Severity Of Negative Symptoms Research Articles

Sex-specific associations between sex hormones and clinical symptoms in late-life schizophrenia

The prevalence of late-life schizophrenia is increasing with high burden. It is well-documented that schizophrenia affects men and women differently in terms of symptoms. Sex hormones, which play a role in the pathology and symptoms of schizophrenia, are greatly affected by aging. To the best of our knowledge, this is a study to examine the sex differences in psychiatric symptoms and their correlation with sex hormones in participants with late-life schizophrenia. Positive and Negative Syndrome Scale (PANSS) factors were evaluated. Testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and prolactin were measured. Male participants with late-life schizophrenia had more severe negative symptoms than female participants (z = −2.56, P = 0.010), while female participants had more severe anxiety/depression compared to male participants (z = 2.64, P = 0.008). Testosterone levels in male participants were positively associated with negative symptoms (β = 0.23, t = 2.27, P = 0.025), while there was no significant association between sex hormones and symptoms in female participants. In conclusion, higher testosterone levels were associated with more severe negative symptoms in male participants with late-life schizophrenia, suggesting that attention should be paid to the sex differences in late-life schizophrenia in clinical practice.

Smoking, Symptoms Improvement, and Total Antioxidant Capacity in Patients with Drug-naive First-episode Schizophrenia: A Prospective Cohort Study.

It has been hypothesized that smoking is associated with the severity of negative symptoms. Until now, no studies have investigated whether the impact of smoking on negative symptoms is dependent on antioxidants. This study was designed to evaluate the effect of smoking on therapeutic response and total antioxidants capacity (TAOC) in antipsychotic-naïve first-episode (ANFE) patients. The severity of the patient's symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). A total of 237 ANFE patients were recruited and treated with risperidone (oral tablets, 4-6 mg/day twice a day) for 12 weeks. PANSS was assessed at baseline and a 12-week follow-up. Plasma TAOC levels were also assayed at baseline and week 12. Relative to nonsmokers with ANFE SZ, smokers had higher PANSS negative subscores. There was no significant difference in TAOC changes after 12 weeks of treatment with risperidone between smokers and non-smokers. However, we found greater improvement in negative symptoms in smokers compared to non-smokers. Further analysis in smokers with SZ demonstrated that improvements in negative symptoms were not associated with changes in TAOC. Our study suggested that smoking affected the severity of baseline negative symptoms and further contributed to their reduction after risperidone treatment. However, improvement in negative symptoms was not dependent on the changes in TAOC.

Association between homotopic connectivity and clinical symptoms in first-episode schizophrenia

BackgroundAbnormal functional connectivity (FC) in the brain has been observed in schizophrenia patients. However, studies on FC between homotopic brain regions are limited, and the results of these studies are inconsistent. The aim of this study was to compare homotopic connectivity between first-episode schizophrenia (FES) patients and healthy subjects and assess its correlation with clinical symptoms. MethodsThirty-one FES patients and thirty-three healthy controls (HC) were included in the study. The voxel-mirrored homotopic connectivity (VMHC) method of resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyse the changes in homotopic connectivity between the two groups. The 5-factor PANSS model was used to quantitatively evaluate the severity of symptoms in FES patients. Partial correlation analysis was used to assess the correlation between homotopic connectivity changes and clinical symptoms. ResultsCompared to those in the HC group, VMHC values were decreased in the paracentral lobule (PL), thalamus, and superior temporal gyrus (STG) in the FES group (P < 0.05, FDR correction). No significant differences in white matter volume (WMV) within the subregion of the corpus callosum or in brain regions associated with reduced VMHC were observed between the two groups. Partial correlation analyses revealed that VMHC in the bilateral STG of FES patients was positively correlated with negative symptoms (rleft = 0.46, p < 0.05; rright = 0.47, p < 0.05), and VMHC in the right thalamus was negatively correlated with disorganized/concrete symptoms (rright = 0.45, p < 0.05). ConclusionOur study revealed that homotopic connectivity is altered in the resting-state brain of FES patients and correlates with the severity of negative symptoms; this change may be independent of structural changes in white matter. These findings may contribute to the development of the abnormal connectivity hypothesis in schizophrenia patients.

