JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
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Cognitive deficits in bipolar disorders: Implications for emotion.

Prominent cognitive deficits have been documented in bipolar disorder, and multiple studies suggest that these deficits can be observed among non-affected first-degree relatives of those with bipolar disorder. Although there is variability in the degree of cognitive deficits, these deficits are robustly relevant for functional outcomes. A separate literature documents clear difficulties in emotionality, emotion regulation, and emotion-relevant impulsivity within bipolar disorder, and demonstrates that these emotion-relevant variables are also central to outcome. Although cognitive and emotion domains are typically studied independently, basic research and emergent findings in bipolar disorder suggest that there are important ties between cognitive deficits and the emotion disturbances observed in bipolar disorder. Understanding these relationships has relevance for fostering more integrative research, for clarifying relevant aspects related to functionality and vulnerability within bipolar disorder, and for the development of novel treatment interventions. Bipolar disorder (BD) is a severe psychiatric illness that has been ranked as one of the 20 leading medical causes of disability (WHO, 2011). BD has been shown to be the psychiatric disorder with the highest rates of completed suicide across two major cohort studies (Ilgen et al., 2010; Nordentoft, Mortensen, & Pedersen, 2011). In a cross-national representative sample, one in four persons diagnosed with bipolar I disorder reported a suicide attempt (Merikangas et al., 2011). Rates of relapse remain high despite available treatments (Gitlin, Swendsen, Heller, & Hammen, 1995), and in the year after hospitalization for manic episode, two-thirds of patients do not return to work (Strakowski et al., 1998). Poverty, homelessness, and incarceration are all too common (Copeland et al., 2009). Despite the often poor outcomes, there is also evidence for outstanding accomplishments and creativity among those with milder forms of the disorder and their family members (Coryell et al., 1989; Jamison, 1993; Murray & Johnson, 2010). Some individuals appear to achieve more than the general population, suggesting the importance of understanding the variables that predict differential outcome within bipolar disorder. Within this paper, we focus on two key predictors of outcomes within bipolar disorder: cognition and emotionality. We review evidence that problems in cognition and emotionality are prominent among those diagnosed with the disorder, are not artifacts of symptom state, and relate substantively to poorer outcomes. Although traditionally studied separately, new work points toward the idea that cognition and emotionality are intricately linked within bipolar disorder. Drawing from research within bipolar disorder as well as outside of bipolar disorder, we build a model of how cognition and emotionality might be tied within bipolar disorder. We then provide suggestions for future research. Before considering findings, it is worth noting that there are several forms of the disorder, defined by varying degrees and duration of manic symptoms (APA, 2013; WHO, 1993). Manic episodes are defined by abnormally elevated or irritable mood, accompanied by increased activity and at least three symptoms (four if mood is only irritable) such as decreased need for sleep, increased self-confidence, racing thoughts or flight of ideas, rapid speech, distractibility, goal-directed activity, and engagement in pleasurable activities without regard to potential negative consequences. To meet criteria for mania, these symptoms must persist for at least one week or require hospitalization, and must lead to difficulties with functioning. If functional impairment is not more than mild and duration is between 4 and 6 days, the episode is considered a hypomanic episode. Bipolar I disorder (BD I) is diagnosed on the basis of at least one lifetime manic episode within the DSM-5 and by at least two episodes within the ICD, whereas bipolar II disorder is diagnosed on the basis of at least one hypomanic episode (and no manic episodes) as well as major depressive episodes. Cyclothymic disorder is defined by chronic but milder fluctuations between manic and depressive symptoms. Most research focuses on BD I. In addition to diagnosed samples, research has focused on those at high risk for bipolar disorder, including first-degree relatives of those with BD. This work draws on the evidence for extremely high heritability of BD I, with estimates from community-based twin studies of 0.85 (Kieseppä, Partonen, Haukka, Kaprio, & Lönnqvist, 2014). Other research has considered high risk for BD by virtue of lifetime subsyndromal symptoms, as measured by scales such as the Hypomanic Personality Scale (Eckblad & Chapman, 1986) or the General Behavior Inventory (Depue, Krauss, Spoont, & Arbisi, 1989). The study of high-risk individuals provides a way to decipher whether deficits are present before the onset of the disorder, of importance given models suggesting that episodes of the disorder may change brain function (Chang, Steiner, & Ketter, 2000; Strakowski, 2012) as well as individuals' perceptions of their emotion regulation. Beyond defining BD, it is worth defining some of the many different neuropsychological tasks that have been widely studied in BD. Perhaps no area has received more attention than executive function. Executive function is related to three core functions: 1) inhibition, the ability to suppress irrelevant information in working memory in order to accomplish an established goal; 2) working memory, the ability to hold and manipulate information in mind; and 3) cognitive flexibility, the ability to shift strategies in response to feedback (Diamond, 2013; Miyake et al., 2000). Attention (defined as the process of selecting information reception from internal or external cues) is implicated in all three of these aspects of executive function. Much of the literature we will discuss focuses on response inhibition, or the ability to suppress a prepotent response, which is considered a subtype of inhibition. Some tests measure multiple facets of executive function; for example the Trails B test likely requires working memory and cognitive flexibility (Sánchez-Cubillo et al., 2009). Aside from executive function, multiple other facets of cognition have been widely studied in bipolar disorder. Verbal and non-verbal memory are related to the ability to register, store and retrieve verbal or visual information (Lezak, 1995). Verbal fluency is measured as the number of verbal responses a person can generate to a given target, such as a specific semantic category (e.g., animals, furniture) or phonetic category (e.g., words that begin with letter F) (Diamond, 2013). Although cognitive tasks have been designed to evaluate these specific functions, it is important to note that most measures are highly inter-correlated and may assess multiple overlapping functions to some extent (for example, the Trails B test is often described as an "executive function" task, although this task likely involves both working memory and cognitive flexibility. Not surprisingly, then, some authors label the function of certain tests differently, and this is particularly evident in meta-analyses of cognition. As we describe findings in this paper, we will use the terms proposed by the authors but will also identify key tests used to define a cognitive construct. With this background in mind, we turn to a discussion of cognitive deficits, then of emotion-related traits. Our hope is that those concise summaries provide evidence for the importance of both domains, but also specificity regarding the facets of emotion and cognition that are most impaired in BD. This specificity then guides our consideration of models that integrate cognition and emotion.

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