Dataset Information

Striatal Hypersensitivity During Stress in Remitted Individuals with Recurrent Depression.

ABSTRACT: Increased sensitivity to stress and dysfunctional reward processing are two primary characteristics of major depressive disorder (MDD) that may persist after remission. Preclinical work has established the pivotal role of the striatum in mediating both stress and reward responses. Human neuroimaging studies have corroborated these preclinical findings and highlighted striatal dysfunction in MDD in response to reward but have yet to investigate striatal function during stress, in particular in individuals with recurrent depression.A validated mild psychological stress task involving viewing of negative stimuli during functional magnetic resonance imaging was conducted in 33 remitted individuals with a history of recurrent major depressive disorder (rMDD) and 35 matched healthy control subjects. Cortisol and anxiety levels were assessed throughout scanning. Stress-related activation was investigated in three striatal regions: caudate, nucleus accumbens, and putamen. Psychophysiologic interaction analyses probed connectivity of regions with central structures of the neural stress circuitry, such as the amygdala and hippocampus.The task increased cortisol and anxiety levels, although to a greater extent in rMDD individuals than healthy control subjects. In response to the negative stimuli, rMDD individuals, but not controls, also exhibited significantly potentiated caudate, nucleus accumbens, and putamen activations and increased caudate-amygdala and caudate-hippocampus connectivity.The findings highlight striatal hypersensitivity in response to a mild psychological stress in rMDD, as manifested by hyperactivation and hyperconnectivity with the amygdala and hippocampus. Striatal hypersensitivity during stress might thus constitute a trait mark of depression, providing a potential neural substrate for the interaction between stress and reward dysfunction in MDD.

SUBMITTER: Admon R

PROVIDER: S-EPMC4383718 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Striatal Hypersensitivity During Stress in Remitted Individuals with Recurrent Depression.

Admon Roee R Holsen Laura M LM Aizley Harlyn H Remington Anne A Whitfield-Gabrieli Susan S Goldstein Jill M JM Pizzagalli Diego A DA

Biological psychiatry 20141002 1

<h4>Background</h4>Increased sensitivity to stress and dysfunctional reward processing are two primary characteristics of major depressive disorder (MDD) that may persist after remission. Preclinical work has established the pivotal role of the striatum in mediating both stress and reward responses. Human neuroimaging studies have corroborated these preclinical findings and highlighted striatal dysfunction in MDD in response to reward but have yet to investigate striatal function during stress, ...[more]

PMID: 25483401

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Project description:Deficits in cognitive control are a hallmark characteristic of depression, however less is known about the degree to which they persist beyond symptom remission and might contribute to symptom recurrence in remitted individuals (rMDD). Evidence indicates that stress interferes with cognitive control, highlighting a potential mechanism by which stress precipitates depression relapse. Therefore, this study examined whether stress exposure elicits deficits in error monitoring - a component of cognitive control thought to be particularly implicated in the ability to adaptively respond to negative feedback - in individuals with rMDD. Unmedicated individuals with rMDD (n=30) and healthy controls (n=34) performed an Eriksen Flanker task before and 45min after an acute stressor while 128-channel event-related potentials (ERPs) were recorded. Flanker interference effects and post-error adjustments were examined, and ERP analyses focused on the error-related negativity (ERN) and error positivity (Pe). Standardized low resolution electromagnetic tomography (sLORETA) was used to examine stress-induced changes in current source density. Individuals with rMDD showed blunted cortisol reactivity to the stressor, coupled with heightened self-reported stress reactivity. Although no significant effects of group or stress were observed in scalp-level ERPs, source-level analyses indicated that among the rMDD group only, stress caused a reduction in activation in frontocingulate regions critically implicated in error monitoring. The magnitude of stress-induced decreases in frontocingulate activation correlated with heightened self-reported stress reactivity, and also predicted heightened levels of stress and depression 18 months later in the entire sample. These findings suggest that individuals with rMDD show a stress-induced disruption in frontocingulate function that is linked to heightened stress reactivity, and this disruption prospectively predicts heightened levels of future stress and depressive symptomatology.

Project description:One of the core symptoms of major depressive disorder is anhedonia, an inability to experience pleasure. In patients with major depressive disorder, a dysfunctional reward-system may exist, with blunted temporal difference reward-related learning signals in the ventral striatum and increased temporal difference-related (dopaminergic) activation in the ventral tegmental area. Anhedonia often remains as residual symptom during remission; however, it remains largely unknown whether the abovementioned reward systems are still dysfunctional when patients are in remission. We used a Pavlovian classical conditioning functional MRI task to explore the relationship between anhedonia and the temporal difference-related response of the ventral tegmental area and ventral striatum in medication-free remitted recurrent depression patients (n = 36) versus healthy control subjects (n = 27). Computational modelling was used to obtain the expected temporal difference errors during this task. Patients, compared to healthy controls, showed significantly increased temporal difference reward learning activation in the ventral tegmental area (PFWE,SVC = 0.028). No differences were observed between groups for ventral striatum activity. A group × anhedonia interaction [t(57) = -2.29, P = 0.026] indicated that in patients, higher anhedonia was associated with lower temporal difference activation in the ventral tegmental area, while in healthy controls higher anhedonia was associated with higher ventral tegmental area activation. These findings suggest impaired reward-related learning signals in the ventral tegmental area during remission in patients with depression. This merits further investigation to identify impaired reward-related learning as an endophenotype for recurrent depression. Moreover, the inverse association between reinforcement learning and anhedonia in patients implies an additional disturbing influence of anhedonia on reward-related learning or vice versa, suggesting that the level of anhedonia should be considered in behavioural treatments.

Project description:Consistent evidence suggests residual symptoms and stress are the most reliable predictors of relapse in remitted depression. Prevailing methodologies often do not enable continuous real-time sampling of stress. Thus, little is known about day-to-day interactions between residual symptoms and stress in remitted depression. In preparation for a full-scale trial, this study aimed to pilot a wrist-worn wearable electrodermal activity monitor: ADI (Analog Devices, Inc.) Study Watch for assessing interactions between physiological stress and residual depressive symptoms following depression remission. 13 individuals remitted from major depression completed baseline, daily diary, and post-daily diary assessments. Self-reported stress and residual symptoms were measured at baseline and post-daily diary. Diary assessments required participants to wear ADI’s Study Watch during waking hours and complete self-report questionnaires every evening over one week. Sleep problems, fatigue, energy loss, and agitation were the most frequently reported residual symptoms. Average skin conductance responses (SCRs) were 16.09 per-hour, with an average of 11.30 hours of wear time per-day. Increased residual symptoms were associated with enhanced self-reported stress on the same day. Increased SCRs on one day predicted increased residual symptoms on the next day. This study showed a wearable electrodermal activity device can be recommended for examining stress as a predictor of remitted depression. This study also provides preliminary work on relationships between residual symptoms and stress in remitted depression. Importantly, significant findings from the small sample of this pilot are preliminary with an aim to follow up with a 3-week full-scale study to draw conclusions about psychological processes explored. Clinical and Translational Impact Statemen—ADI’s wearable electrodermal activity device enables a continuous measure of physiological stress for identifying its interactions with residual depressive symptoms following remission. This novel procedure is promising for future studies.

Dataset Information

Striatal Hypersensitivity During Stress in Remitted Individuals with Recurrent Depression.

Publications

Striatal Hypersensitivity During Stress in Remitted Individuals with Recurrent Depression.

Similar Datasets

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