Self-aggression, reactive aggression, and spontaneous aggression: Mediating effects of self-esteem and psychopathology.

This study examined whether the associations between self-aggression and different forms of externalized aggression (reactive and spontaneous aggression) are influenced by self-esteem and current psychopathological symptoms. For this purpose, we asked 681 participants from the general population (GP) and 282 general psychiatric patients (PPs) to answer the German versions of the Short Questionnaire for Assessing Factors of Aggression (K-FAF), the Multidimensional Self-Esteem Scale (MSWS), and the Brief Symptom Inventory 25 Forensic (BSI-25-F). Statistically, we performed descriptive and mediation analyses. Our findings indicated that in both samples the association between self-aggression and reactive aggression was mediated by self-esteem but not by current psychological problems. The association between self-aggression and spontaneous aggression was mediated by self-esteem in the GP sample and by psychopathological symptoms in the PP sample. We conclude that when examining the association between self-aggression and externalized aggression it is important to consider the various subtypes of externalized aggression and differences between populations.

The Therapeutic Relationship in Forensic and General Psychiatric Settings.

INTRODUCTION: Therapeutic relationship in forensic psychiatry is believed to be affected by the coercive setting and the role conflict of the therapists as both treaters and court-appointed experts. The aim of the study was to examine and compare the therapeutic relationship in forensic and general psychiatric settings. MATERIAL AND METHODS: 52 forensic patients and 66 general psychiatric patients filled in the Psychopathy Personality Inventory - Revised (PPI-R), the Inventory of Interpersonal Problems - German Version (IIP-D), the Questionnaire on Motivation for Psychotherapy (Fragebogen zur Erfassung der Psychotherapiemotivation (FPTM)) as well as the Working Alliance Inventory - Short Revised (WAI-SR). We applied descriptive analyses, calculated univariate t-tests as well as multivariate T-tests and performed general linear models. RESULTS: The quality of the therapeutic alliance does not differ significantly between forensic and general psychiatric patients. Moreover, patients of forensic psychiatry consider therapeutic techniques applied by their therapists as more valuable for achieving their therapeutic aims than patients of the general psychiatry. DISCUSSION: The therapeutic relationship in forensic psychiatry is as viable as in general psychiatry. This can be regarded as a result of the long-term therapy in the context of forensic psychiatry which allows more time to be spent on relationship building than in a general psychiatry setting where therapy is limited to a few weeks.

Cerebellar Contributions to Persistent Auditory Verbal Hallucinations in Patients with Schizophrenia.

There is growing evidence that the cerebellum plays a crucial role in the pathophysiology of schizophrenia symptoms. Despite increasing evidence for cerebellar involvement in affective, attentive, and cognitive functions including language processing and perception, investigations of cerebellar contributions to auditory verbal hallucinations (AVH) in schizophrenia are lacking. Using structural magnetic resonance imaging at 3T, we investigated the data of 20 patients with schizophrenia and 14 matched healthy controls. Ten patients were classified as having chronic and treatment resistant AVH (pAVH), whereas the remaining ten patients either never had AVH in the past or were in full remission with regard to AVH (nAVH). Employing cerebellum-optimized segmentation techniques, i.e., the Spatially Unbiased Infratentorial Template (SUIT) toolbox, we investigated cerebellar gray matter volume (GMV) differences among the pAVH, nAVH, and a healthy control group, the magnitude of their expression between these groups and the relationship between GMV and schizophrenia symptom load. Lower GMV in pAVH patients compared to controls was found in lobules VIIb and VIIIa. Additionally, lower GMV in pAVH compared to nAVH patients was found in lobule VIIIa. A negative relationship between VIIIa GMV and overall positive symptoms was detected. Correlations with AVH-specific psychometric scores were not significant. This study shows that there are structural changes in the cognitive regions of the cerebellum that are linked to a clinical phenotype presenting with persistent positive symptoms such as AVH. The results suggest that the cerebellum and its associated neural circuits do play a role in the emergence of positive symptoms in schizophrenia, but probably not exclusively in AVH symptom expression.

