Amygdala subnuclei volume in bipolar spectrum disorders: Insights from diffusion-based subsegmentation and a high-risk design.

Amygdala abnormalities are widely documented in bipolar spectrum disorders (BSD). Amygdala volume typically is measured after BSD onset; thus, it is not known whether amygdala abnormalities predict BSD risk or relate to the disorder. Additionally, past literature often treated the amygdala as a homogeneous structure, and did not consider its distinct subnuclei and their differential connectivity to other brain regions. To address these issues, we used a behavioral high-risk design and diffusion-based subsegmentation to examine amygdala subnuclei among medication-free individuals with, and at risk for, BSD. The behavioral high-risk design (N = 114) included low-risk (N = 37), high-risk (N = 47), and BSD groups (N = 30). Diffusion-based subsegmentation of the amygdala was conducted to determine whether amygdala volume differences related to particular subnuclei. Individuals with a BSD diagnosis showed greater whole, bilateral amygdala volume compared to Low-Risk individuals. Examination of subnuclei revealed that the BSD group had larger volumes compared to the High-Risk group in both the left medial and central subnuclei, and showed larger volume in the right lateral subnucleus compared to the Low-Risk group. Within the BSD group, specific amygdala subnuclei volumes related to time since first episode onset and number of lifetime episodes. Taken together, whole amygdala volume analyses replicated past findings of enlargement in BSD, but did not detect abnormalities in the high-risk group. Examination of subnuclei volumes detected differences in volume between the high-risk and BSD groups that were missed in the whole amygdala volume. Results have implications for understanding amygdala abnormalities among individuals with, and at risk for, a BSD.

The interactive association of proximal life stress and cumulative HPA axis functioning with depressive symptoms.

BACKGROUND: Stress is consistently implicated in depression. Using a vulnerability-stress framework, the hypothalamic-pituitary-adrenal (HPA) axis may be one factor affecting the stress-depression association. However, the interactive influence of recent life stress and HPA axis functioning on depressive symptoms remains unclear. It is particularly important to understand the synergistic association during adolescence, as this is a developmental period associated with a high risk for depression. METHODS: A community sample of 58 adolescents (67% female, 59% Caucasian; mean age, 15.07 years) participated. Adolescents completed a well-validated measure of depressive symptoms and a structured life events interview to assess recent life stress. Hair cortisol concentration was obtained to measure cumulative exposure to HPA axis functioning. RESULTS: Recent life stress and cumulative HPA axis exposure measured through hair cortisol were directly associated with higher depressive symptoms. Further, cumulative HPA axis exposure moderated the relationship between recent life stress and depressive symptoms. The recent life stress-depression association occurred for adolescents who experienced average and high, but not low, levels of cumulative HPA axis exposure. CONCLUSIONS: The current study builds on prior work and finds both a direct and interactive association of recent life stress and cumulative HPA axis functioning with depressive symptoms during adolescence. Identifying youth who experience high levels of HPA axis exposure is important to prevent the onset of depression.

fMRI prediction of naming change after adult temporal lobe epilepsy surgery: Activation matters.

OBJECTIVE: We aimed to predict language deficits after epilepsy surgery. In addition to evaluating surgical factors examined previously, we determined the impact of the extent of functional magnetic resonance imaging (fMRI) activation that was resected on naming ability. METHOD: Thirty-five adults (mean age 37.5 ± 10.9 years, 13 male) with temporal lobe epilepsy completed a preoperative fMRI auditory description decision task, which reliably activates frontal and temporal language networks. Patients underwent temporal lobe resections (20 left resection). The Boston Naming Test (BNT) was used to determine language functioning before and after surgery. Language dominance was determined for Broca and Wernicke area (WA) by calculating a laterality index following statistical parametric mapping processing. We used an innovative method to generate anatomic resection masks automatically from pre- and postoperative MRI tissue map comparison. This mask provided the following: (a) resection volume; (b) overlap between resection and preoperative activation; and (c) overlap between resection and WA. We examined postoperative language change predictors using stepwise linear regression. Predictors included parameters described above as well as age at seizure onset (ASO), preoperative BNT score, and resection side and its relationship to language dominance. RESULTS: Seven of 35 adults had significant naming decline (6 dominant-side resections). The final regression model predicted 38% of the naming score change variance (adjusted r2  = 0.28, P = 0.012). The percentage of top 10% fMRI activation resected (P = 0.017) was the most significant contributor. Other factors in the model included WA LI, ASO, volume of WA resected, and WA LI absolute value (extent of laterality). SIGNIFICANCE: Resection of fMRI activation during a word-definition decision task is an important factor for postoperative change in naming ability, along with other previously reported predictors. Currently, many centers establish language dominance using fMRI. Our results suggest that the amount of the top 10% of language fMRI activation in the intended resection area provides additional predictive power and should be considered when planning surgical resection.

