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Background: The present status of outpatient treatment of depression in Germany was evaluated with respect to the adherence of general practitioners (GPs) and specialists of psychiatry to clinical practice guidelines. Methods: In total, 488 depressed patients' psychopathology, diagnostic assessment, therapeutic measures and referral frequency were documented at inclusion into study by 43 general practitioners and 23 specialists of psychiatry in three regions of Germany. The investigation of change in depressive symptoms after six to eight weeks by means of self-assessment could be evaluated for 165 patients. Results: The results of diagnostic assessment demonstrated that diagnoses of depression were not always based on the diagnostic criteria for depression (ICD-10): 33% of GPs' and 17% of specialists' patients were included as depressed patients into the study despite not fulfilling the ICD-10 criteria in the standardized documentation. Therapeutic undertreatment was more often found in the group of GPs. Referrals were found not to be oriented towards guidelines. After six to eight weeks, one half of patients reported a reduction in depressed symptoms, the other half of patients reported a stagnation or even a progression. Conclusions: The study has shown that physicians in outpatient settings still fail to orient themselves towards guideline recommendations. This reflects the need for physicians to receive guideline training, with the aim of improving the quality of care for depression. A quality management intervention program consisting of guideline training and an interdisciplinary quality circle to improve depression treatment and networking was supported by the authors and is currently being evaluated.

Background: Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features. Methods: Following a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites (N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPI bipolar). Results: For BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11–0.361) and a balanced accuracy of 63.1% (95% CI 55.9–70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI −0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6–67.8). BARS and EPI bipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance. Conclusions: Individuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features. [ABSTRACT FROM AUTHOR]

Introduction: Numerous studies indicate impaired reward-related learning in individuals with schizophrenia, with various factors such as illness duration, medication, disease severity, and level of analysis (behavioral or neurophysiological data) potentially confounding the results. Patients with schizophrenia who are treated with second-generation antipsychotics have been found to have a less affected reward system. However, this finding does not explain the neural dysfunctions observed in previous studies. This study aimed to address the open question of whether the less impaired reward-related behavior is associated with unimpaired task-related functional connectivity or altered task-related functional connectivity. Methods: The study included 23 participants diagnosed within the schizophrenia spectrumand 23 control participantsmatched in terms of age, sex, and education. Participants underwent an MRI while performing a monetary incentive delay task and a social incentive delay task. The collected data were analyzed in terms of behavior and functional connectivity. Results: Both groups exhibited a main effect of reward type on behavioral performance, indicating faster reaction times in the social incentive delay task, but no main effect of reward level. Altered functional connectivity was observed in predictable brain regions within the patient group, depending on the chosen paradigm, but not when compared to healthy individuals. Discussion: In addition to expected slower response times, patients with schizophrenia demonstrated similar response patterns to control participants at the behavioral level. The similarities in behavioral data may underlie different connectivity patterns. Our findings suggest that perturbations in reward processing do not necessarily imply disturbances in underlying connectivities. Consequently, we were able to demonstrate that patients with schizophrenia are indeed capable of exhibiting goal-directed, reward-responsive behavior, although there are differences depending on the type of reward. [ABSTRACT FROM AUTHOR]

Introduction: One of the most important cognitive functions in our everyday life is the working memory (WM). In several neuropsychiatric diseases such as ADHD or schizophrenia WM deficits can be observed, making it an attractive target for non-invasive brain stimulation methods like transcranial electrical stimulation (tES). However, the literature shows rather heterogeneous results of tES effects on WM performance. fMRI meta-analyses have identified a WM network including frontoparietal brain areas such as the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC). Neurophysiological studies revealed oscillatory activity in the theta band frequency range to be of crucial functional relevance for WM processes. Based on this, transcranial alternating current stimulation (tACS) in the theta frequency range targeting DLPFC and PPC in a spatially optimized way might further improve effects of tES on WM performance. Methods: Sixteen healthy subjects were stimulated with varying stimulation settings on four different days in a counterbalanced within-subject design. These setups included the application of (1) tACS with a frequency of 5 Hz (theta frequency range) over the left DLPFC and (2) the right superior parietal cortex, (3) transcranial direct current stimulation (tDCS) of the DLPFC and (4) a sham stimulation condition during the online performance of a visual delayed-match-to-sample task with varying working memory load. We introduce a procedure to calculate an optimal tES model revealing optimized high-density setups for the present study for 3 cathodes and 1 anode and stimulation currents of 1.5 mA. Results: A significant interaction effect of stimulation type and load condition on working memory capacity was found. This was reflected by a significant improvement of WM performance in the high load condition during tACS over the left DLPFC compared with sham stimulation, which was not the case for our parietal tACS or tDCS setup. Discussion: Working memory performance can be improved with optimized high-definition tACS with a frequency of 5 Hz over the left DLPFC. The conception of different mechanisms underlying transcranial electrical stimulation with alternating and direct currents is supported by these results. Patients suffering from working memory impairments due to neuropsychiatric diseases might potentially benefit from this brain stimulation approach. [ABSTRACT FROM AUTHOR]

