Clustering care pathways of people with alcohol dependence using a data linkage of routine data in Bremen, Germany.

BACKGROUND: Although many individuals with alcohol dependence (AD) are recognized in the German healthcare system, only a few utilize addiction-specific treatment services. Those who enter treatment are not well characterized regarding their prospective pathways through the highly fragmented German healthcare system. This paper aims to (1) identify typical care pathways of patients with AD and their adherence to treatment guidelines and (2) explore the characteristics of these patients using routine data from different healthcare sectors. METHODS: We linked routinely collected register data of individuals with a documented alcohol-related diagnosis in the federal state of Bremen, Germany, in 2016/2017 and their addiction-specific health care: two statutory health insurance funds (outpatient pharmacotherapy for relapse prevention and inpatient episodes due to AD with and without qualified withdrawal treatment (QWT)), the German Pension Insurance (rehabilitation treatment) and a group of communal hospitals (outpatient addiction care). Individual care pathways of five different daily states of utilized addiction-specific treatment following an index inpatient admission due to AD were analyzed using state sequence analysis and cluster analysis. The follow-up time was 307 days (10 months). Individuals of the clustered pathways were compared concerning current treatment recommendations (1: QWT followed by postacute treatment; 2: time between QWT and rehabilitation). Patients' characteristics not considered during the cluster analysis (sex, age, nationality, comorbidity, and outpatient addiction care) were then compared using a multinomial logistic regression. RESULTS: The analysis of 518 individual sequences resulted in the identification of four pathway clusters differing in their utilization of acute and postacute treatment. Most did not utilize subsequent addiction-specific treatment after their index inpatient episode (n = 276) or had several inpatient episodes or QWT without postacute treatment (n = 205). Two small clusters contained pathways either starting rehabilitation (n = 26) or pharmacotherapy after the index episode (n = 11). Overall, only 9.3% utilized postacute treatment as recommended. CONCLUSIONS: A concern besides the generally low utilization of addiction-specific treatment is the implementation of postacute treatments for individuals after QWT.

Recommendations for Reducing the Risk of Cannabis Use-Related Adverse Psychosis Outcomes: A Public Mental Health-Oriented Evidence Review.

Objective: Cannabis use is increasingly normalized; psychosis is a major adverse health outcome. We reviewed evidence on cannabis use-related risk factors for psychosis outcomes at different stages toward recommendations for risk reduction by individuals involved in cannabis use. Methods: We searched primary databases for pertinent literature/data 2016 onward, principally relying on reviews and high-quality studies which were narratively summarized and quality-graded; recommendations were developed by international expert consensus. Results: Genetic risks, and mental health/substance use problem histories elevate the risks for cannabis-related psychosis. Early age-of-use-onset, frequency-of-use, product composition (i.e., THC potency), use mode and other substance co-use all influence psychosis risks; the protective effects of CBD are uncertain. Continuous cannabis use may adversely affect psychosis-related treatment and medication effects. Risk factor combinations further amplify the odds of adverse psychosis outcomes. Conclusions: Reductions in the identified cannabis-related risks factors-short of abstinence-may decrease risks of related adverse psychosis outcomes, and thereby protect cannabis users' health.

Medication adherence and cognitive performance in schizophrenia-spectrum and bipolar disorder: results from the PsyCourse Study.

Existing guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of the patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship between medication adherence and cognitive performance is understudied. Therefore, this study investigated the relationship between medication adherence and cognitive performance by analyzing the data of 862 participants with schizophrenia-spectrum and bipolar disorders (mean [SD] age, 41.9 [12.48] years; 44.8% female) from a multicenter study (PsyCourse Study). Z-scores for three cognitive domains were calculated, global functioning was measured with the Global Assessment of Functioning Scale, and adherence was assessed by a self-rating questionnaire. We evaluated four multiple linear regression models and built three clusters with hierarchical cluster analyses. Higher adherence behavior (p < 0.001) was associated with better global functioning but showed no impact on the cognitive domains learning and memory, executive function, and psychomotor speed. The hierarchical cluster analysis resulted in three clusters with different cognitive performances, but patients in all clusters showed similar adherence behavior. The study identified cognitive subgroups independent of diagnoses, but no differences were found in the adherence behavior of the patients in these new clusters. In summary, medication adherence was associated with global but not cognitive functioning in patients with schizophrenia-spectrum and bipolar disorders. In both diagnostic groups, cognitive function might be influenced by various factors but not medication adherence.

