Association between telomere length with alcohol use disorder and internalizing/externalizing comorbidities in a Brazilian male sample.

BACKGROUND: Shortening telomere length (TL) is an important ageing marker associated with substance use disorder (SUD). However, the influence of psychiatric and clinical comorbidities and alcohol-related outcomes has not been much explored in the context of TL in individuals with alcohol use disorder (AUD) and may be a source of heterogeneity in AUD studies. Therefore, our aim was to investigate the influence of AUD, alcohol-related outcomes, and common psychiatric comorbidities on TL in men with AUD and healthy controls (HC). METHODS: Men with AUD (n=108, mean age=52.4, SD=8.6) were recruited in a detoxification unit, and HC (n=80, mean age=50.04, SD=9.1) from the blood bank, both located in Brazil. HC had no current or lifetime diagnosis of any substance use disorder. Psychiatric comorbidities were assessed using SCID-I. TL ratio was measured in triplicates using quantitative multiplex PCR. RESULTS: Telomere length did not differ between individuals with AUD and HC (p=0.073) or was associated with AUD-related outcomes, trauma, or clinical comorbidities. Individuals with externalizing disorders had longer TL when comparing with those with internalizing disorders (p=0.018) or without comorbidity (p=0.018). CONCLUSION: Our findings indicate that TL was influenced by the presence of psychiatric comorbidity rather than case or control status. These results were adjusted for potential confounders, such as age.

Treatment Approaches for Problematic Pornography Use: A Systematic Review.

Problematic pornography use (PPU) is an emerging condition associated with several negative psychological and sexual outcomes. This study aimed to systematically review treatment approaches for PPU. Potentially eligible studies were searched for in PubMed/MEDLINE, Embase, PsycINFO, and Web of Science up to April 1, 2023. The quality of the evidence was assessed with the use of the Joanna Briggs Institute's checklists, the Cochrane risk-of-bias tools, and the GRADE approach. A total of 8936 references were retrieved, and 28 studies were included in the systematic review (n = 500 participants). Included studies were case reports (k = 16), case series (k = 1), quasi-experimental investigations (k = 7), and randomized clinical trials (k = 4). The majority of included studies presented overall low quality and significant risk of bias, with all interventions receiving a low or very low rating according to the GRADE approach. Most studies investigated psychological interventions, with the predominance of second and third wave cognitive behavioral therapy interventions. Pharmacological treatments included opioid antagonists (naltrexone in most cases) and antidepressants, while one study investigated a protocol that included rTMS. Several investigations described the combination of psychological and pharmacological approaches. Most studies did not report on side effects, with online and self-help interventions presenting significant issues in terms of treatment adherence. Even though there are promising options that may have efficacy for the treatment of patients with PPU, the literature in the topic still presents significant limitations that compromise the reaching of more definitive conclusions.

Withdrawal-like Symptoms in Problematic Pornography Use: A Scoping Review.

OBJECTIVES: There is still debate whether problematic pornography use (PPU) can be understood as an addictive disorder, and little is known about withdrawal-like symptoms in these patients. Therefore, our aim was to summarize the existing scientific literature about this topic in the format of a scoping review. METHODS: Potentially eligible references were retrieved from 6 databases (MEDLINE/PubMed, Web of Science, Embase, PsycINFO, LILACS, and SciELO) up to February 7, 2023. Studies were included if they reported original data about withdrawal-like symptoms in individuals with PPU. Studies investigating child pornography use, or in which it was not possible to extract data of interest were excluded. Data extracted from included studies and their quality assessment were described narratively. RESULTS: A total of 937 references were retrieved, and 14 studies were included (n = 31,009 participants). According to our results, cravings were intense in most cases and frequent reasons for relapse. The proportion of participants experiencing other withdrawal-like symptoms (mental, sexual, and physical symptoms) reached up to 72.2% in the cross-sectional studies with this information available. Severity of withdrawal symptoms was associated with severity of PPU and frequency of pornography use. In some studies, measures of withdrawal symptoms were considered central symptoms of PPU and were significantly higher in individuals considering treatment. Masturbation was reported to alleviate withdrawal-like symptoms in some cases. CONCLUSIONS: There is preliminary evidence for the existence of withdrawal-like symptoms in PPU. Future studies should investigate onset, characteristics, duration, and proportion of withdrawal-like symptoms in PPU with robust methodology, also investigating potential confounding variables.