[Are Depressed People Aggressive People? Differences Between General Population and Depressive Patients]. / Sind depressive Menschen aggressive Menschen? Unterschiede zwischen Allgemeinbevölkerung und depressiven Patienten.

IntroductionThe study aimed to investigate the relationship between depression and aggression. Material and Methods681 depressive and non-depressive subjects of the general population as well as 132 depressive patients completed the Beck Depression Inventory Revised (BDI-II) as well as the Short Questionnaire for Gathering Factors of Aggressiveness (K-FAF). ResultsDepressive patients and depressive subjects of the general population did not merely report the highest levels of self-aggressiveness but also reached the highest scores on the scales of reactive and proactive aggression, indicating a high level of externalizing aggressiveness. DiscussionThe results support the neurobiological approach of the etiology of depressive disorders. Conclusions For future research of depressive disorders and aggression the investigation of the mediating roles of a low serotonin-level is recommended.

Baseline brain perfusion and brain structure in patients with major depression: a multimodal magnetic resonance imaging study.

BACKGROUND: Abnormal regional cerebral blood flow (rCBF) and grey matter volume have been frequently reported in patients with major depressive disorder (MDD). However, it is unclear to what extent structural and functional change co-occurs in patients with MDD and whether markers of neural activity, such as rCBF, can be predicted by structural change. METHODS: Using MRI, we investigated resting-state rCBF and brain structure in patients with MDD and healthy controls between July 2008 and January 2013. We acquired perfusion images obtained with continuous arterial spin labelling, used voxel-based morphometry to assess grey matter volume and integrated biological parametric mapping analyses to investigate the impact of brain atrophy on rCBF. RESULTS: We included 43 patients and 29 controls in our study. Frontotemporal grey matter volume was reduced in patients compared with controls. In patients, rCBF was reduced in the anterior cingulate and bilateral parahippocampal areas and increased in frontoparietal and striatal regions. These abnormalities were confirmed by analyses with brain volume as a covariate. In patients with MDD there were significant negative correlations between the extent of depressive symptoms and bilateral parahippocampal rCBF. We found a positive correlation between depressive symptoms and rCBF for right middle frontal cortical blood flow. LIMITATIONS: Medication use in patients has to be considered as a limitation of our study. CONCLUSION: Our data suggest that while changes of cerebral blood flow and brain volume co-occur in patients with MDD, structural change is not sufficient to explain altered neural activity in patients at rest. Abnormal brain structure and function in patients with MDD appear to reflect distinct levels of neuropathology.

FACTORIAL VALIDITY OF THE SHORT FORM OF THE CHILDHOOD TRAUMA QUESTIONNAIRE (CTQ-SF) IN GERMAN PSYCHIATRIC PATIENTS, INMATES, AND UNIVERSITY STUDENTS.

For the purpose of retrospective assessment and characterization of childhood trauma in adults, the factorial validity of the short form of the Childhood Trauma Questionnaire (CTQ-SF) in Germany was evaluated by conducting confirmatory factor analyses for three samples including 1,524 adult psychiatric patients, 224 inmates, and 295 university students. In addition, sex-specific confirmatory factor analyses were performed within each sample. Because several authors have suggested a different factor structure than that originally proposed in the manual, two competing models focusing on the Physical neglect subscale were examined. In psychiatric patients and inmates, the fit indices were reasonable to good. Among the students, factor loadings were markedly lower, and fit indices were poor. Sex-specific analyses did not indicate sex differences. Comparing the original and the alternative models revealed better fit indices of the original factor structure. The present findings indicate that the German version of the CTQ-SF has factorial validity in psychiatric patients and inmates, but not in students.

Visual system integrity and cognition in early Huntington's disease.

