Alterations in the cortical serotonergic system in schizophrenia: A postmortem study

doi:10.1016/S0006-3223(97)00321-1

Biological Psychiatry

Volume 42, Issue 7, 1 October 1997, Pages 529-545

https://doi.org/10.1016/S0006-3223(97)00321-1 Get rights and content

Previous studies have suggested a disturbance in the cortical serotonergic (5-HT) system in schizophrenia; however, these studies have been confounded by suicide in the patient groups, which in itself is associated with alterations in the 5-HT system. In this study we characterized various components of the 5-HT system in 14 areas of the frontal and parietal cortex in tissue obtained at postmortem from aged chronically hospitalized nonsuicidal schizophrenics compared to age-matched controls. We found no differences between control and schizophrenic subjects in the density of 5-HT uptake sites or other markers of 5-HT innervation. In Brodmann areas 24 and 6 the concentration of 5-HT_2A,C receptors was decreased in all schizophrenics regardless of their antipsychotic treatment history. In all other areas examined 5-HT_2A,C receptor concentrations were dramatically decreased in schizophrenic patients on drugs at time of death, whereas those off drugs at death showed the same values as control subjects. The density of 5-HT_1A receptors was increased in areas 24, 9a (caudal part of area 9), 44, and 6 in subjects with schizophrenia. Antipsychotic treatment did not appear to have a significant effect. Thus, the specific pattern of alterations in the 5-HT system in schizophrenia may depend on the patient population and on antemortem antipsychotic treatment. These data also provide evidence that regulation of the 5-HT₂ receptor may be involved in antipsychotic action.

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Therefore, the changes in the expression of those proteins may indicate increased susceptibility of individuals to develop schizophrenia. However, the results concerning 5-HT1A receptors are inconsistent, and although the majority of studies indicate an increase of 5-HT1A binding (Gurevich and Joyce, 1997; Sumiyoshi et al., 1996; Hashimoto et al., 1993), several reports show their decrease, as well (Gray et al., 2006). In the present study, the 13 days of chronic administration of NMDA antagonist, MK-801 (0.4 mg/kg, i.p) resulted in the up-regulation of 5-HT1A receptors in both the cortex and hippocampus and decreased expression of GAD65 and GAD67 proteins only in the hippocampus.
The modified forced swim test (MFST) has excellent predictive validity for investigating the antipsychotic activity of drugs, with particular emphasis on their activity toward negative symptoms of schizophrenia. However, its face and construct validity are less understood. Therefore, in the present study, some biochemical changes within GABAergic and serotonergic neurotransmission that could be related to observed MK-801-induced disturbances and the activity of compounds active at those neurotransmitters were investigated.
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: This research was supported by a grant from Scottish Rite Schizophrenia Foundation and U.S. Public Health Service Grants MH 56824, MH 43880 (Dr. Raquel Gur, University of Pennsylvania School of Medicine), and AG 09215 (Dr. John Trojanowski, University of Pennsylvania School of Medicine).

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Alterations in the cortical serotonergic system in schizophrenia: A postmortem study

Brain Res

Psychiatry Res

Brain Res

Neuropsychopharmacology

Eur J Pharmacol

Neuropsychopharmacology

Brain Res

Neuropsychopharmacology

Prog Neuropsychopharmacol Biol Psychiatry

Biol Psychiatry

Life Sci

Biol Psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

Schizophr Res

Neuropsychopharmacology

Trends Neurosci

Schizophr Res.

Brain Res

Biol Psychiatry

Brain Res

Brain Res

Age stability of human brain 5-HT terminals studied with [3H]paroxetine binding

Gerontology

Hypofrontality in neuroleptic-naive patients and patients with chronic schizophrenia

Assessment with xenon 133 single-photon emission computed tomography and the Tower of London

Arch Gen Psychiatry

Differential effect of subchronic treatment with various neuroleptic agents on serotonin2 receptors in rat cerebral cortex

J Neurochem

Prospective clinicopathological studies of schizophrenia: Accrual and assessment

Am J Psychiatry

Serotonergic measures in the brains of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects

Am J Psychiatry

Serotonin2 (5-HT2) receptor binding in the frontal cortex of schizophrenic patients

J Neural Transm

Age stability of human brain 5-HT terminals studied with [³H]paroxetine binding

Serotonergic measures in the brains of suicide victims: 5-HT₂ binding sites in the frontal cortex of suicide victims and control subjects

Serotonin₂ (5-HT₂) receptor binding in the frontal cortex of schizophrenic patients