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5-Hydroxytryptamine (5-HT; serotonin) 5-HT(6) receptors (5-HT(6)R) and 5-HT(7) receptors (5-HT(7)R) have been implicated in schizophrenia and as targets of atypical antipsychotic drugs. We have studied the expression of these receptors in the hippocampal formation and dorsolateral prefrontal cortex (DLPFC) of 17 subjects with schizophrenia and 17 controls using reverse transcription-polymerase chain reaction (RT-PCR) with cyclophilin co-amplification. In schizophrenia, 5-HT(6)R mRNA was decreased in the hippocampal formation, and 5-HT(7)R mRNA was decreased in the dorsolateral prefrontal cortex. The mRNAs were unchanged in rats treated for 2 weeks with haloperidol, chlorpromazine, risperidone, olanzapine or clozapine. Regional decreases in 5-HT(6)R and 5-HT(7)R expression in schizophrenia may contribute to the overall serotonergic alterations which occur in the disorder, in part through their interactions with other neurotransmitter systems including glutamate and acetylcholine. [ABSTRACT FROM AUTHOR]

A dysfunctional glutamatergic system has been implicated in the pathophysiology of schizophrenia. The group III metabotropic glutamate receptor (mGluR) types 7 and 8 presynaptically inhibit glutamate release, thereby modulating glutamatergic transmission in the brain. We conducted association studies to investigate the novel Tyr433Phe (mGluR7) variant and the 2846-C/T (mGluR8) polymorphism in schizophrenia. Both variants, present at high frequencies, failed to demonstrate any significant association with schizophrenia (mGluR7 [Tyr433Phe] allele: P=0.33; genotype: P=0.63; mGluR8 [2846-C/T] allele: P=0.72; genotype: P=0.63).

Neuropathological, neuroimaging, clinical and epidemiological evidence suggests that many cases of schizophrenia are developmental in origin. Dysplastic changes in the medial temporal lobes appear to be of particular importance. However, research implicating a neurodevelopmental origin for schizophrenia has proceeded largely in isolation from knowledge concerning the neurochemistry of the disorder. This paper attempts to integrate these disparate lines of research, and examines the role of trophic mechanisms in the formation of the hippocampus. Those neurotransmitters which have been most consistently found to be abnormal in the temporal lobes of schizophrenics (excitatory amino acids and CCK), are involved in the control of hippocampal development. We suggest that these neurotransmitter findings are the residue of abnormalities in their role as trophic factors in foetal or neonatal life, and that the latter contribute to the developmental aberrations considered fundamental to schizophrenia.