The Impact of Prolonged Duration of Untreated Illness on Clinical Correlates in Chronic Schizophrenia: Exploring the Relationship With Suicide Risk.

Studies on duration of untreated psychosis are common in patients with schizophrenia, but few studies have investigated the relationship between duration of untreated illness (DUI) and suicide, especially in patients with chronic schizophrenia. Therefore, we intended to investigate the relationship between DUI and suicide and clinical correlates in patients with chronic schizophrenia. A total of 1,555 Chinese patients with chronic schizophrenia were enrolled in this study. DUI was measured in years, reflecting the prolonged untreated periods observed in this population. Clinical correlates were assessed, including symptoms, cognitive functioning, and body mass index. Suicidal ideation and attempts were also examined. Statistical analyses, including multivariate models, were employed to investigate the associations between DUI and clinical correlates while controlling for potential confounders. The study revealed a significant proportion (23.3%) of patients with chronic schizophrenia in China received their first treatment after a 4-year delay, with the longest untreated duration reaching 39 years. Patients with longer DUI exhibited more severe negative symptoms, lower immediate memory scores, a higher likelihood of being overweight, and surprisingly, a reduced likelihood of suicidal ideation and attempts. Each additional year of untreated illness was associated with a 3% decrease in the risk of suicidal ideation and attempts. The findings underscore the prevalence of extended untreated periods in Chinese patients with chronic schizophrenia and highlight the impact of DUI on negative symptoms, cognitive function, and body weight. Intriguingly, a longer DUI was associated with a lower risk of suicidal ideation and attempts.

Longitudinal inference of multiscale markers in psychosis: from hippocampal centrality to functional outcome.

Multiscale neuroscience conceptualizes mental illness as arising from aberrant interactions across and within multiple biopsychosocial scales. We leverage this framework to propose a multiscale disease progression model of psychosis, in which hippocampal-cortical dysconnectivity precedes impairments in episodic memory and social cognition, which lead to more severe negative symptoms and lower functional outcome. As psychosis represents a heterogeneous collection of biological and behavioral alterations that evolve over time, we further predict this disease progression for a subtype of the patient sample, with other patients showing normal-range performance on all variables. We sampled data from two cross-sectional datasets of first- and multi-episode psychosis, resulting in a sample of 163 patients and 119 non-clinical controls. To address our proposed disease progression model and evaluate potential heterogeneity, we applied a machine-learning algorithm, SuStaIn, to the patient data. SuStaIn uniquely integrates clustering and disease progression modeling and identified three patient subtypes. Subtype 0 showed normal-range performance on all variables. In comparison, Subtype 1 showed lower episodic memory, social cognition, functional outcome, and higher negative symptoms, while Subtype 2 showed lower hippocampal-cortical connectivity and episodic memory. Subtype 1 deteriorated from episodic memory to social cognition, negative symptoms, functional outcome to bilateral hippocampal-cortical dysconnectivity, while Subtype 2 deteriorated from bilateral hippocampal-cortical dysconnectivity to episodic memory and social cognition, functional outcome to negative symptoms. This first application of SuStaIn in a multiscale psychiatric model provides distinct disease trajectories of hippocampal-cortical connectivity, which might underlie the heterogeneous behavioral manifestations of psychosis.

