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Bipolar disorder (BD) is a chronic mood disorder that is characterized by emotional dysregulation. Bipolar disorder has a higher rate of comorbidity with substance use disorders (SUD) than any other Axis I disorder and marijuana tends to be the most abused illicit drug in this population. There is evidence that SUDs are often associated with negative effects on BD treatment outcomes. Cognitive deficits are also more severe in patients who have BD and comorbid SUDs than in those with BD alone. The present study was designed to better understand the neural mechanisms associated with marijuana use in BD and the cognitive and behavioral effects of marijuana use in individuals with BD. We compared four groups of adolescents: adolescents with bipolar disorder with comorbid marijuana use (BPMJ); adolescents with bipolar disorder without comorbid marijuana use (BP); adolescents with marijuana use disorder without a comorbid mood or psychotic disorder (MJ); healthy adolescents (HA). The four groups were compared on tests of brain activation in response to a cue-reactivity task, self-reported craving and performance on a recognition memory task in order to parse the cognitive effects of bipolar disorder and the alteration in cognitive performance related to the effects of craving. We examined fMRI measures of brain activation and self-reported craving in response to a marijuana-specific cue-reactivity task in these four groups. We predicted individuals in the marijuana using groups would exhibit increased self-reported craving and increased activation in specific regions of interest in response to marijuana pictures in brain regions associated with drug craving when compared to the non-marijuana using groups. We also hypothesized that increased craving would increase recognition of marijuana-related images on a recognition task. The primary finding was that recognition memory for total combined stimuli and neutral stimuli was reduced in groups with bipolar disorder. The hypothesis that the MJ and BPMJ groups would display enhanced recognition of marijuana images on the recognition memory test was not supported, nor did these groups demonstrate evidence of a change in craving on either the self-report measure (MCQ) or on fMRI activation in the majority of the identified regions of interest. The only significant group difference that was identified in brain activation was in the right anterior cingulate cortex, with the BPMJ group showing greater activation in response to marijuana images. These findings are in direct contrast to several studies that have found significant groups differences in activation in these regions between craving and non-craving individuals in response to drug-related cues and stimuli. It is a core problem for the present study that the cue-reactivity task did not result in increased craving as measured by the MCQ or by most of the imaging measures. The exact reason for this lack of group differences in craving and brain activation is not fully known. However, it was evident that the cue-reactivity task used in this study did not effectively elicit craving in healthy and bipolar marijuana users. Future studies may focus on developing a standardized cue-reactivity task that reliably induces craving in marijuana users. |
