Reward sensitivity and social rhythms during goal-striving: An ecological momentary assessment investigation of bipolar spectrum disorders.

BACKGROUND: The reward/circadian rhythm model of bipolar spectrum disorders (BSDs) posits that when individuals with hypersensitive reward systems encounter reward-relevant events, they experience social and circadian rhythm disruption, leading to mood symptoms. The aim of the current study is to test an element of this theoretical model by investigating changes in social rhythms during and after an ecologically-valid reward-relevant event and evaluating whether the strength of these associations differ by trait reward sensitivity and BSD diagnostic group. METHODS: Young adults from three groups (low BSD risk with moderate reward sensitivity [MRew], high BSD risk with high reward sensitivity [HRew], and high reward sensitivity with BSD [HRew+BSD]) completed a reward responsiveness task and 20-day ecological momentary assessment study structured around a participant-specific goal occurring on day 15. Social rhythm disruption (SRD) and social rhythm regularity (SRR) were assessed daily. Multilevel models examined whether reward sensitivity and group moderated associations between study phase (baseline [days 1-5], goal-striving [days 16-20], or outcome [days 16-20]) and social rhythms. RESULTS: Participants experienced greater SRD after the goal-striving event during the outcome phase, compared to the baseline phase. The HRew+BSD group had significant decreases in SRR during the outcome phase, and this pattern differed significantly from the low-risk and high-risk groups. Greater task reward responsiveness also was associated with significant decreases in SRR during the outcome phase. LIMITATIONS: This study did not test whether social rhythm irregularity was associated with subsequent mood change. CONCLUSIONS: Participants exhibited social rhythm changes over the course of this ecologically valid goal-striving period, providing evidence for the interplay between reward-activating events and social rhythms. The HRew+BSD group showed a distinct pattern in which their social rhythms were more irregular after completing reward-relevant goal-striving that was not observed for the low-BSD risk or high-BSD risk groups. These findings provide additional support for Interpersonal and Social Rhythms Therapy.

The effect of obstructive sleep apnea severity on PTSD symptoms during the course of esketamine treatment: a retrospective clinical study.

STUDY OBJECTIVES: Intranasal administration of esketamine is Food and Drug Administration-approved for treatment-resistant depression. In a recent retrospective case series, we show that it has promise in reducing symptoms of posttraumatic stress disorder (PTSD) as well. Untreated obstructive sleep apnea (OSA) is prevalent among veterans with PTSD and has been shown to interfere with other PTSD treatments. In the current study, we examined whether OSA impacts esketamine's effectiveness in reducing symptoms of PTSD or depression. METHODS: Participants were 60 veterans with a diagnosis of major depressive disorder and PTSD who received intranasal esketamine treatment at the San Diego Veterans Affairs (VA) Medical Center. We used growth-curve modeling to examine changes in depression and PTSD symptoms following esketamine treatments and, in the subset of individuals screened for OSA (n = 24, all prescribed positive airway pressure therapy), examined the impacts of OSA severity on these trajectories. RESULTS: We first showed that both PTSD and depressive symptoms significantly decreased over the course of esketamine treatment. In the subset of veterans screened for OSA, individuals with lower OSA severity reported the greatest reduction in PTSD symptoms, while veterans with the most severe OSA reported the least reduction in PTSD symptoms. Depression response was not affected by severity of OSA in this analysis. CONCLUSIONS: Veterans with PTSD and depression tend to benefit from esketamine treatment, but OSA may interfere with esketamine effectiveness. Comorbid OSA should be assessed for and treated to maximize esketamine's benefits in PTSD. CITATION: Titone MK, Hunt C, Bismark A, et al. The effect of obstructive sleep apnea severity on PTSD symptoms during the course of esketamine treatment: a retrospective clinical study. J Clin Sleep Med. 2023;19(12):2043-2051.

Are all reasons for living made equally? Reasons for living and dysfunctional attitudes in psychotic disorders and bipolar I.