Effort-cost decision-making associated with negative symptoms in schizophrenia and bipolar disorder

Motivational deficits and reduced goal-directed behavior for external rewards have long been considered an important features of negative symptoms in patients with schizophrenia (SCZ). Negative symptoms have also a high prevalence in bipolar disorder (BP). We used a transdiagnostic approach in order to examine association between negative symptoms and effort allocation for monetary rewards. 41 patients with SCZ and 34 patients with BP were enrolled in the study along with 41 healthy controls (HC). Effort-Expenditure for Rewards Task (EEfRT) was used to measure subjects' effort allocation for monetary rewards. Generalized estimating equation models were used to analyze EEfRT choice behavior. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS). SCZ and BP groups expended lower effort to obtain a monetary rewards compared to HC. Severity of negative symptoms was negatively correlated with EEfRT performance in both diagnostic groups. Each diagnostic group showed lower effort allocation for monetary rewards compared to HC suggesting reduced motivation for monetary rewards. In addition, our results suggest that abnormal effort-based decision-making might be a transdiagnostic factor underlying negative symptoms.

DYNAMICS ASSESSMENT OF PSYCHOPATHOLOGICAL CHARACTERISTICS OF NEGATIVE SYMPTOMS IN SCHIZOPHRENIA

The aim of the study. To determine the dynamics of the psychopathological structure and severity of negative symptoms depending on the stage of the disease in patients with negative symptoms in schizophrenia in order to improve the diagnosis and treatment of patients with schizophrenia.&#x0D; Materials and methods: 252 patients with negative symptoms of schizophrenia took part in the study: 83 patients with the first episode of schizophrenia, 88 patients with schizophrenia in a state of exacerbation, and 81 patients with schizophrenia in a state of remission. A comprehensive approach, which consisted from clinical-psychopathological, psychometric (Scale for Evaluating Negative Disorders, G.V. Logvinovych, 1990) and statistical research methods, were used in the study.&#x0D; Results. Features of the dynamics of negative symptoms in patients with negative symptoms in schizophrenia at different stages of the disease were established: patients with the first episode of schizophrenia were characterized by mild quantitative and qualitative impairments in the emotional sphere, slight quantitative and qualitative changes in the associative sphere, and mild quantitative impairments in the volitional sphere in combination with moderate qualitative changes in the volitional sphere. Patients with schizophrenia in a state of exacerbation were characterized by moderate quantitative impairments of the emotional sphere and manifested distortion of the emotional sphere, manifested quantitative and qualitative impairments in the associative sphere and minor quantitative and qualitative impairments of the volitional sphere. Patients with schizophrenia in a state of remission were characterized by moderate and manifested quantitative and qualitative impairments in the emotional-volitional sphere and moderate quantitative and qualitative impairments in the associative sphere.&#x0D; Conclusions. The obtained data can be used to establish diagnostic criteria for patients with negative symptoms in schizophrenia, depending on the dynamics of the disease.

Subregional thalamic functional connectivity abnormalities and cognitive impairments in first-episode schizophrenia

BackgroundPrevious studies have documented thalamic functional connectivity (FC) abnormalities in schizophrenia, typically examining the thalamus as a whole. The specific link between subregional thalamic FC and cognitive deficits in first-episode schizophrenia (FES) remains unexplored. MethodsUsing data from resting-state functional magnetic resonance imaging, we compared whole-brain FC with thalamic subregions between patients and HCs, and analyzed FC changes in drug-naïve patients separately. We then examined correlations between FC abnormalities with both cognitive impairment and clinical symptoms. ResultsA total of 33 FES patients (20 drug-naïve) and 32 age- and sex-matched healthy controls (HCs) were included. Compared to HCs, FES patients exhibited increased FC between specific thalamic subregions and cortical regions, particularly bilateral middle temporal lobe and cuneus gyrus, left medial superior frontal gyrus, and right inferior/superior occipital gyrus. Decreased FC was observed between certain thalamic subregions and the left inferior frontal triangle. These findings were largely consistent in drug-naïve patients. Notably, deficits in social cognition and visual learning in FES patients correlated with increased FC between certain thalamic subregions and cortical regions involving the right superior occipital gyrus and cuneus gyrus. The severity of negative symptoms was associated with increased FC between a thalamic subregion and the left middle temporal gyrus. ConclusionOur findings suggest FC abnormalities between thalamic subregions and cortical areas in FES patients. Increased FC correlated with cognitive deficits and negative symptoms, highlighting the importance of thalamo-cortical connectivity in the pathophysiology of schizophrenia.

