Perspectives on reasons for suicidal behaviour and recommendations for suicide prevention in Kenya: qualitative study.

BACKGROUND: Little is known about the reasons for suicidal behaviour in Africa, and communities' perception of suicide prevention. A contextualised understanding of these reasons is important in guiding the implementation of potential suicide prevention interventions in specific settings. AIMS: To understand ideas, experiences and opinions on reasons contributing to suicidal behaviour in the Coast region of Kenya, and provide recommendations for suicide prevention. METHOD: We conducted a qualitative study with various groups of key informants residing in the Coast region of Kenya, using in-depth interviews. Audio-recorded interviews were transcribed and translated from the local language before thematic inductive content analysis. RESULTS: From the 25 in-depth interviews, we identified four key themes as reasons given for suicidal behaviour: interpersonal and relationship problems, financial and economic difficulties, mental health conditions and religious and cultural influences. These reasons were observed to be interrelated with each other and well-aligned to the suggested recommendations for suicide prevention. We found six key recommendations from our thematic content analysis: (a) increasing access to counselling and social support, (b) improving mental health awareness and skills training, (c) restriction of suicide means, (d) decriminalisation of suicide, (e) economic and education empowerment and (f) encouraging religion and spirituality. CONCLUSIONS: The reasons for suicidal behaviour are comparable with high-income countries, but suggested prevention strategies are more contextualised to our setting. A multifaceted approach in preventing suicide in (coastal) Kenya is warranted based on the varied reasons suggested. Community-based interventions will likely improve and increase access to suicide prevention in this study area.

Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults.

Childhood maltreatment (CM) and genetic vulnerability are both risk factors for psychosis, but the relations between them are not fully understood. Guided by the recent identification of genetic risk to CM, this study investigates the hypothesis that genetic risk to schizophrenia also increases the risk of CM and thus impacts psychosis risk. The relationship between schizophrenia polygenetic risk, CM, and psychotic-like experiences (PLE) was investigated in participants from the Utrecht Cannabis Cohort (N = 1262) and replicated in the independent IMAGEN cohort (N = 1740). Schizophrenia polygenic risk score (SZ-PRS) were calculated from the most recent GWAS. The relationship between CM, PRS, and PLE was first investigated using multivariate linear regression. Next, mediation of CM in the pathway linking SZ-PRS and PLE was examined by structural equation modeling, while adjusting for a set of potential mediators including cannabis use, smoking, and neuroticism. In agreement with previous studies, PLE were strongly associated with SZ-PRS (B = 0.190, p = 0.009) and CM (B = 0.575, p < 0.001). Novel was that CM was also significantly associated with SZ-PRS (B = 0.171, p = 0.001), and substantially mediated the effects of SZ-PRS on PLE (proportion mediated = 29.9%, p = 0.001). In the replication cohort, the analyses yielded similar results, confirming equally strong mediation by CM (proportion mediated = 34.7%, p = 0.009). Our results suggest that CM acts as a mediator in the causal pathway linking SZ-PRS and psychosis risk. These findings open new perspectives on the relations between genetic and environmental risks and warrant further studies into potential interventions to reduce psychosis risk in vulnerable people.

Suicidal attempts and ideations in Kenyan adults with psychotic disorders: An observational study of frequency and associated risk factors.

