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1.
Nervenarzt ; 2019 Sep 26.
Artigo em Alemão | MEDLINE | ID: mdl-31559478

RESUMO

Cognitive disorders in schizophrenia are highly correlated with the psychosocial level (e.g. relationships, quality of life and work). It has been shown that healthy relatives and people at ultrahigh risk also display cognitive dysfunctions albeit to a lesser degree. The cognitive impairment increases simultaneously with an acute phase and then reverts back to baseline levels. At the psychopathological level, negative symptoms and the disorganization syndrome show the strongest associations with cognitive deficits, whereby the extent of manifestation of deficits increases with increasing symptomatology. Cognitive remediation can improve the cognitive performance through training with small to moderate effects. With respect to drug therapy there is currently no drug with a positive effect on cognitive disorders.

2.
Mol Psychiatry ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471575

RESUMO

Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31382267

RESUMO

Reduced fractional anisotropy (FA) associated with Major Depressive Disorder (MDD) overlaps anatomically with effects of childhood maltreatment experiences. The aim of this study was, therefore, to replicate the negative effect of childhood maltreatment on white matter fiber structure and to demonstrate, that alterations in MDD might be partially attributed to the higher occurrence of childhood maltreatment in MDD. Two independent cohorts (total N = 1 256) were investigated in a diffusion tensor imaging study: The Münster Neuroimaging Cohort (MNC, N = 186 MDD, N = 210 healthy controls, HC) as discovery sample and the Marburg-Münster Affective Disorders Cohort Study (MACS, N = 397 MDD, N = 462 HC) as replication sample. The effects of diagnosis (HC vs. MDD) and Childhood Trauma Questionnaire (CTQ) scores on FA were analyzed. A main effect of diagnosis with higher FA in MDD patients compared with HC was found in the MNC (pFWE = 0.021), but not in the MACS (pFWE = 0.52) before correcting for CTQ. A significant negative correlation of FA with CTQ emerged in both cohorts (MNC: pFWE = 0.006, MACS: pFWE = 0.012) in several tracts previously described in the literature. No CTQ × diagnosis interaction could be detected. Any main effect of diagnosis was abolished after correcting for CTQ (MNC: pFWE = 0.562, MACS: pFWE = 0.115). No differences in FA between MDD and HC could be found after correcting for childhood maltreatment, suggesting that previously reported group differences might be attributed partially to higher levels of maltreatment experiences in MDD rather than diagnosis itself. Furthermore, a well-established finding of reduced FA following childhood maltreatment experiences was replicated.

4.
Am J Psychiatry ; : appiajp201918101144, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31352813

RESUMO

OBJECTIVE: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects. METHODS: The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen's d=0.1. RESULTS: The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset. CONCLUSIONS: Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.

5.
Psychol Med ; : 1-12, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31084657

RESUMO

BACKGROUND: Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age. METHODS: Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer. RESULTS: CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions. CONCLUSIONS: Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

6.
Schizophr Res ; 208: 67-75, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31076262

RESUMO

Schizotypy is a multidimensional risk phenotype distributed in the general population, constituting of subclinical, psychotic-like symptoms. It is associated with psychosis proneness, and several risk genes for psychosis are associated with schizotypy in non-clinical populations. Schizotypy might also modulate cognitive abilities as it is associated with attentional deficits in healthy subjects. In this study, we tested the hypothesis that established genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737 are associated with psychometric schizotypy and that schizotypy mediates their effect on attention or vice versa. In 615 healthy subjects from the FOR2107 cohort study, we analysed the genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737, psychometric schizotypy (schizotypal personality questionnaire-brief SPQB), and a neuropsychological measure of sustained and selective attention (d2 test). ZNF804A rs1344706 C (non-risk) alleles were significantly associated with higher SPQ-B Cognitive-Perceptual subscores in women and with attention deficits in both sexes. This schizotypy dimension also mediated the effect of ZNF804A on attention in women, but not in men. CACNA1C rs1006737-A showed a significant sex-modulated negative association with Interpersonal schizotypy only in men, and no effect on attention. Our multivariate model demonstrates differential genetic contributions of two psychosis risk genes to dimensions of schizotypy and, partly, to attention. This supports a model of shared genetic influence between schizotypy and cognitive functions impaired in schizophrenia.

