempting suicide have an increased risk of cancer. However, this increase does not seem to be associated with low oxytocin levels, but rather to exposures like tobacco smoking and alcohol consumption.

Violent and non-violent methods of attempted and completed suicide in Swedish young men: the role of early risk factors.

BACKGROUND: There is a paucity of studies on the role of early risk factors for the choice of methods for violent suicide attempts. Adolescent risk factors for the choice of violent or non-violent methods for suicide attempts and the risk of subsequent suicide were studied using a longitudinal design. METHODS: A national Swedish cohort of 48 834 18-20-year-old young men conscripted for military service from 1969 to 1970 was followed through official registers during a 37-year period. Two questionnaires concerning their psychosocial background were answered by each conscript. Cox proportional hazard regression analyses were used to estimate the risk for different methods of attempted suicide and later suicide. RESULTS: A total of 1195 (2.4 %) men had made a suicide attempt and of these, 133 (11.1 %) committed suicide later. The number of suicide victims among the non-attempters was 482 (1 %). Half of the suicides occurred during the same year as the attempt. Suicide victims had earlier onset of suicidal behaviour and had more often used hanging as a method of attempted suicide than those who did not later commit suicide. The early risk factors for both violent and non-violent methods of suicide attempt were quite similar. CONCLUSION: Violent suicide attempts, especially by hanging, are associated with a clearly elevated suicide risk in men and require special clinical and public health attention. The early risk factors related to the choice of either a violent or a non-violent suicide attempt method are interlinked and circumstantial factors temporally close to the suicide attempt, such as access to a specific method, may partly explain the choice of method.

Psychiatric and neurological disorders in late adolescence and risk of convictions for violent crime in men.

BACKGROUND: The relationship between mental illness and violent crime is complex because of the involvement of many other confounding risk factors. In the present study, we analysed psychiatric and neurological disorders in relation to the risk of convictions for violent crime, taking into account early behavioural and socio-economic risk factors. METHODS: The study population consisted of 49,398 Swedish men, who were thoroughly assessed at conscription for compulsory military service during the years 1969-1970 and followed in national crime registers up to 2006. Five diagnostic groups were analysed: anxiety-depression/neuroses, personality disorders, substance-related disorders, mental retardation and neurological conditions. In addition, eight confounders measured at conscription and based on the literature on violence risk assessment, were added to the analyses. The relative risks of convictions for violent crime during 35 years after conscription were examined in relation to psychiatric diagnoses and other risk factors at conscription, as measured by odds ratios (ORs) and confidence intervals (CIs) from bivariate and multivariate logistic regression analyses. RESULTS: In the bivariate analyses there was a significant association between receiving a psychiatric diagnosis at conscription and a future conviction for violent crime (OR = 3.83, 95 % CI = 3.47-4.22), whereas no significant association between neurological conditions and future violent crime (OR = 1.03, 95 % CI = 0.48-2.21) was found. In the fully adjusted multivariate logistic regression model, mental retardation had the strongest association with future violent crime (OR = 3.60, 95 % CI = 2.73-4.75), followed by substance-related disorders (OR = 2.81, 95 % CI = 2.18-3.62), personality disorders (OR = 2.66, 95 % CI = 2.21-3.19) and anxiety-depression (OR = 1.29, 95 % CI = 1.07-1.55). Among the other risk factors, early behavioural problem had the strongest association with convictions for violent crime. CONCLUSIONS: Mental retardation, substance-related disorders, personality disorders and early behavioural problems are important predictors of convictions for violent crime in men.