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Background: We sought to examine the association of levels of total tau (t-tau) and phosphorylated tau 181 (p-tau181) protein with brain morphology in mild cognitive impairment, as defined by the concept of aging-associated cognitive decline (AACD) and Alzheimer disease. Methods: Twenty-three participants with AACD, 16 with Alzheimer disease and 15 healthy controls underwent magnetic resonance imaging and lumbar puncture. We performed voxel-based morphometry to investigate the association between tau levels in cerebrospinal fluid (CSF) and cerebral grey matter density throughout the entire brain. Results: Voxel-based morphometry revealed that both elevated t-tau and p-tau181 concentrations were associated with reduced grey matter density in temporal, parietal and frontal regions. Among participants with AACD, elevated levels of p-tau181 (but not t-tau) in CSF were correlated with a pronounced atrophy in the right hippocampus. Limitations: Our study was limited by the small sample, especially with respect to the analysis comprising the AACD subgroups. Moreover, we did not correct our voxel-based morphometry analyses for multiple dependent comparisons, therefore they harbour a risk of false-positive results. Conclusion: Elevated levels of t-tau and p-tau181 in CSF reflect degenerative processes in the cortical regions typically affected in Alzheimer disease. Our findings in participants with AACD support the hypothesis that p-tau181 might be more specifically related to neurodegenerative changes in early Alzheimer disease. [ABSTRACT FROM AUTHOR]

The Clock Drawing Test (CDT) is a widely used instrument in the neuropsychological assessment of Alzheimer's disease (AD). As CDT performance necessitates several cognitive functions (e.g., visuospatial and constructional abilities, executive functioning), an interaction of multiple brain regions is likely. Fifty-one subjects with mild cognitive impairment, 23 with AD and 15 healthy controls underwent high-resolution magnetic resonance imaging. Optimized voxel-based morphometry (VBM) was performed to investigate the putative association between CDT performance and gray matter (GM) density throughout the entire brain. In the first step of analysis (p<.001, uncorrected), VBM revealed a reduced GM density in numerous cortical (temporal lobe, frontal lobe, parietal lobe, cerebellum) and subcortical (thalamus, basal ganglia) brain regions to be associated with poorer CDT performance. When corrected for multiple comparisons (p<.01), the associations remained significant predominantly in the left temporal and--less pronounced--the right temporal lobe. VBM demonstrated CDT performance to depend on the integrity of widely distributed cortical and subcortical areas in both brain hemispheres with accentuation in the left-sided temporal lobe region. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although previous studies demonstrate significant atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD), CC alterations in mild cognitive impairment have not been investigated yet. METHODS: 21 subjects with mild cognitive impairment, 10 with AD and 21 healthy controls were investigated using magnetic resonance imaging. In the mid-sagittal slice the CC was traced manually. Additionally, voxel-based morphometry (VBM) was performed. RESULTS: The CC was significantly smaller in patients with AD compared to healthy controls in both manual tracing and VBM. The atrophy was prominent in rostral parts of the CC. In subjects with mild cognitive impairment, the two rostral CC segments were smaller compared to controls when manually traced. In contrast, VBM revealed no significant difference between subjects with mild cognitive impairment and controls. CONCLUSION: Manual tracing was more sensitive in detecting discrete structural CC changes than VBM. Alterations of the CC in mild cognitive impairment rank in between normal aging and AD, supporting the hypothesis that mild cognitive impairment most often represents a preclinical stage of AD. [ABSTRACT FROM AUTHOR]

Background: Fatigue and psychosocial impairments are highly prevalent in IBD, particularly during active disease. Disturbed brain-gut interactions may contribute to these symptoms. This study examined associations between brain structure, faecal calprotectin, and symptoms of fatigue, depression, and anxiety in persons with Crohn's disease [CD] in different disease states., Methods: In this prospective observational study, n = 109 participants [n = 67 persons with CD, n = 42 healthy controls] underwent cranial magnetic resonance imaging, provided stool samples for analysis of faecal calprotectin, and completed questionnaires to assess symptoms of fatigue, depression, and anxiety. We analysed differences in grey matter volume [GMV] between patients and controls, and associations between regional GMV alterations, neuropsychiatric symptoms, and faecal calprotectin., Results: Symptoms of fatigue, depression, and anxiety were increased in patients with CD compared with controls, with highest scores in active CD. Patients exhibited regionally reduced GMV in cortical and subcortical sensorimotor regions, occipitotemporal and medial frontal areas. Regional GMV differences showed a significant negative association with fatigue, but not with depression or anxiety. Subgroup analyses revealed symptom-GMV associations for fatigue in remitted but not in active CD, whereas fatigue was positively associated with faecal calprotectin in active but not in remitted disease., Conclusion: Our findings support disturbed brain-gut interactions in CD which may be particularly relevant for fatigue during remitted disease. Reduced GMV in the precentral gyrus and other sensorimotor areas could reflect key contributions to fatigue pathophysiology in CD. A sensorimotor model of fatigue in CD could also pave the way for novel treatment approaches., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Evidence for the effectiveness of physical activity (PA) in the treatment of depression prevails for outpatients with mild and moderate symptom levels. For inpatient treatment of severe depression, evidence-based effectiveness exists only for structured and supervised group PA interventions. The Step Away from Depression (SAD) study investigated the effectiveness of an individual pedometer intervention (PI) combined with an activity diary added to inpatient treatment as usual (TAU). In this multicenter randomized controlled trial, 192 patients were randomized to TAU or TAU plus PI. The two primary outcomes at discharge were depression-blindly rated with the Montgomery-Åsberg Depression Rating Scale (MADRS)-and average number of daily steps measured by accelerometers. Secondary outcomes were self-rated depression and PA, anxiety, remission and response rates. Multivariate analysis of variance (MANOVA) revealed no significant difference between both groups for depression and daily steps. Mean MADRS scores at baseline were 29.5 (SD = 8.3) for PI + TAU and 28.8 (SD = 8.1) for TAU and 16.4 (SD = 10.3) and 17.2 (SD = 9.9) at discharge, respectively. Daily steps rose from 6285 (SD = 2321) for PI + TAU and 6182 (SD = 2290) for TAU to 7248 (SD = 2939) and 7325 (SD = 3357). No differences emerged between groups in secondary outcomes. For severely depressed inpatients, a PI without supervision or further psychological interventions is not effective. Monitoring, social reinforcement and motivational strategies should be incorporated in PA interventions for this population to reach effectiveness., (© 2023. The Author(s).)

