Prospective predictors of bipolar disorder

Abstract

Objective: Bipolar disorder (BD) is a common, heritable major psychiatric disorder with typically early onset-age, profound disturbances of mood and behavior, and cognitive deficits. BD is often associated with substance-abuse and anxiety disorders as well as high rates of suicidal ideation/attempts, and excess mortality from co-existing general medical illnesses. The homotypic development, from attenuated mood symptoms and cyclothymic mood swings to more profound BD has been repeatedly reported in retrospective studies. However, some evidence exists for heterotypic trajectories of illness development, with an anxiety or Attention-Deficit Disorder precedes the development of BD. Methods: Prospective reports of precursors (affective symptoms) and risk factors (non-affective symptoms) preceding BD were assessed by systematic review, to characterize the prodromal phase of BD. A systematic literature review of studies investigating early symptoms and other clinical features prior to diagnosis of BD, using the following computerized databases: EMBASE (1980-January 2013); ISI database; MEDLINE (1966-January 2013); PsychInfo; PsycLIT (1967-May 2012). The search used combinations of the following subject headings: [BIPOLAR DISORDER] with: [ANTECEDENT∗] or [EARLY SIGN∗] or [EARLY SYMPTOM∗] or [PREDICT∗] or [PRODROM∗] or [PROSPECT∗] or [RISK∗]. Reports of risk factors (non-affective psychopathology) and additional neuropsychological and developmental features were assessed by systematic review of prospective studies to help define the prodromal phases of BD. We screened more than 3000 on-line abstracts and obtained reprints of 800 potentially eligible reports. A hand-search of references in initially selected reports identified 90 additional relevant articles. Results: Both, homotypic and heterotypic trajectories of illness development have been observed. Sub-syndromal and syndromal signs and symptoms associated with later diagnosis of BD included mood-swings, major and minor depression, BD-NOS, Cyclothymia, attenuated but recurring or persisting hypomanic symptoms including elation, irritability, restlessness, psychotic features, and an onset at a young age or post-partum, of mood disorders. Approxiamtely twenty-five studies provided information obtained prospectively on conversion rates, Odds Ratios or Hazard Ratios. Some variables predicted Bipolar type-I, other predicted type-II. The prodromal phase of Bipolar Disorder extends sometimes over several years, and mood dysregulation, sleep-activity disturbances and role impairment might be a good target for early identification and intervention. Risk factors associated with BD diagnoses, include: anxiety symptoms and disorders, childhood behavioral disorders, exposure to substances of abuse and mood-elevating agents, traumatic and other environmental factors, as well as minor physical anomalies. Risk factors precede the onset of BD by several years and might modify its course. An herotypic trajectory of symptoms' development with early anxiety, aggression and impulsivity is common, and might indicate a propensity to develop BD. Discussion: Precursors of BD typically extended over several years, and were associated with clinically significant morbidity and disability even before DSM-IV-TR diagnostic criteria for BD were met. The effects of modifiable risk factors like exposure to trauma, drugs of abuse and medication might help recognize subjects at environmental or personal risk. Clearer characterization of the prodromal phase of BD can enhance earlier identification as well as both timely and subject-appropriate treatment interventions.