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1.
Psychol Med ; : 1-12, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33827729

RESUMO

BACKGROUND: MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood. METHODS: We extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness. RESULTS: The PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing. CONCLUSIONS: Changes in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33684623

RESUMO

BACKGROUND: Major depressive disorder (MDD) and type 2 diabetes (T2D) are known to share clinical comorbidity and to have genetic overlap. Besides their shared genetics, both diseases seem to be associated with alterations in brain structural connectivity and impaired cognitive performance, but little is known about the mechanisms by which genetic risk of T2D might affect brain structure and function and if so, how these effects could contribute to the disease course of MDD. METHODS: This study explores the association of polygenic risk for T2D with structural brain connectome topology and cognitive performance in 434 nondiabetic MDD patients and 539 healthy controls. RESULTS: Polygenic risk score for T2D across MDD patients and healthy controls was found to be associated with reduced global fractional anisotropy, a marker of white matter microstructure, an effect found to be predominantly present in MDD-related fronto-temporo-parietal connections. A mediation analysis further suggests that this FA variation may mediate the association between PGS and cognitive performance. CONCLUSIONS: Our findings provide preliminary evidence of a polygenic risk for T2D to be linked to brain structural connectivity and cognition in MDD patients and healthy controls, even in the absence of a direct T2D diagnosis. This suggests an effect of T2D genetic risk on white matter integrity, which may mediate an association of genetic risk for diabetes and cognitive impairments.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33648793

RESUMO

Apolipoprotein E (APOE) genotype is the strongest single gene predictor of Alzheimer's disease (AD) and has been frequently associated with AD-related brain structural alterations before the onset of dementia. While previous research has primarily focused on hippocampal morphometry in relation to APOE, sporadic recent findings have questioned the specificity of the hippocampus and instead suggested more global effects on the brain. With the present study we aimed to investigate associations between homozygous APOE ε4 status and cortical gray matter structure as well as white matter microstructure. In our study, we contrasted n = 31 homozygous APOE ε4 carriers (age=34.47 years, including a subsample of n = 12 subjects with depression) with a demographically matched sample without an ε4 allele (resulting total sample: N = 62). Morphometry analyses included a) Freesurfer based cortical segmentations of thickness and surface area measures and b) tract based spatial statistics of DTI measures. We found pronounced and widespread reductions in cortical surface area of ε4 homozygotes in 57 out of 68 cortical brain regions. In contrast, no differences in cortical thickness were observed. Furthermore, APOE ε4 homozygous carriers showed significantly lower fractional anisotropy in the corpus callosum, the right internal and external capsule, the left corona radiata and the right fornix. The present findings support a global rather than regionally specific effect of homozygous APOE ε4 allele status on cortical surface area and white matter microstructure. Future studies should aim to delineate the clinical implications of these findings.

4.
Psychoneuroendocrinology ; 126: 105148, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33513455

RESUMO

Novelty seeking (NS) has previously been identified as a personality trait that is associated with elevated body mass index (BMI) and obesity. Of note, both obesity and reduced impulse control - a core feature of NS - have previously been associated with grey matter volume (GMV) reductions in the orbitofrontal cortex (OFC). Yet, it remains unknown, if body weight-related grey matter decline in the OFC might be explained by higher levels of NS. To address this question, we studied associations between NS, BMI and brain structure in 355 healthy subjects. Brain images were pre-processed using voxel-based morphometry (VBM). BMI was calculated from self-reported height and weight. The Tridimensional Personality Questionnaire (TPQ) was used to assess NS. NS and BMI were associated positively (r = .137, p = .01) with NS being a significant predictor of BMI (B = 0.172; SE B = 0.05; ß = 0.184; p = 0.001). Significant associations between BMI and GMV specifically in the OFC (x = -44, y = 56, z = -2, t(350) = 4.34, k = 5, pFWE = 0.011) did not uphold when correcting for NS in the model. In turn, a significant negative association between NS and OFC GMV was found independent of BMI (x = -2, y = 48, z = -10, t(349) = 4.42, k = 88, pFWE = 0.008). Body mass-related grey matter decrease outside the OFC could not be attributed to NS. Our results suggest that body-weight-related orbitofrontal grey matter reduction can at least partly be linked to higher levels of NS. Given the pivotal role of the OFC in overweight as well as cognitive domains such as impulse inhibition, executive control and reward processing, its association with NS seems to provide a tenable neurobiological correlate for future research.

