Comparing interventions for early psychosis: a systematic review and component network meta-analysis.

Background: 'Early Intervention in Psychosis' (EIP) services have been associated with improved outcomes for early psychosis. However, these services are heterogeneous and many provide different components of treatment. The impact of this variation on the sustained treatment effects is unknown. Methods: We performed a systematic review and component network meta-analysis (cNMA) of randomised controlled trials (RCTs) that compared specialised intervention services for early psychosis. We searched CENTRAL (published and unpublished), EMBASE, MEDLINE, CINAHL, PsycINFO and Web of Science from inception to February 2023. Primary outcomes were negative and positive psychotic symptoms at 3-month and 1-year follow-up and treatment dropouts. Secondary outcomes were depressive symptoms and social functioning at 1-year follow-up. We registered a protocol for our study in PROSPERO (CRD42017057420). Findings: We identified 37 RCTs including 4599 participants. Participants' mean age was 25.8 years (SD 6.0) and 64.0% were men. We found evidence that psychological interventions (this component grouped all psychological treatment intended to treat, or ameliorate the consequences of, psychotic symptoms) are beneficial for reducing negative symptoms (iSMD -0.24, 95% CI -0.44 to -0.05, p = 0.014) at 3-month follow-up and may be associated with clinically relevant benefits in improving social functioning scores at 1-year follow-up (iSMD -0.52, 95% CI -1.05 to 0.01, p = 0.052). The addition of case management has a beneficial effect on reducing negative symptoms (iSMD -1.17, 95% CI -2.24 to -0.11, p = 0.030) and positive symptoms (iSMD -1.05, 95% CI -2.02 to -0.08, p = 0.033) at 1-year follow-up. Pharmacotherapy was present in all trial arms, meaning it was not possible to examine the specific effects of this component. Interpretation: Our findings suggest psychological interventions and case management in addition to pharmacotherapy as the core components of services for early psychosis to achieve sustained clinical benefits. Our conclusions are limited by the small number of studies and sparsely connected networks. Funding: National Institute for Health and Care Research.

The role of Extracellular Genomic Materials (EGMs) in psychiatric disorders.

Extracellular Genomic Materials (EGMs) are the nucleic acids secreted or released from all types of cells by endogenous or exogenous stimuli through varying mechanisms into the extracellular region and inevitably to all biological fluids. EGMs could be found as free, protein-bound, and/ or with vesicles. EGMs can potentially have immunophenotypic and/or genotypic characteristics of a cell of origin, travel to distant organs, and interact with the new microenvironment. To achieve all, EGMs might bi-directionally transit through varying membranes, including the blood-brain barrier. Such ability provides the transfer of any information related to the pathophysiological changes in psychiatric disorders in the brain to the other distant organ systems or vice versa. In this article, many aspects of EGMs have been elegantly reviewed, including their potential in diagnosis as biomarkers, application in treatment modalities, and functional effects in the pathophysiology of psychiatric disorders. The psychiatric disorders were studied under subgroups of Schizophrenia spectrum disorders, bipolar disorder, depressive disorders, and an autism spectrum disorders. EGMs provide a robust and promising tool in clinics for prognosis and diagnosis. The successful application of EGMs into treatment modalities might further provide encouraging outcomes for researchers and clinicians in psychiatric disorders.

New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis.

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends. Living systematic reviews produce rigorous, up-to-date and informative evidence summaries that are particularly important where research is emerging rapidly, current evidence is uncertain and new findings might change policy or practice. Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) aims to tackle the challenges of mental health science research by cataloguing and evaluating the full spectrum of relevant scientific research including both human and preclinical studies. GALENOS will also allow the mental health community-including patients, carers, clinicians, researchers and funders-to better identify the research questions that most urgently need to be answered. By creating open-access datasets and outputs in a state-of-the-art online resource, GALENOS will help identify promising signals early in the research process. This will accelerate translation from discovery science into effective new interventions for anxiety, depression and psychosis, ready to be translated in clinical practice across the world.

Clinical and biological correlates of optical coherence tomography findings in schizophrenia.

