Schizophrenia Research Institute, Sydney, Australia.
Psychoneuroendocrinology. 2010 Jul;35(6):896-905. doi: 10.1016/j.psyneuen.2009.12.002. Epub 2009 Dec 29.
Sex steroids, such as testosterone, can regulate brain development, cognition and modify psychiatric conditions. However, the role of adolescent testosterone in the emergence of cognitive deficits relevant to psychiatric illness has not been directly studied in primates. We examined whether removing testosterone during adolescence in rhesus macaques would affect prepulse inhibition (PPI) and fear-potentiated startle (FPS), which are translational tests of cognition affected in psychiatric disorders. Prepubertal macaques (30 months old) were castrated (n=6) or sham operated (n=6), and PPI and (FPS) were tested before the onset of puberty (34 months old) and after the pubertal surge in sex hormones 16 months later (50 months old). As expected there were no differences between the gonadectomized and intact groups' level of startle amplitude, PPI or (FPS) before puberty. After puberty, the intact group displayed substantially less PPI than the gonadectomized group, consistent with evidence that PPI is attenuated by endogenous increases in sex hormones. At the end of the study, testosterone among the intact monkeys was also correlated with tyrosine hydroxylase levels in the putamen, suggesting the attenuation of PPI by gonadal sex hormones may be influenced by subcortical dopamine. Thus, puberty involves significant increases in sex hormones, which in turn may modulate subcortical dopamine synthesis and affect cognitive functions impaired in psychiatric illnesses such as schizophrenia.
性激素，如睾酮，可调节大脑发育、认知，并改善精神状况。然而，青春期睾酮在灵长类动物中与精神疾病相关的认知缺陷中的作用尚未被直接研究。我们研究了是否在青春期去除恒河猴的睾酮会影响条件性恐惧反射（conditioned fear reflex，CFR）和条件性听觉反射（conditioned acoustic startle response，CSR），这两种认知测验与精神障碍有关。青春期前的恒河猴（30 月龄）被去势（n=6）或假手术（n=6），在青春期前（34 月龄）和 16 个月后青春期激素激增后（50 月龄）测试条件性听觉反射（conditioned acoustic startle response，CSR）和条件性听觉反射（conditioned fear reflex，CFR）。正如预期的那样，在青春期前，去势组和未去势组的惊跳幅度、条件性听觉反射（conditioned acoustic startle response，CSR）或条件性听觉反射（conditioned fear reflex，CFR）水平没有差异。青春期后，完整组的条件性听觉反射（conditioned acoustic startle response，CSR）明显低于去势组，这与内源性性激素增加会减弱条件性听觉反射（conditioned acoustic startle response，CSR）的证据一致。在研究结束时，完整组的猴子的睾酮与壳核中的酪氨酸羟化酶水平呈正相关，这表明性腺性激素对条件性听觉反射（conditioned acoustic startle response，CSR）的抑制作用可能受皮质下多巴胺的影响。因此，青春期涉及性激素的显著增加，而这些性激素反过来可能调节皮质下多巴胺的合成，并影响精神疾病（如精神分裂症）受损的认知功能。
