HPA axis activity in patients with panic disorder: review and synthesis of four studies

Abstract

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may play a role in panic disorder. HPA studies in patients with panic disorder, however, have produced inconsistent results. Seeking to understand the inconsistencies, we reexamined endocrine data from four studies of patients with panic disorder, in light of animal data highlighting the salience of novelty, control, and social support to HPA axis activity. Patients with panic disorder were studied (1) at rest over a full circadian cycle, (2) before and after activation by a panicogenic respiratory stimulant (doxapram) that does not directly stimulate the HPA axis, and (3) before and after a cholecystokinin B (CCK-B) agonist that is panicogenic and does directly stimulate the HPA axis. Patients with panic disorder had elevated overnight cortisol levels, which correlated with sleep disruption. ACTH and cortisol levels were higher in a challenge paradigm (doxapram) than in a resting state study, and paradigm-related ACTH secretion was exaggerated in patients with panic disorder. Panic itself could be elicited without HPA axis activation. Patients with panic disorder showed an exaggerated ACTH response to pentagastrin stimulation, but this response was normalized by prior exposure to the experimental context or psychological preparation to reduce novelty and enhance sense of control. Novelty is one of a number of contextual cues known from animal work to activate the HPA axis. The HPA axis abnormalities seen in patients with panic disorder in the four experiments reviewed here might all be due to exaggerated HPA axis reactivity to novelty cues. Most of the published panic/HPA literature is consistent with the hypothesis that HPA axis dysregulation in panic is due to hypersensitivity to contextual cues. This hypothesis requires experimental testing. Depression and Anxiety 24:66-76,

Depression and anxiety among US adults: associations with body mass index

“…45,46 People with emotional disorders or depression are often more likely to be overeating or have a binge eating disorder [47][48][49] and less likely to engage in physical activity, 50,51 which may contribute to weight gain. An underlying pathophysiological mechanism for overeating or binge eating disorder may result from a dysregulation of the hypothalamic-pituitary-adrenal axis because studies have consistently reported that hypothalamic-pituitaryadrenal axis perturbations (that is, increases in stress hormones such as cortisol and other mediators) occurred in people with major depressive disorders, post-traumatic stress disorder or other anxiety disorders, 45,[52][53][54][55] which stimulate food intake (through neuropeptide Y system) and blunt the efficiency of inhibition of food intake (through leptin system), thereby increasing food intake and body fat accumulation. 45 In addition, the use of psychotropic medications (such as antidepressants or atypical antipsycho- Depression and anxiety in association with BMI G Zhao et al tics) among people with depression or other mental illness may also explain why these people gain weight and become obese as weight gain is a common side effect of psychotropic medications.…”

Exhaustion measured by the SF-36 vitality scale is associated with a flattened diurnal cortisol profile

“…For the assessment of exhaustion the SF-36 vitality scale was utilised. Exhaustion measured by this scale has been shown to be differentiable from measures of depression and anxiety (Lindeberg et al, 2006), which would seem valuable considering evidence of increased HPA activity and elevated cortisol levels in depression and anxiety disorders (Gillespie and Nemeroff, 2005;Abelson et al, 2007).…”

The effect of doxapram on brain imaging in patients with panic disorder

“…Doxapram has been shown to increase anxiety behaviors in a rodent model of panic (Sullivan et al, 2003;Choi et al, 2005). In human studies of doxapram, Abelson and colleagues (Lee et al, 1993;Abelson et al, 1996a, b;Abelson et al, 2007) have shown a panic rate of up to 80% in subjects with PD, compared to 20% in normal volunteers. In a prior study by our group, doxapram (0.5 mg/kg in 10 ml saline) was administered over 15 seconds to six patients with PD and four normal controls (Gutman et al, 2005).…”