ABSTRACT
BACKGROUND: Identification of schizophrenia, a common neuropsychiatric disorder, is based on clinical examination. An easily measurable peripheral marker, which may enable a more rapid and more accurate diagnosis, is not available. A possible candidate is the D3 dopamine receptor on lymphocytes. OBJECTIVE: The D3 receptor is investigated for its clinical significance as a marker for diagnosing schizophrenia. METHODS: From eight schizophrenic patients and eight controls lymphocyte RNA was isolated. A semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was carried out and the intensities of the specific D3 dopamine receptor bands of patients and controls were compared. RESULTS: No difference could be seen between the intensities of the bands from patients and controls. CONCLUSION: An aberrant D3 dopamine receptor mRNA expression in lymphocytes of schizophrenics could not be demonstrated. This might be caused by down-regulation of D3 receptor production by antipsychotic drug treatment. At present, the D3 receptor seems to have no diagnostic value in schizophrenia.
ABSTRACT
A hypofunction of the glutamatergic system and NMDA receptors in schizophrenia has been hypothesized. Therefore, stimulation of these receptors could be of benefit to patients with schizophrenia. D-cycloserine has been used for this purpose. This study reports the effects of 100 mg D-cycloserine, when added to typical antipsychotics in chronic schizophrenic patients exhibiting prominent negative symptoms, using a placebo-controlled, double-blind, parallel, design. D-cycloserine slightly worsened psychotic symptoms and general psychopathology as compared to placebo. D-cycloserine failed to change negative symptoms and had no effect on extrapyramidal symptoms. The exacerbation of schizophrenic symptoms may be explained by the antagonistic effects of this dose of D-cycloserine at the glycine recognition site of the NMDA receptor due to competition with the endogenous agonist glycine. Another explanation for the increase in psychopathology may be an interaction with the effects of antipsychotics on NMDA mediated neurotransmission. Thus, D-cycloserine in this study did not ameliorate schizophrenic symptoms. However, the fact that they actually worsened suggests that NMDA systems may be involved in the pathogenesis of schizophrenia. Further placebo-controlled studies with lower dosages of D-cycloserine, preferably in drug-free patients, are necessary to evaluate if D-cycloserine is of use for the treatment of patients with schizophrenia.
