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Neurological soft signs (NSS) are related to grey matter and functional brain abnormalities in schizophrenia. Studies in healthy subjects suggest, that NSS are also linked to white matter. However, the association between NSS and white matter abnormalities in schizophrenia remains to be elucidated. The present study investigated, if NSS are related to white matter alterations in patients with schizophrenia. The total sample included 42 healthy controls and 41 patients with schizophrenia. We used the Neurological Evaluation Scale (NES), and we acquired diffusion weighted magnetic resonance imaging to assess white matter on a voxel-wise between subject statistic. In patients with schizophrenia, linear associations between NES with fractional anisotropy (FA), radial, axial, and mean diffusivity were analyzed with tract-based spatial statistics while controlling for age, medication dose, the severity of the disease, and motion. The main pattern of results in patients showed a positive association of NES with all diffusion measures except FA in important motor pathways: the corticospinal tract, internal capsule, superior longitudinal fascicle, thalamocortical radiations and corpus callosum. In addition, exploratory tractography analysis revealed an association of the right aslant with NES in patients. These results suggest that specific white matter alterations, that is, increased diffusivity might contribute to NSS in patients with schizophrenia.

Background Entrustable professional activities (EPAs) are increasingly used in undergraduate medical education (UME). We conducted a scoping review to summarize the evidence for the use of EPAs in clinical rotations in UME. Methods We searched multiple databases for scoping reviews based on the PRISMA guidelines for articles reporting qualitative and quantitative research, as well as conceptual and curriculum development reports, on EPAs in UME clinical rotations. Results We identified 3309 records by searching through multiple databases. After the removal of duplicates, 1858 reports were screened. A total of 36 articles were used for data extraction. Of these, 47% reported on EPA and EPA-based curriculum development for clerkships, 50% reported on implementation strategies, and 53% reported on assessment methods and tools used in clerkships. Validity frameworks for developing EPAs in the context of clerkships were inconsistent. Several specialties reported feasible implementation strategies for EPA-based clerkship curricula, however, these required additional faculty time and resources. Limited exposure to clinical activities was identified as a barrier to relevant learning experiences. Educators used nationally defined, or specialty-specific EPAs, and a range of entrustability and supervision scales. We found only one study that used an empirical research approach for EPA assessment. One article reported on the earlier advancement of trainees from UME to graduate medical education based on summative entrustment decisions. Conclusions There is emerging evidence concerning how EPAs can be effectively introduced to clinical training in UME. Specialty-specific, nested EPAs with context-adapted, entrustment-supervision scales might be helpful in better leveraging their formative assessment potential.

Current classification systems use the terms "catatonia" and "psychomotor phenomena" as mere a-theoretical descriptors, forgetting about their theoretical embedment. This was the source of misunderstandings among clinicians and researchers of the European collaboration on movement and sensorimotor/psychomotor functioning in schizophrenia and other psychoses or ECSP. Here, we review the different perspectives, their historical roots and highlight discrepancies. In 1844, Wilhelm Griesinger coined the term "psychic-motor" to name the physiological process accounting for volition. While deriving from this idea, the term "psychomotor" actually refers to systems that receive miscellaneous intrapsychic inputs, convert them into coherent behavioral outputs send to the motor systems. More recently, the sensorimotor approach has drawn on neuroscience to redefine the motor signs and symptoms observed in psychoses. In 1874, Karl Kahlbaum conceived catatonia as a brain disease emphasizing its somatic - particularly motor - features. In conceptualizing dementia praecox Emil Kraepelin rephrased catatonic phenomena in purely mental terms, putting aside motor signs which could not be explained in this way. Conversely, the Wernicke-Kleist-Leonhard school pursued Kahlbaum's neuropsychiatric approach and described many new psychomotor signs, e.g. parakinesias, Gegenhalten. They distinguished 8 psychomotor phenotypes of which only 7 are catatonias. These barely overlap with consensus classifications, raising the risk of misunderstanding. Although coming from different traditions, the authors agreed that their differences could be a source of mutual enrichment, but that an important effort of conceptual clarification remained to be made. This narrative review is a first step in this direction. (C) 2021 Published by Elsevier B.V.

Severin Pinilla,1,2 Andrea Cantisani,3 Stefan Klöppel,1 Werner Strik,3 Christoph Nissen,3 Sören Huwendiek2 1University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland; 2Institute for Medical Education, Department for Assessment and Evaluation, University of Bern, Bern, Switzerland; 3University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, SwitzerlandCorrespondence: Severin Pinilla Email severin.pinilla@upd.unibe.chBackground: Learning management systems (LMSs) have not been explored from an educational design research (EDR) perspective for developing clinical curricula and supporting novice clinical students with self-regulated learning during their early clinical rotations.Methods: An EDR approach was used to inform a de novo implementation of an LMS during an early clinical rotation of medical students. The EDR consisted of three phases: analysis and exploration; design and construction; and evaluation and reflection. Process and evaluation data (including academic years 2018 and 2019) from two student cohorts (total n = 190, 107 without and 83 with LMS exposure) at one academic teaching hospital were analyzed.Results: Learning theories and concepts of self-regulated learning were used to develop and implement an LMS clerkship prototype. For design and construction, the maturing prototype design included flipped-classroom elements, in-class activation, voluntary digital self-assessments, and clinical teaching videos. For evaluation and reflection, global satisfaction improvement was significant (from 3.9 to 4.4 on a 5-point Likert scale, p < 0.05). There was a positive evaluation trend for all evaluation items related to learning climate, self-regulated learning, and perceived usefulness of the LMS prototype; however, these changes were not statistically significant. The teaching hospital also improved its ranking after the introduction of the LMS prototype. Nearly all students (94%) used the LMS material. The average number of times the LMS course was accessed per student was 70 (range: 7– 172), and the average duration students spent online was 58 minutes (range: 9– 165).Conclusion: Our data indicate that using an EDR approach was helpful for systematically introducing an LMS in a clerkship curriculum informed by learning theory. Our evidence-oriented curriculum reform was associated with higher student satisfaction and appeared to support self-regulated learning in the workplace. Further research should explore which elements of an LMS most effectively help to achieve educational outcomes.Keywords: learning-management system, self-regulated learning, clinical education, educational research design, psychiatry