Adherence to a Mediterranean Diet is inversely associated with anxiety and stress but not depression: a cross-sectional analysis of community-dwelling older Australians

An increasing body of evidence has emerged suggesting that lifestyle behaviours, including diet quality, may be an important modifiable risk factor for mental health disorders. The Mediterranean diet (MedDiet), which is often heralded as an anti-inflammatory diet, has been widely investigated and promoted as one of the ‘healthiest’ dietary patterns for reducing chronic disease risk and promoting healthy ageing(1). Greater adherence to a MedDiet and/or anti-inflammatory diet is inversely associated with the risk of depression or depressive symptoms in younger and middle-aged adults(2). However, these findings have been inconsistent, particularly in older adults. We therefore explored the independent associations between adherence to a MedDiet and severity of symptoms related to depression, anxiety and stress in community-dwelling older adults from Australia. We conducted a cross-sectional study of older Australians aged ≥ 60 years. Older adults who were permanent residents of Australia, free from dementia or cognitive decline and could independently complete an anonymous online survey in English were invited to participate. A 75-item self-administered questionnaire was used to assess the relationship between adherence to a MedDiet and severity of symptoms related to depression, anxiety, and stress. MedDiet adherence was assessed using the Mediterranean Diet Adherence Screener (MEDAS)(3) and the Depression, Anxiety and Stress Scale (DASS-21)(4) was used to assess the severity of negative emotional symptoms. Multivariable linear regression analysis (and 95% CI) was used to investigate the independent association between adherence to a MedDiet and severity of symptoms related depression, anxiety and stress using one unadjusted and six adjusted predictor models. A total of n = 294 participants were included in the final analyses (70.4 ± 6.2 years; Females, n = 201; Males, n = 91; n = 2 unspecified). Adherence to a MedDiet was inversely associated with severity of anxiety symptoms (β = −0.118; CI: −0.761, −0.012; P = 0.043) independent of age, gender, BMI, physical activity, sleep, cognitive risk and ability to perform activities of daily living. Furthermore, MedDiet adherence was inversely associated with symptoms of stress (β = −0.151; CI: −0.680, −0.073; P = 0.015) independent of age, gender, BMI, physical activity and sleep. However, no relationship between MedDiet adherence and depressive symptoms was observed. We showed that adherence to a MedDiet is inversely associated with severity of symptoms related to anxiety and stress but not for depression. Exploration of these findings using longitudinal analyses and robust clinical trials are needed to better elucidate these findings in older adults.

Tobacco smoking and nicotine vaping in persons with first episode psychosis

Tobacco smoking is highly prevalent in persons with psychosis and is the leading cause of preventable mortality in this population. Less is known about tobacco smoking in persons with first episode psychosis (FEP) and there have been no estimates about the prevalence of nicotine vaping in FEP. This study reports rates of tobacco smoking and nicotine vaping in young people with FEP enrolled in Coordinated Specialty Care programs in Pennsylvania and Maryland. Using data collected from 2021 to 2023, we examined lifetime and recent smoking and vaping and compared smokers and vapers to nonusers on symptoms, functioning, and substance use. The sample included 445 participants aged 13–35 with recent psychosis onset. Assessments were collected by program staff. Overall, 28 % of participants engaged in either smoking or vaping within 30 days of the admission assessment. Smokers and vapers were disproportionately male, cannabis users, and had lower negative symptom severity than non-smokers. Vapers had higher role and social functioning. Both smoking and vaping were related to a longer time from psychosis onset to program enrollment. We compare these findings to previous studies and suggest steps for addressing smoking and vaping in this vulnerable population.

