Psychosis as an evolutionary adaptive mechanism to changing environments

__Background:__ From an evolutionary perspective it is remarkable that psychotic disorders, mostly occurring during fertile age and decreasing fecundity, maintain in the human population. __Aim:__ To argue the hypothesis that psychotic symptoms may not be viewed as an illness but as an adaptation phenomenon, which can become out of control due to different underlying brain vulnerabilities and external stressors, leading to social exclusion. __Methods:__ A literature study and analysis. __Results:__ Until now, biomedical research has not unravelld the definitive etiology of psychotic disorders. Findings are inconsistent and show non-specific brain anomalies and genetic variation with small effect sizes. However, compelling evidence was found for a relation between psychosis and stressful environmental factors, particularly those influencing social interaction. Psychotic symptoms may be explained as a natural defense mechanism or protective response to stressful environments. This is in line with the fact that psychotic symptoms most often develop during adolescence. In this phase of life, leaving the familiar, and safe home environment and building new social networks is one of the main tasks. This could cause symptoms of "hyperconsciousness" and calls on the capacity for social adaptation. __Conclusions:__ Psychotic symptoms may be considered as an evolutionary maintained phenomenon. Research investigating psychotic disorders may benefit from a focus on underlying general brain vulnerabilities or prevention of social exclusion, instead of psychotic symptoms

The beneficial effect of sulforaphane on platelet responsiveness during caloric load:a single-intake, double-blind, placebo-controlled, crossover trial in healthy participants

Background and aims: As our understanding of platelet activation in response to infections and/or inflammatory conditions is growing, it is becoming clearer that safe, yet efficacious, platelet-targeted phytochemicals could improve public health beyond the field of cardiovascular diseases. The phytonutrient sulforaphane shows promise for clinical use due to its effect on inflammatory pathways, favorable pharmacokinetic profile, and high bioavailability. The potential of sulforaphane to improve platelet functionality in impaired metabolic processes has however hardly been studied in humans. This study investigated the effects of broccoli sprout consumption, as a source of sulforaphane, on urinary 11-dehydro-thromboxane B2 (TXB2), a stable thromboxane metabolite used to monitor eicosanoid biosynthesis and response to antithrombotic therapy, in healthy participants exposed to caloric overload. Methods: In this double-blind, placebo-controlled, crossover trial 12 healthy participants were administered 16g of broccoli sprouts, or pea sprouts (placebo) followed by the standardized high-caloric drink PhenFlex given to challenge healthy homeostasis. Urine samples were collected during the study visits and analyzed for 11-dehydro-TXB2, sulforaphane and its metabolites. Genotyping was performed using Illumina GSA v3.0 DTCBooster. Results: Administration of broccoli sprouts before the caloric load reduced urinary 11-dehydro-TXB2 levels by 50% (p = 0.018). The amount of sulforaphane excreted in the urine during the study visits correlated negatively with 11-dehydro-TXB2 (rs = −0.377, p = 0.025). Participants carrying the polymorphic variant NAD(P)H dehydrogenase quinone 1 (NQO1*2) showed decreased excretion of sulforaphane (p = 0.035). Conclusion: Sulforaphane was shown to be effective in targeting platelet responsiveness after a single intake. Our results indicate an inverse causal relationship between sulforaphane and 11-dehydro-TXB2, which is unaffected by the concomitant intake of the metabolic challenge. 11-Dehydro-TXB2 shows promise as a non-invasive, sensitive, and suitable biomarker to investigate the effects of phytonutrients on platelet aggregation within hours. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT05146804].</p

Temperament and parental child-rearing style: unique contributions to clinical anxiety disorders in childhood

Both temperament and parental child-rearing style are found to be associated with childhood anxiety disorders in population studies. This study investigates the contribution of not only temperament but also parental child-rearing to clinical childhood anxiety disorders. It also investigates whether the contribution of temperament is moderated by child-rearing style, as is suggested by some studies in the general population. Fifty children were included (25 with anxiety disorders and 25 non-clinical controls). Child-rearing and the child’s temperament were assessed by means of parental questionnaire (Child Rearing Practices Report (CRPR) (Block in The Child-Rearing Practices Report. Institute of Human Development. University of California, Berkely, 1965; The Child-Rearing Practices Report (CRPR): a set of Q items for the description of parental socialisation attitudes and values. Unpublished manuscript. Institute of Human Development. University of California, Berkely, 1981), EAS Temperament Survey for Children (Boer and Westenberg in J Pers Assess 62:537–551, 1994; Buss and Plomin in Temperament: early developing personality traits. Lawrence Erlbaum Associates, Inc, Hillsdale, 1984s). Analysis of variance showed that anxiety-disordered children scored significantly higher on the temperamental characteristics emotionality and shyness than non-clinical control children. Hierarchical logistic regression analyses showed that temperament (emotionality and shyness) and child-rearing style (more parental negative affect, and less encouraging independence of the child) both accounted for a unique proportion of the variance of anxiety disorders. Preliminary results suggest that child-rearing style did not moderate the association between children’s temperament and childhood anxiety disorders. The limited sample size might have been underpowered to assess this interaction

Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor

Objective: The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights. Methods: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. Results: The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. Interpretation: This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.publishedVersionPeer reviewe

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMigraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.US National Institute of Neurological Disorders and Stroke (NINDS) of the US National Institutes of Health (NIH) Finnish innovation fund Sitra Finska Lakaresallskapet Academy of Finland Sigrid Juselius Foundation Academy of Finland Appeared in source as:Academy of Finland Center of Excellence in Complex Disease Genetics Finnish Foundation for Cardiovascular Research Novo Nordisk Foundation Novocure Limited CANDY foundation (CEHEAD) South-Eastern Norway Regional Health Authorit