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.

On suicidal ideation: the need for inductive methodologies to advance the field.

Recent scholarly investigation of suicidal ideation has been largely based on identifying associated factors and using ideation-to-action theories to explain its occurrence. However, this approach may not be sufficient, as many aspects of suicidal ideation fall beyond the reach of such conceptualizations. The overemphasis on explaining rather than understanding this phenomenon is a significant factor in this insufficiency. As such, it is argued that qualitative methods that use data to derive theories could offer a more nuanced understanding of suicidal ideation. By adopting bottom-up approaches, researchers can explore how individuals experience and understand suicidal ideation and how it relates to their lives and experiences. Furthermore, use of qualitative research methods could aid in development of more accurate and inclusive definitions that are more firmly grounded in data.

On suicidal ideation: the need for inductive methodologies to advance the field

Abstract Recent scholarly investigation of suicidal ideation has been largely based on identifying associated factors and using ideation-to-action theories to explain its occurrence. However, this approach may not be sufficient, as many aspects of suicidal ideation fall beyond the reach of such conceptualizations. The overemphasis on explaining rather than understanding this phenomenon is a significant factor in this insufficiency. As such, it is argued that qualitative methods that use data to derive theories could offer a more nuanced understanding of suicidal ideation. By adopting bottom-up approaches, researchers can explore how individuals experience and understand suicidal ideation and how it relates to their lives and experiences. Furthermore, use of qualitative research methods could aid in development of more accurate and inclusive definitions that are more firmly grounded in data.

Latent structure and factor reliability of the National Health Service Community Mental Health Service User Questionnaire.

BACKGROUND: National Health Service use the Community Mental Health Service User Questionnaire (NHS-CMH) to assess care quality. However, its reliability and internal validity is uncertain. AIMS: To test the NHS-CMH structure, reliability and item-level characteristics. METHODS: We used data from 11,373 participants who answered the 2017 NHS-CMH survey. First, we estimated the NHS-CMH structure using Exploratory Factor Analysis (EFA) in half of the dataset. Second, we tested the best EFA-derived model with Confirmatory Factor Analysis (CFA). We tested the internal validity, construct reliability (omega - ω), explained common variance of each factor (ECV), and item thresholds. RESULTS: EFA suggested a 4-factor solution. The structure derived from the EFA was confirmed, demonstrating good reliability for the four correlated dimensions: "Relationship with Staff" (ω = 0.952, ECV = 40.1%), "Organizing Care" (ω = 0.855, ECV = 21.4%), "Medication and Treatments" (ω = 0.837, ECV = 13.3%), and "Support and Well-being" (ω = 0.928, ECV = 25.3%). A second-order model with a high-order domain of "Quality of Care" is also supported. CONCLUSIONS: The NHS-CMH can be used to reliably assess four user-informed dimensions of mental health care quality. This model offers an alternative for its current use (item-level and untested sum scores analysis).

Lithium-induced neuroprotective activity in neuronal and microglial cells: A purinergic perspective.

Lithium is the mainstay of pharmacotherapy for treating bipolar disorder (BD). However, despite its wide use for over 60 years in the clinic, its mechanisms of action are not yet well defined. Elucidating lithium's mechanism of action will not only shed light on the pathophysiology of BD, but also potentially uncover new treatment targets. Previous studies suggest that the purinergic system may be involved in lithium's neuroprotective action; thus, the specific aim of this study is to better understand the neuroprotective action of lithium against ATP-induced cellular effect in both neuronal and microglial cellular lineages. We used PC12 neuronal and N9 microglial cells, evaluating cell death by cell counting and Annexin/PI cytometry assay, P2 × 7R immunocontent and ectonucleotidases activity, together with cytokine and nitrite assessment for microglial activity determination. Our results indicate that cells of different neural origins are responsive to ATP, in the sense of neuronal excitotoxicity and microglial switch into an activated M1-like phenotype respectively. Lithium, in turn, modulates the response in neuronal PC12 cells, preventing ATP-induced cell death. On the other hand, in N9 microglial cells, lithium was unable to prevent ATP-induced activation via P2 × 7R, indicating that lithium protective action against the effects of ATP more likely occurs in neurons rather than in microglia. Further studies are needed to better characterize the involvement of the purinergic system in the mechanism of action of lithium against neuronal death and microglial activation, in order to uncover new therapeutic adjunctive targets, such as antagonism of P2 × 7R, as potential approach for bipolar disorder treatment.