There is a growing body of evidence indicating retinal layer thinning in schizophrenia. However, neuropathological processes underlying these retinal structural changes and its clinical correlates are yet to be known. Here, we aim to investigate the clinical and biological correlates of OCT findings in schizophrenia. 50 schizophrenia patients and 40 healthy controls were recruited. Retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and macular and choroidal thicknesses were recorded. A comprehensive battery of neuropsychological tests was applied. Fasting glucose, triglycerides and HDL-cholesterol levels, TNF-α, IL-1ß and IL-6 levels were measured. Right IPL was significantly thinner in patients than the controls after controlling for various confounders (F = 5.42, p = .02). Higher IL-6, IL-1ß, and TNF-α levels were associated with decreased left macular thickness (r = - 0.26, p = .027, r = - 0.30, p = 0.012, and r = - 0.24, p = .046, respectively) and higher IL-6 was associated with thinning of right IPL (r = - 0.27, p = 0.023) and left choroid (r = - 0.23, p = .044) in the overall sample. Thinning of right IPL and left macula were also associated with worse executive functioning (r = 0.37, p = 0.004 and r = 0.33, p = 0.009) and attention (r = 0.31, p = 0.018 and r = 0.30, p = 0.025). In patients with schizophrenia, IPL thinning was associated with increased BMI (r = - 0.44, p = 0.009) and decreased HDL levels (r = 0.43, p = 0.021). Decreased TNF-α level was related to IPL thinning, especially in the left eye (r = 0.40, p = 0.022). These findings support the hypothesis that OCT might provide the opportunity to establish an accessible and non-invasive probe of brain pathology in schizophrenia and related disorders. However, future studies investigating retinal structural changes as a biological marker for schizophrenia should also consider the metabolic state of the subjects.

The Effects of Transcranial Focused Ultrasound Stimulation of Nucleus Accumbens on Neuronal Gene Expression and Brain Tissue in High Alcohol-Preferring Rats.

We investigated the effect of low-intensity focused ultrasound (LIFU) on gene expression related to alcohol dependence and histological effects on brain tissue. We also aimed at determining the miRNA-mRNA relationship and their pathways in alcohol dependence-induced expression changes after focused ultrasound therapy. We designed a case-control study for 100 days of observation to investigate differences in gene expression in the short-term stimulation group (STS) and long-term stimulation group (LTS) compared with the control sham group (SG). The study was performed in our Experimental Research Laboratory. 24 male high alcohol-preferring rats 63 to 79 days old, weighing 270 to 300 g, were included in the experiment. LTS received 50-day LIFU and STS received 10-day LIFU and 40-day sham stimulation, while the SG received 50-day sham stimulation. In miRNA expression analysis, it was found that LIFU caused gene expression differences in NAc. Significant differences were found between the groups for gene expression. Compared to the SG, the expression of 454 genes in the NAc region was changed in the STS while the expression of 382 genes was changed in the LTS. In the LTS, the expression of 32 genes was changed in total compared to STS. Our data suggest that LIFU targeted on NAc may assist in the treatment of alcohol dependence, especially in the long term possibly through altering gene expression. Our immunohistochemical studies verified that LIFU does not cause any tissue damage. These findings may lead to new studies in investigating the efficacy of LIFU for the treatment of alcohol dependence and also for other psychiatric disorders.

Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.

BACKGROUND: Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder. METHODS: In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ. FINDINGS: We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]). INTERPRETATION: Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice. FUNDING: UK National Institute for Health Research Oxford Health Biomedical Research Centre.

Sleep deprivation as a treatment for major depressive episodes: A systematic review and meta-analysis.

Sleep deprivation, alone or in combination with pharmacological treatment and as part of a chronotherapy package, is of potential use for people with major depressive episodes, however the evidence base is still conflicting. The aim of this systematic review and meta-analysis is to assess the clinical effects of sleep deprivation in comparison to any other intervention for the acute and long-term treatment of mood disorders. We searched electronic databases and trial registries (last update: 16th October 2021) for published and unpublished randomised controlled trials recruiting participants with a major depressive episode in unipolar or bipolar affective disorder. The clinical outcomes of interest were the reduction in depressive symptoms at different timepoints and the number of participants experiencing at least one side effect. Overall, 29 trials (1246 participants) were included. We did not find any difference in change in symptoms or all-cause discontinuation between interventions including SD compared to a control of the same intervention except without SD. In the included studies there were no available data for adverse events. Using the most methodologically rigorous approach, we did not find evidence that the addition of sleep deprivation to treatment packages leads to enhanced depressive outcomes.

The relation of optical coherence tomography findings with oxidative stress parameters in patients with bipolar disorder and unaffected first-degree relatives.