Background Entrustable professional activities (EPAs) in competency-based, undergraduate medical education (UME) have led to new formative workplace-based assessments (WBA) using entrustment-supervision scales in clerkships. We conducted an observational, prospective cohort study to explore the usefulness of a WBA designed to assess core EPAs in a psychiatry clerkship. Methods We analyzed changes in self-entrustment ratings of students and the supervisors’ ratings per EPA. Timing and frequencies of learner-initiated WBAs based on a prospective entrustment-supervision scale and resultant narrative feedback were analyzed quantitatively and qualitatively. Predictors for indirect supervision levels were explored via regression analysis, and narrative feedback was coded using thematic content analysis. Students evaluated the WBA after each clerkship rotation. Results EPA 1 (“Take a patient’s history”), EPA 2 (“Assess physical & mental status”) and EPA 8 (“Document & present a clinical encounter”) were most frequently used for learner-initiated WBAs throughout the clerkship rotations in a sample of 83 students. Clinical residents signed off on the majority of the WBAs (71%). EPAs 1, 2, and 8 showed the largest increases in self-entrustment and received most of the indirect supervision level ratings. We found a moderate, positive correlation between self-entrusted supervision levels at the end of the clerkship and the number of documented entrustment-supervision ratings per EPA (p n = 214) of the WBAs. Most narratives addressed the Medical Expert role (77%, n = 208) and used reinforcement (59%, n = 161) as a feedback strategy. Students perceived the feedback as beneficial. Conclusions Using formative WBAs with an entrustment-supervision scale and prompts for written feedback facilitated targeted, high-quality feedback and effectively supported students’ development toward self-entrusted, indirect supervision levels.

Hand gestures are an integral part of social interactions and communication. Several imaging studies in healthy subjects and lesion studies in patients with apraxia suggest the praxis network for gesture production, involving mainly left inferior frontal, posterior parietal and temporal regions. However, little is known about the structural connectivity underlying gesture production. We recruited 41 healthy participants and 39 patients with schizophrenia. All participants performed a gesture production test, the Test of Upper Limb Apraxia, and underwent diffusion tensor imaging. We hypothesized that gesture production is associated with structural network connectivity as well as with tract integrity. We defined the praxis network as an undirected graph comprised of 13 bilateral regions of interest and derived measures of local and global structural connectivity and tract integrity from Finsler geometry. We found an association of gesture deficit with reduced global and local efficiency of the praxis network. Furthermore, reduced tract integrity, for example in the superior longitudinal fascicle, arcuate fascicle or corpus callosum were related to gesture deficits. Our findings contribute to the understanding of structural correlates of gesture production as they first present diffusion tensor imaging data in a combined sample of healthy subjects and a patient cohort with gestural deficits.

BackgroundGeneral clerkship quality criteria have not been studied after introducing a curriculum based on entrustable professional activities (EPAs). Therefore, we conducted a pilot study to explore educational outcomes of an EPA-based clerkship curriculum reform.MethodsWe collected multiple self-assessment and evaluation data on levels 1-3 of the New World Kirkpatrick model (KPM). For level 1 (reaction) we analyzed curriculum evaluations and verbal and written students’ feedback. For level 2 (learning) pre- and post-clerkship self-assessments of perceived need for supervision for each EPA and students’ written learning reflections based on patient mix exposure were analyzed. For level 3 (behavior) we evaluated workplace-based assessments.ResultsThe first student cohort in the new EPA-based clerkship completed 180 self-assessments (18 per student) of need for supervision and 63 documented workplace-based assessments (average of 6.3 per student in four weeks). On KPM level 1 we saw a high overall satisfaction with the clerkship (average of 4.9, range: 4.0-5.0 on a 5-point Likert scale). In written evaluations and feedback rounds students pointed out the importance of structured bedside teaching in the first clerkship week. On KPM level 2 the overall decrease of self-assessed need for supervision before and after the clerkship was two supervision levels (from direct to indirect supervision) and statistically significant (p < 0.05). For three EPAs students reached indirect supervision levels. Learning reflections and patient mix analysis indicated that students were exposed to a wide range of diagnostic categories (ICD-10: F0 – F6) and received actionable feedback for communication skills. On KPM level 3 clinical supervisors predominantly used EPAs 1 (History taking), 2 (Assessing mental status) and 8 (Documentation and presentation) for workplace-based assessments. We saw a decreasing need for supervision from the first to the last week in the clerkship according to the supervisors’ judgements.ConclusionStudents reacted positively to introducing an EPA-based clerkship curriculum. The EPA-oriented formative self-assessments and workplace-based assessments seemed to support achievement of competency-based learning goals. However, more in-depth understanding of the entrustment process in the clerkship context is necessary to fully leverage the potential of an EPA-based clerkship.