7.
Schizophr Res ; 208: 133-137, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30987925

RESUMO

City living represents not only the allegory of modern life, but also - due to attractive living conditions, employment and infrastructure - a crucial reality for a growing portion of the global society. Regarding the remarkable increase of the schizophrenia incidence in individuals exposed to an urban environment during upbringing the understanding of responsible pathogenetic mechanisms is important. Schizophrenia has been conceptualized as a disorder of brain dysconnectivity. We investigated the association between urban upbringing and gray matter as well as white matter in a large sample of healthy subjects (n = 290). Voxelwise analyses revealed a strong inverse correlation of early life urbanicity and gray matter volume of the bilateral dorsolateral prefrontal cortices (DLPFC) and the right inferior parietal lobe (IPL) as well as the white matter characteristics in the left superior longitudinal fasciculus (SLF). A positive correlation was found for the gray matter volume of the left precuneus. These results may point to an altered brain development associated with urban upbringing, which not only affects single brain regions but a fronto-parietal network. Considering a DLPFC susceptibility to stress, our findings support the hypothesis of the pathogenetic role of social stress in an urban environment.

8.
Artigo em Inglês | MEDLINE | ID: mdl-30831198

RESUMO

OBJECTIVE: Learning and memory performance have been reported to be impaired in patients with Major Depressive Disorder (MDD). Impairments are associated with diminished psychosocial functioning. Based on the processing-speed theory, we aimed to examine whether processing speed mediates the relationship between depression status and verbal, visuo-spatial and working memory impairment. METHODS: A neuropsychological test-battery was administered to 106 patients with current MDD, 119 patients with remitted MDD and 120 healthy controls to assess processing speed, learning and memory performance. To examine the impact of diagnosis status and processing speed on learning and memory performance, simple mediation models were computed. RESULTS: Currently depressed patients with MDD showed partially slowed processing speed, impaired short-term verbal and visuo-spatial memory performance compared to healthy controls. A basic deficit in processing speed mediated the relationship between depression status and verbal, visuo-spatial, and working memory impairment. However, there was no processing speed or memory impairment in patients with remitted MDD. CONCLUSION: Processing speed is an important factor regarding learning and memory impairment in patients with current MDD. Thereby, our results highlight novel targets for treatment of diminished learning and memory performance via enhancement of processing speed using pharmacological as well as therapeutic interventions.


Assuntos
Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/psicologia , Transtornos da Memória/complicações , Transtornos da Memória/psicologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Indução de Remissão , Fatores de Tempo , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-30267149

RESUMO

Genetic (G) and environmental (E) factors are involved in the etiology and course of the major psychoses (MP), i.e. major depressive disorder (MDD), bipolar disorder (BD), schizoaffective disorder (SZA) and schizophrenia (SZ). The neurobiological correlates by which these predispositions exert their influence on brain structure, function and course of illness are poorly understood. In the FOR2107 consortium, animal models and humans are investigated. A human cohort of MP patients, healthy subjects at genetic and/or environmental risk, and control subjects (N = 2500) has been established. Participants are followed up after 2 years and twice underwent extensive deep phenotyping (MR imaging, clinical course, neuropsychology, personality, risk/protective factors, biomaterials: blood, stool, urine, hair, saliva). Methods for data reduction, quality assurance for longitudinal MRI data, and (deep) machine learning techniques are employed. In the parallelised animal cluster, genetic risk was introduced by a rodent model (Cacna1c deficiency) and its interactions with environmental risk and protective factors are studied. The animals are deeply phenotyped regarding cognition, emotion, and social function, paralleling the variables assessed in humans. A set of innovative experimental projects connect and integrate data from the human and animal parts, investigating the role of microRNA, neuroplasticity, immune signatures, (epi-)genetics and gene expression. Biomaterial from humans and animals are analyzed in parallel. The FOR2107 consortium will delineate pathophysiological entities with common neurobiological underpinnings ("biotypes") and pave the way for an etiologic understanding of the MP, potentially leading to their prevention, the prediction of individual disease courses, and novel therapies in the future.

