Trends in the incidence of hospital-treated suicide attempts during the COVID-19 pandemic in Oviedo, Spain.

BACKGROUND: The potential impact of the COVID-19 pandemic on suicidal behavior has generated predictions anticipating an increase in suicidal tendencies. The aim of this research is to study its influence on the incidence of hospital-treated suicide attempts throughout the year 2020 in Oviedo, Spain. METHODS: Data were collected on all patients admitted to the emergency department of Central University Hospital of Asturias in Oviedo for attempted suicide during 2020. Incidence rates were calculated for three lockdown periods. Suicide attempt trends in 2020 were compared with a non-COVID-19 year (2009) to avoid seasonal variations bias. Chi-square and Fisher's exact tests were performed. The influence of COVID-19 incidence in Oviedo was analyzed using Spearman's correlation coefficient. RESULTS: The cumulative incidence rate of attempted suicide per 100,000 person-years was 136.33 (pre-lockdown), 115.15 (lockdown), and 90.25 (post-lockdown) in adults (over 19 years old), and 43.63 (pre-lockdown), 32.72 (lockdown), and 72.72 (post-lockdown) in adolescents (10-19 years old). No association was found with COVID-19 incidence rates (Spearman's rho -0.222; p = 0.113). Comparing the years 2020 and 2009, statistically significant differences were observed in adolescents (Fisher's exact test; p = 0.024), but no differences were observed in adults (chi-square test = 3.0401; p = 0.218). CONCLUSIONS: Hospital-treated suicide rates attempted during the COVID-19 outbreak in Oviedo, Spain showed a similar trend compared with a non-COVID-19 year. In contrast, the number of adolescents hospital-treated for attempted suicide increased during lockdown, suggesting more vulnerability to COVID-19 restrictions after the initial lockdown period in this age group.

Phenotypic factors associated with amisulpride-induced weight gain in first-episode psychosis patients (from the OPTiMiSE cohort).

OBJECTIVE: Antipsychotic-induced weight gain (AiWG) is a debilitating adverse effect of most antipsychotics. First-episode psychosis patients are particularly vulnerable to the detrimental consequences of AiWG. Amisulpride has good efficacy and tolerability. We here aimed to identify the phenotypic factors associated with amisulpride-induced weight gain in first-episode psychosis patients. METHOD: Data were collected from the Optimization of Treatment and Management of Schizophrenia in Europe trial. Multivariable regression models with various phenotypic variables (N = 305) were performed with absolute AiWG and clinically relevant AiWG (≥7% AiWG) as outcomes. RESULTS: Four weeks of amisulpride treatment increased body weight from 69.7 to 72.4 kg (P < 0.001). In the regression model of absolute AiWG, unemployment (ß = 0.94, P = 0.016), younger age (ß = -0.07, P = 0.031) and absence of current comorbid major depression disorder (ß = -1.61, P = 0.034) were positively associated with absolute AiWG. In the regression model of clinically relevant AiWG, unemployment (OR = 2.83, P = 0.001), schizophreniform disorder (OR = 2.00, P = 0.025) and low baseline weight (OR = 0.97, P = 0.032) increased the likelihood of clinically relevant AiWG. CONCLUSIONS: Clinicians prescribing amisulpride should consider the relatively high susceptibility to AiWG in unemployed first-episode patients with psychosis, in particular young subjects with a diagnosis of schizophreniform disorder. We advise to carefully monitor these patients and, when needed, implement weight-reducing strategies.

Association of childhood trauma and genetic variability of CRH-BP and FKBP5 genes with suicidal behavior in bipolar patients.