5.
JMIR Ment Health ; 8(1): e24333, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33433392

RESUMO

BACKGROUND: Smartphone-based symptom monitoring has gained increased attention in psychiatric research as a cost-efficient tool for prospective and ecologically valid assessments based on participants' self-reports. However, a meaningful interpretation of smartphone-based assessments requires knowledge about their psychometric properties, especially their validity. OBJECTIVE: The goal of this study is to systematically investigate the validity of smartphone-administered assessments of self-reported affective symptoms using the Remote Monitoring Application in Psychiatry (ReMAP). METHODS: The ReMAP app was distributed to 173 adult participants of ongoing, longitudinal psychiatric phenotyping studies, including healthy control participants, as well as patients with affective disorders and anxiety disorders; the mean age of the sample was 30.14 years (SD 11.92). The Beck Depression Inventory (BDI) and single-item mood and sleep information were assessed via the ReMAP app and validated with non-smartphone-based BDI scores and clinician-rated depression severity using the Hamilton Depression Rating Scale (HDRS). RESULTS: We found overall high comparability between smartphone-based and non-smartphone-based BDI scores (intraclass correlation coefficient=0.921; P<.001). Smartphone-based BDI scores further correlated with non-smartphone-based HDRS ratings of depression severity in a subsample (r=0.783; P<.001; n=51). Higher agreement between smartphone-based and non-smartphone-based assessments was found among affective disorder patients as compared to healthy controls and anxiety disorder patients. Highly comparable agreement between delivery formats was found across age and gender groups. Similarly, smartphone-based single-item self-ratings of mood correlated with BDI sum scores (r=-0.538; P<.001; n=168), while smartphone-based single-item sleep duration correlated with the sleep item of the BDI (r=-0.310; P<.001; n=166). CONCLUSIONS: These findings demonstrate that smartphone-based monitoring of depressive symptoms via the ReMAP app provides valid assessments of depressive symptomatology and, therefore, represents a useful tool for prospective digital phenotyping in affective disorder patients in clinical and research applications.

6.
Transl Psychiatry ; 10(1): 425, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293520

RESUMO

It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent samples comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD; healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33007775

RESUMO

Preclinical evidence indicates that the endocannabinoid system is involved in neural responses to reward. This study aimed to investigate associations between basal serum concentrations of the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) with brain functional reward processing. Additionally, a personality measure of reward dependence was obtained. Brain functional data were obtained of 30 right-handed adults by conducting fMRI at 3 Tesla using a reward paradigm. Reward dependence was obtained using the subscale reward dependence of the Tridimensional Personality Questionnaire (TPQ). Basal concentrations of AEA and 2-AG were determined in serum. Analyzing the fMRI data, for AEA and 2-AG ANCOVAs were calculated using a full factorial model, with condition (reward > control, loss > control) and concentrations for AEA and 2-AG as factors. Regression analyses were conducted for AEA and 2-AG on TPQ-RD scores. A whole-brain analysis showed a significant interaction effect of AEA concentration by condition (positive vs. negative) within the putamen (x = 26, y = 16, z = -8, F13.51, TFCE(1, 54) = 771.68, k = 70, PFWE = 0.044) resulting from a positive association of basal AEA concentrations and putamen activity to rewarding stimuli, while this association was absent in the loss condition. AEA concentrations were significantly negatively correlated with TPQ reward dependence scores (rspearman = -0.56, P = 0.001). These results show that circulating AEA may modulate brain activation during reward feedback and that the personality measure reward dependence is correlated with AEA concentrations in healthy human volunteers. Future research is needed to further characterize the nature of the lipids' influence on reward processing, the impact on reward anticipation and outcome, and on vulnerability for psychiatric disorders.

8.
Psychol Med ; : 1-9, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32921338

RESUMO

BACKGROUND: Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness. METHODS: A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects. RESULTS: Disease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF. CONCLUSIONS: Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32801319

