Abnormal neural sensitivity to rewards as a candidate process of high depression risk in the FMR1 premutation: A pilot study.

The etiological heterogeneity of depression poses a challenge for prevention and intervention efforts. One solution is to map unique etiological pathways for subgroups defined by a singular risk factor. A relevant population for this approach is women who carry the premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene, who are at high risk for adult-onset depression. This study explores a candidate neurophysiological marker of depression risk: reduced reward sensitivity, indexed by the reward positivity (RewP). The RewP has been linked to depression risk in the general population, but is unexplored within FMR1 premutation carriers. 16 women with the FMR1 premutation and a matched control group completed a simple guessing task while the electroencephalogram was recorded. Among premutation carriers, RewP difference score (win versus loss) was reduced. These preliminary finding suggest that the FMR1 premutation may confer increased risk for depression in part through abnormal neural sensitivity to rewards.

Whole-brain mapping of increased manganese levels in welders and its association with exposure and motor function.

Although manganese (Mn) is a trace metal essential for humans, chronic exposure to Mn can cause accumulation of this metal ion in the brain leading to an increased risk of neurological and neurobehavioral health effects. This is a concern for welders exposed to Mn through welding fumes. While brain Mn accumulation in occupational settings has mostly been reported in the basal ganglia, several imaging studies also revealed elevated Mn in other brain areas. Since Mn functions as a magnetic resonance imaging (MRI) T1 contrast agent, we developed a whole-brain MRI approach to map in vivo Mn deposition differences in the brains of non-exposed factory controls and exposed welders. This is a cross-sectional analysis of 23 non-exposed factory controls and 36 exposed full-time welders from the same truck manufacturer. We collected high-resolution 3D MRIs of brain anatomy and R1 relaxation maps to identify regional differences using voxel-based quantification (VBQ) and statistical parametric mapping. Furthermore, we investigated the associations between excess Mn deposition and neuropsychological and motor test performance. Our results indicate that: (1) Using whole-brain MRI relaxometry methods we can generate excess Mn deposition maps in vivo, (2) excess Mn accumulation due to occupational exposure occurs beyond the basal ganglia in cortical areas associated with motor and cognitive functions, (3) Mn likely diffuses along white matter tracts in the brain, and (4) Mn deposition in specific brain regions is associated with exposure (cerebellum and frontal cortex) and motor metrics (cerebellum and hippocampus).

Abnormal neurophysiological sensitivity to rewards in depression is moderated by sex and age in middle adulthood.

A candidate pathophysiological process in major depressive disorder is diminished neural reactivity to reward delivery, which is theorized to give rise to anhedonia. Reduced amplitude in the reward positivity (RewP), which captures initial reward evaluation, has been linked to current symptoms of depression among child, adolescent, and young adult samples. However, the developmental trajectory of this association is incomplete, with relatively few studies in middle and older adulthood. Further, emerging evidence in the literature also suggests that this association may be linked to female sex-specific processes, but no studies to date have directly contrasted the effect of sex on the depression-RewP association. The current study sought to address these gaps by testing how sex and age may moderate the depression-RewP association within a mature adult community sample. Symptoms of depression were evaluated using a survey and a clinical interview, and the RewP was elicited using a simple guessing task. There was a three-way interaction between depression symptom severity, age, and sex in predicting RewP amplitude. This was driven by younger (late 30's to early 40's) female-sexed people such that for this group, elevated symptoms of depression were associated with blunting of the RewP. This association tapered around age 50. This effect was specific to clinician-rated rather than self-reported depressive symptom severity. This pattern of effects suggests that among female-sexed people, developmental processes continue to shape the association between reward responsiveness and depression throughout middle adulthood.