Systemic inflammation, oxidative damage and neurocognition predict telomere length in a transdiagnostic sample stratified by global DNA methylation levels.

Epigenetic mechanisms contribute to the maintenance of both type 2 diabetes mellitus (T2DM) and psychiatric disorders. Emerging evidence suggests that molecular pathways and neurocognitive performance regulate epigenetic dynamics in these disorders. The current combined and transdiagnostic study investigated whether inflammatory, oxidative stress, adhesion molecule, neurocognitive and functional performance are significant predictors of telomere dynamics in a sample stratified by global DNA methylation levels. Peripheral blood inflammation, oxidative stress and adhesion molecule biomarkers and neurocognitive function were assessed twice over a 1-year period in 80 individuals, including 16 with schizophrenia (SZ), 16 with bipolar disorder (BD), 16 with major depressive disorder (MDD), 15 with T2DM, and 17 healthy controls (HCs). Leukocyte telomere length (LTL) was measured by qRT-PCR using deoxyribonucleic acid (DNA) extracted from peripheral blood samples. A posteriori, individuals were classified based on their global methylation score (GMS) at baseline into two groups: the below-average methylation (BM) and above-average methylation (AM) groups. Hierarchical and k-means clustering methods, mixed one-way analysis of variance and linear regression analyses were performed. Overall, the BM group showed a significantly higher leukocyte telomere length (LTL) than the AM group at both time points (p = 0.02; η2p = 0.06). Moreover, the BM group had significantly lower levels of tumor necrosis factor alpha (TNF-α) (p = 0.03; η2p = 0.06) and C-reactive protein (CRP) (p = 0.03; η2p = 0.06) than the AM group at the 1-year follow-up. Across all participants, the regression models showed that oxidative stress (reactive oxygen species [ROS]) (p = 0.04) and global cognitive score [GCS] (p = 0.02) were significantly negatively associated with LTL, whereas inflammatory (TNF-α) (p = 0.04), adhesion molecule biomarkers (inter cellular adhesion molecule [ICAM]) (p = 0.009), and intelligence quotient [IQ] (p = 0.03) were significantly positively associated with LTL. Moreover, the model predictive power was increased when tested in both groups separately, explaining 15.8% and 28.1% of the LTL variance at the 1-year follow-up for the AM and BM groups, respectively. Heterogeneous DNA methylation in individuals with T2DM and severe mental disorders seems to support the hypothesis that epigenetic dysregulation occurs in a transdiagnostic manner. Our results may help to elucidate the interplay between epigenetics, molecular processes and neurocognitive function in these disorders. DNA methylation and LTL are potential therapeutic targets for transdiagnostic interventions to decrease the risk of comorbidities.

Efficiency assessment of follow-up methodology of patients with knee replacement to predict post-surgical functionality: a protocol for randomised control PROKnee trial.

INTRODUCTION: Even when total knee arthroplasty (TKA) is an extended treatment, most patients experience a suboptimal evolution after TKA. The objectives of this study are the following: (1) to determine the effectiveness of two different prosthesis stabilisation systems on the functionality in activities of daily life, and (2) to determine prognostic biomarkers of knee prosthesis function based on radiological information, quantification of cytokines, intra-articular markers and biomechanical functional evaluation to predict successful evolution. METHODS AND ANALYSIS: The PROKnee trial was designed as a randomised controlled patient-blinded trial with two parallel groups that are currently ongoing. The initial recruitment will be 99 patients scheduled for their first TKA, without previous prosthesis interventions in lower limbs, who will be randomly divided into two groups that differed in the stabilisation methodology incorporated in the knee prosthesis: the MEDIAL-pivot group and the CENTRAL-pivot group. The maximum walking speed will be reported as the primary outcome, and the secondary results will be patient-reported questionnaires related to physical status, cognitive and mental state, radiological test, laboratory analysis and biomechanical instrumented functional performance, such as the 6-minute walking test, timed up-and-go test, gait, sit-to-stand, step-over, and ability to step up and down stairs. All the results will be measured 1 week before TKA and at 1.5, 3, 6 and 12 months after surgery. ETHICS AND DISSEMINATION: All procedures were approved by the Ethical Committee for Research with Medicines of the University Clinical Hospital of Valencia on 8 October 2020 (order no. 2020/181). Participants are required to provide informed consent for the study and for the surgical procedure. All the data collected will be treated confidentially since they will be blinded and encrypted. The results from the trial will be published in international peer-reviewed scientific journals, regardless of whether these results are negative or inconclusive. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04850300).

