Kelly A. Ryan

Differential executive functioning performance by phase of bipolar disorder

Ryan KA, Vederman AC, McFadden EM, Weldon AL, Kamali M, Langenecker SA, McInnis MG. Differential executive functioning performance by phase of bipolar disorder. Bipolar Disord 2012: 14: 527–536.

Increased Coupling of Intrinsic Networks in Remitted Depressed Youth Predicts Rumination and Cognitive Control

Objective Functional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD. Method fcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18–23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain. Results Compared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely. Conclusions Findings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.

Reliability of Repeated Cognitive Assessment of Dementia Using a Brief Computerized Battery

Objective: The aim of this study was to evaluate the short-term stability and reliability of a brief computerized cognitive battery in established dementia types. Method: Patients were administered the computerized battery twice with administrations approximately 2 hours apart, with intervening conventional neuropsychological tests. Patients were classified clinically, via consensus conference, as healthy controls (n = 23), mild cognitive impairment (n = 20), Alzheimer’s disease (n = 52), dementia with Lewy Bodies ([DLB], n = 10), or frontotemporal dementia (n = 9). Results: Minimal practice effects were evident across Cog-State test administrations. Small magnitude improvements were seen across all groups on a working memory task, and healthy controls showed a mild practice effect on the accuracy of associative learning. Conclusions: In established dementia, administration of the CogState tasks appears sensitive to cognitive impairment in dementia. Repeat administration also provided acceptable stability and test-retest reliability with minimal practice effects at short test-retest intervals despite intervening cognitive challenges.

Validity of a Brief Computerized Cognitive Screening Test in Dementia

Background: While preliminary evidence supports the criterion validity of the CogState computerized brief battery in mild cognitive impairment (MCI) and Alzheimer disease (AD), definitive validation studies examining a wider range of dementia-related disorders relative to conventional neuropsychological techniques are necessary. Methods: Participants satisfying clinical consensus criteria for dementia (AD, n = 37; frontotemporal dementia, n = 7; and dementia with Lewy bodies, n = 5), MCI (n = 16), and the healthy controls (n = 22) were administered a battery of brief neuropsychological and select computerized (CogState) cognitive tests. The battery, administered through the University of Michigan Alzheimer’s Disease Research Center, included measures of processing speed, attention, working memory, and learning. Results: CogState and standard neuropsychological task scores were significantly lower for dementia participants than that of the nondementia groups (P < .05), with a single CogState test distinguishing control from MCI participants, but minimal differentiation existing between dementias using the CogState. Correlations were modest between conventional and computerized test scores, covering matching domains and mostly reflecting the multidimensional nature of cognitive paradigms. Conclusions: Results support the clinical validity of this brief computerized screening battery when used in established dementias, but not to differentiate between various dementias, and suggest that the select CogState battery’s effectiveness in identifying MCI from controls was not as strong as identifying specific dementias.

Gender differences, clinical correlates, and longitudinal outcome of bipolar disorder with comorbid migraine.

OBJECTIVE Migraine is a common comorbidity of bipolar disorder and is more prevalent in women than men. We hypothesized comorbid migraine would be associated with features of illness and psychosocial risk factors that would differ by gender and impact outcome. METHOD A retrospective analysis was conducted to assess association between self-reported, physician-diagnosed migraine, clinical variables of interest, and mood outcome in subjects with DSM-IV bipolar disorder (N = 412) and healthy controls (N = 157) from the Prechter Longitudinal Study of Bipolar Disorder, 2005-2010. Informed consent was obtained from all participants. RESULTS Migraine was more common in subjects with bipolar disorder (31%) than in healthy controls (6%) and had elevated risk in bipolar disorder women compared to men (OR = 3.5; 95% CI, 2.1-5.8). In men, migraine was associated with bipolar II disorder (OR = 9.9; 95% CI, 2.3-41.9) and mixed symptoms (OR = 3.5; 95% CI, 1.0-11.9). In comparison to absence of migraine, presence of migraine was associated with an earlier age at onset of bipolar disorder by 2 years, more severe depression (β = .13, P = .03), and more frequent depression longitudinally (β = .13, P = .03). Migraine was correlated with childhood emotional abuse (P = .01), sexual abuse (P = 4 × 10⁻³), emotional neglect (P = .01), and high neuroticism (P = 2 × 10⁻³). Protective factors included high extraversion (P = .02) and high family adaptability at the trend level (P = .08). CONCLUSIONS Migraine is a common comorbidity with bipolar disorder and may impact long-term outcome of bipolar disorder, particularly depression. Clinicians should be alert for migraine comorbidity in women and in men with bipolar II disorder. Effective treatment of migraine may impact mood outcome in bipolar disorder as well as headache outcome. Joint pathophysiologic mechanisms between migraine and bipolar disorder may be important pathways for future study of treatments for both disorders.