OBJECTIVES: Persons with schizophrenia, schizoaffective, or bipolar I disorder are more likely to die by suicide compared to the general population. Dysfunctional attitudes have been shown to be significant predictors of cognitive vulnerability to depression, hopelessness, and poor problem-solving skills, which predict suicidal ideation. Dysfunctional attitudes are common in persons with schizophrenia spectrum disorders (SSDs) and bipolar I. The Reasons for Living Inventory (RFLI) examines distinct reasons for not dying by suicide. This study's objectives were to examine the relationship between the RFLI subscales and dysfunctional attitudes among persons with SSDs and bipolar I. We hypothesized significant positive correlations between two RFLI subscales (Fear of Suicide and Fear of Social Disapproval) and total score on the Dysfunctional Attitude Scale (DAS). We did not expect significant correlations between other subscales. DESIGN AND METHODS: This correlational, cross-sectional study examined baseline scores on the RFLI and dysfunctional attitudes (DAS) among N = 102 outpatients with SSDs or bipolar I. RESULTS: Significant positive correlations were observed between RFLI subscales Fear of Suicide and Fear of Social Disapproval and DAS total scores. No other significant relationships were observed. CONCLUSIONS: Certain reasons for living (i.e. fear of suicide and social disapproval) may be associated with dysfunctional attitudes among persons with SSDs or bipolar I. These, in turn, may place these individuals at a greater risk for suicide by increasing their cognitive vulnerability. These findings may inform clinical treatment targets for persons with SSDs and bipolar I.

An examination of bidirectional associations between physical activity and mood symptoms among individuals diagnosed and at risk for bipolar spectrum disorders.

OBJECTIVES: Activation, a construct including energy and activity, is a central feature of Bipolar Spectrum Disorders (BSDs). Prior research found motor activity is associated with affect, and this relationship may be stronger for individuals with BSDs. The aims of this study were to investigate bidirectional relationships between physical activity and mood and evaluate whether bipolar risk status moderated potential associations. METHODS: Young adults at low-risk, high-risk, and diagnosed with BSD participated in a 20-day EMA study in which they wore an actiwatch to measure physical activity and sleep/wake cycles. They also reported depressive and hypo/manic symptoms three times daily. Multilevel linear models were estimated to examine how bipolar risk group moderated bidirectional relationships between physical activity and mood symptoms at within-day and between-day timescales. RESULTS: Physical activity was significantly associated with subsequent mood symptoms at the within-day level. The relationship between physical activity and depressive symptoms was moderated by BSD risk group. An increase in physical activity resulted in a greater reduction of depressive symptoms for the BSD group compared to the low-risk and high-risk groups. CONCLUSIONS: Interventions targeting activity like behavioral activation may improve residual inter-episode mood symptoms.

The relationship between physical activity states and depressive symptoms: Using ambulatory assessment to characterize day-to-day associations among individuals with and without bipolar spectrum disorder.

INTRODUCTION: The role of activation in the pathogenesis of bipolar spectrum disorders (BSD) is of growing interest. Physical activity is known to improve mood, but it is unclear whether low activity levels contribute to inter-episode depressive symptoms observed in BSD. This study examined whether sedentary and vigorous activity, as well as the timing of the activity, were differentially associated with next-day depressive symptoms for individuals at low risk for BSD, high-risk for BSD, and diagnosed with BSD. METHODS: Young adults (n = 111, ages 18-27) from three groups (low BSD risk, high BSD risk, and BSD diagnosis), participated in a 20-day ecological momentary assessment study. Physical activity was measured via wrist actigraphy counts. The percentage of time awake spent in sedentary, light, moderate, and vigorous activity states was calculated, as was the percentage of morning hours and evening hours in each activity state. Multilevel models examined whether the BSD risk group moderated associations between sedentary and vigorous activity and depressive symptoms, which were assessed three times daily. RESULTS: There were no between-group differences in time spent in each activity state, nor were there main effects of sedentary or vigorous activity on depression. Increased time spent engaging in vigorous activity was associated with a greater reduction in subsequent depressive symptoms for the BSD group. An increase in the evening, but not morning, vigorous activity was significantly associated with a reduction in subsequent depressive symptoms for the BSD group after controlling for chronotype. CONCLUSIONS: Interventions targeting physical activity may effectively help regulate inter-episode mood disturbances in BSD.

