A DSM-5-based tool to monitor concurrent mood and premenstrual symptoms: the McMaster Premenstrual and Mood Symptom Scale (MAC-PMSS).

BACKGROUND: Despite high co-morbidity between premenstrual dysphoric disorder and mood disorders, there is a gap of research-based tools to monitor concurrent premenstrual and mood symptoms. In this study, we developed a new DSM-5-based questionnaire to prospectively monitor concurrent premenstrual and mood symptoms. METHODS: Fifty-two females with bipolar or major depressive disorder, ages 16-45, were enrolled in the study. Participants completed two months of prospective symptom charting including the McMaster Premenstrual and Mood Symptom Scale (MAC-PMSS) and the Daily Record of Severity of Problems (DRSP). At the end of the prospective charting, participants also completed the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). The MAC-PMSS was correlated with the DRSP, MADRS, HDRS and YMRS. RESULTS: All individual items of the MAC-PMSS correlated strongly with the individual DRSP scores (all p < 0.001). The mood section of the MAC-PMSS also significantly correlated with MADRS (r = 0.572; p < 0.01), HDRS (r = 0.555; p < 0.01) and YMRS scores (r = 0.456; p < 0.01). CONCLUSIONS: The MAC-PMSS is a reliable to tool to measure concurrent mood and premenstrual symptoms in women with mood disorders.

Investigating biological rhythms disruptions across the menstrual cycle in women with comorbid bipolar disorder and premenstrual dysphoric disorder.

We investigated whether women diagnosed with comorbid bipolar disorder (BD) and premenstrual dysphoric disorder (PMDD) experience higher disruptions in biological rhythms in two independent study samples. The first study has a population-based sample of 727 women, including 104 women with PMDD only, 43 women with BD only, 24 women with comorbid PMDD and BD, and 556 women without BD or PMDD (controls). Biological rhythm disruptions were cross-sectionally evaluated using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). The second study enrolled 77 outpatient women who completed prospective assessments at two timepoints: during the mid-follicular and the late-luteal phases of their menstrual cycles, using the BRIAN, and included 19 women with PMDD, 16 with BD, 17 with comorbid PMDD and BD, and 25 controls. In the population-based sample, all the diagnostic groups (BD, PMDD, BDPMDD) presented greater biological rhythm disruption than controls. In addition, women with BD presented greater overall biological rhythms disruption, and greater disruption in sleep, activity, and eating patterns, than women with PMDD. In the outpatient sample study, women with BDPMDD showed greater disruption in the social domain than women with PMDD. In the outpatient sample, women with BDPMDD reported significantly higher disruptions in biological rhythms across both the follicular and the luteal phases of the menstrual cycle. The comorbidity between BD and PMDD may affect biological rhythms beyond the luteal phase of the menstrual cycle. These results support previous literature on the increased illness burden of women diagnosed with comorbid BD and PMDD.

Association of functioning and quality of life with objective and subjective measures of sleep and biological rhythms in major depressive and bipolar disorder.