BACKGROUND: Around 8% of bipolar disorder (BD) patients die by suicide every year, accounting for the highest rate among the psychiatric population. Suicidal behavior (SB) is mediated by an intertwining system of extrinsic and intrinsic factors. Childhood trauma (CT) and gene variants of the stress-management hypothalamic-pituitary-adrenal (HPA) axis have been reported as risk factors for SB. The aim of this study was to elucidate the association of CT and HPA axis genetic variants with SB. METHODS: 135 BD patients were recruited for clinical assessment of CT and SB by means of the Childhood Trauma Questionnaire (CTQ) and the Columbia Suicide Severity Rating Scale (C-SSRS), respectively. A total of 28 single nucleotide polymorphisms (SNPs) from 8 HPA axis genes (POMC, NR3C2, CRH-BP, NR3C1, FKBP5, CRHR2, CRHR1, and MC2R) were genotyped. RESULTS: The analyses showed an association of total CTQ score (p = 0.003), emotional abuse (p = 0.001), sexual abuse (p = 0.005) and emotional neglect (p = 0.005) with SB. CRH-BP rs7728378-C carriers (p = 0.004; OR = 3.05), FKBP5 rs3777747-AA (p = 0.039; OR = 0.34) and FKBP5 rs2766533-GG genotypes (p = 0.001; OR = 2.93) were associated with SB although only rs2766533 survived multiple test correction. No gene-environment interaction was found. LIMITATIONS: The relatively small sample size limits the statistical power to detect smaller environmental and genetic effects. Cross-sectional data collection in psychometric assessments can yield biased data. CONCLUSIONS: The present study characterizes novel SB risk factors and replicates previous findings in BD patients. CT and variability in CRH-BP and FKBP5 genes should be further studied for a better understanding of SB and ultimately help in suicide prevention.

Early versus late stage schizophrenia. What markers make the difference?

OBJECTIVES: To identify the psychopathological, cognitive, functional, physical health and inflammatory markers that differentiate between early-stage schizophrenia (ESSCH) and late-stage schizophrenia (LSSCH). METHODS: Cross-sectional, naturalistic study of 104 patients with SCH. The sample was divided in two groups: 35 ESSCH (≤7 years' duration of illness) and 69 LSSCH (>10 years' duration of illness). STATISTICAL ANALYSIS: chi-square test and Student's t-test and ANCOVA (or Quade test) controlling for age, sex, BMI and number of cigarettes/day. Finally, a binomial logistic regression was made. RESULTS: ESSCH show greater negative symptom severity (t = 2.465, p = 0.015), lower levels of IκBα (F = 7.644, p = 0.007), were more frequently classified as normal weight (40% vs 18.8%, p = 0.032) compared with LSSCH. The binomial logistic regression model included age (B = 0.127, p = 0.001) and IκBα (B = 0.025, p = 0.002) and accounted for 38.9% of the variance (model df =7, chi-square =41.841, p < 0.0001). CONCLUSIONS: Age and IκBα are the unique markers that differentiate between ESSCH patients whose duration of illness is less than 7 years and LSSCH patients. These results support the hypothesis of toxicity of episodes and highlight the importance of preventing new episodes.

Characterizing decision-making and reward processing in bipolar disorder: A cluster analysis.

The presence of abnormalities in emotional decision-making and reward processing among bipolar patients (BP) has been well rehearsed. These disturbances are not limited to acute phases and are common even during remission. In recent years, the existence of discrete cognitive profiles in this psychiatric population has been replicated. However, emotional decision making and reward processing domains have barely been studied. Therefore, our aim was to explore the existence of different profiles on the aforementioned cognitive dimensions in BP. The sample consisted of 126 euthymic BP. Main sociodemographic, clinical, functioning, and neurocognitive variables were gathered. A hierarchical-clustering technique was used to identify discrete neurocognitive profiles based on the performance in the Iowa Gambling Task. Afterward, the resulting clusters were compared using ANOVA or Chi-squared Test, as appropriate. Evidence for the existence of three different profiles was provided. Cluster 1 was mainly characterized by poor decision ability. Cluster 2 presented the lowest sensitivity to punishment. Finally, cluster 3 presented the best decision-making ability and the highest levels of punishment sensitivity. Comparison between the three clusters indicated that cluster 2 was the most functionally impaired group. The poorest outcomes in attention, executive function domains, and social cognition were also observed within the same group. In conclusion, similarly to that observed in "cold cognitive" domains, our results suggest the existence of three discrete cognitive profiles concerning emotional decision making and reward processing. Amongst all the indexes explored, low punishment sensitivity emerge as a potential correlate of poorer cognitive and functional outcomes in bipolar disorder.

Factors associated with poor functional outcome in bipolar disorder: sociodemographic, clinical, and neurocognitive variables.

