Transdiagnostic and Illness-Specific Functional Dysconnectivity Across Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Huang, Chu-Chung; Luo, Qiang; Palaniyappan, Lena; Yang, Albert C.; Hung, Chia Chun; Chou, Kun Hsien; Lo, Chun Yi Zac; Liu, Mu-N; Tsai, Shih‐Jen; Deanna, M; Feng, Jianfeng; Lin, Ching Po; Robbins, Trevor W.

doi:10.1016/j.bpsc.2020.01.010

Cited by 27 publications

(28 citation statements)

References 54 publications

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“…A disorders-specific alteration (e.g., externalizing-specific) is defined by 1) a significant difference between one patient group and HC group, and 2) a nonsignificant difference (P FDR >0.05) between each of the other two patient groups and HC group. This definition was in line with our prior work [37]. Notably, this definition of disorder specificity does not indicate exclusivity (i.e., absence of a corresponding change in another patient group), but only indicates that a change with an effect size sufficient for detection at group level is specific to a group.…”

Section: Case-control Analysis and Anovasupporting

confidence: 74%

Common and Disorders-Specific Cortical Thickness Alterations in Internalizing, Externalizing and Thought Disorders over a 2-year Period in the Preadolescents of the ABCD Study

et al. 2021

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Objective: Overlap of brain changes across mental disorders has reinforced transdiagnostic models. However, the developmental basis for this overlap is unclear as are neural differences among internalizing, externalizing and thought disorders. These issues are critical to inform the theoretical framework for hierarchical transdiagnostic psychiatric taxonomy. Methods: This study involved 11,878 preadolescents (9-10 years) with baseline and 2-year follow-up data (n=6571) from the Adolescent Brain and Cognitive Development Study release 3.0. Linear mixed models were implemented in comparative and association analyses. Genome-wide association analysis, gene set enrichment analysis and cell type specificity analysis were performed on regional cortical thickness (CT) across 4,716 unrelated European youth. Results: Youth with externalizing or internalizing disorders, but not thought disorders, exhibited significantly thicker cortex than controls. Externalizing and internalizing disorders shared thicker CT in left pars opercularis and caudal middle frontal gyrus, which related to lower cognitive performance. Somatosensory and primary auditory cortex were uniquely affected in externalizing disorders; primary motor cortex and higher-order visual association areas (fusiform and inferior temporal gyrus) were uniquely affected in internalizing disorders. Baseline CT in one externalizing-specific region (left isthmus of cingulate cortex) related to externalizing behaviors at both baseline and 2-year follow-up. Genes associated with CT in common and disorders-specific regions were also implicated in related diagnostic families. Microglia were the cell-type associated with CT for both externalizing/internalizing while dopaminergic/ glutamatergic/GABAergic cells related only to externalizing-specific regions. Conclusions: Distinct anatomical trajectories relevant to internalizing/externalizing phenotypes may result from unique genetic and cell-type changes, but these occur in the background of significantly shared morphological variance.

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Section: Case-control Analysis and Anovasupporting

confidence: 74%

Common and Disorders-Specific Cortical Thickness Alterations in Internalizing, Externalizing and Thought Disorders over a 2-year Period in the Preadolescents of the ABCD Study

et al. 2021

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“…Disturbed functional connectivity of the dorsal prefrontal cortex and anterior temporal or posterior inferior parietal cortices are reported as schizophreniaspecific impairments (especially in adulthood), possibly underlying their unique symptomatology 128 . As supported by the relationships of fronto-temporo-limbic disconnectivity with delusions, hallucinations, and disorganization symptoms in SCZ patients 117,118 , anomalous gyral patterns in the corresponding region may lead to the generation of positive psychotic symptoms.…”

