Speech patterns are modulated by the emotional and neurophysiological state of the speaker. There exists a growing body of work that computationally examines this modulation in patients suffering from depression, autism, and post-traumatic stress disorder. However, the majority of the work in this area focuses on the analysis of structured speech collected in controlled environments. Here we expand on the existing literature by examining bipolar disorder (BP). BP is characterized by mood transitions, varying from a healthy euthymic state to states characterized by mania or depression. The speech patterns associated with these mood states provide a unique opportunity to study the modulations characteristic of mood variation. We describe methodology to collect unstructured speech continuously and unobtrusively via the recording of day-to-day cellular phone conversations. Our pilot investigation suggests that manic and depressive mood states can be recognized from this speech data, providing new insight into the feasibility of unobtrusive, unstructured, and continuous speech-based wellness monitoring for individuals with BP.

Bipolar disorder (BD) is a serious mood disorder associated with circadian rhythm abnormalities. Risk for BD is genetically encoded and overlaps with systems that maintain circadian rhythms. Lithium is an effective mood stabilizer treatment for BD, but only a minority of patients fully respond to monotherapy. Presently, we hypothesized that lithium-responsive BD patients (Li-R) would show characteristic differences in chronotype and cellular circadian rhythms compared to lithium non-responders (Li-NR). Selecting patients from a prospective, multi-center, clinical trial of lithium monotherapy, we examined morning vs. evening preference (chronotype) as a dimension of circadian rhythm function in 193 Li-R and Li-NR BD patients. From a subset of 59 patient donors, we measured circadian rhythms in skin fibroblasts longitudinally over 5 days using a bioluminescent reporter (Per2-luc). We then estimated circadian rhythm parameters (amplitude, period, phase) and the pharmacological effects of lithium on rhythms in cells from Li-R and Li-NR donors. Compared to Li-NRs, Li-Rs showed a difference in chronotype, with higher levels of morningness. Evening chronotype was associated with increased mood symptoms at baseline, including depression, mania, and insomnia. Cells from Li-Rs were more likely to exhibit a short circadian period, a linear relationship between period and phase, and period shortening effects of lithium. Common genetic variation in the IP 3 signaling pathway may account for some of the individual differences in the effects of lithium on cellular rhythms. We conclude that circadian rhythms may influence response to lithium in maintenance treatment of BD.

Polyunsaturated fatty acids (PUFA) profiles associate with risk for mood disorders. This poses the hypothesis of metabolic differences between patients and unaffected healthy controls that relate to the primary illness or are secondary to medication use or dietary intake. However, dietary manipulation or supplementation studies show equivocal results improving mental health outcomes. This study investigates dietary patterns and metabolic profiles relevant to PUFA metabolism, in bipolar I individuals compared to non-psychiatric controls. We collected seven-day diet records and performed metabolomic analysis of fasted plasma collected immediately after diet recording. Regression analyses adjusted for age, gender and energy intake found that bipolar individuals had significantly lower intake of selenium and PUFAs, including eicosapentaenoic acid (EPA) (n-3), docosahexaenoic acid (DHA) (n-3), arachidonic acid (AA) (n-6) and docosapentaenoic acid (DPA) (n-3/n-6 mix); and significantly increased intake of the saturated fats, eicosanoic and docosanoic acid. Regression analysis of metabolomic data derived from plasma samples, correcting for age, gender, BMI, psychiatric medication use and dietary PUFA intake, revealed that bipolar individuals had reduced 13S-HpODE, a major peroxidation product of the n-6, linoleic acid (LA), reduced eicosadienoic acid (EDA), an elongation product of LA; reduced prostaglandins G2, F2 alpha and E1, synthesized from n-6 PUFA; and reduced EPA. These observations remained significant or near significant after Bonferroni correction and are consistent with metabolic variances between bipolar and control individuals with regard to PUFA metabolism. These findings suggest that specific dietary interventions aimed towards correcting these metabolic disparities may impact health outcomes for individuals with bipolar disorder.

Background Hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been reported in bipolar disorder and also in suicidal behavior, but few studies have examined the relationship between suicidal behaviors and the HPA axis function in bipolar disorder, attending to and minimizing confounding factors. We compare HPA axis activity in bipolar individuals with and without suicidal behavior and unaffected healthy controls through measurement of salivary cortisol. Method Salivary cortisol was collected for three consecutive days in 29 controls, 80 bipolar individuals without a history of suicide and 56 bipolar individuals with a past history of suicide. Clinical factors that affect salivary cortisol were also examined. Results A past history of suicide was associated with a 7.4% higher bedtime salivary cortisol level in bipolar individuals. There was no statistical difference between non-suicidal bipolar individuals and controls in bedtime salivary cortisol and awakening salivary cortisol was not different between the three groups. Limitations The measure of salivary cortisol was a home based collection by the study subjects and the retrospective clinical data was primarily based on their historical account. Conclusions Bipolar individuals with a past history of suicidal behavior exhibit hyperactivity in the HPA axis. This biological marker remains significant regardless of demographic factors, mood state, severity and course of illness. This finding in bipolar disorder is consistent with the evidence for altered HPA axis functioning in suicide and mood disorders and is associated with a clinical subgroup of bipolar patients at elevated risk for suicide based on their history, and in need of further attention and study.