Shared dimensions of performance and activation dysfunction in cognitive control in females with mood disorders.

Major depressive disorder and bipolar disorder share symptoms that may reflect core mood disorder features. This has led to the pursuit of intermediate phenotypes and a dimensional approach to understand neurobiological disruptions in mood disorders. Executive dysfunction, including cognitive control, may represent a promising intermediate phenotype across major depressive disorder and bipolar disorder. This study examined dimensions of cognitive control in women with major depressive disorder or bipolar disorder in comparison to healthy control subjects using two separate, consecutive experiments. For Experiment 1, participants completed a behavioural cognitive control task (healthy controls = 150, major depressive disorder = 260, bipolar disorder = 202; age range 17-84 years). A sample of those participants (healthy controls = 17, major depressive disorder = 19, and bipolar disorder = 16) completed a similar cognitive control task in an event-related design functional magnetic resonance imaging protocol for Experiment 2. Results for Experiment 1 showed greater impairments on the cognitive control task in patients with mood disorders relative to healthy controls (P < 0.001), with more of those in the mood disorder group falling into the 'impaired' range when using clinical cut-offs (<5th percentile). Experiment 2 revealed only a few areas of shared activation differences in mood disorder greater than healthy controls. Activation analyses using performance as a regressor, irrespective of diagnosis, revealed within and extra-network areas that were more active in poor performers. In summary, performance and activation during cognitive control tasks may represent an intermediate phenotype for mood disorders. However, cognitive control dysfunction is not uniform across women with mood disorders, and activation is linked to performance more so than disease. These findings support subtype and dimensional approaches to understanding risk and expression of mood disorders and are a promising area of inquiry, in line with the Research Domain Criteria initiative of NIMH.

Stress Response to the Functional Magnetic Resonance Imaging Environment in Healthy Adults Relates to the Degree of Limbic Reactivity during Emotion Processing.

BACKGROUND: Imaging techniques are increasingly being used to examine the neural correlates of stress and emotion processing; however, relations between the primary stress hormone cortisol, the functional magnetic resonance imaging (fMRI) environment, and individual differences in response to emotional challenges are not yet well studied. The present study investigated whether cortisol activity prior to, and during, an fMRI scan may be related to neural processing of emotional information. METHODS: Twenty-six healthy individuals (10 female) completed a facial emotion perception test during 3-tesla fMRI. RESULTS: Prescan cortisol was significantly correlated with enhanced amygdala, hippocampal, and subgenual cingulate reactivity for facial recognition. Cortisol change from pre- to postscanning predicted a greater activation in the precuneus for both fearful and angry faces. A negative relationship between overall face accuracy and activation in limbic regions was observed. CONCLUSION: Individual differences in response to the fMRI environment might lead to a greater heterogeneity of brain activation in control samples, decreasing the power to detect differences between clinical and comparison groups. © 2015 S. Karger AG, Basel.

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

OBJECTIVE: 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. METHODS: Eight cognitive and ten subjective HRQOL domain ratings were measured. Subjects included 80 young (18-29 years) and late middle-aged (50-65 years) BPD patients in the euthymic phase and 70 age-equivalent healthy comparison participants. RESULTS: An age X disease interaction was detected in three domains of cognitive functioning that reflect emotion processing, processing speed, and executive functioning skills, with BPD patients in the older group performing most poorly. There was a double burden of aging and disease on reported ability to perform physical tasks. However, regardless of age, disease status was associated with lower ratings of HRQOL in the psychosocial/affective sphere and the majority of cognitive domains. Post hoc analyses revealed that number of years ill was positively associated with select HRQOL ratings in older, but not younger BPD adults. CONCLUSIONS: These findings may stimulate future longitudinal study of cognition and quality of life in BPD patients across the life span, focusing on additive and interactive effects of aging and disease burden, which could culminate in developing more effective treatment and rehabilitation strategies for this traditionally challenging to treat population.

Differential executive functioning performance by phase of bipolar disorder.

OBJECTIVE: This study examined the influence of illness phase on executive functioning performance using factor-derived cognitive scores in a cross-sectional design. METHODS: Healthy control (HC) subjects (n = 57), and euthymic (E-BD) (n = 117), depressed (D-BD) (n = 73), and hypomanic/mixed (HM/M-BD) (n = 26) patients with bipolar disorder (BD) were evaluated using executive functioning measures (Wisconsin Card Sorting Test, Trail Making Test-Parts A and B, Verbal Fluency, Parametric Go/No-Go, Stroop, and Digit Symbol) comprising Conceptual Reasoning and Set-Shifting (CRSS), Processing Speed with Interference Resolution (PSIR), Verbal Fluency and Processing Speed (VFPS), and Inhibitory Control (IC) factor scores. RESULTS: Two of the four executive functioning factors were significantly different between groups based upon phase of illness. The HM/M group was significantly worse than both of the other BD groups and the HC group in IC. The VFPS factor was sensitive to the active phase of BD, with the HM/M-BD and D-BD groups worse than HC. Extending our prior work, the PSIR factor, and now the CRSS factor were significantly worse in BD relative to HC, irrespective of phase of illness. CONCLUSIONS: Phase of illness had differential cognitive profiles in executive functioning factors, even after considering and excluding the impact of clinical features, illness characteristics, medications, and demographics. Consolidating executive functioning tasks into reliable factor scores provides unique information to measure and define cognitive deficiencies throughout phases of BD, and to measure intermediate phenotypes in BD, and may aid in tracking and clarifying treatment focus.

