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Higher Expression of Serotonin 5-HT_2A Receptors in the Postmortem Brains of Teenage Suicide Victims

OBJECTIVE: Abnormalities of serotonin (5-HT) receptor subtypes have been observed in the postmortem brains of adult suicide victims; however, their role in teenage suicide is unexplored. The authors examined whether 5-HT_2A receptor subtypes are altered in the postmortem brains of teenage suicide victims. METHOD: Levels of 5-HT_2A receptors were determined through examination of [¹²⁵I] LSD binding, protein expression (by use of Western blotting with a specific 5-HT_2A receptor antibody), and mRNA (by means of quantitative reverse transcription polymerase chain reaction) in the prefrontal cortex, hippocampus, and nucleus accumbens of 15 teenage suicide victims and 15 normal matched teenage subjects. The cellular localization of the 5-HT_2A receptors was determined by means of gold immunolabeling. RESULTS: The authors observed significantly higher [¹²⁵I]LSD binding in the prefrontal cortex and greater protein expression and mRNA levels in the prefrontal cortex and hippocampus but not in the nucleus accumbens of suicide victims, compared with normal subjects. Greater protein expression was localized on pyramidal cells in cortical layer V but not in other cortical layers or in the surrounding neuropil of the prefrontal cortex of teenage suicide victims. CONCLUSIONS: The evidence indicates higher levels of 5-HT_2A receptor, protein, and mRNA expression in the prefrontal cortex and hippocampus, which have been implicated in emotion, stress, and cognition. There was no higher level in the nucleus accumbens, which has been implicated in drug dependence and craving. Our findings suggest that a higher level of 5-HT_2A receptors may be one of the neurobiological abnormalities associated with teenage suicide.

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