Approval of a comprehensive psychosocial rehabilitation program for patients with negative symptoms in schizophrenia

The aim of the work is to develop and evaluate the effectiveness of a comprehensive program of psychosocial rehabilitation of patients with negative symptoms in schizophrenia. Materials and methods. The study involved 168 patients with negative symptoms of schizophrenia: 94 patients who underwent a comprehensive psychosocial rehabilitation program (main group) and 74 patients who underwent a course of therapy according to the traditional scheme (control group). The criteria that evaluated the effectiveness of a comprehensive program of psychosocial rehabilitation in patients with negative symptoms in schizophrenia were: clinical dynamics of negative disorders, the degree of improvement/deterioration of compliance and social functioning, and the degree of restoration of basic life functions. Psychometric (Social Avoidance and Distress Scale (SADS), Personal and Social Functioning (PSP), Level of Compliance questionnaire, and the Severity of Negative Symptoms (SANS)) and statistical research methods were used to assess effectiveness. Results. The proposed scheme of a complex program of psychosocial rehabilitation is based on the principles of a complex, individually oriented and differentiated approach, and its targets are defined as clinical manifestations of negative symptoms in schizophrenia, impaired social adaptation, communication skills, decreased motivational sphere, compliance and impaired social functioning. Rehabilitation is implemented in four stages: diagnostic, therapeutic, rehabilitation and preventive. The effectiveness of the proposed scheme of psychosocial rehabilitation of patients with negative symptoms in schizophrenia was proven, which consisted in a more pronounced reduction of clinical manifestations of abulia, anhedonia, inattention, reduction of distress and social avoidance, improvement of social functioning in the main spheres of life, and improvement of social and behavioral compliance. Conclusions. The developed comprehensive program of psychosocial rehabilitation of patients with negative symptoms in schizophrenia has shown its effectiveness and can be used in psychocorrective measures aimed at treating patients with negative symptoms in schizophrenia.

Using Computational Phenotyping to Identify Divergent Strategies for Effort Allocation Across the Psychosis Spectrum.

Disturbances in effort-cost decision-making have been highlighted as a potential transdiagnostic process underpinning negative symptoms in individuals with schizophrenia. However, recent studies using computational phenotyping show that individuals employ a range of strategies to allocate effort, and use of different strategies is associated with unique clinical and cognitive characteristics. Building on prior work in schizophrenia, this study evaluated whether effort allocation strategies differed in individuals with distinct psychotic disorders. We applied computational modeling to effort-cost decision-making data obtained from individuals with psychotic disorders (n = 190) who performed the Effort Expenditure for Rewards Task. The sample included 91 individuals with schizophrenia/schizoaffective disorder, 90 individuals with psychotic bipolar disorder, and 52 controls. Different effort allocation strategies were observed both across and within different disorders. Relative to individuals with psychotic bipolar disorder, a greater proportion of individuals with schizophrenia/schizoaffective disorder did not use reward value or probability information to guide effort allocation. Furthermore, across disorders, different effort allocation strategies were associated with specific clinical and cognitive features. Those who did not use reward value or probability information to guide effort allocation had more severe positive and negative symptoms, and poorer cognitive and community functioning. In contrast, those who only used reward value information showed a trend toward more severe positive symptoms. These findings indicate that similar deficits in effort-cost decision-making may arise from different computational mechanisms across the psychosis spectrum.

Is it more effective for anhedonia and avolition? A systematic review and meta-analysis of non-invasive brain stimulation interventions for negative symptoms in schizophrenia.

