Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice.

Current approaches to the treatment of schizophrenia have mainly focused on the protein-coding part of the genome; in this context, the roles of microRNAs have received less attention. In the present study, we analyze the microRNAome in the blood and postmortem brains of schizophrenia patients, showing that the expression of miR-99b-5p is downregulated in both the prefrontal cortex and blood of patients. Lowering the amount of miR-99b-5p in mice leads to both schizophrenia-like phenotypes and inflammatory processes that are linked to synaptic pruning in microglia. The microglial miR-99b-5p-supressed inflammatory response requires Z-DNA binding protein 1 (Zbp1), which we identify as a novel miR-99b-5p target. Antisense oligonucleotides against Zbp1 ameliorate the pathological effects of miR-99b-5p inhibition. Our findings indicate that a novel miR-99b-5p-Zbp1 pathway in microglia might contribute to the pathogenesis of schizophrenia.

[Genetic studies on forensic-psychiatric inpatients? : Clinical, ethical and legal considerations]. / Genetische Studien an forensisch Untergebrachten? : Klinische, ethische und juristische Überlegungen.

BACKGROUND: Research on people deprived of liberty raises serious questions, especially concerning behavioral genetic studies. QUESTION: Does including criminally detained patients with mental disorders in genetic studies lead to a gain of new knowledge and can this be ethically and legally justified? METHOD: Evaluation of existing literature and interdisciplinary reflection. RESULTS: After a review of research ethics and legal norms, we consider the benefits and risks of behavioral genetic research, taking the unique situation of test persons deprived of their liberty into account. The fundamental right to freedom of research also justifies foundational research in forensic psychiatry and psychotherapy. The possible future benefits of improving treatment plans must be weighed against the risks resulting from potential data leaks and inappropriate public reception of research results. Then we analyze possible threats to voluntary and informed consent to study participation in more detail by the ethical concept of vulnerability. Alongside problems with grasping complex issues, above all dependencies and power dynamics in the correctional system play a pivotal role. Recommendations on the ethical and legal inclusion of this study population are given. CONCLUSION: Including criminally detained study participants can be ethically and legally justified when autonomous consent is supported by specific organizational and legal procedures and measures, for example via a clear professional and organizational separation of correction and research.

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.

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.

Genetic contributions to transdiagnostic symptom dimensions in patients with major depressive disorder, bipolar disorder, and schizophrenia spectrum disorders.

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia spectrum disorders (SZ) exhibit considerable phenotypic and genetic overlap. However, the contribution of genetic factors to their shared psychopathological symptom dimensions remains unclear. The present exploratory study investigated genetic contributions to the symptom dimensions "Depression", "Negative syndrome", "Positive formal thought disorder", "Paranoid-hallucinatory syndrome", and "Increased appetite" in a transdiagnostic subset of the German FOR2107 cohort (n = 1042 patients with MDD, BD, or SZ). As replication cohort, a subset of the German/Austrian PsyCourse study (n = 816 patients with MDD, BD, or SZ) was employed. First, the relationship between symptom dimensions and common variants associated with MDD, BD, and SZ was investigated via polygenic risk score (PRS) association analyses, with disorder-specific PRS as predictors and symptom dimensions as outcomes. In the FOR2107 study sample, PRS for BD and SZ were positively associated with "Positive formal thought disorder", the PRS for SZ was positively associated with "Paranoid-hallucinatory syndrome", and the PRS for BD was negatively associated with "Depression". The effects of PRS for SZ were replicated in PsyCourse. No significant associations were observed for the MDD PRS. Second, genome-wide association studies (GWAS) were performed for the five symptom dimensions. No genome-wide significant associations and no replicable suggestive associations (p < 1e-6 in the GWAS) were identified. In summary, our results suggest that, similar to diagnostic categories, transdiagnostic psychiatric symptom dimensions are attributable to polygenic contributions with small effect sizes. Further studies in larger thoroughly phenotyped psychiatric cohorts are required to elucidate the genetic factors that shape psychopathological symptom dimensions.

Lipid Alteration Signature in the Blood Plasma of Individuals With Schizophrenia, Depression, and Bipolar Disorder.