Posterior cortical volume changes and abnormal visuomotor performance are present in patients with Huntington's disease (HD). However, it is unclear whether posterior cortical volume loss contributes to abnormal neural activity, and whether activity changes predict cognitive dysfunction. Using magnetic resonance imaging (MRI), we investigated brain structure and visual network activity at rest in patients with early HD (n = 20) and healthy controls (n = 20). The symbol digit modalities test (SDMT) and subtests of the Visual Object and Space Perception Battery were completed offline. For functional MRI data, a group independent component analysis was used. Voxel-based morphometry was employed to assess regional brain atrophy, and 'biological parametric mapping' analyses were included to investigate the impact of atrophy on neural activity. Patients showed significantly worse visuomotor and visual object performance than controls. Structural analyses confirmed occipitotemporal atrophy. In patients and controls, two spatiotemporally distinct visual systems were identified. Patients showed decreased activity in the left fusiform cortex, and increased left cerebellar activity. These findings remained stable after correction for brain atrophy. Lower fusiform cortex activity was associated with lower SDMT performance and with higher disease burden scores. These associations were absent when cerebellar function was related to task performance and disease burden. The results of this study suggest that regionally specific functional abnormalities of the visual system can account for the worse visuomotor cognition in HD patients. However, occipital volume changes cannot sufficiently explain abnormal neural function in these patients.

Longitudinal task-negative network analyses in preclinical Huntington's disease.

Functional neuroimaging studies have reported task-related brain activation changes in preclinical individuals carrying the Huntington's disease (HD) gene mutation (preHD). Little is known about "task-negative" activity, i.e., patterns of task-related deactivation in preHD, and about the stability of any deactivation changes over the course of the disease. Here, we explored task-related deactivation and functional connectivity of "task-negative" networks (TNNs) in preHD followed over a time period of 2 years. Thirteen far-from-onset preHD (mean time to estimated motor onset = 19.5 years) and thirteen healthy controls were investigated. We used functional magnetic resonance imaging (fMRI), a verbal working memory task, and uni- and multivariate analysis techniques for fMRI data. Behavior was similar in preHD and controls at baseline and did not change 2 years later. At both time points, deactivation was similar in preHD and controls. Within two spatio-temporally distinct TNNs, preHD had lower functional connectivity in the posterior cingulate cortex and higher functional connectivity in the left anterior prefrontal cortex compared to controls (p < 0.05, cluster-corrected). These findings remained stable at follow-up. Anterior prefrontal connectivity correlated with disease burden scores both at baseline and at follow-up. Over time, preHD exhibited higher connectivity in a dorsal cingulate region. Functional connectivity differences within this region were inversely associated with changes of motor function. These data provide first evidence for TNN connectivity changes in preHD followed over a period of 2 years. The relationship between dorsal cingulate connectivity and motor function suggests that "task-negative" activity may capture time-sensitive neural and functional processes in preHD.

Brain structure in preclinical Huntington's disease: a multi-method approach.

BACKGROUND: Structural magnetic resonance imaging (MRI) of the brain could be a powerful tool for discovering early biomarkers in clinically presymptomatic carriers of the Huntington's disease gene mutation (preHD). So far, structural changes have been found mainly in preHD approaching the estimated motor onset of the disease (i.e., less than 15 years from onset), whereas structural findings in preHD far from the estimated motor onset have been inconclusive. OBJECTIVES: The aims of this study were to investigate the sensitivity of different methodological approaches to structural data in far-from-onset preHD (mean estimated time to motor onset = 21.4 years) and to explore the relationship between brain structure, clinical variables and cognition. METHODS: High-resolution MRI data at 3 T were obtained from 20 preHD individuals and 20 healthy participants and subsequently analyzed using voxel-based morphometry (VBM), cortical surface modeling and subcortical segmentation analysis techniques. RESULTS: VBM analyses did not reveal significant between-group differences, whereas cortical surface modeling and subcortical segmentation analyses showed significant regional cortical thinning and striatal changes in preHD compared to controls. Significant correlations were found between striatal structure, estimated time to motor onset and executive performance, whereas cortical changes were not significantly correlated with these parameters. CONCLUSION: These data suggest that a combined methodological approach to structural MRI data could increase the sensitivity for detecting subtle neurobiological changes in early preHD. As consistently shown across different methods, the association between striatal structure and clinical measures supports the notion that changes in striatal volume could represent a more robust marker of disease progression than cortical changes.

