Dopamine transporter density in schizophrenic subjects with and without tardive dyskinesia

Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States
Schizophrenia Research (Impact Factor: 4.43). 01/2005; 71(2-3):371-5. DOI: 10.1016/j.schres.2004.03.015
Source: PubMed

ABSTRACT Striatal dopamine transporter (DAT) binding potential (BP) was compared between schizophrenic subjects with and without tardive dyskinesia and controls. Although the groups were not statistically different in striatal BP, tardive subjects had apparently lower DAT density than non-tardive schizophrenic subjects. Significant and trend-level inverse correlations were found between DAT BP in the striatum, and especially the severity of negative symptom scores, but also cognitive, and depression/anxiety scores on the PANSS.


Available from: Anantha Shekhar, Jan 07, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Antipsychotics may cause tardive dyskinesia in humans and orofacial dyskinesia in rodents. Although the dopaminergic system has been implicated in these movement disorders, which involve the basal ganglia, their underlying pathomechanisms remain unclear. CB1 cannabinoid receptors are highly expressed in the basal ganglia, and a potential role for endocannabinoids in the control of basal ganglia-related movement disorders has been proposed. Therefore, this study investigated whether CB1 receptors are involved in haloperidol-induced orofacial dyskinesia in rats. Adult male rats were treated for four weeks with haloperidol decanoate (38mg/kg, intramuscularly - i.m.). The effect of anandamide (6nmol, intracerebroventricularly - i.c.v.) and/or the CB1 receptor antagonist SR141716A (30μg, i.c.v.) on haloperidol-induced vacuous chewing movements (VCMs) was assessed 28days after the start of the haloperidol treatment. Anandamide reversed haloperidol-induced VCMs; SR141716A (30μg, i.c.v.) did not alter haloperidol-induced VCM per se but prevented the effect of anandamide on VCM in rats. These results suggest that CB1 receptors may prevent haloperidol-induced VCMs in rats, implicating CB1 receptor-mediated cannabinoid signaling in orofacial dyskinesia.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2014; DOI:10.1016/j.pnpbp.2014.04.006 · 4.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: All current antipsychotic drugs block dopamine (DA) receptors, but the nature of the DA dysfunction in schizophrenia has not been clear. However, consistent evidence now shows that presynaptic dopaminergic function is altered in schizophrenia, specifically in terms of increased DA synthesis capacity, baseline synaptic DA levels, and DA release. Furthermore, presynaptic dopaminergic function is already elevated in prodromal patients who later developed the disorder. Currently available antipsychotics act on postsynaptic receptors, not targeting presynaptic DA abnormalities. This has implications for understanding response and developing new treatments. The lack of normalization of the abnormal presynaptic function could explain why discontinuation is likely to lead to relapse, because the major dopaminergic function persists, meaning that once treatment stops there is nothing to oppose the dysregulated dopamine function reinstating symptoms. Furthermore, it suggests that drugs that target presynaptic dopaminergic function may constitute new treatment possibilities for schizophrenic patients, in particular, for those in whom antipsychotics are poorly effective. In addition, the longitudinal changes with the onset of psychosis indicate the potential to target a defined dynamic neurochemical abnormality to prevent the onset of psychosis.
    CNS Drugs 06/2014; DOI:10.1007/s40263-014-0177-z · 4.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pharmacogenomics is the study of the effects of genetic polymorphisms on medication pharmacokinetics and pharmacodynamics. It offers advantages in predicting drug efficacy and/or toxicity and has already changed clinical practice in many fields of medicine. Tardive dyskinesia (TD) is a movement disorder that rarely remits and poses significant social stigma and physical discomfort for the patient. Pharmacokinetic studies show an association between cytochrome P450 enzyme-determined poor metabolizer status and elevated serum antipsychotic and metabolite levels. However, few prospective studies have shown this to correlate with the occurrence of TD. Many retrospective, case-control and cross-sectional studies have examined the association of cytochrome P450 enzyme, dopamine (receptor, metabolizer and transporter), serotonin (receptor and transporter), and oxidative stress enzyme gene polymorphisms with the occurrence and severity of TD. These studies have produced conflicting and confusing results secondary to heterogeneous inclusion criteria and other patient characteristics that also act as confounding factors. This paper aims to review and summarize the pharmacogenetic findings in antipsychotic-associated TD and assess its clinical significance for psychiatry patients. In addition, we hope to provide insight into areas that need further research.
    Pharmacogenomics and Personalized Medicine 01/2014; 7:317-28. DOI:10.2147/PGPM.S52806