Amino acids in schizophrenia: evidence for lower tryptophan availability during treatment with atypical antipsychotics?

Amino acids play a role in neurotransmitter availability in the central nervous system, in that e.g. the synthesis of brain serotonin depends on the concentration of its precursor tryptophan. Disturbances in amino acid metabolism have been implicated in the pathophysiology of schizophrenia.In the present study the effect of a 14 week treatment with atypical antipsychotics on the plasma levels of amino acids was investigated in patients with schizophrenia and compared to normal controls.Non-responders (< or =20% decrease in BPRS at endpoint) demonstrated lower baseline values of methionine as compared to good responders (> or =50% decrease in BPRS at endpoint; p<.05) and controls (p<.01). The ratio between tryptophan and the other large neutral amino acids (Trp/LNAA ratio) in poor-responders (<40%) decreased during treatment as compared to responders (> or =40%; p<.05). It is concluded that poor or non-response to atypical antipsychotics may be associated with an impaired synthesis of serotonin in the central nervous system.

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.

Quetiapine in relapsing schizophrenia: clinical efficacy and effect on monoaminergic parameters.

METHODS: Tolerability, safety and effectiveness of quetiapine in an in-patient group with a relapse of schizophrenia and the possible role of plasma amino acid concentrations, 5-HT parameters and HVA in the prediction of response to treatment were investigated in an open-label baseline-controlled trial of 14 weeks in 21 hospitalized schizophrenic patients. Responders were defined as those patients who exhibit at least a 40% reduction of BPRS total scores. Secondary efficacy measures were the PANSS, the Clinical Global Impression (CGI)-severity scale and the MADRS. Extrapyramidal side-effects were evaluated with the AIMS. Other side-effects were monitored at regular intervals. Amino acids and the derived tryptophan and tyrosine ratios, as well as monoaminergic parameters, were assessed in plasma at baseline and at weeks 3, 6 and 14. RESULTS: Treatment with quetiapine resulted in the predefined treatment effect in 10 out of the 17 patients who completed at least 4 weeks of treatment. Effect in responders was observed on all efficacy parameters, including lower MADRS scores. No extrapyramidal side-effects emerged. Clinical and biochemical parameters did not predict response to treatment. CONCLUSIONS: This study demonstrates the moderate antipsychotic efficacy of quetiapine on preferentially positive symptoms in a group of relatively young schizophrenics. Some observed changes in biochemical parameters are discussed.

The temperament and character inventory in major depression.

Patients admitted for pharmacological treatment of a non-bipolar major depressive episode completed the Temperament and Character Inventory (TCI) prior to and after at least 6 weeks of treatment. Treatment with various antidepressants resulted in a 43% reduction of symptomatology. Scores on the harm avoidance dimension before and after treatment appeared to be significantly higher as compared to Dutch normative data. TCI scores did not predict response to treatment or show a change during treatment. It is concluded that, in this group of patients, the personality dimension harm avoidance is a trait factor without predictive value for antidepressant responsiveness.