Too little or too much: nonlinear relationship between sleep duration and daily affective well-being in depressed adults.

BACKGROUND: In addition to having higher negative affect and lower positive affect overall, depressed individuals exhibit heightened affective reactivity to external stimuli than non-depressed individuals. Sleep may contribute to day-to-day fluctuations in depressed individuals, given that sleep disturbance is a common symptom of depression. Yet, little is known about changes in daily affect as a function of nightly sleep duration in depressed adults and non-depressed adults. The current study examined whether and how naturally-occurring sleep duration is associated with negative and positive affect, and how these associations differ between depressed vs. non-depressed adults. METHODS: Data were drawn from the second wave of the National Study of Daily Experiences (NSDE), a daily diary project of the Midlife in the United States (MIDUS) study. The sample of 2,012 adults (Mage=56.5; 57% female; 84% white) completed eight-day diary interviews via telephone on their daily experiences including nightly sleep duration and negative and positive affect. They also completed assessments of the Composite International Diagnostic Interview-Short form, and depressed status was determined based on DSM-III. Multilevel regression models with linear, quadratic, and cubic terms of sleep duration examined the nonlinear relationship between nightly sleep duration and daily affect. Interaction terms with depression status were added to examine differences between depressed and non-depressed adults. RESULTS: Depressed adults exhibited significant and greater fluctuations in daily affect as a function of nightly sleep duration than non-depressed adults. Specifically, the degree of decrease in positive affect and increase in negative affect was greater when depressed adults slept 2 or more hours less or longer than their usual sleep hours. Non-depressed adults exhibited relatively stable daily affect regardless of their nightly sleep hours. CONCLUSIONS: Sleep duration is nonlinearly associated with affect in daily lives of depressed adults, highlighting that both having too little sleep and excessive sleep are associated with adverse daily affective well-being. Implementing sleep interventions to promote an appropriate sleep duration may help improve daily affect among depressed adults.

Daily Affective Dynamics in Major Depressive Disorder: The Role of Daily Stressors and Positive Events.

This study examined daily affective dynamic indices among individuals with a major depressive disorder (MDD) diagnosis in the past one year at the time of the interview, focusing on affective variability and change in affect in response to daily events (affective reactivity). Data were from the main survey and daily diary project of the Midlife in the United States (MIDUS) study. Participants (N = 1,970; nMDD = 202; nnon-MDD = 1,768) completed structured clinical interviews on mental health and telephone interviews about their daily experiences spanning eight consecutive days. Multilevel models revealed that the MDD group experienced greater positive (PA) and negative affect (NA) variability than the non-MDD group. On days that at least one stressful event was reported, the MDD group experienced a greater decrease in PA and a greater increase in NA. On days that at least one positive event was reported, the MDD group experienced a greater increase in PA and a greater decrease in NA. Changes in affect to daily events, particularly the mood brightening effect, may be indicators of depression and potential targets for intervention. Limitations of the study include a community sample, reliance on self-reported measures of daily stressors and positive events, inclusion of remitted and current MDD participants, and the DSM-III-R based criteria for MDD diagnosis.

Gender differences in transdiagnostic domains and function of adults measured by DSM-5 assessment scales at the first clinical visit: a cohort study.