The interplay of daily affect and impulsivity measured by mobile surveys in bipolar disorder.

BACKGROUND: Impulsivity is a prominent feature of bipolar disorder associated with various negative sequelae; moreover, it may be a precursor to shifts in affect or mood, but little is known about its association with affect on a day-to-day timescale. Ecological momentary assessments (a method that captures moment-to-moment ratings of psychological states by repeatedly sampling the same individual) of impulsivity and affect using mobile surveys allow for more nuanced examination of mechanisms of mood and behavior dysregulation. However, few existing studies have validated an ecological momentary assessment of impulsivity in bipolar disorder and examined its time-lagged associations with positive and negative affect. 70 participants with bipolar disorder and 102 healthy comparisons participated in an intensive longitudinal study: they underwent 14 days of ecological momentary assessment data collection annually for 1-4 years. Multiple measures of impulsivity and affect were collected using self-report, behavioral, and ecological momentary assessment modalities; these measures were compared, and levels of impulsivity were compared between bipolar disorder and healthy comparison groups. Time-lagged analyses using daily means explored the next-day predictive relationship of impulsivity on positive/negative affect, and vice versa. RESULTS: The ecological momentary measure of impulsivity was moderately correlated with the self-report but not behavioral impulsivity measure. Bipolar disorder participants evinced higher self-report, behavioral, and daily impulsivity than healthy comparison participants. Time-lagged analyses revealed a bi-directional association between high impulsivity and high next-day negative (but not positive) affect. Post hoc analyses showed that impulsivity specifically predicted next-day anger and anxiety. CONCLUSIONS: Our multimodal assessment of impulsivity allowed for an examination of the day-to-day course of impulsivity and affect, crucial steps toward understanding the mechanisms of mood symptom and episode onset in bipolar disorder.

Risk for bipolar spectrum disorders associated with positive urgency and orbitofrontal cortical grey matter volume.

Bipolar spectrum disorders (BSDs) are associated with reward hypersensitivity, impulsivity, and structural abnormalities within the brain's reward system. Using a behavioral high-risk study design based on reward sensitivity, this paper had two primary objectives: 1) investigate whether elevated positive urgency, the tendency to act rashly when experiencing extreme positive affect, is a risk for or correlate of BSDs, and 2) examine the nature of the relationship between positive urgency and grey matter volume in fronto-striatal reward regions, among individuals at differential risk for BSD. Young adults (ages 18-28) screened to be moderately reward sensitive (MReward; N = 42), highly reward sensitive (HReward; N = 48), or highly reward sensitive with a lifetime BSD (HReward + BSD; N = 32) completed a structural MRI scan and the positive urgency subscale of the UPPS-P scale. Positive urgency scores varied with BSD risk (MReward < HReward < HReward + BSD; ps≤0.05), and positive urgency interacted with BSD risk group in predicting lateral OFC volume (p <.001). Specifically, the MReward group showed a negative relationship between positive urgency and lateral OFC volume. By contrast, there was no relationship between positive urgency and lateral OFC grey matter volume among the HReward and HReward + BSD groups. The results suggest that heightened trait positive urgency is a pre-existing vulnerability for BSD that worsens with illness onset, and there is a distinct relationship between positive urgency and lateral OFC volume among individuals at high versus low risk for BSD. These findings have implications for understanding the expression and development of impulsivity in BSDs.

Impulsivity and sleep and circadian rhythm disturbance predict next-day mood symptoms in a sample at high risk for or with recent-onset bipolar spectrum disorder: An ecological momentary assessment study.

