Neurobiological Evidence for the Primacy of Mania Hypothesis

Abstract

Background: Athanasios Koukopoulos proposed the primacy of mania hypothesis (PoM) in a 2006 book chapter and later, in two peer-reviewed papers with Nassir Ghaemi and other collaborators. This hypothesis supports that in bipolar disorder, mania leads to depression, while depression does not lead to mania.Objective: To identify evidence in literature that supports or falsifies this hypothesis.Method: We searched the medical literature (PubMed, Embase, PsycINFO, and the Cochrane Library) for peer-reviewed papers on the primacy of mania, the default mode function of the brain in normal people and in bipolar disorder patients, and on illusion superiority until 6 June, 2016. Papers resulting from searches were considered for appropriateness to our objective. We adopted the PRISMA method for our review. The search for consistency with PoM was filtered through the neurobiological results of superiority illusion studies.Results: Out of a grand total of 139 records, 59 were included in our analysis. Of these, 36 were of uncertain value as to the primacy of mania hypothesis, 22 favoured it, and 1 was contrary, but the latter pooled patients in their manic and depressive phases, so to invalidate possible conclusions about its consistency with regard to PoM. All considered studies were not focused on PoM or superiority illusion, hence most of their results were, as expected, unrelated to the circuitry involved in superiority illusion. A considerable amount of evidence is consistent with the hypothesis, although indirectly so. Limitations. Only few studies compared manic with depressive phases, with the majority including patients in euthymia.Conclusion: It is possible that humans have a natural tendency for elation/optimism and positive self-consideration, that are more akin to mania; the depressive state could be a consequence of frustrated or unsustainable mania. This would be consistent with PoM.

Predominant polarity and hippocampal subfield volumes in Bipolar disorders

“…Specifically, when directly compared, BD‐DP presented with smaller bilateral presubiculum/subiculum than BD‐MP. This could be in line with the opposite dysfunctions in reward processing that patients present during manic and depressive episodes: a state of hyper‐dopaminergia during hypomania/mania and a state of hypo‐dopaminergia during depression . These neurobiological patterns correspond respectively to an excessive involvement in pleasurable activities in mania and to anhedonia in depression.…”

Genetic neuroimaging of bipolar disorder: a systematic 2017–2020 update

“…The first was a FC study and showed reduced FC in risk gene carriers in the right hemisphere, between the amygdala and the anterior subgenual cingulate cortex during a face-matching task, then also during emotional processing of faces (Poletti et al, 2018). Consistently, abnormalities in FC in limbic-cingulate network have been previously found in BD and linked with predominant polarity of mood states (Kotzalidis et al, 2017;Janiri et al, 2017). The second was a DTI study of EAAT2-181A > C (SLC1A2 gene) rs4354668 on WM integrity and found that risk G allele carriers had lower axial diffusivity compared to T/T homozygotes when subjected to high-stress levels, but higher diffusivity than T/T when exposed to low stress.…”

Cortical Correlates of Impulsive Aggressive Behavior in Pediatric Bipolar Disorder

“…Thinner cortical areas in youth with PBD, i.e., ACC, PCC, OFC, IPC, SMG, LC, are part of two interconnected networks involved in emotion regulation and impulse control. The rostral part of the ACC and the medial and lateral parts of the OFC belong to the affective network (AN) (68)(69)(70). The OFC and ACC are densely interconnected with the amygdala and the other subcortical limbic and paralimbic regions through specific feedback and feedforward pathways that serve to convey attention to motivationally relevant stimuli and provide information about the emotional salience or significance of external stimuli in order to rapidly perceive reward contingency (35).…”