Background: Psychotic disorders increase the risk for premature mortality with up to 40% of this mortality attributable to suicide. Although suicidal ideation (SI) and suicidal behavior (SB) are high in persons with psychotic disorders in sub-Saharan Africa, there is limited data on the risk of suicide and associated factors among persons with psychotic disorders. Methods: We assessed SI and SB in persons with psychotic disorders, drawn from a large case-control study examining the genetics of psychotic disorders in a Kenyan population. Participants with psychotic disorders were identified using a clinical review of records, and the diagnosis was confirmed with the Mini-International Neuropsychiatric Interview (MINI). We conducted bivariate and multivariate logistic (for binary suicide outcomes) or linear regression (for suicide risk score) analysis for each of the suicide variables, with demographic and clinical variables as determinants. Results: Out of 619 participants, any current SI or lifetime suicidal attempts was reported by 203 (32.8%) with psychotic disorders, of which 181 (29.2%) had a lifetime suicidal attempt, 60 (9.7%) had SI in the past month, and 38 (20.9%) had both. Family history of suicidality was significantly associated with an increased risk of suicidality across all the following four outcomes: SI [OR = 2.56 (95% CI: 1.34-4.88)], suicidal attempts [OR = 2.01 (95% CI: 1.31-3.06)], SI and SB [OR = 2.00 (95% CI: 1.31-3.04)], and suicide risk score [beta coefficient = 7.04 (2.72; 11.36), p = 0.001]. Compared to persons aged <25 years, there were reduced odds for SI for persons aged ≥ 25 years [OR = 0.30 (95% CI: 0.14-0.62)] and ≥ 45 years [OR = 0.32 (95% CI: 0.12-0.89)]. The number of negative life events experienced increased the risk of SI and SB [OR = 2.91 (95% CI: 1.43-5.94)] for 4 or more life events. Higher negative symptoms were associated with more suicidal attempts [OR = 2.02 (95%CI: 1.15-3.54)]. Unemployment was also associated with an increased risk for suicidal attempts [OR = 1.58 (95%CI: 1.08-2.33)] and SI and SB [OR = 1.68 (95% CI: 1.15-2.46)]. Conclusion: Suicidal ideation and SB are common in persons with psychotic disorders in this African setting and are associated with sociodemographic factors, such as young age and unemployment, and clinical factors, such as family history of suicidality. Interventions targeted at the community (e.g., economic empowerment) or at increasing access to care and treatment for persons with psychotic disorders may reduce the risk of suicide in this vulnerable population group.

The immunologic etiology of psychiatric manifestations in systemic lupus erythematosus: A narrative review on the role of the blood brain barrier, antibodies, cytokines and chemokines.

INTRODUCTION: The aim of this narrative review is to provide an overview of the literature on the possible immunologic pathophysiology of psychiatric manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: A systematic search on PubMed was conducted. English studies with full text availability that investigated the correlation between blood-brain barrier (BBB) dysfunction, intrathecal synthesis of antibodies, antibodies, cytokines, chemokines, metalloproteinases, complement and psychiatric NPSLE manifestations in adults were included. RESULTS: Both transient BBB-dysfunction with consequent access of antibodies to the cerebrospinal fluid (CSF) and intrathecal synthesis of antibodies could occur in psychiatric NPSLE. Anti-phospholipid antibodies, anti-NMDA antibodies and anti-ribosomal protein p antibodies seem to mediate concentration dependent neuronal dysfunction. Interferon-α may induce microglial engulfment of neurons, direct neuronal damage and production of cytokines and chemokines in psychiatric NPSLE. Several cytokines, chemokines and matrix metalloproteinase-9 may contribute to the pathophysiology of psychiatric NPSLE by attracting and activating Th1-cells and B-cells. DISCUSSION: This potential pathophysiology may help understand NPSLE and may have implications for the diagnostic management and therapy of psychiatric NPSLE. However, the presented pathophysiological model is based on correlations between potential immunologic etiologies and psychiatric NPSLE that remain questionable. More research on this topic is necessary to further elucidate the pathophysiology of NPSLE.

Cannabinoids and psychotic symptoms: A potential role for a genetic variant in the P2X purinoceptor 7 (P2RX7) gene.