BACKGROUND: Impulsivity and sleep and circadian rhythm disturbance are core features of bipolar spectrum disorders (BSDs) that are antecedents to onset and persist even between mood episodes; their pervasive presence in BSD suggests that they may be particularly relevant to understanding BSD onset and course. Considerable research demonstrates bidirectional associations between impulsivity and sleep disturbance in healthy individuals; thus, it is important to examine how these features interact to impact BSD symptomatology. METHODS: Young adults (N = 107, 55% female, M age = 21.82 years) at high risk for developing BSD (based on high self-reported reward sensitivity) or with recent-onset BSD participated in ecological momentary assessment (EMA) to examine relationships between impulsivity, sleep and circadian rhythm alterations, and mood symptoms in everyday life. Impulsivity was measured via self-report/behavioral task, sleep was measured via actigraphy, circadian rhythms were measured via dim light melatonin onset (DLMO) time, and mood symptoms were measured three times daily via self-report. RESULTS: Multi-level modeling revealed that less total sleep time predicted increased next-day mood symptoms. Moreover, DLMO, total sleep time, and sleep onset latency moderated the relationship between impulsivity and EMA-assessed mood symptoms. Fewer minutes of sleep and later DLMO strengthened the positive relationship between impulsivity and mood symptoms. LIMITATIONS: Mood symptoms in our sample were mild; future studies should replicate findings in populations with more severe mood symptoms. CONCLUSIONS: This multi-method assessment of dynamic relationships revealed novel associations between impulsivity, sleep and circadian rhythm disturbance, and symptoms within individuals at high-risk for or with recent-onset BSD.

Bipolar spectrum disorders are associated with increased gray matter volume in the medial orbitofrontal cortex and nucleus accumbens.

Objective: Elevated sensitivity to rewards prospectively predicts Bipolar Spectrum Disorder (BSD) onset; however, it is unclear whether volumetric abnormalities also reflect BSD risk. BSDs emerge when critical neurodevelopment in frontal and striatal regions occurs in sex-specific ways. The current paper examined the volume of frontal and striatal brain regions in both individuals with and at risk for a BSD with exploratory analyses examining sex-specificity. Methods: One hundred fourteen medication-free individuals ages 18-27 at low-risk for BSD (moderate-reward sensitivity; N = 37), at high-risk without a BSD (high-reward sensitivity; N = 47), or with a BSD (N = 30) completed a structural MRI scan of the brain. We examined group differences in gray matter volume in a priori medial orbitofrontal cortex (mOFC) and nucleus accumbens (NAcc) regions-of-interest. Results: The BSD group had enlarged frontostriatal volumes (mOFC, NAcc) compared to low individuals (d = 1.01). The mOFC volume in BSD was larger than low-risk (d = 1.01) and the high-risk groups (d = 0.74). This effect was driven by males with a BSD, who showed an enlarged mOFC compared to low (d = 1.01) and high-risk males (d = 0.74). Males with a BSD also showed a greater NAcc volume compared to males at low-risk (d = 0.49), but not high-risk males. Conclusions: An enlarged frontostriatal volume (averaged mOFC, NAcc) is associated with the presence of a BSD, while subvolumes (mOFC vs. NAcc) showed unique patterning in relation to risk. We report preliminary evidence that sex moderates frontostriatal volume in BSD, highlighting the need for larger longitudinal risk studies examining the role of sex-specific neurodevelopmental trajectories in emerging BSDs.

Decreased reward-related brain function prospectively predicts increased substance use.

Substance use and addiction are prominent global health concerns and are associated with abnormalities in reward sensitivity. Reward sensitivity and approach motivation are supported by a fronto-striatal neural circuit including the orbitofrontal cortex (OFC), ventral striatum (VS), and dorsal striatum (DS). Although research highlights abnormalities in reward neural circuitry among individuals with problematic substance use, questions remain about whether such use arises from excessively high, or excessively low, reward sensitivity. This study examined whether reward-related brain function predicted subsequent substance use course. Participants were 79 right-handed individuals (Mage = 21.52, SD = 2.19 years), who completed a monetary incentive delay (MID) fMRI task, and follow-up measures assessing substance use frequency and impairment. The average duration of the follow-up period was 9.1 months. Regions-of-interest analyses focused on the reward anticipation phase of the MID. Decreased activation in the VS during reward anticipation predicted increased substance use frequency at follow-up. Decreased DS activation during reward anticipation predicted increased substance use frequency at follow-up, but this finding did not pass correction for multiple comparisons. Analyses adjusted for relevant covariates, including baseline substance use and the presence or absence of a lifetime substance use disorder prior to MRI scanning. Results support the reward hyposensitivity theory, suggesting that decreased reward-related brain function is a risk factor for increased substance use. Results have implications for understanding the pathophysiology of problematic substance use and highlight the importance of the fronto-striatal reward circuit in the development and maintenance of addiction. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Neural reward circuit dysfunction as a risk factor for bipolar spectrum disorders and substance use disorders: A review and integration.