Background: Extraintestinal symptoms are common in inflammatory bowel diseases (IBD) and include depression and fatigue. These are highly prevalent especially in active disease, potentially due to inflammation-mediated changes in the microbiota-gut-brain axis. The aim of this study was to investigate the associations between structural and functional microbiota characteristics and severity of fatigue and depressive symptoms in patients with active IBD., Methods: We included clinical data of 62 prospectively enrolled patients with IBD in an active disease state. Patients supplied stool samples and completed the questionnaires regarding depression and fatigue symptoms. Based on taxonomic and functional metagenomic profiles of faecal gut microbiota, we used Bayesian statistics to investigate the associative networks and triangle motifs between bacterial genera, functional modules and symptom severity of self-reported fatigue and depression., Results: Associations with moderate to strong evidence were found for 3 genera (Odoribacter, Anaerotruncus and Alistipes) and 3 functional modules (pectin, glycosaminoglycan and central carbohydrate metabolism) with regard to depression and for 4 genera (Intestinimonas, Anaerotruncus, Eubacterium and Clostridiales g.i.s) and 2 functional modules implicating amino acid and central carbohydrate metabolism with regard to fatigue., Conclusions: This study provides the first evidence of association triplets between microbiota composition, function and extraintestinal symptoms in active IBD. Depression and fatigue were associated with lower abundances of short-chain fatty acid producers and distinct pathways implicating glycan, carbohydrate and amino acid metabolism. Our results suggest that microbiota-directed therapeutic approaches may reduce fatigue and depression in IBD and should be investigated in future research., (© 2022. The Author(s).)

Schizophrenia is a severe mental illness associated with a heavy symptom burden and high relapse rates. Digital interventions are increasingly suggested as means to facilitate continuity of care, relapse prevention, and long-term disease management for schizophrenia spectrum disorders. In order to investigate the feasibility of a mobile and internet-based aftercare program, a 2-arm randomized controlled pilot study was conducted. The program could be used by patients for six months after inpatient treatment and included psychoeducation, an individual crisis plan, optional counseling via internet chat or phone and a supportive monitoring module. Due to the slow pace of enrollment, recruitment was stopped before the planned sample size was achieved. Reasons for the high exclusion rate during recruitment were analyzed as well as attitudes, satisfaction, and utilization of the program by study participants. The data of 25 randomized patients suggest overall positive attitudes towards the program, high user satisfaction and good adherence to the monitoring module. Overall, the results indicate that the digital program might be suitable to provide support following discharge from intensive care. In addition, the study provides insights into specific barriers to recruitment which may inform future research in the field of digital interventions for severe mental illness.

Quality of life (QoL) of persons with inflammatory bowel diseases (IBD) is often impaired by symptoms that do not primarily relate to intestinal inflammation. Among the most challenging extraintestinal symptoms are depression and fatigue, which are also frequent in other chronic diseases like multiple sclerosis, rheumatoid arthritis and cancer. Yoga as an ancient Indian tradition containing postures, breathing exercises and meditation may positively influence those symptoms. This review evaluates the current literature with regard to the effect of yoga-based interventions in persons with IBD and with regard to QoL, depression and fatigue in other somatic disorders. A systematic literature search yielded three trials examining the effects of yoga in patients with IBD and 37 trials addressing depressive syndromes or fatigue in somatic disorders. In summary, both in-person and video-based yoga classes are feasible, acceptable and safe as complementary treatment in patients with IBD and significantly improve anxiety and impaired quality of life. Current literature does not provide information on the effect of yoga on depression and fatigue in patients with IBD, but research from other somatic disorders or patients with depressive disorders implies the potential of yoga in this regard for persons with IBD. This should be specifically addressed in interventional trials with standardized yoga modules including patients with IBD suffering from fatigue, depression and/or impaired QoL., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: A growing number of neuroimaging studies suggest distinct neural changes in inflammatory bowel diseases (IBDs). Whether such changes may show similar spatial patterns across distinct neural features within and between specific IBD is unclear. To address this question, we used multivariate multimodal data fusion analysis to investigate structure/function modulation in remitted patients with Crohn's disease (CD) and ulcerative colitis (UC)., Methods: Patients with IBD (n = 46; n = 31 with CD, n = 15 with UC) in stable remission and 17 healthy controls (HC) underwent structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (rs-fMRI) as well as cognitive testing. Anxiety, depression, and fatigue were assessed using self-rating questionnaires. sMRI data were analyzed via voxel-based morphometry (VBM) and rs-fMRI data via amplitude of low-frequency fluctuations (ALFFs) and regional homogeneity (ReHo). Detection of cross-information between VBM, ALFF, and ReHo was conducted by means of a joint independent component analysis (jICA), followed by group-inference statistics., Key Results: Joint independent component analysis detected structural alterations in middle frontal and temporal regions (VBM), and functional changes in the superior frontal gyrus (ReHo) and the medial as well as inferior frontal, inferior temporal, rectal, and subcallosal gyrus (ALFF). One joint component of extracted features of the three modalities differed significantly between IBD patients and controls (p = 0.03), and most distinctly between HC and patients with UC., Conclusions and Inferences: Using a multivariate data fusion technique, this study provides further evidence to brain alterations in IBD. The data suggest distinct neural differences between CD and UC, particularly in frontotemporal regions., (© 2020 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Electroconvulsive therapy (ECT) is a rapid and highly effective treatment option for treatment-resistant major depressive disorder (TRD). The neural mechanisms underlying such beneficial effects are poorly understood. Exploring associations between changes of brain structure and clinical response is crucial for understanding ECT mechanisms of action and relevant for the validation of potential biomarkers that can facilitate the prediction of ECT efficacy. The aim of this explorative study was to identify cortical predictors of clinical response in TRD patients treated with ECT. We longitudinally investigated 12 TRD patients before and after ECT. Twelve matched healthy controls were studied cross sectionally. Demographical, clinical, and structural magnetic resonance imaging data at 3 T and multiple cortical markers derived from surface-based morphometry (SBM) analyses were considered. Multiple regression models were computed to identify predictors of clinical response to ECT, as reflected by Hamilton Depression Rating Scale (HAMD) score changes. Symptom severity differences pre-post-ECT were predicted by models including demographic data, clinical data and SBM of frontal, cingulate, and entorhinal structures. Using all-subsets regression, a model comprising HAMD score at baseline and cortical thickness of the left rostral anterior cingulate gyrus explained most variance in the data (multiple R 2  = 0.82). The data suggest that SBM provides powerful measures for identifying biomarkers for ECT response in TRD. Rostral anterior cingulate thickness and HAMD score at baseline showed the greatest predictive power of clinical response, in contrast to cortical complexity, cortical gyrification, or demographical data.

