Changes in Psychotropic Drug Blood Levels After SARS-CoV-2 Vaccination: A Two-Center Cohort Study.

BACKGROUND: Limited evidence from case reports suggests that coronavirus disease 2019 (COVID-19) vaccination may interact with the treatment outcomes of psychiatric medications. Apart from clozapine, reports on the effect of COVID-19 vaccination on other psychotropic agents are scarce. This study aimed to investigate the impact of COVID-19 vaccination on the plasma levels of different psychotropic drugs using therapeutic drug monitoring. METHODS: Plasma levels of psychotropic agents, including agomelatine, amisulpride, amitriptyline, escitalopram, fluoxetine, lamotrigine, mirtazapine, olanzapine, quetiapine, sertraline, trazodone, and venlafaxine, from inpatients with a broad spectrum of psychiatric diseases receiving COVID-19 vaccinations were collected at 2 medical centers between 08/2021 and 02/2022 under steady-state conditions before and after vaccination. Postvaccination changes were estimated as a percentage of baseline. RESULTS: Data from 16 patients who received COVID-19 vaccination were included. The largest changes in plasma levels were reported for quetiapine (+101.2%) and trazodone (-38.5%) in 1 and 3 patients, respectively, 1 day postvaccination compared with baseline levels. One week postvaccination, the plasma levels of fluoxetine (active moiety) and escitalopram increased by 31% and 24.9%, respectively. CONCLUSIONS: This study provides the first evidence of major changes in the plasma levels of escitalopram, fluoxetine, trazodone, and quetiapine after COVID-19 vaccination. When planning COVID-19 vaccination for patients treated with these medications, clinicians should monitor rapid changes in bioavailability and consider short-term dose adjustments to ensure safety.

Deep Learning in the Identification of Electroencephalogram Sources Associated with Sexual Orientation.

INTRODUCTION: It is unclear if sexual orientation is a biological trait that has neurofunctional footprints. With deep learning, the power to classify biological datasets without an a priori selection of features has increased by magnitudes. The aim of this study was to correctly classify resting-state electroencephalogram (EEG) data from males with different sexual orientation using deep learning and to explore techniques to identify the learned distinguishing features. METHODS: Three cohorts (homosexual men, heterosexual men, and a mixed sex cohort), one pretrained network on sex classification, and one newly trained network for sexual orientation classification were used to classify sex. Further, Grad-CAM methodology and source localization were used to identify the spatiotemporal patterns that were used for differentiation by the networks. RESULTS: Using a pretrained network for classification of males and females, no differences existed between classification of homosexual and heterosexual males. The newly trained network was able, however, to correctly classify the cohorts with a total accuracy of 83%. The retrograde activation using Grad-CAM technology yielded distinctive functional EEG patterns in the Brodmann area 40 and 1 when combined with Fourier analysis and a source localization. DISCUSSION: This study shows that electrophysiological trait markers of male sexual orientation can be identified using deep learning. These patterns are different from the differentiating signatures of males and females in a resting-state EEG.

Athletes are not at greater risk for death by suicide: A review.

INTRODUCTION: Suicide represents a major mental and public health issue. Elite athletes share certain individual and environmental characteristics that may increase their risk for mental illnesses, ultimately leading to suicide. This notion conflicts with the general perception of athletes, being the healthiest representatives of society. METHODS: A comprehensive literature search was carried out through PubMed and Embase databases for relevant publications. RESULTS: Recent calls for investigating suicidality among athletes resulted in a considerable amount of literature providing some evidence regarding lower rates of suicide among professional and high-performance athletes as well as similar incidence and prevalence of mental conditions, which are known as risk factors for suicide. Nevertheless, special attention is required in this population as predisposing and precipitating factors might differ from classical features of suicidality in the general population. Sports physicians, sports psychiatrists, and other mental health professionals in elite sports should be aware of early signs of affective disorders, risk of recreational drug abuse, misuse of performance-enhancing medications, sport-specific environmental stressors, serious physical injuries, and presence of physical or mental illness, all of which may increase suicidality. Traumatic brain injury (TBI) is with suicide with higher severity correlated with increased risk. Compared to active athletes, former athletes may have higher rates of suicide due to common life stressors occurring after sports retirement. CONCLUSIONS: The findings suggest a multidisciplinary approach to suicidality in elite athletes, the main goal of which should be the reduction of suicide-related morbidity and mortality. Further research is required to clarify the existing gaps in the current knowledge of the issue. While having lower rates of suicide, athletes share some similar (affective disorders, drug abuse, mental and physical illness) and unique factors (misuse of performance-enhancing substances, sports-related stressors, sports injuries, TBI) putting them at risk of suicide during active career and retirement.

