Does compulsion explain addiction?

One of the leading drug addiction theories states that habits and the underlying neural process of a ventral to dorsal striatal shift are the building blocks of compulsive drug-seeking behaviour and that compulsion is the maladaptive persistence of responding despite adverse consequences. Here we discuss that compulsive behaviour as defined primarily from the perspective of animal experimentation falls short of the clinical phenomena and their neurobiological correlates. Thus for the human condition, the concept of compulsive habbits should be critically addressed and potentially revised.

Polygenetic risk scores and phenotypic constellations of obsessive-compulsive disorder in clozapine-treated schizophrenia.

Obsessive-compulsive symptoms (OCS) are frequently observed in individuals with schizophrenia (SCZ) treated with clozapine (CLZ). This study aimed to analyze prevalence of OCS and obsessive-compulsive disorder (OCD) in this subgroup and find possible correlations with different phenotypes. Additionally, this is the first study to examine polygenetic risk scores (PRS) in individuals with SCZ and OCS. A multicenter cohort of 91 individuals with SCZ who were treated with CLZ was recruited and clinically and genetically assessed. Symptom severity was examined using the Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI), the Calgary Depression Scale for Schizophrenia (CDSS), Global Assessment of Functioning Scale (GAF) and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Participants were divided into subgroups based on phenotypic OCS or OCD using Y-BOCS scores. Genomic-wide data were generated, and PRS analyses were performed to evaluate the association between either phenotypic OCD or OCS severity and genotype-predicted predisposition for OCD, SCZ, cross-disorder, and CLZ/norclozapine (NorCLZ) ratio, CLZ metabolism and NorCLZ metabolism. OCS and OCD were frequent comorbidities in our sample of CLZ-treated SCZ individuals, with a prevalence of 39.6% and 27.5%, respectively. Furthermore, the Y-BOCS total score correlated positively with the duration of CLZ treatment in years (r = 0.28; p = 0.008) and the PANSS general psychopathology subscale score (r = 0.23; p = 0.028). A significant correlation was found between OCD occurrence and PRS for CLZ metabolism. We found no correlation between OCS severity and PRS for CLZ metabolism. We found no correlation for either OCD or OCS and PRS for OCD, cross-disorder, SCZ, CLZ/NorCLZ ratio or NorCLZ metabolism. Our study was able to replicate previous findings on clinical characteristics of CLZ-treated SCZ individuals. OCS is a frequent comorbidity in this cohort and is correlated with CLZ treatment duration in years and PANSS general psychopathology subscale score. We found a correlation between OCD and PRS for CLZ metabolism, which should be interpreted as incidental for now. Future research is necessary to replicate significant findings and to assess possible genetic predisposition of CLZ-treated individuals with SCZ to OCS/OCD. Limitations attributed to the small sample size or the inclusion of subjects on co-medication must be considered. If the association between OCD and PRS for CLZ metabolism can be replicated, it should be further evaluated if CYP1A2 alteration, respectively lower CLZ plasma level, is relevant for OCD development.

Relapse in clinically stable adult patients with schizophrenia or schizoaffective disorder: evidence-based criteria derived by equipercentile linking and diagnostic test accuracy meta-analysis.

