ReviewDistinguishing between Unipolar Depression and Bipolar Depression: Current and Future Clinical and Neuroimaging Perspectives
Section snippets
The Difficulty in Differentiating between BD and UD Depression
Only 20% of BD individuals during a depressive episode receive the correct diagnosis of BD within the first year of seeking treatment (4), and latency from onset to diagnosis and appropriate treatment averages 5 to 10 years (5, 6). Close to 60% of BD individuals are initially diagnosed as having UD depression (3, 4). Furthermore, despite notions that BD depression may be associated with more psychosis than UD depression, it remains extremely difficult to distinguish depressed patients with BD
Strategies to Identify BD in Depressed Individuals
Clinical strategies have been developed to help detect subthreshold hypomanic symptoms in depressed individuals. These include self- and clinician-administered rating scales, including Bipolar Inventory Symptoms Scale (22), Mood Disorder Questionnaire (23), Screening Assessment of Depression Polarity (24), Hypomania Checklist (25), Bipolar Spectrum Diagnostic Scale (26), and Probabilistic Approach for Bipolar Depression (27). These rating scales vary somewhat, but most include items believed to
Neuroimaging Studies Directly Comparing Individuals with BD Depression Versus UD Depression
Original research studies directly comparing individuals with BD depression with individuals with UD depression were identified through a comprehensive MEDLINE, EMBASE, and PsycINFO search of the English language literature covering publications between January 2000 and February 2012. The search keywords were bipolar disorder, major depressive disorder, and magnetic resonance imaging. Additional articles were identified through the reference lists of these papers.
Studies were included if they
Structural Neuroimaging Studies Directly Comparing Unipolar and Bipolar Depression
One study (51) used diffusion tensor imaging to examine whole-brain fractional anisotropy (FA) in 15 BD-I depressed, 16 UD depressed, and 24 healthy adults. Decreased FA in the left superior longitudinal fasciculus was found in BD versus UD depressed and healthy individuals. Decreased FA was also found in the right uncinate fasciculus in BD depressed versus healthy individuals. Decreased FA was found in the left inferior longitudinal fasciculus in UD depressed versus healthy individuals. These
Functional Neuroimaging Studies Directly Comparing Unipolar and Bipolar Depression
Two studies (61, 62) employed a well-validated emotional facial labeling paradigm to examine the functional integrity of emotion-processing neural circuitry. The paradigm involved displaying negative (fear and sad) and positive (happy) facial expressions as important signals of external threat (fear), internal distress (sad), and social approval (happy) of both prototypical (intense) and mild intensities of each emotion, together with neutral expressions. Fifteen BD-I depressed, 15 BD-I
Neural Circuitry Abnormalities That Differentiate BD from UD in Depressive Episode: Toward Biomarkers of BD
The very small number of structural neuroimaging studies indicates three main findings. First, BD depressed individuals may display more significant abnormalities than UD depressed individuals in white matter connecting key regions in emotion processing and regulation neural circuitry (51). Axonal disorganization, axonal demyelization, or apoptosis, manifested as white matter tract abnormalities, might be related to altered expression of oligodendrocyte and myelin genes (65). Furthermore, lower
Future Approaches in Neuroimaging Research Comparing BD and UD Depression
Here, we highlight novel approaches that should be the focus of future neuroimaging studies of BD and UD depression. These include dimensional approaches, studies of at-risk individuals, and novel neuroimaging approaches.
Dimensional Approaches
An increasing literature conceptualizes BD and recurrent UD along a spectrum of affective disorders, with increasing bipolarity evident in the progression from UD to BD (16, 18, 21, 80, 81).
For example, recent re-analyses of two epidemiologic studies have demonstrated that the dichotomy unipolar/bipolar is questionable and that hypomanic syndromes that do not meet DSM-IV criteria for BD-II are present in about 40% of individuals with recurrent UD (15, 20). The prospective longitudinal study
Studies of Individuals at Risk of Future Affective Disorders
Studies of individuals genetically, or symptomatically, at risk of future affective disorders, including UD and BD, allow identification of biomarkers that may reflect underlying pathophysiologic processes conferring risk or resilience toward future development of these disorders. Prospective, longitudinal studies of these individuals are needed to determine whether abnormalities in neural circuitries identified by neuroimaging predict future development of affective disorders across the
Novel Neuroimaging Approaches
In addition to the development of magnetic resonance imaging technologies, several analytical advances in neuroimaging are under current development. The field is now shifting from conventional analyses of neural activity to more advanced analyses based on functional integration within specific neural circuitries, including analyses of functional (e.g., psychological-physiological interaction [87]) and effective (e.g., dynamic causal modeling [62, 88]) connectivity and resting state
Summary
While BD and UD depression often remain extremely difficult to distinguish in clinical practice, promising findings from studies using different neuroimaging modalities indicate that neuroimaging measures might identify biomarkers to help differentiate BD from UD depression. In parallel, dimensional approaches, including the RDoC initiative, have the potential to help redefine bipolarity in terms of different underlying pathophysiological dimensions. Such approaches may facilitate
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