Neuroimaging studies assessing neurobiological differences between patients with major depressive disorder (MDD) and healthy controls (HC) are often hindered by small sample sizes and heterogeneity of the patient sample. We performed a comprehensive literature search for studies assessing cortical thickness between patient and control groups, including studies investigating treatment effects on cortical thickness. We identified 34 studies meeting criteria for the systematic review and used Seed-based d Mapping to meta-analyze 24 of those that met additional criteria. Analysis of the full sample of subjects (MDD = 1073; HC = 936) revealed significant thinning in the MDD group in the bilateral orbitofrontal gyrus (BA 11), left pars opercularis (BA 45) and left calcarine fissure/lingual gyrus (BA 17), as well as an area of significant thickening in the left supramarginal gyrus (BA 40). These results support other imaging modalities that report disruptions in various frontal and temporal areas in MDD and identify additional areas in all major cerebral lobes likely to be significant when parsing for biomarkers of treatment or relapse.

BackgroundChronic neuropathic pain is a common symptom of multiple sclerosis (MS). MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) has been used as an animal model to investigate the mechanisms of pain in MS. Previous studies have implicated sensitization of spinal nociceptive networks in the pathogenesis of pain in EAE. However, the involvement of supraspinal sites of nociceptive integration, such as the primary somatosensory cortex (S1), has not been defined. We therefore examined functional, structural, and immunological alterations in S1 during the early stages of EAE, when pain behaviors first appear.We also assessed the effects of the antidepressant phenelzine (PLZ) on S1 alterations and nociceptive (mechanical) sensitivity in early EAE. PLZ has been shown to restore central nervous system (CNS) tissue concentrations of GABA and the monoamines (5-HT, NA) in EAE. We hypothesized that PLZ treatment would also normalize nociceptive sensitivity in EAE by restoring the balance of excitation and inhibition (E-I) in the CNS.MethodsWe used in vivo flavoprotein autofluorescence imaging (FAI) to assess neural ensemble responses in S1 to vibrotactile stimulation of the limbs in early EAE. We also used immunohistochemistry (IHC), and Golgi-Cox staining, to examine synaptic changes and neuroinflammation in S1. Mechanical sensitivity was assessed at the clinical onset of EAE with Von Frey hairs.ResultsMice with early EAE exhibited significantly intensified and expanded FAI responses in S1 compared to controls. IHC revealed increased vesicular glutamate transporter (VGLUT1) expression and disrupted parvalbumin+ (PV+) interneuron connectivity in S1 of EAE mice. Furthermore, peri-neuronal nets (PNNs) were significantly reduced in S1. Morphological analysis of excitatory neurons in S1 revealed increased dendritic spine densities. Iba-1+ cortical microglia were significantly elevated early in the disease. Chronic PLZ treatment was found to normalize mechanical thresholds in EAE. PLZ also normalized S1 FAI responses, neuronal morphologies, and cortical microglia numbers and attenuated VGLUT1 reactivity—but did not significantly attenuate the loss of PNNs.ConclusionsThese findings implicate a pro-excitatory shift in the E-I balance of the somatosensory CNS, arising early in the pathogenesis EAE and leading to large-scale functional and structural plasticity in S1. They also suggest a novel antinociceptive effect of PLZ treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0609-4) contains supplementary material, which is available to authorized users.

Highlights Depression was associated with a larger brain-age gap in older individuals. Body mass index was associated with a larger brain-age gap. Brain-age gap was not associated with an overall antidepressant treatment response.

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