Over the last three decades, movement disorder as well as sensorimotor and psychomotor functioning in schizophrenia (SZ) and other psychoses has gained greater scientific and clinical relevance as an intrinsic component of the disease process of psychotic illness; this extends to early psychosis prediction, early detection of motor side effects of antipsychotic medication, clinical outcome monitoring, treatment of psychomotor syndromes (e.g. catatonia), and identification of new targets for non-invasive brain stimulation. In 2017, a systematic cooperation between working groups interested in movement disorder and sensorimotor/psychomotor functioning in psychoses was initiated across European universities. As a first step, the members of this group would like to introduce and define the theoretical aspects of the sensorimotor domain in SZ and other psychoses. This consensus paper is based on a synthesis of scientific evidence, good clinical practice and expert opinions that were discussed during recent conferences hosted by national and international psychiatric associations. While reviewing and discussing the recent theoretical and experimental work on neural mechanisms and clinical implications of sensorimotor behavior, we here seek to define the key principles and elements of research on movement disorder and sensorimotor/psychomotor functioning in psychotic illness. Finally, the members of this European group anticipate that this consensus paper will stimulate further multimodal and prospective studies on hypo- and hyperkinetic movement disorders and sensorimotor/psychomotor functioning in SZ and other psychotic disorders. (C) 2020 Elsevier B.V. and ECNP. All rights reserved.

Despite being a commonly used protocol to treat major depressive disorder (MDD), the underlying mechanism of repetitive transcranial magnetic stimulation (rTMS) on dorsolateral prefrontal cortex (DLPFC) remains unclear. In the current study, we investigated the resting-state fMRI data of 100 healthy subjects by exploring three overlapping functional networks associated with the psychopathologically MDD-related areas (the nucleus accumbens, amygdala, and ventromedial prefrontal cortex). Our results showed that these networks converged at the bilateral DLPFC, which suggested that rTMS over DLPFC might improve MDD by remotely modulating the MDD-related areas synergistically. Additionally, they functionally converged at the DMPFC and bilateral insula which are known to be associated with MDD. These two areas could also be potential targets for rTMS treatment. Dynamic causal modelling (DCM) and Granger causality analysis (GCA) revealed that all pairwise connections among bilateral DLPFC, DMPFC, bilateral insula, and three psychopathologically MDD-related areas contained significant causality. The DCM results also suggested that most of the functional interactions between MDD-related areas and bilateral DLPFC, DMPFC, and bilateral insula can predominantly be explained by the effective connectivity from the psychopathologically MDD-related areas to the rTMS stimulation sites. Finally, we found the conventional functional connectivity to be a more representative measure to obtain connectivity parameters compared to GCA and DCM analysis. Our research helped inspecting the convergence of the functional networks related to a psychiatry disorder. The results identified potential targets for brain stimulation treatment and contributed to the optimization of patient-specific brain stimulation protocols.

Highlights • Dynamic face stimuli activate face processing and limbic brain regions. • Unattractive faces are linked to higher activation of these regions. • Subclinical paranoid beliefs enhance the neural response by perceived attractiveness., The perception of faces and consequent social inferences are fundamental for interpersonal communication. While facial expression is important for interindividual communication, constitutional and acquired features are crucial for basic emotions of attraction or repulsion. An emotional bias in face processing has been shown in schizophrenia, but the neurobiological mechanisms are unclear. Studies on the interaction between face processing and the emotional state of healthy individuals may help to elucidate the pathogenesis of the paranoid syndrome in psychosis. This study addressed facial attractiveness and paranoid ideas in a non-clinical population. Using functional magnetic resonance imaging (fMRI), we investigated neural activation patterns of 99 healthy subjects during the passive perception of a dynamic presentation of faces with different attractiveness. We found that the perceived attractiveness of faces was linked to the activity of face processing and limbic regions including the fusiform gyrus, amygdala, and prefrontal areas. Paranoid beliefs interacted with perceived attractiveness in these regions resulting in a higher response range and increased activation after the presentation of unattractive faces. However, no behavioral interactions between reported subjective attractiveness and paranoid beliefs were found. The results showed that increased activation of limbic brain regions is linked to paranoid beliefs. Since similar correlations were found in clinical populations with paranoid syndromes, we suggest a dimension of emotional dysregulation ranging from subclinical paranoid beliefs to paranoid schizophrenia.

Psychomotor slowing is frequently distressing patients with depression and schizophrenia. Increased neural activity within premotor cortices is linked to psychomotor slowing. This transdiagnostic study tested whether add-on inhibitory repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area (SMA) may alleviate psychomotor slowing. Forty-five patients with severe psychomotor slowing (26 psychosis, 19 major depression) were randomized in this transdiagnostic, double-blind, parallel-group, sham-controlled trial of 15 daily sessions of add-on rTMS over 3 weeks. Treatment arms included inhibitory 1 Hz stimulation of the SMA, facilitatory intermittent theta burst stimulation (iTBS) of the SMA, facilitatory 15 Hz stimulation of the left dorsolateral prefrontal cortex (DLPFC), and sham stimulation of the occipital cortex. The primary outcome was response (>30% reduction from baseline) according to the Salpêtrière Retardation Rating Scale (SRRS). Secondary outcomes were course of SRRS and further symptom rating scales. Last-observation carried forward method was applied to all subjects with baseline data. Response rates differed between protocols: 82% with inhibitory 1 Hz rTMS of the SMA, 0% with facilitatory iTBS of the SMA, 30% with sham, and 33% with 15 Hz DLPFC rTMS (χ 2 = 16.6, P < .001). Dropouts were similarly distributed across protocols. Response rates were similar in the completer analysis. This transdiagnostic trial of rTMS demonstrates that inhibitory SMA stimulation may ameliorate psychomotor slowing in severely ill patients. It further provides proof-of-concept that motor inhibition is linked to increased neural activity in the SMA because the inhibitory protocol performed best in reducing symptoms. Trial registration: NCT03275766 (www.clinicaltrials.gov).

