Probing Brain Reward System Function in Major Depressive Disorder

Tremblay, Lescia K.; Naranjo, Claudio A.; Cárdenas, Laura; Herrmann, Nathan; Busto, Usoa E.

doi:10.1001/archpsyc.59.5.409

Cited by 215 publications

(120 citation statements)

References 71 publications

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“…In line with this hypothesis, studies have found that anhedonia can precede the onset of depression (Dryman and Eaton, 1991); shows temporal stability (Oquendo et al, 2004); predicts poor outcome 12 months later (Spijker et al, 2001); and is associated with dysfunctions within the brain reward system (Keedwell et al, 2005;Tremblay et al, 2002). Moreover, reward dependence, a putatively heritable trait associated with maintenance of behavior in response to reward cues, shows trait-like features associated with familiality of depression (Farmer et al, 2003).…”

Section: Discussionmentioning

confidence: 88%

“…Interestingly, resting activity within left prefrontal regions has been linked to individuals' propensity to respond to rewardrelated cues , providing convergent evidence that depressed subjects might display reduced hedonic capacity. Finally, studies employing various paradigms have shown that depressed subjects display a blunted emotional response to pleasant cues (e.g., Sloan et al, 2001;Suslow et al, 2001), decreased reward responsiveness (e.g., Henriques and Davidson, 2000), a lack of a positivity bias in attentional tasks (e.g., McCabe and Gotlib, 1995;Wang et al, 2006), and dysfunctions within the brain reward system (e.g., Keedwell et al, 2005;Tremblay et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Reduced hedonic capacity in major depressive disorder: Evidence from a probabilistic reward task

Pizzagalli

Iosifescu

Hallett

et al. 2008

Journal of Psychiatric Research

653

693

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Objective-Anhedonia, the lack of reactivity to pleasurable stimuli, is a cardinal feature of depression that has received renewed interest as a potential endophenotype of this debilitating disease. The goal of the present study was to test the hypothesis that individuals with major depression are characterized by blunted reward responsiveness, particularly when anhedonic symptoms are prominent.Methods-A probabilistic reward task rooted within signal-detection theory was utilized to objectively assess hedonic capacity in 23 unmedicated subjects meeting DSM-IV criteria for major depressive disorder (MDD) and 25 matched control subjects recruited from the community. Hedonic capacity was defined as reward responsiveness -i.e., the participants' propensity to modulate behavior as a function of reward.Results-Compared to controls, MDD subjects showed significantly reduced reward responsiveness. Trial-by-trial probability analyses revealed that MDD subjects, while responsive to delivery of single rewards, were impaired at integrating reinforcement history over time and expressing a response bias toward a more frequently rewarded cue in the absence of immediate reward. This selective impairment correlated with self-reported anhedonic symptoms, even after considering anxiety symptoms and general distress.Conclusions-These findings indicate that MDD is characterized by an impaired tendency to modulate behavior as a function of prior reinforcements, and provides initial clues about which aspects of hedonic processing might be dysfunctional in depression.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Reduced hedonic capacity in major depressive disorder: Evidence from a probabilistic reward task

Pizzagalli

Iosifescu

Hallett

et al. 2008

Journal of Psychiatric Research

653

693

View full text Add to dashboard Cite

show abstract

“…In addition, as noted above, corticosterone, which may be elevated during depressive illness, is essential for the expression of a 1B -adrenoceptors in cell culture. Moreover, an increased a 1 -adrenoceptors and epinephrine in activity and depression EA Stone et al euphoric effect of amphetamine has been found in depressed patients (Tremblay et al, 2002), while increases in the self-administration of amphetamine has been shown in an animal model of depression (Holmes et al, 2002). These changes could, of course, reflect sensitized dopaminergic receptors.…”

Section: Effects Of Stress and Depression On Epi-a 1 -Systemmentioning

confidence: 98%

Emerging Evidence for a Central Epinephrine-Innervated α1-Adrenergic System that Regulates Behavioral Activation and is Impaired in Depression

Stone

Yang

Rosengarten

et al. 2003

Neuropsychopharmacol

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Currently, most basic and clinical research on depression is focused on either central serotonergic, noradrenergic, or dopaminergic neurotransmission as affected by various etiological and predisposing factors. Recent evidence suggests that there is another system that consists of a subset of brain a 1B -adrenoceptors innervated primarily by brain epinephrine (EPI) that potentially modulates the above three monoamine systems in parallel and plays a critical role in depression. The present review covers the evidence for this system and includes findings that brain a 1 -adrenoceptors are instrumental in behavioral activation, are located near the major monoamine cell groups or target areas, receive EPI as their neurotransmitter, are impaired or inhibited in depressed patients or after stress in animal models, and are restored by a number of antidepressants. This 'EPI-a 1 system' may therefore represent a new target system for this disorder.

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“…Specifically, neurotrophic factors including cAMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) and the transcription factor delta-FosB may represent molecular mechanisms involved in long-term alterations of the brain reward system (Nestler et al, 2001(Nestler et al, , 2002. Enhanced rewarding effects of dextroamphetamine found in patients with MDD may represent hypofunction of the dopaminergic system associated with anhedonia (Tremblay et al, 2002). Preliminary evidence for the potential heritability of these findings includes a functional polymorphism of the catechol-O-methyltransferase (COMT) gene that has been associated with the individual variation in the brain response to dopaminergic challenge (Mattay et al, 2003).…”

Section: Anhedonia (Impaired Reward Function)mentioning

confidence: 99%

Discovering Endophenotypes for Major Depression

Hasler

Drevets

Manji

et al. 2004

Neuropsychopharmacol

1,023

739

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The limited success of genetic studies of major depression has raised questions concerning the definition of genetically relevant phenotypes. This paper presents strategies to improve the phenotypic definition of major depression by proposing endophenotypes at two levels: First, dissecting the depressive phenotype into key components results in narrow definitions of putative psychopathological endophenotypes: mood bias toward negative emotions, impaired reward function, impaired learning and memory, neurovegetative signs, impaired diurnal variation, impaired executive cognitive function, psychomotor change, and increased stress sensitivity. A review of the recent literature on neurobiological and genetic findings associated with these components is given. Second, the most consistent heritable biological markers of major depression are proposed as biological endophenotypes for genetic studies: REM sleep abnormalities, functional and structural brain abnormalities, dysfunctions in serotonergic, catecholaminergic, hypothalamic-pituitary-adrenocortical axis, and CRH systems, and intracellular signal transduction endophenotypes. The associations among the psychopathological and biological endophenotypes are discussed with respect to specificity, temporal stability, heritability, familiality, and clinical and biological plausibility. Finally, the case is made for the development of a new classification system in order to reduce the heterogeneity of depression representing a major impediment to elucidating the genetic and neurobiological basis of this common, severe, and often life-threatening illness.

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Probing Brain Reward System Function in Major Depressive Disorder

Abstract: The results suggest the presence of a hypersensitive response is present in the brain reward system of depressed patients, which may reflect a hypofunctional state and may provide a novel pathophysiologic and therapeutic target for future studies.

Cited by 215 publications

References 71 publications

Reduced hedonic capacity in major depressive disorder: Evidence from a probabilistic reward task

Reduced hedonic capacity in major depressive disorder: Evidence from a probabilistic reward task

Emerging Evidence for a Central Epinephrine-Innervated α1-Adrenergic System that Regulates Behavioral Activation and is Impaired in Depression

Discovering Endophenotypes for Major Depression

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