10.
J Neural Transm (Vienna) ; 125(10): 1433-1447, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30167933

RESUMO

Patients with major depressive disorder (MDD) exhibit gray matter volume (GMV) reductions in limbic regions. Clinical variables-such as the number of depressive episodes-seem to affect volume alterations. It is unclear whether the observed cross-sectional GMV abnormalities in MDD change over time, and whether there is a longitudinal relationship between GMV changes and the course of disorder. We investigated T1 structural MRI images of 54 healthy control (HC) and 37 MDD patients in a 3-Tesla-MRI with a follow-up interval of 3 years. The Cat12 toolbox was used to analyze longitudinal data (p < 0.05, FWE-corrected, whole-brain analysis; flexible factorial design). Interaction effects indicated increasing GMV in MDD in the bilateral amygdala, and decreasing GMV in the right thalamus between T1 and T2. Further analyses comparing patients with a mild course of disorder (MCD; 0-1 depressive episode during the follow-up) to patients with a severe course of disorder (SCD; > 1 depressive episode during the follow-up) revealed increasing amygdalar volume in MCD. Our study confirms structural alterations in limbic regions in MDD patients and an association between these impairments and the course of disorder. Thus, we assume that the reported volumetric alterations in the left amygdala (i.e. volumetric normalization) are reversible and apparently driven by the clinical phenotype. Hence, these results support the assumption that the severity and progression of disease influences amygdalar GMV changes in MDD or vice versa.

11.
Mol Psychiatry ; 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30185937

RESUMO

Neuroticism has been shown to act as an important risk factor for major depressive disorder (MDD). Genetic and neuroimaging research has independently revealed biological correlates of neurotic personality including cortical alterations in brain regions of high relevance for affective disorders. Here we investigated the influence of a polygenic score for neuroticism (PGS) on cortical brain structure in a joint discovery sample of n = 746 healthy controls (HC) and n = 268 MDD patients. Findings were validated in an independent replication sample (n = 341 HC and n = 263 MDD). Subgroup analyses stratified for case-control status and analyses of associations between neurotic phenotype and cortical measures were carried out. PGS for neuroticism was significantly associated with a decreased cortical surface area of the inferior parietal cortex, the precuneus, the rostral cingulate cortex and the inferior frontal gyrus in the discovery sample. Similar associations between PGS and surface area of the inferior parietal cortex and the precuneus were demonstrated in the replication sample. Subgroup analyses revealed negative associations in the latter regions between PGS and surface area in both HC and MDD subjects. Neurotic phenotype was negatively correlated with surface area in similar cortical regions including the inferior parietal cortex and the precuneus. No significant associations between PGS and cortical thickness were detected. The morphometric overlap of associations between both PGS and neurotic phenotype in similar cortical regions closely related to internally focused cognition points to the potential relevance of genetically shaped cortical alterations in the development of neuroticism.

12.
Mol Psychiatry ; 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30171211

RESUMO

Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47-67.00, ROC-AUC = 71.49%, 95% CI = 69.39-73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70-60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen's Kappa = 0.83, 95% CI = 0.829-0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data.

