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Background: Reductions in the volume of brain white matter are a common feature in schizophrenia and bipolar disorder while the association between white matter and polygenic schizophrenia-related risk is unclear. To look at the intermediate state between health and the full-blown disorder, we investigated this aspect in groups of patients before and after the onset of psychosis. Methods: On a 3 Tesla scanner, total and regional white matter volumes were investigated by structural magnetic resonance imaging (MRI) in the following groups: 37 at-risk mental state patients (ARMS), including 30 with no transition to psychosis (ARMS-NT) and 7 with a transition to psychosis (ARMS-T) pooled with 25 first episode psychosis (FEP) patients. These T1-weighted images were automatically processed with the FreeSurfer software and compared with an odds-ratio-weighted polygenic schizophrenia-related risk score (PSRS) based on the publicly available top white matter single-nucleotide polymorphisms. Results: We found no association, only a trend, between PSRS and white matter volume over all groups (β = 0.24, p = 0.07, 95% confidence interval = [-0.02 – 0.49]). However, a higher PSRS was significantly associated with a higher probability of being assigned to the ARMS-T + FEP group rather than to the ARMS-NT group (β = 0.70, p = 0.02, 95% confidence interval = [0.14 – 1.33]); there was no such association with white matter volume. Additionally, a positive association was found between PSRS and the Brief Psychiatric Rating Scale (BPRS) total score for the pooled ARMS-NT/ARMS-T+FEP sample and for the ARMS-T + FEP group also, but none for the ARMS-NT group only. Conclusion: These findings suggest that at-risk mental state patients with a transition and first-episode psychosis patients have a higher genetic risk for schizophrenia than at-risk mental state patients with no transition to psychosis; this risk was associated with psychopathological symptoms. Further analyses may allow polygenic schizophrenia-related risk scores to be used as biomarkers to predict psychosis.

LSD is an ambiguous substance, said to mimic psychosis and to improve mental health in people suffering from anxiety and depression. Little is known about the neuronal correlates of altered states of consciousness induced by this substance. Limited previous studies indicated profound changes in functional connectivity of resting state networks after the administration of LSD. The current investigation attempts to replicate and extend those findings in an independent sample. In a double-blind, randomized, cross-over study, 100 μg LSD and placebo were orally administered to 20 healthy participants. Resting state brain activity was assessed by functional magnetic resonance imaging. Within-network and between-network connectivity measures of ten established resting state networks were compared between drug conditions. Complementary analysis were conducted using resting state networks as sources in seed-to-voxel analyses. Acute LSD administration significantly decreased functional connectivity within visual, sensorimotor and auditory networks and the default mode network. While between-network connectivity was widely increased and all investigated networks were affected to some extent, seed-to-voxel analyses consistently indicated increased connectivity between networks and subcortical (thalamus, striatum) and cortical (precuneus, anterior cingulate cortex) hub structures. These latter observations are consistent with findings on the importance of hubs in psychopathological states, especially in psychosis, and could underlay therapeutic effects of hallucinogens as proposed by a recent model. Keywords: LSD, fMRI, Functional connectivity, Networks, Hubs

Background: Cognitive functions progressively deteriorate during aging and neurodegenerative diseases. The present study aims at investigating differences in working memory performance as well as functional brain changes during the earliest stages of cognitive decline in health elderly individuals. Methods: 62 elderly individuals (41 females), including 41 controls (35 females) and 21 middle cognitive impairment subjects (6 females), underwent neuropsychological assessment at baseline and an fMRI examination in a N-back paradigm contrasting 2-back vs. 0-back condition. Upon a 18 months follow-up, we identified stable controls (sCON) with preserved cognition and deteriorating controls (dCON) with -1SD decrease of performances in at least two neuropsychological tests. Data analyses included accuracy and reaction time (RT) for the 2-back condition and general linear model (GLM) for the fMRI sequence. Results: At the behavioral level, sCON and dCON performed better than MCI in terms of accuracy and reaction time. At the brain level, functional differences in regions of the fronto-parietal network (FPN) and of the Default Mode Network (DFM) were observed. Significantly lower neural activations in the bilateral inferior and middle frontal gyri were found in MCI versus both dCON / sCON and for dCON versus sCON. Significantly increased activations in the anterior cingulate cortex and posterior cingulate cortex and bilateral insula were found in MCI versus both dCON / sCON and in dCON versus sCON. Conclusion: The present study suggests that brain functional changes in FPN and DMN anticipate differences in cognitive performance in healthy elderly individuals with subsequent subtle cognitive decline.

