The cliff edge model of the evolution of schizophrenia: Mathematical, epidemiological, and genetic evidence.

How has schizophrenia, a condition that significantly reduces an individual's evolutionary fitness, remained common across generations and cultures? Numerous theories about the evolution of schizophrenia have been proposed, most of which are not consistent with modern epidemiological and genetic evidence. Here, we briefly review this evidence and explore the cliff edge model of schizophrenia. It suggests that schizophrenia is the extreme manifestation of a polygenic trait or a combination of traits that, within a normal range of variation, confer cognitive, linguistic, and/or social advantages. Only beyond a certain threshold, these traits precipitate the onset of schizophrenia and reduce fitness. We provide the first mathematical model of this qualitative concept and show that it requires only very weak positive selection of the underlying trait(s) to explain today's schizophrenia prevalence. This prediction, along with expectations about the effect size of schizophrenia risk alleles, are surprisingly well matched by empirical evidence. The cliff edge model predicts a dynamic change of selection of risk alleles, which explains the contradictory findings of evolutionary genetic studies.

Evolutionary perspectives on substance and behavioural addictions: Distinct and shared pathways to understanding, prediction and prevention.

Addiction poses significant social, health, and criminal issues. Its moderate heritability and early-life impact, affecting reproductive success, poses an evolutionary paradox: why are humans predisposed to addictive behaviours? This paper reviews biological and psychological mechanisms of substance and behavioural addictions, exploring evolutionary explanations for the origin and function of relevant systems. Ancestrally, addiction-related systems promoted fitness through reward-seeking, and possibly self-medication. Today, psychoactive substances disrupt these systems, leading individuals to neglect essential life goals for immediate satisfaction. Behavioural addictions (e.g. video games, social media) often emulate ancestrally beneficial behaviours, making them appealing yet often irrelevant to contemporary success. Evolutionary insights have implications for how addiction is criminalised and stigmatised, propose novel avenues for interventions, anticipate new sources of addiction from emerging technologies such as AI. The emerging potential of glucagon-like peptide 1 (GLP-1) agonists targeting obesity suggest the satiation system may be a natural counter to overactivation of the reward system.

The role of psychotic-like experiences in the association between aberrant salience and anxiety: A psychopathological proposal based on a case-control study.

AIM: Aberrant salience (AS) and psychotic-like experiences (PLEs) have been proven to be linked. Moreover, anxiety is a key symptom in psychosis-prone subjects and most psychotic patients. We propose a model that attempts to interpret the role of PLEs in the association between AS and anxiety among healthy controls and psychotic patients. METHODS: Demographic and psychometric data (Aberrant Salience Inventory, Community Assessment of Psychic Experiences, Symptom Check List-90-revised) from 163 controls and 44 psychotic patients was collected. Descriptive statistics, correlations, a linear regression model and a mediation analysis with covariates were subsequently performed. RESULTS: AS correlated with more frequent positive PLEs and higher anxiety levels in both patients and controls. However, positive PLEs' frequency mediated the relationship between AS and anxiety only among controls. CONCLUSIONS: PLEs linked to AS appear to induce anxiety among the control group but not among psychotic patients. The progressive loss of both novelty and insight, which may, respectively, impair the somatic emotional reactivity to PLEs and the ability to recognize some bodily phenomena as the embodied correlates of anxiety, is seen as the most probable theoretical explanation.

Behavior genetics: Causality as a dialectical pursuit.

The overarching theme of causality in behavioral genetics is discussed on epistemological grounds. Evidence is offered in favor of a continuum spectrum in causality, in contrast to discrimination between causal factors and associations. The risk of invalidating exploratory studies in behavior genetics is discussed, especially for the potential impact on those fields of medicine interested in complex behaviors.

Pregorexia: a systematic review and meta-analysis on the constructs of body image dissatisfaction and eating disturbances by gestational age in the peripartum.

PURPOSE: Pregorexia is a phenomenon posited to occur in the peripartum, characterized by an attempt to counter pregnancy's physiological changes in body shape through reduced calorie intake or increased physical activity. METHODS: In this pre-registered systematic review and meta-analysis, body image dissatisfaction and eating psychopathology in the peripartum according to gestational age were formally assessed. PubMed was searched up to May 2023. Selection criteria were represented by studies on body image concerns or eating psychopathology in the peripartum (up to 1 year after delivery). The population needed to include women from the general population or among patients with a history of (or current) eating disorder. For the meta-analysis, 17 studies were included: 10 for body image dissatisfaction (2625 individuals overall), 7 for eating behaviors (2551 individuals overall). The interplay between body image and the following themes was examined in depth: the adoption of breastfeeding, peripartum depression, sociocultural influences on body image, sexual disturbances, experiencing or reporting an altered food intake. RESULTS: Progressive dissatisfaction with body image during pregnancy by gestational age was observed, stably elevated for at least 12 months postpartum. Eating psychopathology was observed as elevated only at 12 months in the postpartum, but not during pregnancy. DISCUSSION: The current work offers normative values of body image satisfaction and eating psychopathology in the peripartum by gestational age. The relevance of current results was discussed, in order to inform both current clinical practice and future public policies. LEVEL OF EVIDENCE: Level I-Evidence obtained from: systematic reviews and meta-analyses.