Bipolar spectrum disorders (BSDs) and substance use disorders (SUDs) are associated with neural reward dysfunction. However, it is unclear what pattern of neural reward function underlies pre-existing vulnerability to BSDs and SUDs, or whether neural reward function explains their high co-occurrence. The current paper provides an overview of the separate literatures on neural reward sensitivity in BSDs and SUDs. We provide a systematic review of 35 studies relevant to identifying neural reward function vulnerability to BSDs and SUDs. These studies include those examining neural reward processing on a monetary reward task with prospective designs predicting initial onset of SUDs, familial risk studies that examine unaffected offspring or first-degree relatives of family members with BSDs or SUDs, and studies that examine individuals with BSDs or SUDs who are not currently in an episode of the disorder. Findings from the review highlight that aberrant responding and connectivity across neural regions associated with reward and cognitive control confers risk for the development of BSDs and SUDs. Discussion focuses on limitations of the extant literature. We conclude with an integration and theoretical model for understanding how aberrant neural reward responding may constitute a vulnerability to the development of both BSDs and SUDs.

The Role of Comorbid Depression in Youth Anxiety Treatment Outcomes.

Findings have been mixed regarding the relationship between comorbid depression and anxiety and treatment outcomes for anxious youth. The current study compared a sample of anxious youth with a comorbid depressive disorder (n = 20) and those without comorbid depression (n = 137). All participants received 16 weekly sessions of Coping Cat and completed measures assessing anxiety/depression severity, impairment, and functioning at pretreatment and posttreatment. Results indicated that anxiety-focused CBT is efficacious for anxious youth with and without comorbid depressive disorders, with a higher rate of symptom improvement for youth with comorbid depression during treatment. However, comorbid depression was associated with higher severity at baseline and after treatment. Thus, despite the higher rate of symptom improvement, anxious youth with comorbid depression may benefit from additional treatment to address remaining symptoms.

Sex and race influence objective and self-report sleep and circadian measures in emerging adults independently of risk for bipolar spectrum disorder.

There is a need to better understand key factors that impact sleep and circadian function for young adults of differing races and sexes. Sex and race are common factors contributing to disparities in health outcomes; however, the influence of these variables on sleep and circadian patterns for young adults are not well known. Multiple objective and self-report facets of sleep and circadian function were assessed (melatonin onset, actigraphy, and sleep diaries) in an ecological momentary assessment study of 150 emerging adults (Mage = 21.8 years; 58.7% female; 56% White, 22.7% Black, 21.3% Other ethnicity) at high or low risk for bipolar spectrum disorder (BSD). Controlling for BSD risk status, sex and race were significant predictors of objective and self-reported sleep and circadian rhythm measures. Males self-reported better sleep efficiency and exhibited later dim light melatonin onset phase than females, whereas females exhibited more actigraphy-measured sleep periods. White participants exhibited more actigraphy-measured total sleep time (TST), better sleep efficiency, and fewer sleep periods, and more self-reported TST and better sleep efficiency than Black participants. Our findings enhance the literature by utilizing robust measurement of sleep and circadian parameters to extend previous findings to a young adult sample at high or low risk for BSD.

Reward Responsiveness and Ruminative Styles Interact to Predict Inflammation and Mood Symptomatology.

Abnormal reward responsiveness and rumination each are associated with elevated inflammation and mood symptoms. Ruminating on positive and negative affect, or dampening positive affect, may amplify, or buffer, the associations of reward hyper/hyposensitivity with inflammation and mood symptoms. Young adults (N = 109) with high or moderate reward sensitivity completed reward responsiveness and ruminative style measures at the initial visit of a longitudinal study of mood symptoms, a blood draw to assess inflammatory biomarkers, and mood symptom measures at the study visits before and after the day of the blood draw. The interaction between high reward responsiveness and rumination on positive affect was associated with higher levels of an inflammatory composite measure and hypomanic symptoms. The interaction between lower reward responsiveness and high dampening of positive affect was associated with higher levels of the inflammatory composite measure and depressive symptoms. Lower reward responsiveness also interacted with low rumination on positive affect to predict increases in depressive symptoms and higher levels of the inflammatory composite. Thus, levels of reward responsiveness and ruminative response styles may synergistically influence the development of inflammatory phenotypes and both hypomanic and depressive mood symptoms.

