Catherine Raymond

Gonads and strife: Sex hormones vary according to sexual orientation for women and stress indices for both sexes.

This study assessed sexual orientation and psychobiological stress indices in relation to salivary sex hormones as part of a well-validated laboratory-based stress paradigm. Participants included 87 healthy adults that were on average 25 years old who self-identified as lesbian/bisexual women (n=20), heterosexual women (n=21), gay/bisexual men (n=26), and heterosexual men (n=20). Two saliva samples were collected fifteen minutes before and fifteen minutes after exposure to a modified Trier Social Stress Test to determine testosterone, estradiol, and progesterone concentrations via enzyme-immune assaying. Mean sex hormones were further tested in association to stress indices related to cortisol systemic output (area under the curve with respect to ground) based on ten measures throughout the two-hour visit, allostatic load indexed using 21 biomarkers, and perceived stress assessed using a well-validated questionnaire. Results revealed that lesbian/bisexual women had higher overall testosterone and progesterone concentrations than heterosexual women, while no differences were found among gay/bisexual men in comparison to heterosexual men. Lesbian/bisexual women and heterosexual men showed positive associations between mean estradiol concentrations and allostatic load, while gay/bisexual men and heterosexual women showed positive associations between mean testosterone and cortisol systemic output. In summary, sex hormone variations appear to vary according to sexual orientation among women, but also as a function of cortisol systemic output, allostatic load, and perceived stress for both sexes.

Early child adversity and psychopathology in adulthood: HPA axis and cognitive dysregulations as potential mechanisms

Early adversity (EA) has been shown to be a potent risk factor for developing a psychopathology in adulthood. Alterations of the stress system in addition to changes in brain development have been suggested to explain some of the psychopathologies associated with EA. The stress response involves the activation of the hypothalamic-pituitary-adrenal (HPA)-axis, which leads to the production of glucocorticoids (GCs; cortisol in humans). Being soluble in lipids, GCs easily cross the blood brain barrier and access GC receptors in the hippocampus, prefrontal cortex and amygdala. These three brain structures do not develop at the same rhythm in humans and recent models suggest that exposition to EA at different times throughout cerebral development can induce a differential vulnerability to diverse mental illnesses. Although these models are of interest, they do not provide any mechanism(s) through which exposition to EA could lead to an increased vulnerability to certain mental illnesses and not others. Interestingly, the main brain structures that are affected by the chronic secretion of stress hormones during childhood (hippocampus, prefrontal cortex and amygdala) are differentially involved in various cognitive functions (memory, emotion regulation, encoding of emotional memories, etc.). It is therefore proposed that exposure to EA, by affecting the development of specific brain structures, might alter the underlying cognitive process of these brain regions, and increase vulnerability to specific mental disorders in adulthood.

The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity

For the last five decades, science has managed to delineate the mechanisms by which stress hormones can impact on the human brain. Receptors for glucocorticoids are found in the hippocampus, amygdala and frontal cortex, three brain regions involved in memory processing and emotional regulation. Studies have shown that chronic exposure to stress is associated with reduced volume of the hippocampus and that chronic stress can modulate volumes of both the amygdala and frontal cortex, suggesting neurotoxic effects of stress hormones on the brain. Yet, other studies report that exposure to early adversity and/or familial/social stressors can increase vulnerability to stress in adulthood. Models have been recently developed to describe the roles that neurotoxic and vulnerability effects can have on the developing brain. These models suggest that developing early stress interventions could potentially counteract the effects of chronic stress on the brain and results going along with this hypothesis are summarized.

Population pharmacokinetic and pharmacodynamic modeling of acetazolamide in peritoneal dialysis patients and healthy volunteers.

PURPOSE To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of acetazolamide (ACTZ) in peritoneal dialysis patients, ACTZ 500 mg was administered intravenously to 7 healthy subjects (HV) and 8 peritoneal dialysis patients (CAPD). METHODS Population PK/PD modeling was performed with ACTZ serum (total and unbound), urine and dialysate concentrations, intra-ocular pressure (IOP) and covariates. A multi-compartment PK model (accounting for non-linear protein binding) and an inhibitory Emax (maximal change in IOP) PD model were selected. RESULTS As expected, renal clearance (which almost equals total body clearance) was severely decreased in CAPD (1.2 vs 80.3 L/h) and the elimination half-life of total ACTZ was prolonged (20.6 vs 3.4 hours). The protein binding was significantly altered with a mean free fraction 4.2% in HV and 8.6% in CAPD. Moreover protein binding of ACTZ was concentration dependent in both HV and CAPD. Despite a higher free fraction of ACTZ, the Emax was lower in CAPD: 4.4±1.4 vs 7.4±2.8 mmHg. CONCLUSION Both PK and PD are significantly altered in dialysis patients.

Parental depression but not parental cancer is associated with high cortisol levels in adolescent males

Background: Parenting dimensions are associatedwith depressive symptoms in adolescents. We investigated gene-environment interactions between perceived parenting dimensions and 5 well knownVariableNumber TandemRepeats (VNTR) in 4 genes associated with monoamine neurotransmission: 5-HTTLPR, STin2 in the serotonin transporter gene and theDAT1, DRD4 andMAOA repeats. Methods: A population sample of 1103 Belgian adolescents and their parents (mean age: 13.79 years, SD=0.94) were asked to fill out questionnaires. From each of them 5 VNTR’s were analyzed using DNA from saliva samples. Perceived parenting dimensions were explored using the LAPPS and VSOG self-report scale. After factor analysis, 5 factors were defined: support, proactive control, psychological control, punishmentandharshpunishment. Thephenotype “depressive symptoms” was investigated using the CES-D self-report scale. Statistical analyses were performed in R using linear regression techniques. Results: Perceived parenting dimensions,more specifically perceived support and psychological control, seem strongly associated with depressive symptoms as reported in CES-D (p<0.001). The only interaction effect that withstood multiple testing (p<0.0014) was seen for 5-HTTLPR and the difference in proactive control as perceived by the adolescents in comparison to the parental perception. Conclusions: Our results suggest that perceived parenting dimensions are strongly associated with depressive symptoms, as reported by the CES-D scale. We only found evidence for 5-HTTLPR to interact with the difference in perceived proactive control in the causation of depressive symptoms in adolescents.