Connecting loneliness with pathological personality traits: Evidence for genetic and environmental mediation from a study of older twins.

Loneliness has broad public health importance, especially in older adulthood, and there is some evidence suggesting it is associated with several personality disorders (PDs). The etiology of these PD-loneliness associations, however, has rarely been studied, especially in the context of the maladaptive traits of the DSM-5 alternative model of personality disorder (AMPD). To address these limitations, we estimated phenotypic, genetic, and unique environmental associations between loneliness and maladaptive personality traits in a sample of older adults from the Minnesota Twin Registry (n = 1,356, Mage = 70.4). Loneliness was moderately to strongly associated with each of the AMPD domains of negative affect, detachment, antagonism, disinhibition, and psychoticism (r = .22-.58), with evidence of both genetic (rg = .45-.75) and unique environmental (re = .10-.48) influences explaining the associations to varying degrees. We argue that loneliness may be an underappreciated concomitant of personality pathology, with PD traits perhaps underlying its development. Indeed, these findings suggest that loneliness may be a manifestation of the genetic and environmental forces that also lead to pathological personality variation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Common genetic and environmental risk for personality disorders and psychotic-like experiences in young adult twins.

INTRODUCTION: Psychotic-like experiences (PLE) have been associated with the subsequent emergence of psychotic disorders as well as several other domains of psychopathology. In this twin study, we estimated the genetic and environmental correlations between PLE and 10 personality disorders (PD). METHODS: Diagnoses of 10 PDs according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and PLE from the Composite International Diagnostic Interview (CIDI) were retrieved for 2793 young adult twins from the Norwegian Twin Registry. Risk for having a PD and PLEs was modeled using item response theory. Biometric twin models were fitted to estimate the genetic and environmental correlations between PDs and PLEs. Co-twin control analysis was performed to estimate additional within-family risk for PLEs when having a PD. RESULTS: Phenotypic overlap between PDs and PLEs ranged from 14% to 44% in males and from 11% to 39% in females, with the highest overlap for borderline PD in both sexes. In general, we found higher genetic correlations (r = 0.14-0.72) than environmental correlations (r = 0.06-0.28) between PDs and PLEs. The highest genetic correlations between PLE and PDs were found for borderline (r = 0.72), paranoid (r = 0.56), schizotypal (r = 0.56) and antisocial PD (r = 0.49). CONCLUSION: We found that the co-occurrence between PDs and PLE is the best explained by shared genetic determinants, with minor contributions from environmental factors. Interestingly, borderline PD was highly genetically correlated with PLE, warranting molecular genetic studies of this association.

Prevalence, Factor Structure, and Heritability of Avoidant Personality Disorder.

ABSTRACT: To review the community prevalence, factor structure, and heritability of avoidant personality disorder (AVPD), we reviewed the literature of empirical studies reported between years 1980 and 2020. Community point prevalence rates ranged from 0.8% to 5%, with one study of women older than 25 years finding a lifetime rate of 9.3%. A weighted point prevalence for studies involving both men and women was 3.3%. All factor analytic studies indicated a one factor solution. The themes were social inadequacy, feeling inferior, and fears of social rejection. Family studies of heritability for AVPD ranged from 0.18 to 0.56. Twin studies ranged from 0.28 to 0.71. The weighted average for heritability was 0.55. AVPD is an important clinical issue because it is prevalent in the community and has high morbidity and high heritability. Its single factor seems to suggest evaluation and treatment should be straightforward, but despite this, it tends to be underdiagnosed and undertreated.

Expanding the clinical and genetic spectrum of SQSTM1-related disorders in family with personality disorder and frontotemporal dementia.