Everyday executive function in focal onset pediatric epilepsy on the parent-report BRIEF2.

Executive function (EF) difficulties are a core neuropsychological feature of pediatric epilepsy, and parent-report measures of EF concerns are an important complement to task-based EF measures. The Behavior Rating Inventory of Executive Function (BRIEF) has shown sensitivity to parent-reported EF concerns in epilepsy and other pediatric populations. We compared profiles of parent-reported EF concerns using the BRIEF and its revision, the BRIEF2, in 117 pediatric patients with focal onset epilepsy to examine the clinical utility of the revised scale. We then compared BRIEF2 profiles between patients and age- and gender-matched healthy controls. Among patients, profiles on the BRIEF did not globally differ from the BRIEF2, and agreement was very good across scales. Patients and controls differed significantly on the BRIEF2, with patients showing higher EF difficulties reported by parents across most scales. High rates of clinical elevation among patients emerged on the Task Monitor, Plan/Organize, Working Memory, and Shift scales. Younger age of epilepsy onset, chronic epilepsy, and right hemisphere seizure focus were associated with higher parent-reported EF concerns. Findings suggest that the BRIEF2 demonstrates similar performance to the BRIEF among pediatric patients with focal onset epilepsy who are most at risk in the areas of task monitoring, working memory, planning and organization, and flexibility. These findings are informative when comparing literature across versions and provide additional insight into the nature of parent-reported EF difficulties among children with focal onset epilepsy.

Impulsive personality dimensions are associated with altered behavioral performance and neural responses in the monetary incentive delay task.

Individual differences in dimensions of impulsivity personality including disinhibition and sensation seeking modulate approach responses to reinforcing stimuli, such as drugs and money. The current study examined the effects of monetary incentive on both behavioral performance and electrophysiological activity among individuals varying in disinhibition and sensation seeking. The monetary incentive delay (MID) task was completed under electroencephalogram (EEG) recording. Behavioral data showed that higher disinhibition and sensation-seeking were associated with lower performance accuracy. Event-related potential (ERP) data showed that high reinforcement cues elicited a larger late positive component (LPC) than other conditions among high disinhibition participants, indicating its strong emotional influence. Additionally, in the neutral incentive condition, the feedback-related negativity (FRN) elicited by correct outcomes was larger than that elicited by incorrect outcomes in the high disinhibition group only. This novel finding indicates that high disinhibition participants were less likely to expect correct outcomes compared to incorrect outcomes in the neutral incentive condition. Finally, the P3 component elicited by outcome presentation showed an interaction between two impulsivity dimensions; when disinhibition level was low, the P3 was larger among high than low sensation seeking participants.

Impulsivity predicts the onset of DSM-IV-TR or RDC hypomanic and manic episodes in adolescents and young adults with high or moderate reward sensitivity.