Alive and kicking: suicide rates and major soccer events in Austria, Germany and Switzerland.

BACKGROUND: Major sporting events are postulated to reduce suicide rates by increased social connectedness, by identifying with winning teams, or, conversely, to increase suicide rates by the 'broken promise effect'. METHODS: In our observational epidemiological study, we investigated changes in suicide rates between 1970 and 2017 in Austria, Germany and Switzerland during the European and World Soccer Championships in general, and on days that the home team played, won or lost. RESULTS: Combining all three studied nations no statistically significant change in the incidence of daily suicides during soccer championships compared to a control period was noted (38.29 ± 9.02 vs. 37.33 ± 10.58; incidence risk ratio = 1.03; 95% confidence interval: 1.01-1.05, P = 0.05). Essentially, no differences in the expected directions were found, and none remained statistically significant after correcting for multiple comparisons in subgroups for country, age and gender in all three studied countries. Compared to a control period, neither a significant difference in the respective national suicide rate was found after Germany's four championship victories nor after Austria's emotional only win over Germany. CONCLUSION: Our results do not support the assumption of increased social connectedness and, thus, lowered suicide risk during major sporting events or changes in suicide risk depending on the outcome of important games as predicted by the broken promise effect or changes in self-efficacy by identification with winning teams.

Effectiveness of crisis resolution home treatment for the management of acute psychiatric crises in Southern Switzerland: a natural experiment based on geography.

BACKGROUND: Crisis Resolution Home Treatment (CRHT) is an alternative to inpatient treatment for acute psychiatric crises management. However, evidence on CRHT effectiveness is still limited. In the Canton of Ticino (Southern Switzerland), in 2016 the regional public psychiatric hospital replaced one acute ward with a CRHT. The current study was designed within this evaluation setting to assess the effectiveness of CRHT compared to standard inpatient treatment. METHODS: CRHT was offered to patients aged 18 to 65 with an acute psychiatric crisis that would have required hospitalization. We used a natural experiment based on geography, where intervention and control groups were formed according to the place of residence. Primary endpoints were reduction of psychiatric symptoms at discharge measured using the Health of the Nation Outcome Scales, treatment duration in days, and rate and length of readmissions during a two-year follow-up period after discharge. Safety during the treatment period was measured with the number of serious adverse events (suicide/suicide attempts, major self-harm episodes, acute alcohol/drug intoxications, aggressions to caregivers or family members). We used linear, log-linear and logistic regression models with propensity scores for the main analysis. RESULTS: We enrolled 321 patients; 67 were excluded because the treatment period was too short and 17 because they were transferred before the end of the treatment. Two hundred thirty-seven patients were available for data analysis, 93 in the intervention group and 144 in the control group. No serious adverse event was observed during the treatment period in both groups. Reduction of psychiatric symptoms at discharge (p-value = 0.359), readmission rates (p-value = 0.563) and length of readmissions (p-value = 0.770) during the two-year follow-up period did not differ significantly between the two groups. Treatment duration was significantly higher in the treatment group (+ 29.6% on average, p-value = 0.002). CONCLUSIONS: CRHT was comparable to standard hospitalization in terms of psychiatric symptoms reduction, readmission rates and length of readmissions, but it was also characterized by a longer first treatment period. However, observational evidence following the study indicated that CRHT duration constantly lowered over time since its introduction in 2016 and became comparable to hospitalization, showing therefore to be an effective alternative also in terms of treatment length. TRIAL REGISTRATION: ISRCTN38472626 (17/11/2020, retrospectively registered).

