Atypical antipsychotics and the relevance of glutamate and serotonin.
In the present study, including 66 schizophrenic patients and 73 healthy controls, the effect of atypical antipsychotic treatment over a period of 14 weeks on psychotic symptoms and plasma levels of glutamate and monoaminergic metabolites was investigated. Treatment induced a modest reduction of psychotic symptoms in 42% of the patients (response criterion: Brief Psychiatric Rating Scale [BPRS] decrease >/=40%). Poor response was associated with severity of psychopathology, age and duration of disease. Glutamate at baseline was significantly higher in patients as compared to controls (p<0.01). During treatment, a significant further increase of glutamate, not related to response, was observed. Glutamate levels correlated significantly with negative symptom scores at baseline and weeks 3, 6 and 14 (p<0.05). At baseline, serotonin (5-HT) in plasma and 5-HT in platelets were significantly lower in the poor responders as compared to controls (p<0.05) and increased significantly during treatment (p<0.05). In the responders, treatment coincided with a decrease of 5-HT parameters. No differences in plasma levels of HVA, 5-HIAA and their ratio were observed between controls and response groups. The results of this study suggest an effect of atypical antipsychotics on glutamatergic neurotransmission and an association between lower pretreatment peripheral 5-HT parameters and response.
van der Heijden
F M M A
FM
Vincent van Gogh Institute for Psychiatry, Stationsweg 46, 5803 AC Venray, The Netherlands. fvanderheijden@vvgi.nl
Tuinier
S
S
Fekkes
D
D
Sijben
A E S
AE
Kahn
R S
RS
Verhoeven
W M A
WM
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000097:blood / Q000627:therapeutic use*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D005971:Glutamates / Q000097:blood*; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012701:Serotonin / Q000097:blood*; D013997:Time Factors
D014150:Antipsychotic Agents; D005971:Glutamates; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid