Sarah H. Sperry

Measuring Cognition in Bipolar Disorder with Psychosis Using the MATRICS Consensus Cognitive Battery

Given the substantial overlap in cognitive dysfunction between bipolar disorder (BD) and schizophrenia (SZ), we examined the utility of the MATRICS Consensus Cognitive Battery (MCCB)-developed for use in SZ-for the measurement of cognition in patients with BD with psychosis (BDP) and its association with community functioning. The MCCB, Multnomah Community Ability Scale, and measures of clinical symptoms were administered to participants with BDP (n=56), SZ (n=37), and healthy controls (HC) (n=57). Groups were compared on clinical and cognitive measures; linear regressions examined associations between MCCB and community functioning. BDP and SZ groups performed significantly worse than HC on most neurocognitive domains; BDP and HC did not differ on Social Cognition. Patients with BDP performed better than patients with SZ on most cognitive measures, although groups only differed on social cognition, working memory, verbal memory, and the composite after controlling for clinical variables. MCCB was not associated with community functioning. The MCCB is an appropriate measure of neurocognition in BDP but does not appear to capture social cognitive deficits in this population. The addition of appropriate social cognitive measures is recommended.

Myelin vs Axon Abnormalities in White Matter in Bipolar Disorder

White matter (WM) abnormalities are among the most commonly reported neuroimaging findings in bipolar disorder. Nonetheless, the specific nature and pathophysiology of these abnormalities remain unclear. Use of a combination of magnetization transfer ratio (MTR) and diffusion tensor spectroscopy (DTS) permits examination of myelin and axon abnormalities separately. We aimed to examine myelination and axon geometry in euthymic patients with bipolar disorder with psychosis (BDP) by combining these two complementary noninvasive MRI techniques. We applied a combined MRI approach using MTR to study myelin content and DTS to study metabolite (N-acetylaspartate, NAA) diffusion within axons in patients with BDP (n=21) and healthy controls (n=24). Data were collected from a 1 × 3 × 3-cm voxel within the right prefrontal cortex WM at 4 Tesla. Clinical and cognitive data were examined in association with MTR and DTS data. MTR was significantly reduced in BDP, suggesting reduced myelin content. The apparent diffusion coefficient of NAA did not differ from healthy controls, suggesting no changes in axon geometry in patients with BDP. These findings suggest that patients with BDP exhibit reduced myelin content, but no changes in axon geometry compared with controls. These findings are in contrast with our recent findings, using the same techniques, in patients with schizophrenia (SZ), which suggest both myelination and axon abnormalities in SZ. This difference may indicate that alterations in WM in BDP may have unique causes and may be less extensive than WM abnormalities seen in SZ.

Treatment to Enhance Cognition in Bipolar Disorder (TREC-BD): Efficacy of a Randomized Controlled Trial of Cognitive Remediation Versus Active Control

OBJECTIVE Cognitive dysfunction is a core symptom dimension in bipolar disorder and a strong predictor of functional outcomes. Cognitive remediation (CR) produces moderate, durable effects on cognition in patients with schizophrenia; however, studies of CR in patients with bipolar disorder are sparse and findings have been mixed. Thus, the aim of this study was to evaluate the effects of CR versus active control in patients with bipolar disorder with psychosis. METHODS Patients with a DSM-IV diagnosis of bipolar disorder with psychosis (n = 75) were randomized to a 70-hour computerized CR program or a dose-matched computer control using a parallel design with 1:1 allocation between July 2011 and November 2015. Cognition (primary outcome) and clinical and community functioning (secondary outcomes) were assessed at baseline, at treatment midpoint (after 20-25 hours of training), posttreatment, and at durability (after 6 months of no study contact). Participants and assessment staff were blind to group membership. RESULTS 75 participants were randomly assigned to a treatment group, and 72 participants initiated the active phase of treatment and were included in the primary, intent-to-treat analysis (CR: n = 39; Control: n = 33). Linear mixed effects models examining the effects of CR versus Control at posttreatment showed medium to large effects of CR on processing speed (d = 0.42), visual learning and memory (d = 0.92), and the composite (d = 0.80). Superiority of CR over Control on processing speed (d = 0.65) and composite (d = 0.83) was maintained or increased at durability. CR was not associated with change in community functioning, although cognitive change was associated with functional change across the sample. CONCLUSIONS Cognitive remediation produced significant improvements over an active control in several cognitive domains and the cognitive composite. While both groups improved on several domains relative to baseline, durability of gains was unique to CR. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01470781.

What can daily life assessment tell us about the bipolar spectrum

Evidence suggests that bipolar psychopathology is better characterized as a spectrum than by categorical diagnoses. The examination of symptoms and impairment associated with bipolar spectrum psychopathology is important and can be enhanced by methods that examine affect, thoughts, and behavior in daily life. The present study extended findings that provide validation of a continuum of bipolar psychopathology in daily life. Young adults (n=294) completed the Hypomanic Personality Scale (HPS) and experience sampling using smartphones. Participants were signaled eight times daily for one week to complete surveys in their normal daily environment. Bipolar spectrum psychopathology was characterized by increased positive and negative affect, confidence, racing thoughts, energy, and impulsivity in daily life. The HPS moderated the association of stress with trouble concentrating, irritability with dysphoria and impulsivity, and confidence with feeling like ones emotions were out of control. This study demonstrated that bipolar spectrum psychopathology is associated with disruptions in affect, thoughts, and behaviors and provided further evidence for a continuum of bipolar psychopathology. ESM is a promising method for examining dynamic constructs such as bipolar spectrum psychopathology and has the potential to be a strong research and clinical tool.

The convergence and divergence of impulsivity facets in daily life

OBJECTIVE Impulsivity appears to be best conceptualized as a multidimensional construct. For example, the UPPS-P model posits that there are five underlying facets of impulsivity. The present study examined the expression of the UPPS-P facets in daily life using experience sampling methodology. A specific goal of the study was to examine positive urgency, a facet added to the original UPPS model, and its convergence and divergence from the negative urgency facet. METHOD A large nonclinical sample of young adults (n = 294) completed the UPPS-P scale and was signaled to complete questionnaires assessing daily affect, cognitions, sense of self, and impulsive behaviors eight times a day for 7 days. RESULTS Results indicated that the UPPS-P facets are associated with disruptions in affect, cognitions, and behavior in daily life. Furthermore, all of the UPPS-P facets were associated with impulsivity in daily life. Contrary to expectation, positive urgency was associated with negative affect rather than positive affect and had a profile indistinguishable from negative urgency. CONCLUSIONS These results generally support a four-factor model of multidimensional impulsivity with a general overall urgency factor instead of separate positive and negative urgency facets.

Psychopathology, everyday behaviors, and autonomic activity in daily life: An ambulatory impedance cardiography study of depression, anxiety, and hypomanic traits

Discrepancies regarding the link between autonomic nervous system (ANS) activity and psychopathology may be due in part to inconsistent measurement of non-psychological factors, including eating, drinking, activity, posture, and interacting with others. Rather than sources of noise, behaviors like being active and being with others may be the behavioral pathways that connect psychopathology symptoms to autonomic activity. The present study examined whether behaviors mediate the association of depression, anxiety, and hypomanic traits with ANS by using experience sampling methodology and ambulatory impedance cardiography. Participants (n = 49) completed measures of affect and one day of experience sampling and ambulatory impedance cardiography. The association of hypomanic traits with heart rate variability and heart rate was mediated by physical activity, and social activity mediated the association of depressive symptoms and respiration. These results highlight the importance of considering the pathways between psychopathology and ANS and the mediating role that everyday behaviors play.