Major depressive disorder (MDD) and schizophrenia (SCZ) share neurobiological and clinical commonalities. Altered functional connectivity of large-scale brain networks has been associated with both disorders. Electroconvulsive therapy (ECT) has proven to be an effective treatment in severe forms of MDD and SCZ. However, the role of ECT on the modulation of the dynamics of brain networks is still unknown. In this study, we used resting state functional magnetic resonance imaging (rs-fMRI) to investigate functional connectivity in 16 pharmacoresistant patients with SCZ or MDD and a matched group of normal controls. Patients were scanned before and after right-sided unilateral ECT. Group spatial independent component analysis was carried out with a multiple analysis of covariance (MANCOVA) approach to estimate the effects of ECT treatment on intrinsic components (INs). Functional network connectivity (FNC) was calculated between pairs of INs. Patients had reduced connectivity within a striato-thalamic network in the thalamus as well as increased low frequency oscillations in a striatal network. ECT reduced low frequency oscillations (LFOs) on a striatal network along with increasing functional connectivity in the medial prefrontal cortex within the DMN. Following ECT treatment, the FNC of the executive network was reduced with the DMN and increased with the salience network, respectively. Our findings suggest transnosological effects of ECT on the connectivity of large-scale networks as well as at the level of their interplay. Furthermore, they support a transnosological approach for the investigation not only of the neural correlates of the disease but also of the brain mechanism of treatment of mental disorders., (Copyright © 2019 Elsevier B.V. and ECNP. All rights reserved.)

Background: Disturbed brain-gut interactions and a bidirectional relationship between inflammation and psychiatric symptoms such as anxiety and depression are being discussed in patients with inflammatory bowel diseases (IBD). Alterations of brain structure and function in IBD have been reported with heterogeneous results. Whether these changes reflect independent localized deficits or rather a systematic disruption in the anatomical organization of large-scale brain networks remains unclear. The present study investigated the gray matter structural connectome in patients with Crohn's disease (CD)., Methods: Sixty participants (30 with quiescent CD and 30 matched healthy controls [HC]) underwent high-resolution brain MRI at 3 Tesla. Well-established graph theoretical metrics were analyzed at the global and regional network level and compared between groups., Key Results: The networks in both groups followed a small-world organization, that is, an architecture that is simultaneously highly segregated and integrated. However, transitivity, a measure of global network segregation, was significantly reduced in patients (P = 0.003). Regionally, patients showed a reduction of nodal betweenness centrality in the right insula and cuneus and the left superior frontal cortex and reduced nodal degree within the left-hemispheric cingulate and the left lateral and right medial orbitofrontal cortex., Conclusion and Inferences: These findings lend support to the hypothesis that CD is accompanied by alterations in both global network organization and regional connectivity. A deeper understanding of neural central networks in IBD may facilitate the development of complementary strategies in the treatment of "extraintestinal" comorbid conditions such as depression or anxiety., (© 2019 John Wiley & Sons Ltd.)

The treatment of schizophrenic psychoses with antipsychotic drugs (AP) is often associated with an increased risk of delayed occurrence of antipsychotic-associated movement disorders. Persistence and chronicity of such symptoms are very frequent. The risk of developing tardive dyskinesia (TD) is associated with the pharmacological effect profile of a particular AP, with treatment duration and age. This systematic review article summarizes the current study situation on prevalence, risk factors, prevention and treatment options and instruments for early prediction of TD in schizophrenic psychoses. The current data situation on treatment strategies for TD is very heterogeneous. For the treatment of TD there is preliminary evidence for reduction or discontinuation of the AP, switching to clozapine, administration of benzodiazepines (clonazepam) and treatment with vesicular monoamine transporter (VMAT2) inhibitors, ginkgo biloba, amantadine or vitamin E. Although TD can be precisely diagnosed it cannot always be effectively treated. Early detection and early treatment of TD can have a favorable influence on the prognosis and the clinical outcome.

Objectives: The clock drawing test (CDT) is one of the worldwide most used screening tests for Alzheimer's disease (AD). MRI studies have identified temporo-parietal regions being involved in CDT impairment. However, the contributions of specific hippocampal subfields and adjacent extrahippocampal structures to CDT performance in AD and mild cognitive impairment (MCI) have not been investigated so far. It is unclear whether morphological alterations or CDT score, or a combination of both, are able to predict AD., Methods: 38 AD patients, 38 MCI individuals and 31 healthy controls underwent neuropsychological assessment and MRI at 3 Tesla. FreeSurfer 5.3 was used to perform hippocampal parcellation. We used a collection of statistical methods to better understand the relationship between CDT and hippocampal formation. We also tested the clinical feasibility of this relationship when predicting AD., Results: Impaired CDT performance in AD was associated with widespread atrophy of the cornu ammonis, presubiculum, and subiculum, whereas MCI subjects showed CDT-related alterations of the CA4-dentate gyrus and subiculum. CDT correlates in AD and MCI showed regional and quantitative overlap. Importantly, CDT score was the best predictor of AD., Conclusions: Our findings lend support for an involvement of different hippocampal subfields in impaired CDT performance in AD and MCI. CDT seems to be more efficient than subfield imaging for predicting AD.

Background: Electroconvulsive therapy (ECT) and depression have been associated with brain volume changes, especially in the hippocampus and the amygdala., Methods: In this retrospective study we collected data from individual pre-post ECT whole brain magnetic resonance imaging scans of depressed patients from six German university hospitals. Gray matter volume (GMV) changes were quantified via voxel-based morphometry in a total sample of 92 patients with major depressive episodes (MDE). Additionally, 43 healthy controls were scanned twice within a similar time interval., Results: Most prominently longitudinal GMV increases occurred in temporal lobe regions. Within specific region of interests we detected significant increases of GMV in the hippocampus and the amygdala. These results were more pronounced in the right hemisphere. Decreases in GMV were not observed. GMV changes did not correlate with psychopathology, age, gender or number of ECT sessions. We ruled out white matter reductions as a possible indirect cause of the detected GMV increase., Conclusion: The present findings support the notion of hippocampus and amygdala modulation following an acute ECT series in patients with MDE. These results corroborate the hypothesis that ECT enables primarily unspecific and regionally dependent neuroplasticity effects to the brain., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Acute antipsychotic-induced movement disorders (AIMD) are clinically relevant since they are frequently associated with high subjective distress, and since over the long-term they can negatively impact treatment adherence of patients with schizophrenic psychoses. This review article summarizes the relevant studies on the prevalence, risk factors, prevention and treatment options and instruments for early prediction of acute AIMD in schizophrenic psychoses. The current evidence and treatment recommendations are divided into three main areas: acute dystonia, akathisia, and parkinsonism. For the treatment of acute dystonia trihexyphenidyl and biperiden have shown their efficacy. Considering pharmacological treatment of akathisia, there is some preliminary evidence for medication with lipophilic beta-receptor blockers (propranolol and pindolol), clonidine, benzodiazepines, mianserin, mirtazapine und trazodone. The treatment options for drug-induced parkinsonism include reduction or switching from one antipsychotic to another with a lower affinity for dopamine D 2 receptors, amantadine or in the regular administration of anticholinergic drugs. In conclusion, acute AIMD is easily to recognize but is not always effectively and durably treated. Early recognition and treatment of acute AIMD could be associated with improved treatment outcomes.