Association of early life stress and cognitive performance in patients with schizophrenia and healthy controls.

As core symptoms of schizophrenia, cognitive deficits contribute substantially to poor outcomes. Early life stress (ELS) can negatively affect cognition in patients with schizophrenia and healthy controls, but the exact nature of the mediating factors is unclear. Therefore, we investigated how ELS, education, and symptom burden are related to cognitive performance. The sample comprised 215 patients with schizophrenia (age, 42.9 ± 12.0 years; 66.0 % male) and 197 healthy controls (age, 38.5 ± 16.4 years; 39.3 % male) from the PsyCourse Study. ELS was assessed with the Childhood Trauma Screener (CTS). We used analyses of covariance and correlation analyses to investigate the association of total ELS load and ELS subtypes with cognitive performance. ELS was reported by 52.1 % of patients and 24.9 % of controls. Independent of ELS, cognitive performance on neuropsychological tests was lower in patients than controls (p < 0.001). ELS load was more closely associated with neurocognitive deficits (cognitive composite score) in controls (r = -0.305, p < 0.001) than in patients (r = -0.163, p = 0.033). Moreover, the higher the ELS load, the more cognitive deficits were found in controls (r = -0.200, p = 0.006), while in patients, this correlation was not significant after adjusting for PANSS. ELS load was more strongly associated with cognitive deficits in healthy controls than in patients. In patients, disease-related positive and negative symptoms may mask the effects of ELS-related cognitive deficits. ELS subtypes were associated with impairments in various cognitive domains. Cognitive deficits appear to be mediated through higher symptom burden and lower educational level.

Estimating the prevalence of alcohol-related disorders and treatment utilization in Bremen 2016/2017 through routine data linkage.

Background: In Germany, most individuals with alcohol dependence are recognized by the health care system and about 16% per year receive addiction-specific care. This paper aimed to analyze the prevalence and treatment utilization rate of people with alcohol dependence by type of addiction-specific care in the federal state of Bremen using routine and survey data. Methods: The number of individuals with alcohol dependence was estimated using data from the 2018 Epidemiological Survey of Substance Abuse (ESA). Furthermore, linked routine data of two statutory health insurances (SHIs), the German pension insurance (GPI), and the communal hospital group Gesundheit Nord - Bremen Hospital Group (GeNo), from 2016/2017, were analyzed. Based on SHI data, the administrative prevalence of various alcohol-related diagnoses according to the International Classification of Diseases (ICD-10), in various treatment settings, was extrapolated to the total population of Bremen. Based on all routine data sources, treatment and care services for individuals with alcohol dependence were also extrapolated to Bremen's total population. Care services included outpatient addiction care visits and addiction-specific treatments, [i.e., qualified withdrawal treatment (QWT), outpatient pharmacotherapy as relapse prevention, and rehabilitation treatment]. Results: Of the survey-estimated 15,792 individuals with alcohol dependence in Bremen, 72.4% (n = 11,427) had a diagnosis documented with an ICD-10 code for alcohol dependence (F10.2) or withdrawal state (F10.3-4). One in 10 individuals with alcohol dependence (n = 1,577) used one or more addiction-specific care services during the observation period. Specifically, 3.7% (n = 675) received outpatient addiction care, 3.9% (n = 736) initiated QWT, 0.8% (n = 133) received pharmacotherapy, and 2.6% (n = 405) underwent rehabilitation treatment. The share of seeking addiction-specific treatment after diagnosis was highest among younger and male patients. Conclusion: Although more than half of the individuals with alcohol dependence are documented in the health system, utilization rates of addiction-specific treatments are low. These low utilization rates suggest that there are existing barriers to transferring patients with alcohol dependence into addiction-specific care. Strengthening primary medical care provision in dealing with alcohol-related disorders and improving networking within the addiction support system appear to be particularly appropriate.

