Symptomatic remission and recovery in major psychosis: Is there a role for BDNF? A secondary analysis of the LABSP cohort data.

Remission, relapse prevention, and clinical recovery are crucial areas of interest in schizophrenia (SCZ) research. Although SCZ is a chronic disorder with poor overall outcomes, years of research demonstrated that recovery is possible. There are considerable data linking brain-derived neurotrophic factor (BDNF) to SCZ, however, evidence on the role of BDNF in remission in SCZ is scarce. This secondary analysis of the Longitudinal Assessment of BDNF in Sardinian patients (LABSP) data aimed to investigate the relationship between serum BDNF levels and symptomatic remission, simultaneous clinical and functional remission, and recovery in patients with SCZ. A total of 105 patients with SCZ or schizoaffective disorder were recruited for a longitudinal assessment of BDNF levels over 24 months. Longitudinal data were analyzed using mixed-effects linear regression models. The study found significant associations between use of long acting injectables (χ2 = 7.075, df = 1, p = 0.008), baseline serum BDNF levels (U = 701, z = -2.543, p = 0.011), and "childhood" (U = 475, z = -2.124, p = 0.034) and "general" (U = 55, z = -2.014, p = 0.044) subscales of the Premorbid Adjustment Scale (PAS) with patients maintaining remission and recovery. The diagnosis of SCZ was significantly associated with lower BDNF levels for patients with simultaneous clinical and functional remission (Z = 2.035, p = 0.0419) and recovery (Z = 2.009, p = 0.0445) compared to those without. There were no significant associations between remission in the entire sample and longitudinal serum BDNF levels or genetic variants within the BDNF gene. These findings provide further insight into the complex relationship between BDNF and SCZ.

Pharmacokinetic Markers of Clinical Outcomes in Severe Mental Illness: A Systematic Review.

The term severe mental illness (SMI) encompasses those psychiatric disorders exerting the highest clinical burden and socio-economic impact on the affected individuals and their communities. Pharmacogenomic (PGx) approaches hold great promise in personalizing treatment selection and clinical outcomes, possibly reducing the burden of SMI. Here, we sought to review the literature in the field, focusing on PGx testing and particularly on pharmacokinetic markers. We performed a systematic review on PUBMED/Medline, Web of Science, and Scopus. The last search was performed on the 17 September 2022, and further augmented with a comprehensive pearl-growing strategy. In total, 1979 records were screened, and after duplicate removal, 587 unique records were screened by at least 2 independent reviewers. Ultimately, forty-two articles were included in the qualitative analysis, eleven randomized controlled trials and thirty-one nonrandomized studies. The observed lack of standardization in PGx tests, population selection, and tested outcomes limit the overall interpretation of the available evidence. A growing body of evidence suggests that PGx testing might be cost-effective in specific settings and may modestly improve clinical outcomes. More efforts need to be directed toward improving PGx standardization, knowledge for all stakeholders, and clinical practice guidelines for screening recommendations.

Psychotropic drug repurposing for COVID-19: A Systematic Review and Meta-Analysis.

Several psychotropic drugs, including antidepressants (AD), mood stabilizers, and antipsychotics (AP) have been suggested to have favorable effects in the treatment of COVID-19. The aim of this systematic review and meta-analysis was to collect evidence from studies concerning the scientific evidence for the repurposing of psychotropic drugs in COVID-19 treatment. Two independent authors searched PubMed-MEDLINE, Scopus, PsycINFO, and ClinicalTrials.gov databases, and reviewed the reference lists of articles for eligible articles published up to 13th December 2021. All computational, preclinical and clinical (observational and/or RCTs) studies on the effect of any psychotropic drug on Sars-CoV-2 or patients with COVID-19 were considered for inclusion. We conducted random effect meta-analyses on clinical studies reporting the effect of AD or AP on COVID-19 outcomes. 29 studies were included in the synthesis: 15 clinical, 9 preclinical, and 5 computational studies. 9 clinical studies could be included in the quantitative analyses. AD did not increase the risk of severe COVID-19 (RR= 1.71; CI 0.65-4.51) or mortality (RR=0.94; CI 0.81-1.09). Fluvoxamine was associated with a reduced risk of mortality for COVID-19 (OR=0.15; CI 0.02-0.95). AP increased the risk of severe COVID-19 (RR=3.66; CI 2.76-4.85) and mortality (OR=1.53; CI 1.15-2.03). Fluvoxamine might be a possible candidate for psychotropic drug repurposing in COVID-19 due to its anti-inflammatory and antiviral potential, while evidence on other AD is still controversial. Although AP are associated with worse COVID-19 outcomes, their use should be evaluated case to case and ongoing treatment with antipsychotics should be not discontinued in psychiatric patients.