Noninvasive brain stimulation (NIBS) techniques are a promising tool for treating the negative symptoms of schizophrenia. Growing evidence suggests that different dimensions of negative symptoms have partly distinct underlying pathophysiological mechanisms. Previous randomized controlled trials (RCTs) have shown inconsistent impacts of NIBS across dimensions. This systematic review and meta-analysis evaluated the effects of NIBS on general negative symptoms, and on specific domains, including blunted affect, alogia, asociality, anhedonia, and avolition. PubMed, Web of Science, Embase, Cochrane CENTRAL, PsycINFO, OpenGrey, and Clinicaltrials.gov from the first date available to October, 2023. Among 1049 studies, we identified eight high-quality RCTs. NIBS significantly affects general negative symptoms (SMD = -0.54, 95% CI [-0.88, -0.21]) and all five domains (SMD = -0.32 to -0.63). Among dimensions, better effects have been shown for improvement of avolition (SMD = -0.47, 95% CI [-0.81, -0.13]) and anhedonia (SMD = -0.63, 95% CI [-0.98, -0.28]). Subgroup analyses of studies that applied once daily stimulation or >10 sessions showed significantly reduced negative symptom severity. NIBS exerts distinct effects across multiple dimensions of negative symptom, with treatment effects related to stimulation frequency and total sessions. These results need to be confirmed in dedicated studies.

Neurofilament light-chain (NfL) and 18 kDa translocator protein in early psychosis and its putative high-risk

Evidence of elevated peripheral Neurofilament light-chain (NfL) as a biomarker of neuronal injury can be utilized to reveal nonspecific axonal damage, which could reflect altered neuroimmune function. To date, only a few studies have investigated NfL as a fluid biomarker in schizophrenia primarily, though none in its putative prodrome (Clinical High-Risk, CHR) or in untreated first-episode psychosis (FEP). Further, it is unknown whether peripheral NfL is associated with 18 kDa translocator protein (TSPO), a validated neuroimmune marker. In this secondary study, we investigated for the first time (1) serum NfL in early stages of psychosis including CHR and FEP as compared to healthy controls, and (2) examined its association with brain TSPO, using [18F]FEPPA positron emission tomography (PET). Further, in the exploratory analyses, we aimed to assess associations between serum NfL and symptom severity in patient group and cognitive impairment in the combined cohort. A large cohort of 84 participants including 27 FEP (24 antipsychotic-naive), 41 CHR (34 antipsychotic-naive) and 16 healthy controls underwent structural brain MRI and [18F]FEPPA PET scan and their blood samples were obtained and assessed for serum NfL concentrations. We found no significant differences in serum NfL levels across clinical groups, controlling for age. We also found no significant association between NfL levels and brain TSPO in the entire cohort. We observed a negative association between serum NfL and negative symptom severity in CHR. Our findings suggest that neither active neuroaxonal deterioration as measured with NfL nor associated neuroimmune activation (TSPO) is clearly identifiable in an early mostly untreated psychosis sample including its putative high-risk.

Independence through community access and navigation: A supported leisure intervention for individuals with negative symptoms.

Promoting leisure participation requires a collaborative approach that emphasizes personal interests, strengths, and motivations. The purpose of this article was to test the effectiveness of the Independence through Community Access and Navigation (ICAN) intervention on community participation, recreation participation, and positive emotions among individuals with schizophrenia spectrum disorders. Using motivational interviewing and an individualized placements and support framework, the ICAN intervention focuses on working with participants to identify and participate in personally meaningful leisure activities by connecting with personal motivations and mainstream community opportunities. This randomized controlled trial was conducted with 74 participants diagnosed with schizophrenia with assessments conducted at baseline and posttreatment. Intervention effects were examined with repeated-measures analysis of variance (ANOVA). Multiple regression analysis was also performed using a change score as an outcome variable and baseline negative symptoms score, condition, and interaction as predictors. There was no significant main effect of ICAN on positive emotions, recreation participation, or community participation; however, among those in the experimental group, those with impairments in motivation and pleasure experienced improvements in community participation. For individuals experiencing greater negative symptoms, a supported leisure intervention may be an effective strategy to explore personal motivations and increase leisure participation. Future research should test the intervention effectiveness specifically targeting a larger sample of individuals with more severe negative symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cognitive Inflexibility Predicts Negative Symptoms Severity in Patients with First-Episode Psychosis: A 1-Year Follow-Up Study.