Brain activation and functional connectivity in premanifest Huntington's disease during states of intrinsic and phasic alertness.

Previous functional neuroimaging studies have shown brain activation abnormalities in clinically presymptomatic carriers of the Huntington's disease (preHD) gene mutation when performing complex cognitive tasks. However, little is known about the neural correlates of attentional processes in preHD. In this study, we used functional magnetic resonance imaging to investigate basic aspects of attentional processing in preHD individuals (n = 18) compared to healthy participants (n = 18) during an alertness task. Uni- and multivariate statistical techniques were used to assess task-related regional brain activation and functional network connectivity. Compared to healthy controls, preHD individuals near to the estimated onset of clinical signs showed lower activation of right frontostriatal regions during phasic alertness (P < 0.001, uncorrected). Decreased striatal activation in this preHD subgroup was also evident when compared with those preHD individuals far from the estimated onset of HD signs. Lower putaminal activity was associated with longer reaction times and with proximity to onset. In addition, preHD participants near to onset had lower functional connectivity of motor regions when compared with controls and preHD individuals far from onset. Our data suggest that while alertness-related performance remains normal, the underlying frontostriatal activity and motor cortex connectivity decline only when approaching the onset of unequivocal signs of HD. However, these attentional network changes might not be the sole explanation for the differences in cognitive task performance previously observed in preHD.

Orbitofrontal cortex and impulsivity in borderline personality disorder: an MRI study of baseline brain perfusion.

Behavioral and neuroimaging studies in patients with borderline personality disorder (BPD) have associated orbitofrontal cortex (OFC) dysfunction with distinct symptom clusters such as impulsivity. It is unclear, however, whether abnormal patterns of OFC activity are also present during resting-state conditions and whether OFC dysfunction is specifically associated with impulsivity in BPD. This study tested the hypothesis that BPD patients would exhibit changes of OFC baseline perfusion and explored the relationship between regional cerebral blood flow and distinct BPD symptom clusters, such as impulsivity, dissociation tension and depressive symptoms. Using continuous arterial spin labeling magnetic resonance imaging at 3 Tesla, we investigated 16 women with BPD according to DSM-IV criteria and 16 healthy female control participants during resting-state conditions. Between-group comparisons were conducted using an analysis of variance (p < 0.05 cluster corrected). Compared to controls, BPD patients exhibited decreased blood flow in the medial OFC, whereas increased blood flow was found in the left and right lateral OFC. Correlation analyses revealed a positive relationship between medial and lateral orbitofrontal blood flow and impulsivity scores, whereas measures of dissociation tension and depression did not exhibit a significant correlation with OFC perfusion. These data suggest that dysfunction of medial and lateral regions of the OFC could specifically mediate symptoms of impulsivity in BPD.

Cerebrospinal fluid biomarker candidates of schizophrenia: where do we stand?

Here, we review the cerebrospinal fluid (CSF) candidate markers with regard to their clinical relevance as potential surrogates for disease activity, prognosis assessment, and predictors of treatment response. We searched different online databases such as MEDLINE and EMBASE for studies on schizophrenia and CSF. Initial studies on cerebrospinal fluid in patients with schizophrenia revealed increased brain-blood barrier permeability with elevated total protein content, increased CSF-to-serum ratio for albumin, and intrathecal production of immunoglobulins in subgroups of patients. Analyses of metabolites in CSF suggest alterations within glutamatergic neurotransmission as well as monoamine and cannabinoid metabolism. Decreased levels of brain-derived neurotrophic factor and nerve growth factor in CSF of first-episode patients with schizophrenia reported in recent studies point to a dysregulation of neuroprotective and neurodevelopmental processes. Still, these findings must be considered as non-specific. A more profound characterization of the particular psychopathological profiles, the investigation of patients in the prodromal phase or within the first episode of schizophrenia promoting longitudinal investigations, implementation of different approaches of proteomics, and rigorous adherence to standard procedures based on international CSF guidelines are necessary to improve the quality of CSF studies in schizophrenia, paving the way for identification of syndrome-specific biomarker candidates.