13.
Brain Imaging Behav ; 2018 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-30191514

RESUMO

Large-scale consortium efforts such as Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) and other collaborative efforts show that combining statistical data from multiple independent studies can boost statistical power and achieve more accurate estimates of effect sizes, contributing to more reliable and reproducible research. A meta- analysis would pool effects from studies conducted in a similar manner, yet to date, no such harmonized protocol exists for resting state fMRI (rsfMRI) data. Here, we propose an initial pipeline for multi-site rsfMRI analysis to allow research groups around the world to analyze scans in a harmonized way, and to perform coordinated statistical tests. The challenge lies in the fact that resting state fMRI measurements collected by researchers over the last decade vary widely, with variable quality and differing spatial or temporal signal-to-noise ratio (tSNR). An effective harmonization must provide optimal measures for all quality data. Here we used rsfMRI data from twenty-two independent studies with approximately fifty corresponding T1-weighted and rsfMRI datasets each, to (A) review and aggregate the state of existing rsfMRI data, (B) demonstrate utility of principal component analysis (PCA)-based denoising and (C) develop a deformable ENIGMA EPI template based on the representative anatomy that incorporates spatial distortion patterns from various protocols and populations.

14.
Soc Cogn Affect Neurosci ; 13(3): 341-348, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29385621

RESUMO

A high frequency of outgroup contact-as experienced by urban dwellers and migrants-possibly increases schizophrenia risk. This risk might be further amplified by genetic and environmental risk factors, such as the A-allele of rs1006737 within the calcium voltage-gated channel subunit alpha1 C gene and childhood interpersonal trauma (CIT). Both have been related to ventral anterior cingulate cortex (vACC) functioning. We investigated vACC functioning, during ingroup and outgroup emotion perception in relation to rs1006737 and CIT. Group membership was manipulated through a minimal group paradigm. Thus, in our functional magnetic resonance imaging study, a group of healthy Caucasian participants (n = 178) viewed video-recorded facial emotions (happy vs angry) of actors artificially assigned to represent the ingroup or the outgroup. Rs1006737 and CIT were related to brain activation for group and emotion specific processing. The group-emotion interaction in the vACC showed reduced sensitivity to emotional valence for outgroup member processing. Specifically for the angry outgroup condition, we found a gene by environment interaction in vACC activity. We speculate that the increased schizophrenia risk in migrants and urban dwellers could therefore be facilitated via this pathophysiological pathway.


Assuntos
Canais de Cálcio Tipo L/genética , Maus-Tratos Infantis/psicologia , Emoções/fisiologia , Giro do Cíngulo/fisiologia , Ferimentos e Lesões/genética , Ferimentos e Lesões/psicologia , Adulto , Ira , Criança , Expressão Facial , Feminino , Interação Gene-Ambiente , Humanos , Imagem por Ressonância Magnética , Masculino , Percepção/fisiologia , Personalidade , Esquizofrenia/epidemiologia , Migrantes , População Urbana , Adulto Jovem
15.
Psychol Med ; 48(14): 2391-2398, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29415775

RESUMO

BACKGROUND: Patients with major depression show reduced hippocampal volume compared to healthy controls. However, the contribution of patients' cumulative illness severity to hippocampal volume has rarely been investigated. It was the aim of our study to find a composite score of cumulative illness severity that is associated with hippocampal volume in depression. METHODS: We estimated hippocampal gray matter volume using 3-tesla brain magnetic resonance imaging in 213 inpatients with acute major depression according to DSM-IV criteria (employing the SCID interview) and 213 healthy controls. Patients' cumulative illness severity was ascertained by six clinical variables via structured clinical interviews. A principal component analysis was conducted to identify components reflecting cumulative illness severity. Regression analyses and a voxel-based morphometry approach were used to investigate the influence of patients' individual component scores on hippocampal volume. RESULTS: Principal component analysis yielded two main components of cumulative illness severity: Hospitalization and Duration of Illness. While the component Hospitalization incorporated information from the intensity of inpatient treatment, the component Duration of Illness was based on the duration and frequency of illness episodes. We could demonstrate a significant inverse association of patients' Hospitalization component scores with bilateral hippocampal gray matter volume. This relationship was not found for Duration of Illness component scores. CONCLUSIONS: Variables associated with patients' history of psychiatric hospitalization seem to be accurate predictors of hippocampal volume in major depression and reliable estimators of patients' cumulative illness severity. Future studies should pay attention to these measures when investigating hippocampal volume changes in major depression.