BACKGROUND: There is no consensus on defining relapse in schizophrenia, and scale-derived criteria with unclear clinical relevance are widely used. We aimed to develop an evidence-based scale-derived set of criteria to define relapse in patients with schizophrenia or schizoaffective disorder. METHODS: We searched the Yale University Open Data Access (YODA) for randomised controlled trials (RCTs) in clinically stable adults with schizophrenia or schizoaffective disorder, and obtained individual participant data on Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity (CGI-S), Personal and Social Performance (PSP), and Social and Occupational Functioning Assessment Scale (SOFAS). Our main outcomes were PANSS-derived criteria based on worsening in PANSS total score. We examined their relevance using equipercentile linking with CGI-S and functioning scales, and their test-performance in defining relapse with diagnostic test accuracy meta-analysis against CGI-S worsening (≥1-point increase together with a score ≥4 points) and psychiatric hospitalisation. FINDINGS: Based on data from seven RCTs (2354 participants; 1348 men [57·3%] and 1006 women [42·7%], mean age of 39·5 years [SD 12·0, range 17-89]; 303 Asian [12.9%], 255 Black [10.8%], 1665 White [70.7%], and other or unspecified 131 [5.6%]), an increase of 12 points or more in PANSS total (range 30-210 points) corresponded to clinically important deterioration in global severity of illness (≥1 point increase in CGI-S, range 1-7) and functioning (≥10 points decline in PSP or SOFAS, range 1-100). The interpretation of percentage changes varied importantly across different baseline scores. An increase of 12 points or more in PANSS total had good sensitivity and specificity using CGI-S as reference standard (sensitivity 82·1% [95% CI 77·1-86·4], specificity 86·9% [82·9-90·3]), as well as good sensitivity but lower specificity compared to hospitalisation (sensitivity 81·7% [74·1-87·7], specificity 69·2% [60·5-76·9]). Requiring either an increase in PANSS total or in specific items for positive and disorganization symptoms further improved test-performance. Cutoffs for situations where high sensitivity or specificity is needed are presented. INTERPRETATION: An increase of either 12 points or more in the PANSS total score, or worsening of specific positive and disorganisation symptom items could be a reasonable evidence-based definition of relapse in schizophrenia, potentially linking symptoms used to define remission and relapse. Percentage changes should not be used to define relapse because their interpretation depends on baseline scores. FUNDING: German Research Foundation (grant number: 428509362).

Increase in presentations with new-onset psychiatric disorders in a psychiatric emergency department in Berlin, Germany during the second wave of the COVID-19 pandemic - a retrospective cross-sectional study.

Introduction: While numerous studies have identified an increase in symptoms of depression as well as anxiety and distress due to the COVID-19 pandemic, relatively few studies have investigated the new-onset of psychiatric diseases during the pandemic. Methods: This study focuses on the number of psychiatric new-onset diagnoses in a psychiatric emergency department (pED) in Berlin, Germany during the second wave of the pandemic (i.e. from 09/15/2020 to 03/01/2021 = COVID-19-period) compared to pre-pandemic times (09/15/2019 to 03/01/2020 = control period). We focused on diagnostic subgroups and performed logistic regression analysis to investigate potential risk groups based on covariables such as age, gender, homelessness, attending in police custody and familial relationship. Results: Overall, there was a 59.7% increase in new-onset psychiatric diagnoses during the COVID-19-period. Increases in the following diagnoses were observed: new-onset of substance-related and addictive disorders (+192.5%), depressive disorders (+115.8%), schizophrenia spectrum and psychotic disorders (+113.3%) and anxiety disorders (+63.6%). These diagnostic subgroups, together with attending in police custody, were found to predict pED presentations with new-onset during the COVID-19-period. Interestingly, in the group of new-onset psychiatric diseases in the COVID-19-period, higher amounts of job loss and living alone as well as a relative decrease in familial relationships were observed. Discussion: COVID-19 infections and post-COVID-19 syndrome are unlikely to have played a substantial role in the increase of new-onset diseases in this study. Conclusion: Our findings underline the role of indirect factors in new-onset of psychiatric diseases during the pandemic and should be a caveat for future pandemic control policies.

Homelessness and associated factors over a 13-year period among psychiatric in-patients in Berlin, Germany: routine data analysis.

