Delayed diagnosis and missed diagnosis is common in bipolar disorder (BD). Up to 60% of BD is initially diagnosed as Unipolar Depression (UD).Delay in correct diagnosis and treatment averages five to ten years. Distinguishing BD from UD is difficult as BD patients experience more depressive symptoms/ present with more depression during the course of illness.In BD, the hallmark symptoms of mania/hypomania occurs very less frequently.ie 9% of the time in BD1 and 1% f the time in BD2. (JuddLL et al, 2002). To complicate things, up to half of individuals might have sub threshold hypomanic symptoms during a depressive episode . The diagnostic significance of these symptoms are hotly debated.
How do we make the correct diagnosis early on?
Clinically– use of rating scales that check the presence of some useful indicators ( early onset, psychotic symptoms, positive family history of BD,expression of hypomanic symptoms).Examples: Bipolar Inventory Symptoms Scale , Mood Disorder Questionnaire , Screening Assessment of Depression Polarity , Hypomania Checklist, Bipolar Spectrum Diagnostic Scale , and Probabilistic Approach for Bipolar Depression. Some of these scales are good in detecting sub threshold hypomanic symptoms.
Are there any objective markers that could help us differentiate BD from UD in early stages of the disorder?. Jorge Renner Cardoso de Almeida and Mary Louise Phillips reviews the field in this article.
1.Structural imaging: Examples of findings: Increased deep white matter hyper intensities in bipolar depression individuals in comparison with unipolar depression and Healthy Individuals , Decreased Fractional Anisometry of the left superior longitudinal fasciculus in bipolar depression individuals compared with unipolar depression and HI.
2.Functional imaging: Examples of findings:Elevated left amygdala activity to negative emotional facial expression in bipolar depression individuals compared with bipolar disorder remission individuals, unipolar depression individuals, and HI.
3.Neural circuitry abnormalities: BD may be characterized by more global, rather than localized, abnormalities in white matter connectivity in emotion regulation neural circuitry than UD depression.BD depressed individuals have a greater number of Deep White Matter Hyper intensities than UD depressed individuals . White matter hyper intensities occur in greater frequency (6 times) than in healthy individuals.This might be due to higher vascular/metabolic comorbidities in BD. BD has abnormally reduced Habenular gray matter volume. Habenula appears to have an inhibitory influence upon ventral tegmental area and its dopamine transmission, this might explain high reward sensitivity and increased activity in reward cicuitry in BD.
Dimensional approaches ( ie UD and BD are two ends of a spectrum) are gaining support from new epidemiological investigations.These studies show increasing bipolarity evident in the progression from UD to BD. In parallel to this,there is push for a reclassification of mental disorders for research purposes in a neuroscience-based framework ie disorders are grouped by underlying pathophysiological similarities rather than by phenomenological observations.(RDoC initiative by NIMH).Dimensional approach may be able to redefine bipolarity in terms of different underlying pathophysiological processes (eg:abnormalities in neural circuitry). Analytical advances like Machine leaning (where computers can automatically learn and recognize complex patterns and make decisions based on large amounts of data) is strengthening our ability to understand of how micro neuronal structures/circuits work. These methods are now experimentally used to discriminate between UD, BD and Normal individuals.
Conclusions: Differentiating UD and BD in early stage of illness is difficult .Current clinical approaches have limitations. Though there are only few studies, Bbiomarker research is pointing to potential differentiating features. Imaging methods that could focus on neural circuits supplemented by the powerful analytic techniques would lead to better understanding of abnormalities at different levels ( genetic, molecular, circuitry, and behavioral) that underlie different dimensions of psychopathology across the affective disorder spectrum.
Comment: Clinical methods (actively looking for bipolarity in all cases of depression through out the course of illness) is the only method currently available to clinicians to distinguish between UD and BD.
Summary of the article:
Distinguishing between Unipolar Depression and Bipolar Depression: Current and Future Clinical and NeuroimagingPerspectives. de Almeida JR, Phillips ML. Biol Psychiatry. 2013 Jan 15;73(2):111-8.