Background: While adolescent-onset schizophrenia (ADO-SCZ) and adolescent-onset bipolar disorder with psychosis (psychotic ADO-BPD) present a more severe clinical course than their adult forms, their pathophysiology is poorly understood. Here, we study potentially state- and trait-related white matter diffusion-weighted magnetic resonance imaging (dMRI) abnormalities along the adolescent-onset psychosis continuum to address this need. Methods: Forty-eight individuals with ADO-SCZ (20 female/28 male), 15 individuals with psychotic ADO-BPD (7 female/8 male), and 35 healthy controls (HCs, 18 female/17 male) underwent dMRI and clinical assessments. Maps of extracellular free-water (FW) and fractional anisotropy of cellular tissue (FAT) were compared between individuals with psychosis and HCs using tract-based spatial statistics and FSL's Randomise. FAT and FW values were extracted, averaged across all voxels that demonstrated group differences, and then utilized to test for the influence of age, medication, age of onset, duration of illness, symptom severity, and intelligence. Results: Individuals with adolescent-onset psychosis exhibited pronounced FW and FAT abnormalities compared to HCs. FAT reductions were spatially more widespread in ADO-SCZ. FW increases, however, were only present in psychotic ADO-BPD. In HCs, but not in individuals with adolescent-onset psychosis, FAT was positively related to age. Conclusions: We observe evidence for cellular (FAT) and extracellular (FW) white matter abnormalities in adolescent-onset psychosis. Although cellular white matter abnormalities were more prominent in ADO-SCZ, such alterations may reflect a shared trait, i.e. neurodevelopmental pathology, present across the psychosis spectrum. Extracellular abnormalities were evident in psychotic ADO-BPD, potentially indicating a more dynamic, state-dependent brain reaction to psychosis. [ABSTRACT FROM AUTHOR]

Background: Targeting the N-methyl-D-aspartate receptor (NMDAR) is a major translational approach for treating negative symptoms of schizophrenia. Ketamine comprehensively produces schizophrenia-like symptoms, such as positive, cognitive and negative symptoms in healthy volunteers. The amplitude of the mismatch negativity (MMN) is known to be significantly reduced not only in patients with schizophrenia, but also in healthy controls receiving ketamine. Accordingly, it was the aim of the present study to investigate whether changes of MMN amplitudes during ketamine administration are associated with the emergence of schizophrenialike negative symptoms in healthy volunteers. Methods: We examined the impact of ketamine during an MMN paradigm with 64-channel electroencephalography (EEG) and assessed the psychopathological status using the Positive and Negative Syndrome Scale (PANSS) in healthy male volunteers using a single-blind, randomized, placebo-controlled crossover design. Lowresolution brain electromagnetic tomography was used for source localization. Results: Twenty-four men were included in our analysis. Significant reductions of MMN amplitudes and an increase in all PANSS scores were identified under the ketamine condition. Smaller MMN amplitudes were specifically associated with more pronounced negative symptoms. Source analysis of MMN generators indicated a significantly reduced current source density (CSD) under the ketamine condition in the primary auditory cortex, the posterior cingulate and the middle frontal gyrus. Limitations: The sample included only men within a tight age range of 20-32 years. Conclusion: The MMN might represent a biomarker for negative symptoms in schizophrenia related to an insufficient NMDAR system and could be used to identify patients with schizophrenia with negative symptoms due to NMDAR dysfunction., Introduction Current pharmaceuticals for the treatment of schizophrenia--the typical and atypical antipsychotics--are dopamine D2 receptor antagonists with a satisfactory clinical benefit on positive symptoms, but with limited to no impact [...]

