Toward a Gene-Brain-Behaviour Model

A number of potential markers of clinical depression have been identified in the literature including depression heterogeneity, anxiety comorbidity, stressful life events, sleep disturbance, emotion perception deficits, cognitive impairment, psychomotor slowing, reduced HRV, reduced arousal, increased right prefrontal activity, impaired emotion and oddball ERPs, specific genotypes in monoaminergic and BDNF candidate genes and interaction between these systems. However, many of these markers have been identified in different studies (and research groups) and based on separate samples.

Aims

The first aim of this study is to integrate candidate markers of clinical depression in the same sample of participants to determine whether these markers are able to explain observed depression severity. This is a particularly important goal given that depression severity has been considered the single most reliable variable for predicting treatment outcome (i.e. the less severe the depression, the better the outcome will be) (Tedlow et al., 1998; Trivedi and Baker, 2001).

It is hypothesised that patients with severe clinical depression will be characterised by melancholia, more comorbidity, increased number of stressful life events, more sleep disturbance, face perception impairment, executive dysfunction and attentional impairment, psychomotor slowing, reduced HRV, reduced arousal (autonomic and brain), increased right prefrontal activity, impaired emotion (reductions in temporal N170) and oddball (increased P200 but reduced P300 amplitudes) ERPs, and possess specific genotypes in monoaminergic (5-HTT short allele) and BDNF (BDNF 66Met allele) candidate genes. 

The second aim of this study is to explore the proposal that specific genotypes and their interaction impact on neural pathways to influence cognitive and emotional features in patients with clinical depression rather than in individuals with subclinical levels of depressed mood. 

We have recently published a peer-reviewed journal in Molecular Psychiatry which reports on a Gene-Brain-Behaviour Model of subclinical depression and anxiety:

Gatt, J.M., Nemeroff, C.B., Dobson-Stone, C., Paul, R.H., Bryant, R.A., Schofield, P.R., Gordon, E., Kemp, A.H., Williams, L.M. (in press). Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Molecular Psychiatry. Accepted 26 November 2008). 

These findings provided the basis for the proposed project. 

This project relates to:

• A prior study conducted in collaboration with Brain Resource and Johnson and Johnson
• NHMRC Postdoctoral Fellowship (Application: 358770, 2005 – 2009), awarded to Dr Kemp