White-matter free-water diffusion MRI in schizophrenia: a systematic review and meta-analysis

White-matter abnormalities, including increases in extracellular free-water, are implicated in the pathophysiology of schizophrenia. Recent advances in diffusion magnetic resonance imaging (MRI) enable free-water levels to be indexed. However, the brain levels in patients with schizophrenia have not yet been systematically investigated. We aimed to meta-analyse white-matter free-water levels in patients with schizophrenia compared to healthy volunteers. We performed a literature search in EMBASE, MEDLINE, and PsycINFO databases. Diffusion MRI studies reporting free-water in patients with schizophrenia compared to healthy controls were included. We investigated the effect of demographic variables, illness duration, chlorpromazine equivalents of antipsychotic medication, type of scanner, and clinical symptoms severity on free-water measures. Ten studies, including five of first episode of psychosis have investigated free-water levels in schizophrenia, with significantly higher levels reported in whole-brain and specific brain regions (including corona radiata, internal capsule, superior and inferior longitudinal fasciculus, cingulum bundle, and corpus callosum). Six studies, including a total of 614 participants met the inclusion criteria for quantitative analysis. Whole-brain free-water levels were significantly higher in patients relative to healthy volunteers (Hedge’s g = 0.38, 95% confidence interval (CI) 0.07–0.69, p = 0.02). Sex moderated this effect, such that smaller effects were seen in samples with more females (z = −2.54, p < 0.05), but antipsychotic dose, illness duration and symptom severity did not. Patients with schizophrenia have increased free-water compared to healthy volunteers. Future studies are necessary to determine the pathological sources of increased free-water, and its relationship with illness duration and severity.

Cortical thickness across the cingulate gyrus in schizophrenia and its association to illness duration and memory performance

Schizophrenia has been associated with structural brain abnormalities and cognitive deficits that partly change during the course of illness. In the present study, cortical thickness in five subregions of the cingulate gyrus was assessed in 44 patients with schizophrenia-spectrum disorder and 47 control persons and related to illness duration and memory capacities. In the patients group, cortical thickness was increased in the posterior part of the cingulate gyrus and related to illness duration whereas cortical thickness was decreased in anterior parts unrelated to illness duration. In contrast, cortical thickness was related to episodic and working memory performance only in the anterior but not posterior parts of the cingulate gyrus. Our finding of a posterior cingulate increase may point to either increased parietal communication that is accompanied by augmented neural plasticity or to effects of altered neurodegenerative processes in schizophrenia.

Mismatch Negativity and P3a Impairment through Different Phases of Schizophrenia and Their Association with Real-Life Functioning

Impairment in functioning since the onset of psychosis and further deterioration over time is a key aspect of subjects with schizophrenia (SCZ). Mismatch negativity (MMN) and P3a, indices of early attention processing that are often impaired in schizophrenia, might represent optimal electrophysiological candidate biomarkers of illness progression and poor outcome. However, contrasting findings are reported about the relationships between MMN-P3a and functioning. The study aimed to investigate in SCZ the influence of illness duration on MMN-P3a and the relationship of MMN-P3a with functioning. Pitch (p) and duration (d) MMN-P3a were investigated in 117 SCZ and 61 healthy controls (HCs). SCZ were divided into four illness duration groups: ≤ 5, 6 to 13, 14 to 18, and 19 to 32 years. p-MMN and d-MMN amplitude was reduced in SCZ compared to HCs, independently from illness duration, psychopathology, and neurocognitive deficits. p-MMN reduction was associated with lower “Work skills”. The p-P3a amplitude was reduced in the SCZ group with longest illness duration compared to HCs. No relationship between P3a and functioning was found. Our results suggested that MMN amplitude reduction might represent a biomarker of poor functioning in SCZ.