Inflammation and weight change related to neurocognitive and functional impairment in diabetes and psychiatric disorders.

INTRODUCTION: Obesity is a global pandemic associated with various cardio-metabolic and psychiatric disorders. Neurocognitive and functional deficits have been associated with several somatic and psychiatric disorders. Adiposity-related inflammation has recently emerged as a key risk factor for neurocognitive and functional impairments. This prospective transdiagnostic study aimed to investigate the role of adiposity-related inflammatory markers in neurocognitive and functional outcomes associated with weight changes. METHODS: Peripheral blood inflammatory and oxidative stress biomarkers and neurocognitive and functional performance were assessed twice over 1 year in 165 individuals, including 30 with schizophrenia, 42 with bipolar disorder, 35 with major depressive disorder, 30 with type 2 diabetes mellitus (T2DM), and 28 healthy controls. Participants were stratified by body mass index into categories of type 2 obesity (T2OB; n=30), type 1 obesity (T1OB; n=42), overweight (OW; n=53), and average weight (NW; n=40). Mixed one-way analysis of covariance and linear and binary logistic regression analyses were performed. RESULTS: Compared with NW, T2OB and T1OB were significantly associated with impaired neurocognitive and functional performance (p<0.01; η2p=0.06-0.12) and higher levels of C-reactive protein and platelets (PLT) (p<0.01; η2p=0.08-0.16), with small-to-moderate effect sizes. IL-6, IL-10, and PLT were key factors for detecting significant weight changes in T1OB and T2OB over time. Regression models revealed that inflammatory and oxidative stress biomarkers and cellular adhesion molecules were significantly associated with neurocognitive and functional performance (p<0.05). DISCUSSION: Obesity is characterized by neurocognitive and functional impairments alongside low-grade systemic inflammation. Adiposity-related inflammatory biomarkers may contribute to neurocognitive and functional decline in individuals with T2DM and psychiatric disorders. Our data suggest that these biomarkers facilitate the identification of specific subgroups of individuals at higher risk of developing obesity.

Inflammation and lipid metabolism as potential biomarkers of memory impairment across type 2 diabetes mellitus and severe mental disorders.

INTRODUCTION: Neurocognitive impairment is a transdiagnostic feature across several psychiatric and cardiometabolic conditions. The relationship between inflammatory and lipid metabolism biomarkers and memory performance is not fully understood. This study aimed to identify peripheral biomarkers suitable to signal memory decline from a transdiagnostic and longitudinal perspective. METHODS: Peripheral blood biomarkers of inflammation, oxidative stress and lipid metabolism were assessed twice over a 1-year period in 165 individuals, including 30 with schizophrenia (SZ), 42 with bipolar disorder (BD), 35 with major depressive disorder (MDD), 30 with type 2 diabetes mellitus (T2DM), and 28 healthy controls (HCs). Participants were stratified by memory performance quartiles, taking as a reference their global memory score (GMS) at baseline, into categories of high memory (H; n = 40), medium to high memory (MH; n = 43), medium to low memory (ML; n = 38) and low memory (L; n = 44). Exploratory and confirmatory factorial analysis, mixed one-way analysis of covariance and discriminatory analyses were performed. RESULTS: L group was significantly associated with higher levels of tumor necrosis factor-alpha (TNF-α) and lower levels of apolipoprotein A1 (Apo-A1) compared to those from the MH and H groups (p < 0.05; η2p = 0.06-0.09), with small to moderate effect sizes. Moreover, the combination of interleukin-6 (IL-6), TNF-α, c-reactive protein (CRP), Apo-A1 and Apo-B compounded the transdiagnostic model that best discriminated between groups with different degrees of memory impairment (χ2 = 11.9-49.3, p < 0.05-0.0001). CONCLUSIONS: Inflammation and lipid metabolism seem to be associated with memory across T2DM and severe mental illnesses (SMI). A panel of biomarkers may be a useful approach to identify individuals at greater risk of neurocognitive impairment. These findings may have a potential translational utility for early intervention and advance precision medicine in these disorders.