BACKGROUND: Homeless patients in psychiatric hospitals are a scarcely studied and there is lack of knowledge about factors associated with homelessness and in-patient treatment. AIMS: To determine the change over time in the number of homeless psychiatric in-patients and to examine factors associated with homelessness. METHOD: Retrospective data analysis of 1205 selected electronic patient files on psychiatric in-patient treatment in a university psychiatric hospital in Berlin, Germany. The rate of patients experiencing homelessness over a 13-year period (2008-2021) and the sociodemographic and clinical factors associated with homelessness are analysed over time. RESULTS: Our study revealed a 15.1% increase in the rate of homeless psychiatric in-patients over the 13-year period. Of the whole sample, 69.3% people lived in secure private housing, 15.5% were homeless and 15.1.% were housed in sociotherapeutic facilities. Homelessness was significantly associated with being male (OR = 1.76 (95% CI 1.12-2.76), born outside of Germany (OR = 2.22, 95% CI 1.47-3.34), lack of out-patient treatment (OR = 5.19, 95% CI 3.35-7.63), psychotic disorders (OR = 2.46, 95% CI 1.16-5.18), reaction to severe stress (OR = 4.19, 95% CI 1.71-10.24), personality disorders (OR = 4.98, 95% CI 1.92-12.91), drug dependency (OR = 3.47, 95% CI 1.5-8.0) and alcohol dependency (OR = 3.57, 95% CI 1.67-7.62). CONCLUSIONS: The psychiatric care system is facing an increasing number of patients in precarious social situations. This should be considered in resource allocation planning in healthcare. Individual solutions for aftercare, along with supported housing, could counteract this trend.

Use of digital technologies by users of psychiatric inpatient services in Berlin, Germany: a cross-sectional patient survey.

Few studies and almost exclusively from the USA have recently investigated mobile phone and computer use among users of psychiatric services, which is of high relevance regarding the increasing development of digital health applications and services. OBJECTIVE, DESIGN AND SETTING: In a cross-sectional patient survey, we examined (a) rates and purposes of mobile phone, computer, internet and social media use, and (b) the role of social and clinical predictors on rates of utilisation among psychiatric inpatients in Berlin, Germany. PARTICIPANTS AND RESULTS: Descriptive analyses showed that among 496 participants, 84.9% owned a mobile phone and 59.3% a smartphone. Among 493 participants, 68.4% used a computer regularly. Multivariate logistic regression models revealed being homeless, diagnosis of a psychotic illness, being of older age and a lower level of education to be significant predictors for not owning a mobile phone, not using a computer regularly or having a social media account, respectively. CONCLUSIONS: Users of psychiatric services may have access to mobile phones and computers, although rates are lower than in the general population. However, key barriers that need to be addressed regarding the development of and engagement with digital health interventions are factors of social exclusion like marginalised housing as well as clinical aspects like psychotic illness.

Predicting psychotic relapse following randomised discontinuation of paliperidone in individuals with schizophrenia or schizoaffective disorder: an individual participant data analysis.

BACKGROUND: Predicting relapse for individuals with psychotic disorders is not well established, especially after discontinuation of antipsychotic treatment. We aimed to identify general prognostic factors of relapse for all participants (irrespective of treatment continuation or discontinuation) and specific predictors of relapse for treatment discontinuation, using machine learning. METHODS: For this individual participant data analysis, we searched the Yale University Open Data Access Project's database for placebo-controlled, randomised antipsychotic discontinuation trials with participants with schizophrenia or schizoaffective disorder (aged ≥18 years). We included studies in which participants were treated with any antipsychotic study drug and randomly assigned to continue the same antipsychotic drug or to discontinue it and receive placebo. We assessed 36 prespecified baseline variables at randomisation to predict time to relapse, using univariate and multivariate proportional hazard regression models (including multivariate treatment group by variable interactions) with machine learning to categorise the variables as general prognostic factors of relapse, specific predictors of relapse, or both. FINDINGS: We identified 414 trials, of which five trials with 700 participants (304 [43%] women and 396 [57%] men) were eligible for the continuation group and 692 participants (292 [42%] women and 400 [58%] men) were eligible for the discontinuation group (median age 37 [IQR 28-47] years for continuation group and 38 [28-47] years for discontinuation group). Out of the 36 baseline variables, general prognostic factors of increased risk of relapse for all participants were drug-positive urine; paranoid, disorganised, and undifferentiated types of schizophrenia (lower risk for schizoaffective disorder); psychiatric and neurological adverse events; higher severity of akathisia (ie, difficulty or inability to sit still); antipsychotic discontinuation; lower social performance; younger age; lower glomerular filtration rate; benzodiazepine comedication (lower risk for anti-epileptic comedication). Out of the 36 baseline variables, predictors of increased risk specifically after antipsychotic discontinuation were increased prolactin concentration, higher number of hospitalisations, and smoking. Both prognostic factors and predictors with increased risk after discontinuation were oral antipsychotic treatment (lower risk for long-acting injectables), higher last dosage of the antipsychotic study drug, shorter duration of antipsychotic treatment, and higher score on the Clinical Global Impression (CGI) severity scale The predictive performance (concordance index) for participants who were not used to train the model was 0·707 (chance level is 0·5). INTERPRETATION: Routinely available general prognostic factors of psychotic relapse and predictors specific for treatment discontinuation could be used to support personalised treatment. Abrupt discontinuation of higher dosages of oral antipsychotics, especially for individuals with recurring hospitalisations, higher scores on the CGI severity scale, and increased prolactin concentrations, should be avoided to reduce the risk of relapse. FUNDING: German Research Foundation and Berlin Institute of Health.

