L-type calcium channels and psychiatric disorders: A brief review.

Emerging evidence from genome-wide association studies (GWAS) support the association of polymorphisms in the alpha 1C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with bipolar disorder. These studies extend a rich prior literature implicating dysfunction of L-type calcium channels (LTCCs) in the pathophysiology of neuropsychiatric disorders. Moreover, calcium channel blockers reduce Ca(2+) flux by binding to the α1 subunit of the LTCC and are used extensively for treating hypertension, preventing angina, cardiac arrhythmias and stroke. Calcium channel blockers have also been studied clinically in psychiatric conditions such as mood disorders and substance abuse/dependence, yielding conflicting results. In this review, we begin with a summary of LTCC pharmacology. For each category of disorder, this article then provides a review of animal and human data. In particular, we extensively focus on animal models of depression and clinical trials in mood disorders and substance abuse/dependence. Through examining rationale and study design of published clinical trials, we provide some of the possible reasons why we still do not have definitive evidence of efficacy of calcium-channel antagonists for mood disorders. Refinement of genetic results and target phenotypes, enrollment of adequate sample sizes in clinical trials and progress in physiologic and pharmacologic studies to synthesize tissue and isoform specific calcium channel antagonists, are all future challenges of research in this promising field. © 2010 Wiley-Liss, Inc.

Attractive men induce testosterone and cortisol release in women.

Recently, Roney et al. (Roney, J.R., Lukaszewski, A.W., Simmons, Z.L., 2007. Rapid endocrine responses of young men to social interactions with young women. Horm. Behav. 52, 326-33; Roney, J.R., Mahler, S.V., Maestripieri, D., 2003. Behavioral and hormonal responses of men to brief interactions with women. Evol. Hum. Behav. 24, 365-375) demonstrated that men release testosterone and cortisol in response to brief social interactions with young women. The current experiment examined whether women show a similar endocrine response to physically and behaviorally attractive men. 120 women (70 naturally-cycling and 50 using hormonal contraceptives) were shown one of four 20-minute video montages extracted from popular films, depicting the following scenarios: 1) an attractive man courting a young woman (experimental stimulus), 2) a nature documentary (video clip control), 3) an unattractive older man courting a woman (male control), and 4) an attractive woman with no men present (female control). Saliva samples were taken before and after presentation of the stimulus, and were later analyzed for testosterone and cortisol content via enzyme immunoassay. Naturally-cycling women experienced a significant increase in both testosterone and cortisol in response to the experimental stimulus but to none of the control stimuli. Participants taking hormonal contraceptives also showed a significant cortisol response to the attractive man. Women may release adrenal steroid hormones to facilitate courtship interactions with high mate-value men.

Rethinking avoidance: Toward a balanced approach to avoidance in treating anxiety disorders.

Avoidance is typically considered a maladaptive behavioral response to excessive fear and anxiety, leading to the maintenance of anxiety disorders. Exposure is a core element of cognitive-behavioral therapy for anxiety disorders. One important aspect of this treatment is repeated and prolonged exposure to a threat while discouraging patients from using avoidance strategies, such as escape or safety behaviors. We will first revisit the role of avoidance learning in the development and maintenance of anxiety disorders, including important insights from the neuroscience literature. Next, we will consider both the negative and positive aspects of avoidance for therapeutic interventions. Finally, we will explore the application of adaptive avoidance in exposure therapy for anxiety disorders. We will argue that there are occasions when avoidance behaviors can serve as effective coping strategies to enhance the person's perception of control over the environment and the potential threat. We conclude that avoidance behaviors can be a valuable therapeutic element, depending on the function of these behaviors.

Lack of emotional gaze preferences using eye-tracking in remitted bipolar I disorder.

BACKGROUND: Bipolar disorder is associated with heightened and persistent positive emotion (Gruber in Curr Dir Psychol Sci 20:217-221, 2011; Johnson in Clin Psychol Rev 25:241-262, 2005). Yet little is known about information processing biases that may influence these patterns of emotion responding. METHODS: The current study adopted eye-tracking methodology as a continuous measure of sustained overt attention to monitor gaze preferences during passive viewing of positive, negative, and neutral standardized photo stimuli among remitted bipolar adults and healthy controls. Percentage fixation durations were recorded for predetermined areas of interest across the entire image presentation, and exploratory analyses were conducted to examine early versus late temporal phases of image processing. RESULTS: Results suggest that the bipolar and healthy control groups did not differ in patterns of attention bias. CONCLUSIONS: Findings provide insight into apparently intact attention processing despite disrupted emotional responding in bipolar disorder.

