Lack of ventral striatal response to positive stimuli in depressed versus normal subjects
ABSTRACT Most of the functional neuroimaging studies of depression have focused primarily on the resting state or responses to negatively valenced stimuli. However, depression consists not only of an accentuation of negative affective processing but of an inability to experience pleasure or positive motivation. The authors tested the hypothesis that depressed subjects would show less activation than healthy comparison subjects, in response to positive stimuli, in ventral striatal regions associated with processing of reward and positive stimuli.
Positive, negative, and neutral words were presented to 10 unmedicated depressed patients and 12 healthy comparison subjects in the context of a 3T functional magnetic resonance imaging (MRI) paradigm. Image processing and analysis were performed using statistical parametric mapping with a mixed-effects model. Significant differences in neural responses were assessed, examining group, condition, and interaction effects of interest within the context of a general linear model.
Relative to comparison subjects, depressed patients demonstrated significantly less bilateral ventral striatal activation to positive stimuli, correlating with decreased interest/pleasure in and performance of activities. They also displayed decreased activation to positive stimuli in a dorsomedial frontal region associated with processing of self-related stimuli. Responses of depressed subjects to negative stimuli were consistent with the growing literature on frontolimbic dysfunction in depression.
This finding 1) supports a pathophysiological model of depression that includes reward/motivational pathway dysfunction, 2) suggests a contributing neural substrate of the inability to experience pleasure or engage in rewarding activities, 3) provides greater specification of abnormalities of basal ganglia function in depression, and 4) may help guide treatment approaches.
Full-textDOI: · Available from: Hong Pan, Aug 07, 2014
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ABSTRACT: Given that depression in men is associated with risk for seriously adverse consequences, evaluating how putative neural mechanisms of depression-such as reward-related frontostriatal connectivity-may be altered in late adolescent boys with a history of depression is an important research aim. Adolescents and adults with depression have been demonstrated to show blunted striatal response and heightened medial prefrontal cortex (mPFC) activation to winning reward. Function in reward circuits appears to be best understood as coordination of regions within frontostriatal circuitry, and alterations to this circuitry could occur in those with a history of depression. The current study evaluated functional connectivity between the nucleus accumbens and mPFC in a sample of 166 ethnically diverse boys with and without a history of depression. Participants completed an fMRI monetary reward paradigm at age 20. Lifetime history of depression and other psychiatric illnesses was measured prospectively and longitudinally, using structured clinical interviews at 7 time points from ages 8 to 20. Boys with a history of depression showed heightened positive connectivity between the nucleus accumbens and the mPFC relative to boys with no psychiatric history when winning rewards relative to losing rewards. This altered frontostriatal connectivity pattern was also associated with greater number of depressive episodes in the boys' lifetime. History of depression in late adolescent boys may be associated with altered coordination between the nucleus accumbens and mPFC when winning reward. This coordination could reflect oversignaling of the mPFC to dampen typical ventral striatum response or enhance weak ventral striatum response.Journal of Clinical Child & Adolescent Psychology 04/2015; DOI:10.1080/15374416.2015.1030753 · 1.92 Impact Factor
From Symptom to Synapse: A Neurocognitive Perspective on Clinical Psychology, 1 edited by J. Mohlman; T. Deckersbach; & A. Weissman, 01/2015: chapter 8: pages 211-246; Routledge.
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ABSTRACT: Introduction: Little is known about the neural correlates of mood states and the specific physiological changes associated with their valence and duration, especially in young people. Arterial spin labeling (ASL) imaging is particularly well-suited to study sustained cerebral states in young people, due to its robustness to low-frequency drift, excellent interscan reliability, and noninvasiveness. Yet, it has so far been underutilized for understanding the neural mechanisms underlying mood states in youth. Methods: In this exploratory study, 21 healthy adolescents aged 16 to 18 took part in a mood induction experiment. Neutral, sad, and happy mood states were induced using film clips and explicit instructions. An ASL scan was obtained following presentation of each film clip. Results: Mood induction led to robust changes in self-reported mood ratings. Compared to neutral, sad mood was associated with increased regional cerebral blood flow (rCBF) in the left middle frontal gyrus and anterior prefrontal cortex, and decreased rCBF in the right middle frontal gyrus and the inferior parietal lobule. A decrease in self-reported mood from neutral to sad condition was associated with increased rCBF in the precuneus. Happy mood was associated with increased rCBF in medial frontal and cingulate gyri, the subgenual anterior cingulate cortex, and ventral striatum, and decreased rCBF in the inferior parietal lobule. The level of current self-reported depressive symptoms was negatively associated with rCBF change in the cerebellum and lingual gyrus following both sad and happy mood inductions. Conclusions: Arterial spin labeling is sensitive to experimentally induced mood changes in healthy young people. The effects of happy mood on rCBF patterns were generally stronger than the effects of sad mood.