BACKGROUND: Measurement-based care has been called for as best practice in psychiatric care and learning health systems and use of transdiagnostic measures was suggested as part of the DSM-5. Our objective is to examine gender differences in first visit socioeconomic, transdiagnostic, and functional characteristics of a dynamic, real-world measurement-based care cohort. METHODS: Transdiagnostic, functional, and clinical measures were collected from 3,556 patients at first visit in an ambulatory psychiatric clinic. All patients were evaluated at the first visit by board-certified psychiatrists or licensed clinical psychologists. Demographic variables and clinical diagnoses were collected from the Electronic Medical Record. Self-report measures were collected that assessed transdiagnostic symptoms (DSM-5 Level 1 Cross-cutting Measure and Level 2 symptom scales), disability, alcohol use, attention deficit hyperactivity disorder (ADHD) symptoms, depression, anxiety, mania, suicidal thoughts and behaviors, and trauma exposure. RESULTS: Men and women did not differ in age, BMI, household income, high school graduation rate, race, or ethnicity, but women were more likely to be formerly married and less likely to have commercial insurance. Compared to men, women reported significantly higher overall psychopathology on the transdiagnostic Level 1 Cross-cutting measure and had higher depression, anxiety, sleep, anger, ADHD combined presentation, and suicidality severity. Women also had higher disability scores than men. However, men reported higher alcohol, tobacco and substance use, and more risky behavior than women. Trauma exposure differed significantly by gender; men reported more exposure to accidents, war-related trauma, serious accidents, and major disasters and women reported more unwanted sexual contact. CONCLUSIONS: This cross-sectional study of a transdiagnostic, ecologically-valid real-word measurement-based care cohort demonstrates gender differences in socioeconomic factors, trauma exposure, transdiagnostic symptoms, and functioning.

Reinforcement-based responsiveness, depression, and anhedonia: A multi-method investigation of intergenerational risk.

Offspring of depressed parents are at an increased risk for depression. Reward- and punishment-based systems might be mechanisms linking maternal outcomes to offspring depression and anhedonia. The current study was designed to investigate the intergenerational relations between maternal markers of reward and punishment responsiveness and their offspring's depression and anhedonia in a community sample of 40 mother (mean age = 44.5; SD = 6.82) and adolescent (mean age = 14.73; SD = 1.25; 52.5% female) dyads. Maternal markers of reward and punishment responsiveness were captured using self-report, behavioral, and neurophysiological methods, and self-reported depression and anhedonia symptoms were used as outcomes among the adolescent offspring. Maternal self-reported reward responsiveness and punishment learning rates were differentially associated with depression across male and female offspring. Regarding anhedonia, maternal punishment learning rate was positively related to adolescent anhedonia regardless of offspring biological sex. Maternal reward learning rate was also positively associated with anhedonia among male offspring. In general, low concurrence across self-report, behavioral, and neurophysiological markers of reward and punishment responsiveness was found. The results from the current study suggest that learning-rates on reinforcement-based behavioral tasks may be important objective markers to consider when evaluating intergenerational risk.

Leveraging Decision Science to Characterize Depression.

This brief review examines the potential to use decision science to objectively characterize depression. We provide a brief overview of the existing literature examining different domains of decision-making in depression. Because this overview highlights the specific role of reinforcement learning as an important decision process affected in the disorder, we then introduce reinforcement learning modeling and explain how this approach has identified specific reinforcement learning deficits in depression. We conclude with ideas for future research at the intersection of decision science and depression, emphasizing the potential for decision science to help uncover underlying mechanisms and targets for the treatment of depression.

Transdiagnostic and functional predictors of depression severity and trajectory in the Penn state psychiatry clinical assessment and rating evaluation system (PCARES) registry.