The Prevalence of Problem Gambling and Gambling Disorder Among Homeless People: A Systematic Review And Meta-Analysis.

Gambling problems are often associated with homelessness and linked to elevated psychiatric morbidity and homelessness chronicity. We performed a systematic review and meta-analysis on prevalence rates of problem gambling (PG) and gambling disorder (GD) in homeless people. Following PRISMA guidelines, we searched databases Medline, Embase and PsycINFO from inception of databases to 4th may 2021. We included studies reporting prevalence estimates on clinical gambling problems in representative samples of homeless people based on standardized diagnostics. Risk of bias was assessed. A random effects meta-analysis was performed, and subgroup analyses based on methodological characteristics of primary studies were conducted. We identified eight studies from five countries, reporting information on 1938 participants. Prevalence rates of clinically significant PG and GD ranged from 11.3 to 31.3%. There was evidence for substantial heterogeneity with I2 = 86% (95% CI 63-97%). A subgroup of four low risk of bias studies displayed a significantly lower results ranging from 11.3 to 23.6%. Additionally, high rates of subclinical problem gambling were reported (11.6-56.4%). At least one in ten homeless persons experiences clinically significant PG or GD. Social support and health care services for the homeless should address this problem by implementing models for early detection and treatment.

Suicidality in psychiatric emergency department situations during the first and the second wave of COVID-19 pandemic.

Psychiatric patients are prone to mental health deterioration during the Covid-19 pandemic. Little is known about suicidality in psychiatric patients during the Covid-19 pandemic. This study is a retrospective chart review of psychiatric emergency department (pED) presentations with present or absent suicidality (5634 pED attendances, 4110 patients) in an academic pED in Berlin, Germany. Poisson regression analysis was performed on the effect of Covid-19 period on suicidality (suicidal ideation (SI), suicide plans (SP) or suicide attempt (SA)) during the first (3/2/2020-5/24/2020 "first-wave") and second (9/15/2020-3/1/2021 "second-wave") wave of the Covid-19 pandemic compared to the same periods one year earlier. During the first-wave the number of pED visits per person with SI, SP and SA was higher compared to one year earlier (SI RR = 1.614; p = 0.016; SP RR = 2.900; p = 0.004; SA RR = 9.862; p = 0.003). SI and SP were predicted by interaction between substance use disorder (SUD) and second-wave (SI RR = 1.305, p = 0.043; SP RR = 1.645, p = 0.018), SA was predicted by interaction between borderline personality disorder (BPD) and second-wave (RR = 7.128; p = 0.012). Suicidality increased during the first-wave of Covid-19 pandemic in our sample. In the second-wave this was found in patients with SUD and BPD. These patients may be at particular risk of suicidality during the Covid-19 pandemic.

A computational solution for bolstering reliability of epigenetic clocks: Implications for clinical trials and longitudinal tracking.