Translation as a notion and procedure is deeply embodied in medical science and education. Translation includes the possibility to translate data across disciplines to improve diagnosis and treatment procedures. The evidence accumulated using translation serves as a vehicle for reification of medical diagnoses. There are promising, established post hoc correlations between the different types of clinical tools (interviews and inventories) and neuroscience. The various measures represent statistical correlations that must now be integrated into diagnostic standards and procedures but this, as a whole, is a step forward towards a better understanding of the mechanisms underlying psychopathology in general and depression in particular. Here, we focus on functional magnetic resonance imaging studies using a trans-disciplinary approach and attempt to establish bridges between the different fields. We will selectively highlight research areas such as imaging genetics, imaging immunology and multimodal imaging, as related to the diagnosis and management of depression

Background: Health services research is of increasing importance in current psychiatry. Therefore, large datasets and aggregation of data generated by electronic routine documentation due to legal, financial, or administrative purposes play an important role. However, paper-based routine documentation is still of interest. It remains relevant in less developed health care systems, in emergency settings, and in long-term retrospective and historical studies. Whereas studies examining the reliability of electronic routine documentation support the application of routine data for research purposes, our knowledge regarding reliability of paper-based routine documentation is still very sparse.Methods: Basic documentation (BADO) was completed on paper forms and digitalized manually for all inpatients of the Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Germany, treated within the time period from 1998 to 2006. Four hundred twelve cases of first-episode psychosis patients were chosen for comparison with clinical data from paper-based patient files. The percentage of missing information, the percentage of correct classifications, sensitivity, and positive predictive value were calculated for all applicable variables.Results: In eight cases (1.9%), a BADO form was available, but was not filled in. In 37 cases (7.0%), the patient files were lost and could not be obtained from the centralized archive. Routine data were available for all other cases in 20 (58.8%) of the examined 34 variables, and the percentage of missing data for the remaining variables ranged between 0.3% and 22.9%, with only the variables education and suicidality during treatment having more than 5% missing data. In general, the overall rate of correct classifications was high, with a median percentage of 86.4% to 99.7% for the examined variables. Sensitivity was above 75% for eight and

For psychiatric patients, compulsory admission and coercive measures can constitute distressing and sometimes traumatizing experiences. As a consequence, clinicians aim at minimizing such procedures. At the same time, they need to ensure high levels of safety for patients, staff and the public. In order to prevent compulsory measures and to favor the use of less restrictive alternatives, innovative interventions improving the management of dangerous situations are needed. Animal-assisted therapy (AAT) is being applied in a variety of diagnoses and treatment settings, and could have the potential to reduce aggression and psychopathology. Therefore, AAT might be of use in the prevention and early treatment of aggression, and might constitute a promising component of treatment alternatives to forced interventions. To our knowledge, no study evaluating the effect of AAT on compulsory measures in persons with psychiatric diseases has been published up to date. This narrative expert review including a systematic literature search examines the published literature about the use of AAT in psychiatry. Studies report reduced anxiety and aggressiveness as well as positive effects on general wellbeing, self-efficacy, quality of life and mindfulness. Although literature on the applicability of AAT as a component of preventive or de-escalating treatment settings is sparse, beneficial effects of AAT have been reported. Therefore, we encourage examining AAT as a promising new treatment approach to prevent compulsory measures.

