Psychoneuroendocrinology最新文献

Background: Antipsychotic-induced hyperprolactinemia is a common and clinically relevant adverse effect that may impair treatment adherence and long-term health outcomes. Although chlorpromazine-equivalent doses (CPZE) are frequently used to standardize antipsychotic exposure, the relative contribution of drug-specific prolactin liability and patient sex in real-world longitudinal settings remains insufficiently characterized.

Methods: We conducted a retrospective longitudinal cohort study including adult patients treated with antipsychotics in inpatient and outpatient psychiatric settings over a ten-year period. Repeated serum prolactin measurements were analyzed using generalized estimating equations to account for within-subject correlations. Antipsychotics were classified into low-, moderate-, and high-risk categories based on established prescribing guidelines. Associations between prolactin levels and sex, antipsychotic risk category, CPZE, therapy type, antidepressant co-treatment, and aripiprazole use were examined.

Results: A total of 251 patients (539 prolactin measurements) were included. Female sex and treatment with high-risk antipsychotics were the strongest independent predictors of prolactin elevation. High-risk agents were associated with an average increase of approximately 40 ng/mL in prolactin levels, whereas low-risk agents were associated with significantly lower concentrations. Abnormal prolactin levels (>20 ng/mL in men; >25 ng/mL in women) were observed in 68.4% of men and 78.7% of women. Analyses using binary outcomes (normal vs abnormal prolactin) yielded conclusions consistent with the continuous models, with high-risk antipsychotic exposure significantly increasing the odds of hyperprolactinemia, particularly among women. After adjustment for drug-specific risk, CPZE was not independently associated with prolactin levels. Sex-stratified analyses showed greater susceptibility to hyperprolactinemia among women. Aripiprazole use was not independently associated with lower prolactin levels.

Conclusion: In this real-world longitudinal cohort, prolactin dysregulation during antipsychotic treatment was driven primarily by drug-specific prolactin risk and biological sex rather than cumulative dose. These findings support a risk-based and sex-informed approach to antipsychotic prescribing and prolactin monitoring, particularly in women treated with high-risk agents.

The 3xTg-AD mouse model is widely used to study the pathomechanisms of Alzheimer's disease (AD) and to test potential therapies. During food-motivated cognitive tasks, however, increased food-directed behavior was observed in these animals, raising the possibility that metabolic factors may influence task performance. This prompted us to investigate the metabolic background of AD, with a focus on the hypothalamic-pituitary-thyroid (HPT) axis. Testing of food-motivated behavior (single pellet reaching, radial arm maze, staircase, and operant conditioning tests) started at 6 months of age in male mice and confirmed increased motivation for food in 3xTg-AD animals. The molecular background was examined at 8 months of age. Separate cohorts of 4- and 8-month-old male mice underwent metabolic measurements. Transgenic mice showed increased food and water intake, reduced fat mass, elevated lean mass, and a stable respiratory exchange ratio (RER), in contrast to the age-related decline in RER observed in controls. Free T4 levels were higher in 3xTg-AD than control animals, and molecular profiling revealed elevated thyrotropin-releasing hormone (TRH) and thyroid hormone-activating deiodinases DIO1 and DIO2 mRNA, alongside reduced expression of the thyroid hormone receptor beta 2 (THRB2) in the paraventricular nucleus (PVN) and pituitary. Expression levels of key appetite-regulating neuropeptides, including pro-opiomelanocortin (POMC), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), and agouti-related peptide (AgRP) were significantly lower in 3xTg-AD mice. These findings indicate early alterations in energy homeostasis and HPT axis-related signaling in 3xTg-AD mice that may be associated with increased food-seeking behavior. Our data provide evidence for metabolic and neuroendocrine changes that accompany the behavioral phenotype of this model.

Acute stress is a primary risk factor for mental disorders. While prior virtual reality (VR) studies have utilized objective physiological measures to address biological heterogeneity, the specific temporal evolution and cross-system coordination of these responses remain less explored. To address this gap, we developed a multi-scenario virtual reality (VR) stress paradigm, and analyzed personality modulation of stress response dynamics in 44 healthy adults via high-density monitoring (continuous heart rate/heart rate variability/galvanic skin response; 9-timepoint cortisol sampling). The VR paradigm effectively elicited multi-system stress responses that are similar to those observed in the Trier Social Stress Test. Personality traits significantly modulated temporal trajectories (15/28 time × trait interactions p_adj < 0.10) but poorly predicted peak intensity (3/36 regressions significant), suggesting personality primarily influences "how responses evolve" rather than "how strong." Psychoticism and trait anxiety predicted autonomic desynchronization, particularly sympathetic-parasympathetic decoupling during recovery (β = 0.339 h, p_adj = 0.031). These findings advance a paradigm shift from "reactivity" to "regulatory capacity" in stress research, providing a scalable digital tool for individualized stress susceptibility assessment.