Acute psychosocial stress activates the physiological and endocrine stress systems and increases the subjective emotional experience of stress. While considerable efforts have been made to link changes in the activity of the biological stress systems with changes in the subjective emotional experience of stress, results so far have been mixed, at best. To investigate this association in a study employing experimental manipulation, we pharmacologically suppressed both the autonomic and the endocrine stress responses, and investigated the effects of acute psychosocial stress on the emotional stress experience. 22 healthy men and women received dexamethasone (2mg) the day before, and propranolol (80mg) one hour before psychosocial stress induction. A control group (n=24) received placebo pills on each occasion. Salivary cortisol, alpha-amylase and heart-rate responses to stress were assessed before, during and after stress induction. Subjective stress, mood, and state self-esteem assessments were made before and after stress. In the pharmacological manipulation group, subjects demonstrated no increase in autonomic or endocrine stress response, after exposure to psychosocial stress. Despite these effects, the emotional stress experience was intact in this group and identical to the control group. Participants in the experimental group showed an increase in subjective stress, greater mood dysregulation, and lower state self-esteem following stress exposure, with the response magnitude comparable to the control group. Our findings suggest that at least acutely, the physiological stress arousal systems and the emotional experience of stress are dissociated. This raises important questions about the efficacy of our measurement of subjective stress, and the unique contributions of the autonomic and endocrine responses in the subjective stress experience.

Although the pathogenesis underlying behavioral variant frontotemporal dementia (bvFTD) has yet to be fully understood, glutamatergic abnormalities have been hypothesized to play an important role. The aim of the present study was to determine the availability of the metabotropic glutamate receptor type 5 (mGluR5) using a novel positron emission tomography (PET) radiopharmaceutical with high selectivity for mGluR5 ([(11)C]ABP688) in a sample of bvFTD patients. In addition, we sought to determine the overlap between availability of mGluR5 and neurodegeneration, as measured using [(18)F]FDG-PET and voxel-based morphometry (VBM). Availability of mGluR5 and glucose metabolism ([(18)F]FDG) were measured in bvFTD (n = 5) and cognitively normal (CN) subjects (n = 10). [(11)C]ABP688 binding potential maps (BPND) were calculated using the cerebellum as a reference region, with [(18)F]FDG standardized uptake ratio maps (SUVR) normalized to the pons. Grey matter (GM) concentrations were determined using VBM. Voxel-based group differences were obtained using RMINC. BvFTD patients showed widespread decrements in [(11)C]ABP688 BPND throughout frontal, temporal and subcortical areas. These areas were likewise characterized by significant hypometabolism and GM loss, with overlap between reduced [(11)C]ABP688 BPND and hypometabolism superior to that for GM atrophy. Several regions were characterized only by decreased binding of [(11)C]ABP688. The present findings represent the first in vivo report of decreased availability of mGluR5 in bvFTD. This study suggests that glutamate excitotoxicity may play a role in the pathogenesis of bvFTD and that [(11)C]ABP688 may prove a suitable marker of glutamatergic neurotransmission in vivo.

Women are twice as likely as men to be diagnosed with anxiety and mood disorders. One potential underlying mechanism is sex differences in physiological and psychological responses to stress; however, no studies to date have investigated this proposed mechanism experimentally. In a double-blind, placebo-controlled design, pharmacological challenges were administered to individually suppress the hypothalamic-pituitary-adrenal (HPA) axis, or the sympathetic nervous system (SNS) prior to stress exposure, to investigate sex differences in the resulting cross talk among the physiological and psychological stress responses. Sex-speciଏc compensatory patterns and psychological effects emerged when the stress systems were manipulated. Men demonstrated heightened SNS reactivity to stress when the HPA axis was suppressed, and greater HPA reactivity after SNS suppression. This ability to react appropriately to the stressor, even with one system, did not lead to signiଏcant negative mood effects. In women, higher baseline activation (but dampened reactivity to stress) of SNS or HPA was observed when the other system was suppressed. This was coupled with worsened mood in response to stress when either stress system was compromised. Our results indicate that men and women may be differentially sensitive to ଏuctuations of their stress systems. This might be a potential link that underlies the sexual dimorphism in vulnerability for psychopathology.

Acute psychosocial stress activates the physiological and endocrine stress systems and increases the subjective emotional experience of stress. While considerable efforts have been made to link changes in the activity of the biological stress systems with changes in the subjective emotional experience of stress, results so far have been mixed, at best. To investigate this association in a study employing experimental manipulation, we pharmacologically suppressed both the autonomic and the endocrine stress responses, and investigated the effects of acute psychosocial stress on the emotional stress experience. 22 healthy men and women received dexamethasone (2 mg) the day before, and propranolol (80 mg) one hour before psychosocial stress induction. A control group (n = 24) received placebo pills on each occasion. Salivary cortisol, alpha-amylase and heart-rate responses to stress were assessed before, during and after stress induction. Subjective stress, mood, and state self-esteem assessments were made before and after stress. In the pharmacological manipulation group, subjects demonstrated no increase in autonomic or endocrine stress response, after exposure to psychosocial stress. Despite these effects, the emotional stress experience was intact in this group and identical to the control group. Participants in the experimental group showed an increase in subjective stress, greater mood dysregulation, and lower state self-esteem following stress exposure, with the response magnitude comparable to the control group. Our findings suggest that at least acutely, the physiological stress arousal systems and the emotional experience of stress are dissociated. This raises important questions about the efficacy of our measurement of subjective stress, and the unique contributions of the autonomic and endocrine responses in the subjective stress experience.