BACKGROUND: A growing body of research suggests that bipolar disorders (BD) are associated with high impulsivity. Using a multi-method approach, the current study provided the first examination of the hypothesis that impulsivity would prospectively predict shorter time to onset of DSM-IV-TR or RDC hypomanic or manic episodes in a sample selected based on reward sensitivity, a biobehavioral trait shown to predict onset and course of BD. METHODS: 163 participants with high reward sensitivity and 114 participants with moderate reward sensitivity were followed every six months for an average of 2.68 years. Participants completed the Barratt Impulsiveness Scale - Version 11 (BIS-11), Balloon Analog Risk Task (BART), Beck Depression Inventory, Altman Self-Rating Mania Scale, and an expanded Schedule for Affective Disorders and Schizophrenia (exp-SADS) - Lifetime Version at baseline and were followed prospectively with the exp-SADS - Change Version to assess onset of hypomanic or manic episodes and treatment seeking for mood problems. RESULTS: Cox proportional hazard regression analyses indicated that impulsivity as measured by a behavioral task (BART; OR=1.04, p=.03) and a self-report measure (BIS-11 Attentional Impulsiveness subscale; OR=1.16, p=.01) predicted shorter time to hypomania/mania onset, after controlling for baseline depressive and manic symptoms, family history of mood disorder, treatment seeking for mood problems, and reward sensitivity. LIMITATIONS: The study was limited by non-comprehensive assessment of impulsivity and unknown generalizability to clinical samples. CONCLUSIONS: Impulsivity confers vulnerability to hypomania or mania. Future studies would benefit from considering how impulsivity can be integrated into existing biopsychosocial models of BD.

Associations between sleep disturbance, cognitive functioning and work disability in Bipolar Disorder.

Bipolar Disorder (BD) is associated with impairment in a number of areas including poor work functioning, often despite the remission of mood symptoms. The present study aimed to examine the role of sleep disturbance and cognitive functioning in occupational impairment in BD. Twenty-four euthymic BD participants and 24 healthy control participants completed a week of prospective assessment of sleep disruption via self-report and actigraphy, a battery of neuropsychological tests of executive functioning, working memory, and verbal learning, and assessments of work functioning. BD participants experienced significantly poorer cognitive functioning as well as greater months of unemployment and greater incidence of being fired than controls. Moderation analyses revealed that both poor sleep and cognitive functioning were associated with poor work performance in BD participants, but not control participants. Sleep and cognitive functioning may be impaired in euthymic BD and are associated with poor work functioning in this population. More research should be conducted to better understand how sleep and cognitive functioning may interact in BD.

Cognitive Styles in Mood Disorders: Discriminative Ability of Unipolar and Bipolar Cognitive Profiles.

Although previous research has identified cognitive styles that distinguish individuals with bipolar disorder (BD), individuals with major depressive disorder (MDD), and individuals without mood disorders from one another, findings have been inconsistent. The current study included 381 participants classified into a BD group, a MDD group, and a no mood disorder group. To differentiate between these groups, this study evaluated cognitive styles with a battery of traditional and more recently-developed measures. Receiver operating characteristics (ROC) analyses were used to determine the discriminate ability of variables with significant between group differences. Results supported that BD and MDD may be characterized by distinct cognitive styles. Given work showing that interventions for MDD may not be effective at treating BD, it is important to directly compare individuals with these disorders. By clarifying the overlapping and divergent cognitive styles characterizing BD and MDD, research can not only improve diagnostic validity, but also provide more efficacious and effective interventions.

Behavioral approach system sensitivity and risk taking interact to predict left-frontal EEG asymmetry.

The Behavioral Approach System (BAS) hypersensitivity theory of bipolar disorder (BD; Alloy & Abramson, 2010; Depue & Iacono, 1989) suggests that hyperreactivity in the BAS results in the extreme fluctuations of mood characteristic of BD. In addition to risk conferred by BAS hypersensitivity, cognitive and personality variables may play a role in determining risk. We evaluated relationships among BAS sensitivity, risk taking, and an electrophysiological correlate of approach motivation, relative left-frontal electroencephalography (EEG) asymmetry. BAS sensitivity moderated the relationship between risk taking and EEG asymmetry. More specifically, individuals who were high in BAS sensitivity showed left-frontal EEG asymmetry regardless of their level of risk-taking behavior. However, among individuals who were moderate in BAS sensitivity, risk taking was positively associated with asymmetry. These findings suggest that cognitive and personality correlates of bipolar risk may evidence unique contributions to a neural measure of trait-approach motivation. Clinical implications of these findings are discussed.