Selective serotonin reuptake inhibitors, post-treatment sexual dysfunction and persistent genital arousal disorder: A systematic review.

PURPOSE: Adverse effects of selective serotonin reuptake inhibitors (SSRIs) on sexual function have been an important area of research for many years. However, the duration of SSRI-associated sexual adverse effects, and their possible persistence after treatment discontinuation, is still uncertain. The aims of the current systematic review were first to identify existing evidence of sexual dysfunction following SSRI discontinuation, and to provide an account of reported symptoms and proposed treatment options; and second, to establish whether current literature allows accurate estimates of the prevalence of such sexual dysfunction. METHODS: A systematic review was conducted on PubMed, Embase, and Google Scholar; papers with clinical data regarding patients with persistent sexual dysfunction after SSRI treatment suspension were included. RESULTS: Overall, two retrospective interventional studies, six observational studies and 11 case reports were judged eligible for inclusion. It was not possible to determine reliable estimates of prevalence. Similarly, a cause-effect relationship between SSRI exposure and persistent sexual impairment could not be ascertained. Nonetheless, the potential for continued sexual disturbances despite discontinuation could not be entirely ruled out. CONCLUSIONS: There is a need to investigate a possible dose-response relationship between SSRI exposure and persistent sexual adverse effects. Treatment options for persistent dysfunctions remain limited, but novel therapeutic approaches may be required in order to address an otherwise neglected need for sexual well-being.

Aberrant Salience Inventory: A meta-analysis to investigate its psychometric properties and identify screening cutoff scores.

INTRODUCTION: The Aberrant Salience Inventory (ASI) is a useful tool to measure salience abnormalities among the general population. There is strong clinical and scientific evidence that salience alteration is linked to psychosis. To the present day, no meta-analysis evaluating ASI's psychometric properties and screening potential has been published. MATERIALS AND METHODS: PubMed, Google Scholar, Scopus, and Embase were searched using terms including "psychosis," "schizophrenia," and "Aberrant Salience Inventory." Observational and experimental studies employing ASI on populations of non-psychotic controls and patients with psychosis were included. ASI scores and other demographic measures (age, gender, ethnicity) were extracted as outcomes. Individual patients' data (IPD) were collected. Exploratory factor analysis (EFA) was performed on the IPD. RESULTS: Eight articles were finally included in the meta-analysis. ASI scores differ significantly between psychotic and non-psychotic populations; a novel three-factor model is proposed regarding subscales structure. Theoretical positive predictive values (PPVs) and negative predictive values (NPVs) were calculated and presented together with different cutoff points depending on preselected specific populations of interest. DISCUSSION: PPV and NPV values reached levels adequate for ASI to be considered a viable screening tool for psychosis. The factor analysis highlights the presence of a novel subscale that was named "Unveiling experiences." Implications regarding the meaning of the new factor structure are discussed, as well as ASI's potential as a screening tool.

Emotional dysregulation, alexithymia and neuroticism: a systematic review on the genetic basis of a subset of psychological traits.

Neuroticism, alexithymia and emotion dysregulation are key traits and known risk factors for several psychiatric conditions. In this systematic review, the aim is to evaluate the genetic contribution to these psychological phenotypes. A systematic review of articles found in PubMed was conducted. Search terms included 'genetic', 'GWAS', 'neuroticism', 'alexithymia' and 'emotion dysregulation'. Risk of bias was assessed utilizing the STREGA checklist. Two hundred two papers were selected from existing literature based on the inclusion and exclusion criteria. Among these, 27 were genome-wide studies and 175 were genetic association studies. Single gene association studies focused on selected groups of genes, mostly involved in neurotransmission, with conflicting results. GWAS studies on neuroticism, on the other hand, found several relevant and replicated intergenic and intronic loci affecting the expression and regulation of crucial and well-known genes (such as DRD2 and CRHR1). Mutations in genes coding for trascriptional factors were also found to be associated with neuroticism (DCC, XKR6, TCF4, RBFOX1), as well as a noncoding regulatory RNA (LINC00461). On the other hand, little GWAS data are available on alexythima and emotional dysregulation.