Education and long-term outcomes in first episode psychosis: 10-year follow-up study of the PAFIP cohort.

BACKGROUND: Lower levels of education have been associated with the development of psychosis. Investigating educational achievement in the first episode of psychosis (FEP) patients may shed light on the origins of the alterations and on the variability of outcomes in psychotic disorders. METHODS: Education achievement was explored in a large sample (n = 659) of FEP patients enrolled in programa de atención a fases iniciales de psicosis (PAFIP), a research and assistance program conducted in Spain. Patients were stratified according to the Spanish educational system according to their attendance in primary (low), secondary (medium) or university studies (high). The three groups were compared on available premorbid, clinical and neuropsychological variables. A subgroup of patients (n = 209), comprising the 10-year follow-up PAFIP cohort, were again compared. RESULTS: Overall, 49% and 37% of FEP patients had low and medium levels of education, respectively. In total, 13% of the patients with a higher level of education were more frequently women (64%) and older at illness onset (36 years old), reported better premorbid adjustment, presented less severe positive symptoms and better functioning; and showed higher premorbid intelligence quotient and better performance on all the explored cognitive domains. Ten years later the FEP patients in the medium- and high-education groups had good global functioning and a neurocognitive performance within the normal limits. CONCLUSIONS: Higher education is associated with better initial conditions and more favourable outcomes after an FEP. Sharing this information with the world's educational systems is essential to targeting resources and designing innovative programs or strategies to compensate for student difficulties.

MICEmi: A method to identify cognitive endophenotypes of mental illnesses.

BACKGROUND: Characterizing neurocognitive endophenotypes of mental illnesses (MIs) could be useful for identifying at-risk individuals, increasing early diagnosis, improving disease subtyping, and proposing therapeutic strategies to reduce the negative effects of the symptoms, in addition to serving as a scientific basis to unravel the physiopathology of the disease. However, a standardized algorithm to determine cognitive endophenotypes has not yet been developed. The main objective of this study was to present a method for the identification of endophenotypes in MI research. METHODS: For this purpose, a 14-expert working group used a scoping review methodology and designed a method that includes a scoring template with five criteria and indicators, a strategy for their verification, and a decision tree. CONCLUSIONS: This work is ongoing since it is necessary to obtain external validation of the applicability of the method in future research.

Immune-Inflammatory Biomarkers Predict Cognition and Social Functioning in Patients With Type 2 Diabetes Mellitus, Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: A 1-Year Follow-Up Study.

Background: Systemic, low-grade immune-inflammatory activity, together with social and neurocognitive performance deficits are a transdiagnostic trait of people suffering from type 2 diabetes mellitus (T2DM) and severe mental illnesses (SMIs), such as schizophrenia (SZ), major depressive disorder (MDD), and bipolar disorder (BD). We aimed to determine if immune-inflammatory mediators were significantly altered in people with SMIs or T2DM compared with healthy controls (HC) and whether these biomarkers could help predict their cognition and social functioning 1 year after assessment. Methods: We performed a prospective, 1-year follow-up cohort study with 165 participants at baseline (TB), including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 HC; and 125 at 1-year follow-up (TY), and determined executive domain (ED), global social functioning score (GSFS), and peripheral blood immune-inflammatory and oxidative stress biomarkers. Results: Participants with SMIs and T2DM showed increased peripheral levels of inflammatory markers, such as interleukin-10 (p < 0.01; η2 p = 0.07) and tumor necrosis factor-α (p < 0.05; η2 p = 0.08); and oxidative stress biomarkers, such as reactive oxygen species (ROS) (p < 0.05; η2 p = 0.07) and mitochondrial ROS (p < 0.01; η2 p = 0.08). The different combinations of the exposed biomarkers anticipated 46-57.3% of the total ED and 23.8-35.7% of GSFS for the participants with SMIs. Limitations: Participants' treatment, as usual, was continued without no specific interventions; thus, it was difficult to anticipate substantial changes related to the psychopharmacological pattern. Conclusion: People with SMIs show significantly increased levels of peripheral immune-inflammatory biomarkers, which may contribute to the neurocognitive and social deficits observed in SMIs, T2DM, and other diseases with systemic immune-inflammatory activation of chronic development. These parameters could help identify the subset of patients who could benefit from immune-inflammatory modulator strategies to ameliorate their functional outcomes.