Epigenetic clocks are widely used aging biomarkers calculated from DNA methylation data, but this data can be surprisingly unreliable. Here we show technical noise produces deviations up to 9 years between replicates for six prominent epigenetic clocks, limiting their utility. We present a computational solution to bolster reliability, calculating principal components from CpG-level data as input for biological age prediction. Our retrained principal-component versions of six clocks show agreement between most replicates within 1.5 years, improved detection of clock associations and intervention effects, and reliable longitudinal trajectories in vivo and in vitro. This method entails only one additional step compared to traditional clocks, requires no replicates or prior knowledge of CpG reliabilities for training, and can be applied to any existing or future epigenetic biomarker. The high reliability of principal component-based clocks is critical for applications to personalized medicine, longitudinal tracking, in vitro studies, and clinical trials of aging interventions.

Perspectives in poverty and mental health.

In recent years, different forms of poverty and their interaction with mental illness have been in the focus of research, although the implementation of action in mental health care and policy making so far is scarce. This perspective article offers different perspectives of poverty and its reciprocal association with mental illness and outlines possible future research and policy implications. We will approach the topic of poverty from various levels: On a micro-level, focusing on absolute poverty with precarious housing and malnutrition. On a meso-level, on neighborhood-related poverty as a factor in individuals' mental illness. On a macro-level, on effects of income inequality on mental health. In several studies, it has been shown that on each level, poverty has a profound impact on mental health, though it must be noted that in some fields, research is still scarce. In the future, an inter- and transdisciplinary approach is of considerable importance, since poverty and its impact on mental health should be addressed from different perspectives, reaching from targeted programs for individual groups (e.g., homeless people) up to national policy measures.

[Associations of mental illness and homelessness: results of a secondary data analysis at a Berlin health center for the homeless]. / Zusammenhänge zwischen psychischen Erkrankungen und Wohnungslosigkeit: Ergebnisse einer Sekundärdatenanalyse in einem Berliner Gesundheitszentrum für Obdachlose.

BACKGROUND: Homelessness is an expression and consequence of a complex problem situation that poses major challenges to the medical and social care systems in Germany. About three quarters of homeless people suffer from mental illness. The aim of this study was to investigate associations between mental illness and homelessness. MATERIAL AND METHODS: A secondary data analysis of patients' records from a Berlin health center for homeless people was conducted. Data from 112 homeless patients who received care at the center between the years 2006 and 2020 were included in the explorative study. RESULTS: Mental illness was present in 84.9% of patients before the onset of homelessness. The factors associated with an early onset of homelessness were low school education and drug abuse. A long duration of homelessness was associated with the factors alcohol abuse as well as imprisonment. Each new episode of street homelessness was associated with an average increase in the duration of homelessness by 7.9 months. DISCUSSION: Since mental illnesses are important factors influencing the development and maintenance of homelessness, preventive strategies as well as specialized services for this vulnerable group need to be increasingly created. In particular, recurring episodes of street homelessness should be prevented as far as possible. The link between imprisonment and homelessness suggests that more intensive support is needed for reintegration after release from prison.

Adverse events after antipsychotic discontinuation: an individual participant data meta-analysis.