Objective:SQSTM1-variants associated with frontotemporal lobar degeneration have been described recently. In this study, we investigated a heterozygous in-frame duplication c.436_462dup p. (Pro146_Cys154dup) in the SQSTM1 gene in a family with a new phenotype characterized by a personality disorder and behavioral variant frontotemporal dementia (bvFTD). We review the literature on frontotemporal dementia (FTD) associated with SQSTM1. Methods: The index case and relatives were described, and a genetic study through Whole Exome Sequencing was performed. The literature was reviewed using Medline and Web of Science. Case reports, case series, and cohort studies were included if they provided information on SQSTM1 mutations associated with FTD. Results: Our patient is a 70-year-old man with a personality disorder since youth, familial history of dementia, and personality disorders with a 10-year history of cognitive decline and behavioral disturbances. A diagnosis of probable bvFTD was established, and the in-frame duplication c.436_462dup in the SQSTM1 gene was identified. Segregation analysis in the family confirmed that both affected sons with personality disorder were heterozygous carriers, but not his healthy 65-year-old brother. A total of 14 publications about 57 patients with SQSTM1-related FTD were reviewed, in which the bvFTD subtype was the main phenotype described (66.6%), with a predominance in men (63%) and positive family history in 61.4% of the cases. Conclusions: We describe a heterozygous in-frame duplication c.436_462dup p.(Pro146_Cys154dup) in the SQSTM1 gene, which affects the zinc-finger domain of p62, in a family with a personality disorder and bvFTD, expanding the genetics and clinical phenotype related to SQSTM1.

"The Heidelberg Five" personality dimensions: Genome-wide associations, polygenic risk for neuroticism, and psychopathology 20 years after assessment.

HeiDE is a longitudinal population-based study that started in the 1990s and, at baseline, assessed an array of health-related personality questionnaires in 5133 individuals. Five latent personality dimensions (The Heidelberg Five) were identified and interpreted as Emotional Lability (ELAB), Lack of Behavioral Control (LBCN), Type A Behavior (TYAB), Locus of Control over Disease (LOCC), and Psychoticism (PSYC). At follow-up, 3268 HeiDE participants (post-QC) were genotyped on single nucleotide polymorphism (SNP) arrays. To further characterize The Heidelberg Five, we analyzed genomic underpinnings, their relations to the genetic basis of the Big Five trait Neuroticism, and longitudinal associations with psychiatric symptoms at follow-up. SNP-based heritability was significant for ELAB (34%) and LBCN (29%). A genome-wide association study for each personality dimension was conducted; only the phenotype PSYC yielded a genome-wide significant finding (p < 5 × 10-8 , top SNP rs138223660). Gene-based analyses identified significant findings for ELAB, TYAB, and PSYC. Polygenic risk scores for Neuroticism were only associated with ELAB. Each of The Heidelberg Five was related to depressive symptoms at follow-up. ELAB, LBCN, and PSYC were also associated with lifetime anxiety symptoms. These results highlight the clinical importance of health-related personality traits and identify LBCN as a heritable "executive function" personality trait.

Caffeine consumption, toxicity, tolerance and withdrawal; shared genetic influences with normative personality and personality disorder traits.

Our main aim was to estimate the extent of overlapping etiology between caffeine consumption and response and normative and pathological personality. Linear mixed-effects models were used to identify normative personality domains and personality disorder (PD) traits for inclusion in multivariate twin analyses together with individual caffeine related measures. Data were obtained from Norwegian adult twins in a face-to-face interview conducted in 1999-2004 as part of a population-based study of mental health and through self-report in 2010-2011 and 2015-2017. Personality disorder data was available for 2,793 twins, normative personality for 3,889 twins, and caffeine for 3,862 twins (mean age 43.0 years). Normative personality was assessed using the self-reported Big Five Inventory, PD traits were assessed by the Structured Interview for DSM-IV Personality, and caffeine consumption, toxicity, tolerance, and withdrawal were assessed through a self-report questionnaire developed at the Norwegian Institute of Public Health. Caffeine measures were found to be moderately heritable, h2 = 30.1%-45.0%. All normative personality domains and four PD traits, antisocial, borderline, dependent and paranoid, were significantly associated with at least one caffeine variable. A small proportion of variance in caffeine consumption was attributable to genetic factors shared with normative personality (1.3%) and personality disorders (11.4%). A modest proportion of variance in caffeine tolerance and toxicity was attributable to genetic factors shared with both normative personality (26.9%, 24.8%) and personality disorders (21.0%, 36.0%). The present study found caffeine consumption and response to be heritable and provides evidence that a small to-modest proportion of this genetic etiology is shared with both normative and pathological personality. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Coupling of autism genes to tissue-wide expression and dysfunction of synapse, calcium signalling and transcriptional regulation.

