Testosterone in Newly Diagnosed, Antipsychotic-Naive Men With Nonaffective Psychosis

Fernández-Egea, Emilio; García-Rizo, Clemente; Miller, Brian J.; Parellada, Eduard; Justicia, Azucena; Bernardo, Miquel; Kirkpatrick, Brian

doi:10.1097/psy.0b013e318230343f

Cited by 39 publications

(14 citation statements)

References 37 publications

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“…For example, testosterone levels decline in older adults, and testosterone replacement therapy has been thought to slow down the aging process [23]. In youth, who represent the other end of the lifespan, elevated levels of testosterone advance maturational processes [19, 24].…”

Section: Introductionmentioning

confidence: 99%

Growing Up or Growing Old? Cellular Aging Linked With Testosterone Reactivity to Stress in Youth

Drury

Shachet

Brett

et al. 2014

The American Journal of the Medical Sciences

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Background Given the established relation between testosterone and aging in older adults, we tested whether buccal telomere length (TL), an established cellular biomarker of aging, was associated with testosterone levels in youth. Methods Children, mean age 10.2 years, were recruited from the greater New Orleans area and salivary testosterone was measured during both an acute stressor and diurnally. Buccal TL was measured using monochrome multiplex quantitative real-time PCR (MMQ-PCR). Testosterone and telomere length data was available on 77 individuals. The association between buccal TL and testosterone was tested using multivariate Generalized Estimating Equations (GEE) to account for clustering of children within families. Results Greater peak testosterone levels (β=-0.87, p < 0.01) and slower recovery (β=-0.56, p < 0.01) and reactivity (β = -1.22, p < 0.01) following a social stressor were significantly associated with shorter buccal TL after controlling for parental age at conception, child age, sex, sociodemographic factors and puberty. No association was initially present between diurnal measurements of testosterone or morning basal testosterone levels and buccal TL. Sex significantly moderated the relation between testosterone reactivity and buccal TL. Conclusions The association between testosterone and buccal TL supports gonadal maturation as a developmentally sensitive biomarker of aging within youth. As stress levels of testosterone were significantly associated with buccal TL, these findings are consistent with the growing literature linking stress exposure and accelerated maturation. The lack of association of diurnal testosterone or morning basal levels with buccal TL bolsters the notion of a shared stress-related maturational mechanism between cellular stress and the hypothalamic pituitary gonadal (HPG) axis. These data provide novel evidence supporting the interaction of aging, physiologic stress and cellular processes as an underlying mechanism linking negative health outcomes and early life stress.

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Section: Introductionmentioning

confidence: 99%

Growing Up or Growing Old? Cellular Aging Linked With Testosterone Reactivity to Stress in Youth

Drury

Shachet

Brett

et al. 2014

The American Journal of the Medical Sciences

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“…The peak in age-of-onset during adolescence suggests a link between exposure to increased androgens and development of schizophrenia in at-risk men. However, a number of studies, including first episode and ultra-high risk, have reported either low or normal circulating testosterone levels in men with schizophrenia [3]–[6]. The evidence for a relationship with testosterone is strengthened by reports of increased negative symptoms and worse cognitive function in association with low endogenous testosterone levels in men with schizophrenia [7]–[11].…”

Section: Introductionmentioning

confidence: 99%

Testosterone Is Inversely Related to Brain Activity during Emotional Inhibition in Schizophrenia

et al. 2013

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Sex steroids affect cognitive function as well as emotion processing and regulation. They may also play a role in the pathophysiology of schizophrenia. However, the effects of sex steroids on cognition and emotion-related brain activation in schizophrenia are poorly understood. Our aim was to determine the extent to which circulating testosterone relates to brain activation in men with schizophrenia compared to healthy men during cognitive-emotional processing. We assessed brain activation in 18 men with schizophrenia and 22 age-matched healthy men during an emotional go/no-go task using fMRI and measured total serum testosterone levels on the same morning. We performed an ROI analysis to assess the relationship between serum testosterone and brain activation, focusing on cortical regions involved the emotional go/no-go task. Slower RT and reduced accuracy was observed when participants responded to neutral stimuli, while inhibiting responses to negative stimuli. Healthy men showed a robust increase in activation of the middle frontal gyrus when inhibiting responses to negative stimuli, but there was no significant association between activation and serum testosterone level in healthy men. Men with schizophrenia showed a less pronounced increase in activation when inhibiting responses to negative stimuli; however, they did show a strong inverse association between serum testosterone level and activation of the bilateral middle frontal gyrus and left insula. Additionally, increased accuracy during inhibition of response to negative words was associated with both higher serum testosterone levels and decreased activation of the middle frontal gyrus in men with schizophrenia only. We conclude that endogenous hormone levels, even within the normal range, may play an enhanced modulatory role in determining the neural and behavioural response during cognitive-emotional processing in schizophrenia.

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“…Reductions in the free androgen index, a measure of biologically active testosterone, were recently found in a study of first episode antipsychotic-naïve men with psychosis (Fernandez-Egea et al, 2011). Similarly, lower testosterone levels were reported in a recent study of CHR male adolescents, suggesting that lower levels may precede illness onset (van Rijn et al, 2011).…”

Section: Hormones and Psychosismentioning

confidence: 89%

The development of psychotic disorders in adolescence: A potential role for hormones

Trotman

Holtzman

Ryan

et al. 2013

Hormones and Behavior

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The notion that adolescence is characterized by dramatic changes in behavior, and often by emotional upheaval, is widespread and longstanding in popular western culture. In recent decades, this notion has gained increasing support from empirical research showing that the peri- and post-pubertal developmental stages are associated with a significant rise in the rate of psychiatric symptoms and syndromes. As a result, interest in adolescent development has burgeoned among researchers focused on the origins of schizophrenia and other psychotic disorders. Two factors have fueled this trend: 1) increasing evidence from longitudinal research that adolescence is the modal period for the emergence of “prodromal” manifestations, or precursors of psychotic symptoms, and 2) the rapidly accumulating scientific findings on brain structural and functional changes occurring during adolescence and young adulthood. Further, gonadal and adrenal hormones are beginning to play a more prominent role in conceptualizations of adolescent brain development, as well as in the origins of psychiatric symptoms during this period (Walker and Bollini, 2002; Walker et al., 2008). In this paper, we begin by providing an overview of the nature and course of psychotic disorders during adolescence/young adulthood. We then turn to the role of hormones in modulating normal brain development, and the potential role they might play in the abnormal brain changes that characterize youth at clinical high-risk (CHR) for psychosis. The activational and organizational effects of hormones are explored, with a focus on how hormone-induced changes might be linked with neuropathological processes in the emergence of psychosis.

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Testosterone in Newly Diagnosed, Antipsychotic-Naive Men With Nonaffective Psychosis

Cited by 39 publications

References 37 publications

Growing Up or Growing Old? Cellular Aging Linked With Testosterone Reactivity to Stress in Youth

Growing Up or Growing Old? Cellular Aging Linked With Testosterone Reactivity to Stress in Youth

Testosterone Is Inversely Related to Brain Activity during Emotional Inhibition in Schizophrenia

The development of psychotic disorders in adolescence: A potential role for hormones

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