There is reported a study performed with a novel paradigm aiming at investigation of the translational validity of von Zerssen’s paranoid-depression scale and its fMRI correlates in terms of focus on exploration of the results on the contrast between the Paranoid Specific (DP) blocks and the Depression Specific (DS) blocks. Patients with schizophrenia demonstrated significant activations in a number of regions (right angular gyrus, left posterior cingulate and precuneus, right transverse temporal gyrus) during responses to paranoia versus depression items which differ topologically from those found in patients with major depression (left middle cingulate and right superior temporal gyrus). The direct comparison between the groups, however, did not yield any residual activations after correction.

Lysergic acid diethylamide (LSD) is a potent hallucinogenic substance that was extensively investigated by psychiatrists during the 1950s and 1960s. Researchers were interested in the unique effects induced by this substance, some of which resemble symptoms seen in schizophrenia. Moreover, during that period LSD was studied and used for the treatment of several mental disorders such as depression, anxiety, addiction and personality disorders. Despite this long history of research, how LSD induces its specific effects on a neuronal level has been relatively unclear. In recent years there has been a revival of research in hallucinogenic drugs and their possible clinical applications. These contemporary studies in the UK and Switzerland include neuroimaging studies using functional magnetic resonance imaging (fMRI). In this review, we collect and interpret these recent neuroimaging findings. Overall, previous results across studies indicate that LSD administration is associated with extensive alterations in functional brain connectivity, measuring the correlated activities between different brain regions. The studies mostly reported increases in connectivity between regions and, more specifically, consistently found increased connectivity within the thalamocortical system. These latter observations are in agreement with models proposing that hallucinogenic drugs exert their effects by inhibiting cerebral filtering of external and internal data. However, studies also face several limitations, including potential biases of neuroimaging measurements.

Background: When persons with a mental illness present a danger to themselves or others, involuntary hospital admission can be used to initiate an immediate inpatient treatment. Often, the patients have the right to appeal against compulsory admission. These processes are implemented in most mental health-care systems, but regulations and legal framework differ widely. In the Swiss canton of Basel-Stadt, a new regulation was implemented in January 2013. While the current literature holds some evidence for factors associated with involuntary admission, knowledge on who uses the right to appeal against admission is sparse.Aims: The study aims to examine if specific sociodemographic and clinical characteristics are associated with involuntary admission and with an appeal against the compulsory admission order.Method: Routine clinical data of all inpatient cases admitted during the period from January 2013 to December 2015 at the Psychiatric University Hospital Basel were extracted. Generalized estimating equation (GEE) analyses were used to examine the association of sociodemographic and clinical characteristics with “involuntary admission” and “appeal against compulsory admission order.”Results: Of the 8,917 cases included in the present study, 942 (10.6%) were admitted involuntarily. Of these, 250 (26.5%) lodged an appeal against the compulsory admission order. Compared with cases admitted on a voluntary legal status, cases admitted involuntarily were older and were admitted more often during the nighttime or weekend. Moreover, involuntarily admitted cases had more often a principal diagnosis of a schizophrenia spectrum disorder. Patients from cases where an appeal was lodged were more often female, had more often Swiss nationality, and were more often diagnosed with schizophrenia spectrum disorder.Conclusion: Despite legal changes, the frequency of involuntary admissions in the observed catchment area seems to be relatively stable across the last 20 years. The percentage of appeals has decreased from 2000 to 2015, and only comparably few patients make use of the possibility to appeal. Better knowledge of the regulations, higher social functioning, and lower insight into illness might be associated with a higher probability of lodging an appeal. Future research should examine if specific patient groups are in need of additional assistance to exert their rights to appeal.

