The three hit hypothesis of psychopathology revisited in a human model exposed to transient endogenous glucocorticoids excess: patients treated for Cushing's syndrome

A fundamental question in the neurobiology of mental disorders is why
depression and psychosis precipitate in some vulnerable individuals, while
others remain healthy and resilient during stress exposure. Genetic variation
in interaction with exposure to emotional neglect in early-life may program
vulnerability to stress in later life as a basis for individual differences in
psychopathology. We recently validated this i.e. 3-hit hypothesis in an animal
model.

To understand, from the perspective of the 3-hit hypothesis of psychopathology,
individual differences in the neuropsychiatric outcome of previous
glucocorticoid (GC) excess in treated Cushing patients.

Subproject 1: extending the phenotyping of treated Cushing patients in more
detail: Psychopathology and personality traits will be assessed. The current
status of attention processing and vigilance of the patients will be measured
by acoustic startle eye-blink response (together with its modulation by
prepulse). Finally, with a facial recognition task we will investigate memory
processes under mild social stress (Trier Social Stress Test).

Subproject 2: validation of the three hit hypothesis of psychopathology in the
human, in treated Cushing patients: We will additionally perform this *3-hit
analysis* on previously published measures of personality and cognitive
performance of the same patients.

The patients are asked to come to the LUMC, where they are asked to:

- provide saliva
- complete a series of questionnaires
- undergo a structured interview
- do a computer task which is interrupted by a social stress task. During the
computer task, the patient gets small electrodes under the eyes to measure the
eye-blink.

Overall, patients spent approximately 3 hours, and there are no risks
associated with this study.