Association between mitochondria-related genes and cognitive performance in the PsyCourse Study.

BACKGROUND: Mitochondria generate energy through oxidative phosphorylation (OXPHOS). The function of key OXPHOS proteins can be altered by variation in mitochondria-related genes, which may increase the risk of mental illness. We investigated the association of mitochondria-related genes and their genetic risk burden with cognitive performance. METHODS: We leveraged cross-sectional data from 1320 individuals with a severe psychiatric disorder and 466 neurotypical individuals from the PsyCourse Study. The cognitive tests analyzed were the Trail-Making Test, Verbal Digit Span Test, Digit-Symbol Test, and Multiple Choice Vocabulary Intelligence Test. Association analyses between the cognitive tests, and single-nucleotide polymorphisms (SNPs) mapped to mitochondria-related genes, and their polygenic risk score (PRS) for schizophrenia (SCZ) were performed with PLINK 1.9 and R program. RESULTS: We found a significant association (FDR-adjusted p < 0.05) in the Cytochrome C Oxidase Assembly Factor 8 (COA8) gene locus of the OXPHOS pathway with the Verbal Digit Span (forward) test. Mitochondrial PRS was not significantly associated with any of the cognitive tests. LIMITATIONS: Moderate statistical power due to relatively small sample size. CONCLUSIONS: COA8 encodes a poorly characterized mitochondrial protein involved in apoptosis. Here, this gene was associated with the Verbal Digit Span (forward) test, which evaluates short-term memory. Our results warrant replication and may lead to better understanding of cognitive impairment in mental disorders.

Feasibility and Short-Term Effects of Low-Threshold Opioid Substitution Treatment during the COVID-19 Pandemic in Hamburg, Germany.

INTRODUCTION: After rapidly opening up a low-threshold clinic to support heavily opioid-dependent persons at the beginning of the COVID-19 pandemic in April 2020 in Hamburg (Germany), this non-interventional study evaluated the feasibility and short-term effects of opioid substitution treatment (OST). The low-threshold concept was customized for the pandemic situation and is the first of its kind in Germany. METHODS: Patients who had already begun treatment were questioned in two assessments, at T1 shortly after beginning treatment and at T2 6 months later. The primary outcome criterion was their quality of life using the OSTQOL. Secondary criteria included retention rate, their mental and physical health (measured by the BSI-18 and the OTI Health Scale), social situation, drug use, COVID-19 status, and satisfaction with treatment. RESULTS: Out of 84 patients included in the study, 51 participated in both assessments, resulting in a 6-month retention rate of 60.7%. 27.5% were females, and 72.5% were males. The feasibility question of the low-threshold OST clinic can clearly be answered positively. During the course of the study over 6 months, the situation mainly remained stable regarding quality of life, physical and mental health, and days of drug consumption. Patients significantly reduced the time they spent on the drug scene from 8.5 (SD = 7.56) to 6.1 (SD = 6.71) hours a day between the beginning of OST and T2 (p = 0.020). While 56.9% answered to be homeless at the beginning of OST, only 33.3% answered not to have found an accommodation by T2 (p = 0.012). The number of patients having contact to social workers increased from 51.0% to 74.5% (p = 0.004). Almost 2 fifths of the patients took part in PCR testing for COVID-19 (that only being done if they had symptoms), and none of the tests were positive. DISCUSSION/CONCLUSIONS: Overall, the low-threshold OST clinic has been successfully implemented in order to help a vulnerable group of people navigate through a global pandemic and support the public health sector. Further conclusions on effects are limited by the short study period and the small number of patients, which calls for further research studies in a larger setting.

[Home Treatment "Bremen ambulant vor Ort (BravO)"]. / Die aufsuchende Behandlung "Bremen ambulant vor Ort (BravO)".