OBJECTIVE: The current investigation aimed at studying the sociodemographic, clinical, and neuropsychological variables related to functional outcome in a sample of euthymic patients with bipolar disorder(BD) presenting moderate-severe levels of functional impairment. METHODS: Two-hundred and thirty-nine participants with BD disorders and with Functioning Assessment Short Test(FAST) scores equal or above 18 were administered a clinical and diagnostic interview, and the administration of mood measure scales and a comprehensive neuropsychological battery. Analyses involved preliminary Pearson bivariate correlations to identify sociodemographic and clinical variables associated with the FAST total score. Regarding neuropsychological variables, a principal component analysis (PCA) was performed to group the variables in orthogonal factors. Finally, a hierarchical multiple regression was run. RESULTS: The best fitting model for the variables associated with functioning was a linear combination of gender, age, estimated IQ, Hamilton Depression Rating Scale (HAM-D), number of previous manic episodes, Factor 1 and Factor 2 extracted from the PCA. The model, including all these previous variables, explained up to 29.4% of the observed variance. CONCLUSIONS: Male gender, older age, lower premorbid IQ, subdepressive symptoms, higher number of manic episodes, and lower performance in verbal memory, working memory, verbal fluency, and processing speed were associated with lower functioning in patients with BD.

Gender differences in C-reactive protein and homocysteine modulation of cognitive performance and real-world functioning in bipolar disorder.

BACKGROUND: Cognitive and psychosocial impairment has been associated with increased levels of C-reactive protein (CRP) and homocysteine in bipolar disorder, but gender differences have seldom been studied. METHODS: Two hundred and twenty-four bipolar outpatients were included. Cognitive performance was assessed through the Screen for Cognitive Impairment in Psychiatry (SCIP). Psychosocial functioning was evaluated using the Functioning Assessment Short Test (FAST) and the General Assessment of Functioning (GAF). Homocysteine and CRP levels were determined. Separate analyses were performed by gender. Partial correlations were calculated to test for associations between biomarkers and cognitive and psychosocial functioning. Hierarchical multiple regression was used to assess factors predicting cognitive and psychosocial functioning. Covariates were: age, education, duration of illness, hospital admissions, depressive symptoms, tobacco consumption, and BMI. RESULTS: A better performance was noted in women in delayed verbal learning (p = 0.010), along with better occupational functioning (p = 0.027) and greater leisure time impairment (p = 0.034). In men, CRP and homocysteine levels were associated with psychosocial dysfunction (interpersonal relationships and financial functioning, respectively). In women, CRP levels correlated with cognitive performance (SCIP total raw score, immediate and delayed verbal learning, and verbal fluency). CRP was a predictor of cognitive performance in women only. LIMITATIONS: The choice of the cognitive scale and covariates and the lack of a control group may be the main limitations. CONCLUSIONS: A gender difference was found in biomarker modulation of cognition and psychosocial functioning. A gender-based approach to cognition and real-world functioning should be considered in bipolar disorder to ensure an optimal outcome.

Inverse association between negative symptoms and body mass index in chronic schizophrenia.

BACKGROUND: We investigated whether negative symptoms, such as poor motivation or anhedonia, were associated with higher body mass index (BMI) in stable patients with schizophrenia chronically treated with antipsychotic medication. METHODS: 62 olanzapine- or clozapine-treated patients with illness duration of at least four years were selected from an international multicenter study on the characterization of negative symptoms. All participants completed the Brief Negative Symptom Scale (BNSS) and the Positive and Negative Syndrome Scale (PANSS). Bivariate correlations between BMI and negative symptoms (BNSS) were explored, as well as multiple regression analyses. We further explored the association of two principal component factors of the BNSS and BMI. Subsidiary analyses re-modeled the above using the negative symptoms subscale of the PANSS and the EMSLEY factor for negative symptoms for convergent validity. RESULTS: Lower negative symptoms (BNSS score) were associated with higher BMI (r=-0.31; p=0.015). A multiple regression analysis showed that negative symptoms (BNSS score) and age were significant predictors of BMI (p=0.037). This was mostly driven by the motivation/pleasure factor of the BNSS. Within this second factor, BMI was negatively associated with anhedonia (r=-0.254; p=0.046) and asociality (r=-0.253; p=0.048), but not avolition (r=-0.169; p=0.188). EMSLEY score was positively associated with BNSS (r=0.873, p<0.001), but negatively associated with BMI (r=-0.308; p=0.015). The association between PANSS and BMI did not reach significance (r=-224, p=0.080). CONCLUSIONS: We conclude that lower negative symptoms were associated with higher BMI (assessed using both the BNSS and EMSLEY) in chronic stable schizophrenia patients, mostly due to lower anhedonia and asociality levels.