Characteristics of deaths by suicide in postmortem studies in Brazil: A systematic review and meta-analysis.

INTRODUCTION: Suicide is one of the leading causes of death, with a trend for its increase in Brazil in past decades. This study aimed to review the characteristics of suicides in Brazilian postmortem studies. METHODS: Studies investigating suicide deaths in Brazil, and based on autopsy or psychological autopsy were included. Proportions were pooled across studies with the use of random and fixed effects models. RESULTS: 6777 references were retrieved from six databases (searches up to January, 2023), and 45 studies included. In autopsy studies (k = 37, n = 16,231), substance use at toxicological analysis was found in 36.42% of cases (95% CI: 30.05-43.32), previous suicide attempts in 23.92% (95% CI: 6.73-57.78). In psychological autopsy studies (k = 8, n = 139), previous suicide attempts were reported in 28.09% (95% CI: 19.74-38.28), psychiatric conditions/symptoms in 90.67% (95% CI: 67.79-97.82), family history of suicidality in 21.33% (95% CI: 13.5-32.03). Most suicide deaths were reported in males and took place at the victim's home, hanging was the most frequent suicide method. Included studies presented significant limitations in quality assessment. CONCLUSION: Future studies should present more robust methodology, including bigger samples, the use of controls, and validated methodology.

Social cognition and psychosocial functioning in schizophrenia and bipolar disorder: Theory of mind as a key to understand schizophrenia dysfunction.

Functional impairment is a common symptom in schizophrenia (SZ) and bipolar disorder (BD). Pharmacological treatments have limited functional recovery in both disorders. Social cognition, a cognitive process, has been associated with functioning in mental disorders. Theory of mind (ToM) is considered a key factor in understanding the social cognitive deficits in SZ and BD. Our study aimed to investigate the relationship between ToM and functioning in SZ, BD, and healthy controls (HC) and compare ToM and functioning impairments between groups. A total of 208 participants (HC n = 69; BD n = 89; SZ n = 50) were evaluated with the Functioning Assessment Short Test (FAST), Reading the Mind in the Eyes Test (RMET), the Vocabulary subtest of the Wechsler Abbreviated Scale for Intelligence (WASI) and the Hopkins Verbal Learning Test - Revised (HVLT-R). Comparisons of RMET between low- and high-functioning individuals and multiple linear regression analyses were conducted for each group. Multiple regression analysis revealed that the association between ToM and psychosocial functioning was observed only in SZ (ß = -1.352, p = 0.008). Low-functioning SZ participants showed a lower ToM performance compared to participants with high-functioning SZ (t = 1.80, p = 0.039, Cohen's d = 0.938). No significant associations were found in the other groups. ToM is essential to understand the functional impairment in SZ, more than in BD. Furthermore, ToM may be a primary target for intervention strategies in improving functioning in SZ.

Country-level gender inequality is associated with structural differences in the brains of women and men.

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.

Functional impairment and post-stroke depression: a 6-month longitudinal study.

BACKGROUND: In recent decades, considerable advances have been made in the treatment of acute ischemic stroke (IS) and its prevention. However, even after treatment, approximately two-thirds of patients with IS have some degree of disability that requires rehabilitation, along with an increased possibility of developing psychiatric disorders, particularly depression. OBJECTIVE: To determine the predictors of post-stroke depression in a 6-month period in patients with IS. METHOD: Ninety-seven patients with IS without previous depression were included in the study. The study protocol was applied during hospitalization and at 30, 90, and 180 days after hospital discharge. A binary logistic regression was then used. Age, sex, marital status, occupation, education, thrombolysis, National Institute of Health Stroke Scale, modified Rankin scale (mRS) score, Barthel index, and Mini-Mental State Examination score were included as independent variables. RESULTS: Of the 97 patients, 24% of patients developed post-stroke depression. In the longitudinal follow-up, an mRS score of > 0 was the lone significant predictor of depression development (odds ratio = 5.38; 95% confidence interval: 1.25-23.12; p < 0.05). CONCLUSION: Our results showed that in patients without previous depression, functional impairment of any degree has a 5-fold greater chance of leading to depression development in the first 6 months post-stroke as compared to that in patients without functional impairment.

