: A study of the interaction of genetic, neuroimaging and endocrine factors, and the effects of childhood adversity, in major depressive disorder

Student thesis: Doctoral ThesisDoctor of Philosophy


My thesis consisted of two studies. The first study was a part of a wider study; within this, we investigated the modulation of amygdala structure by the val66met BDNF (Brain Derived Neurotrophic Factor) polymorphism. Structural Magnetic Resonance Imaging (MRI) scans were obtained at 1.5 T in 87 Major Depressive Disorder (MDD) patients and 74 age, gender, and verbal IQ matched healthy controls. We used Freesurfer version 5.1.0 to examine the grey matter amygdala volume.
In the second study, we investigated neuroendocrine abnormalities˗˗ Hypothalamus-Pituitary-Adrenal Axis (HPA) axis changes˗˗ in MDD and their relation to early life stress (ELS). In total 112 subjects took part, consisting of MDD patients with (n=28) and without (n=15) a history of ELS and healthy controls with (n=26) and without (n=43) a history of ELS. The cortisol awakening response (CAR) was used as an index of HPA axis activity.
In both studies, the data were analyzed using Statistical Package for Social Science (SPSS version 22).
In the first study, we did not find any modulatory effect of the val66met polymorphism on the grey matter of right and left amygdala volumes. In the second study, we showed that the CAR was most elevated in those who were both depressed and had a history of ELS, which supports the argument that the effects of early life stress and MDD on the HPA axis may be additive.
Date of Award2016
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorAnthony Cleare (Supervisor) & Valeria Mondelli (Supervisor)

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