OBJECTIVE: The existing legal framework to foster home treatment for severe mental illness imposes challenges for implementation. 'Bremen ambulant vor Ort (BravO)' provides home treatment on basis of the "Bundespflegesatzverordnung". METHODS: The concept and framework of BravO will be outlined, routine data on the BravO treatment from October 1st, 2019 to September 30th, 2021 were analysed. RESULTS: Financial and staff resources of 20 in-patient treatment places were equivalently transferred into BravO. 298 patients generating 392 cases received treatment. Median treatment span was 36 days, with 21 days (median) of service delivery. 74.7 % were diagnosed either in ICD-10 groups F2 or F3. CONCLUSION: BravO was successfully implemented into routine care. BravO allows flexible home treatment for people with severe mental illness apart from existing treatment framework.

Study protocol of a randomized controlled trial evaluating home treatment with peer support for acute mental health crises (HoPe).

BACKGROUND: Home treatment (HT) is a treatment modality for patients with severe mental illness (SMI) in acute mental crises. It is frequently considered equivalent to psychiatric inpatient treatment in terms of treatment outcome. Peer Support (PS) means that people with lived experience of a mental illness are trained to support others on their way towards recovery. While PS is growing in international importance and despite a growing number of studies supporting its benefits, it is still not comprehensively implemented into routine care. The HoPe (Home Treatment with Peer Support) study investigates a combination of both - HT and PS - to provide further evidence for a recovery-oriented treatment of psychiatric patients. METHODS: In our randomized controlled trial (RCT), HT with PS is compared with HT without PS within a network of eight psychiatric clinical centers from the North, South and East of Germany. We investigate the effects of a combination of both approaches with respect to the prevention of relapse/recurrence defined as first hospitalization after randomization (primary outcome), disease severity, general functioning, self-efficacy, psychosocial health, stigma resistance, recovery support, and service satisfaction (secondary outcomes). A sample of 286 patients will be assessed at baseline after admission to HT care (data point t0) and randomized into the intervention (HT + PS) and control arm (HT). Follow-Up assessments will be conducted 2, 6 and 12 months after admission (resulting in three further data points, t1 to t3) and will be analyzed via intention-to-treat approach. DISCUSSION: This study may determine the positive effects of PS added to HT, prove additional evidence for the efficacy of PS and thereby facilitate its further implementation into psychiatric settings. The aim is to improve quality of mental health care and patients' recovery as well as to reduce the risk of relapses and hospitalizations for patients with SMI. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov: NCT04336527 , April 7, 2020.

A novel longitudinal clustering approach to psychopathology across diagnostic entities in the hospital-based PsyCourse study.

Biological research and clinical management in psychiatry face two major impediments: the high degree of overlap in psychopathology between diagnoses and the inherent heterogeneity with regard to severity. Here, we aim to stratify cases into homogeneous transdiagnostic subgroups using psychometric information with the ultimate aim of identifying individuals with higher risk for severe illness. 397 participants of the PsyCourse study with schizophrenia- or bipolar-spectrum diagnoses were prospectively phenotyped over 18 months. Factor analysis of mixed data of different rating scales and subsequent longitudinal clustering were used to cluster disease trajectories. Five clusters of longitudinal trajectories were identified in the psychopathologic dimensions. Clusters differed significantly with regard to Global Assessment of Functioning, disease course, and-in some cases-diagnosis while there were no significant differences regarding sex, age at baseline or onset, duration of illness, or polygenic burden for schizophrenia. Longitudinal clustering may aid in identifying transdiagnostic homogeneous subgroups of individuals with severe psychiatric disease.

Patient-centered placement matching of alcohol-dependent patients based on a standardized intake assessment: process evaluation within an exploratory randomized controlled trial.