Automaticity of Early Sexual Attention: An Event-Related Potential Study.

A promising line of research on forensic assessment of paraphilic sexual interest focuses on behavioral measures of visual attention using sexual stimuli as distractors. The present study combined event-related potentials (ERPs) with behavioral measures to investigate whether detection of a hidden sexual preference can be improved with ERPs. Normal variants of sexual orientation were used for a proof-of-concept investigation. Accordingly, 40 heterosexual and 40 gay men participated in the study. Within each group, half of the participants were instructed to hide their sexual orientation. The results showed that a match between sexual orientation and stimulus delays responses and influences ERP before motor responses. Late ERP components showed higher potential in differentiating hidden sexual preferences than motor responses, thereby showing how ERPs can be used in combination with reaction time measures to potentially facilitate the detection of hidden sexual preferences.

mGluR5 receptor availability is associated with lower levels of negative symptoms and better cognition in male patients with chronic schizophrenia.

Consistent findings postulate disturbed glutamatergic function (more specifically a hypofunction of the ionotropic NMDA receptors) as an important pathophysiologic mechanism in schizophrenia. However, the role of the metabotropic glutamatergic receptors type 5 (mGluR5) in this disease remains unclear. In this study, we investigated their significance (using [11 C]ABP688) for psychopathology and cognition in male patients with chronic schizophrenia and healthy controls. In the patient group, lower mGluR5 binding potential (BPND ) values in the left temporal cortex and caudate were associated with higher general symptom levels (negative and depressive symptoms), lower levels of global functioning and worse cognitive performance. At the same time, in both groups, mGluR5 BPND were significantly lower in smokers (F[27,1] = 15.500; p = .001), but without significant differences between the groups. Our findings provide support for the concept that the impaired function of mGluR5 underlies the symptoms of schizophrenia. They further supply a new perspective on the complex relationship between tobacco addiction and schizophrenia by identifying glutamatergic neurotransmission-in particularly mGluR5-as a possible connection to a shared vulnerability.

'Placement budgets' for supported employment: impact on employment rates in a multicentre randomised controlled trial.

BACKGROUND: The most effective rehabilitation model for job (re-)entry of people with mental illness is supported employment. A barrier to introducing supported employment into standard care is its temporally unlimited provision, which conflicts with health and social legislation in many European countries. AIMS: To test the impact of different 'placement budgets', i.e. a predefined maximum time budget for job seeking until take-up of competitive employment. METHOD: Participants (116) were randomly assigned to 25 h, 40 h or 55 h placement budgets in an intent-to-treat analysis. We applied the individual placement and support model over 24 months, following participants for 36 months. Primary outcome was employment in the labour market for at least 3 months. RESULTS: The proportion of participants obtaining competitive employment was 55.1% in the 25 h group, 37.8% in the 40 h group and 35.8% in the 55 h group. In a Cox regression analysis, time to employment was slightly lower in the 25 h group relative to the 40 h (hazard ratio 1.78, 95% CI 0.88-3.57, P = 0.107) and 55 h groups (hazard ratio 1.74, 95% CI 0.86-3.49, P = 0.122), but this was not statistically significant. The vast majority of all participants who found a job did so within the first 12 months (80.4%). CONCLUSION: A restricted time budget for job finding and placement does not affect the rate of successful employment. In accordance with legislation, a restriction of care provision seems justified and enhances the chances of supported employment being introduced in statutory services.

Home treatment for acute mental healthcare: randomised controlled trial.