Gender Differences in the Psychopharmacological Treatment of Forensic In-Patients With Schizophrenia.

Background: In forensic psychiatry, psychopharmacological treatment plays a crucial role for patients with schizophrenia in improving their medical as well as legal prognosis. However, an increase in the number of females entering forensic treatment has yet to yield empirical research on the outcome of psychopharmacological treatment of female patients with schizophrenia in terms of efficacy and tolerability. Aims: The aim of the present study is to elucidate pharmacological treatment strategies of women with schizophrenia in forensic psychiatry in comparison with men. Methods: This study compares psychopharmacological treatment strategies, psychopathological features, as well as neurological and metabolic side effects of treatment between 29 female and 29 male in-patients with schizophrenia in three forensic facilities in Bavaria, Germany. Results: Results show significant differences between genders. Poorer psychopathological and neurological features were found in the female sample, while men registered worse metabolic parameters. In terms of psychopharmacological treatment strategies, female in-patients were more often prescribed second-generation depot antipsychotics. Surprisingly, the potency of the dosages did not differ between genders. The results suggest that female forensic patients with schizophrenia have more severe and refractory diseases than their male counterparts. Conclusion: Recommendations for gender-specific treatment strategies are derived.

Aberrant connectivity of resting-state networks in borderline personality disorder.

BACKGROUND: Several functional neuroimaging studies have reported regionally abnormal activation of the frontal cortex in individuals with borderline personality disorder (BPD) during cognitive and affective task performance. However, little is known about neural function in individuals with BPD during the resting state. Using functional magnetic resonance imaging (fMRI), this study investigated the functional connectivity of prefrontal and limbic networks in patients with BPD. METHODS: Between January 2009 and March 2010, we investigated patients with BPD according to DSM-IV criteria and healthy controls by means of resting-state fMRI. The data were analyzed using a spatial group independent component analysis, and random effects t tests were used to compare spatial components between groups (p < 0.005, uncorrected). RESULTS: There were 17 women with BPD and 17 female healthy controls enrolled in this study. Within a network comprising cortical midline regions ("default mode network"), patients with BPD showed an increase in functional connectivity in the left frontopolar cortex (FPC) and the left insula, whereas decreased connectivity was found in the left cuneus. Within a network comprising predominantly right lateral prefrontal and bilateral parietal regions, patients with BPD showed decreased connectivity of the left inferior parietal lobule and the right middle temporal cortex compared with healthy controls. Two networks comprising lateral prefrontal and cingulate regions did not exhibit significant between-group differences. We found correlations between functional connectivity of the FPC and measures of impulsivity as well as between connectivity of the insula/cuneus and dissociation tension. LIMITATIONS: Co-occurrent axis I disorders and medication use in this sample of patients with BPD have to be considered as potential limitations. CONCLUSION: These data suggest that abnormal functional connectivity of temporally coherent resting-state networks may underlie certain symptom clusters in patients with BPD.

Dysconnectivity of multiple resting-state networks in patients with schizophrenia who have persistent auditory verbal hallucinations.