To investigate the biological mechanisms underlying the higher risk for psychosis in those that use cannabis, we conducted a genome-wide environment-interaction study (GWEIS). In a sample of individuals without a psychiatric disorder (N = 1262), we analyzed the interactions between regular cannabis use and genotype with psychotic-like experiences (PLE) as outcome. PLE were measured using the Community Assessment of Psychic Experiences (CAPE). The sample was enriched for those at the extremes of both cannabis use and PLE to increase power. A single nucleotide polymorphism in the P2RX7 gene (rs7958311) was associated with risk for a high level of psychotic experiences in regular cannabis users (p = 1.10 x10-7) and in those with high levels of lifetime cannabis use (p = 4.5 × 10-6). This interaction was replicated in individuals with high levels of lifetime cannabis use in the IMAGEN cohort (N = 1217, p = 0.020). Functional relevance of P2RX7 in cannabis users was suggested by in vitro experiments on activated monocytes. Exposure of these cells to tetrahydrocannabinol (THC) or cannabidiol (CBD) reduced the immunological response of the P2X7 receptor, which was dependent on the identified genetic variant. P2RX7 variants have been implicated in psychiatric disorders before and the P2X7 receptor is involved in pathways relevant to psychosis, such as neurotransmission, synaptic plasticity and immune regulation. We conclude that P2RX7 plays a role in vulnerability to develop psychotic symptoms when using cannabis and point to a new pathway that can potentially be targeted by newly developed P2X7 antagonists.

Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype.

Cannabis produces a broad range of acute, dose-dependent psychotropic effects. Only a limited number of neuroimaging studies have mapped these effects by examining the impact of cannabis on resting state brain neurophysiology. Moreover, how genetic variation influences the acute effects of cannabis on resting state brain function is unknown. Here we investigated the acute effects of ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on resting state brain neurophysiology, and their modulation by catechol-methyl-transferase (COMT) Val158Met genotype. Thirty-nine healthy volunteers participated in a pharmacological MRI study, where we applied Arterial Spin Labelling (ASL) to measure perfusion and functional MRI to assess resting state connectivity. THC increased perfusion in bilateral insula, medial superior frontal cortex, and left middle orbital frontal gyrus. This latter brain area showed significantly decreased connectivity with the precuneus after THC administration. THC effects on perfusion in the left insula were significantly related to subjective changes in perception and relaxation. These findings indicate that THC enhances metabolism and thus neural activity in the salience network. Furthermore, results suggest that recruitment of brain areas within this network is involved in the acute effects of THC. Resting state perfusion was modulated by COMT genotype, indicated by a significant interaction effect between drug and genotype on perfusion in the executive network, with increased perfusion after THC in Val/Met heterozygotes only. This finding suggests that prefrontal dopamine levels are involved in the susceptibility to acute effects of cannabis.

Liprin alfa 2 gene expression is increased by cannabis use and associated with neuropsychological function.

The relation of heavy cannabis use with decreased neuropsychological function has frequently been described but the underlying biological mechanisms are still largely unknown. This study investigates the relation of cannabis use with genome wide gene expression and subsequently examines the relations with neuropsychological function. Genome-wide gene expression in whole blood was compared between heavy cannabis users (N = 90) and cannabis naïve participants (N = 100) that were matched for psychotic like experiences. The results were validated using quantitative real-time PCR. Psychotic like experiences were assessed using the Comprehensive Assessment of Psychotic Experiences (CAPE). Neuropsychological function was estimated using four subtasks of the Wechsler Adult Intelligence Scale (WAIS). Subsequent in vitro studies in monocytes and a neuroblastoma cell line investigated expression changes in response to two major psychotropic components of cannabis; tetrahydrocannabinol (THC) and cannabidiol (CBD). mRNA expression of Protein Tyrosine Phosphatase Receptor Type F Polypeptide-Interacting-Protein Alpha-2 (PPFIA2) was significantly higher in cannabis users (LogFold Change 0.17) and confirmed by qPCR analysis. PPFIA2 expression level was negatively correlated with estimated intelligence (B=-22.9, p = 0.002) also in the 100 non-users (B=-28.5, p = 0.037). In vitro exposure of monocytes to CBD led to significant increase in PPFIA2 expression. However, exposure of monocytes to THC and neuroblastoma cells to THC or CBD did not change PPFIA2 expression. Change in PPFIA2 gene expression in response to cannabinoids is a putative mechanism by which cannabis could influence neuropsychological functions. The findings warrant further exploration of the role of PPFIA2 in cannabis induced changes of neuropsychological function, particularly in relation to CBD.

Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole.

