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Gene expression microarray analysis in postmortem brains is one of the fastest growing fields of psychiatric research. Here we show that common polymorphisms (SNPs) present on probe sets can masquerade as significant "gene expression" differences. After first observing this artifact in the Catechol-O-methyl transferase (COMT) gene, we replicate the finding in two additional genes predicted to show this artifact. Many Affymetrix chips contain thousands of SNPs that are both common and in the central probe region affecting hybridization, and thus have the potential to confound expression analysis.

There are major concerns that specific agonal conditions, including coma and hypoxia, might affect ribonucleic acid (RNA) integrity in postmortem brain studies. We report that agonal factors significantly affect RNA integrity and have a major impact on gene expression profiles in microarrays. In contrast to agonal factors, gender, age, and postmortem factors have less effect on gene expression profiles. The Average Correlation Index is proposed as a method for evaluating RNA integrity on the basis of similarity of microarray profiles. Reducing the variance due to agonal factors is critical in investigating small but validated gene expression differences in messenger RNA levels between psychiatric patients and control subjects.

Background: Schizophrenia, bipolar illness, and major depressive disorder have distinct presentations, but share some common symptoms. Hence, some common cellular and molecular abnormalities may be identifiable in these disorders., Methods: We examined cell-specific markers in the dorsolateral prefrontal cortex of brains from 18 patients with bipolar or major depressive disorder, and 18 matched controls, using in situ hybridization histochemistry and staining for nicotinamide-dinucleotide phosphate-diaphorase (NADPH). The distribution of NADPH-positive interstitial cells of the white matter and the expression of the mRNA for the 67 KD form of glutamic acid decarboxylase (GAD(67)) had previously been shown to be altered in prefrontal cortex of schizophrenics. Other markers identifying glutamatergic neuronal populations were alpha-type II calcium/calmodulin dependent protein kinase (CAMKII-alpha), brain derived neurotrophic factor, (BDNF) and the putative transcription factor, T-brain-1 (TBR1)., Results: Expression of GAD67 and the distribution of NADPH-positive cells in the white matter were not significantly altered in the dorsolateral prefrontal cortex of depressed subjects. Expression of CAMKII-alpha and TBR1 mRNAs was significantly increased in bipolar patients but not in major depressed patients, and there was a trend toward reduced BDNF expression in both groups. Abnormal patterns of gene expression and neuronal distribution in schizophrenics are markedly different from those in depressed patients., Conclusions: The findings that TBR1 and CAMKII-alpha expression is increased only in bipolar patients suggests abnormalities of specific genes related to a major cortical cell type and its connectivity.

Cajal's many contributions to understanding the thalamus have been hidden by his body of work on the cerebral cortex. He delineated many thalamic nuclei in rodents, defined afferent fibers, thalamocortical relay neurons and interneurons, was first to demonstrate thalamocortical fibers and their terminations in the cortex, and recognized the feed-back provided by corticothalamic fibers. This presentation outlines modern methods for identifying classes of thalamic neurons, their chemical characteristics, synaptology and differential connections, and describes the intrinsic circuitry of the thalamus, showing how interactions between GABAergic cells of the reticular nucleus and glutamatergic relay cells underlie rhythmic activities of neurons in the thalamo-cortico-thalamic network, activities associated with changes in the conscious state, and which are generated and maintained by the corticothalamic projection. Corticothalamic fibers interact with reticular nucleus cells and relay cells through NMDA, AMPA and metabotropic receptors while interactions between reticular nucleus cells and relay cells are mediated by GABAA and GABAB receptors. Differing strengths of synaptic input to the two cell types, from which oscillatory behavior commences, depend upon differential expression at individual synapses of specific AMPA receptor subunits which modulate excitatory postsynaptic conductances. Two classes of relay cells can be distinguished by differential staining for calbindin and parvalbumin. The first forms a matrix in the thalamus, unconstrained by nuclear borders; the second is concentrated in certain nuclei in which it forms the topographically organized core. In projecting diffusely to the cortex, calbindin cells provide a substrate for binding together activities of multiple cortical areas that receive focused input from single thalamic nuclei. This, and the presence of specific and diffuse corticothalamic projections may serve to promote coherent activity of large populations of cortical and thalamic neurons in perception, attention and conscious awareness.

The National Youth Sports Program (NYSP) is an annual event sponsored by the National Collegiate Athletic Association that provides structured sports and enrichment programs to youth of low socioeconomic status. As part of the program, youths undergo a free medical examination that uses a physical examination checklist but does not include a section on medical history. To determine what additional information a medical history would provide, a history form was used in conjunction with the regular preparticipation examination for participants in the 1996 NYSP at the North Carolina Agricultural and Technical State University. The history form provided information such as family history of sudden death, personal history of asthma or bone injury, and whether participants took medications or used corrective lenses. Seventy-nine percent of the completed history forms documented a positive response to at least one question. Of these, only 5% had physical findings on examination. Conversely, 15% of participants had physical findings that were not reported on the history form. Because much of what is discovered by a medical history often is not found on physical examination and because history information can be used to prevent the occurrence of an accident or illness, this study suggests that the use of such a form is beneficial in providing a more comprehensive screening.

Adult rats may utilize two metabolites of methionine for the biosynthesis of this essential amino acid. In separate experiments methionine, labeled with 14C or with 35S was observed in plasma and urine following the administration of [2-14C]-alpha-amino-n-butyric acid or [35S]-5'-methylthioadenosine by stomach tube. Although alpha-amino-n-butyric acid (ABA) or homoserine, alone or with dietary sodium sulfate, choline, and/or S-methylcysteine, was not utilized for growth, weight loss in weanling rats was decreased by dietary cysteine when fed as an additive to a basal methionine-free, cysteine-free, labile methyl-free, sulfur-free diet. Following the addition of 10 mg ABA and 28 mg 5'-methylthioadenosine/day to the basal diet, growth response was equivalent to that occurring in rats receiving 27 mg of methionine/day with the basal diet. The implications of these findings for adaptation to protein restriction and a discussion of equilibrium and steady state conditions related to the increase in methionine content in the blood are presented.