RESUMO

Childhood maltreatment is associated with cognitive deficits that in turn have been predictive for therapeutic outcome in psychiatric patients. However, previous studies have either investigated maltreatment associations with single cognitive domains or failed to adequately control for confounders such as depression, socioeconomic environment, and genetic predisposition. We aimed to isolate the relationship between childhood maltreatment and dysfunction in diverse cognitive domains, while estimating the contribution of potential confounders to this relationship, and to investigate gene-environment interactions. We included 547 depressive disorder and 670 healthy control participants (mean age: 34.7 years, SD = 13.2). Cognitive functioning was assessed for the domains of working memory, executive functioning, processing speed, attention, memory, and verbal intelligence using neuropsychological tests. Childhood maltreatment and parental education were assessed using self-reports, and psychiatric diagnosis was based on DSM-IV criteria. Polygenic scores for depression and for educational attainment were calculated. Multivariate analysis of cognitive domains yielded significant associations with childhood maltreatment (η²p = 0.083, P < 0.001), depression (η²p = 0.097, P < 0.001), parental education (η²p = 0.085, P < 0.001), and polygenic scores for depression (η²p = 0.021, P = 0.005) and educational attainment (η²p = 0.031, P < 0.001). Each of these associations remained significant when including all of the predictors in one model. Univariate tests revealed that maltreatment was associated with poorer performance in all cognitive domains. Thus, environmental, psychopathological, and genetic risk factors each independently affect cognition. The insights of the current study may aid in estimating the potential impact of different loci of interventions for cognitive dysfunction. Future research should investigate if customized interventions, informed by individual risk profiles and related cognitive preconditions, might enhance response to therapeutic treatments.

10.
Hum Brain Mapp ; 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32648625

RESUMO

Reduced sleep duration and sleep deprivation have been associated with cognitive impairment as well as decreased white matter integrity as reported by experimental studies. However, it is largely unknown whether differences in sleep duration and sleep quality might affect microstructural white matter and cognition. Therefore, the present study aims to examine the cross-sectional relationship between sleep duration, sleep quality, and cognitive performance in a naturalistic study design, by focusing on the association with white matter integrity in a large sample of healthy, young adults. To address this, 1,065 participants, taken from the publicly available sample of the Human Connectome Project, underwent diffusion tensor imaging. Moreover, broad cognitive performance measures (NIH Cognition Toolbox) and sleep duration and quality (Pittsburgh Sleep Quality Index) were assessed. The results revealed a significant positive association between sleep duration and overall cognitive performance. Shorter sleep duration significantly correlated with fractional anisotropy (FA) reductions in the left superior longitudinal fasciculus (SLF). In turn, FA in this tract was related to measures of cognitive performance and was shown to significantly mediate the association of sleep duration and cognition. For cognition only, associations shift to a negative association of sleep duration and cognition for participants sleeping more than 8 hr a day. Investigations into subjective sleep quality showed no such associations. The present study showed that real-world differences in sleep duration, but not subjective sleep quality are related to cognitive performance measures and white matter integrity in the SLF in healthy, young adults.

11.
Eur Neuropsychopharmacol ; 36: 10-17, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32451266

RESUMO

While the hippocampus remains a region of high interest for neuropsychiatric research, the precise contributors to hippocampal morphometry are still not well understood. We and others previously reported a hippocampus specific effect of a tescalcin gene (TESC) regulating single nucleotide polymorphism (rs7294919) on gray matter volume. Here we aimed to replicate and extend these findings. Two complementary morphometric approaches (voxel based morphometry (VBM) and automated volumetric segmentation) were applied in a well-powered cohort from the Marburg-Münster Affective Disorder Cohort Study (MACS) including N=1137 participants (n=636 healthy controls, n=501 depressed patients). rs7294919 homozygous T-allele genotype was significantly associated with lower hippocampal gray matter density as well as with reduced hippocampal volume. Exploratory whole brain VBM analyses revealed no further associations with gray matter volume outside the hippocampus. No interaction effects of rs7294919 with depression nor with childhood trauma on hippocampal morphometry could be detected. Hippocampal subfield analyses revealed similar effects of rs7294919 in all hippocampal subfields. In sum, our results replicate a hippocampus specific effect of rs7294919 on brain structure. Due to the robust evidence for a pronounced association between the reported polymorphism and hippocampal morphometry, future research should consider investigating the potential clinical and functional relevance of the reported association.