BACKGROUND: We aimed to evaluate the optical coherence tomography(OCT) findings and oxidative stress parameters in patients with bipolar disorder(BD) and their unaffected first-degree relatives(FDRs) and to explore OCT findings and oxidative stress parameters as potential endophenotype candidates. METHODS: Fifty patients with BD, 40 FDRs of BD, and 50 healthy controls(HCs) were included. OCT was performed to measure peripapillary retinal nerve fiber layer(RNFL), ganglion cell layer(GCL), inner plexiform layer(IPL), central macular, and minimum foveal thicknesses(CMT and MFT), choroidal thickness(ChT). 4-hydroxy-2-nonenal(HNE), total thiol(TT), native thiol(NT), total oxidant status(TOS), total antioxidant status(TAS), disulfide(DIS) and oxidative stress index(OSI) were measured from serum samples. RESULTS: TOS was higher patients with BD and FDRs than HCs (p < .001 and p = .012, respectively). OSI, DIS, HNE levels were higher patients with BD and FDRs than HCs (p < .001). TAS, TT, NT levels were lower patients and FDRs than HCs (p < .001). MFT of patients was thinner than HCs (p = .001). CMT of patients was thinner than HCs (p = .006); the same trend was observed in FDRs but did not reach the statistical significance level (p = .07). The groups did not differ on RNFL and choroidal thickness or GCL and IPL volume. LIMITATIONS: Evaluation of only a few retinal layers. CONCLUSIONS: TOS, TAS, OSI, TT, NT, DIS, HNE can be useful endophenotype biomarkers in BD. Among the OCT findings, CMT was determined as the closest parameter to being an endophenotype biomarker. Our study corroborates that oxidative stress parameters are more effective than OCT findings in endophenotype studies.

Oxidative stress and schizophrenia: A comparative cross-sectional study of multiple oxidative markers in patients and their first-degree relatives.

OBJECTIVE: Schizophrenia (SCZ) is a chronic, disruptive mental disorder with unknown pathogenic mechanisms. Several studies evidenced that oxidative stress (OS) may be one of the causal factors to play a role in the pathophysiology of the disease. Our study aims to contribute to the SCZ research by investigating a possible relationship between the severity of illness (scored with "The Positive and Negative Syndrome Scale [PANSS]") and OS biomarkers in patients. We additionally assess the "first-degree-relatives (FDRs)" oxidative status with multiple parameters to test the idea of oxidative imbalance leads to disease progression as a genetical susceptibility factor. METHODS: This study included: 50 adult patients with SCZ, 50 unaffected FDRs, and 50 controls. OS biomarkers included myeloperoxidase (MPO), total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), native thiol (NT). Photometric methods were used to measure the parameters in the peripheral blood samples of participants. Disulphide (DS) and oxidative stress index (OSI) parameters were calculated. RESULTS: TOS, DS, OSI levels were significantly higher, and TAS, TT, NT levels were significantly lower in both SCZ and FDRs than controls. In the SCZ group, MPO activity was significantly higher compared with other groups. Results in this study did not provide a strong correlation between the PANSS and selected biomarkers. There was a slightly negative correlation between TT and PANSS in the SCZ group (P = .041, r = -.297). CONCLUSION: OS biomarkers increased significantly in the peripheral blood of SCZ patients compared with other groups indicates the presence of OS in the aetiology of the disease. Mid-levels of oxidative markers found in FDRs imply that unaffected first-degree relatives have an increased risk for turning up to the clinical presentation stage.

Eating disorders in patients with irritable bowel syndrome / Trastornos de la alimentación en pacientes con síndrome de colon irritable

INTRODUCTION: Eating disorders (ED) constitute an important group of conditions that commonly occur in adolescents. Gastrointestinal complaints are frequently reported in ED patients. Few studies assessed the association of irritable bowel syndrome (IBS) with ED. The aim of the current study is to determine the prevalence of ED in a group of IBS patients and compare it with a healthy control group and assess the relationship of IBS sub-types, it's duration and severity with ED. PATIENTS AND METHODS: 100 IBS patients diagnosed according to the Rome-IV criteria and a control group consisting of 100 healthy adults, between 18 and 65 years old, were enrolled in this study. Sub-type, duration and severity of IBS were determined. All participants were requested to fill questionnaires to screen for ED. RESULTS: 200 subjects participated in the study. 118(59%) were female and 92(41%) were male. The Eating Attitudes Test (EAT) score was significantly higher in the IBS group (Odds ratio: 5.3 CI 95%:4.3-9.3; p < 0.001). The number of subjects with EAT score >30 was significantly higher in the IBS group (p < 0.001). EAT scores were significantly higher in female IBS patients and in younger patients (p = 0.013 and p = 0.043; respectively). No significant association between the IBS sub-type and EAT score was found (p > 0.05). However, IBS severity and duration positively correlated with EAT scores. DISCUSSION: ED should be considered in the management of IBS patients. Since many psychological factors can exacerbate IBS symptoms a multidisciplinary approach consisting of medical and behavioral therapeutic modalities should be employed for a better management of these patients