BACKGROUND: Functional neuroimaging studies on schizophrenia have suggested abnormal task-related functional connectivity in patients with schizophrenia who have auditory verbal hallucinations (AVHs). However, little is known about intrinsic functional connectivity in these patients. METHODS: Between January 2009 and February 2010, we studied patients with schizophrenia who had persistent and treatment-refractory AVHs in comparison with healthy controls. Using functional magnetic resonance imaging, we studied the functional connectivity of multiple resting state networks (RSNs) and their relation to symptom severity. We analyzed the data using a spatial group independent component analysis, and we used random-effects t tests to compare spatial components between groups. RESULTS: There were 10 patients and 14 controls enrolled in this study. In total, 16 RSNs were identified, from which we selected 4 networks of interest for further analyses. Within a speech-related network, patients showed increased connectivity in bilateral temporal regions and decreased connectivity in the cingulate cortex. Within 2 additional RSNs associated with attention and executive control, respectively, patients exhibited abnormal connectivity in the precuneus and right lateral prefrontal areas. We found correlations between measures of AVH severity and functional connectivity of the left anterior cingulate, left superior temporal gyrus and right lateral prefrontal cortex. LIMITATIONS: The relatively small sample size, the patients' use of antipsychotic medication and the lack of a clinical control group have to be considered as potential limitations. CONCLUSION: Our findings indicate that disrupted intrinsic connectivity of a speech-related network could underlie persistent AVHs in patients with schizophrenia. In addition, the occurrence of hallucinatory symptoms seems to modulate RSNs associated with attention and executive control.

Increasing contextual demand modulates anterior and lateral prefrontal brain regions associated with proactive interference.

Using a parametric version of a modified item-recognition paradigm with three different load levels and by means of event-related functional magnetic resonance imaging, this study tested the hypothesis that cerebral activation associated with intratrial proactive interference (PI) during working memory retrieval is influenced by increased context processing. We found activation of left BA 45 during interference trials across all levels of cognitive processing, and left lateralized activation of the dorsolateral prefrontal cortex (DLPFC, BA 9/46) and the frontopolar cortex (FPC, BA 10) with increasing contextual load. Compared with high susceptibility to PI, low susceptibility was associated with activation of the left DLPFC. These results suggest that an intratrial PI effect can be modulated by increasing context processing of a transiently relevant stimulus set. Moreover, PI resolution associated with increasing context load involves multiple prefrontal regions including the ventro- and dorsolateral prefrontal cortex as well as frontopolar brain areas. Furthermore, low susceptibility to PI might be influenced by increased executive control exerted by the DLPFC.

Cortical dysfunction in patients with Huntington's disease during working memory performance.

Previous functional neuroimaging studies on executive function suggested multiple functionally aberrant cortical regions in patients with Huntington's disease (HD). However, little is known about the neural mechanisms of working memory (WM) function in this patient population. The objective of this study was to investigate the functional neuroanatomy of WM in HD patients. We used event-related functional magnetic resonance imaging and a parametric verbal WM task to investigate cerebral function during WM performance in 16 healthy control subjects and 12 mild to moderate stage HD patients. We excluded incorrectly performed trials to control for potential accuracy-related activation confounds. Voxel-based morphometry (VBM) was used to control for confounding cortical and subcortical atrophy. We found that HD patients were slower and less accurate than healthy controls across all WM load levels. In addition, HD patients showed lower activation in the left dorso- and ventrolateral prefrontal cortex, the left inferior parietal cortex, the left putamen, and the right cerebellum at high WM load levels only. VBM revealed gray matter differences in the bilateral caudate nucleus and the thalamus, as well as in inferior parietal and right lateral prefrontal regions. However, volumetric abnormalities in the patient group did not affect the activation differences obtained during WM task performance. These findings demonstrate that WM-related functional abnormalities in HD patients involve distinct WM network nodes associated with cognitive control and subvocal rehearsal. Moreover, aberrant cortical function in HD patients may occur in brain regions, which are relatively well preserved in terms of brain atrophy.

Regional brain activation changes and abnormal functional connectivity of the ventrolateral prefrontal cortex during working memory processing in adults with attention-deficit/hyperactivity disorder.

