The neurobiology of subjective tolerability to antipsychotic medications in Schizophrenia - is it...
1
MEETING ABSTRACT Open Access The neurobiology of subjective tolerability to antipsychotic medications in Schizophrenia - is it also relevant to the genesis of comorbid addiction? George Awad From 1 st International Congress on Neurobiology and Clinical Psychopharmacology and European Psychiatric Association Conference on Treatment Guidance Thessaloniki, Greece. 19-22 November 2009 One of the frequent but unrecognized side-effects of antipsychotic medications is the subtle alterations in subjective tolerability to these medications, including feelings of anxiety, distress and lack of pleasure, and which often lead to dislike and aversion to medications, with known serious clinical consequences. Yet, those very patients take to frequent abuse of illicit drugs. One popular and frequently accepted explanation for such a high association has been the self-medication hypothesis, which proved inadequate to explain all aspects of this phenomenon. Until recently, the neuro- biological basis for alteration in subjective tolerability and the negative dysphoric responses to antipsychotic medications has not been clear, though it was generally understood that somehow it relates to dopamine, since all antipsychotic medications have antidopaminergic properties. In a series of studies, including our recent experimental dopamine depletion SPECT study, we demonstrated for the first time the relationship between negative subjective tolerability and dopamine-binding ratio in the nigro-striatal area. Our findings explain to a large 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-blocking effects. Meanwhile, emerging evidence from research in the addiction field has implicated dopamine in the same neural circuitry in motivational and reinforcement beha- viour, which is central to initiation and continuation of dependency states. It’ s plausible, then, that what links vulnerability to addictions and negative subjective toler- ability lies in a dysregulated dopamine signaling in the nucleus acumbens, resulting from frontal cortical and hippocampal dysfunction. Such a proposal, though many aspects of it have not yet been worked out clearly, and if confirmed represents a new rethinking of the concept of 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-S61 Cite this article as: Awad: The neurobiology of subjective tolerability to antipsychotic medications in Schizophrenia - is it also relevant to the genesis of comorbid addiction?. Annals of General Psychiatry 2010 9(Suppl 1):S61. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit University of Toronto, Humber River Regional Hospital, Toronto, Canada Awad Annals of General Psychiatry 2010, 9(Suppl 1):S61 http://www.annals-general-psychiatry.com/content/9/S1/S61 © 2009 Awad; licensee BioMed Central Ltd.
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Transcript of The neurobiology of subjective tolerability to antipsychotic medications in Schizophrenia - is it...
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.
Submit your next manuscript to BioMed Centraland take full advantage of:
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at www.biomedcentral.com/submit
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.