BACKGROUND: Timely, accurate diagnosis and subsequent identification of risk factors for depression that is difficult-to-treat can aid in decreasing the burden of depressive illness and reducing probability of future disability. We aimed to identify sociodemographic, clinical, and functional factors that predict depression severity over one year in a real-world, naturalistic, transdiagnostic clinical sample. A subset sample with moderate depression was examined to determine the magnitude of improvement. METHODS: The Penn State Psychiatry Clinical Assessment and Rating System (PCARES) Registry houses data from systematically-structured patient-reported outcomes and clinical data from an Electronic Medical Record (EMR) gathered during routine clinical care of patients seeking mental health care at a mid-Atlantic clinic. Self-report symptom and functional measures were obtained, and sociodemographic features and clinical diagnoses were extracted from the EMR from 1,766 patients between 2/6/2016 to 9/30/2019. The Patient Health Questionnaire 9 (PHQ-9) depression scale was obtained at each visit. Using a discrete mixture clustering model, the study population was divided into five longitudinal trajectory groups, termed depression severity groups, based on intra-individual PHQ-9 score trajectories over one year. Multinomial logistic regression models were estimated to evaluate associations between characteristics and the likelihood of depression severity group membership. To determine the magnitude of improvement, predictors of the slope of the PHQ-9 trajectory were examined for patients with moderate depression. RESULTS: The strongest predictors of high depression severity over one year were poor functioning, high transdiagnostic DSM-5 Level 1 crosscutting symptom score, diagnosis of Post-Traumatic Stress Disorder (PTSD), public/self-pay insurance, female gender, and non-White race. Among the subset of patients with moderate depression, strong predictors of improvement were commercial insurance and exposure to trauma; the strongest predictors of worsening were high functional impairment, high transdiagnostic Level 1 symptom score, diagnosis of PTSD, diagnosis of bipolar disorder, and marital status of single or formerly married; depression-specific symptom measures were not predictive. LIMITATIONS: Limitations include inferring education and income status from zip code level-data, the non-random missingness of data, and the use of diagnoses collected from the electronic medical record. CONCLUSION: Functional impairment, transdiagnostic measures of symptom burden, and insurance status are strong predictors of depression severity and poor outcome.

Adjunctive dietary intervention for bipolar disorder: a randomized, controlled, parallel-group, modified double-blinded trial of a high n-3 plus low n-6 diet.

OBJECTIVE: To investigate the preliminary efficacy of a high n-3 plus low n-6 (H3-L6) dietary intervention in improving mood stability in Bipolar Disorder (BD) when compared to dietary intervention with usual U.S. levels of n-6 and n-3 polyunsaturated fatty acid (PUFA) intakes (control diet, CD). METHODS: This 2-arm, parallel-group, randomized, modified double-blind, controlled 48-week study of 12-week intensive diet intervention in subjects with BD was conducted at a single suburban-rural site in the mid-Atlantic region. Participants with DSM-IV TR BD I or II with hypomanic or depressive symptoms were randomized, stratified on gender (N = 82). The intervention included the provision of group-specific study foods and dietary counseling. Variability of mood symptoms was measured by a twice-daily, 12-week ecological momentary analysis (EMA) paradigm, and group differences were analyzed using multilevel models. Circulating n-3 and n-6 fatty acids were measured at baseline and after 4, 8, and 12 weeks of diet exposure. RESULTS: All 82 randomized participants were included in biochemical analyses. Seventy participants completed at least 2 EMA surveys and were included in primary EMA analyses. Variability in mood, energy, irritability, and pain as measured using EMA was reduced in the H3-L6 group compared to the CD group. No significant differences in mean ratings of mood symptoms, or any other symptom measures, were detected. The dietary intervention effect on target PUFAs significantly differed by the group over time. CONCLUSIONS: A dietary intervention adjunctive to usual care showed preliminary efficacy in improving variability in mood symptoms in participants with BD. TRIAL REGISTRATION: ClinicalTrials.Gov NCT02272010.

Evidence from an fMRI study that dessert-flavored e-cigarettes engage taste-related, but not smoking-related, brain circuitry for female daily smokers.

