Peripheral NF-κB dysregulation in people with schizophrenia drives inflammation: putative anti-inflammatory functions of NF-κB kinases

Elevations in plasma levels of pro-inflammatory cytokines and C-reactive protein (CRP) in patient blood have been associated with impairments in cognitive abilities and more severe psychiatric symptoms in people with schizophrenia. The transcription factor nuclear factor kappa B (NF-κB) regulates the gene expression of pro-inflammatory factors whose protein products trigger CRP release. NF-κB activation pathway mRNAs are increased in the brain in schizophrenia and are strongly related to neuroinflammation. Thus, it is likely that this central immune regulator is also dysregulated in the blood and associated with cytokine and CRP levels. We measured levels of six pro-inflammatory cytokine mRNAs and 18 mRNAs encoding NF-κB pathway members in peripheral blood leukocytes from 87 people with schizophrenia and 83 healthy control subjects. We then assessed the relationships between the alterations in NF-κB pathway genes, pro-inflammatory cytokine and CRP levels, psychiatric symptoms and cognition in people with schizophrenia. IL-1β and IFN-γ mRNAs were increased in patients compared to controls (both p < 0.001), while IL-6, IL-8, IL-18, and TNF-α mRNAs did not differ. Recursive two-step cluster analysis revealed that high levels of IL-1β mRNA and high levels of plasma CRP defined ‘high inflammation’ individuals in our cohort, and a higher proportion of people with schizophrenia were identified as displaying ‘high inflammation’ compared to controls using this method (p = 0.03). Overall, leukocyte expression of the NF-κB-activating receptors, TLR4 and TNFR2, and the NF-κB subunit, RelB, was increased in people with schizophrenia compared to healthy control subjects (all p < 0.01), while NF-κB-inducing kinase mRNAs IKKβ and NIK were downregulated in patients (all p < 0.05). We found that elevations in TLR4 and RelB appear more related to inflammatory status than to a diagnosis of schizophrenia, but changes in TNFR2 occur in both the high and low inflammation patients (but were exaggerated in high inflammation patients). Further, decreased leukocyte expression of IKKβ and NIK mRNAs was unique to high inflammation patients, which may represent schizophrenia-specific dysregulation of NF-κB that gives rise to peripheral inflammation in a subset of patients.

Gender Differences of Schizophrenia Patients With and Without Depressive Symptoms in Clinical Characteristics

Objectives: To investigate the differences in psychotic symptoms and cognitive function in schizophrenics with and without depression and to compare gender differences in the correlation between depressive symptoms and clinical characteristics in those patients.Methods: A total of 190 schizophrenia patients and 200 healthy controls were recruited in the study. We used the Positive and Negative Symptom Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to evaluate the psychiatric symptoms, depressive symptoms and cognitive function, respectively. Patients with CDSS score ≥7 were divided into depression group, and CDSS &lt; 7 was viewed as without depression.Results: Patients with schizophrenia had lower total scores of RBANS and five subscale (immediate memory, visual span, verbal function, attention, and delayed memory) scores compared to healthy controls. In the case group, patients who concomitant with depression had higher PANSS scores (Ps &lt; 0.001) and lower RBANS (Ps &lt; 0.05) scores than those without depression. After gender stratification, PANSS total scores and subscale scores were significantly different between schizophrenics with and without depressive symptoms in both male and female groups (Ps &lt; 0.001). For cognitive function, there were significant differences in RBANS total score and subscale scores except attention between female patients with and without schizophrenia but not in male schizophrenia patients. Furthermore, the correlation analysis showed that the total CDSS score was positively correlated with PANSS score (P &lt; 0.001) and RBANS score in male and female groups (male: P = 0.010, female: P = 0.001).Conclusion: Our findings provided evidence supporting the gender differences in psychiatric symptoms and cognitive function between schizophrenia patients with and without depressive symptoms.

Clinical Features and Therapeutic Effects of Anti-leucine-rich Glioma Inactivated 1 Encephalitis: A Systematic Review

Background: Clinical presentations and treatment programs about anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis still remain incompletely understood.Objective: This study analyzed the clinical features and therapeutic effects of anti-LGI1 encephalitis.Methods: PubMed, EMBASE, and the Cochrane Library were searched to identify published English and Chinese articles until April 2021. Data were extracted, analyzed, and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.Results: A total of 80 publications detailing 485 subjects matched our inclusion criteria. Short-term memory loss (75.22%), faciobrachial dystonic seizures (FBDS) (52.53%), other seizures excluding FBDS (68.48%), psychiatric symptoms (57.67%), and sleep disturbances (34.30%) were the most frequently described symptoms in anti-LGI1 encephalitis. Hyponatremia (54.90%) was the most common hematologic examination change. The risk of incidence rate of malignant tumors was higher than in healthy people. The positive rate of anti-LGI1 in serum (99.79%) was higher than CSF (77.38%). Steroids (93.02%), IVIG (87.50%), and combined use (96.67%) all had a high remission rate in the initial visit. A total of 35 of 215 cases relapsed, of which 6/35 (17.14%) did not use first-line treatment, and 21 (60.00%) did not maintain long-term treatment. Plasma exchange (PE) could be combined in severe patients, immunosuppressant could be used for refractory patients or for recurrence and using an anti-epileptic drug to control seizures may benefit cognition.Conclusions: Short-term memory loss, FBDS, psychiatric symptoms, and hyponatremia were key features in identifying anti-LGI1 encephalitis. Serum and CSF antibody tests should be considered in diagnosis criteria. Steroids with IVIG should be recommended, PE was combined for use in severe patients, immunosuppressant therapy might improve outcomes if recurrence or progression occurred, and control seizures might benefit cognition. The useful ways to reduce relapse rate were early identification, clear diagnosis, rapid treatment, and maintaining long-term treatment. The follow-up advice was suggested according to the research of paraneoplastic syndrome, and concern about tumors was vital as well.