Converging Evidence Points to BDNF as Biomarker of Depressive Symptoms in Schizophrenia-Spectrum Disorders.

Brain-derived neurotrophic factor (BDNF) is a key modulator of neuroplasticity and has an important role in determining the susceptibility to severe psychiatric disorder with a significant neurodevelopmental component such as major psychoses. Indeed, a potential association between BDNF serum levels and schizophrenia (SCZ) and schizoaffective disorder (SAD) has been tested in diverse studies and a considerable amount of them found reduced BDNF levels in these disorders. Here, we aimed at testing the association of BDNF serum levels with several demographic, clinical, and psychometric measures in 105 patients with SCZ and SAD, assessing the moderating effect of genetic variants within the BDNF gene. We also verified whether peripheral BDNF levels differed between patients with SCZ and SAD. Our findings revealed that BDNF serum levels are significantly lower in patients affected by SCZ and SAD presenting more severe depressive symptomatology. This finding awaits replication in future independent studies and points to BDNF as a possible prognostic indicator in major psychoses.

Exploring the association between brain-derived neurotrophic factor levels and longitudinal psychopathological and cognitive changes in Sardinian psychotic patients.

BACKGROUND AND HYPOTHESIS: Schizophrenia spectrum disorders are among the most debilitating mental disorders and has complex pathophysiological underpinnings. There is growing evidence that brain-derived neurotrophic factor (BDNF) can play a role in its pathogenesis. The present study investigated the longitudinal variation of serum BDNF levels in a 24-month observational prospective cohort study of Sardinian psychotic patients and its relationship with psychopathological and cognitive changes. Furthermore, we examined whether genetic variation within the BDNF gene could moderate these relationships. STUDY DESIGN: Every 6 months, 105 patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and social measures. We performed a targeted analysis of four tag single nucleotide polymorphisms within the BDNF gene that were selected and analyzed using polymerase chain reaction. Longitudinal data were analyzed using mixed-effects linear regression models. STUDY RESULTS: We observed a declining longitudinal trajectory of BDNF levels in psychotic patients in general, and in relation to the severity of depressive and negative symptoms. BDNF serum levels also declined in patients scoring lower in cognitive measures such as attention and speed of information processing and verbal fluency. The rs7934165 polymorphism moderated the significant association between verbal fluency and BDNF levels. CONCLUSIONS: These findings in patients from real-world settings suggest a plausible role of peripheral BDNF levels as a marker of illness burden in schizophrenia spectrum disorders.

Are Nonfatal Suicide Attempts Instrumental in Achieving Personal and Interpersonal Goals?

This study focused on the well-being of the survivors of suicide attempts and the well-being of their interpersonal relationships after the attempt. The data came from a sample of 392 college students from 10 Muslim majority countries who reported having attempted suicide in the last 4 years. Suicide was conceptualized as a goal-directed behavior embedded in a sociocultural context and motivated by personal or interpersonal goals. We tested a process that linked culturally shaped self-construal to the postsuicidal personal and interpersonal well-being. We posited that this process would operate through the attitudes towards suicide, motives for suicide, the strength of the intention to die. Our model indicated that the acceptability of suicide was positively associated with escape motives, and this association was even stronger for the individuals with interdependent self-construals. Escape motives were negatively associated with postsuicidal personal and interpersonal well-being, but communication motives were not associated with these outcomes. We also found evidence that having an interdependent self-construal might be beneficial for postsuicidal personal and interpersonal well-being. Our results further suggested that the postsuicidal personal and interpersonal well-being of highly interdependent individuals may depend on the interpretation of their act of suicide by their close others.

Cultural and interpersonal risk factors for suicide ideation and suicide attempts among Muslim college students from 11 nations.

