Molecular neurobiology for the clinician by Dennis S Charney

By Dennis S Charney

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1985). This is consistent with a reported firstdegree relative recurrence rate of around 9%. The recurrence rate is higher among male relatives. When affection status is broadened to include chronic tics or OCD, a much higher recurrence rate is observed. On the other hand, the relative recurrence risk in childhood-onset OCD is less well studied. Family studies using adult probands have found that an early age at onset of obsessivecompulsive symptoms is strongly related to a more familial form of the disorder (Nestadt et al.

A second animal model resulted from knockout of the Hoxb8 gene, one of a group of “homeobox-containing” transcription factor genes that determine the morphology of different body segments. These knockout mice show excessive grooming behavior that leaves portions of their bodies bare or even bleeding, much as in trichotillomania (Greer and Capecchi 2002). As these models and the understanding of the molecular basis of the human disorders start to converge, investigators may be able to develop and test novel treatments in animals before application to humans.

Postmortem molecular studies have also been applied to other neurotransmitter systems. Autoradiography in the hippocampus revealed reduced radioligand binding to GABAA receptors but no change in binding to serotonin 5-HT1A or serotonin 5-HT2A, muscarinic acetylcholine receptor M1, glutamate NMDA, or kainate receptors, or high-affinity choline uptake sites (Blatt et al. 2001). One study used microarray technology to identify differing gene expression patterns in the cerebellum from people with autism and found increased mRNA for the genes encoding a glutamate transporter (EAAT1), one of the glutamate AMPA receptors (GLUR1), a GABA receptor (GABRA5), and a glial protein (GFAP), as well as changes in expression levels of a number of other genes (Purcell et al.

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