Abnormal gray matter volume has been consistently reported in patients with major depressive disorder (MDD), but markers of cortical neurodevelopment have been rarely investigated. Also, it is unclear whether there exist common versus distinct spatial patterns of abnormal cortical development across different disorders presenting with negative emotions and deficient affective regulation. In this study, we used structural MRI at 3T to investigate the local gyrification index (LGI), a marker of fetal/infant neurodevelopment, in adult female patients with MDD (n = 22), in adult female patients with borderline personality disorder (BPD) (n = 17), and in controls (n = 22). Reduced cortical folding of the precuneus, the superior parietal gyrus and the parahippocampal gyrus was found in both MDD and BPD patients when compared to controls (p < 0.05, cluster-wise probability [CWP] corrected). MDD patients showed additional hypogyrification of the middle frontal gyrus and the fusiform gyrus when compared to both controls and BPD patients (p < 0.05, CWP corrected). In MDD patients, lower LGI of prefrontal regions was significantly associated with the age of disease onset and with the number of depressive episodes. In BPD patients, lower LGI of orbitofrontal regions was associated with impulsivity. Our findings suggest abnormal early cortical development in MDD, affecting brain regions that have been frequently implied in MDD pathophysiology. However, LGI abnormalities may not be specific for MDD, since MDD and BPD patients also exhibited common patterns of hypogyrification. Hypogyrification of cortical regions associated with higher-order cognition appears to be most pronounced in MDD. Abnormal early cortical neurodevelopment may mediate vulnerability to disorders of emotion., (Copyright © 2018. Published by Elsevier B.V.)

Primary motor abnormalities (PMA), as found in patients with schizophrenia, are quantitatively and qualitatively distinct markers of motor system abnormalities. PMA have been often referred to phenomena that are present across schizophrenia-spectrum disorders. A dysfunction of frontoparietal and subcortical networks has been proposed as core pathophysiological mechanism underlying the expression of PMA. However, it is unclear at present if such mechanisms are a common within schizophrenia and other psychotic disorders. To address this question, we review recent neuroimaging studies investigating the neural substrates of PMA in schizophrenia and so-called "nonschizophrenic nonaffective psychoses" (NSNAP) such as schizophreniform, schizoaffective, brief psychotic, and other unspecified psychotic disorders. Although the extant data in patients with schizophrenia suggests that further investigation is warranted, MRI findings in NSNAP are less persuasive. It is unclear so far which PMA, if any, are characteristic features of NSNAP or, possibly even specific for these disorders. Preliminary data suggest a relationship between relapsing-remitting PMA in hyper-/hypokinetic cycloid syndromes and neurodegenerative disorders of the basal ganglia, likely reflecting the transnosological relevance of subcortical abnormalities. Despite this evidence, neural substrates and mechanisms underlying PMA that are common in schizophrenia and NSNAP cannot be clearly delineated at this stage of research. PMA and their underlying brain circuits could be promising intermediate phenotype candidates for psychotic disorders, but future multimodal neuroimaging studies in schizophrenia and NSNAP patients and their unaffected first-degree relatives are needed to answer fundamental transnosologic questions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Impulsivity is an essential human personality trait and highly relevant for the development of several mental disorders. There is evidence that impulsivity is heritable, yet little is known about neural correlates reflecting early brain development. Here, we address the question whether motor, attentional and non-planning components, as reflected by the Barratt Impulsiveness Scale (BIS-11), are distinctly associated with cortical thickness and surface area variations in young healthy individuals., Method: We investigated cortical thickness and surface area in 54 healthy volunteers (m/f = 30%/70%; age mean/SD = 24.9/4.02) using structural magnetic resonance imaging at 3 T together with surface-based analysis techniques. Impulsivity was examined on the Barratt impulsiveness scale (BIS-11) and related to the two distinct cortical measurements., Results: Higher BIS-11 total scores were negatively associated with cortical thickness variations in the left lingual gyrus, left superior temporal gyrus, right cuneus, and right superior parietal gyrus (p < 0.05 cluster-wise probability [CWP] corrected). Higher BIS-11 nonplanning scores were negatively associated with cortical thickness variations in bilateral pericalcarine gyrus (p < 0.05 CWP corr.). In the orbitofrontal cortex, the association between impulsivity and cortical thickness differed significantly between males and females., Conclusion: These data suggest distinct neurodevelopmental trajectories underlying impulsivity in healthy subjects. Impulsivity total scores appear to be specifically related to cortical thickness variations, in contrast to variations of cortical surface area. Furthermore, our findings underscore the importance of better characterizing gender-specific structural correlates of impulsivity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Impulsiveness is a central human personality trait and of high relevance for the development of several mental disorders. Impulsiveness is a multidimensional construct, yet little is known about dimension-specific neural correlates. Here, we address the question whether motor, attentional and non-planning components, as measured by the Barratt Impulsiveness Scale (BIS-11), are associated with distinct or overlapping neural network activity. In this study, we investigated brain activity at rest and its relationship to distinct dimensions of impulsiveness in 30 healthy young adults (m/f = 13/17; age mean/SD = 26.4/2.6 years) using resting-state functional magnetic resonance imaging at 3T. A spatial independent component analysis and a multivariate model selection strategy were used to identify systems loading on distinct impulsivity domains. We first identified eight networks for which we had a-priori hypotheses. These networks included basal ganglia, cortical motor, cingulate and lateral prefrontal systems. From the eight networks, three were associated with impulsiveness measures (p < 0.05, FDR corrected). There were significant relationships between right frontoparietal network function and all three BIS domains. Striatal and midcingulate network activity was associated with motor impulsiveness only. Within the networks regionally confined effects of age and gender were found. These data suggest distinct and overlapping patterns of neural activity underlying specific dimensions of impulsiveness. Motor impulsiveness appears to be specifically related to striatal and midcingulate network activity, in contrast to a domain-unspecific right frontoparietal system. Effects of age and gender have to be considered in young healthy samples.

Schizophrenia is a severe behavioral syndrome of neurodevelopmental nature marked by primary or genuine motor abnormalities (GMA), which refer to spontaneous and medication-independent motor phenomena. Since motor dysfunction thus might be a consequence of events occurring during early childhood and adolescence, GMA can be detected in the period preceding manifest schizophrenia. However, the question whether motor system dysfunction might be a promising motor intermediate phenotype for schizophrenia remains unanswered. In this review, we systematically evaluate the evidence on GMA in healthy persons, individuals with schizotypal personality traits, persons at ultra-high risk for psychosis, and unaffected first-degree relatives of schizophrenia patients. What becomes evident is a continuum of GMA expression, which appears to be linked to abnormalities of cerebello-thalamo-cortical, fronto-parietal, and cortico-subcortical motor circuits. According to current evidence, motor dysfunction is a key aspect of the neurodevelopmental risk factor model of schizophrenia. Insights provided by this research will help promoting the RDoC Motor System construct and expand the clinical relevance of the motor domain in the period preceding manifest schizophrenia., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