Specific metabolic syndrome components predict cognition and social functioning in people with type 2 diabetes mellitus and severe mental disorders.

OBJECTIVE: Obesity and metabolic diseases such as metabolic syndrome (MetS) are more prevalent in people with type 2 diabetes mellitus (T2DM), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). MetS components might be associated with neurocognitive and functional impairments in these individuals. The predictive and discriminatory validity of MetS and its components regarding those outcomes were assessed from prospective and transdiagnostic perspectives. METHODS: Metabolic syndrome components and neurocognitive and social functioning were assessed in 165 subjects, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HCs). A posteriori, individuals were classified into two groups. The MetS group consisted of those who met at least three of the following criteria: abdominal obesity (AO), elevated triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL), elevated blood pressure (BP), and elevated fasting glucose (FPG); the remaining participants comprised the No-MetS group. Mixed one-way analysis of covariance and linear and binary logistic regression analyses were performed. RESULTS: Cognitive impairment was significantly greater in the MetS group (n = 82) than in the No-MetS group (n = 83), with small effect sizes (p < 0.05; η²p = 0.02 - 0.03). In both groups, the most robust associations between MetS components and neurocognitive and social functioning were observed with TG and FPG (p < 0.05). There was also evidence for a significant relationship between cognition and BP in the MetS group (p < 0.05). The combination of TG, FPG, elevated systolic BP and HDL best classified individuals with greater cognitive impairment (p < 0.001), and TG was the most accurate (p < 0.0001). CONCLUSIONS: Specific MetS components are significantly associated with cognitive impairment across somatic and psychiatric disorders. Our findings provide further evidence on the summative effect of MetS components to predict cognition and social functioning and allow the identification of individuals with worse outcomes. Transdiagnostic, lifestyle-based therapeutic interventions targeted at that group hold the potential to improve health outcomes.

Relevance of Sociodemographics and Clinical Tests in Single- and Dual-Task Conditions as Gait Speed Predictors of Parkinson's Disease.

This cross-sectional study aimed to identify the patient characteristics and clinical test results that predict the functional gait speed of people with Parkinson's disease (PD). The impact of dual tasks on gait in Parkinson's disease (PD) reveals a lack of automaticity and increased cognitive demands. We explored which characteristics explained walking speed with and without dual-task interference and if they reflected the cognitive demands of the task. The preferred gait speed, stride length, and cadence were measured in individuals with PD through five conditions: single-task (ST) and visual, verbal, auditory, and motor dual-tasks (DTs). Sociodemographic and disease characteristics and the results from clinical tests such as the Dynamic Parkinson's Disease Gait Scale (DYPAGS), Frontal Assessment Battery (FAB), and Parkinson's Disease Questionnaire-39 (PDQ-39), among others, were also recorded. Two models of multiple regression analysis were used to explore the predictive value of outcomes concerning speed. In Model I, clinical results were included, and in Model II, spatiotemporal variables were added to the significant predictors of Model I. Forty PD patients (aged 66.72 (7.5) years) completed the assessments. All the models generated were significant (p < 0.01). Models I and II accounted for 47% and 93% of the variance, respectively, in the single-task condition. A patient's gender, prescribed medication (drugs), academic level, and Hoehn and Yahr (H&Y) stage, along with the FAB, DYPAGS, and PDQ-39 scores, were significant predictors of gait speed in Model I for the ST and DT conditions. In Model II, the H&Y stage and prescribed medication (drugs), along with the FAB and DYPAGS scores, remained significant predictors. This research found that sociodemographics, the patient's stage disease, and their clinical test results contribute to their walking speed, highlighting the multifactorial nature of gait in demanding environments.

Transdiagnostic neurocognitive deficits in patients with type 2 diabetes mellitus, major depressive disorder, bipolar disorder, and schizophrenia: A 1-year follow-up study.

