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This Month in Archives of General Psychiatry
December 2000

This Month in Archives of General Psychiatry

Arch Gen Psychiatry. 2000;57(12):1097. doi:10.1001/archpsyc.57.12.1097

Human behavior arises from both genotype and experience. A measurable portion of the variance in behavior is hereditary, and such inheritance is ultimately attributable to functional variants of genes programming brain development and function. The sequence of the human genome is revealing a complex pattern of gene sequence variation. Cravchik and GoldmanArticle analyze the sequence diversity in human neurotransmitter receptor and transporter genes, and propose that it might represent an example of "neurochemical individuality."

Driessen et alArticle aim to answer the question of whether traumatized patients with borderline personality disorders (BPD) show trauma-related brain abnormalities or neuropsychological deficits. They found that patients with BPD have smaller volumes of the hippocampus and the amygdala than healthy controls but no neuropsychological deficits when the results were contolled for levels of depression. Volumes of the hippocampus were negatively correlated with early traumatization when all subjects were considered. The hypothesis of trauma-induced volume reductions of the brain in BPD can only be partly supported by this study.

Schizophrenia is associated with deficits in the ability to perform tasks that require transient information storage. Javitt et alArticle used electrophysiological and behavioral measures to evaluate whether such deficits reflect impaired ability to form precise memory traces, or impaired ability to maintain such traces once they are formed. Patients showed impaired ability to process information in both an attention-dependent visual paradigm and an attention-independent auditory paradigm, but no deficit in information retention. Similar effects are observed following administration of ketamine in normal volunteersArticle, suggesting that N-methyl-D-aspartate receptor dysfunction may play a prominent role in the disorder.

Deficient functioning of N-methyl-D-aspartate receptors (NMDARs) has been implicated in the impairment of short-duration, transient memory in schizophrenia. Umbricht et alArticle used electrophysiological and behavioral measures to investigate the effects of the NMDAR antagonist ketamine in healthy volunteers in 2 tasks that require transient information storage at the preattentive, sensory, and attention-dependent levels, respectively. They demonstrate that ketamine administration induced patterns of abnormalities similar to those observed in schizophreniaArticle. Thus, NMDAR-related dysfunction may underlie deficits in the formation and utilization of transient memory traces at different levels of information processing in schizophrenia.

Individuals with schizophrenia show severe deficits in the ability to perform simple sensory tasks, such as the ability to match 2 tones following brief delay. Rabinowicz et alArticle evaluated the relative contributions of auditory vs prefrontal dysfunction in producing this deficit. Auditory cortical lesions are known to increase tone-matching thresholds whether or not distracting tones are present, whereas prefrontal lesions affect performance only in the presence of same-modality (auditory) distractors. Patients showed increased thresholds but no increased distractability, suggesting that deficits are due to sensory imprecision and cannot be attributed to prefrontal dysfunction.

Major depression is more common in women, with these gender differences appearing at puberty. Young et alArticle examined reproductive hormones in depressed premenopausal women and matched controls and found lower mean estradiol levels in the follicular phase. These data complement other findings of a beneficial effect of estrogen on mood.

A commentary by Halbreich is included.Article

Hallucinations and delusions, 2 hallmarks of psychosis, occur commonly in patients with Alzheimer disease and have been associated with a more rapid cognitive decline. Farber et alArticle report that, as compared with nonpsychotic subjects, psychotic subjects have a greater density of neocortical neurofibrillary tangles, one of the major neuropathological hallmarks of Alzheimer disease. A similar increase was not found for senile plaques, another neuropathological hallmark of Alzheimer disease, or for neurofibrillary tangles in non-neocortical brain regions. These findings suggest that the mechanism(s) underlying psychosis may be associated with disease specific processes involved in the production of neocortical neurofibrillary tangles.

Although several models of schizophrenia hypothesize that the exacerbation of psychotic symptoms involves the interaction of psychobiological vulnerability and environmental stressors, little research has examined this issue directly. Rosenfarb et alArticle studied whether the combination of neurocognitive deficits and interpersonal criticism would predict the emergence of unusual thinking during stressful family transactions. A model that included the joint interaction of patients' working-memory deficits and interpersonal criticism from relatives best accounted for patients' unusual thinking. The data provide empirical support for a specific form of vulnerability-stress interaction in schizophrenia.

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