The Pathology of Synapses in Brain Networks Implicated in Depression

Abstract

Non-invasive brain imaging has identified changes in the prefrontal–limbic network (Fig. 6.1) in patients suffering from major depression disease (MDD), principally in prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex, hippocampus and the amygdala. For example, different regions in the medial prefrontal cortex and orbitofrontal cortex normally exert an inhibitory influence over activity in the amygdala, but fail to do so in depression according to functional magnetic resonance imaging (fMRI) studies (Drevets 2007; Savitz and Drevets 2009). Furthermore the evidence suggests there is a lack of functional connection in depressed patients between the subgenual anterior cingulate cortex (ACC) on the one hand and the rostral (pregenual) ACC and hippocampus on the other, as well as between the rostral ACC and the amygdala (Anand et al. 2009; Savitz and Drevets 2009). In depressed patients there is increased activity in the subgenual ACC accompanied by decreased activity in the dorsolateral prefrontal cortex (Drevets et al. 2008; Mayberg et al. 1999) leading to the conjecture that it is failure of inhibitory control from the dorsal areas over the ventral areas that leads to increased activity in the ventral areas (Taylor and Liberzon 2007). Use of multivariate techniques combined with structural equation modeling, applied to resting-state positron emission tomography (PET) scans of acutely depressed patients, show differences in known anatomical and physiological pathways. An estimate has been made of the strength and direction of ‘effective connections’ between these areas (James et al. 2009). Changes are observed between subgenual ACC, pregenual ACC, orbitofrontal cortex, hippocampus/amygdala, and the prefrontal cortex (Fig. 6.1).