Regulation of inflammatory pathways in schizophrenia: A comparative study with bipolar disorder and healthy controls.

BACKGROUND: Immune-inflammatory processes have been implicated in schizophrenia (SCH), but their specificity is not clear. MAIN AIM: To identify potential differential intra-/intercellular biochemical pathways controlling immune-inflammatory response and their oxidative-nitrosative impact on SCH patients, compared with bipolar disorder (BD) patients and healthy controls (HC). METHODS: Cross-sectional, naturalistic study of a cohort of SCH patients (n=123) and their controls [BD (n=102) and HC (n=80)]. STATISTICAL ANALYSIS: ANCOVA (or Quade test) controlling for age and gender when comparing the three groups, and controlling for age, gender, length of illness, cigarettes per day, and body mass index (BMI) when comparing SCH and BD. RESULTS: Pro-inflammatory biomarkers: Expression of COX-1 was statistically higher in SCH and BD than HC (P<0.0001; P<0.0001); NFκB and PGE2 were statistically higher in SCH compared with BD (P=0.001; P<0.0001) and HC (P=0.003; P<0.0001); NLRP3 was higher in BD than HC (P=0.005); and CPR showed a gradient among the three groups. Anti-inflammatory biomarkers: BD patients had lower PPARγ and higher 15d-PGJ2 levels than SCH (P=0.005; P=0.008) and HC (P=0.001; P=0.001). Differences between SCH and BD: previous markers of SCH (NFκB and PGE2) and BD (PPARγ and 15d-PGJ2) remained statistically significant and, interestingly, iNOS and COX-2 (pro-inflammatory biomarkers) levels were statistically higher in SCH than BD (P=0.019; P=0.040). CONCLUSIONS: This study suggests a specific immune-inflammatory biomarker pattern for established SCH (NFκB, PGE2, iNOS, and COX-2) that differentiates it from BD and HC. In future, their pharmacological modulation may constitute a promising therapeutic target.

Clinical features, impulsivity, temperament and functioning and their role in suicidality in patients with bipolar disorder.

OBJECTIVE: Our aim was to analyse sociodemographic and clinical differences between non-suicidal (NS) bipolar patients (BP), BP reporting only suicidal ideation (SI) and BP suicide attempters according to Columbia-Suicide Severity Rating Scale (C-SRSS) criteria. Secondarily, we also investigated whether the C-SRSS Intensity Scale was associated with emergence of suicidal behaviour (SB). METHOD: A total of 215 euthymic bipolar out-patients were recruited. Semistructured interviews including the C-SRSS were used to assess sociodemographic and clinical data. Patients were grouped according to C-SRSS criteria: patients who scored ≤1 on the Severity Scale were classified as NS. The remaining patients were grouped into two groups: 'patients with history of SI' and 'patients with history of SI and SB' according to whether they did or did not have a past actual suicide attempt respectively. RESULTS: Patients from the three groups differed in illness onset, diagnosis, number of episodes and admissions, family history, comorbidities, rapid cycling and medication, as well as level of education, functioning, impulsivity and temperamental profile. CONCLUSION: Our results suggest that increased impulsivity, higher rates of psychiatric admissions and a reported poor controllability of SI significantly increased the risk for suicidal acts among patients presenting SI.

Reasons for Attempted Suicide in Europe: Prevalence, Associated Factors, and Risk of Repetition.

To examine the prevalence of specific reasons for attempted suicide, factors associated with them, and whether reasons for attempted suicide influence risk of repetition. As part of the Monitoring Suicide in Europe (MONSUE) project, data on 4,683 suicide attempters from nine European countries were collected. Independence tests were used to study the influence of age, gender, and other factors on reported reasons. We examined risk of repetition using logistic regression analysis. Interpersonal conflict was common for all patients except those widowed, living alone, or retired. Mental health problems were prevalent among over 45 year-olds, patients unable to work, and patients with a history of at least three suicide attempts. Financial difficulties were cited more often by patients who were 45-64 years old, divorced or separated, living with children only, and unemployed. Close bereavement/serious illness and own physical illness were associated with those over 65 years of age. Two reasons for suicide attempt, interpersonal conflict and mental health problems, were associated with increased risk of repetition independent of other factors. Suicide attempters have a multitude of problems of varying prevalence depending on age, gender, and other factors. They present a range of clinical profiles that require a multidisciplinary response.