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 role of lifetime anxiety history in the course of bipolar spectrum disorders.

Individuals with bipolar spectrum disorder (BSD) frequently meet criteria for comorbid anxiety disorders, and anxiety may be an important factor in the etiology and course of BSDs. The current study examined the association of lifetime anxiety disorders with prospective manic/hypomanic versus major depressive episodes. Participants were 244 young adults (aged 17-26) with milder forms of BSDs (i.e., bipolar-II, cyclothymia, BD-NOS). First, bivariate analyses assessed differences in baseline clinical characteristics between participants with and without DSM-IV anxiety diagnoses. Second, negative binomial regression analyses tested whether lifetime anxiety predicted number of manic/hypomanic or major depressive episodes developed during the study. Third, survival analyses evaluated whether lifetime anxiety predicted time to onset of manic/hypomanic and major depressive episodes. Results indicated that anxiety history was associated with greater illness severity at baseline. Over follow-up, anxiety history predicted fewer manic/hypomanic episodes, but did not predict number of major depressive episodes. Anxiety history also was associated with longer time to onset of manic/hypomanic episodes, but shorter time to onset of depressive episodes. Findings corroborate past studies implicating anxiety disorders as salient influences on the course of BSDs. Moreover, results extend prior research by indicating that anxiety disorders may be linked with reduced manic/hypomanic phases of illness.

Aggression Protects Against the Onset of Major Depressive Episodes in Individuals With Bipolar Spectrum Disorder.

A growing body of research suggests that bipolar spectrum disorders (BSDs) are associated with high aggression. However, little research has prospectively examined how aggression may affect time to onset of hypomanic/manic versus major depressive episodes. In a longitudinal study, we tested the hypothesis that aggression would prospectively predict a shorter time to the onset of hypomanic/manic episodes and a longer time to the onset of major depressive episodes, based on the behavioral approach system theory of BSDs. Young adults (N = 120) diagnosed with cyclothymia, bipolar II disorder, or bipolar disorder not otherwise specified were followed every 4 months for an average of 3.55 years. Participants completed measures of depressive and manic symptoms, family history of mood disorder, impulsivity, and aggression at baseline and were followed prospectively with semistructured diagnostic interview assessments of hypomanic/manic and major depressive episodes and treatment seeking for mood problems. Cox proportional hazard regression analyses indicated that overall, physical, and verbal aggression predicted a longer time to major depressive episode onset, even after controlling for baseline depressive and manic symptoms, family history of mood disorder, treatment seeking for mood problems, and impulsivity. Aggression, however, did not significantly predict time to onset of hypomanic/manic episodes, controlling for the same covariates. The findings suggest that approach-related behaviors may be utilized to delay the onset of major depressive episodes among people with BSDs.

Circadian Rhythm Dysregulation in Bipolar Spectrum Disorders.

PURPOSE OF REVIEW: We review recent evidence for circadian rhythm dysregulation in bipolar spectrum disorders (BSDs). We examine evidence for endogenous abnormalities in the biological clock and disruptions in the external entrainment of circadian rhythms in BSDs. We also address whether circadian dysregulation provides vulnerability to onset of BSD and evidence for a new integration of reward and circadian dysregulation in BSD. RECENT FINDINGS: Relative circadian phase delay (e.g., later melatonin peak, evening chronotype) is associated with BSD, particularly in the depressive phase. More consistent evidence supports irregularity of social rhythms, sleep/wake and activity patterns, and disruptions of social rhythms by life events, as stable trait markers of BSD and potential vulnerabilities for BSD onset. Growing research supports an integrative reward/circadian model. Both endogenous abnormalities in the biological clock pacemaking function and disruptions in the external entrainment of circadian rhythms by physical and social cues are involved in BSDs. Circadian dysregulation may provide vulnerability to BSD onset.

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.