Brain structural correlates of insomnia severity in 1053 individuals with major depressive disorder: results from the ENIGMA MDD Working Group

Abstract

It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent samples comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD; healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD.

Polygenic risk scores for major psychiatric and neurodevelopmental disorders contribute to sleep disturbance in childhood: Adolescent Brain Cognitive Development (ABCD) Study

“…Our main findings suggest that the PRSs for ADHD and MDD may explain a portion of the etiology of sleep disturbance regardless of current diagnostic status. Furthermore, reduced cortical areas, which are more strongly determined by genetic influences 51 , are specifically associated with insomnia severity, not with depression severity in MDD 52 . Given these findings, sleep disturbance may play a role in the intermediation between genetic risk and the onset of these psychiatric and neurodevelopmental disorders, e.g., via reduced cortical areas.…”

Cross disorder comparisons of brain structure in schizophrenia, bipolar disorder, major depressive disorder, and 22q11.2 deletion syndrome: A review of ENIGMA findings

“…These findings suggest that cortical thickness may be more reflective of an adult onset MDD subtype and chronicity, while smaller cortical surface area may reflect an early developmental subtype of depressive disorder, induced by genetic factors or early life adversity 29 . We speculate that the observed presence of cortical thickness deficiencies in the adult but not adolescent MDD sample may be due to the older mean age of the adult than adolescent MDD sample, and may be suggestive of a more pronounced effect of aging on cortical thickness in MDD versus controls69; though longitudinal studies are needed to test this hypothesis 72 …”

“…71 Leerssen and colleagues investigated whether insomnia severity was associated with global and regional differences in cortical thickness, cortical surface areas, and volumes of subcortical regions in a sample of 1053 individuals with MDD from 15 cohorts worldwide. 72 Only cortical surface area, and neither subcortical volumes or cortical thickness, was predictive of insomnia severity in MDD. Regionally, insomnia severity was associated with smaller right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus surface area.…”

“…Leerssen and colleagues investigated whether insomnia severity was associated with global and regional differences in cortical thickness, cortical surface areas, and volumes of subcortical regions in a sample of 1053 individuals with MDD from 15 cohorts worldwide 72 . Only cortical surface area, and neither subcortical volumes or cortical thickness, was predictive of insomnia severity in MDD.…”

Relation of Decreased Functional Connectivity Between Left Thalamus and Left Inferior Frontal Gyrus to Emotion Changes Following Acute Sleep Deprivation

“…The inferior frontal gyrus is comprised of the orbital inferior frontal gyrus, triangular inferior frontal gyrus and opercular inferior frontal gyrus (44). The study found significant changes in frontal lobe function during sleep deprivation (45), and certain studies have suggested that functional changes in the left inferior frontal gyrus during sleep deprivation are associated with anxiety, depression and mood swings (7,43,46,47). Given the various functions of the left inferior frontal gyrus, it is difficult to distinguish whether it is the responsible center or relay station of emotion changes according to the existing research, but it is clear that the left inferior frontal gyrus is an important hub of the emotional pathways.…”