The brain is the most complex of human organs, and the pathophysiology underlying abnormal brain function in psychiatric disorders is largely unknown. Despite the rapid development of diagnostic tools and treatments in most areas of medicine, our understanding of mental disorders and their treatment has made limited progress during the last decades. While recent advances in genetics and neuroscience have a large potential, the complexity and multidimensionality of the brain processes hinder the discovery of disease mechanisms that would link genetic findings to clinical symptoms and behavior. This applies also to schizophrenia, for which genome-wide association studies have identified a large number of genetic risk loci, spanning hundreds of genes with diverse functionalities. Importantly, the multitude of the associated variants and their prevalence in the healthy population limit the potential of a reductionist functional genetics approach as a stand-alone solution to discover the disease pathology. In this review, we outline the key concepts of a “biophysical psychiatry,” an approach that employs large-scale mechanistic, biophysics-founded computational modelling to increase transdisciplinary understanding of the pathophysiology and strive toward robust predictions. We discuss recent scientific advances that allow a synthesis of previously disparate fields of psychiatry, neurophysiology, functional genomics, and computational modelling to tackle open questions regarding the pathophysiology of heritable mental disorders. We argue that the complexity of the increasing amount of genetic data exceeds the capabilities of classical experimental assays and requires computational approaches. Biophysical psychiatry, based on modelling diseased brain networks using existing and future knowledge of basic genetic, biochemical, and functional properties on a single neuron to a microcircuit level, may allow a leap forward in deriving interpretable biomarkers and move the field toward novel treatment options.

Background and methods: Aggression in psychosis is clinically important. We systematically compiled the evidence on functional correlates of aggression in psychosis searching PubMed, EMBASE, ScienceDirect, and PsycINFO until September 2017. We included studies reporting functional brain imaging correlates of aggression comparing: (1) affective or non-affective psychosis groups with a history of violence or with aggression operationalized using questionnaires, (2) affective or non-affective psychosis groups with a history of violence or with aggression operationalized using questionnaires to controls, (3) affective or non-affective psychosis groups with a history of violence or with aggression operationalized using questionnaires to controls with diagnoses other than affective or non-affective psychoses. We applied no language restriction and required patients to have a DSM or ICD diagnosis of affective or non-affective psychosis.Results: Our sample consisted of 12 studies with 334 patients and 113 controls. During n-back tasks, violent (VS) as opposed to non-violent persons with schizophrenia (NVS) hypoactivated their inferior parietal lobe. When anticipating shock, VS vs. NVS hyperactivated their medial prefrontal gyrus, cuneus, middle temporal gyrus, and middle occipital gyrus. When viewing negative emotional pictures, VS vs. NVS hyperactivated the middle frontal gyrus, inferior frontal gyrus, anterior cingulate, lingual gyrus, precentral gyrus, globus pallidus, mid-cingulate, and precuneus.Limitations: Due to the small number of available studies, sample overlap, and insufficient reporting of relevant moderators we could not conduct a meta-analysis.Conclusions: We found non-systematic functional correlates of aggression in schizophrenia. Only few studies using varied paradigms and often overlapping samples have been conducted. There have been no attempts to replicate any of the observed findings in the published literature. Focusing on future directions, we recommend that authors adhere to clear definitions of aggression, measurements of psychopathology, comorbidities, and medication. In particular, replication studies would allow for a better synthesis of the findings.PROSPERO Registration Number: CRD42016048579

Objectives: Current risk assessment tools can predict problematic behavior and the need for coercive measures, but only with a moderate level of accuracy. The aim of this study was to assess antecedents and triggers of seclusion.Methods: Narrative notes of health care professionals on psychiatric inpatients were analyzed daily starting 3 days prior to seclusion in the case group (n = 26) and compared to a matched control group without seclusion (n = 26) by use of quantitative and qualitative research methods, based on qualitative content analysis.Results: Quantitative measures showed more aggression in the case group with highly significant differences between the groups (p < 0.001) at all measurement times. Seclusion was significantly associated with the total word count of the narrative notes. Subjective emotional expressions by staff were more apparent before seclusion (p = 0.003). Most frequently, subjective expressions regarding “arduous/provocative” (p < 0.001) and “anxious” (p = 0.010) sentiments could be identified in the case group. Description of patients' behavior in the case group included more negatively assessed terms (p = 0.001). Moreover, sleep loss, refusing medication, high contact frequency, demanding behavior and denied requests were present in a significantly higher frequency before seclusion. Expressions like “threatening” (p = 0.001) were found only before seclusion and appeared to have the function of personal risk assessment. The expression “manageable” (p = 0.035) appeared often in difficult situations that could still be handled.Conclusion: Several factors preceding seclusion could be identified. Narrative notes of staff already showed differences 3 days before the escalation. Particularly the word count, the analysis of terms describing patients' behavior, subjective expressions of staff, and terms used as a function of personal risk assessment could help to provide better predictions of aggressive incidents and to prevent coercive measures.