Regulations limiting the sale of flavored e-cigarette products are controversial for their potential to interfere with e-cigarette use as a cessation aid in addition to curbing youth use. Limited research suggests that flavor might enhance the addictive potential of e-cigarettes; however, the acute effects of flavored aerosols on brain function among humans have not been assessed. The present study aimed to isolate and compare the neural substrates of flavored and unflavored e-cigarette aerosols on brain function among nine female daily smokers. Participants inhaled aerosolized e-liquid with 36 mg/mL of nicotine with and without a strawberry-vanilla flavor while undergoing functional magnetic resonance imaging. We used general linear modeling to compare whole-brain mean neural activation and seed-to-voxel task-based functional connectivity between the flavored and unflavored inhalation runs. Contrary to our hypothesis, the flavored aerosol was associated with weaker activation than the unflavored aerosol in the brain stem and bilateral parietal-temporal-occipital region of the cortex. Instead, the flavor engaged taste-related brain regions while suppressing activation of the neural circuits typically engaged during smoking and nicotine administration. Alternatively, functional connectivity between subcortical dopaminergic brain seeds and cortical brain regions involved in motivation and reward salience were stronger during the flavored compared to unflavored aerosol run. The findings suggest that fruity and dessert-flavored e-cigarettes may dampen the reward experience of aerosol inhalation for smokers who initiate e-cigarette use by inhibiting activation of dopaminergic brain circuits. These preliminary findings may have implications for understanding how regulations on flavored e-cigarettes might impact their use as cessation aids. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Dysregulated Diurnal Cortisol Pattern and Heightened Night-Time Cortisol in Individuals with Bipolar Disorder.

INTRODUCTION: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may contribute to the symptom burden in bipolar disorder (BD). Further characterization of cortisol secretion is needed to improve understanding of the connection between mood, sleep, and the HPA axis. Here, we observe diurnal cortisol patterns in individuals with BD and healthy controls (HCs) to determine time points where differences may occur. METHODS: Salivary cortisol was measured at 6 time points (wake, 15, 30, and 45 min after wake, between 2:00 and 4:00 p.m. and 10:00 p.m.) for 3 consecutive days in individuals with symptomatic BD (N = 27) and HC participants (N = 31). A general linear model with correlated errors was utilized to determine if salivary cortisol changed differently throughout the day between the 2 study groups. RESULTS: A significant interaction (F = 2.74, df = 5, and p = 0.02) was observed between the time of day and the study group (BD vs. HC) when modeling salivary cortisol over time, indicating that salivary cortisol levels throughout the day significantly differed between the study groups. Specifically, salivary cortisol in BD was elevated compared to HCs at the 10:00 p.m. time point (p = 0.01). CONCLUSION: Significantly higher levels of cortisol in participants with BD in the night-time suggest that the attenuation of cortisol observed in healthy individuals may be impaired in those with BD. Reregulation of cortisol levels may be a target of further study and treatment intervention for individuals with BD.

Reregulation of cortisol levels and sleep in patients with prescription opioid use disorder during long-term residential treatment.

OBJECTIVE: Research has demonstrated that hypothalamic-pituitary-adrenal (HPA) axis function and sleep patterns are dysregulated in patients diagnosed with opioid use disorder (OUD). It is unclear whether and/or when cortisol and sleep might re-regulate over time, and, whether re-regulation is associated with abstinence following discharge from residential treatment. The current study evaluated changes in sleep and basal cortisol levels in prescription OUD patients in residential treatment, and the association between these measures and treatment outcome following discharge. METHOD: As part of a larger study, 55 participants with prescription OUD provided two days of salivary cortisol samples and 12 consecutive nights of sleep actigraphy between days 19-30 of residential treatment (Time Point 1; TP1). Thirteen of the original 55 participants remained in residence and repeated the measures between days 60-72 (Time Point 2; TP2). Thirty-seven healthy controls (HC) provided baseline measures (TP1) of salivary cortisol and sleep. Treatment outcome data, abstinence vs relapse, were established at 120 days following discharge. RESULTS: Prescription OUD patients had higher cortisol levels and lower total sleep time (TST) than HC at TP1. At TP2, TST and cortisol levels no longer differed from HCs in the subgroup of patients who remained abstinent following discharge after TP2. Individuals whose cortisol and TST did not change from TP1 to TP2 were more likely to relapse following discharge from residential treatment. CONCLUSION: Re-regulation of TST and cortisol levels while in residential treatment was associated with better treatment outcome following discharge for prescription OUD patients.

Predictors of diagnostic delay: Assessment of psychiatric disorders in the clinic.