BACKGROUND: Home treatment has been proposed as an alternative to acute in-patient care for mentally ill patients. However, there is only moderate evidence in support of home treatment. AIMS: To test whether and to what degree home treatment services would enable a reduction (substitution) of hospital use. METHOD: A total of 707 consecutively admitted adult patients with a broad spectrum of mental disorders (ICD-10: F2-F6, F8-F9, Z) experiencing crises that necessitated immediate admission to hospital, were randomly allocated to either a service model including a home treatment alternative to hospital care (experimental group) or a conventional service model that lacked a home treatment alternative to in-patient care (control group) (trial registration at ClinicalTrials.gov: NCT02322437). RESULTS: The mean number of hospital days per patient within 24 months after the index crisis necessitating hospital admission (primary outcome) was reduced by 30.4% (mean 41.3 v. 59.3, P<0.001) when a home treatment team was available (intention-to-treat analysis). Regarding secondary outcomes, average overall treatment duration (hospital days + home treatment days) per patient (mean 50.4 v. 59.3, P = 0.969) and mean number of hospital admissions per patient (mean 1.86 v. 1.93, P = 0.885) did not differ statistically significantly between the experimental and control groups within 24 months after the index crisis. There were no significant between-group differences regarding clinical and social outcomes (Health of the Nation Outcome Scales: mean 9.9 v. 9.7, P = 0.652) or patient satisfaction with care (Perception of Care questionnaire: mean 0.78 v. 0.80, P = 0.242). CONCLUSIONS: Home treatment services can reduce hospital use among severely ill patients in acute crises and seem to result in comparable clinical/social outcomes and patient satisfaction as standard in-patient care.

Impact of Chronic Cannabis Use on Auditory Mismatch Negativity Generation in Schizophrenia Patients.

INTRODUCTION: Cannabis use disorders (CUD) are highly prevalent among patients with schizophrenia (SCZ). Deficient mismatch negativity (MMN) generation is a characteristic finding in SCZ patients and cannabis users. This study therefore examined the effects of CUD on MMN generation in SCZ patients. METHODS: Twenty SCZ - CUD patients, 21 SCZ+CUD patients, and 20 healthy controls (HC) were included in this study. MMN to frequency and duration deviants was elicited within an auditory oddball paradigm and recorded by 32 channel EEG. RESULTS: As expected, SCZ - CUD patients showed reduced frontocentral MMN amplitudes to duration deviants compared to HC. Interestingly, SCZ+CUD patients demonstrated greater MMN amplitudes to duration deviants compared to SCZ - CUD patients at central electrodes with no differences compared to HC. DISCUSSION: These results demonstrate that comorbid cannabis use in SCZ patients might be associated with superior cognitive functioning. It can be assumed that the association between cannabis use and better cognitive performance may be due to a subgroup of cognitively less impaired SCZ patients characterized by lower genetic vulnerability for psychosis.

Pure delta-9-tetrahydrocannabinol and its combination with cannabidiol in treatment-resistant Tourette syndrome: A case report.

OBJECTIVES: Anecdotal reports and preliminary studies suggest a therapeutic potential of cannabis in Tourette syndrome. We report the case of a female patient suffering from treatment-resistant Tourette syndrome. METHODS: Guideline-directed antipsychotic treatment with risperidone and aripiprazole as well as pure delta-9-tetrahydrocannabinol had no significant effect on Tourette syndrome symptomatology. RESULTS: Following administration of a daily dosage of 10 mg delta-9-tetrahydrocannabinol combined with 20 mg cannabidiol (CBD), the patient showed a rapid and highly significant improvement in the Yale Global Tic Severity Scale. CONCLUSIONS: It can be speculated whether the beneficial effects may rely on the pharmacological properties of cannabidiol.

Association between Cortical GABA and Loudness Dependence of Auditory Evoked Potentials (LDAEP) in Humans.

Loudness dependence of auditory evoked potentials (LDAEP) is a widely used EEG-based biomarker for central serotonergic activity. Serotonin has been shown to be associated with different psychiatric disorders such as depression and schizophrenia. Despite its clinical significance, the underlying neurochemical mechanism of this promising marker is not fully understood, and further research is needed to improve its validity. Other neurotransmitters might have a significant impact on this measure. Thus, we assessed the inhibitory action through individual GABA/H20 concentrations and GABA/glutamate ratios by means of magnetic resonance spectroscopy at 3T in healthy subjects. The measurements were assessed in the primary auditory cortex to investigate the association with the LDAEP, whose generators are mainly in the primary auditory cortex. For the first time, this study examines the link between GABAergic neurotransmission and LDAEP, and the data preliminary show that GABA may not contribute to the generation of EEG-based LDAEP.