Functional remediation in bipolar disorder: 1-year follow-up of neurocognitive and functional outcome.

BACKGROUND: Few randomised clinical trials have examined the efficacy of an intervention aimed at improving psychosocial functioning in bipolar disorder. AIMS: To examine changes in psychosocial functioning in a group that has been enrolled in a functional remediation programme 1 year after baseline. METHOD: This was a multicentre, randomised, rater-masked clinical trial comparing three patient groups: functional remediation, psychoeducation and treatment as usual over 1-year follow-up. The primary outcome was change in psychosocial functioning measured by means of the Functioning Assessment Short Test (FAST). Group×time effects for overall psychosocial functioning were examined using repeated-measures ANOVA (trial registration NCT01370668). RESULTS: There was a significant group×time interaction for overall psychosocial functioning, favouring patients in the functional remediation group (F = 3.071, d.f. = 2, P = 0.049). CONCLUSIONS: Improvement in psychosocial functioning is maintained after 1-year follow-up in patients with bipolar disorder receiving functional remediation.

Effects of functional remediation on neurocognitively impaired bipolar patients: enhancement of verbal memory.

BACKGROUND: Functional remediation is a novel intervention with demonstrated efficacy at improving functional outcome in euthymic bipolar patients. However, in a previous trial no significant changes in neurocognitive measures were detected. The objective of the present analysis was to test the efficacy of this therapy in the enhancement of neuropsychological functions in a subgroup of neurocognitively impaired bipolar patients. METHOD: A total of 188 out of 239 DSM-IV euthymic bipolar patients performing below two standard deviations from the mean of normative data in any neurocognitive test were included in this subanalysis. Repeated-measures analyses of variance were conducted to assess the impact of the treatment arms [functional remediation, psychoeducation, or treatment as usual (TAU)] on participants' neurocognitive and functional outcomes in the subgroup of neurocognitively impaired patients. RESULTS: Patients receiving functional remediation (n = 56) showed an improvement on delayed free recall when compared with the TAU (n = 63) and psychoeducation (n = 69) groups as shown by the group × time interaction at 6-month follow-up [F 2,158 = 3.37, degrees of freedom (df) = 2, p = 0.037]. However, Tukey post-hoc analyses revealed that functional remediation was only superior when compared with TAU (p = 0.04), but not with psychoeducation (p = 0.10). Finally, the patients in the functional remediation group also benefited from the treatment in terms of functional outcome (F 2,158 = 4.26, df = 2, p = 0.016). CONCLUSIONS: Functional remediation is effective at improving verbal memory and psychosocial functioning in a sample of neurocognitively impaired bipolar patients at 6-month follow-up. Neurocognitive enhancement may be one of the active ingredients of this novel intervention, and, specifically, verbal memory appears to be the most sensitive function that improves with functional remediation.

Predictive factors of functional capacity and real-world functioning in patients with schizophrenia.

PURPOSE: This study was performed to identify the predictive factors of functional capacity assessed by the Spanish University of California Performance Skills Assessment (Sp-UPSA) and real-world functioning assessed by the Spanish Personal and Social Performance scale (PSP) in outpatients with schizophrenia. METHODS: Naturalistic, 6-month follow-up, multicentre, validation study. Here, we report data on 139 patients with schizophrenia at their baseline visit. ASSESSMENT: Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), Sp-UPSA and PSP. STATISTICS: Pearson's correlation coefficient (r) was used to determine the relationships between variables, and multivariable stepwise linear regression analyses to identify predictive variables of Sp-UPSA and PSP total scores. RESULTS: Functional capacity: scores on the PSP and PANSS-GP entered first and second at P<0.0001 and accounted for 21% of variance (R(2)=0.208, model df=2, F=15.724, P<0.0001). Real-world functioning: scores on the CGI-S (B=-5.406), PANSS-N (B=-0.657) and Sp-UPSA (B=0.230) entered first, second and third, and accounted for 51% of variance (model df=3, F=37.741, P<0.0001). CONCLUSION: In patients with schizophrenia, functional capacity and real-world functioning are two related but different constructs. Each one predicts the other along with other factors; general psychopathology for functional capacity, and severity of the illness and negative symptoms for real-world functioning. These findings have important clinical implications: (1) both types of functioning should be assessed in patients with schizophrenia and (2) strategies for improving them should be different.