BACKGROUND: Neurocognition impairments are critical factors in patients with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ), and also in those with somatic diseases such as type 2 diabetes mellitus (T2DM). Intriguingly, these severe mental illnesses are associated with an increased co-occurrence of diabetes (direct comorbidity). This study sought to investigate the neurocognition and social functioning across T2DM, MDD, BD, and SZ using a transdiagnostic and longitudinal approach. METHODS: A total of 165 participants, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HC), were assessed twice at a 1-year interval using a comprehensive, integrated test battery on neuropsychological and social functioning. RESULTS: Common neurocognitive impairments in somatic and psychiatric disorders were identified, including deficits in short-term memory and cognitive reserve (p < 0.01, η²p=0.08-0.31). Social functioning impairments were observed in almost all the disorders (p < 0.0001; η²p=0.29-0.49). Transdiagnostic deficits remained stable across the 1-year follow-up (p < 0.001; η²p=0.13-0.43) and could accurately differentiate individuals with somatic and psychiatric disorders (χ² = 48.0, p < 0.0001). LIMITATIONS: The initial sample size was small, and high experimental mortality was observed after follow-up for one year. CONCLUSIONS: This longitudinal study provides evidence of some possible overlap in neurocognition deficits across somatic and psychiatric diagnostic categories, such as T2DM, MDD, BD, and SZ, which have high comorbidity. This overlap may be a result of shared genetic and environmental etiological factors. The findings open promising avenues for research on transdiagnostic phenotypes of neurocognition in these disorders, in addition to their biological bases.

Is processing speed a valid neurocognitive endophenotype in bipolar disorder? Evidence from a longitudinal, family study.

BACKGROUND: Substantial evidence supports the existence of neurocognitive endophenotypes in bipolar disorder (BD), but very few longitudinal studies have included unaffected relatives. In a 5-year, follow-up, family study, we have recently suggested that deficits in manual motor speed and visual memory could be endophenotype candidates for BD. We aimed to explore whether this also applies to processing speed. METHODS: A sample of 348 individuals, including 163 BD patients, 65 unaffected first-degree relatives (BD-Rel) and 120 genetically unrelated healthy controls (HC), was assessed with the Digit Symbol Substitution Test (DSST) on two occasions over a 2-year period (T1, T2). DSST values were controlled for age, years of education, occupational status, and subsyndromic mood symptoms. Differences between groups were evaluated with ANCOVAs. RESULTS: At T1 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.38) and BD-Rel (p < 0.001; Cohen's d = 0.82). BD-Rel showed an intermediate performance with significant differences with HC (p < 0.01; Cohen's d = 0.50). Similarly, at T2 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.44) and BD-Rel (p < 0.01; Cohen's d = 0.51). BD-Rel performance was intermediate and significantly lower than that of HC (p < 0.01; Cohen's d = 0.97). A Repeated Measures ANOVA revealed no significant between-group differences in performance over time (p > 0.05). CONCLUSIONS: The results of this longitudinal, family study suggest that impaired processing speed may represent a suitable cognitive endophenotype for BD. Further research on the field is required to confirm these preliminary findings.

Grip Strength, Neurocognition, and Social Functioning in People WithType-2 Diabetes Mellitus, Major Depressive Disorder, Bipolar Disorder, and Schizophrenia.

BACKGROUND: Frailty is a common syndrome among older adults and patients with several comorbidities. Grip strength (GS) is a representative parameter of frailty because it is a valid indicator of current and long-term physical conditions in the general population and patients with severe mental illnesses (SMIs). Physical and cognitive capacities of people with SMIs are usually impaired; however, their relationship with frailty or social functioning have not been studied to date. The current study aimed to determine if GS is a valid predictor of changes in cognitive performance and social functioning in patients with type-2 diabetes mellitus and SMIs. METHODS: Assessments of social functioning, cognitive performance, and GS (measured with an electronic dynamometer) were conducted in 30 outpatients with type 2 diabetes mellitus, 35 with major depressive disorder, 42 with bipolar disorder, 30 with schizophrenia, and 28 healthy controls, twice during 1-year, follow-up period. Descriptive analyses were conducted using a one-way analysis of variance for continuous variables and the chi-squared test for categorical variables. Differences between groups for the motor, cognitive, and social variables at T1 and T2 were assessed using a one-way analysis of covariance, with sex and age as co-variates (p < 0.01). To test the predictive capacity of GS at baseline to explain the variance in cognitive performance and social functioning at T2, a linear regression analysis was performed (p < 0.05). RESULTS: Predictive relationships were found among GS when implicated with clinical, cognitive, and social variables. These relationships explained changes in cognitive performance after one year of follow-up; the variability percentage was 67.7%, in patients with type-2 diabetes mellitus and 89.1% in patients with schizophrenia. Baseline GS along with other variables, also predicted changes in social functioning in major depressive disorder, bipolar disorder, and schizophrenia, with variability percentages of 67.3, 36, and 59%, respectively. CONCLUSION: GS combined with other variables significantly predicted changes in cognitive performance and social functioning in people with SMIs or type-2 diabetes mellitus. Interventions aimed to improve the overall physical conditions of patients who have poor GS could be a therapeutic option that confers positive effects on cognitive performance and social functioning.