BACKGROUND: Adverse events can occur after antipsychotic discontinuation but evidence from antipsychotic drug trials is scarce. We aimed to estimate the occurrence of adverse events after discontinuing antipsychotics. METHODS: For this two-stage individual participant data meta-analysis, we searched the Yale University Open Data Access Project's database for randomised controlled trials of antipsychotics from database inception until May 6, 2021. We included placebo-controlled antipsychotic randomised controlled trials with individual participant data of participants (aged ≥ 18 years, of any sex and ethnicity) with schizophrenia, schizoaffective disorder, or bipolar disorder. Studies were excluded if treatment with antidepressants, lithium, or antiepileptic drugs was initiated as additive therapy at the start of the placebo phase. Starting from the screening or washout phase, we divided participants who were randomised to placebo into two groups: the discontinuation group (participants who discontinued prestudy antipsychotics at the start of the screening or washout phase) and control group (participants who did not take prestudy antipsychotics for at least 4 weeks before the start of the screening or washout phase). Participants were excluded from the discontinuation and control groups if they discontinued prestudy treatment with antidepressants, lithium, or antiepileptic drugs up to 4 weeks before baseline, received an antipsychotic as a tolerability test, or received a long-acting injection of an antipsychotic within 12 weeks before baseline. In the discontinuation group, individuals were excluded if they discontinued prestudy antipsychotic treatment more than 3 days before, or any day after, the start of screening or washout phase. The prespecified primary outcome was occurrence of at least one new somatic adverse event with an onset within 4 weeks after the start of the screening or washout phase. We implemented a generalised linear model that accounted for potential confounders, to estimate the effect of antipsychotic discontinuation. This study is registered with PROSPERO (CRD42021224350). FINDINGS: We identified 409 records of which 18 were eligible and included in the analysis. From these 18 studies, 692 individuals (242 [35·0%] women and 450 [65·0%] men) were eligible for the discontinuation group and 935 individuals (339 [36·3%] women and 596 [63·7%] men) were eligible for the control group (median age in both groups: 39 years [IQR 30-47]). New somatic adverse events occurred in 295 (43%) individuals in the discontinuation group and 293 (31%) individuals in the control group (OR 1·74; 95% CI 1·27-2·39; τ2=0·15; moderate strength of evidence). New psychiatric adverse events were also more frequent in the discontinuation group than the control group (OR 2·01; 95% CI 1·38-2·94). Longer duration of treatment before discontinuation (OR for doubling the duration of treatment: 1·08; 95% CI 1·01-1·14) was associated with a higher probability of new somatic adverse events after antipsychotic discontinuation, and tapered discontinuation (compared with abrupt discontinuation: 0·54; 0·32-0·91) and no history of somatic illness (compared with history of somatic illness: 0·63; 0·43-0·91) were associated with lower probabilities of new somatic adverse events after antipsychotic discontinuation. The risk of bias was moderate in 13 (72·2%) studies and serious in five (27·8%) studies. INTERPRETATION: We detected moderate evidence of emerging somatic adverse events after discontinuation of first-generation and second-generation antipsychotics, particularly after discontinuation of longer durations of treatment. Tapered discontinuation can mitigate the risk of emerging somatic adverse events after antipsychotic discontinuation. These findings have implications for the safety of treatment discontinuation and could be used for tailored treatment planning. FUNDING: German Research Foundation.

No party, no drugs? Use of stimulants, dissociative drugs, and GHB/GBL during the early COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is presumably having an impact on the consumption of psychoactive substances. Social distancing and lockdown measures may particularly affect the use of "party drugs" (e.g., stimulants, dissociatives, and GHB/GBL) through the absence of typical use settings. We aimed to analyse the use patterns of those substances and underlying motivations before and during the pandemic. METHODS: A subsample of 1,231 users of stimulants (amphetamine, methamphetamine, MDMA/ecstasy, cocaine), dissociative drugs (ketamine, dextromethorphan, PCP), and GHB/GBL was assessed from 30th April to 4th August 2020 as part of the Corona Drug Survey, a cross-sectional international online survey in five languages that included a total of 5,049 participants. The reported use of distinct substances and the underlying motivations were ascertained before (retrospectively) and during the pandemic. Furthermore, associations between drug use as a coping mechanism, pandemic-related stressors, and substance use were examined. RESULTS: Regarding the reported frequency of use during the pandemic, 48.0-64.8% of the sample ceased or decreased, 11.9-25.5% maintained, and 23.6-29.1% increased their consumption. MDMA/ecstasy showed the strongest decrease and GHB/GBL and dissociatives the highest increase. Participants reported that price, quality, and supply were mostly unaffected by the pandemic. The most common motivations before and during the pandemic were mood-related factors, such as a desire to feel exhilarated, euphoric, high, or buzzed. The relevance of social purposes and mood-related motivators declined during the pandemic, whereas dealing with boredom increased. Overall, 16.4-35.6% perceived drug use as helpful for dealing with pandemic-related stressors, which were associated with an increased consumption frequency. CONCLUSION: The early stage of the COVID-19 pandemic was associated with major changes in the use of "party drugs". Those who increased their level of drug use and perceived it as a coping strategy in particular might be targeted with adaptive preventive and therapeutic measures.