BACKGROUND: Research on suicidality in low to middle-income countries is scarce. We addressed this issue by investigating suicidality in a cross-national college student samples from 11 predominantly low to middle-income majority Muslim countries. METHODS: The sample consisted of 7427 college students (56% female) who reported to be affiliated with Islam. Data on self-construal, social support, negative life-events, acceptability of suicide, suicidal ideation, and suicide attempts were collected with self-administered questionnaires. RESULTS: Acceptability of suicide and the experience of negative life-events were positively, and perceived social support was negatively associated with suicidal ideation. Interdependent self-construal was negatively related to the acceptability of suicide and positively associated with perceived social support, implying a negative indirect effect on suicidal ideation although its direct effect was positive. The number of negative life-events was the strongest positive predictor of ever attempting suicide. The interdependent self-construal moderated the association of negative life-events with suicide attempts. LIMITATIONS: Cross-sectional and self-report nature of the study were its major limitations. Participants may have suppressed their responses about suicide because of religious and legal reasons. CONCLUSION: Remarkable similarities across 11 country samples emerged in the linkages between cultural and interpersonal factors with suicidality. Our findings highlight the value of a nuanced approach to suicidality, that can recognize the differences in the processes associated with suicidal ideation and suicide attempts, as well as the need to consider the interplay of a broad range of personal, interpersonal, and cultural influences.

Associations of religiosity, attitudes towards suicide and religious coping with suicidal ideation and suicide attempts in 11 muslim countries.

OBJECTIVE: The study investigated the associations of religiosity, religious coping and suicide acceptance to suicide ideation and attempts in 7427 young adults affiliating with Islam from 11 Muslim countries. METHOD: A self-administered questionnaire was used to collect the data. We used F and χ2 tests and correlation analyses to report descriptive statistics. Multi-group path models with (i) a zero-inflated Poisson distribution and, (ii) a Binomial distribution were used to model the number of occurrences of suicidal ideation, and occurrence of a suicide attempt, respectively. RESULTS: Religiosity was negatively associated with acceptability of suicide, but it was positively related to punishment after death across the 11 countries. Religiosity was negatively associated with ever experiencing suicidal ideation, both directly and indirectly through its association with attitudes towards suicide, especially the belief in acceptability of suicide. Neither positive nor negative religious coping were related to suicidal ideation. However, religiosity was negatively related to suicide attempts among those who experienced suicidal ideation at least once. This association was mediated through the belief in acceptability of suicide and religious coping. Negative religious coping was positively associated with suicide attempts probably because it weakened the protective effects of religiosity. CONCLUSIONS: Findings from this study suggest that the effects of religiosity in the suicidal process operate through attitudes towards suicide. We therefore conclude that clinical assessment as well as research in suicidology may benefit from paying due attention to attitudes towards suicide.

Suicidal Thoughts, Attempts and Motives Among University Students in 12 Muslim-Majority Countries.

There is a scarcity of research on suicidal phenomena in the Muslim world. Therefore, this study aimed at investigating the self-reported prevalence of suicidal thoughts, attempts and motives in 12 Muslim countries. A total of 8417 (54.4% women) university students were surveyed by means of a self-report questionnaire. Overall, 22% of the participants reported suicidal ideation and 8.6% reported attempting suicide. The odds of suicidal thoughts were elevated in Azerbaijan, Indonesia and Saudi Arabia, while reduced ORs were recorded in Egypt, Jordan, Lebanon and Malaysia. While odds of suicide attempts were high in Azerbaijan, Palestine and Saudi Arabia reduced odds ratios (OR) were detected in Indonesia, Iran, Jordan, Lebanon, Malaysia and Tunisia. Taking drugs and using a sharp instrument were the two most frequently used methods to attempt suicide. Only 32.7% of attempts required medical attention. Escape motives were endorsed more than social motives by participants who attempted suicide. Suicidal behaviors were more frequent in women than in men. Compered to men, fewer attempts by women required medical attention. Moreover, our results show that making suicide illegal does not reduce the frequency of suicidal behavior. Results from this comparative study show that suicidal thoughts and attempts are frequent events in young adults in countries where religious scripture explicitly prohibit suicide and the frequencies of nonfatal suicidal behavior show large variation in nations adhering to the same religion.