Mismatch negativity generation in subjects at risk for psychosis: source analysis is more sensitive than surface electrodes in risk prediction.

Background: Deficits of mismatch negativity (MMN) in patients with schizophrenia have been demonstrated many times and there is growing evidence that alterations of MMN already exist in individuals at risk for psychosis. The present study examines differences in MMN between subjects fulfilling ultra-high risk (UHR) or only basic symptoms criteria and it addresses the question, if MMN source analysis can improve prediction of transition to psychosis. Methods: The MMN to duration, frequency, and intensity deviants was recorded in 50 healthy controls and 161 individuals at risk for psychosis classified into three subgroups: only basic symptoms (n = 74), only ultra-high risk (n = 13) and persons who fulfill both risk criteria (n = 74). Based on a three-source model of MMN generation, we conducted an MMN source analysis and compared the amplitudes of surface electrodes and sources among the three groups. Results: Significant differences in MMN generation among the four groups were revealed at surface electrodes Cz and C4 (p < 0.05) and at the frontal source (p < 0.001) for duration deviant stimuli. The 15 subjects from the risk groups who subsequently developed a manifest psychosis had a significantly lower MMN amplitude at frontal source (p = 0.019) without showing significant differences at surface electrodes. Low activity at frontal MMN source increased the risk of transition to manifest disease by the factor 3.12 in UHR subjects. Conclusion: MMN activity differed significantly between subjects presenting only basic symptoms and subjects which additionally meet UHR criteria. The largest differences between groups as well as between individuals with and without transition were observed at the frontal source. The present results suggest that source analysis is more sensitive than surface electrodes in psychosis risk prediction by MMN.

[The Value of Deep Brain Stimulation in Difficult-To-Treat and Treatment-Refractory Depression]. / Der Stellenwert der tiefen Hirnstimulation bei der schwer behandelbaren sowie therapierefraktären Depression.

The Value of Deep Brain Stimulation in Difficult-To-Treat and Treatment-Refractory Depression Abstract: Deep Brain Stimulation ("DBS") is a minimally invasive, neurosurgical and hypothesis-driven therapeutic procedure for permanent local regulation of pathological circuits. While depression represents a heterogeneous syndrome with multifactorial etiopathogenesis, neuroscience research is advancing evidence to identify network-level mechanisms that play an important role in the pathophysiology of depression. In the following article, we will review the role of DBS in treatment-resistant or difficult-to-treat depression. The aim is to increase the awareness of DBS and to discuss the challenges of its therapy and implementation.

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.

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.

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.

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.

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).

mGluR5 binding changes during a mismatch negativity task in a multimodal protocol with [11C]ABP688 PET/MR-EEG.

Currently, the metabotropic glutamate receptor 5 (mGluR5) is the subject of several lines of research in the context of neurology and is of high interest as a target for positron-emission tomography (PET). Here, we assessed the feasibility of using [11C]ABP688, a specific antagonist radiotracer for an allosteric site on the mGluR5, to evaluate changes in glutamatergic neurotransmission through a mismatch-negativity (MMN) task as a part of a simultaneous and synchronized multimodal PET/MR-EEG study. We analyzed the effect of MMN by comparing the changes in nondisplaceable binding potential (BPND) prior to (baseline) and during the task in 17 healthy subjects by applying a bolus/infusion protocol. Anatomical and functional regions were analyzed. A small change in BPND was observed in anatomical regions (posterior cingulate cortex and thalamus) and in a functional network (precuneus) after the start of the task. The effect size was quantified using Kendall's W value and was 0.3. The motor cortex was used as a control region for the task and did not show any significant BPND changes. There was a significant ΔBPND between acquisition conditions. On average, the reductions in binding across the regions were - 8.6 ± 3.2% in anatomical and - 6.4 ± 0.5% in the functional network (p ≤ 0.001). Correlations between ΔBPND and EEG latency for both anatomical (p = 0.008) and functional (p = 0.022) regions were found. Exploratory analyses suggest that the MMN task played a role in the glutamatergic neurotransmission, and mGluR5 may be indirectly modulated by these changes.

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.

Home Treatment for Acute Mental Health Care: Protocol for the Financial Outputs, Risks, Efficacy, Satisfaction Index and Gatekeeping of Home Treatment (FORESIGHT) Study.