As established in a wealth of studies subtle motor and sensory neurological abnormalities or neurological soft signs (NSS) are frequently found in patients with schizophrenia at any stage of their illness. However, the potential impact of chronicity and age on NSS was scarcely investigated. Therefore, we assessed NSS in 90 patients with subchronic ( n  = 22) or chronic ( n  = 68) schizophrenia and in 60 healthy controls who were assigned to three age groups (18-29, 30-49, and +50 years). NSS were measured on the Heidelberg Scale, psychopathological symptoms including apathy were rated on established instruments. As demonstrated by analysis of variance, NSS scores in patients were significantly ( p  < 0.05) increased relative to healthy controls. Significant age effects arose in all NSS subscores, with older subjects scoring well above the younger ones. These age effects were more pronounced in patients than controls, indicating that NSS in chronic schizophrenia exceed age-associated changes. Moreover, the NSS scores in patients were significantly associated with duration of illness, thought disturbance, positive symptoms, and apathy. These results were confirmed after age/duration of illness and years of education were partialed out and via regression analyses. Our findings conform to the hypothesis that NSS are associated with chronicity of the disorder as indicated by the correlations of NSS with both, duration of illness and apathy. The correlations between NSS and positive symptoms/thought disturbance correspond to the fluctuation of positive symptoms during the course of the disorder. The significantly more pronounced age effects on NSS in patients may either point to ongoing cerebral changes or to a greater susceptibility of patients toward physiological age effects, which may be mediated among other factors by a lower cognitive reserve.

In schizophrenia temporal cortical volume loss differs between patients presenting with persistent auditory verbal hallucinations (pAVH) in contrast to those without hallucinatory symptoms (nAVH). However, it is unknown whether this deficit reflects a neural signature of neurodevelopmental origin or if abnormal temporal cortical volume is reflective of factors which may be relevant at later stages of the disorder. Here, we tested the hypothesis that local gyrification index (LGI) in regions of the temporal cortex differs between patients with pAVH (n=10) and healthy controls (n=14), and that abnormal temporal LGI discriminates between pAVH and nAVH (n=10). Structural magnetic resonance imaging at 3T along with surface-based data analysis methods was used. Contrary to our expectations, patients with pAVH showed lower LGI in Broca´s region compared to both healthy persons and nAVH. Compared to nAVH, those individuals presenting with pAVH also showed lower LGI in right Broca's homologue and right superior middle frontal cortex, together with increased LGI in the precuneus and superior parietal cortex. Regions with abnormal LGI common to both patient samples were found in anterior cingulate and superior frontal areas. Inferior cortical regions exhibiting abnormal LGI in pAVH patients were associated with overall symptom load (BPRS), but not with measures of AVH symptom severity. The pattern of abnormal cortical folding in this sample suggests a neurodevelopmental signature in Broca's region, consistent with current AVH models emphasizing the pivotal role of language circuits and inner speech. Temporal cortical deficits may characterize patients with pAVH during later stages of the disorder., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

Despite a growing body of evidence on motor dysfunction in schizophrenia spectrum disorders, the neuronal correlates of genuine motor abnormalities (GMA) are not fully elucidated at present. Moreover, the clinical relevance of a potential "motor intermediate phenotype" remains controversial. This systematic review aims at characterizing a "motor intermediate phenotype" in schizophrenia spectrum disorders. The second goal of this systematic review is to discuss GMA-associated brain alterations as potential biomarkers of psychosis risk syndrome and manifest motor symptoms against the background of current neuroimaging evidence. The detailed clinical assessment of GMA in the context of multimodal imaging could, in the future promote the early recognition of psychotic disorders and the initiation of disorder-oriented and individualized treatment. Taken as a whole the data provide initial evidence that motor dysfunction in schizophrenic spectrum disorders must be considered dimensionally. The predictive value of neurobiological results with respect to the transition to a life-threatening catatonia or the development of chronic dyskinesia, cannot currently be conclusively assessed.

Besides positive and negative symptoms, motor abnormalities have been increasingly recognized as central symptoms of schizophrenia. Recent investigations of antipsychotic-naive first-episode patients with schizophrenia found significantly higher rates of genuine motor abnormalities (GMA) when compared to healthy individuals. The first part of this article introduces the historical and clinical background of GMA in schizophrenia. In the second part the relevance of scientific research and clinical implication of GMA in schizophrenia are discussed. Finally, this article aims at presenting a conceptual framework and a reference system involving both genuine and drug-induced motor abnormalities. The future clinical implications of GMA research are presented and multimodal and transdiagnostic studies are advocated. Future research on GMA will not only essentially enrich the formation of psychiatric theories but also promote progress in clinical neuroscience.

Impulsivity is associated with distinct mental disorders but is also considered as a personality trait exhibited by healthy individuals. Current studies suggest that early stressful life events might cause higher impulsivity in the adulthood. Morphological features, which reflect early brain development, could provide valuable information regarding the origin of impulsive behavior. However, none of the previous MRI studies employed a methodology specifically designed to investigate the relationship between impulsivity and markers of brain development. In this regard, we aimed to investigate the relationship between cortical folding and the three distinct factors of impulsivity (attention, motor, and non-planning) in young healthy adults. Fifty-four right-handed healthy individuals were recruited for the study and underwent magnetic resonance imaging (MRI) at 3 Tesla. A surface-based analysis was used to calculate a local gyrification index (LGI). Impulsivity was examined by the Barratt Impulsiveness Scale (BIS-11) and related to LGI. Associations between LGI and BIS-11 scores were assessed using within-group correlations (p < 0.05, "cluster-wise probability" [CWP] corr.). BIS subscores were positively correlated with cortical folding in several distinct areas: Total and attention scores were positively correlated with LGI in the left postcentral gyrus, cingulate gyrus, precentral gyrus, pars opercularis of the inferior frontal gyrus, right middle temporal gyrus, superior parietal gyrus, pericalcarine gyrus, and lateral occipital gyrus (each p < 0.05 CWP corr.). BIS motor score was positively correlated with LGI in the left superior temporal, lingual and supramarginal gyrus (each p < 0.05 CWP corr.). BIS non-planning score showed a positive correlation with LGI in the pars opercularis of the right inferior frontal gyrus and the left middle temporal, precentral and superior parietal gyrus (each p < 0.05 CWP corr.). Furthermore, we found gender-specific differences in BIS-11-LGI-correlation in the middle and inferior frontal gyrus. Our findings illustrate the advantages of cortical folding as a marker of early brain development when investigating structural brain correlates of impulsivity in young adulthood. Further, they lend additional support to the notion that alterations in early neurodevelopment comprising fronto-temporo-parietal regions might give rise to higher impulsivity in healthy individuals.