Importance: No clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers. Objective: To define a reproducible profile of lipid alterations in the blood plasma of patients with schizophrenia (SCZ) independent of demographic and environmental variables and to investigate its specificity in association with other psychiatric disorders, ie, major depressive disorder (MDD) and bipolar disorder (BPD). Design, Setting, and Participants: This was a multicohort case-control diagnostic analysis involving plasma samples from psychiatric patients and control individuals collected between July 17, 2009, and May 18, 2018. Study participants were recruited as consecutive and volunteer samples at multiple inpatient and outpatient mental health hospitals in Western Europe (Germany and Austria [DE-AT]), China (CN), and Russia (RU). Individuals with DSM-IV or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of SCZ, MDD, BPD, or a first psychotic episode, as well as age- and sex-matched healthy controls without a mental health-related diagnosis were included in the study. Samples and data were analyzed from January 2018 to September 2020. Main Outcomes and Measures: Plasma lipidome composition was assessed using liquid chromatography coupled with untargeted mass spectrometry. Results: Blood lipid levels were assessed in 980 individuals (mean [SD] age, 36 [13] years; 510 male individuals [52%]) diagnosed with SCZ, BPD, MDD, or those with a first psychotic episode and in 572 controls (mean [SD] age, 34 [13] years; 323 male individuals [56%]). A total of 77 lipids were found to be significantly altered between those with SCZ (n = 436) and controls (n = 478) in all 3 sample cohorts. Alterations were consistent between cohorts (CN and RU: [Pearson correlation] r = 0.75; DE-AT and CN: r = 0.78; DE-AT and RU: r = 0.82; P < 10-38). A lipid-based predictive model separated patients with SCZ from controls with high diagnostic ability (area under the receiver operating characteristic curve = 0.86-0.95). Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were found to be similar to those of SCZ (BPD: r = 0.89; MDD: r = 0.92; P < 10-79). Assessment of detected alterations in individuals with a first psychotic episode, as well as patients with SCZ not receiving medication, demonstrated only limited association with medication restricted to particular lipids. Conclusions and Relevance: In this study, SCZ was accompanied by a reproducible profile of plasma lipidome alterations, not associated with symptom severity, medication, and demographic and environmental variables, and largely shared with BPD and MDD. This lipid alteration signature may represent a trait marker of severe psychiatric disorders, indicating its potential to be transformed into a clinically applicable testing procedure.

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.

Stability over time of scores on psychiatric rating scales, questionnaires and cognitive tests in healthy controls.

BACKGROUND: Case-only longitudinal studies are common in psychiatry. Further, it is assumed that psychiatric ratings and questionnaire results of healthy controls stay stable over foreseeable time ranges. For cognitive tests, improvements over time are expected, but data for more than two administrations are scarce. AIMS: We comprehensively investigated the longitudinal course for trends over time in cognitive and symptom measurements for severe mental disorders. Assessments included the Trail Making Tests, verbal Digit Span tests, Global Assessment of Functioning, Inventory of Depressive Symptomatology, the Positive and Negative Syndrome Scale, and the Young Mania Rating Scale, among others. METHOD: Using the data of control individuals (n = 326) from the PsyCourse study who had up to four assessments over 18 months, we modelled the course using linear mixed models or logistic regression. The slopes or odds ratios were estimated and adjusted for age and gender. We also assessed the robustness of these results using a longitudinal non-parametric test in a sensitivity analysis. RESULTS: Small effects were detected for most cognitive tests, indicating a performance improvement over time (P < 0.05). However, for most of the symptom rating scales and questionnaires, no effects were detected, in line with our initial hypothesis. CONCLUSIONS: The slightly but consistently improved performance in the cognitive tests speaks of a test-unspecific positive trend, while psychiatric ratings and questionnaire results remain stable over the observed period. These detectable improvements need to be considered when interpreting longitudinal courses. We therefore recommend recruiting control participants if cognitive tests are administered.

Investigating the phenotypic and genetic associations between personality traits and suicidal behavior across major mental health diagnoses.

Personality traits influence risk for suicidal behavior. We examined phenotype- and genotype-level associations between the Big Five personality traits and suicidal ideation and attempt in major depressive, bipolar and schizoaffective disorder, and schizophrenia patients (N = 3012) using fixed- and random-effects inverse variance-weighted meta-analyses. Suicidal ideations were more likely to be reported by patients with higher neuroticism and lower extraversion phenotypic scores, but showed no significant association with polygenic load for these personality traits. Our findings provide new insights into the association between personality and suicidal behavior across mental illnesses and suggest that the genetic component of personality traits is unlikely to have strong causal effects on suicidal behavior.

Genetic risk for psychiatric illness is associated with the number of hospitalizations of bipolar disorder patients.

OBJECTIVES: Bipolar disorder (BD) has a highly heterogeneous clinical course that is characterized by relapses and increased health care utilization in a significant fraction of patients. A thorough understanding of factors influencing illness course is essential for predicting disorder severity and developing targeted therapies. METHODS: We performed polygenic score analyses in four cohorts (N = 954) to test whether the genetic risk for BD, schizophrenia, or major depression is associated with a severe course of BD. We analyzed BD patients with a minimum illness duration of five years. The severity of the disease course was assessed by using the number of hospitalizations in a mental health facility and a composite measure of longitudinal illness severity (OPCRIT item 90). RESULTS: Our analyses showed that higher polygenic scores for BD (ß = 0.11, SE = 0.03, p = 1.17 × 10-3) and schizophrenia (ß = 0.09, SE = 0.03, p = 4.24 × 10-3), but not for major depression, were associated with more hospitalizations. None of the investigated polygenic scores was associated with the composite measure of longitudinal illness severity (OPCRIT item 90). LIMITATIONS: We could not account for non-genetic influences on disease course. Our clinical sample contained more severe cases. CONCLUSIONS: This study demonstrates that the genetic risk burden for psychiatric illness is associated with increased health care utilization, a proxy for disease severity, in BD patients. The findings are in line with previous observations made for patients diagnosed with schizophrenia or major depression. Therefore, in the future psychiatric disorder polygenic scores might become helpful for stratifying patients with high risk of a chronic manifestation and predicting disease course.