Psychotic depression in hospitalized patients: Longitudinal outcomes of psychotic vs. nonpsychotic depression among inpatients.

Even though psychotic depression is related to worse outcomes than nonpsychotic depression, there is increasing evidence that this greater severity is not solely explained by the depressive symptoms. We evaluated the socio-demographic and clinical characteristics, as well as the differences in clinical outcomes of psychiatric hospitalization between psychotic and non-psychotic depression. Two-hundred-eighty-eight depressive inpatients were assessed within 72 h after hospitalization and 24 h before discharge. We compared scores of Hamilton Depression Rating Scale 17-items (HDRS-17), Clinical Global Impression (CGI), Brief Psychiatric Rating Scale (BPRS), and Global Assessment of Functioning (GAF) between psychotic and nonpsychotic patients. Instruments were compared both cross-sectionally - on admission and discharge - and longitudinally. Longitudinal outcomes were corrected for potential confounders (sex, age, age at disease onset, years of study, previous history of mania/hypomania, electroconvulsive therapy in current hospitalization, history of attempted suicide, number of suicide attempts, and previous hospitalizations). One-hundred-thirty-one depressive inpatients (45.4%) presented psychotic features. Both groups showed similar HDRS-17 scores at admission and discharge. However, psychotic patients had worse scores on BPRS, CGI, and GAF at both timepoints. Both groups had similar improvement on HDRS-17 (P = 0.75), CGI (P = 0.5), and GAF (P = 0.84), but psychotic patients had greater improvement on BPRS (P < 0.001). Psychotic inpatients showed worse clinical and functional parameters. Nonetheless, the groups did not differ in depressive symptom severity. These findings reinforce the hypothesis that depressive episode with psychotic features is a more severe form of the disease irrespective of intensity of affective symptomatology.

Case report on the multiple pathways to posttraumatic stress disorder following suicide.

Trauma pathology is not only a sum of risk factors, but emerges as a result of complex causal interaction. The case presented here illustrates the pathway from suicide exposure to the development of fully-fledged treatment-resistant posttraumatic stress disorder (PTSD), demonstrating how recognized risk factors can act in tandem to generate a difficult to treat syndrome. From a clinical perspective, bottom-up approaches that take into account real coping experiences of people bereaved by suicide are more effective to facilitate recovery and prevent adverse outcomes. Finally, even though treatment is often implemented, the diagnosis can be missed further complicating coping and treatment.

P2X7 Purinergic Receptor Is Involved in the Pathophysiology of Mania: a Preclinical Study.

The pathophysiology of bipolar disorder remains incompletely elucidated. The purinergic receptor, P2X7 (P2X7R), plays a central role in neuroinflammation, the establishment, and maintenance of microglial activation and neuronal damage/death, all characteristics of bipolar disorder pathology. The present study aims to explore the participation of the P2X7R in a preclinical pharmacological model of mania. We analyzed the modulatory effects of the P2X7R antagonist, brilliant blue, on behavior, monoamines, gene expression, serum purine levels, and cell typing in a pharmacological model of mania induced by D-amphetamine (AMPH) in mice. Our results corroborate an association between the P2X7 receptor and the preclinical animal model of mania, as demonstrated by the decreased responsiveness to AMPH in animals with pharmacologically blocked P2X7R. This study further suggests a possible dopaminergic mechanism for the action of P2X7 receptor antagonism. Additionally, we observed increased peripheral levels of adenosine, a neuroprotective molecule, and increased central expression of Entpd3 and Entpd1 leading to the hydrolysis of ATP, a danger signal, possibly as an attempt to compensate for the damage induced by AMPH. Lastly, P2X7R antagonism in the AMPH model was found to potentially modulate astrogliosis. Our results support the hypothesis that P2X7R plays a vital role in the pathophysiology of mania, possibly by modulating the dopaminergic pathway and astrogliosis, as reflected in the behavioral changes observed. Taken together, this study suggests that a purinergic system imbalance is associated with the AMPH-induced preclinical animal model of mania. P2X7R may represent a promising molecular therapeutic target for bipolar disorder.

