Exercise4Psychosis: A randomised control trial assessing the effect of moderate-to-vigorous exercise on inflammatory biomarkers and negative symptom profiles in men with first-episode psychosis.

INTRODUCTION: First-Episode Psychosis (FEP) is a devastating mental health condition that commonly emerges during early adulthood, and is characterised by a disconnect in perceptions of reality. Current evidence suggests that inflammation and perturbed immune responses are involved in the pathology of FEP and may be associated specifically with negative symptoms. Exercise training is a potent anti-inflammatory stimulus that can reduce persistent inflammation, and can improve mood profiles in general populations. Therefore, exercise may represent a novel adjunct therapy for FEP. The aim of this study was to assess the effect of exercise on biomarkers of inflammation, negative symptoms of psychosis, and physiological health markers in FEP. METHODS: Seventeen young males (26.67 ± 6.64 years) were recruited from Birmingham Early Intervention in Psychosis Services and randomised to a 6-week exercise programme consisting of two-to-three sessions per week that targeted 60-70 % heart-rate max (HRMax), or a treatment as usual (TAU) condition. Immune T-helper (Th-) cell phenotypes and cytokines, symptom severity, functional wellbeing, and cognition were assessed before and after 6-weeks of regular exercise. RESULTS: Participants in the exercise group (n = 10) achieved 81.11 % attendance to the intervention, with an average exercise intensity of 67.54 % ± 7.75 % HRMax. This led to favourable changes in immune cell phenotypes, and a significant reduction in the Th1:Th2 ratio (-3.86 %) compared to the TAU group (p = 0.014). After the exercise intervention, there was also a significant reduction in plasma IL-6 concentration (-22.17 %) when compared to the TAU group (p = 0.006). IL-8, and IL-10 did not show statistically significant differences between the groups after exercise. Symptomatically, there was a significant reduction in negative symptoms after exercise (-13.54 %, Positive and Negative Syndrome Scale, (PANSS) Negative) when compared to the TAU group (p = 0.008). There were no significant change in positive or general symptoms, functional outcomes, or cognition (all p > 0.05). DISCUSSION: Regular moderate-to-vigorous physical activity is feasible and attainable in clinical populations. Exercise represents a physiological tool that is capable of causing significant inflammatory biomarker change and concomitant symptom improvements in FEP cohorts, and may be useful for treatment of symptom profiles that are not targeted by currently prescribed antipsychotic medication.

Pilot study indicates that a gluten-free diet lowers oxidative stress for gluten-sensitive persons with schizophrenia.

One-third of people with schizophrenia have elevated levels of anti-gliadin antibodies (AGA IgG). A 5-week randomized double-blind pilot study was performed in 2014-2017 in an inpatient setting to test the effect of a gluten-free diet (GFD) on participants with schizophrenia or schizoaffective disorder who also had elevated AGA IgG (≥ 20 U) but were negative for celiac disease. This earlier pilot study reported that the GFD-group showed improved gastrointestinal and psychiatric symptoms, and also improvements in TNF-α and the inflammatory cytokine IL-23. Here, we performed measurements of these banked plasma samples to detect levels of oxidative stress (OxSt) using a recently developed iridium (Ir)-reducing capacity assay. Triplicate measurements of these samples showed an Intraclass Correlation Coefficient of 0.84 which indicates good reproducibility. Further, a comparison of the OxSt measurements at the baseline and 5-week end-point for this small sample size shows that the GFD-group (N = 7) had lowered OxSt levels compared to the gluten-containing diet group (GCD; N = 9; p = 0.05). Finally, we showed that improvements in OxSt over these 5 weeks were correlated to improvements in gastrointestinal (r = +0.64, p = 0.0073) and psychiatric (r = +0.52, p = 0.039) symptoms. Also, we showed a possible association between the decrease in OxSt and the lowered levels of IL-23 (r = +0.44, p = 0.087), although without statistical significance. Thus, the Ir-reducing capacity assay provides a simple, objective measure of OxSt with the results providing further evidence that inflammation, redox dysregulation and OxSt may mediate interactions between the gut and brain.