Retinal layers and symptoms and inflammation in schizophrenia.

Schizophrenia is a neurodevelopmental disorder that affects brain structure and function. The retina, as well as the brain, consists of neuronal and glial cells packed in layers. Cortical volume and brain thickness are associated with inflammatory biomarkers, however, no study has been performed associating inflammatory biomarkers and retina in schizophrenia. our study aims to compare the retinal macular thickness and volume and peripapillary thickness in patients with schizophrenia and controls, and associate it to symptoms of schizophrenia, to interleukin-6 (IL-6) and C Reactive Protein (CRP) levels. Optical coherence tomography was performed to assess retinal layer thickness and volume, and CRP and IL-6 levels were measured in patients with schizophrenia and controls. Positive, negative, and general symptoms of schizophrenia were measured with the Positive and Negative Syndrome Scale (PANSS). A linear regression controlling for confounding factors was performed. 70 subjects were included, 35 patients, and 35 controls matched for sex and age. Patients with schizophrenia presented a significantly lower macular volume (p < 0.05) and thickness (< 0.05) than controls. PANSS positive, general and total scores were associated with retinal nerve fiber layer (RNFL) thickness (p < 0.05). There was no association between inflammatory markers (CRP and IL-6) levels and the retinal layer. A reduction in macular volume and thickness was found in patients with schizophrenia. The severity of schizophrenia symptoms was associated with RNFL thickness. CRP and IL-6 are not associated with retinal thickness/volume in schizophrenia or controls.

Depression in mothers at childhood: Direct and indirect association with problematic gaming in late adolescence/young adulthood.

OBJECTIVES: Little is known about the relationship between depression in mothers and problematic gaming in their children. Therefore, we aimed to investigate the potential role of mothers' depression in childhood as a risk factor for problematic gaming in their offspring in late adolescence/young adulthood. METHODS: We assessed data from 1557 participants on three waves (T0 collected in 2010/2011, T1 in 2013/2014, and T2 in 2018/2019) of a large Brazilian school-based cohort. Mother's depression at T0 was tested as a predictor of problematic gaming at T2 in a logistic regression model. In mediation analyses, we individually assessed internalizing or externalizing disorders at T1 as mediators in this association, with participants' sex being tested as a moderator in both models. Inverse probability weights were used to account for sample attrition at T2. All models were adjusted for maternal and participant-related covariates. RESULTS: Mother's depression at T0 was significantly associated with problematic gaming at T2 (OR = 2.09, p < 0.001) even after adjusting for multiple confounding factors. The presence of any internalizing disorder at T1 was a partial mediator of this relationship, accounting for 8.18% (p = 0.032) of the total effect, while the presence of any externalizing disorder at T1 was not a significant mediator. Participants' sex was not a significant moderator in mediation models. CONCLUSIONS: These findings suggest mother's depression in childhood as a risk factor for problematic gaming in later developmental stages, which may be partially mediated by internalizing psychopathology.

Executive functions in migraine patients: a systematic review with meta-analysis.

Introduction: Migraine, a common neurological disease, is known to impact the quality of life of individuals with this condition.Methods: We performed a systematic review with meta-analysis to investigate the abnormalities associated with executive functions of migraineurs as compared with healthy controls. In addition, we investigated the differences between patients with and without aura.Results: A total of 25 studies were included in the systematic review and 19 in the meta-analysis. Meta-analysis was conducted using random effects models, with the unit of analysis as the standardised mean difference (calculated as Hedges'g). Patients with migraine had worse performance in the trail making test A (g = 0.40; 95% confidence interval [CI] 0.05-0.74; p = 0.0271) and B (g = 0.40; 95% CI 0.16-0.64; p = 0.0026), and digit span backward test (g = -0.20; 95% CI - 0.31, - 0.09; p = 0.0105). Subgroup analysis revealed no difference between migraine with and without aura.Conclusion: These results suggest that migraine patients may present worse performance for specific executive functional domains, including attention, working memory, and mental flexibility.