BACKGROUND: Diagnostic delay contributes to morbidity in psychiatric disorders. METHODS: Patients in an ambulatory psychiatry clinic were given patient-reported outcome measures at an initial visit, and a subset (N = 493) were given a structured interview (MINI International Neuropsychiatric Interview, MINI), in addition to the clinical encounter (CLIN). Diagnostic agreement between MINI and CLIN was assessed at an initial and follow-up visit. Diagnostic delay was identified if diagnostic disagreement between MINI and CLIN occurred at the initial visit and changed to an agreement at a follow-up visit. Registry data was compiled by an honest broker. RESULTS: Significant agreement occurred between MINI and CLIN diagnoses for major depressive disorder (MDD), bipolar disorder (BD), generalized anxiety disorder, and panic disorder. Diagnostic agreement for MDD occurred at initial visit for 63% of patients, and at follow-up for 87% of those with initial diagnostic disagreement; for BD, 75% at initial visit and 28% at follow-up. No demographic, socioeconomic, symptom severity or functioning measures predicted diagnostic agreement for the MDD group at the first visit, however initial psychopathological symptom complexity predicted diagnostic agreement in the diagnostic delay group. Initial diagnostic agreement for BD was predicted by lower symptom burden and better social, physical, and occupational functioning. No factors predicted additional diagnostic agreement at the second visit in the diagnostic delay group. CONCLUSION: Initial assessment by a structured interview aided physicians in identifying MDD by the second visit in patients with complex psychopathology. Patients with high complexity/severity of symptoms and more difficulty with functioning were less commonly identified with BD even with the assistance of a structured interview. Use of structured assessment tools may improve the detection of psychiatric illness by clinicians at the first visit.

Reward and punishment reversal-learning in major depressive disorder.

Depression has been associated with impaired reward and punishment processing, but the specific nature of these deficits is still widely debated. We analyzed reinforcement-based decision making in individuals with major depressive disorder (MDD) to identify the specific decision mechanisms contributing to poorer performance. Individuals with MDD (n = 64) and matched healthy controls (n = 64) performed a probabilistic reversal-learning task in which they used feedback to identify which of two stimuli had the highest probability of reward (reward condition) or lowest probability of punishment (punishment condition). Learning differences were characterized using a hierarchical Bayesian reinforcement learning model. Depressed individuals made fewer optimal choices and adjusted more slowly to reversals in both the reward and punishment conditions. Computational modeling revealed that depressed individuals showed lower learning-rates and, to a lesser extent, lower value sensitivity in both the reward and punishment conditions. Learning-rates also predicted depression more accurately than simple performance metrics. These results demonstrate that depression is characterized by a hyposensitivity to positive outcomes, but not a hypersensitivity to negative outcomes. Additionally, we demonstrate that computational modeling provides a more precise characterization of the dynamics contributing to these learning deficits, offering stronger insights into the mechanistic processes affected by depression. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Multiple Facets of Value-Based Decision Making in Major Depressive Disorder.

Depression is clinically characterized by obvious changes in decision making that cause distress and impairment. Though several studies suggest impairments in depressed individuals in single tasks, there has been no systematic investigation of decision making in depression across tasks. We compare participants diagnosed with Major Depressive Disorder (MDD) (n = 64) to healthy controls (n = 64) using a comprehensive battery of nine value-based decision-making tasks which yield ten distinct measures. MDD participants performed worse on punishment (d = -0.54) and reward learning tasks (d = 0.38), expressed more pessimistic predictions regarding winning money in the study (d = -0.47) and were less willing to wait in a persistence task (d = -0.39). Performance on learning, expectation, and persistence tasks each loaded on unique dimensions in a factor analysis and punishment learning and future expectations each accounted for unique variance in predicting depressed status. Decision-making performance alone could predict depressed status out-of-sample with 72% accuracy. The findings are limited to MDD patients ranging between moderate to severe depression and the effects of medication could not be accounted for due to the cross sectional nature of the study design. These results confirm hints from single task studies that depression has the strongest effects on reinforcement learning and expectations about the future. Our results highlight the decision processes that are impacted in major depression, and whose further study could lead to a more detailed computational understanding of distinct facets of this heterogeneous disorder.

