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.

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.

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.

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.

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.

BIRTH ORDER AND ANDROPHILIC MALE-TO-FEMALE TRANSSEXUALISM IN BRAZIL.

Previous research has indicated that biological older brothers increase the odds of androphilia in males. This finding has been termed the fraternal birth order effect. The maternal immune hypothesis suggests that this effect reflects the progressive immunization of some mothers to male-specific antigens involved in fetal male brain masculinization. Exposure to these antigens, as a result of carrying earlier-born sons, is hypothesized to produce maternal immune responses towards later-born sons, thus leading to female-typical neural development of brain regions underlying sexual orientation. Because this hypothesis posits mechanisms that have the potential to be active in any situation where a mother gestates repeated male fetuses, a key prediction is that the fraternal birth order effect should be observable in diverse populations. The present study assessed the association between sexual orientation and birth order in androphilic male-to-female transsexuals in Brazil, a previously unexamined population. Male-to-female transsexuals who reported attraction to males were recruited from a specialty gender identity service in southern Brazil (n=118) and a comparison group of gynephilic non-transsexual men (n=143) was recruited at the same hospital. Logistic regression showed that the transsexual group had significantly more older brothers and other siblings. These effects were independent of one another and consistent with previous studies of birth order and male sexual orientation. The presence of the fraternal birth order effect in the present sample provides further evidence of the ubiquity of this effect and, therefore, lends support to the maternal immune hypothesis as an explanation of androphilic sexual orientation in some male-to-female transsexuals.

WHOQOL-100 Before and After Sex Reassignment Surgery in Brazilian Male-to-Female Transsexual Individuals.

INTRODUCTION: The 100-item World Health Organization Quality of Life Assessment (WHOQOL-100) evaluates quality of life as a subjective and multidimensional construct. Currently, particularly in Brazil, there are controversies concerning quality of life after sex reassignment surgery (SRS). AIM: To assess the impact of surgical interventions on quality of life of 47 Brazilian male-to-female transsexual individuals using the WHOQOL-100. METHODS: This was a prospective cohort study using the WHOQOL-100 and sociodemographic questions for individuals diagnosed with gender identity disorder according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The protocol was used when a transsexual person entered the ambulatory clinic and at least 12 months after SRS. MAIN OUTCOME MEASURES: Initially, improvement or worsening of quality of life was assessed using 6 domains and 24 facets. Subsequently, quality of life was assessed for individuals who underwent new surgical interventions and those who did not undergo these procedures 1 year after SRS. RESULTS: The participants showed significant improvement after SRS in domains II (psychological) and IV (social relationships) of the WHOQOL-100. In contrast, domains I (physical health) and III (level of independence) were significantly worse after SRS. Individuals who underwent additional surgery had a decrease in quality of life reflected in domains II and IV. During statistical analysis, all results were controlled for variations in demographic characteristics, without significant results. CONCLUSION: The WHOQOL-100 is an important instrument to evaluate the quality of life of male-to-female transsexuals during different stages of treatment. SRS promotes the improvement of psychological aspects and social relationships. However, even 1 year after SRS, male-to-female transsexuals continue to report problems in physical health and difficulty in recovering their independence.

Discordant transsexualism in male monozygotic twins: neuroanatomical and psychological differences.

One monozygotic male twin pair discordant for transsexualism is described. Both twins were interviewed and tested with the Wechsler Adult Intelligence Scale battery for cognitive functions and they underwent magnetic resonance imaging to measure the volumes of specific cerebral structures. Interviews with the twins and their mother indicated no unusual medical or life history events that could have had a causal role in the emergence of the disorder. Both cognitive function testing and neuroimaging detected differences between the twins that could be related to unexplained epigenetic effects and exogenous hormone usage.

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.

Increased COVID-19 mortality in patients with schizophrenia: A retrospective study in Brazil.

The risk that COVID-19 poses for mortality risk in individuals with schizophrenia in low- and middle-income countries has only been the subject of a few studies. In this retrospective study, we examined the standardized mortality ratio (SMR), by age group and sex, in a cohort of patients diagnosed with schizophrenia (n = 20,417), with second-generation antipsychotics, in a South Brazilian State database (Paraná-Brazil). We performed a linkage with the Brazilian Mortality Information System database between 2020 and 2021. We also assessed in a logistic regression how clozapine could affect COVID-19 mortality controlling by sex, age, and presence of obesity. A secondary analysis was to compare mortality with SMR due to COVID-19 in individuals with and without obesity. Compared to the State population (8,850,682 individuals), those with schizophrenia had more than two times greater risk of dying from COVID-19 (SMR = 2.21, 95 % CI: 1.90-2.55). Between the ages of 16 and 29, their risk is more than ten times higher than the state population (SMR = 10.18, 95 % CI: 4.73-19.33). Obesity showed an almost twofold risk of dying from COVID-19 in the patient's group (OR = 1.89, 95 % CI: 1.39-2.57). Clozapine was not found as a protector or a risk factor for COVID-19 mortality. In Brazil, a middle-income nation, people with schizophrenia are more likely to die prematurely from COVID-19. The burden of schizophrenia is higher in younger and in patients with obesity.

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.

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.

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.

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.

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.

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.

Pharmacological treatment of bipolar depression: qualitative systematic review of double-blind randomized clinical trials.

Randomized clinical trial (RCT) is the best study design for treatment-related issues, yet these studies may present a number of biases and limitations. The objective of this study is to carry out a qualitative analysis of RCT methodology in the treatment of bipolar depression (BD). A systematic review covering the last 20 years was performed on PubMed selecting double-blind RCTs for BD. The identification items of the articles, their design, methodology, outcome and grant-related issues were all analyzed. Thirty articles were included, all of which had been published in journals with an impact factor >3. While almost half studies (46.7%) used less than 50 patients as a sample, 70% did not describe or did not perform sample size calculation. The Last Observation Carried Forward (LOCF) method was used in 2/3 of the articles and 53.4% of the studies had high sample losses (>20%). Almost half the items were sponsored by the pharmaceutical industry and 33.3% were sponsored by institutions or research foundations. Articles on the pharmacological treatment of BD have several limitations which hinder the extrapolation of the data to clinical practice. Methodological errors and biases are common and statistical simplifications compromise the consistency of the findings.

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.

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.