Formal thought disorder (FTD) is a core feature of schizophrenia, a marker of illness severity and a predictor of outcome. The underlying neural mechanisms are still a matter of debate. This study aimed at 1) reviewing the literature on the neural correlates of FTD in schizophrenia, and 2) testing the hypothesis that FTD correlates with structural and functional aberrations in the language network. Medline, PsychInfo, and Embase were searched for neuroimaging studies, which applied a clinical measure to assess FTD in adults with schizophrenia and were published in English or German in peer-reviewed journals until December 2016. Of 412 articles identified, 61 studies were included in the review. Volumetric studies reported bilateral grey matter deficits (L > R) to be associated with FTD in the inferior frontal gyrus, the superior temporal gyrus and the inferior parietal lobe. The same regions showed hyperactivity in resting state functional magnetic resonance imaging (fMRI) studies and both hyper- and hypoactivity in fMRI studies that employed semantic processing or free speech production tasks. Diffusion tensor imaging studies demonstrated white matter aberrations in fibre tracts that connect the frontal and temporo-parietal regions. FTD in schizophrenia was found to be associated with structural and functional aberrations in the language network. However, there are studies that did not find an association between FTD and neural aberrations of the language network and regions not included in the language network have been associated with FTD. Thus, future research is needed to clarify the specificity of the language network for FTD in schizophrenia.

Schizophrenia is characterized by deficits in gesturing that is important for nonverbal communication. Research in healthy participants and brain-damaged patients revealed a left-lateralized fronto-parieto-temporal network underlying gesture performance. First evidence from structural imaging studies in schizophrenia corroborates these results. However, as of yet, it is unclear if cortical thickness abnormalities contribute to impairments in gesture performance. We hypothesized that patients with deficits in gesture production show cortical thinning in 12 regions of interest (ROIs) of a gesture network relevant for gesture performance and recognition. Forty patients with schizophrenia and 41 healthy controls performed hand and finger gestures as either imitation or pantomime. Group differences in cortical thickness between patients with deficits, patients without deficits, and controls were explored using a multivariate analysis of covariance. In addition, the relationship between gesture recognition and cortical thickness was investigated. Patients with deficits in gesture production had reduced cortical thickness in eight ROIs, including the pars opercularis of the inferior frontal gyrus, the superior and inferior parietal lobes, and the superior and middle temporal gyri. Gesture recognition correlated with cortical thickness in fewer, but mainly the same, ROIs within the patient sample. In conclusion, our results show that impaired gesture production and recognition in schizophrenia is associated with cortical thinning in distinct areas of the gesture network., Highlights • Impairments in gesture production and recognition in schizophrenia are related to altered brain structure. • Brain alterations in schizophrenia are located in areas that are generally damaged in apraxia. • Schizophrenia patients with gesture deficits show cortical thinning of several regions in the gesture network. • Deficits of gesture production and recognition are both related to a fronto-parieto-temporal gesture network.

BackgroundFirst rank symptoms (FRS) of schizophrenia have been used for decades for diagnostic purposes. In the new version of the DSM-5, the American Psychiatric Association (APA) has abolished any further reference to FRS of schizophrenia and treats them like any other “criterion A” symptom (e.g. any kind of hallucination or delusion) with regard to their diagnostic implication. The ICD-10 is currently under revision and may follow suit. In this review, we discuss central points of criticism that are directed against the continuous use of first rank symptoms (FRS) to diagnose schizophrenia.MethodsWe describe the specific circumstances in which Schneider articulated his approach to schizophrenia diagnosis and discuss the relevance of his approach today. Further, we discuss anthropological and phenomenological aspects of FRS and highlight the importance of self-disorder (as part of FRS) for the diagnosis of schizophrenia. Finally, we will conclude by suggesting that the theory and rationale behind the definition of FRS is still important for psychopathological as well as neurobiological approaches today.ResultsResults of a pivotal meta-analysis and other studies show relatively poor sensitivity, yet relatively high specificity for FRS as diagnostic marker for schizophrenia. Several methodological issues impede a systematic assessment of the usefulness of FRS in the diagnosis of schizophrenia. However, there is good evidence that FRS may still be useful to differentiate schizophrenia from somatic causes of psychotic states. This may be particularly important in countries or situations with little access to other diagnostic tests. FRS may thus still represent a useful aid for clinicians in the diagnostic process.ConclusionIn conclusion, we suggest to continue a tradition of careful clinical observation and fine-grained psychopathological assessment, including a focus on symptoms regarding self-disorders, which reflects a key aspect of psychosis. We suggest that the importance of FRS may indeed be scaled down to a degree that the occurrence of a single FRS alone should not suffice to diagnose schizophrenia, but, on the other hand, absence of FRS should be regarded as a warning sign that the diagnosis of schizophrenia or schizoaffective disorder is not warranted and requires specific care to rule out other causes, particularly neurological and other somatic disorders. With respect to the current stage of the development of ICD-11, we appreciate the fact that self-disorders are explicitly mentioned (and distinguished from delusions) in the list of mandatory symptoms but still feel that delusional perceptions and complex hallucinations as defined by Schneider should be distinguished from delusions or hallucinations of “any kind”. Finally, we encourage future research to explore the psychopathological context and the neurobiological correlates of self-disorders as a potential phenotypic trait marker of schizophrenia.

