•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.
Infection-triggered perturbation of the immune system could induce psychopathology, and psychiatric sequelae were observed after previous coronavirus outbreaks. The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. We investigated the psychopathological impact of COVID-19 in survivors, also considering the effect of clinical and inflammatory predictors.
We screened for psychiatric symptoms 402 adults surviving COVID-19 (265 male, mean age 58), at one month follow-up after hospital treatment. A clinical interview and a battery of self-report questionnaires were used to investigate post-traumatic stress disorder (PTSD), depression, anxiety, insomnia, and obsessive-compulsive (OC) symptomatology. We collected sociodemographic information, clinical data, baseline inflammatory markers and follow-up oxygen saturation levels.
A significant proportion of patients self-rated in the psychopathological range: 28% for PTSD, 31% for depression, 42% for anxiety, 20% for OC symptoms, and 40% for insomnia. Overall, 56% scored in the pathological range in at least one clinical dimension. Despite significantly lower levels of baseline inflammatory markers, females suffered more for both anxiety and depression. Patients with a positive previous psychiatric diagnosis showed increased scores on most psychopathological measures, with similar baseline inflammation. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, positively associated with scores of depression and anxiety at follow-up.
PTSD, major depression, and anxiety, are all high-burden non-communicable conditions associated with years of life lived with disability. Considering the alarming impact of COVID-19 infection on mental health, the current insights on inflammation in psychiatry, and the present observation of worse inflammation leading to worse depression, we recommend to assess psychopathology of COVID-19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions.
Patients with bipolar disorder (BD) experience difficulties in information processing and in the cognitive control of emotions. Mood-congruent biases, which parallel illness episodes, find a neural ...correlate in abnormal reactivity to stimuli in specific brain regions, and in disrupted functional connectivity among brain areas pertaining to corticolimbic circuitries. It is suggested that a reduced integrity of white matter tracts could underpin dysfunctions in networks implicated in the generation and control of affect. Recent studies using diffusion tensor imaging techniques found that (1) independent of drug treatment, patients with BD show widespread signs of disrupted white matter microstructure, suggesting significant demyelination/dysmyelination without axonal loss, and (2) effective long-term treatment with lithium is associated with increased axial connectivity, proportional to the duration of treatment. These findings suggest that changes of white matter microstructure in specific brain networks could parallel disrupted neural connectivity during illness episodes in BD and that these changes might play a major role in the mechanistic explanation of the biological underpinnings of BD psychopathology.
Objective:Structural brain imaging studies in obsessive-compulsive disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small ...samples and clinical heterogeneity related to variation in illness profile and developmental stage. To address these limitations, the authors conducted meta- and mega-analyses of data from OCD sites worldwide.Method:T1 images from 1,830 OCD patients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCD patients and healthy subjects. The authors performed a meta-analysis on the mean of the left and right hemisphere measures of each subcortical structure, and they performed a mega-analysis by pooling these volumetric measurements from each site. The authors additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients.Results:The meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen’s d=−0.13; % difference=−2.80) and larger pallidum volumes (d=0.16; % difference=3.16) compared with adult controls. Both effects were stronger in medicated patients compared with controls (d=−0.29, % difference=−4.18, and d=0.29, % difference=4.38, respectively). Unmedicated pediatric patients had significantly larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric controls. None of these findings were mediated by sample characteristics, such as mean age or scanning field strength. The mega-analysis yielded similar results.Conclusions:The results indicate different patterns of subcortical abnormalities in pediatric and adult OCD patients. The pallidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD may be useful.
COVID-19 survivors are at increased risk of persistent psychopathology after the infection. Despite long-term sequelae are an increasing concern, long-term neuropsychiatric consequences remain ...largely unclear. This cohort study aimed at investigating the psychopathological impact of COVID-19 in Italy one year after infection, outlining the trajectory of symptomatology at one, six-, and twelve-months follow-up.
We evaluated 402, 216, and 192 COVID-19 survivors respectively at one, six, and 12 months. A subgroup of 95 patients was evaluated longitudinally both at one, six, and 12 months. Validated self-report questionnaires were administered to assess depression, fatigue, anxiety, and post-traumatic distress. Socio-demographics and setting of care information were gathered for each participant.
At six and twelve months, respectively 94 (44%) and 86 (45%) patients self-rated in the clinical range in at least one psychopathological dimension. Pathological fatigue at twelve months was detected in 63 patients (33%). Considering the longitudinal cohort an interaction effect of sex and time was observed for depression (F = 8.63, p < 0.001) and anxiety (F = 5.42, p = 0.005) with males showing a significant increasing trend of symptoms, whereas an opposite course was observed in females.