The pathophysiology of bipolar disorder (BD) remains mostly unclear. Yet, a valid biomarker is necessary to improve upon the early detection of this serious disorder. Patients with manifest BD display reduced volumes of the hippocampal subfields and amygdala nuclei. In this pre-registered analysis, we used structural MRI (n = 271, 7 sites) to compare volumes of hippocampus, amygdala and their subfields/nuclei between help-seeking subjects divided into risk groups for BD as estimated by BPSS-P, BARS and EPIbipolar. We performed between-group comparisons using linear mixed effects models for all three risk assessment tools. Additionally, we aimed to differentiate the risk groups using a linear support vector machine. We found no significant volume differences between the risk groups for all limbic structures during the main analysis. However, the SVM could still classify subjects at risk according to BPSS-P criteria with a balanced accuracy of 66.90% (95% CI 59.2–74.6) for 10-fold cross-validation and 61.9% (95% CI 52.0–71.9) for leave-one-site-out. Structural alterations of the hippocampus and amygdala may not be as pronounced in young people at risk; nonetheless, machine learning can predict the estimated risk for BD above chance. This suggests that neural changes may not merely be a consequence of BD and may have prognostic clinical value. [ABSTRACT FROM AUTHOR]

Disrupted auditory networks play an important role in the pathophysiology of psychosis, with abnormalities already observed in individuals at clinical high-risk for psychosis (CHR). Here, we examine structural and functional connectivity of an auditory network in CHR utilising state-of-the-art electroencephalography and diffusion imaging techniques. Twenty-six CHR subjects and 13 healthy controls (HC) underwent diffusion MRI and electroencephalography while performing an auditory task. We investigated structural connectivity, measured as fractional anisotropy in the Arcuate Fasciculus (AF), Cingulum Bundle, and Superior Longitudinal Fasciculus-II. Gamma-band lagged-phase synchronisation, a functional connectivity measure, was calculated between cortical regions connected by these tracts. CHR subjects showed significantly higher structural connectivity in the right AF than HC (p <.001). Although non-significant, functional connectivity between cortical areas connected by the AF was lower in CHR than HC (p =.078). Structural and functional connectivity were correlated in HC (p =.056) but not in CHR (p =.29). We observe significant differences in structural connectivity of the AF, without a concomitant significant change in functional connectivity in CHR subjects. This may suggest that the CHR state is characterised by a decoupling of structural and functional connectivity, possibly due to abnormal white matter maturation. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Patients with hearing impairment (HI) may experience hearing sounds without external sources, ranging from random meaningless noises (tinnitus) to music and other auditory hallucinations (AHs) with meaningful qualities. To ensure appropriate assessment and management, clinicians need to be aware of these phenomena. However, sensory impairment studies have shown that such clinical awareness is low. Study Design An online survey was conducted investigating awareness of AHs among clinicians and their opinions about these hallucinations. Study Results In total, 125 clinicians (68.8% audiologists; 18.4% Ear-Nose-Throat [ENT] specialists) across 10 countries participated in the survey. The majority (96.8%) was at least slightly aware of AHs in HI. About 69.6% of participants reported encountering patients with AHs less than once every 6 months in their clinic. Awareness was significantly associated with clinicians' belief that patients feel anxious about their hallucinations (β =.018, t (118) = 2.47, P <.01), their belief that clinicians should be more aware of these hallucinations (β =.018, t (118) = 2.60, P <.01), and with confidence of clinicians in their skills to assess them (β =.017, t (118) = 2.63, P <.01). Clinicians felt underequipped to treat AHs (Median = 31; U = 1838; P FDRadj <.01). Conclusions Awareness of AHs among the surveyed clinicians was high. Yet, the low frequency of encounters with hallucinating patients and their belief in music as the most commonly perceived sound suggest unreported cases. Clinicians in this study expressed a lack of confidence regarding the assessment and treatment of AHs and welcome more information. [ABSTRACT FROM AUTHOR]

NMDA-receptor hypofunction is increasingly considered to be an important pathomechanism in schizophrenia. However, to date, it has not been possible to identify patients with relevant NMDA-receptor hypofunction who would respond to glutamatergic treatments. Preclinical models, such as the ketamine model, could help identify biomarkers related to NMDA-receptor function that respond to glutamatergic modulation, for example, via activation of the glycine-binding site. We, therefore, aimed to investigate the effects of opposing modulation of the NMDA receptor on gamma activity (30–100 Hz) at rest, the genesis of which appears to be highly dependent on NMDA receptors. The effects of subanesthetic doses of S-ketamine and pretreatment with glycine on gamma activity at rest were examined in twenty-five healthy male participants using 64-channel electroencephalography. Psychometric scores were assessed using the PANSS and the 5D-ASC. While S-ketamine significantly increased psychometric scores and gamma activity at the scalp and in the source space, pretreatment with glycine did not significantly attenuate any of these effects when controlled for multiple comparisons. Our results question whether increased gamma activity at rest constitutes a suitable biomarker for the target engagement of glutamatergic drugs in the preclinical ketamine model. They might further point to a differential role of NMDA receptors in gamma activity generation. [ABSTRACT FROM AUTHOR]