Background and Aims: Young adults with Attention Deficit/Hyperactivity Disorder (ADHD) show higher substance use disorder (SUD) prevalence relative to non-ADHD controls; few longitudinal studies have examined the course of substance use with reference to conduct disorder (CD). We compared initiation and escalation of substance use at 15-month follow up in men screened positive or negative for ADHD (ADHD+ vs. ADHD-), controlling for CD presence in early adolescence. Design: Participants were recruited during August 2010 and November 2011 from the census of all young men who have to pass mandatory army conscription from three out of six Swiss Army recruitment centres. A two-wave data collection was performed via questionnaires at baseline and 15-month follow up as a part of the longitudinal Cohort Study on Substance Use Risk Factors. Setting: Recruitment centres in Lausanne, Windisch, and Mels, responsible for twenty-one cantons in German- and French-speaking areas of Switzerland. Participants: Consecutive sample of 5,103 male Swiss Army conscripts who provided informed consent and responded to questionnaires at baseline and 15-month follow-up. Their mean age was 20.0 (SD = 1.21) years at baseline. Measurements: ADHD and CD were assessed using the adult ADHD Self-Report Scale and the MINI International Neuropsychiatric Interview Plus questionnaire, respectively, at baseline, and substance use was measured via self-administered substance use questionnaires at baseline and follow up. Findings: Compared with the ADHD- group, the ADHD+ group (n = 215, 4.2%) showed heavier baseline substance use and increased likelihood of alcohol (Chi2=53.96;p

INTRODUCTION The neural correlates of impaired performance of gestures are currently unclear. Lesion studies showed variable involvement of the ventro-dorsal stream particularly left inferior frontal gyrus (IFG) in gesture performance on command. However, findings cannot be easily generalized as lesions may be biased by the architecture of vascular supply and involve brain areas beyond the critical region. The neuropsychiatric syndrome of schizophrenia shares apraxic-like errors and altered brain structure without macroanatomic lesions. Schizophrenia may therefore qualify as a model disorder to test neural correlates of gesture impairments. METHODS We included 45 schizophrenia patients and 44 healthy controls in the study to investigate the structural brain correlates of defective gesturing in schizophrenia using voxel based morphometry. Gestures were tested in two domains: meaningful gestures (transitive and intransitive) on verbal command and imitation of meaningless gestures. Cut-off scores were used to separate patients with deficits, patients without deficits and controls. Group differences in gray matter (GM) volume were explored in an ANCOVA. RESULTS Patients performed poorer than controls in each gesture category (p

Background: Despite several previous attempts at subtyping schizophrenia, a typology that reflects neurobiological knowledge and reliably predicts course and outcome is lacking. We applied the system-specific concept of the Bern Psychopathology Scale (BPS) to generate a course typology based on three domains: language, affectivity, and motor behaviour. Sampling and Methods: A cohort of 100 patients with schizophrenia or schizoaffective disorders according to DSM-IV criteria underwent psychopathological assessment, and all their available medical records were retrospectively analysed on the basis of the BPS. Results: Overall, 39% of the patients showed dominant abnormalities in only one domain, 37% in two domains, and 24% in all three domains. The motor domain was affected in the majority of patients (76%), followed by affectivity (63%) and language (46%). Eighty-six percent of patients showed a bipolar course pattern in at least one domain. Conclusions: In a retrospective analysis of 100 patient records we described system-specific course patterns of schizophrenia by using a neurobiologically informed psychopathological assessment. The results showed a surprisingly high proportion of bipolar courses and a pattern of pure and mixed subtypes, which speaks for an overlap of domains with regards to psychopathological symptoms. A limitation of this heuristic and retrospective approach is that it was largely based on clinical judgement. Prospective studies with more rigorous threshold definitions are needed to clarify the neurobiological and clinical implications of the proposed reorganization of psychotic disorders.

Background/Aim: Gesturing plays an important role in social behavior and social learning. Deficits are frequent in schizophrenia and may contribute to impaired social functioning. Information about deficits during the course of the disease and presence of severity and patterns of impairment in first-episode patients is missing. Hence, we aimed to investigate gesturing in first- compared to multiple-episode schizophrenia patients and healthy controls. Methods: In 14 first-episode patients, 14 multiple-episode patients and 16 healthy controls matched for age, gender and education, gesturing was assessed by the comprehensive Test of Upper Limb Apraxia. Performance in two domains of gesturing - imitation and pantomime - was recorded on video. Raters of gesture performance were blinded. Results: Patients with multiple episodes had severe gestural deficits. For almost all gesture categories, performance was worse in multiple- than in first-episode patients. First-episode patients demonstrated subtle deficits with a comparable pattern. Conclusions: Subjects with multiple psychotic episodes have severe deficits in gesturing, while only mild impairments were found in first-episode patients independent of age, gender, education and negative symptoms. The results indicate that gesturing is impaired at the onset of disease and likely to further deteriorate during its course.

Background In mental illnesses, the language domain, including speech and thought, is often affected. The spectrum of language symptoms shows a great variability between patients with psychosis. In previous studies, we have not only demonstrated that patients and healthy controls show activation differences in the neural language circuitry, but also within the different patient groups. The Bern psychopathology scale is a tool to help differentiate patients, which presents with disinhibited or inhibited language symptoms. This aids to examine the continuum from health to psychosis in a dimensional approach. To understand the bipolarity within the patient groups on the continuum of language domain, the healthy population needs to be examined as well. Therefore, in the current study, a healthy population was tested to investigate this heterogeneity in the language domain during a lexical decision task. Additionally, a subjective rating of one’s language aptitude was measured, to gain an insight on where they would see themselves on the continuum. The aim was to examine the spectrum of inter-individual differences and its association with language-related brain networks, specifically Broca’s and Wernicke’s area. This observed heterogeneity of a healthy population would allow an extrapolation to clinical ends of the spectrum. Methods While measuring brain activity with fMRI, 102 healthy adult subjects performed a lexical priming task. Subjects had to decide if a visually presented target word would form the generic term of a previously shown prime word, in terms of its relation (e.g. Dog – Cat) or its category (e.g. Dog – Animal). To group the participants, each subject rated their own language aptitude on 7-point Likert scale. According to their rating they were then sorted into high, mid or low language aptitude groups. Results Although, we found differences in brain activation in Broca (BA44/ BA45) and Wernicke (pMTG) among the groups, the behavioral outcome, specifically reaction time (RT) and accuracy, showed no significant differences between the groups. We studied the activation patterns in the region of Broca’s area (BA45, BA44) and Wernicke’s area (pMTG) during preparation (waiting for the target after the indication of task type) and processing (target word processing) phases. We found group differences in BA45 during both preparation and processing phases. The Post hoc analysis revealed that the high group showed significantly greater activation in BA45 compared to the low group. While BA44 and pMTG showed only a significant group difference during the processing phase. Also, here the Post hoc analysis revealed that the high group showed greater activation in both areas during the processing phase. Furthermore, the psychophysiological interaction (PPI) analysis of BA44, during preparation phase, with RT as covariate revealed distinct functional connectivity patterns from seed area BA44 among the high and low language aptitude groups. We found, that a stronger connectivity from BA44 to the left posterior middle temporal gyrus (pMTG) was related with faster RT in the high group. The low group showed a same pattern from BA44 to the left fusiform gyrus, also known as the visual word form area. Discussion These results indicate that, one utilizes the language-related brain areas differently, as well as their connectivity, during the language task according to the subjective evaluation of oneself language aptitude. These new insights into the dimension of language is facilitating further research in psychosis, that analyzes the continuum from the healthy population profiles to the profiles of the population with psychosis. With this, it supports the efforts to improve diagnostic tools and treatment options for patients with psychosis.