INTRODUCCIÓN: Los trastornos de la alimentación (TA) constituyen un grupo importante de afecciones que suelen aparecer en adolescentes. Los pacientes con TA refieren con frecuencia molestias abdominales. La asociación del síndrome de colon irritable (SCI) con los TA se ha evaluado en un número reducido de estudios. El objetivo del estudio actual es determinar la prevalencia de los TA en un grupo de pacientes con SCI y compararla con un grupo de control sano para evaluar la relación de los subtipos de SCI, así como su duración e intensidad con los TA. PACIENTES Y MÉTODOS: En este estudio se incluyeron 100 pacientes con SCI diagnosticados según los criterios Rome-IV y un grupo de control compuesto por 100 adultos sanos de entre 18 y 65 años. Se determinaron el subtipo, la duración y la intensidad del SCI. Se pidió a todos los pacientes que cumplimentaran cuestionarios de detección de TA. RESULTADOS: En el estudio participaron 200 sujetos. Ciento dieciocho (59%) eran mujeres y 92 (41%) eran varones. La puntuación en las pruebas de actitudes alimentarias (Eating Attitudes Test [EAT]) fue significativamente superior en el grupo de SCI (cociente de probabilidades: 5,3; IC del 95%: 4,3-9,3; p < 0,001). El número de sujetos con puntuación de EAT>30 fue significativamente superior en el grupo de SCI (p < 0,001). Las puntuaciones de EAT fueron significativamente superiores en pacientes mujeres con SCI y en pacientes más jóvenes (p = 0,013 y p = 0,043, respectivamente). No se halló una asociación significativa entre el subtipo de SCI y la puntuación de EAT (p > 0,05). Sin embargo, la intensidad y la duración del SCI presentaron una correlación positiva con las puntuaciones de EAT. DISCUSIÓN: El TA debe tenerse en cuenta en el tratamiento de los pacientes con SCI. Puesto que muchos factores psicológicos pueden exacerbar los síntomas del SCI, deberá emplearse un enfoque multidisciplinar compuesto por modalidades terapéuticas médicas y conductuales para un mejor tratamiento de estos pacientes

Eating disorders in patients with irritable bowel syndrome.

INTRODUCTION: Eating disorders (ED) constitute an important group of conditions that commonly occur in adolescents. Gastrointestinal complaints are frequently reported in ED patients. Few studies assessed the association of irritable bowel syndrome (IBS) with ED. The aim of the current study is to determine the prevalence of ED in a group of IBS patients and compare it with a healthy control group and assess the relationship of IBS sub-types, it's duration and severity with ED. PATIENTS AND METHODS: 100 IBS patients diagnosed according to the Rome-IV criteria and a control group consisting of 100 healthy adults, between 18 and 65 years old, were enrolled in this study. Sub-type, duration and severity of IBS were determined. All participants were requested to fill questionnaires to screen for ED. RESULTS: 200 subjects participated in the study. 118(59%) were female and 92(41%) were male. The Eating Attitudes Test (EAT) score was significantly higher in the IBS group (Odds ratio: 5.3 CI 95%:4.3-9.3; p<0.001). The number of subjects with EAT score >30 was significantly higher in the IBS group (p<0.001). EAT scores were significantly higher in female IBS patients and in younger patients (p=0.013 and p=0.043; respectively). No significant association between the IBS sub-type and EAT score was found (p>0.05). However, IBS severity and duration positively correlated with EAT scores. DISCUSSION: ED should be considered in the management of IBS patients. Since many psychological factors can exacerbate IBS symptoms a multidisciplinary approach consisting of medical and behavioral therapeutic modalities should be employed for a better management of these patients.