The double burden of age and disease on cognition and quality of life in bipolar disorder

Bipolar disorder (BPD) and normal aging are known to impact cognitive skills and health‐related quality of life (HRQOL). This study investigated how aging and disease interact in predicting cognitive and psychosocial outcomes.

Neuropsychiatric Symptoms and Executive Functioning in Patients with Mild Cognitive Impairment: Relationship to Caregiver Burden

Background: Caregivers of patients with mild cognitive impairment (MCI) need similar levels of support services as Alzheimer’s disease (AD) caregivers, but it is unclear if this translates to increased caregiver burden. Methods: 135 participants and their caregivers (40 MCI, 55 AD and 40 normal controls, NC) completed questionnaires, and the patients were administered neuropsychological tests. Results: The MCI caregivers reported significantly more overall caregiving burden than the NC, but less than the AD. They showed similar levels of emotional, physical and social burden as the AD caregivers. Among the MCI caregivers, the neuropsychiatric symptoms and executive functioning of the patients were related to a greater burden, and the caregivers with a greater burden reported lower life satisfaction and social support, and a greater need for support services. Conclusion: These results indicate that MCI caregivers are at increased risk for caregiver stress, and they require enhanced assistance and/or education in caring for their loved ones.

Greater executive and visual memory dysfunction in comorbid bipolar disorder and substance use disorder

Measures of cognitive dysfunction in Bipolar Disorder (BD) have identified state and trait dependent metrics. An influence of substance abuse (SUD) on BD has been suggested. This study investigates potential differential, additive, or interactive cognitive dysfunction in bipolar patients with or without a history of SUD. Two hundred fifty-six individuals with BD, 98 without SUD and 158 with SUD, and 97 Healthy Controls (HC) completed diagnostic interviews, neuropsychological testing, and symptom severity scales. The BD groups exhibited poorer performance than the HC group on most cognitive factors. The BD with SUD exhibited significantly poorer performance than BD without SUD in visual memory and conceptual reasoning/set-shifting. In addition, a significant interaction effect between substance use and depressive symptoms was found for auditory memory and emotion processing. BD patients with a history of SUD demonstrated worse visual memory and conceptual reasoning skills above and beyond the dysfunction observed in these domains among individuals with BD without SUD, suggesting greater impact on integrative, gestalt-driven processing domains. 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.

Decoupling of the amygdala to other salience network regions in adolescent-onset recurrent major depressive disorder

BACKGROUND Recent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes. METHOD Resting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted. RESULTS Young adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN. CONCLUSIONS This is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.

Sleep quality during euthymia in bipolar disorder: the role of clinical features, personality traits, and stressful life events

BackgroundPoor sleep quality is known to precede the onset of mood episodes and to be associated with poor treatment outcomes in bipolar disorder (BD). We sought to identify modifiable factors that correlate with poor sleep quality in BD independent of residual mood symptoms.MethodsA retrospective analysis was conducted to assess the association between the Pittsburgh Sleep Quality Index and clinical variables of interest in euthymic patients with DSM-IV BD (n = 119) and healthy controls (HC; n = 136) participating in the Prechter Longitudinal Study of Bipolar Disorder. Multivariable linear regression models were constructed to investigate the relationship between sleep quality and demographic and clinical variables in BD and HC participants. A unified model determined independent predictors of sleep quality.Results and discussionEuthymic participants with BD and HC differed in all domains. The best fitting unified multivariable model of poor sleep quality in euthymic participants with BD included rapid cycling (β = .20, p = .03), neuroticism (β = .28, p = 2 × 10−3), and stressful life events (β = .20, p = .02). Poor sleep quality often persists during euthymia and can be a target for treatment. Clinicians should remain vigilant for treating subjective sleep complaints independent of residual mood symptoms in those sensitive to poor sleep quality, including individuals with high neuroticism, rapid cycling, and recent stressful life events. Modifiable factors associated with sleep quality should be targeted directly with psychosocial or somatic treatment. Sleep quality may be a useful outcome measure in BD treatment studies.