Recent studies investigating neural correlates of human thirst have identified various subcortical and telencephalic brain areas. The experience of thirst represents a homeostatic emotion and a state that slowly evolves over time. Therefore, the present study aims at systematically examining cerebral perfusion during the parametric progression of thirst. We measured subjective thirst ratings, serum parameters and cerebral blood flow in 20 healthy subjects across four different thirst stages: intense thirst, moderate thirst, subjective satiation and physiological satiation. Imaging data revealed dehydration-related perfusion differences in previously identified brain areas, such as the anterior cingulate cortex, the middle temporal gyrus and the insular cortex. However, significant differences across all four thirst stages (including the moderate thirst level), were exclusively found in the posterior insular cortex. The subjective thirst ratings over the different thirst stages, however, were associated with perfusion differences in the right anterior insula. These findings add to our understanding of the insular cortex as a key player in human thirst - both on the level of physiological dehydration and the level of the subjective thirst experience.

Psychotic symptoms are supposed to be expression of highest order brain functions such as symbolic thinking, language, planning, empathy or complex emotional reactions. However, due to its historical roots, current psychiatric symptomatology is based on descriptions of disturbed behavior, which refer to metaphysic concepts rather than to brain function. Therefore, modern biological research suffers from an important gap between psychiatric semiology and contemporary knowledge in systems neurophysiology. The authors argue for a redefinition of psychiatric symptoms in a neurobiologically meaningful way. Based on recent empirical studies, this strategy is exemplified for auditory verbal hallucinations and formal thought disorder. In these examples, characteristic psychiatric symptoms can be related to circumscribed structural and functional alterations in the language system, allowing the description of clinical phenomena in terms of neurobiological events. This strategy is also applicable to other psychotic symptoms like emotional dysregulation and catatonia, where disturbances of the functional circuits of mood and motor regulation, respectively, are predicted. This approach to psychiatric symptoms is based on contemporary evidence concerning systems neurophysiology and is expected to provide meaningful and testable hypotheses for future research aimed to a better understanding of the pathogenesis of psychiatric disorders, to more accurate prognosis and to better targeted therapeutic strategies.

Zusammenfassung: Der Morbus Darier ist eine seltene Hauterkrankung, die autosomal-dominant vererbt wird und durch eine Mutation im SERCA (sarco/endoplasmatic reticulum calcium transporter)-2-Gen verursacht wird. In einigen Stammbäumen ist das Auftreten des Morbus Darier eng mit dem Vorkommen affektiver Erkrankungen verknüpft. Die wahrscheinlichste Ursache ist ein Suszeptibilitätsgen für affektive Erkrankungen in der Nähe des SERCA-2-Gens. Als Suszeptibilitätslokus konnte eine 6,5-Mb-Region identifiziert werden. Auch Studien mit affektiv erkrankten Stichproben, die nicht an Morbus Darier leiden, weisen ein Signal in der gleichen Region auf. Das zugrunde liegende Gen ist jedoch noch nicht identifiziert

Schizophrenia is characterized by social interaction deficits contributing to poor functional outcome. Hand gesture use is particularly impaired, linked to frontal lobe dysfunction and frontal grey matter deficits. The functional neural correlates of impaired gesturing are currently unclear. We therefore investigated aberrant brain activity during impaired gesturing in schizophrenia. We included 22 patients with schizophrenia and 25 healthy control participants matched for age, gender, and education level. We obtained functional magnetic resonance imaging data using an event-related paradigm to assess brain activation during gesture planning and execution. Group differences in whole brain effects were calculated using factorial designs. Gesture ratings were performed by a single rater, blind to diagnoses and clinical presentation. During gesture planning and execution both groups activated brain areas of the praxis network. However, patients had reduced dorsolateral prefrontal cortex (DLPFC) and increased inferior parietal lobe (IPL) activity. Performance accuracy was associated with IPL activity in patients. Furthermore, patients activated temporal poles, amygdala and hippocampus during gesture planning, which was associated with delusion severity. Finally, patients demonstrated increased dorsomedial prefrontal cortex activity during planning of novel gestures. We demonstrate less prefrontal, but more IPL and limbic activity during gesturing in schizophrenia. IPL activity was associated with performance accuracy, whereas limbic activity was linked to delusion severity. These findings may reflect impaired social action planning and a limbic interference with gestures in schizophrenia contributing to poor gesture performance and consequently poor social functioning in schizophrenia.