The role of semantic clustering in the relationship between verbal memory and psychosocial functioning in schizophrenia and bipolar disorder: Possible distinct cognitive pathway compared to healthy controls.

BACKGROUND: Verbal memory (VM) is impaired in schizophrenia (SZ) and bipolar disorder (BD), and predicts psychosocial functioning. However, there is a lack of research exploring the role of VM component processes, including semantic clustering, in these disorders. Semantic clustering might impact this association, as effective semantic memory strategies may reflect unimpaired executive control, leading to an adequate functioning. We aimed to investigate VM components in SZ and BD, and the role of semantic clustering in the relationship between VM and functioning. METHODS: We included 495 participants (156 SZ, 172 BD, and 167 healthy controls (HC)) that underwent an assessment using the Hopkins Verbal Learning Test - Revised for VM and the Functioning Assessment Short Test for psychosocial functioning. We compared groups through ANOVAs and investigated the effect of semantic clustering in the relationship between VM total immediate free recall and functioning through linear regression models. RESULTS: SZ had worse overall VM performance compared to BD, which performed worse than HCs. HCs used more semantic clustering than SZ and BD, but there were no differences between the two clinical groups. In HCs, semantic clustering impacted the relationship between VM performance and functioning, while no interaction was observed in SZ or BD. LIMITATIONS: Cross-sectional design; no medication effects or other cognitive functions were assessed. CONCLUSIONS: SZ and BD may use an alternative cognitive pathway in which the relationship between VM and functioning is independent of complex cognitive processes such as semantic clustering, supporting the cognitive remediation targeting of VM in these disorders.

Clozapine prescription trends in Brazil in the last decade

Objective: Clozapine is a second-generation antipsychotic indicated for treatment-resistant schizophrenia. Studies in several countries have shown a low rate of clozapine use despite the fact that approximately 30% of schizophrenia cases are treatment-resistant. In Brazil, few studies have addressed the frequency and variety of antipsychotic use in individuals diagnosed with schizophrenia (ICD F20). The objective of this study was to measure the rates of clozapine use in this population in the last decade using Brazilian Ministry of Health data. Methods: Prescriptions made between 2010 and 2020 in all 26 states and the Federal District registered at the Outpatient Information System Database from the Brazilian Health System (SIASUS) were evaluated. Results: A total of 25,143,524 prescriptions were recorded in this period, with clozapine representing 8.86% of all antipsychotics. The most frequently prescribed antipsychotic for patients with schizophrenia was olanzapine (35.8%), followed by quetiapine (27.5%). From 2010 to 2020, the rate of clozapine prescriptions in Brazil increased from 7.2% to 10.9%. Conclusions: Despite a slight increase in prescriptions in the last decade, clozapine is still underutilized in Brazil.

Clozapine prescription trends in Brazil in the last decade.

OBJECTIVE: Clozapine is a second-generation antipsychotic indicated for treatment-resistant schizophrenia. Studies in several countries have shown a low rate of clozapine use despite the fact that approximately 30% of schizophrenia cases are treatment-resistant. In Brazil, few studies have addressed the frequency and variety of antipsychotic use in individuals diagnosed with schizophrenia (ICD F20). The objective of this study was to measure the rates of clozapine use in this population in the last decade using Brazilian Ministry of Health data. METHODS: Prescriptions made between 2010 and 2020 in all 26 states and the Federal District registered at the Outpatient Information System Database from the Brazilian Health System (SIASUS) were evaluated. RESULTS: A total of 25,143,524 prescriptions were recorded in this period, with clozapine representing 8.86% of all antipsychotics. The most frequently prescribed antipsychotic for patients with schizophrenia was olanzapine (35.8%), followed by quetiapine (27.5%). From 2010 to 2020, the rate of clozapine prescriptions in Brazil increased from 7.2% to 10.9%. CONCLUSIONS: Despite a slight increase in prescriptions in the last decade, clozapine is still underutilized in Brazil.