Negative symptoms and cognitive deficits play a major role in psychosis and significantly influence the functional outcomes of patients, particularly those with a first episode of psychosis (FEP). However, limited research has explored the predictive capacity of cognitive deficits during FEP for subsequent negative symptomatology. Drawing from the Athens FEP research study, we conducted a retrospective longitudinal study in 80 individuals with FEP. All patients were drug naive at admission. Cognitive tests were administered at 1-month and 1-year post-admission, while negative symptomatology was assessed at the same time points using PANSS by trained raters. We considered confounding factors such as age, gender, duration of untreated psychosis (DUP), treatment received, premorbid social adjustment, and premorbid IQ. Univariate regression analysis identified cognitive domains that correlated with negative symptomatology. These, along with the confounders, were incorporated into a multiple regression, with the 1-year PANSS negative scale serving as the dependent variable. Employing the backward elimination technique, we found a statistically significant inverse relationship between the categories completed in the Wisconsin card sorting test (WCST) and the 1-year PANNS negative scale (p = 0.01), beyond the associations with DUP and the 1-month PANSS negative scale. Our results suggest that cognitive flexibility, a key component of executive functions, predicts negative symptom severity one year after FEP.

Adherence to a Mediterranean Diet Is Inversely Associated with Anxiety and Stress but Not Depression: A Cross-Sectional Analysis of Community-Dwelling Older Australians.

Diet quality may be an important modifiable risk factor for mental health disorders. However, these findings have been inconsistent, particularly in older adults. We explored the independent associations between adherence to a Mediterranean diet (MedDiet) and severity of symptoms related to depression, anxiety and stress in older adults from Australia. This was a cross-sectional analysis of older Australians ≥ 60 years. MedDiet adherence was assessed using the Mediterranean Diet Adherence Screener (MEDAS), and the Depression, Anxiety and Stress Scale (DASS-21) was used to assess the severity of negative emotional symptoms. A total of n = 294 participants were included in the final analyses (70.4 ± 6.2 years). Adherence to a MedDiet was inversely associated with the severity of anxiety symptoms (β = -0.118; CI: -0.761, -0.012; p = 0.043) independent of age, gender, BMI, physical activity, sleep, cognitive risk and ability to perform activities of daily living. Furthermore, MedDiet adherence was inversely associated with symptoms of stress (β = -0.151; CI: -0.680, -0.073; p = 0.015) independent of age, gender, BMI, physical activity and sleep. However, no relationship between MedDiet adherence and depressive symptoms was observed. We showed that adherence to a MedDiet is inversely associated with the severity of symptoms related to anxiety and stress but not depression. Exploring these findings with the use of longitudinal analyses and robust clinical trials are needed to better elucidate these findings in older adults.

Associations of gut microbiota alterations with clinical, metabolic, and immune-inflammatory characteristics of chronic schizophrenia