Offspring's risk for suicidal behaviour in relation to parental death by suicide: systematic review and meta-analysis and a model for familial transmission of suicide.

BACKGROUND: Exposure to parental suicide has been associated with increased risk for suicide and suicide attempts, although the strength of this association is unclear as evidence remains inconsistent. AIMS: To quantify this risk using meta-analysis and identify potential effect modifiers. METHOD: A systematic search in PubMed, PsycInfo and Embase databases to 2020 netted 3614 articles. Inclusion criteria were: observation of history of parental death by suicide, comparison with non-exposed populations and definition of suicide and suicide attempt according to standardised criteria. We focused on population-based studies. The primary outcome was the pooled relative risk (RR) for incidence of suicide attempt and suicide in offspring of a parent who died by suicide compared with offspring of two living parents. Additionally, we compared the RR for attempted and completed suicide after parental suicide with the RR for attempted and completed suicide after parental death by other causes. RESULTS: Twenty studies met our inclusion criteria. Offspring exposed to parental suicide were more likely to die by suicide (RR = 2.97, 95% CI 2.50-3.53) and attempt suicide (RR = 1.76, 95% CI 1.58-1.96) than offspring of two living parents. Furthermore, their risk of dying by or attempting suicide was significantly higher compared with offspring bereaved by other causes of death. CONCLUSIONS: The experience of losing a parent to suicide is a strong and independent risk factor for suicidal behaviour in offspring. Our findings highlight the need for prevention strategies, outreach programmes and support interventions that target suicide-related outcomes in the exposed population.

Cannabis use during the early COVID-19 pandemic: Use patterns, predictors, and subjective experiences.

Background: Even in the early stages, global crises such as the COVID-19 pandemic lead to serious dislocations of social life, secondary adjustment reactions to external restrictions and individual concerns. Coping mechanisms may also include dysfunctional strategies like an increase of drug use. Considering the wide-spread use of cannabis, the aim of this study was to elucidate the interplay of social restrictions, psychopathology, concerns related to the pandemic in addition to the users' experiences, motivations and consumption quantities during the early COVID-19 pandemic. It was presumed that cannabis intake would increase during the early phase of the crisis and that consumption quantities would be related to corona-related restrictions, concerns as well as subjective substance effects and psychopathology. Materials and methods: As part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages, consumption quantities and patterns of cannabis use in the early phase of the pandemic from April to August 2020 were examined. Participants retrospectively rated restrictions and concerns related to the pandemic, motives of cannabis use prior to and during 1 month the pandemic, and subjective consumption effects. Results: Cannabis use behavior showed no significant differences when consumption quantities prior and during 1 month after the COVID-19 outbreak were compared. Higher quantities of cannabis intake prior and during 1 month of the pandemic as well as more corona-related concern were associated with an increased perception of positive effects of cannabis during the pandemic. Predictors of its use during 1 month of pandemic were higher pre-pandemic consumption quantity, older age, quarantinization, a lesser degree of being affected by negative effects of the pandemic and a stronger subjective experience of corona-related positive effects of cannabis. Comparisons of the motives for cannabis intake in the pre-pandemic versus the pandemic period showed that all rationales for consumption were reported less frequently, except boredom. Conclusion: Frequencies of cannabis intake remained relatively stable in the early pandemic phase. Risk factors for increased use seem related to habitual consumption patterns that become more prominent under quarantinization. The use of cannabis as a dysfunctional coping strategy might not be amenable via self-report and should therefore receive special attention in clinical contexts.

[Changes in ICD-11: Disorders Due to Substance Use or Addictive Behaviours]. / Veränderungen in der ICD-11: Störungen durch Substanzgebrauch und Verhaltenssüchte.