Use of ecological momentary assessment to detect variability in mood, sleep and stress in bipolar disorder.

OBJECTIVE: Our aim was to study within-person variability in mood, cognition, energy, and impulsivity measured in an Ecological Momentary Assessment paradigm in bipolar disorder by using modern statistical techniques. Exploratory analyses tested the relationship between bipolar disorder symptoms and hours of sleep, and levels of pain, social and task-based stress. We report an analysis of data from a two-arm, parallel group study (bipolar disorder group N = 10 and healthy control group N = 10, with 70% completion rate of 14-day surveys). Surveys of bipolar disorder symptoms, social stressors and sleep hours were completed on a smartphone at unexpected times in an Ecological Momentary Assessment paradigm twice a day. Multi-level models adjusted for potential subject heterogeneity were adopted to test the difference between the bipolar disorder and health control groups. RESULTS: Within-person variability of mood, energy, speed of thoughts, impulsivity, pain and perception of skill of tasks was significantly higher in the bipolar disorder group compared to health controls. Elevated bipolar disorder symptom domains in the evening were associated with reduced sleep time that night. Stressors were associated with worsening of bipolar disorder symptoms. Detection of symptoms when an individual is experiencing difficulty allows personalized, focused interventions.

Interest Among Primary Care Patients in Group Problem-Solving Gameplay for Mental Health.

Mental health programs to improve problem-solving skills and reduce stress through social gameplay can improve psychiatric outcomes, but little is known about whether adult patients are interested in using them. Primary care patients (n = 467) completed a cross-sectional survey to assess interest in using 2 types of group programs for mental health. A significantly greater percentage (23.7%) of patients expressed interest in a gameplay-based program than in interpersonal therapy (17.6%) (P < .001). Lonely patients and younger patients were more likely to report interest in gameplay. Results suggest that diverse patient populations are interested in using gameplay programs for mental health.

Subjective and objective sleep discrepancy in symptomatic bipolar disorder compared to healthy controls.

BACKGROUND: Bipolar disorder (BD) is associated with sleep misperception. The objective of this study was to investigate the correlation between subjective and objective measures of sleep in persons with symptomatic bipolar disorder (BDS) compared to healthy controls (HC). METHODS: We studied 24 BDS and 30 HC subjects similar in age, race and sex. Subjective sleep was measured with Pittsburgh Sleep Quality Index (PSQI) and objective sleep with 7-days of actigraphy. Absolute discrepancy variables were calculated by subtracting objective sleep latency (SL) and total sleep time (TST) on actigraphy from their respective subjective estimates from PSQI. Mood symptoms were measured with Young Mania Rating Scale and Hamilton Depression Rating Scale. RESULTS: In the BDS group, subjective TST did not significantly correlate with objective TST, while it correlated in the HC group. The BDS group had significantly higher absolute discrepancy between subjective and objective SL and TST compared to the HC group. Multivariable regression analysis showed that severity of depression was associated with greater absolute discrepancy between subjective and objective TST within the BDS group. LIMITATIONS: Subjects are from a tertiary care center and were on medications for treatment of BD symptoms. CONCLUSION: There is low correlation between subjective and objective TST in BDS subjects and more severe depressive symptoms are associated with greater absolute discrepancy in TST. Objective rather than subjective measures of sleep, such as actigraphy, may be needed to evaluate sleep in BD subjects. Cognitive-behavioral interventions to address sleep misperception and associated depressed mood may be indicated in BD.

A longitudinal examination of event-related potentials sensitive to monetary reward and loss feedback from late childhood to middle adolescence.

