Dataset Information

Intrinsic connectivity of the prefrontal cortex and striato-limbic system respectively differentiate major depressive from generalized anxiety disorder.

ABSTRACT: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent and debilitating disorders. The high overlap on the symptomatic and neurobiological level led to ongoing debates about their diagnostic and neurobiological uniqueness. The present study aims to identify common and disorder-specific neuropathological mechanisms and treatment targets in MDD and GAD. To this end we combined categorical and dimensional disorder models with a fully data-driven intrinsic network-level analysis (intrinsic connectivity contrast, ICC) to resting-state fMRI data acquired in 108 individuals (n = 35 and n = 38 unmedicated patients with first-episode GAD, MDD, respectively, and n = 35 healthy controls). Convergent evidence from categorical and dimensional analyses revealed MDD-specific decreased whole-brain connectivity profiles of the medial prefrontal and dorsolateral prefrontal cortex while GAD was specifically characterized by decreased whole-brain connectivity profiles of the putamen and decreased communication of this region with the amygdala. Together, findings from the present data-driven analysis suggest that intrinsic communication of frontal regions engaged in executive functions and emotion regulation represent depression-specific neurofunctional markers and treatment targets whereas dysregulated intrinsic communication of the striato-amygdala system engaged in reinforcement-based and emotional learning processes represent GAD-specific markers.

SUBMITTER: Xu X

PROVIDER: S-EPMC8027677 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Intrinsic connectivity of the prefrontal cortex and striato-limbic system respectively differentiate major depressive from generalized anxiety disorder.

Xu Xiaolei X Dai Jing J Chen Yuanshu Y Liu Congcong C Xin Fei F Zhou Xinqi X Zhou Feng F Stamatakis Emmanuel A EA Yao Shuxia S Luo Lizhu L Huang Yulan Y Wang Jinyu J Zou Zhili Z Vatansever Deniz D Kendrick Keith M KM Zhou Bo B Becker Benjamin B

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20200922 4

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent and debilitating disorders. The high overlap on the symptomatic and neurobiological level led to ongoing debates about their diagnostic and neurobiological uniqueness. The present study aims to identify common and disorder-specific neuropathological mechanisms and treatment targets in MDD and GAD. To this end we combined categorical and dimensional disorder models with a fully data-driven intrinsic networ ...[more]

PMID: 32961541

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Project description:Major depressive disorder is a leading cause of disability and significant mortality, yet mechanistic understanding remains limited. Over the past decade evidence has accumulated from case-control studies that depressive illness is associated with blunted reward activation in the basal ganglia and other regions such as the medial prefrontal cortex. However it is unclear whether this finding can be replicated in a large number of subjects. The functional anatomy of the medial prefrontal cortex and basal ganglia has been extensively studied and the former has excitatory glutamatergic projections to the latter. Reduced effect of glutamatergic projections from the prefrontal cortex to the nucleus accumbens has been argued to underlie motivational disorders such as depression, and many prominent theories of major depressive disorder propose a role for abnormal cortico-limbic connectivity. However, it is unclear whether there is abnormal reward-linked effective connectivity between the medial prefrontal cortex and basal ganglia related to depression. While resting state connectivity abnormalities have been frequently reported in depression, it has not been possible to directly link these findings to reward-learning studies. Here, we tested two main hypotheses. First, mood symptoms are associated with blunted striatal reward prediction error signals in a large community-based sample of recovered and currently ill patients, similar to reports from a number of studies. Second, event-related directed medial prefrontal cortex to basal ganglia effective connectivity is abnormally increased or decreased related to the severity of mood symptoms. Using a Research Domain Criteria approach, data were acquired from a large community-based sample of subjects who participated in a probabilistic reward learning task during event-related functional MRI. Computational modelling of behaviour, model-free and model-based functional MRI, and effective connectivity dynamic causal modelling analyses were used to test hypotheses. Increased depressive symptom severity was related to decreased reward signals in areas which included the nucleus accumbens in 475 participants. Decreased reward-related effective connectivity from the medial prefrontal cortex to striatum was associated with increased depressive symptom severity in 165 participants. Decreased striatal activity may have been due to decreased cortical to striatal connectivity consistent with glutamatergic and cortical-limbic related theories of depression and resulted in reduced direct pathway basal ganglia output. Further study of basal ganglia pathophysiology is required to better understand these abnormalities in patients with depressive symptoms and syndromes.

Dataset Information

Intrinsic connectivity of the prefrontal cortex and striato-limbic system respectively differentiate major depressive from generalized anxiety disorder.

Publications

Intrinsic connectivity of the prefrontal cortex and striato-limbic system respectively differentiate major depressive from generalized anxiety disorder.

Similar Datasets

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