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

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.

Effectiveness of Visual vs. Acoustic Closed-Loop Stimulation on EEG Power Density during NREM Sleep in Humans.

The aim of the study was to investigate whether visual stimuli have the same potency to increase electroencephalography (EEG) delta wave power density during non-rapid eye movement (NREM) sleep as do auditory stimuli that may be practical in the treatment of some sleep disturbances. Nine healthy subjects underwent two polysomnography sessions-adaptation and experimental-with EEG electrodes positioned at Fz-Cz. Individually adjusted auditory (pink noise) and visual (light-emitting diode (LED) red light) paired 50-ms signals were automatically presented via headphones/eye mask during NREM sleep, shortly (0.75-0.90 s) after the EEG wave descended below a preset amplitude threshold (closed-loop in-phase stimulation). The alternately repeated 30-s epochs with stimuli of a given modality (light, sound, or light and sound simultaneously) were preceded and followed by 30-s epochs without stimulation. The number of artifact-free 1.5-min cycles taken in the analysis was such that the cycles with stimuli of different modalities were matched by number of stimuli presented. Acoustic stimuli caused an increase (p < 0.01) of EEG power density in the frequency band 0.5-3.0 Hz (slow waves); the values reverted to baseline at post-stimuli epochs. Light stimuli did not influence EEG slow wave power density (p > 0.01) and did not add to the acoustic stimuli effects. Thus, dim red light presented in a closed-loop in-phase fashion did not influence EEG power density during nocturnal sleep.

No Alterations of Brain Structural Asymmetry in Major Depressive Disorder: An ENIGMA Consortium Analysis.

OBJECTIVE: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects. METHODS: The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen's d=0.1. RESULTS: The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset. CONCLUSIONS: Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.