Effects of autism on 30-year outcome of anorexia nervosa

Background Long-term consequences of comorbid autism spectrum disorder (ASD) in individuals with anorexia nervosa (AN) are inadequately investigated. Methods In the 1980s, 51 adolescent-onset AN cases (AN group) and 51 matched controls (COMP group) were recruited from the community. They have been examined on five occasions. The four last assessments included the Morgan-Russell Outcome Assessment Schedule (MROAS) to assess eating disorder outcomes (weight, dieting, menstruation), and related problems including psychiatric, psychosexual and socioeconomic state. In the present study, at age 44, when 30 years had elapsed, MROAS data were compared with previous results. At age 16, 21, 24 and 32 years, all individuals had been assessed regarding ASD. At the 30-year follow-up, the impact of the ASD on the MROAS data was analysed. Results In the AN group, all core anorectic symptoms (weight, dieting, menstruation) were on a par with the COMP group at the 30-year follow-up, but the positive outcomes were limited to those who had never had an ASD diagnosis. Psychiatric state was significantly worse in the AN group, particularly in the subgroup who had an ASD diagnosis assigned. The AN group—again particularly those with ASD—had a more negative attitude to sexual matters than the COMP group. The AN group had worse outcomes than the COMP group for ‘personal contacts’, ‘social contacts,’ and ‘employment record’ at the 30-year follow-up and the outcomes were worse the more often an ASD diagnosis had been assigned. Limitations Rare data collection points throughout 30 years (only 5 assessments). ASD was assessed in the first four studies but was not assessed again at the 30-year follow-up. Conclusions Mental health, psychosexual, and socioeconomic status were compromised up to 30 years after AN onset. Coexisting ASD contributed to the poor outcome. Core anorectic symptoms had “normalised” three decades after AN onset. Plain English summary Some individuals with anorexia nervosa (AN) also suffer from autism. In this study we have investigated outcome of AN 30 years after the onset of AN and whether the presence of autism affects the outcome. Since the 1980s we have followed 51 individuals with teenage-onset AN and 51 healthy controls. They have been examined on five occasions, and an instrument that measures symptoms of AN (weight, dieting, body image), psychiatric symptoms, ability to work, and relationships with partner, family, and friends has been used to assess outcome. Autism was assessed in the first four studies. Symptoms of AN had normalised at 30-year follow-up, but only among those without autism. Psychiatric symptoms, ability to work, and relationships were issues that persisted after 30 years in the AN group, and those who had both autism and a history of AN had even more pronounced problems in these areas. The AN group had a more negative attitude to sexual matters than the control group, the outcome was worse the more often an autism diagnosis had been assigned. Conclusions Mental health, psychosexual, and socioeconomic status are affected up to 30 years after AN onset, particularly among those with autism.

Psychometric Properties of the Emotional Processing Scale in Individuals with Psychiatric Symptoms and the Development of a Brief 15-Item Version

Objective The 25-item Emotional Processing Scale (EPS) is a measure of emotional processing. There is a scarcity of research about its factor structure, test-retest reliability, and validity in individuals with psychiatric symptoms. Method We administered the EPS-25 to a sample (N=512) of people with elevated psychiatric symptoms, using confirmatory factor analysis to evaluate three a priori models from previous research. We then evaluated discriminant and convergent validity against measures of alexithymia (Toronto Alexithymia Scale-20; TAS-20), depressive symptoms (Patient Health Questionaire-9; PHQ-9) and anxiety symptoms (Generalized Anxiety Disorder-7; GAD-7). Results None of the a priori models achieved acceptable fit, and subsequent exploratory factor analysis did not lead to a convincing factor solution for the 25 items. A 5-factor model did, however, achieve acceptable fit if we retained only 15 items (EPS-15) and this solution could be replicated in a holdout sample. Convergent and discriminant validity for EPS-15 was r=-.19-.46 vs. TAS-20, r=.07-.25 vs. PHQ-9, r=.29-.57 vs. GAD-7. Test-retest reliability was ICC=.73. Conclusions This study strengthens the case for the reliability and validity of the five factor Emotional Processing Scale but suggest that only 15 items should be retained. Future studies should further examine the reliability and validity of the EPS-15.

Computerized cognitive training in people with depression: a protocol for a systematic review and meta-analysis

Background People with depression often present with concurrent cognitive impairment. Computerized cognitive training (CCT) is a safe and efficacious strategy to maintain or enhance cognitive performance in a range of clinical populations. However, its efficacy in people with depression and how it varies across populations and design factors are currently unclear. Methods We searched MEDLINE, EMBASE, and PsycINFO from inception to 13 July 2021 for randomised controlled trials examining the efficacy of CCT vs any control condition on cognitive, mood, psychiatric symptoms, psychosocial, and daily functioning in adults with depression. Eligible samples include studies specifically targeting people with major depressive disorder as well as those with other diagnoses where at least 50% of the sample meets the clinical criteria for depression, with the exception of major psychiatric disorders or dementia. The primary outcome is change in the overall cognitive performance. Multivariate analyses will be used to examine the effect sizes on each outcome category as well as possible effect modifiers and correlations between categories. The risk of bias will be assessed using the Cochrane risk of bias tool version 2. Discussion To the best of our knowledge, this will be the first systematic review and meta-analysis of narrowly defined CCT across clinical populations with depression. We aim to investigate not only whether CCT is efficacious for cognition, but also how such effects vary across design factors, what other clinically relevant outcomes might respond to CCT, and the extent to which they differ across populations. Systematic review registration PROSPERO CRD42020204209