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Cortical thinning in persons at increased familial risk for major depression.

ABSTRACT: The brain disturbances that place a person at risk for developing depression are unknown. We imaged the brains of 131 individuals, ages 6 to 54 years, who were biological descendants (children or grandchildren) of individuals identified as having either moderate to severe, recurrent, and functionally debilitating depression or as having no lifetime history of depression. We compared cortical thickness across high- and low-risk groups, detecting large expanses of cortical thinning across the lateral surface of the right cerebral hemisphere in persons at high risk. Thinning correlated with measures of current symptom severity, inattention, and visual memory for social and emotional stimuli. Mediator analyses indicated that cortical thickness mediated the associations of familial risk with inattention, visual memory, and clinical symptoms. These findings suggest that cortical thinning in the right hemisphere produces disturbances in arousal, attention, and memory for social stimuli, which in turn may increase the risk of developing depressive illness.

SUBMITTER: Peterson BS

PROVIDER: S-EPMC2669378 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Cortical thinning in persons at increased familial risk for major depression.

Peterson Bradley S BS Warner Virginia V Bansal Ravi R Zhu Hongtu H Hao Xuejun X Liu Jun J Durkin Kathleen K Adams Phillip B PB Wickramaratne Priya P Weissman Myrna M MM

Proceedings of the National Academy of Sciences of the United States of America 20090327 15

The brain disturbances that place a person at risk for developing depression are unknown. We imaged the brains of 131 individuals, ages 6 to 54 years, who were biological descendants (children or grandchildren) of individuals identified as having either moderate to severe, recurrent, and functionally debilitating depression or as having no lifetime history of depression. We compared cortical thickness across high- and low-risk groups, detecting large expanses of cortical thinning across the late ...[more]

PMID: 19329490

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Project description:Identifying reliable trait markers of familial risk for major depressive disorder (MDD) is a challenge in translational psychiatric research. In individuals with acute MDD, dysfunctional connectivity patterns of prefrontal areas have been shown repeatedly. However, it has been unclear in which neuronal networks functional alterations in individuals at familial risk for MDD might be present and to what extent they resemble findings previously reported in those with acute MDD.We investigated differences in blood oxygen level-dependent (BOLD) response of the medial orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) to aversive stimuli between acute MDD and familial risk for the disorder in healthy first-degree relatives of acutely depressed patients with MDD (HC-FH+), healthy age- and sex-matched controls without any family history of depression (HC-FH-), and acutely depressed patients with MDD with (MDD-FH+) and without a family history of depression (MDD-FH-) during a frequently used emotional face-matching paradigm. Analyses of task-specific network connectivity were conducted in terms of psychophysiological interactions (PPI).The present analysis included a total of 100 participants: 25 HC-FH+, 25 HC-FH-, 25 MDD-FH+ and 25 MDD-FH-. Patients with MDD exhibited significantly increased activation in the medial OFC to negative stimuli irrespective of familial risk status, whereas healthy participants at familial risk and patients with MDD alike showed significant hypoactivation in the DLPFC compared with healthy participants without familial risk. The PPI analyses revealed significantly enhanced task-specific coupling between the medial OFC and differing cortical areas in individuals with acute MDD and those with familial risk for the disorder.The main limitation of our study is its cross-sectional design.Whereas hypoactivation during negative emotion processing in the DLPFC appears as a common feature in both healthy high-risk individuals and acutely depressed patients, activation patterns of the medial OFC and its underlying connectivity seem to distinguish familial risk from acute disorder.

Project description:INTRODUCTION:Anhedonia, a core symptom of Major Depressive Disorder (MDD), manifests as a lack or loss of motivation as reflected by decreased reward responsiveness, at both behavioral and neural (i.e., striatum) levels. Exposure to stressful life events is another important risk factor for MDD. However, the mechanisms linking reward-deficit and stress to MDD remain poorly understood. Here, we explore whether the effects of stress exposure on reward processing might differentiate between Healthy Vulnerable adults (HVul, i.e., positive familial MDD) from Healthy Controls (HCon). Furthermore, the well-described reduction in cognitive resources in MDD might facilitate the stress-induced decrease in reward responsiveness in HVul individuals. Accordingly, this study includes a manipulation of cognitive resources to address the latter possibility. METHODS:16 HVul (12 females) and 16 gender- and age-matched HCon completed an fMRI study, during which they performed a working memory reward task. Three factors were manipulated: reward (reward, no-reward), cognitive resources (working memory at low and high load), and stress level (no-shock, unpredictable threat-of-shock). Only the reward anticipation phase was analyzed. Imaging analyses focused on striatal function. RESULTS:Compared to HCon, HVul showed lower activation in the caudate nucleus across all conditions. The HVul group also exhibited lower stress-related activation in the nucleus accumbens, but only in the low working memory (WM) load condition. Moreover, while stress potentiated putamen reactivity to reward cues in HVul when the task was more demanding (high WM load), stress blunted putamen reactivity in both groups when no reward was at stake. CONCLUSION:Findings suggest that HVul might be at increased risk of developing anhedonic symptoms due to weaker encoding of reward value, higher difficulty to engage in goal-oriented behaviors and increased sensitivity to negative feedback, particularly in stressful contexts. These findings open new avenues for a better understanding of the mechanisms underlying how the complex interaction between the systems of stress and reward responsiveness contribute to the vulnerability to MDD, and how cognitive resources might modulate this interaction.

Dataset Information

Cortical thinning in persons at increased familial risk for major depression.

Publications

Cortical thinning in persons at increased familial risk for major depression.

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