Motor and Cognitive Performance in Patients with Liver Cirrhosis with Minimal Hepatic Encephalopathy.

Minimal hepatic encephalopathy (MHE) is associated with mild cognitive impairment and frailty. This study aims to identify cognitive and motor differences in cirrhotic patients with and without MHE, and the correlations between motor signs and cognitive performance. Gait, balance, hand strength and motor speed performance were evaluated in 66 cirrhotic patients (38 without and 28 with MHE, according to the Psychometric Hepatic Encephalopathy Score (PHES). Cognitive performance was measured with the Mini-Mental State Examination, Verbal Fluency Test, Aprendizaje Verbal España-Complutense Test (TAVEC), Wechsler Adult Intelligence Scale III, Hamilton Depression and Anxiety Rating Scale and Functioning Assessment Short Test (FAST). MHE patients performed worse than patients without MHE in cognitive and autonomous functioning, learning and long-term memory, and verbal fluency. The same pattern was found in gait, center of pressure movement, variability of hand strength performance and hand motor speed. In MHE patients, high correlations were found between balance and FAST test, gait velocity and verbal skills, hand strength variability and anxiety and depression, and motor speed and FAST and TAVEC. MHE patients showed worse motor and cognitive performance than patients without MHE. MHE patients could have impaired movement control expressed as bradykinesia, and this reduced motor performance could correlate with cognitive performance.

Visual memory dysfunction as a neurocognitive endophenotype in bipolar disorder patients and their unaffected relatives. Evidence from a 5-year follow-up Valencia study.

BACKGROUND: Scarce research has focused on Visual Memory (VM) deficits as a possible neurocognitive endophenotype of bipolar disorder (BD). The main aim of this longitudinal, family study with healthy controls was to explore whether VM dysfunction represents a neurocognitive endophenotype of BD. METHODS: Assessment of VM by Rey-Osterrieth Complex Figure Test (ROCF) was carried out on a sample of 317 subjects, including 140 patients with BD, 60 unaffected first-degree relatives (BD-Rel), and 117 genetically-unrelated healthy controls (HC), on three occasions over a 5-year period (T1, T2, and T3). BD-Rel group scores were analyzed only at T1 and T2. RESULTS: Performance of BD patients was significantly worse than the HC group (p < 0.01). Performance of BD-Rel was also significantly different from HC scores at T1 (p < 0.01) and T2 (p = 0.05), and showed an intermediate profile between the BD and HC groups. Only among BD patients, there were significant differences according to sex, with females performing worse than males (p = 0.03). Regarding other variables, education represented significant differences only in average scores of BD-Rel group (p = 0.01). LIMITATIONS: Important attrition in BD-Rel group over time was detected, which precluded analysis at T3. CONCLUSIONS: BD patients show significant deficits in VM that remain stable over time, even after controlling sociodemographic and clinical variables. Unaffected relatives also show stable deficits in VM. Accordingly, the deficit in VM could be considered a potential endophenotype of BD, which in turn may be useful as a predictor of the evolution of the disease. Further studies are needed to confirm these findings.

Age of onset of Cannabis use and cognitive function in first-episode non-affective psychosis patients: Outcome at three-year follow-up.

