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Adverse Subjective Responses to Antipsychotics: Insights from Molecular Pet
Imaging Studies

Jong-Hoon Kim

Gachon University, Gil Medical Center, Korea

Background/Objective: Adverse subjective responses to antipsychotic drugs include various
affective disturbances such as depressive, unpleasant or dysphoric mood, anhedonic feelings, anxiety,
and inner restlessness, and cognitive complaints. These may lead to poor compliance with
medications and may still be a source of concern in the treatment of schizophrenia even in the era of
second generation antipsychotics.This presentation synthesizes the phenomenology, clinical
importance, and neurobiological mechanisms of subjective negative responses to antipsychotics in
schizophrenia. In particular, we aims to focus on the neurochemical mechanisms based on the
molecular positron emission tomography (PET) imaging studies, highlighting the effects of current
antipsychotics on neurotransmitter systems in specific striatal subregions and related neural circuits.

Method: Studies on the relationship between subjective responses to antipsychotics and
neurotransmitter receptor/transporter availability measured by PET with radiotracers were reviewed.

Result: The dopamine D2/3 receptor blockade in the limbic subdivision of the striatum and its
reciprocally connected brain regions is significantly associated with adverse subjective responses to
antipsychotics. The cortical dopamine D1 receptor, serotonin 5-HT1A receptor, and metabotropic
glutamate receptor 5 (mGlu5) may play a role in modulating subjective responses particularly
cognitive experiences.

Conclusion: A greater understanding of the pathogenesis and the development of individualized
treatment strategies for OCS will improve clinical courses and optimize outcomes.

Reference: Kim JH, Son YD, Kim HK, Lee SY, Cho SE, Kim YB, Cho ZH.
Antipsychotic-associated mental side effects and their relationship to dopamine D2 receptor
occupancy in striatal subdivisions: a high-resolution PET study with [11C]raclopride. J Clin
Psychopharmacol. 2011;31(4):507-11 Mizrahi R, Mamo D, Rusjan P, Graff A, Houle S, Kapur S.
The relationship between subjective well-being and dopamine D2 receptors in patients treated with a
dopamine partial agonist and full antagonist antipsychotics. Int J Neuropsychopharmacol. 2009;12(5)