Psychological factors and comorbidities play an important role in inflammatory bowel diseases. Such comorbidity could be associated with a specific neural phenotype. Brain regions associated with emotion regulation and self-referential processing, including areas assigned to the "default mode network" (DMN), could be promising candidates in this regard. We investigated the functional integrity of multiple intrinsic neural networks in remitted patients with Crohn's disease (CD) and sought to establish relationships between neural network connectivity and psychiatric symptoms. Fifteen CD patients in remission and 14 controls were investigated. We employed resting-state functional magnetic resonance imaging (fMRI) at 3 Tesla followed by a spatial Independent Component Analysis for fMRI data. Abnormal connectivity in CD patients was observed in DMN subsystems only (p < 0.05, cluster-corrected). Increased connectivity was found in the anterior cingulate and left superior medial frontal gyrus (aDMN) and the middle cingulate cortex (pDMN). Middle cingulate activity showed a significant association with anxiety scores in patients (p = 0.029). This study provides first evidence of selectively disrupted intrinsic neural network connectivity in CD and suggests abnormalities of self-referential neural networks. An increased sensitivity to self-related affective and somatic states in CD patients could account for these findings and explain a higher risk for anxiety symptoms.

It is unclear whether clock drawing test (CDT) performance relies on a widely distributed cortical network, or whether this test predominantly taps into parietal cortex function. So far, associations between cortical integrity and CDT impairment in Alzheimer's disease (AD) and mild cognitive impairment (MCI) largely stem from cortical volume analyses. Given that volume is a product of thickness and surface area, investigation of the relationship between CDT and these two cortical measures might contribute to better understanding of this cognitive screening tool for AD. 38 patients with AD, 38 individuals with MCI and 31 healthy controls (HC) underwent CDT assessment and MRI at 3 Tesla. The surface-based analysis via Freesurfer enabled calculation of cortical thickness and surface area. CDT was scored according to the method proposed by Shulman and related to the two distinct cortical measurements. Higher CDT scores across the entire sample were associated with cortical thickness in bilateral temporal gyrus, the right supramarginal gyrus, and the bilateral parietal gyrus, respectively (p < 0.001 CWP corr.). Significant associations between CDT and cortical thickness reduction in the parietal lobe remained significant when analyses were restricted to AD individuals. There was no statistically significant association between CDT scores and surface area (p < 0.001 CWP corr.). In conclusion, CDT performance may be driven by cortical thickness alterations in regions previously identified as "AD vulnerable", i.e. regions predominantly including temporal and parietal lobes. Our results suggest that cortical features of distinct evolutionary and genetic origin differently contribute to CDT performance., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Neurological soft signs (NSS) are core features of psychiatric disorders with significant neurodevelopmental origin. However, it is unclear whether NSS correlates are associated with neuropathological processes underlying the disease or if they are confounded by medication. Given that NSS are also present in healthy persons (HP), investigating HP could reveal NSS correlates, which are not biased by disease-specific processes or drug treatment. Therefore, we used a combination of diffusion MRI analysis tools to provide a framework of specific white matter (WM) microstructure variations underlying NSS in HP., Method: NSS of 59 HP were examined on the Heidelberg Scale and related to diffusion associated metrics. Using tract-based spatial statistics (TBSS), we studied WM variations in fractional anisotropy (FA) as well as radial (RD), axial (AD), and mean diffusivity (MD). Using graph analytics (clustering coefficient-CC, local betweenness centrality -BC), we then explored DTI-derived structural network variations in regions identified by previous MRI studies on NSS., Results: NSS scores were negatively associated with RD, AD and MD in corpus callosum, brainstem and cerebellum (P < 0.05, corr.). NSS scores were negatively associated with CC and BC of the pallidum, the superior parietal gyrus, the precentral sulcus, the insula, and the cingulate gyrus (P < 0.05, uncorr.)., Conclusion: The present study supports the notion that WM microstructure variations in subcortical and cortical sensorimotor regions contribute to NSS expression in young HP. Hum Brain Mapp 38:3552-3565, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

The clinical picture of catatonia includes impressive motor phenomena, such as rigidity, dyskinesia, festination, negativism, posturing, catalepsy, stereotypies and mannerisms, along with affective (e. g. aggression, anxiety, anhedonism or emotional lability) and behavioral symptoms (e.g. mutism, autism, excitement, echolalia or echopraxia). In English speaking countries seven catatonia rating scales have been introduced, which are widely used in clinical and scientific practice. In contrast, only one validated catatonia rating scale is available in Germany so far. In this paper, we introduce the German version of the Northoff catatonia rating scale (NCRS-dv). The original English version of the NCRS consists of 40 items describing motor (13 items), affective (12 items) and behavioral (15 items) catatonic symptoms. The NCRS shows high internal reliability (Crombachs alpha = 0.87), high interrater (r = 0.80-0.96) and high intrarater (r = 0.80-0.95) reliability. Factor analysis of the NCRS revealed four domains: affective, hyperactive or excited, hypoactive or retarded and behavior with individual eigenvalues of 8.98, 3.61, 2.98 and 2.82, respectively, which explained 21.5 %, 9.3 %, 7.6 % and 7.2 % of variance, respectively. In conclusion, the NCRS-dv represents a second validated instrument which can be used by German clinicians and scientists for the assessment of catatonic symptoms.

Autobiographical memory (AM) is part of declarative memory and includes both semantic and episodic aspects. AM deficits are among the major complaints of patients with Alzheimer's disease (AD) even in early or preclinical stages. Previous MRI studies in AD patients have showed that deficits in semantic and episodic AM are associated with hippocampal alterations. However, the question which specific hippocampal subfields and adjacent extrahippocampal structures contribute to deficits of AM in individuals with mild cognitive impairment (MCI) and AD patients has not been investigated so far. Hundred and seven participants (38 AD patients, 38 MCI individuals and 31 healthy controls [HC]) underwent MRI at 3 Tesla. AM was assessed with a semi-structured interview (E-AGI). FreeSurfer 5.3 was used for hippocampal parcellation. Semantic and episodic AM scores were related to the volume of 5 hippocampal subfields and cortical thickness in the parahippocampal and entorhinal cortex. Both semantic and episodic AM deficits were associated with bilateral hippocampal alterations. These associations referred mainly to CA1, CA2-3, presubiculum, and subiculum atrophy. Episodic, but not semantic AM loss was associated with cortical thickness reduction of the bilateral parahippocampal and enthorinal cortex. In MCI individuals, episodic, but not semantic AM deficits were associated with alterations of the CA1, presubiculum and subiculum. Our findings support the crucial role of CA1, presubiculum, and subiculum in episodic memory. The present results implicate that in MCI individuals, semantic and episodic AM deficits are subserved by distinct neuronal systems., (© 2017 Wiley Periodicals, Inc.)