Sociodemographic, criminal and forensic characteristics of a sample of female children and adolescents murdered in Brazil. 2010-2016 / Características sociodemográficas, criminales y médico-legales de una muestra de niñas y adolescentes víctimas de homicidio en Brasil. 2010-2016

Abstract Introduction: In Brazil, violence, regardless of the type, is the leading cause of death in adolescents and young adults. Objective: To describe the characteristics of the homicides in which female children and adolescents were the victims based on the autopsy reports recorded in the morgue of the city of Porto Alegre, Brazil. Materials and methods: Cross-sectional study in which 70 autopsy reports of girls and female adolescents who were killed between January 2010 and December 2016 were analyzed. The cases were evaluated according to the homicide motive or the homicide perpetrator, and five categories were established: drug trafficking related death, femicide, homicide perpetrated by a family member, death preceded by sexual violence, and death related to other transgressions. Results: There was a significant increase in the number of girls and female adolescents who were murdered between 2010 (n=7) and 2016 (n=19). Most of the homicides (64.2%) were related to drug, while femicide occurred in 15.7% of the cases. Homicides perpetrated by a family member, or preceded by sexual violence or related with other transgressions were less frequent as they occurred in 10%, 5.7% and 4.2% of the cases, respectively. Conclusion: Greater attention must be paid to the increase in the number of drug trafficking related homicides among female adolescents when creating and implementing relevant public policies.

Resumen Introducción. En Brasil, la violencia, en sus diferentes manifestaciones, es la primera causa de muerte entre adolescentes y adultos jóvenes de ambos sexos. Objetivo. Describir las características de los homicidios de niñas y adolescentes registrados en la morgue de Porto Alegre, Brasil. Materiales y métodos. Estudio transversal que analizó 70 pericias de necropsia de jóvenes víctimas de homicidio entre enero de 2010 y diciembre de 2016. Los casos fueron evaluados según los motivos de los crímenes, identificando 5 categorías: muertes causadas por tráfico de drogas, feminicidios, homicidios familiares, muertes por violencia sexual y homicidios relacionados con otras infracciones legales. Resultados. Hubo un aumento significativo en el número de niñas y mujeres adolescentes víctimas de homicidio entre 2010 (n=7) y 2016 (n=19). La mayoría de casos estuvieron relacionados con el tráfico de estupefacientes (64.2%), mientras que los casos de feminicidio representaron 15.7% da la muestra. Los homicidios cometidos por un familiar, los precedidos de violencia sexual y aquellos relacionados con otras actividades ilegales fueron menos frecuentes con un 10%, 5.7% y 4.2%, respectivamente. Conclusiones. Es necesario prestar más atención al aumento de los homicidios en esta población relacionados con el tráfico de estupefacientes a la hora de crear e implementar políticas públicas al respecto.

Clinical outcomes and childhood trauma in bipolar disorder: A community sample of young adults.

Childhood trauma is a complex experience, much reported by subjects with bipolar disorder. There are still few studies that assess its consequences in a community sample of bipolar in early stage. The aim of the present study is to assess the association between childhood trauma and clinical outcomes, including the global functioning, in a community sample of young adults with bipolar disorder. This is a cross-sectional study with a community sample of subjects with bipolar disorder, from 23 to 30 years old, with and without childhood trauma. The trauma experiences during childhood were assessed by Childhood Trauma Questionnaire (CTQ). The functioning was assessed by Functioning Assessment Short Test (FAST). Ninety subjects with bipolar disorder were included in the study (30 with childhood trauma and 60 without childhood trauma). Young adults with bipolar disorder and childhood trauma showed higher prevalence of current suicide risk, higher severity of depressive symptoms, and higher functioning impairment as compared to subjects with bipolar disorder without childhood trauma. The childhood trauma experiences appear to be an environmental risk factor for worse clinical outcomes and higher functional impairment.

Age and sex trends for suicide in Brazil between 2000 and 2016.