Brain regions involved in reward processing undergo developmental changes from childhood to adolescence, and alterations in reward-related brain function are thought to contribute to the development of psychopathology. Event-related potentials (ERPs), such as the reward positivity (RewP) component, are valid measures of reward responsiveness that are easily assessed across development and provide insight into temporal dynamics of reward processing. Little work has systematically examined developmental changes in ERPs sensitive to reward. In this longitudinal study of 75 youth assessed 3 times across 6years, we used principal components analyses (PCA) to differentiate ERPs sensitive to monetary reward and loss feedback in late childhood, early adolescence, and middle adolescence. We then tested reliability of, and developmental changes in, ERPs. A greater number of ERP components differentiated reward and loss feedback in late childhood compared to adolescence, but components in childhood accounted for only a small proportion of variance. A component consistent with RewP was the only one to consistently emerge at each of the 3 assessments. RewP demonstrated acceptable reliability, particularly from early to middle adolescence, though reliability estimates varied depending on scoring approach and developmental period. The magnitude of the RewP component did not significantly change across time. Results provide insight into developmental changes in the structure of ERPs sensitive to reward, and indicate that RewP is a consistently observed and relatively stable measure of reward responsiveness, particularly across adolescence.

Total sleep time and kynurenine metabolism associated with mood symptom severity in bipolar disorder.

OBJECTIVE: Chronic, low-level inflammation is associated with symptomatic bipolar disorder (BD) and with chronic insomnia. Disrupted sleep is a feature of episodes of both mania and depression. We examined the effect of neopterin, a marker of cellular immune activation, and kynurenine (KYN), an inflammatory byproduct of the serotonin pathway, on the association between total sleep time and depression severity in BD. METHOD: Twenty-one symptomatic BD participants and 28 healthy controls (HC) were recruited and followed during usual clinical care. At baseline and after symptomatic recovery, total sleep time was objectively measured with actigraphy for 1 week and blood plasma was collected to measure the serotonin precursor tryptophan (TRP), KYN, the KYN/TRP ratio, and neopterin levels. Statistical analyses were conducted using chi-square, independent t tests and hierarchical linear multiple regression models. RESULTS: Total sleep time was correlated positively with depressive severity and negatively with manic severity. TRP was significantly reduced in BD participants compared to HC. KYN, TRP, and the KYN/TRP ratio were associated with depressive severity when total sleep time and body mass index (BMI) were included in the model. The KYN/TRP ratio trended towards a negative association with mania symptoms, controlling for BMI and total sleep time, in acutely symptomatic BD participants. Neopterin was not associated with sleep or mood severity. After usual clinical care, BD participants showed significantly decreased clinical symptoms but no significant differences in sleep phenotype or biomarkers. CONCLUSION: Inflammation, sleep, and mood are closely intertwined. Future research into the effect of inflammation on sleep in BD may lead to clinical markers of outcome.

Peripheral zinc and neopterin concentrations are associated with mood severity in bipolar disorder in a gender-specific manner.

Bipolar disorder (BD) is a recurrent, episodic mood disorder for which there are no current diagnostic, prognostic or theranostic biomarkers. Two peripheral markers of the acute phase immune response, zinc and neopterin, are consistently associated with severity of depression in literature. Given gender differences in clinical presentation of BD and in inflammatory processes, we aimed to explore the interaction between gender and immune biomarkers to predict mood severity in BD. Participants with DSM IV BD I and II were recruited through the Pennsylvania Psychiatric Institute during an acute mood episode. Healthy controls (HC) were recruited through advertisements. Participants fasted for at least 6h when blood was drawn for biomarkers. We found that zinc concentrations were significantly lower in the BD group at baseline (p<.05), and there was also a significant interaction between gender and zinc (p<.05), associated with depression severity. Also, we found a significant interaction between gender and neopterin, associated with mania severity (p<.05). We found that mania severity was associated with neopterin in men, while depression severity was positively associated with zinc in women. Our report bears replication in larger samples and highlights the potential for differences in the underlying pathophysiology between men and women with BD.