BACKGROUND: In recent years, the effects of cannabis use on cognitive functions in patients with psychosis have been widely studied. Recently, special emphasis has been placed on the impact of age at the onset of consumption on cognition in these patients. METHOD: 349 patients with a first episode of non-affective psychosis were studied. Patients were classified as cannabis users and non-users. Users were divided, according to their age when they began using cannabis, into: early-onset (age < 16) and late-onset (age ≥ 16) users. Differences between groups at baseline were studied based on sociodemographic, clinical, and cognitive variables. The groups were longitudinally (3-year) compared on cognitive variables. RESULTS: Out of the 349 patients included in this study, 38.7% (N = 135) were cannabis users. Of them, 39.3% (N = 53) were early-onset and 60.7% (N = 82) were late-onset cannabis users. No baseline differences were found between the early-onset and late-onset groups on cognitive domains. Longitudinally, only patients who had withdrawn from cannabis use during follow-up showed a significant improvement in verbal memory. CONCLUSION: Our results did not show differences between the early-onset group and the other two groups in long-term cognitive performance, even if they kept consuming cannabis during the first three years of disease progression. Further studies are needed to elucidate the true relationship between early-onset cannabis use and cognitive function in patients with a first episode of psychosis.

Staging, Neurocognition and Social Functioning in Bipolar Disorder.

Introduction: Bipolar disorder (BD) is associated with significant neurocognitive and functional impairment, which may progress across stages. The 'latent stage' of BD remains understudied. This cross-sectional study assessed staging, neurocognition and social functioning among BD patients and their healthy siblings. Methods: Four groups were included: euthymic type I BD patients in the early (n = 25) and late (n = 23) stages, their healthy siblings (latent stage; n = 23) and healthy controls (n = 21). All 92 subjects underwent a comprehensive neuropsychological battery of processing speed, verbal learning/memory, visual memory, working memory, verbal fluency, executive cognition, and motor speed. Social functioning was assessed using the FAST scale. Results: Siblings' social functioning was identical to that of controls, and significantly better than both early- (p < 0.005) and late- (p < 0.001) stage patients. Although all patients were strictly euthymic, those at late stages had a significantly worse social functioning than early-stage patients (p < 0.001). Compared to controls, increasingly greater neurocognitive dysfunction was observed across stages of BD (F = 1.59; p = 0.005). Healthy siblings' performance lied between those of controls and patients, with deficits in tasks of processing speed, executive attention, verbal memory/learning, and visual memory. Both early- and late-stage patients had a more severe and widespread dysfunction than siblings, with no significant differences between them. Conclusions: Genetic vulnerability to BD-I seems to be associated with neurocognitive impairments, whereas social dysfunction would be the result of the clinical phenotype. Staging models of BD should take into account these divergent findings in the latent stage.

Cannabis use in male and female first episode of non-affective psychosis patients: Long-term clinical, neuropsychological and functional differences.

BACKGROUND: Numerous studies show the existence of a high prevalence of cannabis use among patients with psychosis. However, the differences between men and women who debut with a first episode of psychosis (FEP) regarding cannabis use have not been largely explored. The aim of this study was to identify the specific sex factors and differences in clinical evolution associated with cannabis use. METHOD: Sociodemographic characteristics at baseline were considered in our sample of FEP patients to find differences depending on sex and the use of cannabis. Clinical, functional and neurocognitive variables at baseline, 1-year, and 3-years follow-up were also explored. RESULTS: A total of 549 patients, of whom 43% (N = 236) were cannabis users, 79% (N = 186) male and 21% (N = 50) female, were included in the study. There was a clear relationship between being male and being a user of cannabis (OR = 5.6). Cannabis users were younger at illness onset. Longitudinal analysis showed that women significantly improved in all three dimensions of psychotic symptoms, both in the subgroup of cannabis users and in the non-users subgroup. Conversely, subgroups of men did not show improvement in the negative dimension. In cognitive function, only men presented a significant time by group interaction in processing speed, showing a greater improvement in the subgroup of cannabis users. CONCLUSION: Despite knowing that there is a relationship between cannabis use and psychosis, due to the high prevalence of cannabis use among male FEP patients, the results showed that there were very few differences in clinical and neurocognitive outcomes between men and women who used cannabis at the start of treatment compared to those who did not.