BACKGROUND: In the implementation of placement matching guidelines, feasibility has been concerned in previous research. Objectives of this process evaluation were to investigate whether the patient-centered matching guidelines (PCPM) are consistently applied in referral decision-making from an inpatient qualified withdrawal program to a level of care in aftercare, which factors affect whether patients actually receive matched aftercare according to PCPM, and whether its use is feasible and accepted by clinic staff. METHODS: The study was conducted as process evaluation within an exploratory randomized controlled trial in four German psychiatric clinics offering a 7-to-21 day qualified withdrawal program for patients suffering from alcohol dependence, and with measurements taken during detoxification treatment and six months after the initial assessment. PCPM were used with patients in the intervention group by feeding back to them a recommendation for a level of care in aftercare that had been calculated from Measurements in the Addictions for Triage and Evaluation (MATE) and discussed with the staff on the treatment unit. As measurements, The MATE, the Client Socio-Demographic and Service Receipt Inventory-European Version, a documentation form, the Control Preference Scale, and the Motivation for Treatment Scale were administered. A workshop for the staff at the participating trial sites was conducted after data collection was finished. RESULTS: Among 250 patients participating in the study, 165 were interviewed at follow-up, and 125 had received aftercare. Although consistency in the application of PCPM was moderate to substantial within the qualified withdrawal program (Cohen's kappa ≥ .41), it was fair from discharge to follow-up. In multifactorial multinomial regression, the number of foregoing substance abuse treatments predicted whether patients received more likely undermatched (Odds Ratio=1.27; p=.018) or overmatched (Odds Ratio=0.78; p=.054) treatment. While the implementation process during the study was evaluated critically by the staff, they stated a potential of quality assurance, more transparency and patient-centeredness in the use of PCPM. CONCLUSIONS: While the use of PCPM has the potential to enhance the quality of referral decision making within treatment, it may not be sufficient to determine referral decisions for aftercare. TRIAL REGISTRATION: German Clinical Trials Register DRKS00005035 . Registered 03/06/2013.

[Weighing the benefits and harms of psychotropic and analgesic substances - A perspective of German addiction medicine experts]. / Abwägung von Nutzen und Schädlichkeit von berauschenden und schmerzlindernden Substanzen aus der Perspektive von deutschen Suchtmedizinern.

BACKGROUND: In Europe, there have been several addiction-expert rankings of harms related to the use of psychotropic substances in the last 15 years. Among them, only one expert ranking took into account the potential benefits of these drugs. Non-Opioidergic Analgesics (NOAs), such as gabapentinoids and NSAIDs, which have been increasingly the subject of abuse / misuse reports, have not been considered in such expert rankings. Likewise, there is currently no multi-substance comparison as to whether the valuation rank of the harmfulness of an illegal drug may change along with an imagined change in legal status in Germany. OBJECTIVES AND METHODS: Using a questionnaire, 101 experienced addiction physicians (first cohort) evaluated 33 psychoactive substances including analgesics with regard to their health and social harms as well as potential usefulness for the consumer and their environment / society ('others'). In addition, this cohort investigated whether the harmfulness assessment of an illegal substance changes if it would be legalized. In order to obtain the average overall harmfulness (overall risk) of a substance, the percentage contribution of each dimension to the overall harmfulness was determined in a second survey (second cohort, 36 experienced addiction medicine experts). Finally, the average benefit and overall risk ratings of each substance were related to each other. RESULTS: Prescription psychoactive substances such as analgesics, NOAs (including gabapentinoids) and opioidergic maintenance medications to treat opiate dependence were judged to have a favorable benefit-harm profile. Cannabis and ketamine were placed in the midfield of both, the harm and benefit rankings. Together with most illicit narcotic drugs, alcohol and nicotine, have been ranked among the most harmful and least useful substances, whereby alcohol was judged on average to be more harmful but also more useful than nicotine. In the event of potential legalization, the overall harm of the traditional illegal drugs methamphetamine, heroin, cocaine and cannabis was estimated to be reduced. This was mainly due to a more favorable valuation of the harm to others under these virtual conditions. CONCLUSION: Prescription substances including opioidergic and non-opioidergic analgesics as well as opioid maintenance therapy medications (methadone and buprenorphine) were assigned a favorable benefit-harm profile. Alcohol, nicotine and traditional illicit drugs (with the exception of cannabis and ketamine) were determined to have an unfavorable profile. The overall harm of traditional illicit drugs was assessed to decrease along with legalization, mainly by decreasing the harm to others in this virtual event.

