Elsevier

Behaviour Research and Therapy

Volume 62, November 2014, Pages 74-87
Behaviour Research and Therapy

Elevated reward-related neural activation as a unique biological marker of bipolar disorder: Assessment and treatment implications

https://doi.org/10.1016/j.brat.2014.08.011Get rights and content

Highlights

  • We review research on reward-related neural activation in bipolar disorder.

  • We suggest reward-related neural activation is a biological marker of bipolar.

  • We discuss challenges to using neuroscience techniques in assessment and diagnosis.

  • We discuss treatment implications of reward-related neural activation in bipolar.

Abstract

Growing evidence indicates that risk for bipolar disorder is characterized by elevated activation in a fronto-striatal reward neural circuit involving the ventral striatum and orbitofrontal cortex, among other regions. It is proposed that individuals with abnormally elevated reward-related neural activation are at risk for experiencing an excessive increase in approach-related motivation during life events involving rewards or goal striving and attainment. In the extreme, this increase in motivation is reflected in hypomanic/manic symptoms. By contrast, unipolar depression (without a history of hypomania/mania) is characterized by decreased reward responsivity and decreased reward-related neural activation. Collectively, this suggests that risk for bipolar disorder and unipolar depression are characterized by distinct and opposite profiles of reward processing and reward-related neural activation. The objective of the present paper is threefold. First, we review the literature on reward processing and reward-related neural activation in bipolar disorder, and in particular risk for hypomania/mania. Second, we propose that reward-related neural activation reflects a biological marker of differential risk for bipolar disorder versus unipolar depression that may help facilitate psychiatric assessment and differential diagnosis. We also discuss, however, the challenges to using neuroscience techniques and biological markers in a clinical setting for assessment and diagnostic purposes. Lastly, we address the pharmacological and psychosocial treatment implications of research on reward-related neural activation in bipolar disorder.

Section snippets

Behavioral approach system (BAS)/Reward hypersensitivity model of bipolar disorder

The BAS/reward hypersensitivity model of bipolar disorder argues that abnormalities in reward processing and approach-related affect play an important role in the pathophysiology of bipolar disorder, and in particular hypomanic/manic symptoms (Alloy and Abramson, 2010, Johnson, 2005, Johnson, Edge, et al., 2012, Urosevic et al., 2008). Reward processing relates to the value an individual places on potential rewards, the perceived probability of reward receipt, and the mechanisms by which an

Neurophysiological indices of reward hypersensitivity in bipolar disorder

Research has recently begun examining the neurophysiological and neurobiological basis of reward hypersensitivity in bipolar disorder. With respect to neurophysiology, much of this work has focused on relative left versus right frontal electroencephalographic (EEG) activity. Close to thirty years of research suggests that relative left frontal EEG activity may reflect a neurophysiological index of approach system sensitivity and reward-related affect (see Coan & Allen, 2004 for review).

The fronto-striatal reward-neural circuit

Although many regions in the brain respond to reward, the fronto-striatal neural circuit is at the heart of the reward system (Berridge et al., 2009, Haber and Knutson, 2010, Kringelbach and Berridge, 2009, Schultz, 2000, Schultz et al., 2000). This circuit involves dopaminergic projections from midbrain nuclei (e.g., the ventral tegmental area), to subcortical regions that are central to processing the rewarding properties of stimuli (e.g., the ventral striatum, including the nucleus

Fronto-striatal indices of reward hypersensitivity in bipolar disorder

Structural and functional neuroimaging studies implicate the fronto-striatal neural circuit in the pathophysiology of bipolar disorder. Structural imaging studies report abnormalities in prefrontal volume (Lopez-Larson, DelBello, Zimmerman, Schwiers, & Strakowski, 2002) and increased striatal size (Strakowski et al., 2002) in individuals with bipolar disorder. Gray matter deficits in the striatum and the ACC are also present in individuals at genetic risk for bipolar disorder, but who have not

Assessment implications of reward-related neural activation in bipolar disorder

In the beginning of the present paper we highlighted the fact that close to 70% of individuals with bipolar disorder were initially misdiagnosed (Hirschfeld et al., 2003) and that it can take 6–10 years or longer for an individual with bipolar disorder to receive an accurate diagnosis and treatment (Ghaemi et al., 1999, Ghaemi et al., 2000). Certain researchers have argued that biological markers could be used to compliment self-report based diagnostic strategies to facilitate accurate

Treatment implications of reward-related neural activation in bipolar disorder

Research on reward-related neural activation in bipolar disorder has important pharmacological and psychosocial treatment implications. With respect to pharmacology, dopamine neurotransmission is at the heart of the fronto-striatal reward circuit (Haber and Knutson, 2010, Schultz, 2002, Wise, 2002), as summarized above. Critically, there is converging data highlighting the central role of dopamine in bipolar disorder, and pharmacological models suggest a role of increased dopaminergic drive in

Concluding remarks

A considerable challenge in the management and treatment of bipolar disorder is the fact that it can take upwards of ten years for an individual with bipolar disorder to receive an accurate diagnosis (Ghaemi et al., 1999, Ghaemi et al., 2000), and over 60% of bipolar individuals report being initially misdiagnosed as having unipolar depression (Hirschfeld et al., 2003). Certain researchers have argued that biological markers could be used to compliment self-report based diagnostic strategies to

Conflict of interest

The authors report no conflict of interest in the reporting of this research.

Acknowledgments

Robin Nusslock's contribution to this work was supported by National Institute of Mental Health (NIMH) grant R01 MH100117-01 and R01 MH077908-01A1, as well as a Young Investigator Grant from the Ryan Licht Sang Bipolar Foundation and the Chauncey and Marion D. McCormick Family Foundation. Christina Young's contribution to this work was supported by a National Science Foundation (NSF) Graduate Research Fellowship.

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