Autism Spectrum Disorder (ASD) is a heterogeneous disorder that is often accompanied with many co-morbidities. Recent genetic studies have identified various pathways from hundreds of candidate risk genes with varying levels of association to ASD. However, it is unknown which pathways are specific to the core symptoms or which are shared by the co-morbidities. We hypothesised that critical ASD candidates should appear widely across different scoring systems, and that comorbidity pathways should be constituted by genes expressed in the relevant tissues. We analysed the Simons Foundation for Autism Research Initiative (SFARI) database and four independently published scoring systems and identified 292 overlapping genes. We examined their mRNA expression using the Genotype-Tissue Expression (GTEx) database and validated protein expression levels using the human protein atlas (HPA) dataset. This led to clustering of the overlapping ASD genes into 2 groups; one with 91 genes primarily expressed in the central nervous system (CNS geneset) and another with 201 genes expressed in both CNS and peripheral tissues (CNS+PT geneset). Bioinformatic analyses showed a high enrichment of CNS development and synaptic transmission in the CNS geneset, and an enrichment of synapse, chromatin remodelling, gene regulation and endocrine signalling in the CNS+PT geneset. Calcium signalling and the glutamatergic synapse were found to be highly interconnected among pathways in the combined geneset. Our analyses demonstrate that 2/3 of ASD genes are expressed beyond the brain, which may impact peripheral function and involve in ASD co-morbidities, and relevant pathways may be explored for the treatment of ASD co-morbidities.

Internal and external validity of the brief version of the Multidimensional Personality Questionnaire: Exploratory structural equation modelling.

The present study used exploratory structural equation modelling (ESEM) to examine the theorized dimension structure of the brief version of the Multidimensional Personality Questionnaire (MPQ-BR) at the scale-level (i.e., 11 lower-order primary factors loading on four higher-order factors) and item-level (sets of 12 items loading on 11 lower-order primary factors). A total of 214 adults from the community addressed the MPQ-BR and the Behavioral Inhibition System (BIS)/Behavioral Approach System (BAS) scales. The findings revealed poor fit and poorly defined factors at the item-level alongside adequate fit and well-defined factors at the scale-level. The higher-order factors in the latter model were supported for external validity in terms of demonstrating the expected theoretical and empirical correlations with the scales of the BIS/BAS scales. Result related implications for professional application, as well as potential revisions of the MPQ-BF are illustrated.

Swiprosin-1/ EFhd2: from Immune Regulator to Personality and Brain Disorders.

BACKGROUND/AIMS: Swiprosin-1/ EF-hand domain 2 (EFhd2) is a Ca2+ sensor protein that plays an important role in the immune system. Its abundant expression in the brain, however, suggested also a role in neuronal circuits and behavior. METHODS: Here we review recent discoveries on the structure and molecular function, its role in immunity and its function in the brain regarding behavioral control and pathologies. RESULTS: While EFhd2 did not emerge as a vital protein for brain development, changes in its expression may nevertheless shape the adult behavioral repertoire significantly and contribute to adult personality traits. A defective function of EFhd2 may also render individuals more prone to the development of psychiatric disorders. Most prominently, EFhd2 proved to be a resilience factor protecting from fast establishment of drug addiction. Moreover, EFhd2 is critical for adult neurogenesis and as a modulator of monoaminergic systems. CONCLUSION: Dysregulated activity of EFhd2 is increasingly considered as a contributing factor for the development of numerous neurodegenerative disorders. Whether EFhd2 can be used as biomarker or in therapeutic approaches has to be addressed in future research.

The Longitudinal Israeli Study of Twins (LIST) Reaches Adolescence: Genetic and Environmental Pathways to Social, Personality and Moral Development.

