Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress.

Despite the prevalence of stress in everyday life and its impact on happiness, health, and cognition, little is known about the neural substrate of the experience of everyday stress in humans. We use a quantitative and noninvasive neuroimaging technique, arterial spin-labeling perfusion MRI, to measure cerebral blood flow (CBF) changes associated with mild to moderate stress induced by a mental arithmetic task with performance monitoring. Elicitation of stress was verified by self-report of stress and emotional state and measures of heart rate and salivary-cortisol level. The change in CBF induced by the stress task was positively correlated with subjective stress rating in the ventral right prefrontal cortex (RPFC) and left insula/putamen area. The ventral RPFC along with right insula/putamen and anterior cingulate showed sustained activation after task completion in subjects reporting a high stress level during arithmetic tasks. Additionally, variations of baseline CBF in the ventral RPFC and right orbitofrontal cortex were found to correlate with changes in salivary-cortisol level and heart rate caused by undergoing stress tasks. We further demonstrated that the observed right prefrontal activation could not be attributed to increased cognitive demand accompanying stress tasks and extended beyond neural pathways associated with negative emotions. Our results provide neuroimaging evidence that psychological stress induces negative emotion and vigilance and that the ventral RPFC plays a key role in the central stress response.

The role of stress-induced cortisol in the relationship between depression and decreased bone mineral density.

BACKGROUND: This study was designed to test the hypothesis that cortisol mediates the relationship between bone density and depression in postmenopausal women. METHODS: Nineteen women aged 52-79 who had been assessed for bone mineral density by dual-energy x-ray absorptiometer (DEXA) were evaluated for depression and anxiety. Diurnal and stress-induced measures of salivary cortisol were obtained during the following week and at a laboratory session involving a speech task. RESULTS: Nine volunteers reported depression while 10 were never depressed. Ever depressed women had significantly lower total lumbar and right femur DEXA Z scores than never depressed (t(17) = 2.5, p = .019 and t(17) = 2.06, p = .05, respectively). Ever depressed women demonstrated a significant increase in salivary cortisol (area under the curve (AUC) = 27.83, SD = 37.64) compared to never depressed women (AUC = -13.34, SD = 19.55) (t(17) = -3.041, p = .007) during a psychological challenge. There were significant inverse relationships between salivary cortisol AUC values and bone density Z scores at every measured bone site. Mediation analyses suggest that 51 - 67% of the association between depression and bone density could be attributed to stress-induced changes in cortisol. CONCLUSIONS: Cortisol hypersecretion in response to stress may, in part, explain the impact of depression on bone density in post-menopausal women.

SSRIs do not cause affective blunting in healthy elderly volunteers.

OBJECTIVE: This study was undertaken to evaluate the effects of selective serotonin reuptake inhibitors (SSRIs) on affective experience in healthy older adults. METHODS: After 1 week of observation, normal elderly volunteers (age range: 65-84 years) were given placebo, paroxetine (10 mg-40 mg/day), or sertraline (50 mg-150 mg/day) for 3 weeks in a double-blind study. Paroxetine- and sertraline-treated subjects were analyzed together as the SSRI group (N=30). Volunteers were assessed weekly and recorded mood and events in a daily diary each evening. All data were analyzed with mixed-effects random-regression models. RESULTS: There were significant relationships between daily affect and events reported in the daily diary for the sample as a whole, with no differences between groups in mean slopes of positive or negative affect across the length of the study. There were no differences between groups in affective variability. However, the SSRI group, but not the placebo group, demonstrated a significant drug-dependent decrease in negative affect related to negative events. There were no other observed group differences on any other measure. CONCLUSION: Interpreting the results conservatively, they demonstrate that SSRIs are not associated with affective toxicity in elderly persons.