Schizophrenia research has been in a deadlock for many decades. Despite important advances in clinical treatment, there are still major concerns regarding long-term psychosocial reintegration and disease management, biological heterogeneity, unsatisfactory predictors of individual course and treatment strategies, and a confusing variety of controversial theories about its etiology and pathophysiological mechanisms. In the present perspective on schizophrenia research, we first discuss a methodological pitfall in contemporary schizophrenia research inherent in the attempt to link mental phenomena with the brain: we claim that the time-honored phenomenological method of defining mental symptoms should not be contaminated with the naturalistic approach of modern neuroscience. We then describe our Systems Neuroscience of Psychosis (SyNoPsis) project, which aims to overcome this intrinsic problem of psychiatric research. Considering schizophrenia primarily as a disorder of interindividual communication, we developed a neurobiologically informed semiotics of psychotic disorders, as well as an operational clinical rating scale. The novel psychopathology allows disentangling the clinical manifestations of schizophrenia into behavioral domains matching the functions of three well-described higher-order corticobasal brain systems involved in interindividual human communication, namely, the limbic, associative, and motor loops, including their corticocortical sensorimotor connections. The results of several empirical studies support the hypothesis that the proposed three-dimensional symptom structure, segregated into the affective, the language, and the motor domain, can be specifically mapped onto structural and functional abnormalities of the respective brain systems. New pathophysiological hypotheses derived from this brain system-oriented approach have helped to develop and improve novel treatment strategies with noninvasive brain stimulation and practicable clinical parameters. In clinical practice, the novel psychopathology allows confining the communication deficits of the individual patient, shifting attention from the symptoms to the intact resources. We have studied this approach and observed important advantages for therapeutic alliances, personalized treatment, and de-escalation strategies. Future studies will further conjoin clinical definitions of psychotic symptoms with brain structures and functions, and disentangle structural and functional deficit patterns within these systems to identify neurobiologically distinct subsyndromes. Neurobiologically homogeneous patient groups may provide new momentum for treatment research. Finally, lessons learned from schizophrenia research may contribute to developing a comprehensive perspective on human experience and behavior that integrates methodologically distinct, but internally consistent, insights from humanities and neuroscience.

Schizophrenia is a severe and, at the same time fascinating disorder. It is traditionally defined as a &laquo, dissociation&raquo, of higher brain functions, which implies a modular organization of the brain up to its highest levels of organization. This short review shows how the study of the disorder is still flawed by fundamentally different definitions of the disorder, and that a consistent naturalistic approach may help to revise the vocabulary of psychiatric disorders, opening the way towards a neurobiologically informed psychiatry. Empirical studies and clinical importance supporting this novel approach are summarized.

Aims: In randomized controlled trials with high internal validity, pharmacotherapy using acamprosate, naltrexone, and, to a somewhat lesser extent, disulfiram has proved effective in preventing relapse in patients with alcohol use disorders (AUD). There remains, however, a paucity of studies with sufficient external validity in which the effectiveness of pharmacotherapy in clinical practice is investigated. This study aimed to make a contribution to close this gap in research. Methods: In this naturalistic, prospective study, a comparison on indices of substance use, psychiatric symptoms, and treatment service utilization was carried out using samples of 92 patients who received pharmacotherapy and 323 patients who did not receive pharmacotherapy following discharge from 12 residential AUD programmes (index stay). Results: Patients that received pharmacotherapy were more likely to use alcohol during the index stay and at the 1-year follow-up. Moreover, this patient group more readily utilized treatment services during a 2-year period prior to and a 1-year period following index stay than patients who were not given pharmacotherapy. Nevertheless, when pharmacotherapy was prescribed before first post-treatment alcohol use, it was associated with delay of alcohol use, fewer relapses, and a reduced need for inpatient treatment. In many cases, however, medication was not prescribed until alcohol use and relapse had occurred. The length of time to first alcohol use was longer, and the cumulative abstinence rate higher, for disulfiram than for acamprosate, the latter being generally prescribed for more severely alcohol-dependent patients. Conclusions: There is a need for further studies to probe the reasons why medication for relapse prevention is not prescribed upon discharge from residential treatment and for less severely alcohol-dependent patients.

Background: Formal thought disorders (FTD) are a core symptom in schizophrenia. One key challenge remains the heterogeneity of FTD. Here we focus on state cerebral blood flow (rCBF) linked to severity of subtypes of FTD. We hypothesized distinguishable alterations in the language network linked to subtypes of FTD in schizophrenia associated with functioning after 6 month.

Glucocorticoids -- stress hormones released from the adrenal cortex -- reduce phobic fear in anxiety disorders and enhance psychotherapy, possibly by reducing the retrieval of fear memories. Glucocorticoid signaling in the basolateral amygdala can influence connected fear and memory related cortical regions, but this is not fully understood. Previous studies investigated specific pathways moderated by glucocorticoids, for example, visual-temporal pathways, however, these analyses are limited to a priori selected regions. Here, we performed whole-brain pattern analysis to localize phobic stimulus decoding related to the fear-reducing effect of glucocorticoids. We analyzed functional magnetic resonance imaging (fMRI) data from a randomized, double-blind, placebo-controlled study with spider-phobic patients while they were looking at spider images. The patients either received oral glucocorticoids (20 mg of hydrocortisone) or a placebo. Patients with phobia had higher decoding in the anterior cingulate cortex (ACC) and the left and right anterior insula compared to controls. Decoding in the ACC and the right insula showed the highest correlations with experienced fear and explained 40% of the variance across all participants. Patients with cortisol reported a reduction of fear by 10-13% and showed decoding of phobic images in the precuneus, the cerebellum, and the opercular cortex. Patients in the placebo group with increased fear showed decoding in the insula, the ACC and the right frontal lateral pole which have been shown to be related to the fear circuitry and episodic memory. This study demonstrates phobic decoding in fear-related frontal regions and suggests that cortisol administration alters these fears-specific processing areas.