12.
Brain Stimul ; 13(4): 1051-1058, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32388195

RESUMO

BACKGROUND: In treatment-resistant major depressive disorder (MDD), electroconvulsive therapy (ECT) is a treatment with high efficacy. While knowledge regarding changes in brain structure following ECT is growing, the effects of ECT on brain function during emotional processing are largely unknown. OBJECTIVE: We investigated the effects of ECT on the activity of the anterior cingulate cortex (ACC) and amygdala during negative emotional stimuli processing and its association with clinical response. METHODS: In this non-randomized longitudinal study, patients with MDD (n = 37) were assessed before and after treatment with ECT. Healthy controls (n = 37) were matched regarding age and gender. Functional magnetic resonance imaging (fMRI) was obtained twice, at baseline and after six weeks using a supraliminal face-matching paradigm. In order to evaluate effects of clinical response, additional post-hoc analyses were performed comparing responders to non-responders. RESULTS: After ECT, patients with MDD showed a statistically significant increase in ACC activity during processing of negative emotional stimuli (pFWE = .039). This effect was driven by responders (pFWE = .023), while non-responders showed no increase. Responders also had lower pre-treatment ACC activity compared to non-responders (pFWE = .025). No significant effects in the amygdala could be observed. CONCLUSIONS: ECT leads to brain functional changes in the ACC, a relevant region for emotional regulation during processing of negative stimuli. Furthermore, baseline ACC activity might serve as a biomarker for treatment response. Findings are in accordance with recent studies highlighting properties of pre-treatment ACC to be associated with general antidepressive treatment response.

13.
Brain Stimul ; 13(3): 696-704, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32289700

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment option for major depressive disorder, so understanding whether its clinical effect relates to structural brain changes is vital for current and future antidepressant research. OBJECTIVE: To determine whether clinical response to ECT is related to structural volumetric changes in the brain as measured by structural magnetic resonance imaging (MRI) and, if so, which regions are related to this clinical effect. We also determine whether a similar model can be used to identify regions associated with electrode placement (unilateral versus bilateral ECT). METHODS: Longitudinal MRI and clinical data (Hamilton Depression Rating Scale) was collected from 10 sites as part of the Global ECT-MRI research collaboration (GEMRIC). From 192 subjects, relative changes in 80 (sub)cortical areas were used as potential features for classifying treatment response. We used recursive feature elimination to extract relevant features, which were subsequently used to train a linear classifier. As a validation, the same was done for electrode placement. We report accuracy as well as the structural coefficients of regions included in the discriminative spatial patterns obtained. RESULTS: A pattern of structural changes in cortical midline, striatal and lateral prefrontal areas discriminates responders from non-responders (75% accuracy, p < 0.001) while left-sided mediotemporal changes discriminate unilateral from bilateral electrode placement (81% accuracy, p < 0.001). CONCLUSIONS: The identification of a multivariate discriminative pattern shows that structural change is relevant for clinical response to ECT, but this pattern does not include mediotemporal regions that have been the focus of electroconvulsive therapy research so far.


Assuntos
Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia/métodos , Adulto , Idoso , Encéfalo/patologia , Eletroconvulsoterapia/instrumentação , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
Neuropsychopharmacology ; 45(10): 1758-1765, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32272482

RESUMO

Transgender individuals (TIs) show brain-structural alterations that differ from their biological sex as well as their perceived gender. To substantiate evidence that the brain structure of TIs differs from male and female, we use a combined multivariate and univariate approach. Gray matter segments resulting from voxel-based morphometry preprocessing of N = 1753 cisgender (CG) healthy participants were used to train (N = 1402) and validate (20% holdout N = 351) a support-vector machine classifying the biological sex. As a second validation, we classified N = 1104 patients with depression. A third validation was performed using the matched CG sample of the transgender women (TW) application sample. Subsequently, the classifier was applied to N = 26 TW. Finally, we compared brain volumes of CG-men, women, and TW-pre/post treatment cross-sex hormone treatment (CHT) in a univariate analysis controlling for sexual orientation, age, and total brain volume. The application of our biological sex classifier to the transgender sample resulted in a significantly lower true positive rate (TPR-male = 56.0%). The TPR did not differ between CG-individuals with (TPR-male = 86.9%) and without depression (TPR-male = 88.5%). The univariate analysis of the transgender application-sample revealed that TW-pre/post treatment show brain-structural differences from CG-women and CG-men in the putamen and insula, as well as the whole-brain analysis. Our results support the hypothesis that brain structure in TW differs from brain structure of their biological sex (male) as well as their perceived gender (female). This finding substantiates evidence that TIs show specific brain-structural alterations leading to a different pattern of brain structure than CG-individuals.

16.
Hum Brain Mapp ; 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32198905

RESUMO

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = -0.164 to -0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = -0.173 to -0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.

17.
Eur Arch Psychiatry Clin Neurosci ; 270(7): 921-932, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31802253

RESUMO

Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.