OBJECTIVE: Disruptions in biological rhythms and sleep are a core aspect of mood disorders, with sleep and rhythm changes frequently occurring prior to and during mood episodes. Wrist-worn actigraphs are increasingly utilized to measure ambulatory activity rhythm and sleep patterns. METHODS: A comprehensive study using subjective and objective measures of sleep and biological rhythms was conducted in 111 participants (40 healthy volunteers [HC], 38 with major depressive disorder [MDD] and 33 with bipolar disorder [BD]). Participants completed 15-day actigraphy and first-morning urine samples to measure 6-sulfatoxymelatonin levels. Sleep and biological rhythm questionnaires were administered: Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), Munich Chronotype Questionnaire (MCTQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Actigraph data were analyzed for sleep and daily activity rhythms, light exposure and likelihood of transitioning between rest and activity states. RESULTS: Mood groups had worse subjective sleep quality (PSQI) and biological rhythm disruption (BRIAN) and higher objective mean nighttime activity than controls. Participants with BD had longer total sleep time, higher circadian quotient and lower 6-sulfatoxymelatonin levels than HC group. The MDD group had longer sleep onset latency and higher daytime probability of transitioning from rest to activity than HCs. Mood groups displayed later mean timing of light exposure. Multiple linear regression analysis with BRIAN scores, circadian quotient, mean nighttime activity during rest and daytime probability of transitioning from activity to rest explained 43% of variance in quality-of-life scores. BRIAN scores, total sleep time and probability of transitioning from activity to rest explained 52% of variance in functioning (all p < 0.05). CONCLUSIONS: Disruption in biological rhythms is associated with poorer functioning and quality of life in bipolar and MDD. Investigating biological rhythms and sleep using actigraphy variables, urinary 6-sulfatoxymelatonin and subjective measures provide evidence of widespread sleep and circadian system disruptions in mood disorders.

Performance of the biological rhythms interview for assessment in neuropsychiatry: An item response theory and actigraphy analysis.

BACKGROUND: Biological rhythm disturbances are widely associated with the pathophysiology of mood disorders. The Biological Rhythms Interview for Assessment in Neuropsychiatry (BRIAN) is a self-report that indexes rhythm disturbance in sleep, activity, social and eating patterns. The aim of this study was to perform an Item Response Theory (IRT) analysis of the BRIAN and investigate its associations with objective sleep and rhythm disturbance measures. METHODS: 103 subjects (31 bipolar, 32 major depression and 40 healthy volunteers) wore an actiwatch for fifteen days, and completed a first morning urine sample and the BRIAN on day 15. IRT analysis assessed individual BRIAN items and their relationship to total score. Individual actiwatch records were processed to produce a sequence of transitions between rest/activity, and a likelihood of transitioning between states was calculated to investigate sleep-wake dynamics. Cosinor analysis produced daily activity rhythms (DARs). Spearman correlations were used to assess the association between sleep/DAR variables and the BRIAN. RESULTS: IRT analyses showed that 11 of 18 BRIAN items displayed a high level of discrimination between item options across a range of BRIAN total scores. Total BRIAN score correlated with wake after sleep onset, total activity count during sleep, and urinary 6-sulphatoxymelatonin. BRIAN Activity domain correlated with the daytime transition probability from rest to activity. LIMITATIONS: The sample size may have been underpowered for the graded-response model employed in IRT. The study lacked an objective comparison for BRIAN eating and social domain. CONCLUSION: The present study reveals the BRIAN displays promising external validity compared to objective parameters of circadian rhythmicity.

Influence of endogenous estradiol, progesterone, allopregnanolone, and dehydroepiandrosterone sulfate on brain resting state functional connectivity across the menstrual cycle.

OBJECTIVE: To [1] study brain resting state functional connectivity (Rs-FC) in a well-characterized sample of healthy women in the mid-follicular and late luteal phases of the menstrual cycle; and [2] examine the correlation between endogenous E2, P, allopregnanolone, and DHEAS and patterns of Rs-FC across the menstrual cycle. DESIGN: We studied the Rs-FC of the default mode network, salience network, meso-paralimbic network, fronto-parietal network, visual network, and sensorimotor network in the mid-follicular and late luteal phases. Serum levels of E2, P, allopregnanolone, and DHEAS were correlated to patterns of functional connectivity. SETTING: University medical center. PATIENT(S): Twenty-five healthy women with regular menstrual cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Functional connectivity of key brain networks at rest and correlations of hormones to Rs-FC in the mid-follcuar and late luteal menstrual phases. RESULT(S): There were no differences in Rs-FC between the mid-follicular and late luteal menstrual phases using either independent component analysis or seed-based analysis. However, specific correlations between each hormone and patterns of functional connectivity were found in both menstrual cycle phases. CONCLUSION(S): It seems that the association between female sex hormones and brain Rs-FC is menstrual cycle phase-dependent. Future studies should examine the cognitive and behavioral correlates of this association in regularly cycling women.

