Nedra Lexow

Serotonin Uptake Sites and Serotonin Receptors Are Altered in the Limbic System of Schizophrenics

Serotonin (5-HT) uptake sites were mapped by antoradiographic means with [3H]cyano-imipramine [[3H)]CN-IML), the 5-HT1A receptor with [3H]8-hydroxy-2-[di-n-propyl-amino]tetralin ([3H]8-OH-DPAT), and the 5-HT2 receptor with both [3H]ketanserin and [125I]lysergic acid diethylamide ([125I]LSD) in eight unneurologic controls and 10 cases with a diagnosis of schizophrenia. In the striatum, there was a marked heterogeneous patterning of 5-HT uptake sites that corresponded to the striosomal/matrix compartmentalization of the striatum. This organization m not matched with an equally heterogeneous pattern of either 5-HT2 or 5-HT1A receptors. For the isocortex, a general organizational scheme was observed with the 5-HT1A receptor expression high in the external laminae and deep laminae, but 5-HT2 receptor expression was higher in the internal laminae. There was a laminar distribution of 5-HT uptake sites that approximated the combined distributions of the 5-HT1A receptor and the 5-HT2 receptor. In the parahippocampal gyrus and hippocampus, the distribution of 5-HT uptake sites was Complementary to the distribution of 5-HT1A and 5-HT2 receptors. In schizophrenic cases, there was a large increase in the number and altered striosomal/matrix organization of 5-HT uptake sites in the striatum. There was also an increase in the numbers of 5-HT2 receptors in the nucleus accumbens and ventral putamen of the schizophrenics. The number of 5-HT1A receptors was not modified. There was a marked reduction in 5-HT uptake sites in the external and middle laminae of the anterior Cingulate, frontal cortex, and posterior cingulate, and no changes were observed in the motor cortex, temporal cortex, or hippocampus. Increased numbers of 5-HT1A receptors were found in the posterior cingulate, motor cortex, and hippocampus. Serotonin2 receptors were substantially elevated in the posterior cingulate, temporal cortex, and hippocampus, but not in the frontal, anterior cingulate, or motor cortices. Examination of the temporal lobe and hippocampus of a group of nonschizophrenic suicides (n = 8) indicated the alterations in 5-HT system in the limbic regions of the striatum, the limbic cortex, and hippocampus of the schizophrenic cases may be disease specific.

Thyrotropin-releasing hormone phase shifts circadian rhythms in hamsters

The role of thyrotropin-releasing hormone (TRH) in regulating circadian rhythms was investigated by assessing the ability of TRH microinjections into the suprachiasmatic nucleus (SCN) to induce phase shifts in hamster wheel-running behavior. TRH injected into the SCN at 10 and 100 nM doses produced phase advances in wheel-running activity of 18.3 +/- 1.9 and 34.8 +/- 2.9 minutes, respectively, when administered at circadian time (CT) 6. Injections at CT 18 produced no effects. The temporal sensitivity of the SCN to TRH administration was examined by administering TRH at specific circadian times. TRH produced significant phase advances at CT 4, 6, and 8, while no significant changes in wheel-running onset were observed at other CT times. These studies represent the first evidence of TRHs ability to affect circadian function.

Alterations in bilateral distribution of beta-adrenergic receptor subtypes in schizophrenia and suicide

401 lyzing the data of 39 suicides and 85 controls, we again found significantly elevated SHIAA among suicides. Furthermore, after statistical elimination of the confounding interactions, suicides still showed a significant association with elevated SHIAA. This finding suggests that instead of the “low serotonin-suicide“ relationship, a more complex serotonergic dysfunction appears to be implicated in the biological background of suicidal behavior.

Schizophrenic postmortem studies: Alterations in the distribution of trh receptors in the temporal lobe

125 ineglect (p = .003). These findings suggest that in humans as in rodents, ischemic insults to antero-lateral cortex may be a not uncommon antecedent of striatal DA hyperactivity. We hypothesize that penetrance of some common psychosis genes may be variable because these genes merely predispose carriers to responding to minor cortical ischemia with a marked subcortical DA supersensitivity. Other data in support of this hypothesis will be reviewed. (Supported by the VA and R29-MH43530-01)