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 microRNA signature that correlates with cognition and is a target against cognitive decline.

While some individuals age without pathological memory impairments, others develop age-associated cognitive diseases. Since changes in cognitive function develop slowly over time in these patients, they are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for the identification of inexpensive and minimal invasive approaches that could be used for screening with the aim to identify individuals at risk for cognitive decline that can then undergo further diagnostics and eventually stratified therapies. In this study, we use an integrative approach combining the analysis of human data and mechanistic studies in model systems to identify a circulating 3-microRNA signature that reflects key processes linked to neural homeostasis and inform about cognitive status. We furthermore provide evidence that expression changes in this signature represent multiple mechanisms deregulated in the aging and diseased brain and are a suitable target for RNA therapeutics.

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.

The Genetics of Response to and Side Effects of Lithium Treatment in Bipolar Disorder: Future Research Perspectives.

Although the mood stabilizer lithium is a first-line treatment in bipolar disorder, a substantial number of patients do not benefit from it and experience side effects. No clinical tool is available for predicting lithium response or the occurrence of side effects in everyday clinical practice. Multiple genetic research efforts have been performed in this field because lithium response and side effects are considered to be multifactorial endophenotypes. Available results from linkage and segregation, candidate-gene, and genome-wide association studies indicate a role of genetic factors in determining response and side effects. For example, candidate-gene studies often report GSK3ß, brain-derived neurotrophic factor, and SLC6A4 as being involved in lithium response, and the latest genome-wide association study found a genome-wide significant association of treatment response with a locus on chromosome 21 coding for two long non-coding RNAs. Although research results are promising, they are limited mainly by a lack of replicability and, despite the collaboration of consortia, insufficient sample sizes. The need for larger sample sizes and "multi-omics" approaches is apparent, and such approaches are crucial for choosing the best treatment options for patients with bipolar disorder. In this article, we delineate the mechanisms of action of lithium and summarize the results of genetic research on lithium response and side effects.

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.

Gamma transcranial alternating current stimulation improves mood and cognition in patients with major depression.

Major depression is one of the most common psychiatric disorders with a high rate of treatment resistance where new treatment options are urgently warranted. One of these new options are non-invasive brain stimulation techniques like transcranial magnetic or electric stimulation. One of the latter is transcranial Alternating Current Stimulation (tACS) in various frequencies. Here, we report a case series of six patients suffering from major depression treated with tACS in gamma (40 Hz) frequency. Patients were randomized to two groups, receiving either two 10-min stimulations (group 1) or a 20-min stimulation or per day (group 2) over ten days. Hamilton Depression Rating Scale and Beck Depression Inventory decreased during treatment in both study groups by 85% and 78% (group 1), or 62% and 24% respectively (group 2). Results also showed an improvement in cognitive functions assessed by word fluency and n-back test. It is hypothesized that gamma tACS could help to synchronize disturbed frequency bands in frontal and prefrontal cortex areas and thus restore dysbalanced neural connectivity in psychiatric disorders.

Gamma transcranial alternating current stimulation (γtACS) in obsessive-compulsive disorder: a case report

Die Zwangsstörung hat oftmals einen chronischen Verlauf mit Therapieresistenz gegenüber Psychopharmakotherapie und Psychotherapie. Neue nichtinvasive Hirnstimulationsverfahren könnten helfen, Zwangssymptome zu vermindern. In diesem Fallbericht wird die Behandlung einer Patientin mit Zwangsstörung dargestellt, die mit 10 transkraniellen Wechselstromstimulationen in Gamma-Frequenz (40 Hz) im Rahmen eines Heilversuchs behandelt wurde. Die Yale-Brown Obsessive-Compulsive Scale verminderte sich von 70 auf 59 Punkte, und die Hamilton Depression Rating Scale sank von 25 auf 12 Punkte. Daneben konnte eine Verbesserung des Regensburger Wortflüssigkeitstests, des Pfadfindertests und eines computergestützten n-back-Tests verzeichnet werden. Eine Hypothese für die Verbesserung der Zwangsstörung durch Gamma-Wechselstromstimulation könnte eine Auswirkung auf die bei psychischen Erkrankungen (Depression, Zwangsstörung) veränderte alpha-Frequenz sein. Der hier vorgestellte Fall bestätigt die Ergebnisse einer früheren Fallserie und gibt Anlass zur weiteren Untersuchung dieses Verfahrens.