Childhood Adversity Is Associated with Left Basal Ganglia Dysfunction During Reward Anticipation in Adulthood

Department of Psychology, Harvard University, Cambridge, Massachusetts 02138, USA.
Biological psychiatry (Impact Factor: 10.26). 05/2009; 66(3):206-13. DOI: 10.1016/j.biopsych.2009.02.019
Source: PubMed

ABSTRACT Childhood adversity increases the risk of psychopathology, but the neurobiological mechanisms underlying this vulnerability are not well-understood. In animal models, early adversity is associated with dysfunction in basal ganglia regions involved in reward processing, but this relationship has not been established in humans.
Functional magnetic resonance imaging was used to examine basal ganglia responses to: 1) cues signaling possible monetary rewards and losses; and 2) delivery of monetary gains and penalties, in 13 young adults who experienced maltreatment before age 14 years and 31 nonmaltreated control subjects.
Relative to control subjects, individuals exposed to childhood adversity reported elevated symptoms of anhedonia and depression, rated reward cues less positively, and displayed a weaker response to reward cues in the left globus pallidus. There were no group differences in right hemisphere basal ganglia response to reward cues or in basal ganglia response to loss cues, no-incentive cues, gains, or penalties.
Results indicate that childhood adversity in humans is associated with blunted subjective responses to reward-predicting cues as well as dysfunction in left basal ganglia regions implicated in reward-related learning and motivation. This dysfunction might serve as a diathesis that contributes to the multiple negative outcomes and psychopathologies associated with childhood adversity. The findings suggest that interventions that target motivation and goal-directed action might be useful for reducing the negative consequences of childhood adversity.