Resting state functional connectivity in women with bipolar disorder during clinical remission.

OBJECTIVES: Periods of euthymia in bipolar disorder (BD) serve as a valuable time to study trait-based pathophysiology. The use of resting state functional connectivity (Rs-FC) can aid in the understanding of BD pathophysiology free of task or mood state biases. The present study investigated two unexplored areas of Rs-FC research in bipolar remission: (i) Rs-FC in women, controlling for the potential influence of premenstrual symptoms, and (ii) the use of both independent component analysis (ICA) and seed-based analysis (SBA) to investigate Rs-FC. METHODS: We investigated Rs-FC of the default mode network, meso-paralimbic network and fronto-parietal network in a sample of 32 euthymic women with BD and 36 age-matched controls during the mid-follicular phase of their menstrual cycle. Rs-FC was assessed with ICA and SBA using the posterior cingulate cortex (PCC), amygdala and dorsolateral prefrontal cortex (dlPFC) as seed points for their respective resting state networks. RESULTS: In BD, compared to controls, SBAs revealed increased coupling between the PCC and the angular gyrus (P=.002, false discovery rate [FDR]-corrected) and between the right dlPFC and the brainstem (P=.03, FDR-corrected). In BD only, PCC-angular gyrus coupling was correlated with anxiety symptoms. Group differences in Rs-FC using ICA did not survive multiple comparisons. CONCLUSIONS: Negative findings from whole-brain ICA Rs-FC may reflect a state of clinical remission in BD. Heightened activation between the PCC and the angular gyrus and between the dlPFC and the brainstem may reflect (i) an abnormal trait integration of affective information during clinical remission and/or (ii) an adaptive compensatory mechanism required for clinical stabilization.

Brain Structure and Function in Women with Comorbid Bipolar and Premenstrual Dysphoric Disorder.

INTRODUCTION: Hormonal fluctuations associated with female reproductive life events may precipitate or worsen affective episodes in women with bipolar disorder (BD). Previous studies have shown that women with BD report higher rates of premenstrual dysphoric disorder (PMDD) than controls. Further, bipolar women who report premenstrual worsening of mood display a worse course of their bipolar illness. Despite this, the neural correlates of comorbid BD and PMDD have not been investigated. METHODOLOGY: Eighty-five [CTRL, n = 25; PMDD, n = 20; BD, n = 21; BD with comorbid PMDD (BDPMDD), n = 19], regularly cycling women, not on hormonal contraception, underwent two MRI scans: during their mid-follicular and late luteal menstrual phases. We investigated resting-state functional connectivity (Rs-FC), cortical thickness, and subcortical volumes of brain regions associated with the pathophysiology of BD and PMDD between groups, in the mid-follicular and late luteal phases of the menstrual cycle. All BD subjects were euthymic for at least 2 months prior to study entry. RESULTS: Women in the BDPMDD group displayed greater disruption in biological rhythms and more subthreshold depressive and anxious symptoms through the menstrual cycle compared to other groups. Rs-FC was increased between the L-hippocampus and R-frontal cortex and decreased between the R-hippocampus and R-premotor cortex in BDPMDD vs. BD (FDR-corrected, p < 0.05). Cortical thickness analysis revealed decreased cortical thickness of the L-pericalcarine, L-superior parietal, R-middle temporal, R-rostral middle frontal, and L-superior frontal, as well as increased cortical thickness of the L-superior temporal gyri in BDPMDD compared to BD. We also found increased left-caudate volume in BDPMDD vs. BD (pCORR < 0.05). CONCLUSION: Women with BD and comorbid PMDD display a distinct clinical and neurobiological phenotype of BD, which suggests differential sensitivity to endogenous hormones.