UNLABELLED: In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs. LEARNING POINTS: Prolactinoma coinciding with psychosis can represent a therapeutic challenge.In contrast to many other antipsychotic drugs, aripiprazole is associated with a decrease in prolactin levels.Aripiprazole can be a valuable pharmaceutical tool to treat both prolactinoma and psychosis.

Does assessment type matter? A measurement invariance analysis of online and paper and pencil assessment of the Community Assessment of Psychic Experiences (CAPE).

BACKGROUND: The psychometric properties of an online test are not necessarily identical to its paper and pencil original. The aim of this study is to test whether the factor structure of the Community Assessment of Psychic Experiences (CAPE) is measurement invariant with respect to online vs. paper and pencil assessment. METHOD: The factor structure of CAPE items assessed by paper and pencil (N = 796) was compared with the factor structure of CAPE items assessed by the Internet (N = 21,590) using formal tests for Measurement Invariance (MI). The effect size was calculated by estimating the Signed Item Difference in the Sample (SIDS) index and the Signed Test Difference in the Sample (STDS) for a hypothetical subject who scores 2 standard deviations above average on the latent dimensions. RESULTS: The more restricted Metric Invariance model showed a significantly worse fit compared to the less restricted Configural Invariance model (χ(2)(23) = 152.75, p<0.001). However, the SIDS indices appear to be small, with an average of -0.11. A STDS of -4.80 indicates that Internet sample members who score 2 standard deviations above average would be expected to score 4.80 points lower on the CAPE total scale (ranging from 42 to 114 points) than would members of the Paper sample with the same latent trait score. CONCLUSIONS: Our findings did not support measurement invariance with respect to assessment method. Because of the small effect sizes, the measurement differences between the online assessed CAPE and its paper and pencil original can be neglected without major consequences for research purposes. However, a person with a high vulnerability for psychotic symptoms would score 4.80 points lower on the total scale if the CAPE is assessed online compared to paper and pencil assessment. Therefore, for clinical purposes, one should be cautious with online assessment of the CAPE.

A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes.

Despite large-scale genome-wide association studies (GWAS), the underlying genes for schizophrenia are largely unknown. Additional approaches are therefore required to identify the genetic background of this disorder. Here we report findings from a large gene expression study in peripheral blood of schizophrenia patients and controls. We applied a systems biology approach to genome-wide expression data from whole blood of 92 medicated and 29 antipsychotic-free schizophrenia patients and 118 healthy controls. We show that gene expression profiling in whole blood can identify twelve large gene co-expression modules associated with schizophrenia. Several of these disease related modules are likely to reflect expression changes due to antipsychotic medication. However, two of the disease modules could be replicated in an independent second data set involving antipsychotic-free patients and controls. One of these robustly defined disease modules is significantly enriched with brain-expressed genes and with genetic variants that were implicated in a GWAS study, which could imply a causal role in schizophrenia etiology. The most highly connected intramodular hub gene in this module (ABCF1), is located in, and regulated by the major histocompatibility (MHC) complex, which is intriguing in light of the fact that common allelic variants from the MHC region have been implicated in schizophrenia. This suggests that the MHC increases schizophrenia susceptibility via altered gene expression of regulatory genes in this network.

Treatment of unipolar psychotic depression: the use of evidence in practice guidelines.

INTRODUCTION: In a recent meta-analysis we found no evidence that an antidepressant plus an antipsychotic is more effective than an antidepressant alone in unipolar psychotic depression. However, most current guidelines recommend the combination over an antidepressant alone. METHOD: We assessed available guidelines by the AGREE instrument and discuss their recommendations in relation to the evidence as referred to in the guidelines. RESULTS: The UK-NICE guideline had the highest AGREE quality score, followed by the Dutch, Australian, and US-APA guidelines. Guidelines are not always consistent with at date of publication available evidence and (with exception of the UK-NICE and Dutch guidelines) also not with the in that guideline referred evidence. CONCLUSION: Physicians (and patients) should be aware that in guidelines treatment recommendations may be less evidence-based than asserted, even when treatment recommendations are stated as being based on the highest level of evidence.