Differentiating bipolar disorder from unipolar depression and ADHD: the utility of the general behavior inventory.

Adolescence and early adulthood are the peak ages for the onset of unipolar and bipolar mood disorders. Moreover, for most individuals with attention-deficit/hyperactivity disorder (ADHD), symptoms and impairment begin in childhood but persist well into adolescence and adulthood (e.g., Barkley, 2010). Thus, adolescence and early adulthood represent a developmental window wherein individuals can be affected by mood disorders, ADHD, or both. Because treatment protocols for unipolar depression (UPD), bipolar disorder (BD), and ADHD are quite different, it is crucial that assessment instruments used among adolescents and young adults differentiate between these disorders. The primary objectives of this study were to evaluate the predictive and diagnostic validity of General Behavior Inventory (GBI; Depue et al., 1981) scores in discriminating BD from UPD and ADHD. Participants were drawn from adolescent (n = 361) and young adult (n = 614) samples. Based on findings from logistic regression and receiver-operating characteristics analyses, the diagnostic efficiency of the GBI scales range from fair (discriminating UPD from BD) to good (discriminating BD participants from nonclinical controls). Multilevel diagnostic likelihood ratios are also provided to facilitate individual decision making.

Aggression and impulsivity as predictors of stress generation in bipolar spectrum disorders.

BACKGROUND: Some evidence suggests that individuals with bipolar spectrum disorders (BSD) generate stressful life events, contributing to a more severe course of disorder. A recent update to the Behavioral Approach System (BAS) dysregulation theory of BSD highlights the need to investigate anger as approach motivation. Although research has shown that individuals with BSD generate stress, it is unclear whether personality traits characteristic of BSD, such as aggression and impulsivity, are related to this stress generation. METHODS: The current longitudinal study employed multilevel modeling to examine stress generation in a sample of 104 individuals with BSD and 96 healthy controls. We examined rates of BAS-deactivating, BAS-activating, and Anger-evoking life events over a period of up to 4.5 years as a function of levels of aggression and impulsivity. RESULTS: Individuals with BSD reported significantly higher numbers of dependent Anger-evoking events and BAS-deactivating events, but not dependent BAS-activating events, than controls. Trait levels of hostility and impulsivity predicted all types of events, although bipolar diagnosis remained a significant predictor of BAS-deactivating and Anger-evoking events. LIMITATIONS: The life events measures were not designed to assess Anger-evoking events; further research should replicate these findings and develop more finely tuned assessments of stressful anger events. In addition, the sample was not a clinical sample. CONCLUSIONS: This study adds to the literature on stress generation in BSD; trait level personality differences predict stress generation, beyond bipolar diagnosis. This also further establishes the importance of including anger-evoking events in the BAS model of BSDs and stress generation.

Positive overgeneralization and Behavioral Approach System (BAS) sensitivity interact to predict prospective increases in hypomanic symptoms: a behavioral high-risk design.

Recent work has identified Behavioral Approach System (BAS) sensitivity as a risk factor for the first onset and recurrence of mood episodes in bipolar disorder, but little work has evaluated risk factors for the prospective development of hypomanic symptoms in individuals at risk for, but without a history of, bipolar disorder. The present study used a prospective behavioral high-risk design to evaluate the impact of positive overgeneralization, a cognitive correlate of risk for hypomania, on hypomanic symptoms in individuals with high vs. moderate BAS sensitivity, but without a history of mood elevation. Hierarchical linear regressions indicated that upward positive overgeneralization and BAS sensitivity interacted to predict increased levels of hypomanic symptoms at follow-up, controlling for initial hypomanic symptoms. The pattern of this interaction was such that positive overgeneralization predicted higher levels of hypomanic symptoms among high-BAS, but not moderate-BAS, individuals. Thus, the self-reported tendency to experience grandiose increases in confidence following success may confer additional risk for mood elevation among individuals already at risk for developing bipolar disorder. Potential implications for prevention and treatment are discussed.