Mixed state bipolar episodes reconceptualized

Major finding: This study uncovered five factors of bipolar episodes: psychosis, euphoric mania, mixity, dysphoria, and inhibited depression.

Data source: An assessment of 187 DSM-IV-TR-diagnosed bipolar I patients using the Brief Psychiatric Rating Scale (BPRS 4.0)

Disclosures: The study was funded by several entities, including the Spanish Ministry of Economy and Competitiveness, and the Instituto de Salud Carlos III, Madrid.



A new study has proposed a more nuanced approach for the diagnosis and treatment of mixed episodes in bipolar I patients.

The study, conducted by Dr. Isabella Pacchiarotti and her colleagues implemented a "factor structure" approach toward acute mood episodes, with the goal of deconstructing mixed episodes in particular.

Researchers studied 187 bipolar I patients hospitalized for an acute episode – manic, depressive, or mixed – and diagnosed using DSM-IV-TR criteria. Patients were evaluated for manic, mixed, and depressive symptoms using the Brief Psychiatric Rating Scale (BPRS 4.0), the Hamilton Depression Rating Scale (HDRS-21), and the Young Mania Rating Scale (YMRS). Patients also completed a self-reported temperament evaluation after discharge, reported Dr. Pacchiarotti of the Bipolar Disorders Program at the Institute of Clinical Neuroscience, University of Barcelona.

A principal component factor analysis performed on the BPRS found five clinically relevant factors: psychosis (factor 1), euphoric mania (factor 2), "mixity" (factor 3), dysphoria (factor 4), and inhibited depression (factor 5).

Psychosis was characterized by positive loading for bizarre behavior, unusual thought content, hallucinations, disorientation, conceptual disorganization, mannerisms and posturing, distractibility, and self-neglect. Euphoric mania was characterized by elevated mood and grandiosity, with negative loading for depression, guilt, suicidality, somatic concern, tension, and anxiety. "Mixity" was defined by suicidality, excitement, motor hyperactivity, tension, and anxiety, with negative loading for motor retardation. Dysphoria had positive loading for hostility, uncooperativeness, and suspiciousness. Lastly, inhibited depression was defined by depression, guilt, motor retardation, emotional withdrawal, and blunted affect.

The investigators also performed an analysis to determine which factors were associated with depressive, manic, and mixed mood. No association was found between depressive episodes and any of the five factors. However, manic episodes were a predictor of psychosis and euphoric mania (factors 1 and 2), and mixed episodes were associated with mixity (factor 3). None of the episode types were predictors of dysphoria or inhibited depression (factors 3 and 4).

An important result of this study is the discovery of the mixity factor, which provides a more comprehensive profile of mixed episodes than does the conventional combination of manic and depressive symptoms. "Most mixed state scholars feel DSM-IV criteria for mixed states to be too restrictive," the authors wrote in their report. This study endorses the existence of two subtypes of mixed episodes: one defined by factor 3 and characterized by an anxious-agitated dimension, and the other defined by factor 4, characterized by irritability and dysphoria.

In addition, the authors provided recommendations for diagnostic improvements based on the findings of this paper. First, the DSM-IV excludes anxiety and includes psychomotor retardation in the diagnosis of mixed states, though the current research has found at least one group of bipolar I patients who presented with anxiety and did not have psychomotor retardation. The researchers suggested expanding the current diagnostic criteria to include this subset of bipolar patients.

The authors listed a few limitations to this study. First, the sample size was rather small. Second, this study analyzed only bipolar I patients, and did not assess individuals who were bipolar hypomanic or depressed with subsyndromal symptoms of opposite polarity. Third, this study did not evaluate patients over all phases of illness, only when they were admitted to the hospital. Fourth, most patients in this study were on medication when they were hospitalized, which might have affected results, particularly in factor 3. Lastly, further research is needed to generate more psychometric measures of mixed states, as few are currently available.

The authors of this study expressed hope that these new insights into the factor structure of bipolar episodes will result in improved diagnostic and treatment options in the future.

The study was funded by the several entities, including the Spanish Ministry of Economy and Competitiveness, and the Instituto de Salud Carlos III, Madrid.

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