Depression, anxiety, stress levels of physicians and associated factors in Covid-19 pandemics.

AIM: To investigate anxiety, stress, and depression levels of physicians during the Covid-19 outbreak and explored associated factors in both clinical and general site. METHODS: An online survey is conducted to asses psychological responses of healthcare workers and related factors during Covid-19 outbreak. It is consisted of three subsections covering the following areas: 1) sociodemographic data 2) information on individuals` working condition 3) Depression Anxiety and Stress Scale-21 (DAS-21). RESULTS: Of all 442 participants, 286 (64.7%) had symptoms of depression, 224 (51.6%) anxiety, and 182 (41.2%) stress. Being female, young, and single, having less work experience, working in frontline were associated with higher scores, whereas having a child was associated with lower scores in each subscale. Factors found to be associated with higher DAS-21 total scores in frontline workers were as follows: increased weekly working hours, increased number of Covid-19 patients cared for, lower level of support from peers and supervisors, lower logistic support, and lower feelings of competence during Covid-19 related tasks. CONCLUSIONS: Our findings highlight the factors which need to be taken into consideration to protect the mental wellbeing of doctors while fighting with a disaster that has major impacts on society worldwide.

Psychiatric symptoms, challenging behaviour and utilization of psychiatric services among adults with intellectual disabilities in Turkey.

BACKGROUND: The aim of this study was to investigate the prevalence of and the factors associated with psychiatric symptoms (PS) and challenging behaviour (CB) in adults with intellectual disabilities, and the utilization of psychiatric services in Turkey. METHOD: Psychiatric Assessment Schedule for Adults with Developmental Disorders Checklist-Revised was used for PS and a structured form for other variables in 771 participants. RESULTS: Of the participants, 50.1% had PS and 36.4% presented with CB. Multivariate analysis revealed that a higher level of needs, better verbal ability, residential living, incontinence and CB, and lifetime suicidal ideation/attempt were independently associated with PS. For CB, it emerged as male carer, PS, lifetime suicidal attempt/ideation, lower level of verbal ability and autism spectrum disorder. Barriers were experienced by 64.7% of participants within the previous year. CONCLUSIONS: Psychiatric symptoms and CB seem to be problems for a significant proportion of adults with intellectual disabilities in Turkey, and there are certain barriers to psychiatric services.

Reduced regulatory T cells with increased proinflammatory response in patients with schizophrenia.

AIM: To investigate whether circulating T cells including regulatory T cells (Treg) and derived cytokines contribute to the immune imbalance observed in schizophrenia. METHODS: Forty patients with schizophrenia and 40 age, sex, body mass index, education, and smoking status-matched healthy controls (HC) are included in the study. We stained cells with anti-CD14, anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-CD20, and anti-CD16/56. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with the human FoxP3 kit containing anti-CD4/anti-CD25 and intracellular anti-Foxp3. PBMCs were cultured for 72 h and stimulated with anti-CD3/anti-CD28. Cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17A) were measured from the culture supernatant and plasma using the Th1/Th2/Th17 cytokine bead array kit. RESULTS: In comparison with HC, Treg percentages in schizophrenia were higher (1.17 ± 0.63 vs 0.81 ± 0.53, P = 0.005) in unstimulated but lower in the stimulated condition (0.73 ± 0.69 vs 0.97 ± 0.55, P = 0.011). Activated T cell percentages were higher in schizophrenia than HC in unstimulated (2.22 ± 0.78 vs 1.64 ± 0.89, P = 0.001) and stimulated (2.25 ± 1.01 vs 1.72 ± 1.00, P = 0.010) conditions. The culture supernatant levels of IL-6 (7505.17 ± 5170.07 vs 1787.81 ± 1363.32, P < 0.001), IL-17A (191.73 ± 212.49 vs 46.43 ± 23.99, P < 0.001), TNF-α (1557 ± 1059.69 vs 426.57 ± 174.62, P = 0.023), and IFN-γ (3204.13 ± 1397.06 vs 447.79 ± 270.13, P < 0.001); and plasma levels of IL-6 (3.83 ± 3.41vs 1.89 ± 1.14, P = 0.003) and IL-17A (1.20 ± 0.84 vs 0.83 ± 0.53, P = 0.033) were higher in patients with schizophrenia than HC. CONCLUSION: Our explorative study shows reduced level of Foxp3 expressing Treg in a stimulated condition with induced levels of proinflammatory cytokines in patients with schizophrenia.

