Our results confirm that significant impairment in cognitive functioning exists in Bipolar Disorder, as both BD groups demonstrated poorer performance than the HC group on most cognitive factors, including psychomotor speed and dexterity, visual memory, verbal fluency and processing speed, conceptual reasoning and set-shifting, processing speed with interference resolution, and inhibitory control. These results extend our previous work with the initial sample of individuals recruited by capturing the poorer performance in the domain of inhibitory control (Langenecker et al., 2010
In support of our hypothesis, BD patients with a lifetime history of comorbid SUD showed significantly worse visual memory and conceptual reasoning above and beyond the dysfunction observed in these factors in BD without SUD. This finding suggests that SUD has diffuse impact on integrated gestalt oriented functions more so then specific cognitive domains. Our results remained as stated even after evaluating the additional influence of current depressive symptoms, suggesting that it may be a more stable feature of comorbidity. Our results suggest that such deficits cannot be entirely explained by state factors such as depression, which is consistent with previous research showing that SUD is associated with significant neuropsychological deficits even after prolonged abstinence (Adams et al., 1980
; Grant et al., 1984
; Parsons, 1998
), including impaired function of cerebral tissue in the medial frontal region (Adams et al., 1993
). Similarly, Robinson and Kolb (2004)
reported that exposure to amphetamine, cocaine, nicotine, or morphine produces perpetual changes in the structure of dendrites and dendritic spines on cells in brain regions involved in incentive motivation and reward, as well as judgment and inhibitory control even after discontinued use of the drug; thus, suggesting that drugs of abuse create a persistent reorganization of patterns of synaptic connectivity in these brain regions.
There was also an interaction between a history of substance use and current significant depressive symptoms on auditory memory and emotion processing. Individuals with current significant depressive symptoms in the context of lifetime history of SUD had poorer auditory memory and emotion processing than did individuals with either depression or SUD alone. This finding suggests that SUD may potentiate the impact of depression during the active phase of illness in BD while weakening cognitive reserve in the key areas responsible for auditory memory and emotion processing. These state effects are consistent with prior research by our group and others and help to further disambiguate the impact of state and trait features of mood disorders (Langenecker et al., 2005
, Langenecker et al., 2007
, Considine et al., 2011
There were also clinical and demographic features of the comorbid BD and SUD group that are noteworthy. Individuals with BD and SUD had an earlier age of onset of illness, earlier age at first depressive episode, and also had more self-reported manic episodes. These findings suggest that individuals with BD with a history of comorbid SUD have a more chronic and severe course of illness, which is consistent with previous research showing that a history of SUD is predictive of a poorer future course of Bipolar Disorder (Gaudiano et al., 2008
; Jaworski et al., 2011
). Moreover, it was found that nearly half of our BD with SUD sample (47.5%) had a history of abusing multiple substances, which is consistent with previous studies (Goldberg et al., 1999
), while also lending support to the notion that those BD with SUD exhibit greater risk-taking behaviors (e.g., abusing multiple substances). In addition, these findings raise some degree of doubt as to the genesis of comorbidity-related, and greater, difficulties in visual memory and conceptual reasoning/set-shifting. Without a longitudinal study, we cannot comment on the relative influence of genetic factors, illness severity, substance abuse, and/or manic episodes in relation to greater memory and executive dysfunction. Earlier treatments directed towards those with recent onset of illness, in a longitudinal design could help clarify the origin, either unique or combined, of these specific areas of cognitive weaknesses.
The current study has several strengths and limitations. A major strength is the large, well-powered sample size of the carefully characterized patient group. Our sample is considerably larger than any that has previously been examined in related investigations and lends support to the generalizability of our findings. Although we observed demographic differences (e.g., education and gender) between the BD groups in the course of this naturalistic, observational study, when we statistically examined the impact of each of these potential confounds, their impact on results were not significant. Moreover, the groups did not differ in a crystalized, “hold” measure of cognitive ability (i.e., Wechsler Vocabulary score). As such, the educational attainment differences may have been influenced by the early course of illness, as opposed to innate cognitive abilities at the time of schooling. However, demographic differences cannot be definitively excluded from explanatory consideration via the methods we have employed (Adams et al., 1985
; Lord, 1967
). An additional limitation of the current study is our inability to fully rule-out the impact of medication on cognitive functioning within our sample. However, no differences were detected between the two BD groups in medication load, suggesting that any differences in cognitive functioning are not likely attributable to medication side-effects. Another important limitation of the study is the cross-sectional design, which prevents examination of intra-individual differences in cognitive functioning over time. To address limitations of the current study, future research might address longitudinal outcome as a function of BD, SUD, and combined BD/SUD to evaluate neural systems involved in risk for and effects of these illnesses. Such methodology would also allow for more thorough examination of the risks and effects comprised by both cognitive and affective factors. We were unable to investigate the effects of specific substances within our current sample, given that nearly half were abusing multiple substances. However, from the foundation of this well-powered study of bipolar disorder and SUD, in general, future research might address the impact of specific substances. Legality, class of drugs (e.g., stimulant, depressant), length of abuse/dependence, and duration of recovery from SUD are all clinical factors that may impact cognitive and affective sequelae and therefore warrant further investigation.
Overall, our findings support the presence of persistent cognitive dysfunction, especially within integrated brain networks, as well as a more chronic course in euthymic BD with a history of SUD. With regard to clinical practice, our results highlight the need of additional screening and monitoring of individuals who are at risk of abusing substances, as early identification could provide additional interventions and resources which might mitigate the long term cognitive effects of these conditions.