Ictal mnemestic aura and verbal memory function.

Déjà vu aura is a well-known phenomenon experienced by some patients with epilepsy. This study sought to explore the relationship between verbal memory and the experience of déjà vu or other types of mnemestic auras in 42 individuals with intractable seizures and 42 age- and education-matched patient controls. Verbal memory was assessed with indices of learning, long delay recall, and recognition from the California Verbal Learning Test. Results indicated that auras of any type were not associated with memory performance on the California Verbal Learning Test. As expected, age and education were related to verbal memory performance. Mnemestic auras were associated with clinical indices of illness, suggesting that the presence of these auras may be regarded as a risk factor for greater chronicity and severity in epilepsy.

Reduced emotion processing efficiency in healthy males relative to females.

This study examined sex differences in categorization of facial emotions and activation of brain regions supportive of those classifications. In Experiment 1, performance on the Facial Emotion Perception Test (FEPT) was examined among 75 healthy females and 63 healthy males. Females were more accurate in the categorization of fearful expressions relative to males. In Experiment 2, 3T functional magnetic resonance imaging data were acquired for a separate sample of 21 healthy females and 17 healthy males while performing the FEPT. Activation to neutral facial expressions was subtracted from activation to sad, angry, fearful and happy facial expressions. Although females and males demonstrated activation in some overlapping regions for all emotions, many regions were exclusive to females or males. For anger, sad and happy, males displayed a larger extent of activation than did females, and greater height of activation was detected in diffuse cortical and subcortical regions. For fear, males displayed greater activation than females only in right postcentral gyri. With one exception in females, performance was not associated with activation. Results suggest that females and males process emotions using different neural pathways, and these differences cannot be explained by performance variations.

Emotion perception and executive functioning predict work status in euthymic bipolar disorder.

Functional recovery, including return to work, in Bipolar Disorder (BD) lags behind clinical recovery and may be incomplete when acute mood symptoms have subsided. We examined impact of cognition on work status and underemployment in a sample of 156 Euthymic-BD and 143 controls (HC) who were divided into working/not working groups. Clinical, health, social support, and personality data were collected, and eight cognitive factors were derived from a battery of neuropsychological tests. The HC groups outperformed the BD groups on seven of eight cognitive factors. The working-BD group outperformed the not working-BD group on 4 cognitive factors composed of tasks of emotion processing and executive functioning including processing speed and set shifting. Emotion processing and executive tasks were predictive of BD unemployment, after accounting for number of mood episodes. Four cognitive factors accounted for a significant amount of the variance in work status among the BD participants. Results indicate that patients with BD who are unemployed/unable to work exhibit greater difficulties processing emotional information and on executive tasks that comprise a set shifting or interference resolution component as compared to those who are employed, independent of other factors. These cognitive and affective factors are suggested as targets for treatment and/or accommodations.

Modality-specific alterations in the perception of emotional stimuli in Bipolar Disorder compared to Healthy Controls and Major Depressive Disorder.

OBJECTIVES: Affect identification accuracy paradigms have increasingly been utilized to understand psychiatric illness including Bipolar Disorder (BD) and Major Depressive Disorder (MDD). This investigation focused on perceptual accuracy in affect identification in both visual and auditory domains among patients with BD, relative to Healthy Controls (HC) and patients with MDD. Demographic and clinical variables, in addition to medications were also investigated. METHOD: The visual Facial Emotion Perception Test (FEPT) and auditory Emotional Perception Test (EPT) were administered to adults with BD (n=119) and MDD (n=78) as well as HC (n=66). RESULTS: Performance on the FEPT was significantly stronger than on the EPT irrespective of group. Performance on the EPT did not significantly differentiate the groups. On the FEPT, BD samples had the greatest difficulty relative to HC in identification of sad and fearful faces. BD participants also had greater difficulty identifying sad faces relative to MDD participants though not after controlling for severity of illness factors. For the BD (but not MDD) sample several clinical variables were also correlated with FEPT performance. CONCLUSIONS: The findings suggest that disruptions in identification of negative emotions such as sadness and fear may be a characteristic trait of BD. However, this effect may be moderated by greater illness severity found in our BD sample.