Natural language processing for structuring clinical text data on depression using UK-CRIS.

BACKGROUND: Utilisation of routinely collected electronic health records from secondary care offers unprecedented possibilities for medical science research but can also present difficulties. One key issue is that medical information is presented as free-form text and, therefore, requires time commitment from clinicians to manually extract salient information. Natural language processing (NLP) methods can be used to automatically extract clinically relevant information. OBJECTIVE: Our aim is to use natural language processing (NLP) to capture real-world data on individuals with depression from the Clinical Record Interactive Search (CRIS) clinical text to foster the use of electronic healthcare data in mental health research. METHODS: We used a combination of methods to extract salient information from electronic health records. First, clinical experts define the information of interest and subsequently build the training and testing corpora for statistical models. Second, we built and fine-tuned the statistical models using active learning procedures. FINDINGS: Results show a high degree of accuracy in the extraction of drug-related information. Contrastingly, a much lower degree of accuracy is demonstrated in relation to auxiliary variables. In combination with state-of-the-art active learning paradigms, the performance of the model increases considerably. CONCLUSIONS: This study illustrates the feasibility of using the natural language processing models and proposes a research pipeline to be used for accurately extracting information from electronic health records. CLINICAL IMPLICATIONS: Real-world, individual patient data are an invaluable source of information, which can be used to better personalise treatment.

An investigation of retinal layer thicknesses in unaffected first-degree relatives of schizophrenia patients.

INTRODUCTION: A large number of studies using different neuroimaging methods showed various structural changes both in patients and their unaffected first-degree relatives (FDRs) over the past years. Optical coherence tomography (OCT) is a relatively new, non-invasive imaging method used to obtain high-resolution cross-sectional images of the retina. A growing body of evidence reports thinning of retinal layers in patients with schizophrenia which is considered as a proxy for CNS alterations. We hypothesized that retinal layer changes would be observed in FDRs, in parallel with those seen in patients, as a potential endophenotype candidate. METHODS: Thirty-eight schizophrenia patients, 38 FDRs of schizophrenia and 38 age and gender-matched healthy subjects with no family history (HCs) were recruited to this study. OCT measurements were performed and peripapillary retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) and macular thicknesses were measured. RESULTS: The groups did not differ on RNFL, macular or GCL thickness. However, IPL thickness was significantly lower in both patients and FDRs than HCs (p = .025 and p = .041, respectively). The difference between groups remained significant after controlling for confounders such as age, gender, smoking status, comorbid medical diseases and BMI (p = .016 patients vs HCs and p = .014 FDRs vs HCs). CONCLUSION: Our findings suggest that IPL thinning may hold promise as a useful endophenotype for genetic and early detection studies. The evaluation of this area could provide an important avenue for elucidating some of the neurodevelopmental aberrations in the disorder.

Evidence for an association of serum melatonin concentrations with recognition and circadian preferences in patients with schizophrenia.

Melatonin, a neuro-differentiation factor, may play a role in the neurodevelopmental origins of schizophrenia. Cognitive impairment and decreased melatonin are reported in schizophrenia; however, the relationship between them remains unclear. We hypothesised that patients with schizophrenia would have lower concentrations of circulating melatonin than healthy controls and that melatonin levels would be associated with cognitive impairment. This study included 47 patients with schizophrenia and 40 healthy controls (HC). Serum melatonin concentrations were measured using the enzyme-linked immunosorbent assay. Positive and Negative Syndrome Scales (PANSS), The Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI), the Stroop and Oktem verbal memory processes (VMPT) tests were applied. Patients with schizophrenia had lower levels of melatonin compared to the HC group (p = 0.016), also after controlling for age, sex, and body mass index (BMI) (p = 0.024). In patients with schizophrenia, melatonin concentrations were associated with higher BMI (rho = 0.34, p = 0.01) and lower MEQ score (rho = -0.29, p = 0.035). The patient sample was split into low and high melatonin categories by using the median melatonin concentration in HC as the cut-off. Patients in the low melatonin group had poorer performance in VMPT-Recognition (p = 0.026) and Stroop-Colour Error (p = 0.032). Notwithstanding its limitations, the findings of this exploratory study suggest that decreased serum melatonin concentrations observed in schizophrenia might also be associated with cognitive impairment and circadian preferences. Future studies are required to investigate the role of melatonergic pathways in patients with schizophrenia.