High prevalence of psychiatric sequelae six and 12 months after COVID-19 was reported for the first time. These findings confirm the need to provide integrated multidisciplinary services to properly address long-lasting mental health sequelae of COVID-19 and to treat them with the aim of reducing the disease burden and related years of life lived with disability.
Abstract Background Bipolar disorder (BD) is associated with elevated biomarkers of cell-mediated immune activation and inflammation and with signs of widespread disruption of white matter (WM) ...integrity in adult life. Consistent findings in animal models link WM damage in inflammatory diseases of the brain and serum levels of cytokines. Methods With an exploratory approach, we tested the effects of 22 serum analytes, including pro- and anti-inflammatory cytokines and neurotrophic/hematopoietic factors, on DTI measures of WM microstructure in a sample of 31 patients with a major depressive episode in course of BD. We used whole brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial (AD), radial (RD), and mean diffusivity (MD), and fractional anisotropy (FA). Results The inflammation-related cytokines TNF-α, IL-8, IFN-γ and IL-10, and the growth factors IGFBP2 and PDGF-BB, shared the same significant associations with lower FA, and higher MD and RD, in large overlapping networks of WM fibers mostly located in the anterior part of the brain and including corpus callosum, cingulum, superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculi, uncinate, forceps, corona radiata, thalamic radiation, internal capsule. Conclusions Higher RD is thought to signify increased space between fibers, suggesting demyelination or dysmyelination. The pattern of higher RD and MD with lower FA suggests that inflammation-related cytokine and growth factor levels inversely associate with integrity of myelin sheaths. The activated inflammatory response system might contribute to BD pathophysiology by hampering structural connectivity in critical cortico-limbic networks.
Major Depressive Disorder (MDD) is a worldwide-spread pathology, characterized by lifetime-recurrent episodes. Adverse childhood experiences (ACE) increase the lifetime risk of developing depression ...and affect the structure of the brain. Recent stressful events (RSE) can trigger the onset of depressive episodes, and affect grey matter volume. The aim of our study is to analyse the effect of both early and recent stress events on white matter microstructure in MDD patients and healthy volunteers.
Sixty-five MDD inpatients and fifty-nine healthy controls underwent MRI acquisition of diffusion tensor images with a 3.0T scanner. Severity of ACE and RSE was rated, respectively, on the Risky Families Questionnaire and on the Social Readjustment Rating Scale.
A significant effect of diagnosis was observed, with MDD subjects showing reduced fractional anisotropy (FA) and axial diffusivity (AD) compared to healthy controls in all the major association, projection and commissural tracts. In patients with MDD, but not in healthy controls, both ACE and RSE correlated with measures of WM microstructure: ACE correlated negatively with AD and MD, whereas RSE correlated negatively with FA.
The two diagnostic groups differed for age and education, previous and current medications, and treatment periods. Conclusions. Exposure to both early and recent stress exerts a widespread effect on WM microstructure of MDD patients, with a different impact possibly depending from the developmental period in which the stress has occurred.
•Depressed patients show reduced white matter integrity compared to controls.•Higher early stress associates to lower axial and mean diffusivity in depression.•Higher recent stress associates to lower fractional anisotropy in depression.•Early and recent stress impact respectively on early and late development tracts.
Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. ...Here we carried out what is by far the largest study of brain structural asymmetry in OCD.
We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.
In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen’s d = 0.19) and the pallidum (less leftward; d = −0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.
The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.
Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive–compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable ...limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi‐site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA‐OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.
Abstract Background Changes of white matter (WM) microstructure have been proposed as structural biomarkers of bipolar disorder (BD). The chronotherapeutic combination of repeated total sleep ...deprivation and morning light therapy (TSD+LT) can acutely reverse depressive symptoms in approximately 60% of patients, and it has been proposed as a model antidepressant treatment to investigate the neurobiological correlates of rapid antidepressant response. Methods We tested if baseline DTI measures can predict response to treatment in 70 in-patients affected by a major depressive episode in the course of BD, treated with chronotherapeutics for one week. We performed whole-brain tract-based spatial statistics with threshold-free cluster enhancement for the DTI measures of WM microstructure integrity: fractional anisotropy, axial, radial, and mean diffusivity. Results Increased mean and radial water diffusivity correlated with poor antidepressant response to TSD+LT in core WM tracts which are crucial for the functional integrity of the brain, including corpus callosum, corona radiata, cingulum bundle, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and thalamic radiation. Limitations Limitations include issues such as generalizability, possible population stratification, medications and their effects on DTI measures, and no placebo control for chronotherapeutics. We could not consider other factors such as gene–environment interactions. Conclusions The association of increased radial and mean diffusivity with poor response to chronotherapeutic treatment warrants interest for the study of DTI measures of WM microstructure as markers for treatment response in bipolar depression.
Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies ...have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.
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