Background: Electroconvulsive therapy (ECT) is one of the most effective treatments in severe and treatment-resistant major depressive disorder (MDD). ECT has been also shown to be effective in schizophrenia (SZ), particularly when rapid symptom reduction is needed or in cases of resistance to drug-treatment. However, its precise mechanisms of action remain largely unknown., Objective/hypothesis: This study examined whether ECT exerts disorder-specific or unspecific modulation of brain structure and function in SZ and MDD., Methods: We investigated neuromodulatory effects of right-sided unilateral ECT in pharmacoresistant patients with SZ or MDD. Magnetic resonance imaging was conducted before and after ECT to investigate treatment-related effects on brain structure and function. Imaging data were analyzed by means of Voxel Based Morphometry and Resting State Functional Connectivity (RSFC) methods., Results: Right unilateral ECT induced transdiagnostic regional increases of limbic gray matter and modulations of neural coupling at rest. Structural effects were accompanied by a decrease in RSFC within temporoparietal, prefrontal and cortical midline structures, and an increase in hypothalamic RSFC. The extent of structural and functional change was partially inversely associated with the baseline measures., Conclusion: The present findings provide first evidence for transdiagnostic changes of brain structure together with modulation of brain function after ECT. The data indicate diagnosis-unspecific mechanisms of action with respect to regional gray matter volume and resting-state functional connectivity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Electroconvulsive therapy (ECT) is remarkably effective in severe major depressive disorder (MDD). Growing evidence has accumulated for brain structural and functional changes in response to ECT, primarily within cortico-limbic regions that have been considered in current neurobiological models of MDD. Despite increasing evidence for important cerebellar contributions to affective, cognitive and attentional processes, investigations on cerebellar effects of ECT in depression are yet lacking. In this study, using cerebellum-optimized voxel-based analysis methods, we investigated cerebellar volume in 12 MDD patients who received right-sided unilateral ECT. 16 healthy controls (HC) were included. Structural MRI data was acquired before and after ECT and controls were scanned once. Baseline structural differences in MDD compared to HC were located within the "cognitive cerebellum" and remained unchanged with intervention. ECT led to gray matter volume increase of left cerebellar area VIIa crus I, a region ascribed to the "affective/limbic cerebellum". The effects of ECT on cerebellar structure correlated with overall symptom relief. These findings provide preliminary evidence that structural change of the cerebellum in response to ECT may be related to the treatment's antidepressant effects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Abnormal cortical volume is well-documented in patients with major depressive disorder (MDD), but cerebellar findings have been heterogeneous. It is unclear whether abnormal cerebellar structure relates to disease state or medication. In this study, using structural MRI, we investigated cerebellar volume in clinically acute (with and without psychotropic treatment) and remitted MDD patients. High-resolution structural MRI data at 3T were obtained from acute medicated (n=29), acute unmedicated (n=14) and remitted patients (n=16). Data from 29 healthy controls were used for comparison purposes. Cerebellar volume was investigated using cerebellum-optimized voxel-based analysis methods. Patients with an acute MDD episode showed increased volume of left cerebellar area IX, and this was true for both medicated and unmedicated individuals (p<0.05 cluster-corrected). Remitted patients exhibited bilaterally increased area IX volume. In remitted, but not in acutely ill patients, area IX volume was significantly associated with measures of depression severity, as assessed by the Hamilton Depression Rating Scale (HAMD). In addition, area IX volume in remitted patients was significantly related to the duration of antidepressant treatment. In acutely ill patients, no significant relationships were established using clinical variables, such as HAMD, illness or treatment duration and number of depressive episodes. The data suggest that cerebellar area IX, a non-motor region that belongs to a large-scale brain functional network with known relevance to core depressive symptom expression, exhibits abnormal volume in patients independent of clinical severity or medication. Thus, the data imply a possible trait marker of the disorder. However, given bilaterality and an association with clinical scores at least in remitted patients, the current findings raise the possibility that cerebellar volume may be reflective of successful treatment as well., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objective: Alterations of brain morphology in Crohn's disease have been reported, but data is scarce and heterogenous and the possible impact of disease predisposition on brain development is unknown. Assuming a systemic course of the disease, brain involvement seems more probable in presence of extraintestinal manifestations, but this question has not yet been addressed. The present study examined the relationship between Crohn's disease and brain structure and focused on the connection with extraintestinal manifestations and markers of brain development., Methods: In a pilot study, brains of 15 patients with Crohn's disease (of which 9 had a history of extraintestinal manifestations, i.e. arthritis, erythema nodosum and primary sclerosing cholangitis) were compared to matched healthy controls using high resolution magnetic resonance imaging. Patients and controls were tested for depression, fatigue and global cognitive function. Cortical thickness, surface area and folding were determined via cortical surface modeling., Results: The overall group comparison (i.e. all patients vs. controls) yielded no significant results. In the patient subgroup with extraintestinal manifestations, changes in cortical area and folding, but not thickness, were identified: Patients showed elevated cortical surface area in the left middle frontal lobe (p<0.05) and hypergyrification in the left lingual gyrus (p<0.001) compared to healthy controls. Hypogyrification of the right insular cortex (p<0.05) and hypergyrification of the right anterior cingulate cortex (p<0.001) were detected in the subgroup comparison of patients with against without extraintestinal manifestations. P-values are corrected for multiple comparisons., Conclusions: Our findings lend further support to the hypothesis that Crohn's disease is associated with aberrant brain structure and preliminary support for the hypothesis that these changes are associated with a systemic course of the disease as indicated by extraintestinal manifestations. Changes in cortical surface area and folding suggest a possible involvement of Crohn's disease or its predisposition during brain development., Competing Interests: The authors have declared that no competing interests exist.

Electroconvulsive therapy (ECT) is one of the most effective treatments in severe and treatment-resistant major depressive disorder (MDD). In schizophrenia (SZ), ECT is frequently considered in drug-resistant cases, as an augmentation of antipsychotic treatment or in cases when rapid symptom relief is indicated. Accumulating neuroimaging evidence suggests modulation of medial temporal lobe and prefrontal cortical regions in MDD by ECT. In SZ, ECT-effects on brain structure have not been systematically investigated so far. In this study, we investigated brain volume in 21 ECT-naïve patients (12 with MDD, 9 with SZ) who received right-sided unilateral ECT. Twenty-one healthy controls were included. Structural magnetic resonance imaging data were acquired before and after ECT. Healthy participants were scanned once. Source-based morphometry was used to investigate modulation of structural networks pre/post ECT. ECT had an impact on distinct structural networks in MDD and SZ. In both MDD and SZ SBM revealed a medial temporal lobe (MTL) network (including hippocampus and parahippocampal cortex) which showed a significant increase after ECT. The increase in MTL network strength was not associated with clinical improvement in either MDD or SZ. In SZ a lateral prefrontal/cingulate cortical network showed a volume increase after ECT, and this effect was accompanied by clinical improvement. These findings provide preliminary evidence for structural network change in response to ECT in MDD and SZ. The data suggest both diagnosis-specific and transdiagnostic ECT-effects on brain volume. In contrast to SZ, in MDD structural network modulation by ECT was not associated with clinical improvement., (Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.)

