Inhibitory control deficits are considered a key pathogenic factor in anxiety disorders. To assess inhibitory control, the antisaccade task is a well-established measure that assesses antisaccade ...performance via latencies and error rates. The present study follows three aims: (1) to investigate inhibitory control via antisaccade latencies and errors in an antisaccade task, and their associations with multiple measures of fear in patients with spider phobia (SP) versus healthy controls (HC), (2) to investigate the modifiability of antisaccade performance via a fear-specific antisaccade training in patients with SP and HC, and (3) to explore associations between putative training-induced changes in antisaccade performance in SPs and changes in diverse measures of fear.
Towards aim 1, we assess antisaccade latencies (primary outcome) and error rates (secondary outcome) in an emotional antisaccade task. Further, the baseline assessment includes assessments of psychophysiological, behavioral, and psychometric indices of fear in patients with SP and HCs. To address aim 2, we compare effects of a fear-specific antisaccade training with effects of a prosaccade training as a control condition. The primary and secondary outcomes are reassessed at a post-1-assessment in both SPs and HCs. Aim 3 employs a cross-over design and is piloted in patients with SP, only. Towards this aim, primary and secondary outcomes, as well as psychophysiological, behavioral, and psychometric measures of fear are reassessed at a post-2-assessment after the second training block.
This study aims to better understand inhibitory control processes and their modifiability in spider phobia. If successful, antisaccade training may assist in the treatment of specific phobia by directly targeting the putative underlying inhibitory control deficits. This study has been preregistered with ISRCTN (ID: ISRCTN12918583) on 28th February 2022.
Abstract
Former prospective studies showed that the occurrence of relapse in Major Depressive Disorder (MDD) is associated with volume loss in the insula, hippocampus and dorsolateral prefrontal ...cortex (DLPFC). However, these studies were confounded by the patient’s lifetime disease history, as the number of previous episodes predict future recurrence. In order to analyze neural correlates of recurrence irrespective of prior disease course, this study prospectively examined changes in brain structure in patients with first-episode depression (FED) over 2 years.
N
= 63 FED patients and
n
= 63 healthy controls (HC) underwent structural magnetic resonance imaging at baseline and after 2 years. According to their disease course during the follow-up interval, patients were grouped into
n
= 21 FED patients with recurrence (FEDrec) during follow-up and
n
= 42 FED patients with stable remission (FEDrem). Gray matter volume changes were analysed using group by time interaction analyses of covariance for the DLPFC, hippocampus and insula. Significant group by time interactions in the DLPFC and insula emerged. Pairwise comparisons showed that FEDrec had greater volume decline in the DLPFC and insula from baseline to follow-up compared with FEDrem and HC. No group by time interactions in the hippocampus were found. Cross-sectional analyses at baseline and follow-up revealed no differences between groups. This longitudinal study provides evidence for neural alterations in the DLPFC and insula related to a detrimental course in MDD. These effects of recurrence are already detectable at initial stages of MDD and seem to occur without any prior disease history, emphasizing the importance of early interventions preventing depressive recurrence.
Current interventions for adverse childhood experiences have only limited effectiveness.
We sought to identify optimal targets for the development of new interventions against adverse childhood ...experiences (ACE), that is, ACEs that a) are so central in the network of childhood adversity that curbing them is likely to impact other types of adversity, too, and b) are so central to the link of childhood adversity and adult mental ill-health that curbing them is likely to prevent this negative long-term effect from developing.
384 adult psychiatric inpatients.
Using the R packages qgraph and IsingFit, we analyzed the ACE network and the common network of ACEs and adult mental disorders.
We found two clusters of ACEs: direct interactions with the child and indirect traumatization via adverse circumstances. When controlling for interrelatedness, the associations of sexual abuse with posttraumatic stress disorder and borderline personality disorder were the only direct links between ACEs and adult mental disorders.
As neglect and violence against the mother were the most influential ACEs, curbing them is likely to destabilize the whole network of adversity. Thus, neglect and violence against the mother lend themselves as candidate targets for the development of new interventions. As sexual abuse was the only link between childhood adversity and adult mental ill-health, interventions against it seem most likely to keep this negative long-term effect from developing. Further, ideally prospective, research is needed to corroborate these findings.
This meta-analysis examined inhibitory control performance in the antisaccade task across mental disorders.
Following PRISMA guidelines, we analyzed data from k = 146 studies (n = 13,807 ...participants) on antisaccade performance. Effect sizes were estimated using random-effects models and restricted maximum-likelihood estimation, with robustness tests for study heterogeneity and publication bias.
Most disorders displayed elevated error rates, with schizophrenia showing the greatest impairments, followed by autism spectrum disorder, bipolar disorder and attention deficit hyperactivity disorder. Small to medium impairments were also found in eating disorders, major depressive disorder, obsessive-compulsive disorder and substance use disorder. Results were robust against corrections for publication bias and largely unaffected by confounding variables. Prolonged latencies were observed in schizophrenia, attention deficit hyperactivity disorder, bipolar disorder and obsessive compulsive disorder, with smaller and less robust effect sizes.
Results indicate inhibitory control deficits in the antisaccade task across mental disorders, especially evident for error rates. While present in most disorders, results imply varying degrees of impairments, ranging from small to large in effect sizes, with largest impairments in schizophrenia.
Keywords
•We conducted a transdiagnostic meta-analysis of the antisaccade task in mental disorders, including data from 13,807 participants across 146 studies.•We found impairments in antisaccade performance in most of the investigated disorders, with especially large and robust impairments in schizophrenia.•Impairments were generally larger and more robust for antisaccade error rates compared to antisaccade latencies.•Results imply impairments in inhibitory control measured by the antisaccade task as a transdiagnostic dimension of mental disorders with graded severity across diagnostic domains.
Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia spectrum disorder (SSD, schizophrenia, and schizoaffective disorder) overlap in symptomatology, risk factors, genetics, and ...other biological measures. Based on previous findings, it remains unclear what transdiagnostic regional gray matter volume (GMV) alterations exist across these disorders, and with which factors they are associated. GMV (3-T magnetic resonance imaging) was compared between healthy controls (HC; n = 110), DSM-IV-TR diagnosed MDD (n = 110), BD (n = 110), and SSD patients (n = 110), matched for age and sex. We applied a conjunction analysis to identify shared GMV alterations across the disorders. To identify potential origins of identified GMV clusters, we associated them with early and current risk and protective factors, psychopathology, and neuropsychology, applying multiple regression models. Common to all diagnoses (vs. HC), we identified GMV reductions in the left hippocampus. This cluster was associated with the neuropsychology factor working memory/executive functioning, stressful life events, and with global assessment of functioning. Differential effects between groups were present in the left and right frontal operculae and left insula, with volume variances across groups highly overlapping. Our study is the first with a large, matched, transdiagnostic sample to yield shared GMV alterations in the left hippocampus across major mental disorders. The hippocampus is a major network hub, orchestrating a range of mental functions. Our findings underscore the need for a novel stratification of mental disorders, other than categorical diagnoses.
Altered brain structural connectivity has been implicated in the pathophysiology of psychiatric disorders including schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). ...However, it is unknown which part of these connectivity abnormalities are disorder specific and which are shared across the spectrum of psychotic and affective disorders. We investigated common and distinct brain connectivity alterations in a large sample (N = 1743) of patients with SZ, BD, or MDD and healthy control (HC) subjects.
This study examined diffusion-weighted imaging-based structural connectome topology in 720 patients with MDD, 112 patients with BD, 69 patients with SZ, and 842 HC subjects (mean age of all subjects: 35.7 years). Graph theory–based network analysis was used to investigate connectome organization. Machine learning algorithms were trained to classify groups based on their structural connectivity matrices.
Groups differed significantly in the network metrics global efficiency, clustering, present edges, and global connectivity strength with a converging pattern of alterations between diagnoses (e.g., efficiency: HC > MDD > BD > SZ, false discovery rate–corrected p = .028). Subnetwork analysis revealed a common core of edges that were affected across all 3 disorders, but also revealed differences between disorders. Machine learning algorithms could not discriminate between disorders but could discriminate each diagnosis from HC. Furthermore, dysconnectivity patterns were found most pronounced in patients with an early disease onset irrespective of diagnosis.
We found shared and specific signatures of structural white matter dysconnectivity in SZ, BD, and MDD, leading to commonly reduced network efficiency. These results showed a compromised brain communication across a spectrum of major psychiatric disorders.
Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the ...number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD.
Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables.
Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18 <d < 0.22). More (hypo)manic episodes were associated with faster cortical thinning, primarily in the prefrontal cortex.
In the hitherto largest longitudinal MRI study on BD, we did not detect accelerated cortical thinning but noted faster ventricular enlargements in BD. However, abnormal frontocortical thinning was observed in association with frequent manic episodes. Our study yields insights into disease progression in BD and highlights the importance of mania prevention in BD treatment.
BackgroundMajor depressive disorder (MDD) has been associated with alterations in brain white matter (WM) microstructure. However, diffusion tensor imaging studies in biological relatives have ...presented contradicting results on WM alterations and their potential as biomarkers for vulnerability or resilience. To shed more light on associations between WM microstructure and resilience to familial risk, analyses including both healthy and depressed relatives of MDD patients are needed.MethodsIn a 2 (MDD v. healthy controls, HC) × 2 (familial risk yes v. no) design, we investigated fractional anisotropy (FA) via tract-based spatial statistics in a large well-characterised adult sample (N = 528), with additional controls for childhood maltreatment, a potentially confounding proxy for environmental risk.ResultsAnalyses revealed a significant main effect of diagnosis on FA in the forceps minor and the left superior longitudinal fasciculus (ptfce−FWE = 0.009). Furthermore, a significant interaction of diagnosis with familial risk emerged (ptfce−FWE = 0.036) Post-hoc pairwise comparisons showed significantly higher FA, mainly in the forceps minor and right inferior fronto-occipital fasciculus, in HC with as compared to HC without familial risk (ptfce−FWE < 0.001), whereas familial risk played no role in MDD patients (ptfce−FWE = 0.797). Adding childhood maltreatment as a covariate, the interaction effect remained stable.ConclusionsWe found widespread increased FA in HC with familial risk for MDD as compared to a HC low-risk sample. The significant effect of risk on FA was present only in HC, but not in the MDD sample. These alterations might reflect compensatory neural mechanisms in healthy adults at risk for MDD potentially associated with resilience.
Stressful life events (SLEs) in adulthood are a risk factor for various disorders such as depression, cancer or infections. Part of this risk is mediated through pathways altering brain physiology ...and structure. There is a lack of longitudinal studies examining associations between SLEs and brain structural changes. High‐resolution structural magnetic resonance imaging data of 212 healthy subjects were acquired at baseline and after 2 years. Voxel‐based morphometry was used to identify associations between SLEs using the Life Events Questionnaire and grey matter volume (GMV) changes during the 2‐year period in an ROI approach. Furthermore, we assessed adverse childhood experiences as a possible moderator of SLEs‐GMV change associations. SLEs were negatively associated with GMV changes in the left medial prefrontal cortex. This association was stronger when subjects had experienced adverse childhood experiences. The medial prefrontal cortex has previously been associated with stress‐related disorders. The present findings represent a potential neural basis of the diathesis‐stress model of various disorders.
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