Martina Ruzickova

Clinical Features of Bipolar Disorder with and without Comorbid Diabetes Mellitus

Objective: Several papers have reported higher prevalence of diabetes mellitus (DM) type 2 in patients suffering from bipolar disorder (BD). The possible links between these 2 disorders include treatment, lifestyle, alterations in signal transduction, and possibly, a genetic link. To study this relation more closely, we investigated whether there are any differences in the clinical characteristics of BD patients with and without DM. Method: We compared the clinical data of 26 diabetic and 196 nondiabetic subjects from The Maritime Bipolar Registry. Subjects were aged 15 to 82 years, with psychiatric diagnoses of BD I (n = 151), BD II (n = 65), and BD not otherwise specified (n = 6). The registry included basic demographic data and details on the clinical course of bipolar illness, its treatment, and physical comorbidity. In a subsequent analysis using logistic regression, we examined the variables showing differences between groups, with diabetes as an outcome variable. Results: The prevalence of DM in our sample was 11.7% (n = 26). Diabetic patients were significantly older than nondiabetic patients (P < 0.001), had higher rates of rapid cycling (P = 0.02) and chronic course of BD (P = 0.006), scored lower on the Global Assessment of Functioning Scale (P = 0.01), were more often on disability for BD (P < 0.001), and had higher body mass index (P < 0.001) and increased frequency of hypertension (P = 0.003). Lifetime history of treatment with antipsychotics was not significantly associated with an elevated risk of diabetes (P = 0.16); however, the data showed a trend toward more frequent use of antipsychotic medication among diabetic subjects. Conclusions: Our findings suggest that the diagnosis of DM in BD patients is relevant for their prognosis and outcome.

An admixture analysis of the age at index episodes in bipolar disorder

The interaction between polarity at onset (PAO) and age at onset (AAO) appears to be important for interpreting results of previous analyses of AAO in bipolar disorder (BD). Using an admixture analysis, we examined independently the distributions of age at first depressive and hypomanic/manic episodes in 379 BD I and II patients. Subsequently, we examined the association of PAO and AAO with specific clinical variables, using parametric and nonparametric analyses. Both depressive and manic onsets showed bimodal distributions. For depressive episodes, the means were: 18.5±4.1 (early onset) and 33.6±10.4 (late onset) years; and for manic episodes 18.9±3.3 (early onset) and 34.8±10.9 (late onset) years. For the overall AAO the best fit was for a mixture of three lognormal distributions (mean±S.D.): 15.5±2.0, 22.8±4.6, and 36.1±10.1years. Overall, an early onset was significantly associated with a chronic course of the disorder, a stronger family history of affective disorder, higher rates of rapid cycling, suicidal behavior, psychotic symptoms, and co-morbid anxiety disorders. Early onset depressive episodes were associated with higher rates of suicidal behavior and anxiety disorders, whereas early onset manic episodes were associated with psychotic symptoms and rapid cycling. Our results suggest the presence of a bimodal distribution of age at onset in BD according to the polarity of the index episode, and denote that an early onset BD, irrespective of polarity, may be a more serious subtype of the disorder.

Insulin resistance and outcome in bipolar disorder

BACKGROUND Little is known about the impact of insulin resistance on bipolar disorder. AIMS To examine the relationships between insulin resistance, type 2 diabetes and clinical course and treatment outcomes in bipolar disorder. METHOD We measured fasting glucose and insulin in 121 adults with bipolar disorder. We diagnosed type 2 diabetes and determined insulin resistance. The National Institute of Mental Health Life Chart was used to record the course of bipolar disorder and the Alda scale to establish response to prophylactic lithium treatment. RESULTS Patients with bipolar disorder and type 2 diabetes or insulin resistance had three times higher odds of a chronic course of bipolar disorder compared with euglycaemic patients (50% and 48.7% respectively v. 27.3%, odds ratio (OR) = 3.07, P = 0.007), three times higher odds of rapid cycling (38.5% and 39.5% respectively v. 18.2%, OR = 3.13, P = 0.012) and were more likely to be refractory to lithium treatment (36.8% and 36.7% respectively v. 3.2%, OR = 8.40, P<0.0001). All associations remained significant after controlling for antipsychotic exposure and body mass index in sensitivity analyses. CONCLUSIONS Comorbid insulin resistance may be an important factor in resistance to treatment in bipolar disorder.

Genetic risk of suicidal behavior in bipolar spectrum disorder: analysis of 737 pedigrees

Suicide is a significant cause of mortality in patients with major affective disorders (MAD), and suicidal behavior and MAD co‐aggregate in families. However, the transmission of suicidal behavior is partially independent from that of MAD. We analyzed the lifetime prevalence of completed and attempted suicides in a large sample of families with bipolar disorder (BD), its relation to family history of MAD and BD, and the contribution of clinical and treatment factors to the risk of suicidal behavior.

Early-onset and very-early-onset bipolar disorder: distinct or similar clinical conditions?

This study aimed to examine differences in the clinical presentation of very‐early‐onset (VEO) and early‐onset (EO) bipolar disorder (BD) not fully explored previously.

Pharmacogenetics and mood stabilization in bipolar disorder

Bipolar disorder is a severe psychiatric disease characterized by varying treatment response among individual patients. Effects of certain treatments, for instance, lithium, can be predicted from clinical characteristics of patients and their family histories. This led to a suggestion that a treatment response could identify subtypes of bipolar disorder particularly suited for gene‐mapping studies. In this paper we review family and molecular studies of bipolar disorder responsive to lithium, as well as studies aiming to identify polymorphisms associated with the treatment response itself. While molecular genetic research and gene expression studies promise to bring new insights into the pathophysiology of the illness and the nature of treatment response, and thus provide new information for better treatment of bipolar disorder in the future, results from family studies and studies of clinical correlates of treatment response may already be utilized in the management of bipolar disorder.

Course of bipolar illness worsens after onset of insulin resistance

Cross-sectional studies indicate that comorbid insulin resistance (IR) and type 2 diabetes are associated with a more severe course of bipolar disorder (BD); however, this relationship has not previously been assessed longitudinally. To address this, we reviewed health records of a case series of six patients with BD and comorbid IR. Severity and length of affective episodes (both mania and depression) over the lifetime were recorded using the Affective Morbidity Index; these data were obtained from ongoing prospective follow-up and from detailed retrospective chart reviews. All six patients with a previously episodic, relapsing-remitting course of illness experienced a worsening of morbidity after the onset of laboratory-demonstrated IR. These results suggest that IR may be a potential testable, modifiable factor in the progression of BD from a treatment responsive (episodic) to a non-responsive (chronic) course of illness.