Background: Schizophrenia spectrum disorders result in enormous individual suffering and financial burden on patients and on society. In Germany, there are about 1,000,000 individuals suffering from schizophrenia (SZ) or schizoaffective disorder (SAD), a combination of psychotic and affective symptoms. Given the heterogeneous nature of these syndromes, one may assume that there is a difference in treatment costs among patients with paranoid SZ and SAD. However, the current the national system of cost accounting in psychiatry and psychosomatics in Germany assesses all schizophrenia spectrum disorders within one category., Methods: The study comprised a retrospective audit of data from 118 patients diagnosed with paranoid SZ (F20.0) and 71 patients with SAD (F25). We used the mean total costs as well as partial cost, i.e., mean costs for medication products, mean personal costs and mean infrastructure costs from each patient for the statistical analysis. We tested for differences in the four variables between SZ and SAD patients using ANCOVA and confirmed the results with bootstrapping., Results: SAD patients had a longer duration of stay than patients with SZ (p = .02). Mean total costs were significantly higher for SAD patients (p = .023). Further, we found a significant difference in mean personnel costs (p = .02) between patients with SZ and SAD. However, we found no significant differences in mean pharmaceutical costs (p = .12) but a marginal difference of mean infrastructure costs (p = .05) between SZ and SAD. We found neither a common decrease of costs over time nor a differential decrease in SZ and SAD., Conclusion: We found evidence for a difference of case related costs of inpatient treatments for paranoid SZ and SAD. The differences in mean total costs seem to be primarily related to the mean personnel costs in patients with paranoid SZ and SAD rather than mean pharmaceutical costs, possibly due to higher personnel effort and infrastructure.

Neurological soft signs (NSS) are frequently found in psychiatric disorders of significant neurodevelopmental origin. Previous MRI studies in schizophrenia have shown that NSS are associated with abnormal cortical, thalamic and cerebellar structure and function. So far, however, no neuroimaging studies investigated brain correlates of NSS in individuals with Asperger-Syndrome (AS) and the question whether the two disorders exhibit common or disease-specific cortical correlates of NSS remains unresolved. High-resolution MRI data at 3 T were obtained from 48 demographically matched individuals (16 schizophrenia patients, 16 subjects with AS and 16 healthy individuals). The surface-based analysis via Freesurfer enabled calculation of cortical thickness, area and folding (local gyrification index, LGI). NSS were examined on the Heidelberg Scale and related to cortical measures. In schizophrenia, higher NSS were associated with reduced cortical thickness and LGI in fronto-temporo-parietal brain areas. In AS, higher NSS were associated with increased frontotemporal cortical thickness. This study lends further support to the hypothesis that disorder-specific mechanisms contribute to NSS expression in schizophrenia and AS. Pointing towards dissociable neural patterns may help deconstruct the complex processes underlying NSS in these neurodevelopmental disorders.

Minor motor and sensory deficits or neurological soft signs (NSS) are frequently found in patients with schizophrenia at any stage of their illness. Although previous studies have reported that NSS are associated with altered structure and function within fronto-parietal areas, it remains unclear whether the neuroanatomical basis of NSS may be confounded by underlying pathological processes, and by antipsychotic treatment. Morphological brain correlates of NSS in healthy subjects have seldom been investigated. This study evaluated the relationship between NSS levels and abnormalities of subcortical and cortical structures in healthy individuals. High-resolution MRI data at 3 Tesla were obtained from 68 healthy individuals. Automated segmentation of caudate nucleus, putamen, globus pallidus, thalamus, and brainstem was performed using both FSL-FIRST and Freesurfer. The surface-based analysis via Freesurfer enabled calculation of cortical thickness, area and folding (local gyrification index). NSS were examined on the Heidelberg Scale and related to both subcortical and cortical measurements. Using two fully automated brain segmentations methods, we found no significant association between NSS levels and morphological changes in subcortical structures. Higher NSS scores were associated with morphological changes of cortical thickness, area and folding in multiple areas comprising superior frontal, middle temporal, insular and postcentral regions. Our findings demonstrate the benefit of surface-based approaches when investigating brain correlates of NSS. The data lend further support to the hypothesis that NSS in healthy individuals involve multiple cortical rather than subcortical brain regions.

Major depressive disorder (MDD) and borderline personality disorder (BPD) show substantial overlap in both affective symptom expression and in regional brain volume reduction. To address the specificity of structural brain change for the respective diagnostic category, we investigated structural networks in MDD and BPD to identify shared and distinct patterns of abnormal brain volume associated with these phenotypically related disorders. Using magnetic resonance imaging at 3 T, we studied 22 females with MDD, 17 females with BPD and without comorbid posttraumatic stress disorder, and 22 age-matched female healthy controls. We used “source-based morphometry” (SBM) to investigate naturally grouping patterns of gray matter volume variation (i.e. “structural networks”) and the magnitude of their expression between groups. SBM identified three distinct structural networks which showed a significant group effect (p b 0.05, FDR-corrected). A bilateral frontostriatal network showed reduced volume in MDD compared to both controls and BPD patients. A medial temporal/medial frontal network was found to be significantly reduced in BPD compared to both controls and MDD patients. Decreased cingulate and lateral prefrontal volume was found in both MDD and BPD when compared to healthy individuals. In MDD significant relationships were found between depressive symptoms and a cingulate/lateral prefrontal structural pattern. In contrast, overall BPD symptoms and impulsivity scores were significantly associated with medial temporal/medial frontal network volume. The data suggest both distinct and common patterns of abnormal brain volume in MDD and BPD. Alterations of distinct structural networks differentially modulate clinical symptom expression in these disorders.

Neurological soft signs (NSS) are frequently found in psychiatric disorders of significant neurodevelopmental origin, e.g., in patients with schizophrenia and autism. Yet NSS are also present in healthy individuals suggesting a neurodevelopmental signature of motor function, probably as a continuum between health and disease. So far, little is known about the neural mechanisms underlying these motor phenomena in healthy persons, and it is even less known whether the cerebellum contributes to NSS expression. Thirty-seven healthy young adults (mean age = 23 years) were studied using high-resolution structural magnetic resonance imaging (MRI) and "resting-state" functional MRI at three Tesla. NSS levels were measured using the "Heidelberg Scale." Cerebellar gray matter volume was investigated using cerebellum-optimized voxel-based analysis methods. Cerebellar function was assessed using regional homogeneity (ReHo), a measure of local network strength. The relationship between cerebellar structure and function and NSS was analyzed using regression models. There was no significant relationship between cerebellar volume and NSS (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). Positive associations with cerebellar lobule VI activity were found for the "motor coordination" and "hard signs" NSS domains. A negative relationship was found between lobule VI activity and "complex motor task" domain (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). The data indicate that in healthy young adults, distinct NSS domains are related to cerebellar activity, specifically with activity of cerebellar subregions with known cortical somatomotor projections. In contrast, cerebellar volume is not predictive of NSS in healthy persons.