18.
Mol Psychiatry ; 25(7): 1550-1558, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31758093

RESUMO

Major depressive disorder (MDD) is associated to affected brain wiring. Little is known whether these changes are stable over time and hence might represent a biological predisposition, or whether these are state markers of current disease severity and recovery after a depressive episode. Human white matter network ("connectome") analysis via network science is a suitable tool to investigate the association between affected brain connectivity and MDD. This study examines structural connectome topology in 464 MDD patients (mean age: 36.6 years) and 432 healthy controls (35.6 years). MDD patients were stratified categorially by current disease status (acute vs. partial remission vs. full remission) based on DSM-IV criteria. Current symptom severity was assessed continuously via the Hamilton Depression Rating Scale (HAMD). Connectome matrices were created via a combination of T1-weighted magnetic resonance imaging (MRI) and tractography methods based on diffusion-weighted imaging. Global tract-based metrics were not found to show significant differences between disease status groups, suggesting conserved global brain connectivity in MDD. In contrast, reduced global fractional anisotropy (FA) was observed specifically in acute depressed patients compared to fully remitted patients and healthy controls. Within the MDD patients, FA in a subnetwork including frontal, temporal, insular, and parietal nodes was negatively associated with HAMD, an effect remaining when correcting for lifetime disease severity. Therefore, our findings provide new evidence of MDD to be associated with structural, yet dynamic, state-dependent connectome alterations, which covary with current disease severity and remission status after a depressive episode.

19.
Neuroimage Clin ; 25: 102114, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31884221

RESUMO

A growing number of recent studies has suggested that the neuroplastic effects of electroconvulsive therapy (ECT) might be prominent enough to be detected through changes of regional gray matter volumes (GMV) during the course of the treatment. Given that ECT patients are difficult to recruit for imaging studies, most publications, however, report only on small samples. Addressing this challenge, we here report results of a structural imaging study on ECT patients that pooled patients from five German sites. Whole-brain voxel-based morphometry (VBM) analysis was performed to detect structural differences in 85 patients with unipolar depression before and after ECT, when compared to 86 healthy controls. Both task-independent and task-dependent physiological whole-brain functional connectivity patterns of these regions were modeled using additional data from healthy subjects. All emerging regions were additionally functionally characterized using the BrainMap database. Our VBM analysis detected a significant increase of GMV in the right hippocampus/amygdala region in patients after ECT compared to healthy controls. In healthy subjects this region was found to be enrolled in a network associated with emotional processing and memory. A region in the left fusiform gyrus was additionally found to have higher GMV in controls when compared with patients at baseline. This region showed minor changes after ECT. Our data points to a GMV increase in patients post ECT in regions that seem to constitute a hub of an emotion processing network. This appears as a plausible antidepressant mechanism and could explain the efficacy of ECT not only in the treatment of unipolar depression, but also of affective symptoms across heterogeneous disorders.

20.
Psychol Med ; 50(2): 187-209, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31858931

RESUMO

Antidepressive pharmacotherapy (AD), electroconvulsive therapy (ECT) and cognitive behavioural therapy (CBT) are effective treatments for major depressive disorder. With our review, we aim to provide a systematic overview of neuroimaging studies that investigate the effects of AD, ECT and CBT on brain grey matter volume (GMV) and biomarkers associated with response. After a systematic database research on PubMed, we included 50 studies using magnetic resonance imaging and investigating (1) changes in GMV, (2) pre-treatment GMV biomarkers associated with response, or (3) the accuracy of predictions of response to AD, ECT or CBT based on baseline GMV data. The strongest evidence for brain structural changes was found for ECT, showing volume increases within the temporal lobe and subcortical structures - such as the hippocampus-amygdala complex, anterior cingulate cortex (ACC) and striatum. For AD, the evidence is heterogeneous as only 4 of 11 studies reported significant changes in GMV. The results are not sufficient in order to draw conclusions about the structural brain effects of CBT. The findings show consistently that higher pre-treatment ACC volume is associated with response to AD, ECT and CBT. An association of higher pre-treatment hippocampal volume and response has only been reported for AD. Machine learning approaches based on pre-treatment whole brain patterns reach accuracies of 64-90% for predictions of AD or ECT response on the individual patient level. The findings underline the potential of brain biomarkers for the implementation in clinical practice as an additive feature within the process of treatment selection.


Assuntos
Encéfalo/patologia , Transtorno Depressivo Maior/terapia , Imagem por Ressonância Magnética , Antidepressivos/uso terapêutico , Biomarcadores/análise , Encéfalo/diagnóstico por imagem , Terapia Cognitivo-Comportamental , Transtorno Depressivo Maior/diagnóstico por imagem , Eletroconvulsoterapia , Humanos , Aprendizado de Máquina , Neuroimagem , Resultado do Tratamento
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