PURPOSE: To evaluate changes in standardized suicide rates in Brazil between 2000 and 2016, stratified by sex and age. METHODS: Descriptive analyses of data from the Brazilian Mortality Information System were performed. RESULTS: 156,292 suicides were registered in the period, with a standardized rate of 4.82/100,000. The risk for males was 3.81 times higher than for females, without meaningful regional variations. This ratio was 8.2 at the 80+ group. An increase from 2000 to 2016 was demonstrated in nearly all subgroups over the 17, especially men aged 20-39 and women aged 40-59. CONCLUSIONS: Suicide rates continue to rise in Brazil, especially among young men and middle-aged women. Older men remain exposed to the highest absolute risk.

Bipolar disorder and 1513A>C P2RX7 polymorphism frequency.

Although the etiology of Bipolar Disorder (BD) remains unknown, a strong genetic component to the pathogenesis and risk for this disorder has been widely hypothesized. Several risk genes for BD have been identified; of these, the purinergic P2 × 7 receptor (P2 × 7R) constitutes a pro-inflammatory receptor and a potential risk gene candidate. The purpose of the present study was to assess the frequency of the 1513 A > C P2RX7 polymorphism (rs3751143; Glu496Ala), which leads to receptor loss-of-function, in 154 BD patients versus 184 control subjects. The existence of a differential modulation of P2 × 7R was also analyzed in 22 euthymic BD patients, in comparison to 18 healthy controls. Our data show a decrease in 1513C allele frequency (p = 0.045) and a potential increase in 1513 A A/AC (p = 0.055) genotype frequency in BD patients, compared to controls, indicating an enhanced function of the pro-inflammatory P2 × 7 receptor in BD subjects. Interestingly, no differences in P2RX7 gene and protein expression were found between euthymic BD patients and matched healthy controls. In conclusion, our results suggest that P2 × 7R might play a role in the pathophysiology of BD and add new information regarding this receptor as a potential biomarker for the prediction and diagnosis of the disorder.

Metabolic syndrome, depression and anhedonia among young adults.

The aim of this study was to assess the association between anhedonia and metabolic syndrome (MetS) in a well-characterized community sample of individuals with a current depressive episode. This is a cross-sectional study with young adults aged 24-30 years old. Depressive episode and the presence of anhedonia was assessed using the Mini International Neuropsychiatric Interview - Plus version (MINI Plus). The MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). The sample included 931 subjects, being 22 had depression without anhedonia, whereas 55 had depression with anhedonia. MetS was more prevalent among subjects with depression and anhedonia (43.6%) when compared to individuals without anhedonia and population control group. Moreover, subjects with depression and anhedonia have a significant increase of levels of glucose, triglycerides, total-cholesterol and LDL-cholesterol, as well as significant decreased in the HDL-cholesterol level. The present study showed that individuals with depression and anhedonia present higher prevalence of MetS. Our study suggests that the use of the concept of anhedonia may contribute to a better understanding of the complex relationship between depression and metabolic syndrome.

Prevalence and factors associated with Premenstrual Dysphoric Disorder: A community sample of young adult women.

Premenstrual Dysphoric Disorder (PMDD) was recently included in DSM-5 as a full diagnostic category. Few studies have investigated PMDD in a community sample of young adults, especially in Brazil. Thus, the objective of this study was to evaluate the prevalence and the factors associated with PMDD in a community sample of 727 young adult women between the 18 and 24 years of age in southern Brazil. This was a cross-sectional population-based study. The data were collected from 2012 to 2014. PMDD was assessed using the Mini International Neuropsychiatry Interview (M.I.N.I. - Plus). The prevalence of PMDD was 17.6%. PMDD was significantly higher among older women, and in women from lower socio-economic status. A trend towards significance was found for women without a current occupation (study or work). The comorbidities significantly associated with PMDD were current major depression disorder, agoraphobia, bipolar disorder, current suicide risk, generalized anxiety disorder, social phobia, and specific phobia. The high prevalence found in the present study should be interpreted considering a retrospective report. However, our data showed that clinicians should be alert for PMDD symptoms, especially among young adult women.

The impact of substance use disorders on recovery from bipolar depression: Results from the Systematic Treatment Enhancement Program for Bipolar Disorder psychosocial treatment trial.