[Screening for Problematic Alcohol Consumption - A Survey on Guideline Implementation in Transdisciplinary Health Care of a Model Region]. / Screening auf problematischen Alkoholkonsum ­ Erhebung zur Umsetzung der S3-Leitlinienempfehlungen in der transdisziplinären Versorgung einer Modellregion.

AIM: Recording the frequency of screenings for problematic alcohol consumption by professionals involved in the health care of respective patients. The German S3-guideline "screening, diagnosis and treatment of alcohol-related disorders" recommends the use of questionnaire-based screenings for all patients in all settings. METHODS: Cross-sectional survey on screening frequency among general practitioners, gynecologists, psychiatrists, child- and adolescent therapists, psychotherapists, social workers and midwives. Logistic regression was used to explore how healthcare professionals' attributes were associated with the implementation of screenings. RESULTS: With response rates of about 20%, health care professionals reported using screening instruments for an average of 6.9% of all patients during the previous four weeks. Most of the time, custom-made questions were used instead of the recommended instruments (AUDIT, AUDIT-C). Higher screening rates were reported for patients with newly diagnosed hypertension (21.2%), alcohol-related disorders (43.3%) and mental disorders (39.3%). Knowledge of the guideline was associated with implementation of screenings (OR=4.67; 95% KI 1.94-11.25, p<0.001). CONCLUSIONS: Comprehensive screening for problematic alcohol use with questionnaire-based instruments in accordance with guidelines is far from being routinely implemented in the studied health care settings. Measures to increase the knowledge of the guidelines are necessary in order to increase the frequency of alcohol screening in health care.

Polygenic risk scores across the extended psychosis spectrum.

As early detection of symptoms in the subclinical to clinical psychosis spectrum may improve health outcomes, knowing the probabilistic susceptibility of developing a disorder could guide mitigation measures and clinical intervention. In this context, polygenic risk scores (PRSs) quantifying the additive effects of multiple common genetic variants hold the potential to predict complex diseases and index severity gradients. PRSs for schizophrenia (SZ) and bipolar disorder (BD) were computed using Bayesian regression and continuous shrinkage priors based on the latest SZ and BD genome-wide association studies (Psychiatric Genomics Consortium, third release). Eight well-phenotyped groups (n = 1580; 56% males) were assessed: control (n = 305), lower (n = 117) and higher (n = 113) schizotypy (both groups of healthy individuals), at-risk for psychosis (n = 120), BD type-I (n = 359), BD type-II (n = 96), schizoaffective disorder (n = 86), and SZ groups (n = 384). PRS differences were investigated for binary traits and the quantitative Positive and Negative Syndrome Scale. Both BD-PRS and SZ-PRS significantly differentiated controls from at-risk and clinical groups (Nagelkerke's pseudo-R2: 1.3-7.7%), except for BD type-II for SZ-PRS. Out of 28 pairwise comparisons for SZ-PRS and BD-PRS, 9 and 12, respectively, reached the Bonferroni-corrected significance. BD-PRS differed between control and at-risk groups, but not between at-risk and BD type-I groups. There was no difference between controls and schizotypy. SZ-PRSs, but not BD-PRSs, were positively associated with transdiagnostic symptomology. Overall, PRSs support the continuum model across the psychosis spectrum at the genomic level with possible irregularities for schizotypy. The at-risk state demands heightened clinical attention and research addressing symptom course specifiers. Continued efforts are needed to refine the diagnostic and prognostic accuracy of PRSs in mental healthcare.