Glucocorticoids reduce phobic fear in patients with anxiety disorders. Previous studies have shown that fear related activation of the amygdala can be mediated through the visual cortical pathway which includes the fusiform gyrus or through other pathways. However it is not clear which of the pathways that activate the amygdala is responsible for the pathophysiology of a specific phobia and how glucocorticoid treatment alleviates fear processing in these neural networks. We recorded the brain activity with functional magnetic resonance imaging in patients with spider phobia who received either 20?mg of cortisol or a placebo while viewing pictures of spiders. We also tested healthy participants who did not receive any medication during the same task. We performed dynamic causal modelling (DCM) a connectivity analysis to examine the effects of cortisol on the networks involved in processing fear and to examine if there was an association between these networks and the symptoms of the phobia. Cortisol administration suppressed the phobic stimuli related amygdala activity to levels comparable to the healthy participants and reduced subjective phobic fear. The DCM analysis revealed that cortisol administration suppressed the aberrant inputs into the amygdala that did not originate from the visual cortical pathway but rather from a fast subcortical pathway mediated by the pulvinar nucleus and suppressed the interactions between the amygdala and fusiform gyrus. This network changes were distinguishable from healthy participants and considered the residual changes under cortisol administration. We also found that the strengths of the aberrant inputs into the amygdala were positively correlated with the severity of spider phobia. This study demonstrates that patients with spider phobia show an aberrant functional connectivity of the amygdala when they are exposed to phobia related stimuli and that cortisol administration can alleviate this fear specific neural connectivity.Neuropsychopharmacology advance online publication 12 October 2016; doi:10.1038/npp.2016.207.

This study examined whether patients’ drinking goals at admission to and discharge from 12 residential alcohol use disorder treatment programs were associated with alcohol-related outcomes at 1-year follow-up. Detoxified patients (N D 289) completed assessments at admission, after treatment, and at 1-year follow-up. Drinking goals of abstinence, conditional abstinence (in principle abstinence but potential occurrence of lapses or drinking, when urges are strong), and controlled drinking changed during treatment and predicted the 1-year follow-up outcomes (abstinence, number of standard drinks, and number of days to the first alcohol use). Goals at discharge had a better predictive value. The goal of abstinence at discharge had better outcomes than conditional abstinence; the poorest had controlled drinking.

OBJECTIVES: Patients' motivation to change their substance use is usually viewed as a crucial component of successful treatment. The objective of this study was to examine whether motivation contributes to drinking outcomes after residential treatment for alcohol dependence. METHODS: Our sample included 415 Swiss patients from 12 residential alcohol treatment programs. We statistically controlled for important predictors, such as sex, employment, alcohol consumption before admission, severity of alcohol dependence, severity of psychiatric symptoms at admission, and alcohol-related self-efficacy at discharge. Abstinence, alcohol consumption, and time to first drink were used as primary outcome measures and were assessed 1 year after discharge from treatment. RESULTS: Action-oriented motivation to change substance use had a modest impact on drinking outcomes. At the 1-year follow-up, only the Taking Steps subscale of the Stages of Change Readiness and Treatment Eagerness Scale and alcohol-related self-efficacy were found to be significant predictors of abstinence and the number of standard drinks. CONCLUSIONS: The impact of action-oriented motivation at admission to residential treatment is modest but still relevant, compared with other outcome predictors. It may be useful to focus treatment on improving action-oriented motivation to reduce substance use

Introduction Substantial heterogeneity remains across studies investigating changes in gray matter in schizophrenia. Differences in methodology, heterogeneous symptom patterns and symptom trajectories may contribute to inconsistent findings. To address this problem, we recently proposed to group patients by symptom dimensions, which map on the language, the limbic and the motor systems. The aim of the present study was to investigate whether patients with prevalent symptoms of emotional dysregulation would show structural neuronal abnormalities in the limbic system. Method 43 right-handed medicated patients with schizophrenia were assessed with the Bern Psychopathology Scale (BPS). The patients and a control group of 34 healthy individuals underwent structural imaging at a 3T MRI scanner. Whole brain voxel-based morphometry (VBM) was compared between patient subgroups with different severity of emotional dysregulation. Group comparisons (comparison between patients with severe emotional dysregulation, patients with mild emotional dysregulation, patients with no emotional dysregulation and healthy controls) were performed using a one way ANOVA and ANCOVA respectively. Results Patients with severe emotional dysregulation had significantly decreased gray matter density in a large cluster including the right ventral striatum and the head of the caudate compared to patients without emotional dysregulation. Comparing patients with severe emotional dysregulation and healthy controls, several clusters of significant decreased GM density were detected in patients, including the right ventral striatum, head of the caudate, left hippocampus, bilateral thalamus, dorsolateral prefrontal and orbitofrontal cortex. The significant effect in the ventral striatum was lost when patients with and without emotional dysregulation were pooled and compared with controls. Discussion Decreased gray matter density in a large cluster including the right ventral striatum was associated with severe symptoms of emotional dysregulation in patients with schizophrenia. The ventral striatum is an important part of the limbic system, and was indicated to be involved in the generation of incentive salience and psychotic symptoms. Only patients with severe emotional dysregulation had decreased gray matter in several brain structures associated with emotion and reward processing compared to healthy controls. The results support the hypothesis that grouping patients according to specific clinical symptoms matched to the limbic system allows identifying patient subgroups with structural abnormalities in the limbic network., Highlights • We examined whole brain VBM in schizophrenia patients and healthy controls. • We compared patients with different severity of emotional dysregulation (ED). • Symptoms of ED were associated with GM density in the ventral striatum. • Grouping patients according to symptoms identified specific GM abnormalities.