Neurobiological Markers of Familial Risk for Depression

Abstract

Major depression is associated with a wide range of neurobiological disturbances, including anomalies in the structure and function of cortical and subcortical gray matter and dysregulation of the HPA axis. In this chapter, we review research demonstrating that many of these abnormalities are also present in never-depressed offspring of adults with recurrent depression and discuss how such findings might reflect dysfunctional neuroregulatory systems that precede the onset of this disorder. We also briefly discuss candidate genes and environmental factors that have been posited to be directly involved in the transmission of neural and HPA-axis abnormalities from depressed parents to their offspring, and we review how, by obtaining a better understanding of the neurobiological markers of depression risk, we can facilitate the development of targeted strategies for the prevention and treatment of major depression.

Orbital and Medial Prefrontal Cortex Functional Connectivity of Major Depression Vulnerability and Disease

“…This region has dense anatomical connections to autonomic centers (41, 42), and has been implicated in assessment salience and affective value of emotional information (43), conflict monitoring in the presence of emotional distractors (40, 44–49) as well as in awareness and regulation of emotional responses (40, 50–52). This affective bias hypothesis is furthermore in agreement with behavioral characteristics observed in people with genetic MD susceptibility and remitted depressed (53, 54) such as difficulty directing attention away from negative stimuli (54), reappraising (55) and suppressing negative distractors (56). …”

Fetal Exposure to Maternal Depressive Symptoms Is Associated With Cortical Thickness in Late Childhood

“…However, we are reluctant to draw the conclusion based on our methods that maternal cortisol is not an important signal to the fetus of maternal depressive state. For instance, morning salivary cortisol levels are higher in patients diagnosed with depression than they are in never-depressed individuals[69–71] and different forms of depression (melancholic and atypical) is associated either with hyper- or hypoactivation of the HPA axis[72]. Hyperactivity of the HPA axis in major depression is one of the most reliably reported neurobiological characteristics of affective disorders[73] and when depression is linked with elevated or temporally dysregulated cortisol secretion, the symptoms are more severe[74].…”

Prefrontal brain responsiveness to negative stimuli

“…5,6 However, the few existing studies focusing on functional alterations associated with familial risk for MDD have reported differing results. 4 For example, Joorman and colleagues 7 found reduced DLPFC activation in female participants at high familial risk for MDD during automatic mood regulation. These findings were confirmed by a study reporting reduced DLPFC activation in individuals at familial risk for MDD during presentation of fearful faces.…”

“…2,3 In recent years neuroimaging studies have described overlapping structural alterations in individuals with MDD and corresponding risk factors, whereas evidence for reliable functional biomarkers of different MDD risk factors is still widely absent. 4 Acute MDD is frequently reported to be characterized by overactive bottom-up signalling during emotion processing, probably combined with decreased top-down or regulatory mechanisms in cortical brain areas. More precisely, over the last decade enhanced neural response in a ventromedial neur al circuit, including the medial orbitofrontal cortex (OFC), the amygdala and the insula, and decreased neural response in a dorsal network, predominantly involving the Background: Identifying reliable trait markers of familial risk for major depressive disorder (MDD) is a challenge in translational psych iatric research.…”