Inflammatory cytokines and alcohol use disorder: systematic review and meta-analysis

Objective: To assess differences in blood inflammatory cytokines between people with alcohol use disorder (AUD) and healthy controls (HC). Methods: Searches were performed from inception through April 14, 2021. Meta-analyses with random-effects models were used to calculate the standardized mean difference ([SMD], 95%CI), and potential sources of heterogeneity were explored trough meta-regressions and subgroup analysis. Results: The meta-analysis included 23 studies on the following 14 cytokines: tumor necrosis factor (TNF)-α, IL-1, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL15, interferon (IFN)-γ and sCD14. There were significantly higher concentrations of IL-6 (n=462 AUD and 408 HC; SMD = 0.523; 95%CI 0.136-0.909; p = 0.008) in AUD than HC. No significant differences were found in the other 13 cytokines. Conclusion: We found that IL-6 levels were significantly higher in individuals with AUD than HC and that other cytokines were not altered. This can be explained by the small number of studies, their methodological heterogeneity, and confounding factors (active use, abstinence, quantity, and physical or psychiatric illnesses, for example). Despite a great deal of evidence about alcohol and inflammatory diseases, studies assessing the role of neuroimmune signaling in the development and severity of AUD are still lacking.

Inflammatory cytokines and alcohol use disorder: systematic review and meta-analysis.

OBJECTIVE: To assess differences in blood inflammatory cytokines between people with alcohol use disorder (AUD) and healthy controls (HC). METHODS: Searches were performed from inception through April 14, 2021. Meta-analyses with random-effects models were used to calculate the standardized mean difference ([SMD], 95%CI), and potential sources of heterogeneity were explored trough meta-regressions and subgroup analysis. RESULTS: The meta-analysis included 23 studies on the following 14 cytokines: tumor necrosis factor (TNF)-a, IL-1, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL15, interferon (IFN)-g and sCD14. There were significantly higher concentrations of IL-6 (n=462 AUD and 408 HC; SMD = 0.523; 95%CI 0.136-0.909; p = 0.008) in AUD than HC. No significant differences were found in the other 13 cytokines. CONCLUSION: We found that IL-6 levels were significantly higher in individuals with AUD than HC and that other cytokines were not altered. This can be explained by the small number of studies, their methodological heterogeneity, and confounding factors (active use, abstinence, quantity, and physical or psychiatric illnesses, for example). Despite a great deal of evidence about alcohol and inflammatory diseases, studies assessing the role of neuroimmune signaling in the development and severity of AUD are still lacking.

Bipolar disorder: an association between body mass index and cingulate gyrus fractional anisotropy not mediated by systemic inflammation.

OBJECTIVE: To investigate associations between body mass index (BMI), white matter fractional anisotropy (FA), and C-reactive protein (CRP) in a group of individuals with bipolar disorder (BD) during euthymia and compare them with a control group of healthy subjects (CTR). METHODS: The sample consisted of 101 individuals (BD n = 35 and CTR n = 66). Regions of interest (ROI) were defined using a machine learning approach. For each ROI, a regression model tested the association between FA and BMI, controlling for covariates. Peripheral CRP levels were assayed, correlated with BMI, and included in a mediation analysis. RESULTS: BMI predicted the FA of the right cingulate gyrus in BD (AdjR2 = 0.312 F(3) = 5.537 p = 0.004; ß = -0.340 p = 0.034), while there was no association in CTR. There was an interaction effect between BMI and BD diagnosis (F(5) = 3.5857 p = 0.012; Fchange = 0.227 AdjR2 = 0.093; ß = -1.093, p = 0.048). Furthermore, there was a positive correlation between BMI and CRP in both groups (AdjR2 = 0.170 F(3) = 7.337 p < 0.001; ß = 0.364 p = 0.001), but it did not act as a mediator of the effect on FA. CONCLUSION: Higher BMI is associated with right cingulate microstructure in BD, but not in CTR, and this effect could not be explained by inflammatory mediation alone.

