Genetic variants associated with longitudinal changes in brain structure across the lifespan.

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

The neuroscience of sadness: A multidisciplinary synthesis and collaborative review.

Sadness is typically characterized by raised inner eyebrows, lowered corners of the mouth, reduced walking speed, and slumped posture. Ancient subcortical circuitry provides a neuroanatomical foundation, extending from dorsal periaqueductal grey to subgenual anterior cingulate, the latter of which is now a treatment target in disorders of sadness. Electrophysiological studies further emphasize a role for reduced left relative to right frontal asymmetry in sadness, underpinning interest in the transcranial stimulation of left dorsolateral prefrontal cortex as an antidepressant target. Neuroimaging studies - including meta-analyses - indicate that sadness is associated with reduced cortical activation, which may contribute to reduced parasympathetic inhibitory control over medullary cardioacceleratory circuits. Reduced cardiac control may - in part - contribute to epidemiological reports of reduced life expectancy in affective disorders, effects equivalent to heavy smoking. We suggest that the field may be moving toward a theoretical consensus, in which different models relating to basic emotion theory and psychological constructionism may be considered as complementary, working at different levels of the phylogenetic hierarchy.