Previous studies on working memory (WM) function in adults with attention-deficit/hyperactivity disorder (ADHD) suggested aberrant activation of the prefrontal cortex and the cerebellum. Although it has been hypothesized that activation differences in these regions most likely reflect aberrant frontocerebellar circuits, the functional coupling of these brain networks during cognitive performance has not been investigated so far. In this study, functional magnetic resonance imaging (fMRI) and both univariate and multivariate analytic techniques were used to investigate regional activation changes and functional connectivity differences during cognitive processing in healthy controls (n = 12) and ADHD adults (n = 12). Behavioral performance during a parametric verbal WM paradigm did not significantly differ between adults with ADHD and healthy controls. During the delay period of the activation task, however, ADHD patients showed significantly less activation in the left ventrolateral prefrontal cortex (VLPFC), as well as in cerebellar and occipital regions compared with healthy control subjects. In both groups, independent component analyses revealed a functional network comprising bilateral lateral prefrontal, striatal, and cingulate regions. ADHD adults had significantly lower connectivity in the bilateral VLPFC, the anterior cingulate cortex, the superior parietal lobule, and the cerebellum compared with healthy controls. Increased connectivity in ADHD adults was found in right prefrontal regions, the left dorsal cingulate cortex and the left cuneus. These findings suggest both regional brain activation deficits and functional connectivity changes of the VLPFC and the cerebellum as well as functional connectivity abnormalities of the anterior cingulate and the parietal cortex in ADHD adults during WM processing.

Neuropsychological profile of pedophilic child sexual offenders compared with an IQ-matched non-offender sample - Results of a pilot study.

Child sexual offenders have been found to have a lower average IQ than the general population. Several studies indicate that they also exhibit executive dysfunction, but the specificity of this dysfunction is unclear; the inconclusive results have been attributed to methodological problems and the heterogeneity of the population. Our study aimed to describe the neuropsychological profiles of convicted child sexual offenders with pedophilia (n = 15). To control for IQ-related effects on neuropsychological performance, we compared the sample with an IQ-matched control group (n = 15). Test scores in both groups were significantly lower than the norms, but we did not find significant differences between the two study groups. The findings of our pilot study indicate that the neuropsychological deficits of pedophilic sexual offenders are unspecific rather than the result of a pedophilia-specific brain dysfunction.

Aberrant cortical neurodevelopment in major depressive disorder.

BACKGROUND: There is strong neuroimaging evidence that cortical alterations represent a core pathophysiological feature of major depressive disorder (MDD). Differential contributions of cortical features of neurodevelopmental origin, which may distinctly contribute to MDD vulnerability, disease-onset, or symptom expression, are unclear at present. METHODS: We investigated distinct markers of cortical neurodevelopment, i.e. local cortical gyrification (LGI) and thickness (CT) in patients with MDD (n = 38) and healthy controls (HC, n = 22) using 3 T structural magnetic resonance imaging data and surface-based data analysis techniques. CT and LGI were computed using the Computational Anatomy Toolbox (CAT12). Analyses were performed for the entire cortical surface followed by a complementary regions-of-interest approach. RESULTS: MDD patients showed significantly greater LGI in frontal, cingulate, parietal, temporal, and occipital regions compared to HC (FDR-corrected at p < 0.05 using threshold-free cluster enhancement). No significant differences of CT were found. In the MDD-group, correlations were found between duration of illness in years and number of depressive episodes and LGI of frontal, temporal, and parietal regions (p < 0.05). LIMITATIONS: Main limitations are the relatively modest sample size and a cross-sectional study design. We did not control for early environmental factors potentially influencing neurodevelopment, such as childhood trauma. We report associations uncorrected for multiple comparisons. CONCLUSIONS: The data suggest different local trajectories of cortical change in MDD. In addition, our data support the notion that aberrant cortical development may serve as a vulnerability marker of MDD, as well as a potential predictor of disease course.