Discovering imaging endophenotypes for major depression

Abstract

Psychiatry research lacks an in-depth understanding of mood disorders phenotypes, leading to limited success of genetics studies of major depressive disorder (MDD). The dramatic progress in safe and affordable magnetic resonance-based imaging methods has the potential to identify subtle abnormalities of neural structures, connectivity and function in mood disordered subjects. This review paper presents strategies to improve the phenotypic definition of MDD by proposing imaging endophenotypes derived from magnetic resonance spectroscopy measures, such as cortical gamma-amino butyric acid (GABA) and glutamate/glutamine concentrations, and from measures of resting-state activity and functional connectivity. The proposed endophenotypes are discussed regarding specificity, mood state-independence, heritability, familiarity, clinical relevance and possible associations with candidate genes. By improving phenotypic definitions, the discovery of new imaging endophenotypes will increase the power of candidate gene and genome-wide associations studies. It will also help to develop and evaluate novel therapeutic treatments and enable clinicians to apply individually tailored therapeutic approaches. Finally, improvements of the phenotypic definition of MDD based on neuroimaging measures will contribute to a new classification system of mood disorders based on etiology and pathophysiology.

The Default Mode Network and Recurrent Depression: A Neurobiological Model of Cognitive Risk Factors

“…These authors suggested that, given the role of the caudate nucleus in reward processing (Yacubian et al, 2006), this connectivity pattern may be related to anhedonia in depression. While these inconsistent results may simply be due to the use of different methods of analysis (Hasler and Northoff, 2011), they could also be linked to different stages of the depressive illness (e.g. strengthened vs. decoupled links between emotion, cognition and bodily sensations), whereby early (or first onset) and recurrent (or chronically) depressed individuals may show different connectivity patterns.…”

“…Unfortunately no studies have investigated this issue in depressed patients thus far, but it has been proposed that the divergence between structural and functional connectivity might be strong in mood disorders, perhaps mediated by neurochemical imbalance (Hasler and Northoff, 2011 Ochsner et al, 2004), recent studies have investigated how these regions respond to emotional stimuli in depression, and specifically whether rest-to-task transition in emotional contexts is affected by TN-persistence and TP-deficiency ( Figure 4). …”

“…Several recent attempts have been made to relate different facets of depressive phenomenology to DMN (Hasler and Northoff, 2011;Pizzagalli, 2011). Among others, proposed a DMN system theory of depression, focusing on underlying mechanisms of symptoms.…”

“…rFIC) functioning differently in depressed compared with healthy subjects (Hamilton et al, 2010); (v) less segregation between TP, TN and other resting state networks (Epstein et al, 2011;Zhang et al, 2011) and a strong role for the DMPFC across these networks in depression (Sheline et al, 2010); (vi) at-risk individuals seem to show a depressionlike DMN pattern (Di Simplicio et al, 2011;Norbury et al, 2011). Recently, several theoretical models try to account for different aspects of current depression in relation to DMN (Hasler and Northoff, 2011;Pizzagalli, 2011).…”

Situacioni Činioci Afektivnog Stanja – Afektivne Promene Tokom Mirovanja I Indukcije Afekta

“…Neuronska mreža mirovanja je jedna od tri velike neuralne mreže za koje se pretpostavlja da međusobnim delovanjem u velikoj meri učestvuju u obradi informacija tokom emocionalnih i kognitivnih procesa (Chen et al, 2013). Nekoliko teorijskih modela ponudilo je objašnjenje za povezanost različitih aspekata aktuelne depresivne epizode i disfunkcija neuronske mreže mirovanja (Hasler & Northoff, 2011;Marchetti et al, 2012;Whitfield-Gabrieli & Ford, 2012). Psihološki procesi poput autobiografskih sećanja, projekcije u budućnost, i misli o sebi se dovode u vezu sa aktivnošću ove mreže, te se smatra da ona odslikava unutrašnji fokus osobe (Christoff, Cosmelli, Legrand, & Thompson, 2011;Fossati et al, 2003;Ochsner, Bunge, Gross, & Gabrieli., 2002).…”