OBJECTIVE: Up to 60% of patients with bipolar disorder develop a substance use disorder during their lifetime. The purpose of this paper was to assess the impact of substance use disorders on depression recovery among bipolar patients randomly assigned to different psychotropic medications and psychosocial interventions. We hypothesized that patients with a comorbid substance use disorder would benefit less from psychotherapy regardless of treatment intensity/length compared to patients without a comorbid substance use disorder. METHOD: We conducted post hoc analyses among bipolar disorder patients ( n = 270) with and without comorbid substance use disorders enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder randomized psychosocial intervention trial. All patients entered during or shortly after the onset of a bipolar depressive episode. Logistic regression and Cox proportional hazard models were used to assess whether current or past substance use disorders moderated the response of patients to intensive psychosocial intervention or brief psychoeducation with collaborative care, operationalized as full recovery from an episode of bipolar depression. RESULTS: Current comorbid substance use disorders significantly predicted likelihood of recovery (odds ratio = 2.25, p = 0.025) and time to recovery (odds ratio = 1.71, p = 0.006) from bipolar depression. We found that 74.5% of patients with a current substance use disorder, compared to 56.5% without a current substance use disorder, recovered from bipolar depression. Past substance use disorders did not predict likelihood of recovery or time to recovery. Current substance use disorders did not significantly moderate response to intensive psychotherapy versus collaborative care. CONCLUSION: Contrary to our hypotheses, bipolar disorder participants with a current comorbid substance use disorder were more likely to recover from psychosocial treatment for bipolar depression than patients without a current comorbid substance use disorder. If this finding is replicated, it has implications for the ordering of treatment for patients with comorbid bipolar disorder and substance use disorders.

Inflammatory cytokines and functional impairment in drug-free subjects with mood disorder.

OBJECTIVE: To assess the association between peripheral levels of inflammatory cytokines and functional impairment in subjects with Bipolar Disorder (BD), Major Depressive Disorder (MDD) and population controls. METHODS: This was a cross-sectional study with a matched sample of drug-free young adults with BD (n=48), MDD (n=48) and population controls (n=48). Mood disorder was confirmed by a certified psychologist using the Structured Clinical Interview for DSM-IV (SCID-I). Functional impairment was assessed using the Functional Assessment Short Test (FAST). Serum levels of IL-6 and IL-10 were measured by ELISA. RESULTS: Peripheral levels of IL-6 and IL-10 were not significantly different between subjects with BD, MDD compared to controls. Higher levels of functional impairment were verified in subjects with BD and MDD compared to population controls (p≤0.001). In addition, IL-6 and IL-10 levels were positively correlated with functional impairment in subjects with BD (IL-6: r=0.349, p=0.016; and IL-10: r=0.351, p=0.016). CONCLUSION: Inflammatory dysregulation was associated with functional impairment among drug-free subjects with BD. This finding suggests that inflammatory dysregulation may be involved in the neuroprogression of BD.

Metabolic syndrome in subjects with bipolar disorder and major depressive disorder in a current depressive episode: Population-based study: Metabolic syndrome in current depressive episode.

OBJECTIVE: To assess the differences in the prevalence of the metabolic syndrome (MetS) and their components in young adults with bipolar disorder (BD) and major depressive disorder (MDD) in a current depressive episode. METHODS: This was a cross-sectional study with young adults aged 24-30 years old. Depressive episode (bipolar or unipolar) was assessed using the Mini International Neuropsychiatric Interview - Plus version (MINI Plus). The MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). RESULTS: The sample included 972 subjects with a mean age of 25.81 (±2.17) years. Both BD and MDD patients showed higher prevalence of MetS compared to the population sample (BD = 46.9%, MDD = 35.1%, population = 22.1%, p < 0.001). Higher levels of glucose, total cholesterol and LDL cholesterol, Body Mass Index, low levels of HDL cholesterol, and a higher prevalence of abdominal obesity were observed in both BD and MDD individuals with current depressive episode compared to the general population. Moreover, there was a significant difference on BMI values in the case of BD and MDD subjects (p = 0.016). CONCLUSION: Metabolic components were significantly associated with the presence of depressive symptoms, independently of the diagnosis.