Baseline Predictors of Adherence in a Randomised Controlled Trial of a New Group Psychological Intervention for People with Recurrent Binge Eating Episodes Associated to Overweight or Obesity

Purpose: Understanding the high rate of treatment adherence in trials of people with eating disorders is important as it can compromise the quality of the trials. In clinical practice, it may also contribute to illness chronicity, relapse, and costs. Thus, we investigated factors associated with adherence to a new treatment HAPIFED, which integrates cognitive behavioural therapy having extended sessions with body weight loss therapy compared to cognitive behavioural therapy with extended sessions alone, for individuals with Bulimia Nervosa or Binge Eating Disorder or other eating disorders comorbid with overweight or obesity. Methods: In total, 98 participants having bulimia nervosa, binge eating disorder and other specified and unspecified eating disorders were recruited with 50 randomised to HAPIFED and 48 to the control intervention CBT-E, all administered in groups of up to 10 participants. An investigator external to the site conducted the random allocation, which was concealed from the statistician involved in the analysis, and known only to the therapists until the finalization of the 12-month follow-up after the end of active treatment. Three scenarios in the timeline treatment of a total of 30 sessions were assessed: 33% or 60% or 75% of presence. Mixed-effects logistic regression analysis was performed to find the correlates of adherence after adjusting for clustering by number of group participants. To account for heterogeneity by types of eating disorders in the sample, the latter variable was considered as a control factor in the models. A subgroup analysis was performed for those with binge eating disorder as this was the largest (N = 66) eating disorder group. Results: None of the six variables—frequency of binge eating episodes, purging, eating disorder symptom severity, weight, illness duration and mental health-related quality of life—significantly predicted adherence at 33%, but longer illness duration predicted higher treatment adherence at both 60% and 75% presence of the interventions. Also for 75% presence, higher body weight predicted lower treatment adherence. For the subgroup analysis, those having higher illness duration had significantly higher odds of treatment adherence for 60% and 75% of the sessions. Conclusions: Higher adherence due to late treatment completion was associated with longer binge eating illness length and a lower body weight. More research is needed to recognize factors that may interfere with engagement in treatments aiming to avoid early dropout.

Processing speed and clinical features of schizophrenia: comparison between men and women

Evidence about differences in processing speed (PS) performance between men and women with schizophrenia is inconclusive. Moreover, PS deconstruction into its subcomponents has not been compared among sexes. The aim of this study was to compare PS and its subcomponents (i.e., response processing – RP; accuracy – AC; and psychomotor speed - PmS) performance between men and women with schizophrenia and to explore its associations with clinical variables. Fiftysix patients (36 men, 20 women) were recruited. The PS domain tasks from the MATRICS Consensus Cognitive Battery were used. Women outperformed men in RP and AC but were slower in PmS. For men, correlations were found between functionality, RP and AC; age of onset was associated with AC; in women, illness duration and symptomatology correlated with AC. Sex-related differences regarding PS performance in schizophrenia resemble those observed in healthy individuals. Remediation strategies should consider sex differences in PS for more accurate interventions.

Illness characteristics of COVID-19 in children infected with the SARS-CoV-2 Delta variant

Background The Delta (B.1.617.2) SARSCoV2 variant became the predominant UK circulating strain in May 2021. Whether COVID19 from Delta infection differs to infection with other variants in children is unknown. Methods Through the prospective COVID Symptom Study, 109,626 UK school-aged children were proxy-reported between December 28, 2020 and July 8, 2021. We selected all symptomatic children who tested positive for SARS-CoV-2 and were proxy-reported at least weekly, within two timeframes: December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) the main UK circulating variant); and May 26 to July 8, 2021 (Delta the main UK circulating variant). We assessed illness profiles (symptom prevalence, duration, and burden), hospital presentation, and presence of long (>28 day) illness; and calculated odds ratios for symptoms presenting within the first 28 days of illness. Findings 694 (276 younger [5 11 years], 418 older [12 17 years]) symptomatic children tested positive for SARS-CoV-2 with Alpha infection and 706 (227 younger and 479 older) children with Delta infection. Median illness duration was short with either variant (overall cohort: 5 days (IQR 2 9.75) with Alpha, 5 days (IQR 2 9) with Delta). The seven most prevalent symptoms were common to both variants. Symptom burden over the first 28 days was slightly greater with Delta compared with Alpha infection (in younger children, 3 (IQR 2 5) with Alpha, 4 (IQR 2 7) with Delta; in older children 5 (IQR 3 8) with Alpha and 6 (IQR 3 9) with Delta infection in older children). The odds of several symptoms were higher with Delta than Alpha infection, including headache and fever. Few children presented to hospital, and long illness duration was uncommon, with either variant. Interpretation COVID-19 in UK school-aged children due to SARSCoV2 Delta strain B.1.617.2 resembles illness due to the Alpha variant B.1.1.7., with short duration and similar symptom burden.