The inflamed brain.

Autoimmune conditions underlie some cases of psychosis. Scientists are expanding their search for patients, who often benefit from treatment.

Association of rheumatological markers with neuronal antibodies, cerebrospinal fluid, electroencephalography, and magnetic resonance imaging findings in 224 patients with psychotic syndromes.

INTRODUCTION: Psychotic syndromes can have autoimmune-mediated causes in some patients. Thus, this retrospective work aims to investigate the role of rheumatological markers in the development of psychosis. PATIENTS AND METHODS: In total, 224 patients with psychotic syndromes receiving a "rheumatological laboratory screening" (including C-reactive protein [CRP], immunofixation, complement factors, rheumatoid factor [RF], antiphospholipid antibodies [APAs], antineutrophil cytoplasmic antibodies [ANCAs], and antinuclear antibodies [ANAs]) were analyzed. A further diagnostic work-up included investigations of neuronal antibodies and cerebrospinal fluid (CSF), as well as electroencephalography (EEG) and magnetic resonance imaging (MRI) of the brain. ANA testing was routinely performed in all patients using serum on human epithelioma-2 (Hep2) cells, and a subset of patients (N = 73) also underwent tissue-based assays from serum and CSF. The number of cases with autoimmune psychotic syndromes was descriptively collected, and ANA-positive and -negative patients were compared in detail. RESULTS: CRP was elevated in 9 % of patients, immunofixation identified alterations in 8 %, complement factor C3 was decreased in 14 %, RF was elevated in 1 %, APAs were elevated in 7 %, ANCAs were not clearly positive, and ANAs were positive in 19 % (extractable nuclear antigen [ENA] differentiation resulted in positive findings in 14 patients). From the 73 patient samples additionally investigated using tissue-based assays, there were 26 positive results for some kind of ANA (36 %), and overall using both methods, 54 patients (24 %) were considered positive for ANAs. A neuropsychiatric evaluation revealed a possible autoimmune psychotic syndrome in seven patients (3 %) and a probable autoimmune psychotic syndrome in two patients (1 %). ANA-positive patients were more frequently treated with antidepressants (p = 0.040) and had a higher number of somatic comorbidities (p < 0.001). In addition, (chronic) inflammatory MRI lesions (p = 0.008) and focal atrophies (p = 0.012) were found more frequently in ANA-positive than ANA-negative patients. DISCUSSION: Rheumatological screening led to suspicion of a possible or probable autoimmune psychotic syndrome in 4%. ANAs were associated with MRI pathologies. Therefore, rheumatological processes may contribute to the development of psychotic syndromes in rare cases.

Immune Cell Alterations in Psychotic Disorders: A Comprehensive Systematic Review and Meta-Analysis.

BACKGROUND: A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with healthy control participants has been lacking. METHODS: Multiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO) were searched for eligible studies up until October 18, 2022. All studies investigating circulating immune cells in the blood and CSF from patients with psychotic disorders (ICD-10: F20 and F22-29) compared with healthy control participants were included. RESULTS: A total of 86 studies were included in the meta-analysis. In the blood, the following categories of immune cells were elevated: leukocyte count (31 studies, standardized mean difference [SMD] = 0.35; 95% CI, 0.24 to 0.46), granulocyte count (4 studies, SMD = 0.57; 95% CI, 0.12 to 1.01), neutrophil granulocyte count (21 studies, SMD = 0.32; 95% CI, 0.11 to 0.54), monocyte count (23 studies, SMD = 0.40; 95% CI, 0.23 to 0.56), and B lymphocyte count (10 studies, SMD = 0.26; 95% CI, 0.04 to 0.48). Additionally, the neutrophil/lymphocyte ratio (23 studies, SMD = 0.40; 95% CI, 0.19 to 0.60), the monocyte/lymphocyte ratio (9 studies, SMD = 0.31; 95% CI, 0.04 to 0.57), and the platelet/lymphocyte ratio (10 studies, SMD = 0.23; 95% CI, 0.03 to 0.43) were elevated. The CSF cell count showed a similar tendency but was not significantly elevated (3 studies, SMD = 0.14; 95% CI, -0.04 to 0.32). CONCLUSIONS: The results indicate a broad activation of the immune system in psychotic disorders, with cells from both the myeloid and the lymphoid line being elevated. However, CSF analyses were lacking in most of the studies, and many studies were hampered by insufficient adjustment for confounding factors such as body mass index and smoking.