Interplay between the genetics of personality traits, severe psychiatric disorders and COVID-19 host genetics in the susceptibility to SARS-CoV-2 infection.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with its impact on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behaviour and, therefore, the risk of contracting the virus. AIMS: We examined overlapping genetic underpinnings between major psychiatric disorders, personality traits and susceptibility to SARS-CoV-2 infection. METHOD: Linkage disequilibrium score regression was used to explore the genetic correlations of coronavirus disease 2019 (COVID-19) susceptibility with psychiatric disorders and personality traits based on data from the largest available respective genome-wide association studies (GWAS). In two cohorts (the PsyCourse (n = 1346) and the HeiDE (n = 3266) study), polygenic risk scores were used to analyse if a genetic association between, psychiatric disorders, personality traits and COVID-19 susceptibility exists in individual-level data. RESULTS: We observed no significant genetic correlations of COVID-19 susceptibility with psychiatric disorders. For personality traits, there was a significant genetic correlation for COVID-19 susceptibility with extraversion (P = 1.47 × 10-5; genetic correlation 0.284). Yet, this was not reflected in individual-level data from the PsyCourse and HeiDE studies. CONCLUSIONS: We identified no significant correlation between genetic risk factors for severe psychiatric disorders and genetic risk for COVID-19 susceptibility. Among the personality traits, extraversion showed evidence for a positive genetic association with COVID-19 susceptibility, in one but not in another setting. Overall, these findings highlight a complex contribution of genetic and non-genetic components in the interaction between COVID-19 susceptibility and personality traits or mental disorders.

A genome-wide association study of the longitudinal course of executive functions.

Executive functions are metacognitive capabilities that control and coordinate mental processes. In the transdiagnostic PsyCourse Study, comprising patients of the affective-to-psychotic spectrum and controls, we investigated the genetic basis of the time course of two core executive subfunctions: set-shifting (Trail Making Test, part B (TMT-B)) and updating (Verbal Digit Span backwards) in 1338 genotyped individuals. Time course was assessed with four measurement points, each 6 months apart. Compared to the initial assessment, executive performance improved across diagnostic groups. We performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with performance change over time by testing for SNP-by-time interactions using linear mixed models. We identified nine genome-wide significant SNPs for TMT-B in strong linkage disequilibrium with each other on chromosome 5. These were associated with decreased performance on the continuous TMT-B score across time. Variant rs150547358 had the lowest P value = 7.2 × 10-10 with effect estimate beta = 1.16 (95% c.i.: 1.11, 1.22). Implementing data of the FOR2107 consortium (1795 individuals), we replicated these findings for the SNP rs150547358 (P value = 0.015), analyzing the difference of the two available measurement points two years apart. In the replication study, rs150547358 exhibited a similar effect estimate beta = 0.85 (95% c.i.: 0.74, 0.97). Our study demonstrates that longitudinally measured phenotypes have the potential to unmask novel associations, adding time as a dimension to the effects of genomics.

Influence of gender on cytokine induced depression and treatment: Gender aspects of IFN-α-induced depression.

BACKGROUND: Cytokine treatment with Interferon-alpha (IFN-α) represents a clinical model of immune associated depression, but it remains unclear if it is of the same entity as major depressive disorder (MDD). The study focuses on possible gender differences in IFN-α induced depression and effects of a pre-emptive antidepressant treatment. METHODS: Data from 181 patients with chronic hepatitis C infection (cHC) without history of mental illnesses undergoing treatment with IFN-α 2a and ribavirin were re-analyzed for gender effects. Patients with a pre-emptive antidepressant therapy with Escitalopram (n = 90, verum group) to prevent IFN-induced depression were compared to patients who received placebo (n = 91). Depressive symptoms before and during HCV-treatment were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), Beck's Depression Inventory (BDI) and the Hamilton Anxiety Rating Scale. RESULTS: We found significant differences regarding the incidence and severity of depressive symptoms between men and women for patients without antidepressant pre-treatment (placebo group). Significantly more women without pre-emptive antidepressant therapy suffered from clinically relevant depression (MADRS values ≥ 13, p = 0.041) and self-rated depressive symptoms (BDI ≥ 17, p = 0.024). Antidepressant pre-treatment showed comparable effects regarding the reduction of incidence and severity of depression in both women and men. CONCLUSIONS: Compared to MDD, IFN-alpha-induced depression in patients with cHC is also characterized by gender differences with an increased risk for women but no gender difference regarding the effects of an antidepressant pre-treatment is found. Our data strengthens the hypothesis that Interferon-induced depression serves as a clinical model for immune related depressive disorders.

Substitution treatment for opioid dependence with slow-release oral morphine: Retention rate, health status, and substance use after switching to morphine.