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Available from: Karlen Lyons-Ruth, Sep 26, 2015
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    • "Disturbances in the neural circuits associated with dopaminergic neurotransmission have been strongly implicated in the pathophysiology of the disorders mentioned above (Schultz, 2007; Van den Heuvel and Pasterkamp, 2008). Interestingly, many functional neuroimaging studies in the human brain have shown correlations between ELS and dopaminergic system dysfunction and have suggested that ELS interferes with brain development and/or maturation, thus leading to dopaminergic circuitry dysfunction and later psychopathology (Pruessner et al., 2004; Dillon et al., 2009; Oswald et al., 2014). "
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    ABSTRACT: Clinical studies have suggested that early-life stress (ELS) increases the risk of psychopathologies that are strongly associated with dysfunction of dopaminergic neurotransmission. Thus, ELS may interfere with the development and maturation of the dopaminergic system; however, the mechanisms involved in such interference are poorly understood. In the present study, we investigated the effect of ELS on the survival of specific populations of neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) during postnatal development. First, we injected bromodeoxyuridine (BrdU) into pregnant rat dams on embryonic days 12, 13 and 14 to permanently label midbrain neurons. Then, after birth, the dams and litters were subjected to a maternal separation (MS) procedure to model ELS conditions. The number of BrdU+ neurons and the total number of neurons (cresyl violet+, CV+) were estimated in both male and female juvenile, adolescent, and adult rats. Moreover, sucrose preference and anxiety-like behavior were studied during adulthood. We found that MS permanently increased the number of BrdU+ and CV+ neurons in the VTA of males. In the SNc, a temporary increase in the number of BrdU+ neurons was observed in juvenile MS males; however, only adult MS males displayed an increase in the number of CV+ neurons. Immunofluorescence analysis implied that MS affected the fate of non-dopaminergic neurons. MS males displayed anxiolytic-like behavior and an increase in sucrose preference. These results suggest that ELS induces distinct dysregulation in the midbrain circuitry of males, which may lead to sex-specific psychopathology of the reward system. Copyright © 2015. Published by Elsevier Ltd.
    International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 05/2015; 44. DOI:10.1016/j.ijdevneu.2015.05.002 · 2.58 Impact Factor
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    • "Recent research has established that early life stress has enduring effects on the adult brain, many of which closely resemble the changes observed in the depressed brain, and which are therefore likely to underlie the established cognitive and temperamental vulnerabilities to depression (Heim et al., 2008; Pechtel and Pizzagalli, 2011). For example, people who had been abused or institutionalized as children were more anhedonic than nonabused controls, and they had decreased rewardrelated activity in the NAc (Dillon et al., 2009; Mehta et al., 2010). Adults who have been traumatized as children also show greater electrophysiological responses to angry faces or voices (Pechtel and Pizzagalli, 2011), as well as a greater amygdalar response to negative events (Taylor et al., 2006; Joormann et al., 2012). "
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    ABSTRACT: The first half of this paper briefly reviews the evidence that (i) stress precipitates depression by damaging the hippocampus, leading to changes in the activity of a distributed neural system involving, inter alia, the amygdala, the ventromedial and dorsolateral prefrontal cortex, the lateral habenula and ascending monoamine pathways, and (ii) antidepressants work by repairing the damaged hippocampus, thus restoring the normal balance of activity within that circuitry. In the second half of the paper we review the evidence that heightened vulnerability to depression, either because of a clinical history of depression or because of the presence of genetic, personality or developmental risk factors, also confers resistance to antidepressant drug treatment. Thus, although antidepressants provide an efficient means of reversing the neurotoxic effects of stress, they are much less effective in conditions where vulnerability to depression is elevated and the role of stress in precipitating depression is correspondingly lower. Consequently, the issue of vulnerability should feature much more prominently in antidepressant research. Most of the current animal models of depression are based on the induction of a depressive-like phenotype by stress, and pay scant attention to vulnerability. As antidepressants are relatively ineffective in vulnerable individuals, this in turn implies a need for the development of different clinical and preclinical methodologies, and a shift of focus away from the current preoccupation with the hippocampus as a target for antidepressant action in vulnerable patients.
    Behavioural Pharmacology 09/2014; 25(5 and 6):352-371. DOI:10.1097/FBP.0000000000000066 · 2.15 Impact Factor
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    • "Early-life stress resulting from parental abuse or neglect is accompanied by increased drug abuse and addiction vulnerability later in life (Andersen and Teicher, 2009), which is probably mediated by CRT. In line with this, neuroimaging studies also show blunted striatal responses to rewards or reward-cues in adults who experienced early-life stress (Dillon et al., 2009; Goff et al., 2012). "
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    ABSTRACT: Research in rodents and humans has shown divergent effects of the glucocorticoids corticosterone and cortisol (CRT) on reward processing. In rodents, administration of CRT increases reward drive by facilitating dopamine release in the ventral striatum. In humans, correspondingly, risky decision-making increases when CRT levels are elevated. Human stress studies contrariwise show that elevated CRT is accompanied by a decrease in reward-related brain activity. There are however no direct insights into how CRT acts on the reward system in the human brain. Accordingly, we used pharmacological functional magnetic resonance imaging (pharmaco-fMRI) to investigate the effects of CRT on the brain's reward system. In a randomized within-subject design we administered a high dose of CRT (40 mg) and placebo to twenty healthy male volunteers on separate days, and used a monetary incentive delay task to assess the effects of the hormone on the striatum and the amygdala in anticipation of potential reward. In contrast to animal studies, we show that this high dose of CRT strongly decreases activity of the striatum in both reward and non-reward conditions. Furthermore, we observed reductions in activity in the basolateral amygdala, a key regulator of the brain's reward system. Crucially, the overall down-regulation of the brain's reward circuit was verified on the subjective level as subjects reported significantly reduced reward preference after CRT. In sum, we provide here direct evidence in humans that CRT acts on brain regions involved in reward-related behavior, that is, the basolateral amygdala and the striatum. Our findings suggest that CRT in the quantity and time course presently globally down-regulates the reward system, and thereby decreases motivational processing in general.
    Psychoneuroendocrinology 09/2014; 47. DOI:10.1016/j.psyneuen.2014.04.022 · 4.94 Impact Factor
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