Section: Distinct Clinical Manifestations Sczmentioning

confidence: 99%

Anomalous brain gyrification patterns in major psychiatric disorders: a systematic review and transdiagnostic integration

et al. 2021

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Anomalous patterns of brain gyrification have been reported in major psychiatric disorders, presumably reflecting their neurodevelopmental pathology. However, previous reports presented conflicting results of patients having hyper-, hypo-, or normal gyrification patterns and lacking in transdiagnostic consideration. In this article, we systematically review previous magnetic resonance imaging studies of brain gyrification in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder at varying illness stages, highlighting the gyral pattern trajectory for each disorder. Patients with each psychiatric disorder may exhibit deviated primary gyri formation under neurodevelopmental genetic control in their fetal life and infancy, and then exhibit higher-order gyral changes due to mechanical stress from active brain changes (e.g., progressive reduction of gray matter volume and white matter integrity) thereafter, representing diversely altered pattern trajectories from those of healthy controls. Based on the patterns of local connectivity and changes in neurodevelopmental gene expression in major psychiatric disorders, we propose an overarching model that spans the diagnoses to explain how deviated gyral pattern trajectories map onto clinical manifestations (e.g., psychosis, mood dysregulation, and cognitive impairments), focusing on the common and distinct gyral pattern changes across the disorders in addition to their correlations with specific clinical features. This comprehensive understanding of the role of brain gyrification pattern on the pathophysiology may help to optimize the prediction and diagnosis of psychiatric disorders using objective biomarkers, as well as provide a novel nosology informed by neural circuits beyond the current descriptive diagnostics.

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“…As a flexible hub of cognitive control (Zanto and Gazzaley, 2013), FPN plays a crucial role in the top-down modulation of attention preparation and orientation during WM processing (Wallis et al, 2015), and the integrity of its microstructural connectivity seems to predict WM performance (Burzynska et al, 2011). Relevant to this work, mounting evidence suggests a prominent role for both cingulo-opercular (Huang et al, 2020) and FPN abnormalities in the WM deficits of MDD (Vasic et al, 2009; Yuksel et al, 2018).…”

Section: Introductionmentioning

confidence: 67%

Decreased integration of the frontoparietal network during a working memory task in major depressive disorder

Tan

Liu

et al. 2020

Aust N Z J Psychiatry

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Background: Working memory deficits are a common feature in major depressive disorder and are associated with poor functional outcomes. Intact working memory performance requires the recruitment of large-scale brain networks. However, it is unknown how the disrupted recruitment of distributed regions belonging to these large-scale networks at the whole-brain level brings about working memory impairment seen in major depressive disorder. Methods: We used graph theory to examine the functional connectomic metrics (local and global efficiency) at the whole-brain and large-scale network levels in 38 patients with major depressive disorder and 41 healthy controls during a working memory task. Altered connectomic metrics were studied in a moderation model relating to clinical symptoms and working memory accuracy in patients, and a machine learning method was employed to assess whether these metrics carry enough illness-specific information to discriminate patients from controls. Results: Global efficiency of the frontoparietal network was reduced in major depressive disorder (false discovery rate corrected, p = 0.014); this reduction predicted worse working memory performance in patients with less severe illness burden indexed by Brief Psychiatric Rating Scale (β =–0.43, p = 0.035, t =–2.2, 95% confidence interval = [–0.043,–0.002]). We achieved a classification accuracy and area under the curve of 73.42% and 0.734, respectively, to discriminate patients from controls based on connectomic metrics, and the global efficiency of the frontoparietal network contributed most to the diagnostic classification. Conclusions: We report a putative mechanistic link between the global efficiency of the frontoparietal network and impaired n-back performance in major depressive disorder. This relationship is more pronounced at lower levels of symptom burden, indicating the possibility of multiple pathways to cognitive deficits in severe major depressive disorder.

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Transdiagnostic and Illness-Specific Functional Dysconnectivity Across Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Cited by 27 publications

References 54 publications

Common and Disorders-Specific Cortical Thickness Alterations in Internalizing, Externalizing and Thought Disorders over a 2-year Period in the Preadolescents of the ABCD Study

Common and Disorders-Specific Cortical Thickness Alterations in Internalizing, Externalizing and Thought Disorders over a 2-year Period in the Preadolescents of the ABCD Study

Anomalous brain gyrification patterns in major psychiatric disorders: a systematic review and transdiagnostic integration

Decreased integration of the frontoparietal network during a working memory task in major depressive disorder

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