BACKGROUND: Crisis Resolution and Home Treatment (CRHT) teams represent a community-based mental health service offering a valid alternative to hospitalization. CRHT teams have been widely implemented in various mental health systems worldwide, and their goal is to provide care for people with severe acute mental disorders who would be considered for admission to acute psychiatric wards. The evaluation of several home-treatment experiences shows promising results; however, it remains unclear which specific elements and characteristics of CRHT are more effective and acceptable. OBJECTIVE: This study aims to assess the acceptability, effectiveness, and cost-effectiveness of a new CRHT intervention in Ticino, Southern Switzerland. METHODS: This study includes an interventional, nonrandomized, quasi-experimental study combined with a qualitative study and an economic evaluation to be conducted over a 48-month period. The quasi-experimental evaluation involves two groups: patients in the northern area of the region who were offered the CRHT service (ie, intervention group) and patients in the southern area of the region who received care as usual (ie, control group). Individual interviews will be conducted with patients receiving the home treatment intervention and their family members. CRHT members will also be asked to participate in a focus group. The economic evaluation will include a cost-effectiveness analysis. RESULTS: The project is funded by the Swiss National Science Foundation as part of the National Research Program NRP74 for a period of 48 months starting from January 2017. As of October 2021, data for the nonrandomized, quasi-experimental study and the qualitative study have been collected, and the results are expected to be published by the end of the year. Data are currently being collected for the economic evaluation. CONCLUSIONS: Compared to other Swiss CRHT experiences, the CRHT intervention in Ticino represents a unique case, as the introduction of the service is backed by the closing of one of its acute wards. The proposed study will address several areas where there are evidence gaps or contradictory findings relating to the home treatment of acute mental crisis. Findings from this study will allow local services to improve their effectiveness in a challenging domain of public health and contribute to improving access to more effective care for people with severe mental disorders. TRIAL REGISTRATION: ISRCTN registry ISRCTN38472626; https://www.isrctn.com/ISRCTN38472626. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28191.

Long-Term Effects of the Individual Placement and Support Intervention on Employment Status: 6-Year Follow-Up of a Randomized Controlled Trial.

People with mental illness often experience difficulties with reintegration into the workplace, although employment is known to assist these individuals in their recovery process. Traditional approaches of "first train, then place" have been recently replaced by supported employment (SE) methods that carry strategy of "first place, then train." Individual placement and support (IPS) is one of the best-studied methods of SE, which core principles are individualized assistance in rapid job search with consequent placement in a paid employment position. A considerable amount of high-quality evidence supported the superiority of IPS over conventional methods in providing improved employment rates, longer job tenure, as well as higher salaries in competitive job markets. Nonetheless, our knowledge about the IPS-mediated long-term effects is limited. This non-interventional follow-up study of a previously published randomized controlled trial (RCT) called ZhEPP aimed to understand the long-term impact of IPS after 6 years since the initial intervention. Participants from the ZhEPP trial, where 250 disability pensioners with mental illnesses were randomized into either IPS intervention group or treatment as usual group (TAU), were invited to face-to-face interviews, during which employment status, job tenure, workload, and salaries were assessed. One hundred and fourteen individuals agreed to participate in this follow-up study. Although during the first 2 years post-intervention, the IPS group had higher employment rates (40% (IPS) vs. 28% (TAU), p < 0.05 at 24 months), these differences disappeared by the time of follow-up assessments (72 months). The results indicated no substantial differences in primary outcome measures between IPS and TAU groups: employment rate (36 vs. 33%), workload (10.57 vs. 10.07 h per week), job tenure (29 vs. 28 months), and salary (20.21CHF vs. 25.02 CHF). These findings provide important insights regarding the long-term effects of IPS among individuals with mental health illnesses. Further research is required to advance the current knowledge about IPS intervention and its years-long impact.

Sociodemographic and Clinical Predictors of the Length of Psychiatric Inpatient Stay of Immigrants in Switzerland.