Background/Aims: Taste perception is one of the most important primary oral reinforcers, driving nutrient and energy intake as well as toxin avoidance. Taste receptors in the gastrointestinal tract might as well impact appetitive or aversive behavior and thus influence learning tasks and a close relation of neural taste processing and working memory networks seems plausible. Methods: In the present pilot study, we determined the effects of five taste qualities “bitter” (quinine), “sweet” (glucose), “sour” (citric acid), “salty” (NaCl) and “umami” (monosodium glutamate, MSG) on working memory processing using functional MRI and their effect on plasma insulin and glucose levels. On six separate occasions, subjects received one of the following test substances dissolved in 200 mL tap water via a nasogastric tube (to circumvent the oral cavity): 1) 2g citric acid corresponding to 52 mM, 2) 2g NaCl; 171 mM, 3) 0.017g quinine; 0.26 mM, 4) 1g monosodium glutamate; 30 mM, 5) 25g glucose; 694 mM and 6) 200 mL tap water (placebo). Results: The taste qualities “bitter” and “umami” significantly altered brain activation patterns in the primary gustatory cortex as well as in subcortical structures, previously reported to be involved in emotional learning and memory. In contrast, glucose did not reveal any statistically significant brain activation difference. Working memory performance was not different over the six treatments. Plasma insulin and glucose levels were not affected by the different taste substances (MSG, quinine, NaCl and citric acid). Conclusions: in this pilot trial, we demonstrate that acute intragastric administration of different taste substances does not affect working memory performance in humans. However, “umami” and “bitter” have effects on brain areas involved in neural working memory, overpowering the effects of “sweet”, “salty” and “sour” reception.

We constructed a novel design integrating the administration of a clinical self-assessment scale with simultaneous acquisition of functional Magnetic Resonance Imaging (fMRI), aiming at cross-validation between psychopathology evaluation and neuroimaging techniques. We hypothesized that areas demonstrating differential activation in two groups of patients (the first group exhibiting paranoid delusions in the context of paranoid schizophrenia—SCH—and second group with a depressive episode in the context of major depressive disorder or bipolar disorder—DEP) will have distinct connectivity patterns and structural differences. Fifty-one patients with SCH (n = 25) or DEP (n = 26) were scanned with three different MRI sequences: a structural and two functional sequences—resting-state and task-related fMRI (the stimuli represent items from a paranoid-depressive self-evaluation scale). While no significant differences were found in gray matter volumes, we were able to discriminate between the two clinical entities by identifying two significant clusters of activations in the SCH group—the left Precuneus (PreCu) extending to the left Posterior Cingulate Cortex (PCC) and the right Angular Gyrus (AG). Additionally, the effective connectivity of the middle frontal gyrus (MFG), a part of the Dorsolateral Prefrontal Cortex (DLPFC) to the Anterior Insula (AI), demonstrated a significant difference between the two groups with inhibitory connection demonstrated only in SCH. The observed activations of PreCu, PCC, and AG (involved in the Default Mode Network DMN) might be indirect evidence of the inhibitory connection from the DLPFC to AI, interfering with the balancing function of the insula as the dynamic switch in the DMN. The findings of our current study might suggest that the connectivity from DLPFC to the anterior insula can be interpreted as evidence for the presence of an aberrant network that leads to behavioral abnormalities, the manifestation of which depends on the direction of influence. The reduced effective connectivity from the AI to the DLPFC is manifested as depressive symptoms, and the inhibitory effect from the DLPFC to the AI is reflected in the paranoid symptoms of schizophrenia.