16.
Prog Neuropsychopharmacol Biol Psychiatry ; 84(Pt A): 39-49, 2018 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-29421266

RESUMO

BACKGROUND: Patients suffering from major depressive disorder (MDD) show deficits in working memory (WM) performance accompanied by bilateral fronto-parietal BOLD signal changes. It is unclear whether patients with a first depressive episode (FDE) exhibit the same signal changes as patients with recurrent depressive episodes (RDE). METHODS: We investigated seventy-four MDD inpatients (48 RDE, 26 FDE) and 74 healthy control (HC) subjects performing an n-back WM task (0-back, 2-back, 3-back condition) in a 3T-fMRI. RESULTS: FMRI analyses revealed deviating BOLD signal in MDD in the thalamus (0-back vs. 2-back), the angular gyrus (0-back vs. 3-back), and the superior frontal gyrus (2-back vs. 3-back). Further effects were observed between RDE vs. FDE. Thus, RDE displayed differing neural activation in the middle frontal gyrus (2-back vs. 3-back), the inferior frontal gyrus, and the precentral gyrus (0-back vs. 2-back). In addition, both HC and FDE indicated a linear activation trend depending on task complexity. CONCLUSIONS: Although we failed to find behavioral differences between the groups, results suggest differing BOLD signal in fronto-parietal brain regions in MDD vs. HC, and in RDE vs. FDE. Moreover, both HC and FDE show similar trends in activation shapes. This indicates a link between levels of complexity-dependent activation in fronto-parietal brain regions and the stage of MDD. We therefore assume that load-dependent BOLD signal during WM is impaired in MDD, and that it is particularly affected in RDE. We also suspect neurobiological compensatory mechanisms of the reported brain regions in (working) memory functioning.

17.
Schizophr Res ; 2018 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-29409757

RESUMO

Schizophrenia is a disorder with a high heritability. Patients as well as their first degree relatives display lower levels of performance in a number of cognitive domains compared to subjects without genetic risk. Several studies could link these aberrations to single genetic variants, however, only recently, polygenic risk scores as proxies for genetic risk have been associated with cognitive domains and their neural correlates. In the present study, a sample of healthy subjects (n=137) performed a letter version of the n-back task while scanned with 3-T fMRI. All subjects were genotyped with the PsychChip and polygenic risk scores were calculated based on the PGC2 schizophrenia GWAS results. Polygenic risk for schizophrenia was associated with a lower degree of brain activation in prefrontal areas during the 3-back compared to the 0-back baseline condition. Furthermore, polygenic risk was associated with lower levels of brain activation in the right inferior frontal gyrus during the 3-back compared to a 2-back condition. Polygenic risk leads to a shift in the underlying activation pattern to the left side, thus resembling results reported in patients with schizophrenia. The data may point to polygenic risk for schizophrenia being associated with brain function in a cognitive task known to be impaired in patients and their relatives.

18.
Prog Neuropsychopharmacol Biol Psychiatry ; 79(Pt B): 67-76, 2017 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-28624581

