Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with several neurologic manifestations including the development of cerebral lesions resembling CNS vasculitis in elderly patients with severe coronavirus disease 2019 (COVID-19). [1][2][3][4] Here, we report additional evidence for COVID-19-related CNS vasculitis, confirmed by biopsy, in a young healthy patient with otherwise mild COVID-19 infection.

Objective To assess the initial features and evolution of neurologic Postacute Sequelae of SARS‐CoV‐2 infection (neuro‐PASC) in patients with and without prior neurologic disease. Methods Participants with neurologic symptoms following acute SARS‐CoV‐2 infection were recruited from October 9, 2020 to October 11, 2021. Clinical data included a SARS‐CoV‐2 infection history, neurologic review of systems, neurologic exam, Montreal cognitive assessment (MoCA), and symptom‐based self‐reported surveys at baseline (conducted after acute infection) and 6‐month follow‐up assessments. Results Fifty‐six participants (69% female, mean age 50 years, 29% with prior neurologic disease such as multiple sclerosis) were enrolled, of which 27 had completed the 6‐month follow‐up visit in this ongoing study. SARS‐CoV‐2 infection severity was largely described as mild (39.3%) or moderate (42.9%). At baseline, following acute infection, the most common neurologic symptoms were fatigue (89.3%) and headaches (80.4%). At the 6‐month follow‐up, memory impairment (68.8%) and decreased concentration (61.5%) were the most prevalent, though on average all symptoms showed a reduction in reported severity score at the follow‐up. Complete symptom resolution was reported in 33.3% of participants by 6 months. From baseline to 6 months, average MoCA scores improved overall though 26.3% of participants’ scores decreased. A syndrome consisting of tremor, ataxia, and cognitive dysfunction (PASC‐TAC) was observed in 7.1% of patients. Interpretation Early in the neuro‐PASC syndrome, fatigue and headache are the most commonly reported symptoms. At 6 months, memory impairment and decreased concentration were most prominent. Only one‐third of participants had completed resolution of neuro‐PASC at 6 months, although persistent symptoms trended toward improvement at follow‐up.