Spanish adaptation and validation of the Brief Negative Symptoms Scale.

Negative symptoms prevalent in schizophrenia are associated with poor outcome. Developing new instruments to identify new treatments was highlighted at the NIMH-MATRICS Consensus Development Conference on Negative Symptoms. The new Brief Negative Symptoms scale (BNSS) demonstrated strong psychometric properties, but there is a need for validating it in non-English languages. A multi-center study was conducted to validate the Spanish version of the BNSS (BNSS-Sp) in 20 schizophrenia patients, following the original BNSS validation methodology. We found strong inter-rater, test-retest and internal consistency properties (for the total BNSS-Sp, intraclass correlation coefficient=0.97, Pearson's correlation coefficient r=0.95 (p<0.001), Cronbach's alpha=0.98).

Genetic variability at IMPA2, INPP1 and GSK3ß increases the risk of suicidal behavior in bipolar patients.

Bipolar patients (BP) are at high risk of suicide. Causal factors underlying suicidal behavior are still unclear. However, it has been shown that lithium has antisuicidal properties. Genes involved in its putative mechanism of action such as the phosphoinositol and the Wnt/ß-catenine pathways could be considered candidates for suicidal behavior (SB). Our aim was to investigate the association of the IMPA1 and 2, INPP1, GSK3α and ß genes with suicidal behavior in BP. 199 BP were recruited. Polymorphisms at the IMPA1 (rs915, rs1058401 and rs2268432) and IMPA2 (rs66938, rs1020294, rs1250171 and rs630110), INPP1 (rs3791809, rs4853694 and 909270), GSK3α (rs3745233) and GSK3ß (rs334558, rs1732170 and rs11921360) genes were genotyped. All patients were grouped and compared according to the presence or not of history of SB (defined as the presence of at least one previous suicidal attempt). Single SNP analyses showed that suicide attempters had higher frequencies of AA genotype of the rs669838-IMPA2 and GG genotype of the rs4853694-INPP1gene compared to non-attempters. Results also revealed that T-allele carriers of the rs1732170-GSK3ß gene and A-allele carriers of the rs11921360-GSK3ß gene had a higher risk for attempting suicide. Haplotype analysis showed that attempters had lower frequencies of A:A haplotype (rs4853694:rs909270) at the INPP1 gene. Higher frequencies of the C:A haplotype and lower frequencies of the A:C haplotype at the GSK-3ß gene (rs1732170:rs11921360) were also found to be associated to SB in BP. Therefore, our results suggest that genetic variability at IMPA2, INPP1 and GSK3ß genes is associated with the emergence of SB in BP.

Impact of substance use on the physical health of patients with bipolar disorder.

OBJECTIVE: To describe the impact of tobacco, alcohol and cannabis on metabolic profile and cardiovascular risk in bipolar patients. METHOD: Naturalistic, cross-sectional, multicenter Spanish study. Current use of tobacco, alcohol and cannabis was determined based on patient self-reports. Metabolic syndrome was defined using the National Health and Nutrition Examination Survey 1999-2000 and the American Heart Association/National Heart, Lung and Blood Institute criteria, and cardiovascular risk using the Framingham and the Systematic Coronary Risk Evaluation functions. RESULTS: Mean age was 46.6 years, 49% were male. Substance use: 51% tobacco, 13% alcohol and 12.5% cannabis. Patients who reported consuming any substance were significantly younger and a higher proportion was male. After controlling for confounding factors, tobacco was a risk factor for coronary heart disease (CHD) (unstandardized linear regression coefficient 3.47, 95% confidence interval 1.85-5.10). CONCLUSION: Substance use, mainly tobacco, was common in bipolar patients. Tobacco use negatively impacted CHD risk.