The present study had the following aims: 1) to compare gut microbiota composition in patients with schizophrenia and controls and 2) to investigate the association of differentially abundant bacterial taxa with markers of inflammation, intestinal permeability, lipid metabolism, and glucose homeostasis as well as clinical manifestation. A total of 115 patients with schizophrenia during remission of positive and disorganization symptoms, and 119 controls were enrolled. Altogether, 32 peripheral blood markers were assessed. A higher abundance of Eisenbergiella, Family XIII AD3011 group, Eggerthella, Hungatella, Lactobacillus, Olsenella, Coprobacillus, Methanobrevibacter, Ligilactobacillus, Eubacterium fissicatena group, and Clostridium innocuum group in patients with schizophrenia was found. The abundance of Paraprevotella and Bacteroides was decreased in patients with schizophrenia. Differentially abundant genera were associated with altered levels of immune-inflammatory markers, zonulin, lipid profile components, and insulin resistance. Moreover, several correlations of differentially abundant genera with cognitive impairment, higher severity of negative symptoms, and worse social functioning were observed. The association of Methanobrevibacter abundance with the level of negative symptoms, cognition, and social functioning appeared to be mediated by the levels of interleukin-6 and RANTES. In turn, the association of Hungatella with the performance of attention was mediated by the levels of zonulin. The findings indicate that compositional alterations of gut microbiota observed in patients with schizophrenia correspond with clinical manifestation, intestinal permeability, subclinical inflammation, lipid profile alterations, and impaired glucose homeostasis. Subclinical inflammation and impaired gut permeability might mediate the association of gut microbiota alterations with psychopathological symptoms and cognitive impairment.

Diminished social motivation in early psychosis is associated with polygenic liability for low vitamin D

Insufficiency of vitamin D levels often occur in individuals with schizophrenia and first-episode psychosis (FEP). However, it is unknown whether this represents a biological predisposition, or it is essentially driven by illness-related alterations in lifestyle habits. Lower vitamin D has also been associated with adverse neurodevelopmental outcomes and predominant negative psychotic symptoms. This study aimed to investigate the contribution of polygenic risk score for circulating 25-hydroxyvitamin D concentration (PRS-vitD) to symptom presentation among individuals with FEP enrolled in the Athens First-Episode Psychosis Research Study (AthensFEP n = 205) and the Psychosis Incident Cohort Outcome Study (PICOS n = 123). The severity of psychopathology was evaluated using the Positive and Negative Syndrome Scale at baseline and follow-up assessments (AthensFEP: 4-weeks follow-up, PICOS: 1-year follow-up). Premorbid intelligence and adjustment domains were also examined as proxy measures of neurodevelopmental deviations. An inverse association between PRS-vitD and severity of negative symptoms, in particular lack of social motivation, was detected in the AthensFEP at baseline (adjusted R2 = 0.04, p < 0.001) and follow-up (adjusted R2 = 0.03, p < 0.01). The above observation was independently validated in PICOS at follow-up (adjusted R2 = 0.06, p < 0.01). No evidence emerged for a relationship between PRS-vitD and premorbid measures of intelligence and adjustment, likely not supporting an impact of lower PRS-vitD on developmental trajectories related to psychotic illness. These findings suggest that polygenic vulnerability to reduced vitamin D impairs motivation and social interaction in individuals with FEP, thereby interventions that encourage outdoor activities and social engagement in this patient group might attenuate enduring negative symptoms.

The network characteristics in schizophrenia with prominent negative symptoms: a multimodal fusion study

Previous studies on putative neural mechanisms of negative symptoms in schizophrenia mainly used single modal imaging data, and seldom utilized schizophrenia patients with prominent negative symptoms (PNS).This study adopted the multimodal fusion method and recruited a homogeneous sample with PNS. We aimed to identify negative symptoms-related structural and functional neural correlates of schizophrenia. Structural magnetic resonance imaging (sMRI) and resting-state functional MRI (rs-fMRI) were performed in 31 schizophrenia patients with PNS and 33 demographically matched healthy controls.Compared to healthy controls, schizophrenia patients with PNS exhibited significantly altered functional activations in the default mode network (DMN) and had structural gray matter volume (GMV) alterations in the cerebello-thalamo-cortical network. Correlational analyses showed that negative symptoms severity was significantly correlated with the cerebello-thalamo-cortical structural network, but not with the DMN network in schizophrenia patients with PNS.Our findings highlight the important role of the cerebello-thalamo-cortical structural network underpinning the neuropathology of negative symptoms in schizophrenia. Future research should recruit a large sample and schizophrenia patients without PNS, and apply adjustments for multiple comparison, to verify our preliminary findings.