Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment.

OBJECTIVES: Omega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n-3 PUFAs would be lower and those of n-6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n-3 but lower n-6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids. METHODS: This observational, parallel group study compared biomarkers between HCs (n = 31) and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow-up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n-3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n-6:n-3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t-tests, and between the BD group at baseline and follow-up using paired t-tests. Comparison of categorical variables was performed using chi-square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis. RESULTS: UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d = 0.86, p < 0.002); however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between the BD and HC groups after Bonferroni correction for 40 comparisons, at p < 0.001. Neither depressive severity nor mania severity was correlated significantly with any PUFA concentration. Exploratory comparison showed lower UE:E EPA in the BD than the HC group (p < 0.0001). At follow-up in the BD group, UE, E DHA:ALA, and UE EPA:ALA were decreased (p < 0.002). Exploratory correlations of clinical variables revealed that mania severity and suicidality were positively correlated with UE:E EPA ratio, and that several plasma levels and ratios correlated with panic disorder and psychosis. Depressive severity was not correlated with any ratio. No plasma fatty acid level or ratio correlated with self-reported n-3 PUFA intake or use of medication by class. CONCLUSIONS: A large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio of EPA in the symptomatic BD state may be important factors in vulnerability to a mood state. Altered n-3 PUFA ratios could indicate changes in PUFA metabolism concurrent with symptom improvement. Our findings are consistent with preclinical and postmortem data and suggest testing interventions that increase n-3 and decrease n-6 dietary PUFA intake.

CPAP-induced mania in bipolar disorder: a case report.

OBJECTIVE: In this case report we present our clinical observations of two patients with bipolar disorder with comorbid obstructive sleep apnea (OSA) who were treated with continuous positive airway pressure (CPAP) for their sleep apnea. BACKGROUND: Bipolar disorder is a psychiatric disorder characterized by the presence of one or more episodes of mania and frequent episodes of depression. This disorder affects approximately 0.8% of the adult population, with estimates from community samples ranging between 0.4% and 1.6%. OSA syndrome is a severe sleep disorder with a prevalence of 2-4% in the general population, the risk of which is increased by obesity. The prevalence of OSA is expected to be high in bipolar disorder due to high comorbid obesity. It is expected that improvement in OSA in patients with bipolar disorder with CPAP will improve mood and other symptoms of bipolar disorder. However, there is a relative lack of data examining this aspect. RESULTS: In both cases of bipolar disorder, CPAP was started after a polysomnographic diagnosis of OSA and CPAP titration study indicating that most of the apneas/hypopneas were eliminated with a significant improvement in oxygen saturation. To our surprise, we noted that in both of these cases initiation of CPAP resulted in manic symptoms. CONCLUSIONS: Clinicians need to monitor patients with bipolar disorder closely for worsening of manic symptoms when they are started on CPAP for underlying OSA.

Impulsivity, anxiety, and alcohol misuse in bipolar disorder comorbid with eating disorders.

BACKGROUND: Eating disorders (ED) are noted to occur with bipolar disorder (BD), but relationships between additional comorbidities, clinical correlates, and personality factors common to both remain largely unknown. METHODS: Using data from the Prechter Longitudinal Study of Bipolar Disorder, we measured the prevalence and demographic factors of comorbid ED with BD, presence of additional comorbidity of anxiety and substance use disorders, psychosis, suicide attempts, mixed symptoms, childhood abuse, impact of NEO-Personality Inventory (NEO-PI) personality factors, and mood outcome in 354 patients with BD. We analyzed the prevalence of ED using both broad and narrow criteria. RESULTS AND DISCUSSION: ED was more common in the Prechter BD sample than the general population, with the majority of those with ED being female. Anxiety disorders, alcohol abuse/dependence, and NEO-PI N5 impulsiveness were independently associated with ED in a multivariable linear regression analysis. BD age at onset was earlier in the ED group than that in the non-ED group and was earlier than the average onset of ED. Anxiety occurred before ED and alcohol use disorders after both BD and ED. Childhood trauma was associated with ED. Impulsivity and anxiety associated with BD may fuel ED and put patients at risk for other impulsivity-related disorders such as alcohol use disorders. ED was associated with more severe and variable moods and more frequent depression. Patients with BD should be regularly screened for ED, anxiety disorders, and alcohol use disorders, and comorbidity should be promptly addressed.

Sleep quality during euthymia in bipolar disorder: the role of clinical features, personality traits, and stressful life events.

BACKGROUND: Poor sleep quality is known to precede the onset of mood episodes and to be associated with poor treatment outcomes in bipolar disorder (BD). We sought to identify modifiable factors that correlate with poor sleep quality in BD independent of residual mood symptoms. METHODS: A retrospective analysis was conducted to assess the association between the Pittsburgh Sleep Quality Index and clinical variables of interest in euthymic patients with DSM-IV BD (n = 119) and healthy controls (HC; n = 136) participating in the Prechter Longitudinal Study of Bipolar Disorder. Multivariable linear regression models were constructed to investigate the relationship between sleep quality and demographic and clinical variables in BD and HC participants. A unified model determined independent predictors of sleep quality. RESULTS AND DISCUSSION: Euthymic participants with BD and HC differed in all domains. The best fitting unified multivariable model of poor sleep quality in euthymic participants with BD included rapid cycling (ß = .20, p = .03), neuroticism (ß = .28, p = 2 × 10(-3)), and stressful life events (ß = .20, p = .02). Poor sleep quality often persists during euthymia and can be a target for treatment. Clinicians should remain vigilant for treating subjective sleep complaints independent of residual mood symptoms in those sensitive to poor sleep quality, including individuals with high neuroticism, rapid cycling, and recent stressful life events. Modifiable factors associated with sleep quality should be targeted directly with psychosocial or somatic treatment. Sleep quality may be a useful outcome measure in BD treatment studies.