ICD-11 will discriminate 3 subcategories of harmful patterns of substance use and 5 subcategories of dependence. According to a pre-version, the 6 diagnostic criteria of substance dependence in ICD-10 will be condensed in 3 pairs in ICD-11. The term "persistent substance use despite clear evidence of overly harmful consequence" shall be replaced by "substance use often continues despite the occurrence of problems". Pathological gambling and pathological gaming will be listed as addictive behaviors next to substance use disorders.The reduction from 6 to 3 criteria of substance dependence may be problematic in some cases. First studies report an increase of alcohol and cannabis dependence under use of ICD-11. The change of the description of "persistent substance use despite clear evidence of overly harmful consequence" to "substance use often continues despite the occurrence of problems" could imply legal and social problems, which could lead to pathologization of social problems.

The effect of second-generation antipsychotic withdrawal on the occurrence of vacuous chewing movements in animal models: A review.

INTRODUCTION: Abrupt discontinuation of antipsychotics is associated with an increased risk of adverse events such as extrapyramidal symptoms in humans. In animal models, vacuous chewing movements may occur after antipsychotic discontinuation. We aim to assess vacuous chewing movements after the discontinuation of second-generation antipsychotics in animal models. METHODS: PubMed, EMBASE, and Web of Science databases were searched for studies since inception until January 2, 2021. In addition, we manually searched references from included and relevant studies. Studies were included if a behavioral assessment of vacuous chewing movements (VCMs) in animal models was performed after discontinuation of a second-generation antipsychotic (SGA). Findings will be reviewed qualitatively and discussed with regard to clinical implications. RESULTS: 5607 studies were screened and five studies were considered eligible for the qualitative analysis. The five studies reported results of behavioral assessments of VCMs after discontinuation of clozapine, olanzapine, and risperidone. VCMs were not reported to be increased after discontinuation of clozapine and olanzapine. However, VCMs were reported to be increased after discontinuation of higher but not lower dosages of risperidone. DISCUSSION: These findings, based on a limited series of studies, suggest differences in the occurrence of extrapyramidal symptoms between second-generation antipsychotics. More research is needed to determine the magnitude of differences between antipsychotics and implications for clinical practice in humans.

[ICD-11: changes in the diagnostic criteria of substance dependence]. / ICD-11: Änderungen der diagnostischen Kriterien der Substanzabhängigkeit.

BACKGROUND: In ICD(International Classification of Diseases)-11 the criteria for the diagnosis of substance dependence have been revised. OBJECTIVE: Discussion of the advantages and disadvantages of the revised diagnostic criteria. MATERIAL AND METHODS: Discussion of criteria with respect to neurobiological, social and clinical research. RESULTS: In the new ICD-11, harmful drug use and substance dependence remain separate diagnostic categories. Regarding substance dependence, the former six diagnostic criteria are condensed into three pairs, two of which must be fulfilled to diagnose this disorder. Within the pairs, one affirmed symptom or aspect is sufficient for the new criterion to be fulfilled. With reference to scientific findings in the field of addiction, this appears to provide advantages as well as disadvantages. The specificity of the diagnosis of substance dependence might get worse compared to ICD-10, because only one symptom of the syndrome pairs has to be fulfilled in each newly constructed pair in order to fulfill the criterion. Therefore, the risk of false positive diagnosis of substance dependence could increase. This is a potential reason for concern because the definition of ICD-10 "persisting substance use despite clear evidence of overtly harmful consequences", is more broadly reworded in ICD-11 as "substance use often continues despite the occurrence of problems". This criterion may hence simply be fulfilled because a substance is illegal in a certain country. In the largest multinational study in 10 countries concerning concordance of diagnostic systems, alcohol dependence was diagnosed approximately 10% more often using ICD-11 compared to ICD-10. CONCLUSION: In ICD-11 the well-established distinction between substance dependence and harmful drug use is preserved. Systematic studies are required to assess whether the new diagnostic criteria are clinically helpful or increase social problems by increasing false positive diagnoses of addiction.