Longitudinal hypothalamic-pituitary-adrenal axis trait and state effects in recurrent depression

Area of Science:

• Neuroendocrinology
• Psychiatry
• Clinical Psychology

Background:

• Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity is inconsistently observed in major depressive disorder (MDD).
• Longitudinal studies are needed to differentiate state-dependent effects from persistent traits in HPA-axis activity in recurrent MDD.
• The relationship between HPA-axis activity, stress, and recurrence in MDD requires further investigation.

Purpose of the Study:

• To determine if HPA-axis hyperactivity in remitted recurrent MDD is a persistent trait.
• To assess if HPA-axis activity is influenced by depressive state, stress, or prior episodes.
• To investigate the impact of cognitive therapy on HPA-axis activity and recurrence in MDD.

Main Methods:

• Compared salivary cortisol levels (morning/evening) in 187 remitted recurrent MDD patients and 72 controls.
• Employed a two-staged patient-control and prospective-cohort design with follow-up at 3 months and 2 years.
• Assessed the association of HPA-axis activity with daily hassles, childhood events, and recurrence, and the effect of cognitive therapy.

Main Results:

• Remitted MDD patients exhibited significantly higher cortisol concentrations than controls.
• Cortisol levels did not correlate with daily hassles or childhood life events but were lower with more previous episodes.
• Cognitive therapy was associated with enhanced cortisol declines over the day during the 2-year follow-up.

Conclusions:

• Remitted recurrent MDD patients possess a persistent trait of elevated cortisol concentrations, independent of stress.
• Cortisol levels in MDD patients remained stable across new episodes, supporting a state-independent endophenotype.
• Findings suggest hypercortisolemia may be a trait marker for recurrent depression, potentially modifiable by cognitive therapy.