Primary Insomnia and Major Depressive Disorder May Share Underlying Neurobiology
Key findings
- Previous research has documented that people with both major depressive disorder (MDD) and primary insomnia (PI) have a range of white matter (WM) abnormalities on brain MRI
- This cross-sectional study compared diffusion tensor imaging (DTI) findings in seven WM tracts in 50 individuals with only MDD, 25 with only primary insomnia, and 25 healthy controls
- Both MDD and PI diagnostic groups are characterized by significant sleep disruption, the investigators hypothesized that both MDD and PI cohorts might demonstrate impaired WM integrity in a subset of these WM tracts
- In three WM tracts, significant diffusion-related abnormalities were found in both MDD and PI cohorts: the genu of the corpus callosum, superior longitudinal fasciculus, and inferior longitudinal fasciculus
- These data don't imply that impaired WM integrity is causally related to a diagnosis of MDD or PI; in fact, WM impairment may be the consequence of disordered sleep, a common feature of both disorders
Insomnia is the most frequent sleep complaint among people with major depressive disorder (MDD), increasing the risk of MDD in never-depressed individuals. Brain MRI research recently published in Frontiers in Neuroscience showed that people with MDD who also reported insomnia had abnormalities in white matter (WM) that weren't present in people with MDD who had normal sleep efficiency.
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Harvard researchers built on that study by comparing WM integrity in people with only MDD, those with only primary insomnia (PI), and healthy controls. In the Journal of Sleep Research, they report further evidence of shared underlying neurobiology for MDD and PI.
The authors are Kathleen L. Benson, PhD, of McLean Imaging Center at McLean Hospital, John W. Winkelman, MD, PhD, chief of the Sleep Disorders Clinical Research Program in the Department of Psychiatry at Massachusetts General Hospital, and Atilla Gönenç, PhD, also of the McLean Imaging Center.
Background
WM is typically evaluated with diffusion tensor imaging (DTI), which maps microstructural anatomic details. Specifically, investigators calculate fractional anisotropy (FA), a parameter describing the diffusion pattern of water molecules in the fibers to quantify the directionality and integrity of the WM tract. They also calculated complementary diffusion measures: axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD).
Methods
Candidates for the study underwent an intensive clinical assessment, completed sleep–wake diaries for two weeks, wore a wrist actigraph for two weeks that recorded sleep patterns, and underwent home polysomnography for two nights. They also recorded their caffeine, alcohol, and medication intake and the number of cigarettes for two weeks.
Potential participants were excluded if they smoked >10 cigarettes/day, drank >2 standard alcoholic drinks/day (assuming no history of alcohol abuse), or consumed >300 mg/day of caffeine (equivalent to about three standard cups of coffee). Urine toxicology was used at baseline and the end of the study to exclude participants who used psychoactive agents near the time of MRI despite requests not to.
The final cohort included 100 participants, ages 18 to 70, divided into three cohorts: 50 with MDD, 25 with PI, and 25 without a sleep complaint, history of any psychiatric conditions, or current depressive symptoms.
The researchers calculated DTI-derived FA, AD, RD, and MD from seven white matter tracts: the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus, posterior thalamic radiation, body of the corpus callosum, genu of the corpus callosum (GenuCC), and anterior limb of the internal capsule (ALIC).
White Matter Findings
- GenuCC—Relative to controls, FA was significantly reduced in both the MDD and PI cohorts
- SLF—Relative to controls, FA and AD were significantly reduced in both MDD and PI cohorts
- ILF—Relative to controls, AD and MD were significantly reduced in both MDD and PI cohorts
Supplemental Findings
In an exploratory analysis of the combined cohorts, FA in the GenuCC and FA in the SLF were negatively correlated with depression severity and positively correlated with total sleep time.
Caveat
These data don't necessarily signify that impaired WM integrity is causally related to a diagnosis of MDD or PI. In fact, WM impairment might be the consequence of disordered sleep, a common feature of both disorders.
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