Effects of socioeconomic status in cognition of people with schizophrenia: results from a Latin American collaboration network with 1175 subjects.

BACKGROUND: Cognition heavily relies on social determinants and genetic background. Latin America comprises approximately 8% of the global population and faces unique challenges, many derived from specific demographic and socioeconomic variables, such as violence and inequality. While such factors have been described to influence mental health outcomes, no large-scale studies with Latin American population have been carried out. Therefore, we aim to describe the cognitive performance of a representative sample of Latin American individuals with schizophrenia and its relationship to clinical factors. Additionally, we aim to investigate how socioeconomic status (SES) relates to cognitive performance in patients and controls. METHODS: We included 1175 participants from five Latin American countries (Argentina, Brazil, Chile, Colombia, and Mexico): 864 individuals with schizophrenia and 311 unaffected subjects. All participants were part of projects that included cognitive evaluation with MATRICS Consensus Cognitive Battery and clinical assessments. RESULTS: Patients showed worse cognitive performance than controls across all domains. Age and diagnosis were independent predictors, indicating similar trajectories of cognitive aging for both patients and controls. The SES factors of education, parental education, and income were more related to cognition in patients than in controls. Cognition was also influenced by symptomatology. CONCLUSIONS: Patients did not show evidence of accelerated cognitive aging; however, they were most impacted by a lower SES suggestive of deprived environment than controls. These findings highlight the vulnerability of cognitive capacity in individuals with psychosis in face of demographic and socioeconomic factors in low- and middle-income countries.

Bipolar disorder: an association between body mass index and cingulate gyrus fractional anisotropy not mediated by systemic inflammation

Abstract Objective To investigate associations between body mass index (BMI), white matter fractional anisotropy (FA), and C-reactive protein (CRP) in a group of individuals with bipolar disorder (BD) during euthymia and compare them with a control group of healthy subjects (CTR). Methods The sample consisted of 101 individuals (BD n = 35 and CTR n = 66). Regions of interest (ROI) were defined using a machine learning approach. For each ROI, a regression model tested the association between FA and BMI, controlling for covariates. Peripheral CRP levels were assayed, correlated with BMI, and included in a mediation analysis. Results BMI predicted the FA of the right cingulate gyrus in BD (AdjR2 = 0.312 F(3) = 5.537 p = 0.004; β = -0.340 p = 0.034), while there was no association in CTR. There was an interaction effect between BMI and BD diagnosis (F(5) = 3.5857 p = 0.012; Fchange = 0.227 AdjR2 = 0.093; β = -1.093, p = 0.048). Furthermore, there was a positive correlation between BMI and CRP in both groups (AdjR2 = 0.170 F(3) = 7.337 p < 0.001; β = 0.364 p = 0.001), but it did not act as a mediator of the effect on FA. Conclusion Higher BMI is associated with right cingulate microstructure in BD, but not in CTR, and this effect could not be explained by inflammatory mediation alone.

Ficolin activation as a potential biomarker of the severity of schizophrenia.

Several studies have examined the complement system in schizophrenia, suggesting an involvement of the lectin pathway. We analyzed 49 patients with schizophrenia and explored the association between psychopathology of schizophrenia and complement component 3 (C3) serum levels, C-reactive protein (CRP) serum levels, ficolin activation, and mannose-binding lectin (MBL) activation. In the multiple regression analysis, a negative association was observed between the Positive and Negative Syndrome Scale (PANSS) total score and ficolin activation. Body mass index (BMI) was positively associated with the serum levels of C3 and CRP. MBL activation was not associated with any independent variables. Our findings facilitate a better understanding of the complement system in schizophrenia. Additional studies with a large sample population are needed to confirm our results.