Choosing how to feel: emotion regulation choice in bipolar disorder.

Individuals with bipolar disorder experience emotion regulation difficulties, even during remission, but are able to effectively employ emotion regulation strategies when instructed. We hypothesized that this puzzling discrepancy might be due to their maladaptive emotion regulation choices. To test this hypothesis, we used a previously validated paradigm (Sheppes, Scheibe, Suri, & Gross, 2011; Sheppes et al., 2014), and asked remitted individuals with bipolar I disorder (n = 25) and healthy individuals (n = 26) to view standardized positive and negative images of high and low intensity, and choose reappraisal or distraction to decrease their emotion intensity. Replicating and extending prior results, participants across both groups showed a pattern of choosing distraction more for high versus low intensity positive and negative images, but no between-groups differences were evident. These results suggest that emotion regulation choice patterns may be robust across samples, and add to growing evidence that several basic emotion regulation elements may remain intact in bipolar disorder.

Rethinking emotion: cognitive reappraisal is an effective positive and negative emotion regulation strategy in bipolar disorder.

Bipolar disorder involves difficulties with emotion regulation, yet the precise nature of these emotion regulatory difficulties is unclear. The current study examined whether individuals with remitted bipolar I disorder (n = 23) and healthy controls (n = 23) differ in their ability to use one effective and common form of emotion regulation, cognitive reappraisal. Positive, negative, and neutral films were used to elicit emotion, and participants were cued to watch the film carefully (i.e., uninstructed condition) or reappraise while measures of affect, behavior, and psychophysiology were obtained. Results showed that reappraisal was associated with reductions in emotion reactivity across subjective (i.e., positive and negative affect), behavioral (i.e., positive facial displays), and physiological (i.e., skin conductance) response domains across all participants. Results suggest that reappraisal may be an effective regulation strategy for both negative and positive emotion across both healthy adults and individuals with bipolar disorder. Discussion focuses on clinical and treatment implications for bipolar disorder.

Feeling stuck in the present? Mania proneness and history associated with present-oriented time perspective.

Humans have the ability to mentally time travel through past, present, and future. But can a disruption in emotion characteristic of emotional disorders cause this ability to unwind, leaving people "stuck" in the present emotional moment? Two studies are presented that examine emotional time-perspective in a disorder (mania) characterized by present-oriented tendencies, including impulsivity and emotion dysregulation. In Study 1, associations were reported between mania proneness and emotion time-perspective (n = 509), and Study 2 compared emotion time-perspective between individuals with a clinical history of mania (n = 32), and controls (n = 30). We show that mania is associated with increased present and decreased future focus. These findings suggest that emotional disorders can be understood, at least in part, by examining how people understand and use time to guide their behavior and feelings.

Sleep disturbance in euthymic bipolar patients.

Sleep disturbance is a common feature during mood episodes in bipolar disorder. The aim of this study was to investigate the prevalence of such symptoms among euthymic bipolar patients, and their association with risk for mood episode recurrence. A cohort of bipolar I and II subjects participating in the Systematic Treatment Enhancement Program for Bipolar Disorder who were euthymic for at least 8 weeks were included in this analysis. Survival analysis was used to examine the association between sleep disturbance on the Montgomery-Asberg Depression Rating Scale (MADRS) and recurrence risk. A total of 73/483 bipolar I and II subjects reported at least mild sleep disturbance (MADRS sleep item ≥2) for the week prior to study entry. The presence of sleep problems was associated with a history of psychosis, number of previous suicide attempts, and anticonvulsant use. Sleep disturbance at study entry was significantly associated with risk for mood episode recurrence. Sleep disturbance is not uncommon between episodes for individuals with bipolar disorder and may be associated with a more severe course of illness. This suggests that sleep disturbance is an important prodromal symptom of bipolar disorder and should be considered a target for pharmacologic or psychosocial maintenance treatment.