RESUMO

INTRODUCTION: Major depressive disorder (MDD) patients show impairments of cognitive functioning such as working memory (WM), and furthermore alterations during WM-fMRI tasks especially in frontal and parietal brain regions. The calculation of a polygenic risk score (PRS) can be used to describe the genetic influence on MDD, hence imaging genetic studies aspire to combine both genetics and neuroimaging data to identify the influence of genetic factors on brain functioning. We aimed to detect the effect of MDD-PRS on brain activation during a WM task measured with fMRI and expect healthy individuals with a higher PRS to be more resembling to MDD patients. METHOD: In total, n=137 (80 men, 57 women, aged 34.5, SD=10.4years) healthy subjects performed a WM n-back task [0-back (baseline), 2-back and 3-back condition] in a 3T-MRI-tomograph. The sample was genotyped using the Infinium PsychArray BeadChip and a polygenic risk score was calculated for MDD using PGC MDD GWAS results. RESULTS: A lower MDD risk score was associated with increased activation in the bilateral middle occipital gyri (MOG), the bilateral middle frontal gyri (MFG) and the right precentral gyrus (PCG) during the 2-back vs. baseline condition. Moreover, a lower PRS was associated with increased brain activation during the 3-back vs. baseline condition in the bilateral cerebellum, the right MFG and the left inferior parietal lobule. A higher polygenic risk score was associated with hyperactivation in brain regions comprising the right MFG and the right supplementary motor area during the 3-back vs. 2-back condition. DISCUSSION: The results suggest that part of the WM-related brain activation patterns might be explained by genetic variants captured by the MDD-PRS. Furthermore we were able to detect MDD-associated activation patterns in healthy individuals depending on the MDD-PRS and the task complexity. Additional gene loci could contribute to these task-dependent brain activation patterns.


Assuntos
Encéfalo/fisiologia , Transtorno Depressivo Maior/genética , Predisposição Genética para Doença , Memória de Curto Prazo/fisiologia , Herança Multifatorial , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Estudo de Associação Genômica Ampla , Técnicas de Genotipagem , Humanos , Imagem por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Análise de Regressão
19.
Fortschr Neurol Psychiatr ; 85(5): 292-304, 2017 May.
Artigo em Alemão | MEDLINE | ID: mdl-28561180

RESUMO

Cognitive disorders in schizophrenia can be observed in relatives and persons even before the first episode. The patterns of these disorders may be specific to the occurrence of a later episode. After the first episode, the disorders remain relatively stable and are partly correlated with negative symptoms. Furthermore, the cognitive deficits have a negative impact on the social and occupational functional level. Recent studies suggest that cognitive remediation has small to moderate effects on cognition, and thus can also improve overall patient function.


Assuntos
Transtornos Cognitivos/etiologia , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Transtornos Cognitivos/psicologia , Terapia Cognitivo-Comportamental , Humanos , Testes Neuropsicológicos
20.
Schizophr Res ; 184: 59-68, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28012640

RESUMO

Impaired fiber bundle connectivity between brain regions is a key neuropathological finding in schizophrenia. Symptom dimensions in schizophrenia can be clustered into factor models. Single syndromes have been related to grey and white matter brain structure alterations. We associated all core syndromes of schizophrenia in a single patient group with changes in white matter integrity. Diffusion weighted images (3T MRI) and SAPS/SANS scores were measured in 26 male patients and 26 healthy controls. First, group differences in fractional anisotropy (FA) were calculated with TBSS. Second, core symptom dimensions of schizophrenia were correlated with FA within these altered tracts. We found differences between groups in nine white matter tracts. Hallucinations were positively correlated with FA in the left uncinate fasciculus and left corticospinal tract. Ego-disturbances (passivity phenomena) showed a positive correlation with FA in the right anterior thalamic radiation. Positive formal thought disorders (FTD) corresponded negatively with FA in the right cingulum bundle. Negative symptoms were positively associated with the right anterior thalamic radiation and negatively with the right ventral cingulum bundle. For the first time, we analyzed the whole range of psychopathological factors in one schizophrenia patient group. We could validate our novel results for positive FTD and passivity phenomena by replicating findings for hallucinations and negative symptoms. Only those brain circuits which are most vulnerable at a given time during neurodevelopment are affected by a particular pathological impact (genetic, environmental). This scenario could explain the predominance of particular psychopathological syndromes related to specific white matter anomalies.


Assuntos
Imagem de Tensor de Difusão/métodos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Substância Branca/diagnóstico por imagem , Adulto , Feminino , Alucinações/etiologia , Alucinações/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/complicações , Pensamento/fisiologia , Adulto Jovem
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