Papel de los estrógenos en el sistema nervioso central y su implicancia en los trastornos psiquiátricos: segunda parte / Role of estrogens in the central nervous system and their Implication for psychiatric disorders: second part

En esta segunda parte del trabajo se focaliza en cómo los estrógenos, con sus diferentes concentraciones a lo largo de las distintas etapas de la vida, por su presencia o ausencia, vulnerabilizan a padecer determinadas patologías neuropsiquiátricas, así como también protegen de algunas otras. En este sentido, se considera que la patología de la mujer debería incluir profundos conocimientos sobre la implicancia que las hormonas sexuales tienen en el desarrollo de determinadas enfermedades neuropsiquiátricas. Se relevan también otros estudios sobre la administración de terapia hormonal de reemplazo, ya que son los procesos neurodegenerativos, como la enfermedad de Alzheimer, los que mayor lugar han tenido entre las investigaciones de las últimas décadas. Allí los resultados se vislumbran promisorios, pues la administración de estrógenos inmediatamente después de la menopausia revela tener efecto en la prevención del desarrollo de estos procesos, lo que no ocurre una vez iniciados los procesos neurodegenerativos. Se incluyen, a su vez, otros trabajos en otras patologías psiquiátricas, en donde se ha evaluado la eficacia de la prescripción de estrógenos, como ser en determinadas formas de depresión mayor (como coadyuvante), con buenos resultados. A pesar de los avances en el campo de la neurociencia y la influencia que ésta ha tenido en el conocimiento de las enfermedades psiquiátricas, es necesario proseguir con las investigaciones en donde se incluyan nuevos fármacos, como ser hormonas sexuales y SERMs, que seguramente traerán aportes promisorios en determinadas patologías neuropsiquiátricas.

The second part of the article focuses on estrogens, with their varying concentrations, throughout the different stages of life, which, whether by their presence or absence, predispose to suffering from certain neuropsychiatric diseases, just as they protect the individual from some others. In this sense, it is considered that female pathology should involve a deep knowledge on the impact that sexual hormones have on the development of certain neuropsychiatric diseases. The article also includes other studies on the administration of hormone replacement therapy, since it is neurodegenerative processes, such as Alzheimer's Disease, which occupied a leading place in investigations during the past decades. In such investigations, outcomes seem to be promising, since the administration of estrogens right after menopause demonstrates to have an impact on preventing the development of these processes, which does not occur once neurodegenerative processes have started. Also included are other investigations conducted on other psychiatric pathologies, in which the efficacy of prescribing estrogens, such as for certain forms of major depression (as adjunctive therapy) are evaluated, with positive results. Despite the advances in neuroscience and its influence on the knowledge of psychiatric diseases, it is necessary to continue preforming investigations that include new pharmacological drugs, such as sexual hormones and SERMs, which will possibly bring about promissory contributions to certain neuropsychiatric diseases.

Aspectos inmunológicos de los pacientes psicóticos / Immunological aspects of psychotic patients

En un estudio de pacientes con tiroideopatías en el Hospital Escuela de Tegucigalpa, se encontraron cuatro pacientes con psicosis y valores altos de anticuerpos antimicrosomales y antitiroglobulinas. En un estudio control la presencia de anticuerpos antitiroideos (ATT) esta asociada con alta incidencia de antecedentes familiares de enfermedades inmunológicas, tiroideas y mentales, especialmente esquizofrenia