Sticky-switch model of bipolar disorder
Pettigrew and Miller (1998) presented a novel pathophysiological model of bipolar disorder, based on their research data and pre-existing evidence in the literature: (i) they had discovered that the rate of binocular rivalry was slower in subjects with bipolar disorder than in controls; (ii) they had proposed a novel IHS model of binocular rivalry; and (iii) they merged these two facts with a wide variety of evidence for hemispheric asymmetries of mood and mood disorders. The result was a pathophysiological model (the ‘sticky switch’ model) that views mania as the endpoint of unopposed (relative) left-hemisphere activation and depression as the endpoint of unopposed (relative) right-hemisphere activation. Prior to Pettigrew and Miller’s (1998) proposal, evidence already existed for the left lateralization of mania and the right lateralization of depression, however, such evidence had not been synthesized into a coherent mechanistic model of bipolar disorder that accounted for the alternationbetween these hemispheric activation asymmetries.
A number of conceptual steps are taken by Pettigrew and Miller (1998) in linking slow rivalry rate in bipolar disorder to the IHS model and the phenomenology of the disorder. The key elements are the following: temporoparietal IHSs mediating rivalry (of the order of seconds) are genetically coupled to more anterior (prefrontal) IHSs mediating alternations of cognitive style and mood (of the order of minutes). This coupling implies that in bipolar disorder, slowed temporoparietal IHSs are associated with slowed anterior IHSs.
Slower switches are biophysically more easily held in one or the other position (i.e., are considered ‘stickier’ than faster switches); thus, once ‘stuck’ in the left or right position (perhaps following environmental triggers with top-down modulation of the subcortical switch), the resulting hemispheric activation asymmetry in turn results in extremes of that hemisphere’s cognitive style and thus the phenomenology of mania and depression, respectively (of the order of days to weeks). The genetic anomaly in bipolar disorder,
according to the sticky-switch model, was postulated to be a reduction in cationic channels that control oscillator switch rate.
A clearly stated prediction of Pettigrew and Miller’s (1998) sticky-switch model was the potential hemisphere-specific therapeutic utility of CVS in mania and depression. Thus, it was predicted that left-ear CVS, through its activation of the right hemisphere, would restore toward normal, the hemispheric imbalance (left over right) in mania and thus reduce manic signs and symptoms. Conversely, CVS of the right ear was predicted to reduce the signs and symptoms of depression. The prediction of a left-ear CVS effect on the signs and symptoms of mania has since been assessed, albeit in a single case study, and the results were impressive.
Dodson (2004), based on Pettigrew and Miller’s (1998) proposal (Dodson, personal communication), reported the effects of left-ear CVS in an acutely manic female patient with a long history of bipolar disorder. The patient had become intolerant of medication and ECT treatments had become ineffective. However, in a therapeutic trial, left-ear CVS reduced her Young Mania Rating Scale (YMRS) score almost immediately from 32 to 10, with a lowering of mood and a return of appropriate behaviour. The patient, who had previously lacked insight into her elevated mood and inappropriate behaviour, regained insight following CVS and felt embarrassed by her pre-CVS behaviour. The CVS effect wore off after approximately 24 h but repeated administration 72 h later, again caused a reduction in YMRS score that appeared to be longer lasting.
Clearly, a single case study is not proof of Pettigrew and Miller’s model (1998), but it is a striking finding. Replication of such effects in a larger sample of subjects with mania, and demonstration of the corresponding prediction for depression, would be sound evidence in favour of their pathophysiological model. It would also raise the possibility of a new therapeutic option for treating mania and depression; one that is safe, non-invasive, free from serious side-effects, inexpensive and easily applied (which is particularly relevant for rural areas and developing countries). At the Monash Alfred Psychiatry Research Centre (MAPRC), we are conducting just such a clinical trial of the potential therapeutic effects of CVS in mania and depression. The potential use of CVS as a therapeutic technique was outlined in detail by Miller and Ngo (2007).
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