Immigrants with mental disorders have consistently been reported to spend shorter time in the psychiatric hospital compared to native patients. The aim of this study was to identify sociodemographic, clinical and migration-related predictors of a shorter length of psychiatric inpatient stay among immigrants in Switzerland. All patients of a foreign nationality admitted for inpatient treatment in the year 2016 (N = 279) were included in this study. The sample characteristics were drawn from the register of the psychiatric hospital. Within this sample, self-harm and substance use predicted a shorter inpatient treatment episode whereas disturbances of general psychosocial functioning were a predictor of a longer length of stay. As similar results were also reported for non-immigrant patients, the impact of these specific behavioral and social problems on the length of inpatient stay does not appear to be migrant-specific. Moreover, a country of origin outside Europe was a strong predictor of shorter length of stay pointing to inequalities of inpatient psychiatric treatment within the group of immigrants. Therefore, the cultural background and migrant history of immigrants in psychiatry need stronger consideration in order to eliminate disadvantages in mental health care.

Treating Schizophrenia: Open Conversations and Stronger Relationships Through Psychoeducation and Shared Decision-Making.

Integrated pharmacological and psychosocial treatments, such as psychoeducation (PE) and shared decision-making (SDM), have been shown to significantly improve outcomes for people living with schizophrenia (PLWS). Underpinning the success of these interventions is a strong therapeutic relationship between PLWS, their carers, and their healthcare team. While many recognize the value of this relationship, implementation of the interventions necessary to facilitate its construction remain low. In this article, we identify the barriers to developing productive therapeutic relationships and explain how PE and SDM, taking into account cultural difference, can improve adherence to treatment, strengthen therapeutic relationships, and ultimately equip patients to achieve better functional outcomes.

Psychiatric Acute Day Hospital as an Alternative to Inpatient Treatment.

For the first time in the Swiss health care system, this evaluation study examined whether patients with acute psychiatric illness who were admitted for inpatient treatment could be treated in an acute day hospital instead. The acute day hospital is characterized by the possibility of direct admission of patients without preliminary consultation or waiting time and is open every day of the week. In addition, it was examined whether and to what extent there are cost advantages for day hospital treatment. Patients who were admitted to the hospital with a referral to an inpatient admission were treated randomly either fully inpatient or in the acute day hospital. As a pilot study, 44 patients were admitted to the study. Evidence of efficacy could be provided for both treatment settings based on significant reduction in psychopathological symptoms and improvement in functional level in the course of treatment. There were no significant differences between the two settings in terms of external assessment of symptoms, subjective symptom burden, functional level, quality of life, treatment satisfaction, and number of treatment days. Treatment in the day hospital was about 45% cheaper compared to inpatient treatment. The results show that acutely ill psychiatric patients of different symptom severity can be treated just as well in an acute day hospital instead of being admitted to the hospital. In addition, when direct treatment costs are considered, there are clear cost advantages for day hospital treatment.

Frontal brain activity in individuals at risk for schizophrenic psychosis and bipolar disorder during the emotional Stroop task - an fNIRS study.

OBJECTIVES: The emotional Stroop effect is defined as increased reaction times to emotional stimuli compared to neutral ones. It has been often reported in the literature, on both behavioral and neurophysiological level. The goal of this study was to investigate the frontal brain activation in individuals at risk for schizophrenic psychosis and bipolar disorder during an emotional Stroop task. We expected to observe decreased activation in the at-risk individuals compared to the healthy controls. METHODS: Individuals at high risk for psychosis (HR), at ultra-high risk for psychosis (UHR), at risk for bipolar disorder (BIP) and healthy controls (HC) performed an emotional Stroop task, which included positively, negatively and neutrally valenced words. Functional near-infrared spectroscopy (fNIRS) was used to measure levels of oxygenated hemoglobin (O2Hb) representing brain activity in the dorsolateral prefrontal and frontotemporal cortex. RESULTS: Results showed significantly decreased levels of O2Hb in the right dorsolateral prefrontal cortex (DLPFC) in the HR and UHR groups compared to the HC, indicating lower activity. Even though the decrease was independent from the valence of the words, it was the most visible for the negative ones. Moreover, significantly lower O2Hb levels in the frontotemporal cortex (FTC) were observed in all at risk groups compared to the HC. CONCLUSIONS: Lower activity in the FTC in groups at risk for psychosis and bipolar disorder reflects unspecific dysfunctions. Decreased activity in the DLPFC in the HR and UHR groups indicates that hypofrontality can be found already in individuals at risk for schizophrenic psychosis.

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.