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

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.

Reward Processing in Unipolar and Bipolar Depression: A Functional MRI Study

“…Given the differences between our paradigm and that of Chase et al (2013), the findings are not necessarily conflicting. However, in light of recent findings that indicate state-independent elevated striatal activity (Nusslock et al, 2014), but other researchers reporting results in the opposite direction (Trost et al, 2014), it seems to be important to separate the investigation of reward anticipation and reward outcome processing to gain a clearer picture in future studies.…”

“…Studies in BD reported more heterogeneous results, probably because of a higher variation of mood states. A recent review by Nusslock et al (2014) suggested increased NAcc responsiveness across all mood states in BD. However, not all available data support this notion.…”

Biomarkers for bipolar disorder: current insights

“…41 Excessive activation of this neural circuit has been implicated in BD. 42 Using fMRI, one study reported elevated activation of the left lateral orbital frontal cortex (OFC; BA11/47) in patients with BD assessed during the manic …”

“…43 Increased OFC and ventral striatal responses during reward anticipation were also found in a subset of euthymic patients compared with non-psychiatric controls, suggesting that reward activation is not state-dependent. 42 Increased left frontal cortical activity is supported by electroencephalographic (EEG) assessment -a neurophysiological index of reward sensitivity -in individuals susceptible to bipolar spectrum diagnosis. 44 Another neurophysiological index is event-related potential (ERP), which is used to examine neuronal responses to feedback (feedback-related negativity [FRN]).…”

“…5 Although dysfunction of the reward system is thought to play an important role in both unipolar depression and BD, it can be used for differential diagnosis and assessment. 42,46 EEG and ERP studies have identified diminished left frontal cortical activity 47 and decreased FRN in patients with unipolar depression, 48 suggesting deficits in reward processing and responses. Similarly, diminished activity of the frontostriatal neural circuitry was also seen in other psychiatric illnesses, such as schizophrenia.…”