Progressive brain structural abnormality in depression assessed with MR imaging by using causal network analysis

Background As a neuroprogressive illness, depression is accompanied by brain structural abnormality that extends to many brain regions. However, the progressive structural alteration pattern remains unknown. Methods To elaborate the progressive structural alteration of depression according to illness duration, we recruited 195 never-treated first-episode patients with depression and 130 healthy controls (HCs) undergoing T1-weighted MRI scans. Voxel-based morphometry method was adopted to measure gray matter volume (GMV) for each participant. Patients were first divided into three stages according to the length of illness duration, then we explored stage-specific GMV alterations and the causal effect relationship between them using causal structural covariance network (CaSCN) analysis. Results Overall, patients with depression presented stage-specific GMV alterations compared with HCs. Regions including the hippocampus, the thalamus and the ventral medial prefrontal cortex (vmPFC) presented GMV alteration at onset of illness. Then as the illness advanced, others regions began to present GMV alterations. These results suggested that GMV alteration originated from the hippocampus, the thalamus and vmPFC then expanded to other brain regions. The results of CaSCN analysis revealed that the hippocampus and the vmPFC corporately exerted causal effect on regions such as nucleus accumbens, the precuneus and the cerebellum. In addition, GMV alteration in the hippocampus was also potentially causally related to that in the dorsolateral frontal gyrus. Conclusions Consistent with the neuroprogressive hypothesis, our results reveal progressive morphological alteration originating from the vmPFC and the hippocampus and further elucidate possible details about disease progression of depression.

Assessing Stigma Towards Chronic Insomnia: The Role of Health Status and Life Quality

Background The objective of this study was to explore the stigma and related influencing factors in patients with chronic insomnia disorder (CID). Methods A total of 70 CID patients and 70 healthy controls (CON) were enrolled in the study. The Pittsburgh Sleep Quality Index (PSQI) and the 17-Item Hamilton Depression Rating Scale (HAMD-17) were used to assess sleep quality and depressive symptoms, respectively. The Chinese-Beijing version of the Montreal Cognitive Assessment scale (MoCA-C) was used to assess cognitive function. Stigma and life quality were measured using the Chronic Stigma Scale and the 36-Item Short-Form Health Survey (SF-36). Results The ratio of individuals with stigma was significantly different between CID and CON groups (C2 = 35.6, p < 0.001). Compared with the CON group, the CID group had higher scores for total stigma (U = 662.0, p < 0.001), internalized stigma (U = 593.0, p < 0.001), enacted stigma (U = 1568.0, p < 0.001), PSQI (U = 2485.0, p < 0.001) and HAMD-17 (U = 69.5, p < 0.001) as well as lower scores for MoCA-C (U = 3997.5, p < 0.001) and SF-36 for the items of physical role (U = 1560.5, p < 0.001), body pain (U = 1633.5, p < 0.001), general health (U = 1194.0, p < 0.001), vitality (U = 1169.5, p < 0.001), social function (U = 1703.0, p = 0.001), emotional role (U = 1451.5, p < 0.001), mental health (U = 1147.0, p < 0.001) and health transition (U = 1341.0, p < 0.001). Partial correlation analysis showed that different items of the Chronic Stigma Scale were positively correlated with illness duration, PSQI and HAMD-17 scores, while negatively correlated with one or more items of the SF-36. Multivariate regression analysis showed that illness duration and the mental health domain of the SF-36 were independent risk factors for one or more items of stigma in CID patients. Conclusion Patients with CID have an increased risk of stigma. Moreover, illness duration and mental health may be primary factors related to stigma.