INTRODUCTION: Since April 2015, slow-release oral morphine (SROM) has been approved for opioid agonist treatment (OAT) in Germany. Experimental studies show that benefits of SROM over methadone include less heroin craving, better tolerability, and higher patient satisfaction and mental stability. The SROMOS study (Efficacy and Tolerability of Slow-Release Oral Morphine in Opioid Substitution Treatment) aims to investigate the long-term effects (effectiveness and safety) of morphine substitution under routine care in Germany. MATERIAL AND METHODS: This is a prospective, noninterventional, naturalistic, observational study. Between July 2016 and November 2017, this study recruited patients in OAT who decided to switch to SROM from 23 outpatient addiction treatment centers in Germany. The study collected data on mental health (Brief Symptom Inventory - BSI-18), substance use, somatic health (Opiate Treatment Index Health-Symptoms-Scale - OTI-HSS), opioid craving (visual analogue scale), and withdrawal symptoms (Short Opiate Withdrawal Scale) at baseline (t0) and after 3 (t3), 6 (t6) and 12 (t12) months. Physicians documented side effects as adverse events (AEs) and adverse drug reactions (ADRs). RESULTS: Three-quarters of the enrolled study participants (N = 180) were male. The average age was 44.4 years. Patients were opioid-dependent for 23 years and had been in OAT for almost seven years on average. After 12 months, 60.6% were still being treated with SROM. Mental health improved significantly under SROM treatment between t0 and t12. The intention-to-treat (ITT), as well as the per-protocol (PP) analysis, shows a statistically significant improvement of the mean Global Severity Index (GSI) of the BSI-18 value of 20% (ITT) and 24% (PP). Physical health also improved significantly under SROM treatment. There were no statistically significant changes in the use of cannabis, cocaine, amphetamines, and tranquillizers in the past 30 days, but heroin use, intravenous consumption, and the number of drinking days significantly decreased. CONCLUSIONS: This study provides some of the first long-term data on OAT with SROM under routine care conditions. SROM treatment is an effective alternative for a subgroup of opioid-dependent patients with an unsatisfactory course of OAT or in cases where undesirable side effects due to alternative substances have occurred. ETHICAL STATEMENT: The study protocol was approved by the Ethics Committee of the Chamber of Physicians in Hamburg in March 2016 (No. PV5222). The study was conducted by following the Declaration of Helsinki and is registered with the German Register of Clinical Trials (DRKS, ID: DRKS00010712).

Medication Adherence in a Cross-Diagnostic Sample of Patients From the Affective-to-Psychotic Spectrum: Results From the PsyCourse Study.

INTRODUCTION: According to the World Health Organization, medication adherence is defined as the extent to which a person's behavior corresponds with an agreed recommendation from a healthcare provider. Approximately 50% of patients do not take their medication as prescribed, and non-adherence can contribute to the progress of a disease. For patients suffering from mental diseases non-adherence plays an important role. Various factors have been proposed as contributing to non-adherence, however the literature remains heterogeneous dependent on the analyzed patient subgroups. This study comprehensively evaluates the association of sociodemographic, clinical, personality and quality of life related factors with medication adherence by analyzing data from the PsyCourse study. The PsyCourse study is a large and cross-diagnostic cohort of psychiatric patients from the affective-to-psychotic spectrum. METHODS: The study sample comprised 1,062 patients from the PsyCourse study with various psychiatric diagnoses (mean [SD] age, 42.82 [12.98] years; 47.4% female). Data were analyzed to identify specific factors associated with medication adherence, and adherence was measured by a self-rating questionnaire. Odds ratios (OR) were estimated by a logistic regression for binary outcomes. Missing data were imputed using multiple imputation. RESULTS: The following factors showed the strongest association with medication adherence: never having used illicit drugs (OR, 0.71), number of prescribed antipsychotics (OR, 1.40), the personality trait conscientiousness (OR, 1.26), and the environmental domain of quality of life (OR, 1.09). CONCLUSION: In a large and cross-diagnostic sample, we could show that a higher level of conscientiousness, a higher number of antipsychotic medication, a better quality of life within the environmental domain, and the absence of substance abuse contribute to a better medication adherence independent of the underlying disorder.