MEETING ABSTRACT Open Access

The neurobiology of subjective tolerabilityto antipsychotic medications in Schizophrenia -is it also relevant to the genesisof comorbid addiction?George Awad

From 1st International Congress on Neurobiology and Clinical Psychopharmacology and EuropeanPsychiatric Association Conference on Treatment GuidanceThessaloniki, Greece. 19-22 November 2009

One of the frequent but unrecognized side-effects ofantipsychotic medications is the subtle alterations insubjective tolerability to these medications, includingfeelings of anxiety, distress and lack of pleasure, andwhich often lead to dislike and aversion to medications,with known serious clinical consequences. Yet, thosevery patients take to frequent abuse of illicit drugs.One popular and frequently accepted explanation for

such a high association has been the self-medicationhypothesis, which proved inadequate to explain allaspects of this phenomenon. Until recently, the neuro-biological basis for alteration in subjective tolerabilityand the negative dysphoric responses to antipsychoticmedications has not been clear, though it was generallyunderstood that somehow it relates to dopamine, sinceall antipsychotic medications have antidopaminergicproperties. In a series of studies, including our recentexperimental dopamine depletion SPECT study, wedemonstrated for the first time the relationship betweennegative subjective tolerability and dopamine-bindingratio in the nigro-striatal area. Our findings explain to alarge part why only some patients, not all receiving anti-psychotic medications, experience dysphoric responses,since only those who have low baseline dopamine func-tion are more susceptible to further dopamine-blockingeffects.Meanwhile, emerging evidence from research in the

addiction field has implicated dopamine in the sameneural circuitry in motivational and reinforcement beha-viour, which is central to initiation and continuation of

dependency states. It’s plausible, then, that what linksvulnerability to addictions and negative subjective toler-ability lies in a dysregulated dopamine signaling in thenucleus acumbens, resulting from frontal cortical andhippocampal dysfunction. Such a proposal, though manyaspects of it have not yet been worked out clearly, andif confirmed represents a new rethinking of the conceptof schizophrenia and its varied domains and manifesta-tions and also has clinical implications in management.

Published: 22 April 2010

doi:10.1186/1744-859X-9-S1-S61Cite this article as: Awad: The neurobiology of subjective tolerability toantipsychotic medications in Schizophrenia - is it also relevant to thegenesis of comorbid addiction?. Annals of General Psychiatry 20109(Suppl 1):S61.

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University of Toronto, Humber River Regional Hospital, Toronto, Canada

Awad Annals of General Psychiatry 2010,9(Suppl 1):S61http://www.annals-general-psychiatry.com/content/9/S1/S61

© 2009 Awad; licensee BioMed Central Ltd.