Highlights COVID-19, such as other coronaviruses, is associated with psychiatric implication. 55% of the sample presented a clinical score for at least one mental disorder. Psychiatric history, setting, and length of hospitalization influenced psychopathology. Females suffered more than males, scoring higher in all the measures. There is the need to diagnose and treat psychiatric sequelae in COVID-19 survivors.

COVID-19 outbreak is associated with mental health implications during viral infection and at short-term follow-up. Data on psychiatric and cognitive sequelae at medium-term follow-up are still lacking. During an ongoing prospective cohort study, the psychopathological and cognitive status of 226 COVID-19 pneumonia survivors (149 male, mean age 58) were prospectively evaluated one and three months after hospital discharge. Psychiatric clinical interview, self-report questionnaires, and neuropsychological profiling of verbal memory, working memory, psychomotor coordination, executive functions, attention and information processing, and verbal fluency were performed. Three months after discharge from the hospital, 35.8% still self-rated symptoms in the clinical range in at least one psychopathological dimension. We observed persistent depressive symptomatology, while PTSD, anxiety, and insomnia decreased during follow-up. Sex, previous psychiatric history, and the presence of depression at one month affected the depressive symptomatology at three months. Regardless of clinical physical severity, 78% of the sample showed poor performances in at least one cognitive domain, with executive functions and psychomotor coordination being impaired in 50% and 57% of the sample. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, predicted self-rated depressive symptomatology and cognitive impairment at three-months follow-up; and changes of SII predicted changes of depression during follow-up. Neurocognitive impairments associated with severity of depressive psychopathology, and processing speed, verbal memory and fluency, and psychomotor coordination were predicted by baseline SII. We hypothesize that COVID-19 could result in prolonged systemic inflammation that predisposes patients to persistent depression and associated neurocognitive dysfunction. The linkage between inflammation, depression, and neurocognition in patients with COVID-19 should be investigated in long-term longitudinal studies, to better personalize treatment options for COVID-19 survivors.

Reduced FA with increased mean and radial diffusivity suggests significant demyelination and/or dysmyelination without axonal loss. Comparing our findings with other observations in homogeneous samples of euthymic and manic patients, it can be hypothesized that changes in measures of WM integrity might parallel illness phases of bipolar illness.

Reduced GM volumes in critical cortical areas of suicidal patients could be a biological correlate of an impaired ability to associate choices and outcomes and to plan goal-directed behaviors based on a lifetime historical perspective, which, coupled with mood-congruent depressive cognitive distortions, could lead to more hopelessness and suicide. Lithium could exert its specific therapeutic effect on suicide by acting in the same areas.

We detected specific WM abnormalities, suggestive of disrupted integrity of fiber bundles in the brains of patients with BD. These abnormalities might contribute to understanding both mood dysregulation and cognitive disturbances in BD, and might provide an objective marker to monitor treatment efficacy in this condition.

No abstract

Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits glycogen synthase kinase 3-b (GSK3-b). The less active GSK3-b promoter gene variants have been associated with less detrimental clinical features of BD. GSK3-b gene variants and lithium can influence brain gray matter structure in psychiatric conditions. Diffusion tensor imaging (DTI) measures of white matter (WM) integrity showed widespred disruption of WM structure in BD. In a sample of 70 patients affected by a major depressive episode in course of BD, we investigated the effect of ongoing long-term lithium treatment and GSK3-b promoter rs334558 polymorphism on WM microstructure, using DTI and tract-based spatial statistics with threshold-free cluster enhancement. We report that the less active GSK3-b rs334558*C gene-promoter variants, and the long-term administration of the GSK3-b inhibitor lithium, were associated with increases of DTI measures of axial diffusivity (AD) in several WM fiber tracts, including corpus callosum, forceps major, anterior and posterior cingulum bundle (bilaterally including its hippocampal part), left superior and inferior longitudinal fasciculus, left inferior fronto-occipital fasciculus, left posterior thalamic radiation, bilateral superior and posterior corona radiata, and bilateral corticospinal tract. AD reflects the integrity of axons and myelin sheaths. We suggest that GSK3-b inhibition and lithium could counteract the detrimental influences of BD on WM structure, with specific benefits resulting from effects on specific WM tracts contributing to the functional integrity of the brain and involving interhemispheric, limbic, and large frontal, parietal, and fronto-occipital connections.

Diffusion tensor imaging (DTI) allows the study of white matter (WM) structure. Literature suggests that WM structure could be altered in obsessive-compulsive disorder (OCD) proportional to the severity of the disease. Heterogeneity of brain imaging methods, of the studied samples, and of drug treatments make localization, nature, and severity of the WM abnormalities unclear. We applied Tract-Based Spatial Statistics (TBSS) of DTI measures to compare fractional anisotropy (FA), mean, axial, and radial diffusivity of the WM skeleton in a group of 40 consecutively admitted inpatients affected by severe OCD (18 drug-naive, and 22 with an ongoing drug treatment) and 41 unrelated healthy volunteers from the general population. Data were analyzed accounting for the effects of multiple comparisons, and of age, sex, and education as nuisance covariates. Compared to controls, OCD patients showed a widespread reduction of FA with a concurrent increase of mean and radial diffusivity. In no brain areas patients had higher FA or lower diffusivity values than controls. These differences were observed in drug-treated patients compared to drug-naive patients and healthy controls, which in turn did not differ among themselves in any DTI measure. Reduced FA with increased mean and radial diffusivity suggests significant changes in myelination of WM tracts, without axonal loss. Drug treatments could modify the structure of cell membranes and myelin sheaths by influencing cellular lipogenesis, cholesterol homeostasis, autophagy, oligodendrocyte differentiation and remyelination. Changes of DTI measures in drug-treated OCD patients could reflect pathophysiological underpinnings of OCD, or a yet unexplored part of the mechanism of action of drugs.