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

Behav Res Ther. 2014 Nov;62:74-87. doi: 10.1016/j.brat.2014.08.011. Epub 2014 Sep 1.


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.

Keywords: Assessment; Bipolar disorder; Depression; Fronto-striatal neural circuitry; Reward; Treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers
  • Bipolar Disorder / diagnosis*
  • Bipolar Disorder / physiopathology*
  • Bipolar Disorder / psychology
  • Bipolar Disorder / therapy
  • Brain / physiopathology*
  • Humans
  • Motivation
  • Reward


  • Biomarkers