Self-stigma as a barrier to recovery: a longitudinal study.

Stigma limits life opportunities of persons with mental illness. Self-stigma, the internalization of negative stereotypes, undermines empowerment and could hinder recovery. Here we examined self-stigma's effect on recovery among 222 disability pensioners with mental illness over 2 years, controlling for age, gender, symptoms and recovery at baseline measured by the Recovery Assessment Scale. More self-stigma at baseline was associated with a significant decrease in recovery after 1 year (not significant after 2 years). An increase of self-stigma from baseline to follow-up predicted less recovery 1 and 2 years later. Interventions that reduce self-stigma could therefore improve recovery.

The gravitational force of mental health services: distance decay effects in a rural Swiss service area.

BACKGROUND: Previous research suggested a distance decay effect in health services systems, with people living closer to service facilities being more likely to use them. METHOD: In this ecological cross sectional study, we conducted spatial and statistical analyses in a Swiss mental health services system being legally bound to provide primary mental health care to approximately 620,000 inhabitants. We examined a cohort of all patients who were over 18 years old and who were treated in the mental health services system between January and December 2011. RESULTS: There were 5574 treatment cases during the 12-month period, 2161 inpatient cases and 3413 outpatient cases. Travel time by public transportation between patients' residence and the closest mental health service facility negatively predicted the utilization of outpatient services for all mental disorders, even after controlling for variability in ecological (e.g. socioeconomic) characteristics of the communities in the service provision area. For utilization of inpatient wards no geographical distance decay effect was observed, except for organic mental disorders. CONCLUSIONS: Based on these findings, outpatient clinics should be most effectively located decentralized and in the largest communities to meet the needs of the population as close as possible to where people live and to avoid remote areas being insufficiently supplied with mental health care. For mental hospitals and inpatient services decentralized location seems to be less important.

GABA metabolism and its role in gamma-band oscillatory activity during auditory processing: An MRS and EEG study.

Gamma-aminobutyric acid (GABA) and glutamate are believed to have inhibitory and exhibitory neuromodulatory effects that regulate the brain's response to sensory perception. Furthermore, frequency-specific synchronization of neuronal excitability within the gamma band (30-80 Hz) is attributable to a homeostatic balance between excitation and inhibition. However, our understanding of the physiological mechanism underlying gamma rhythms is based on animal models. Investigations of the relationship between GABA concentrations, glutamate concentrations, and gamma band activity in humans were mostly restricted to the visual cortex and are conflicting. Here, we performed a multimodal imaging study combining magnetic resonance spectroscopy (MRS) with electroencephalography (EEG) in the auditory cortex. In 14 healthy subjects, we investigated the impact of individual differences in GABA and glutamate concentration on gamma band response (GBR) following auditory stimulus presentation. We explored the effects of bulk GABA on the GBR across frequency (30-200 Hz) and time (-200 to 600 ms) and found no significant relationship. Furthermore, no correlations were found between gamma peak frequency or power measures and metabolite concentrations (GABA, glutamate, and GABA/glutamate ratio). These findings suggest that, according to MRS measurements, and given the auditory stimuli used in this study, GABA and glutamate concentrations are unlikely to play a significant role in the inhibitory and excitatory drive in the generation of gamma band activity in the auditory cortex. Hum Brain Mapp 38:3975-3987, 2017. © 2017 Wiley Periodicals, Inc.

Self-stigma and suicidality: a longitudinal study.

Mental illness stigma is a source of distress for persons with mental illness. Self-stigma occurs when negative stereotypes are internalized, leading to low self-esteem, shame and hopelessness. Due to its consequences self-stigma may contribute to suicidality and be a modifiable target for suicide prevention. Based on 222 disability pensioners with mental illness we examined whether self-stigma at baseline is associated with suicidal ideation over a 2-year period, controlling for baseline suicidal ideation, symptoms, age and gender. More self-stigma predicted suicidal ideation at baseline and longitudinally. Interventions on different levels to reduce self-stigma could improve suicide prevention.

Recovery and decision-making involvement in people with severe mental illness from six countries: a prospective observational study.

BACKGROUND: Clinical decision-making is the vehicle of health care provision, and level of involvement predicts implementation and satisfaction. The aim of this study was to investigate the impact of decision-making experience on recovery. METHODS: Data derived from an observational cohort study "Clinical decision making and outcome in routine care for people with severe mental illness" (CEDAR). Adults (aged 18-60) meeting standardised criteria for severe mental illness were recruited from caseloads of outpatient and community mental health services in six European countries. After consenting, they were assessed using standardised measures of decision-making, clinical outcome and stage of recovery at baseline and 1 year later. Latent class analysis was used to identify course of recovery, and proportional odds models to investigate predictors of recovery stage and change. RESULTS: Participants (n = 581) clustered into three stages of recovery at baseline: Moratorium (N = 115; 19.8%), Awareness/Preparation (N = 145; 25.0%) and Rebuilding/Growth (N = 321; 55.2%). Higher stage was cross-sectionally associated with being male, married, living alone or with parents, and having better patient-rated therapeutic alliance and fewer symptoms. The model accounted for 40% of the variance in stage of recovery. An increased chance of worse outcome (change over 1 year to lower stage of recovery) was found for patients with active involvement compared with either shared (OR = 1.84, 95% CI 1.15-2.94) or passive (OR = 1.71, 95% CI = 1.00-2.95) involvement. Overall, both process (therapeutic relationship) and outcome (symptomatology) are cross-sectionally associated with stage of recovery. CONCLUSIONS: Patient-rated decision-making involvement and change in stage of recovery are associated. Joint consideration of decision practise within the recovery process between patient and clinician is supposed to be a useful strategy to improve clinical practice (ISRCTN registry: ISRCTN75841675. Retrospectively registered 15 September 2010).

Helping Alliance and Unmet Needs in Routine Care of People With Severe Mental Illness Across Europe: A Prospective Longitudinal Multicenter Study.

The helping alliance (HA) refers to the collaborative bond between patient and therapist, including shared goals and tasks. People with severe mental illness have a complex mixture of clinical and social needs. Using mixed-effects regression, this study examined in 588 people with severe mental illness whether an increase in the HA is associated with fewer unmet needs over time, and whether change in the HA precedes change in unmet needs. It was found that a reduction in unmet needs was slower in patients with higher HA (B = 0.04, p < 0.0001) only for patient-rated measures. Improvement in both patient-rated and staff-rated HA over time was associated with fewer subsequent patient-rated (B = -0.10, p < 0.0001) and staff-rated (B = -0.08, p = 0.0175) unmet needs. With positive changes in the HA preceding fewer unmet needs, findings provide further evidence for a causal relationship between alliance and outcome in the treatment of people with severe mental illness.

Effectiveness of Medical Rehabilitation on Return-to-Work Depends on the Interplay of Occupation Characteristics and Disease.

Introduction Work disability causes high costs for economy, organizations, and employees. However, medical rehabilitation does not always enable employees to return to their old jobs. In the present study, we investigated how disease classification and work characteristics interact in predicting the success of medical rehabilitation in terms of one's ability to return to a former job. Methods To this end, we matched 2009 patient data from the German Statutory Pension Insurance agency with job characteristics data from the Occupational Information Network (O*NET) 17.0 database. We used a multilevel approach and a sample of N = 72,029, nested in 194 occupational groups. Results We found that workers are less likely to reenter a former job if mental illnesses coincide with emotionally demanding labor and if musculoskeletal diseases coincide with extreme environmental conditions. We did not find different effects between occupational groups for other types of diseases (circulatory system, neoplasms, injuries, others). Conclusion Thus, the contextual overlap of disease and occupational characteristics notably lowers the chances of a successful return-to-work. These findings should be taken into account by physicians when attempting to set realistic goals for rehabilitation in collaboration with the patient and the funding agency.