The Longitudinal Israeli Study of Twins (LIST) focuses on the developmental, genetic and environmental contributions to individual differences in children's and adolescents' social behavior. Key variables have been empathy, prosocial behavior, temperament and values. Another major goal of LIST has been to study gene-environment correlations, mainly concerning parenting. LIST includes 1657 families of Hebrew-speaking Israeli twins who have participated at least once in the study. Children's environment and their development are assessed in a multivariate, multimethod fashion, including observed, parent-reported and self-reported data. The current article summarizes and updates recent findings from LIST. For example, LIST provided evidence for the heritability of human values with the youngest sample to date, and the first genetic investigation of adolescents' identity formation. Finally, future aims of LIST are discussed.

The Study of Personality Architecture and Dynamics (SPeADy): A Longitudinal and Extended Twin Family Study.

The Study of Personality Architecture and Dynamics (SPeADy) is a German research project that aims to investigate the sources of interindividual differences in intraindividual personality development. The main focus lies in the dynamic interplay between more stable core characteristics and more environmentally malleable surface characteristics, as well as between personality and life experiences over time. SPeADy includes a twin family study encompassing data from 1962 individuals (age: 14-94) of 682 families, including 570 complete twin pairs (plus 1 triplet set), 327 parents, 236 spouses and 145 children of twins. Data collection started in 2016 and data from the first wave are currently obtainable as open source. Available data comprise a broad range of personality variables, such as personality trait constructs, motives, interests, values, moral foundations, religiosity and self-related concepts. For the currently ongoing second wave of data collection, we added retrospective reports on major life events. Special features of this genetically informative study are the extended twin family data and its longitudinal design. Three assessment waves in 2 years' intervals are planned until 2022. In this article, we briefly describe the design and contents of the SPeADy twin family study as well as some recent findings, future plans and open science issues.

The Oslo University Adolescent and Young Adult Twin Project: Recruitment and Attrition.

The Oslo University Adolescent and Young Adult Twin Project started in 2006 with the first of three questionnaire data collection waves, 2 years apart. All twins from the birth cohorts 1988-1994 were invited to participate, and both the twins and their parents were asked to sign consent forms. The twins were 12-18 years old at Wave 1, at which time parents were asked to complete similar questionnaires. The parents' questionnaire enquired about the parents' ratings of their twin's traits. In addition, the parents answered questions regarding their own education, demographics and socioeconomic situation. When the twins were 18 years old, they were invited to a face-to-face interview and two new questionnaires were presented. The questionnaires for the waves included a number of personality scales, internalization and externalization traits, affective and behavioral problems, as well as measures of environment and coping. The most common DSM-IV mental disorders and all personality disorders were covered in the interview. Zygosity was established both by questionnaire and gene markers. The original sample consisted of 5374 twin families, and among these, 4668 pairs were alive and living in Norway. Of these, 2486 families (53.3%) consented to participate. Of these, again 1538 twin families (61.9%) actually participated in at least one wave and twins from 1422 pairs (57.3%) participated in the interview. Female gender, but not zygosity, predicted staying in the project. Moreover, having a planning, structured personality (being more conscientious, open to experience [i.e., curious and interested in learning], having higher resilience and better school habits) increased the chance of carrying on in the project. Interestingly, the attrition did not seem to bias the heritability estimates.

The structure of genetic and environmental influences on normative personality, abnormal personality traits, and personality disorder symptoms.

BACKGROUND: Can the structure of genetic and environmental influences on normative personality traits (NPTs), abnormal personality traits (APTs), and DSM-IV criteria for personality disorders (PD) fit a high or low congruence model positing, respectively, close or more limited etiologic continuity? METHOD: Exploratory factor analysis was applied to transformed correlation matrices from Cholesky twin decompositions obtained in OpenMx. In 2801 adult twins from the Norwegian Institute of Public Health Twin Panel, NPTs and APTs were assessed by self-report using the Big Five Inventory (BFI) and PID-5-Norwegian Brief Form (PID-5-NBF), respectively. PDs were assessed at interview using the Structured Interview for DSM-IV Personality (SIDP-IV). RESULTS: The best model yielded three genetic and three unique environmental factors. Genetic factors were dominated, respectively, by (i) high loadings on nearly all PDs and NPT/APT neuroticism and compulsivity, (ii) negative loadings on NPT agreeableness/conscientiousness and positive loadings on APT/PD measures of antisocial traits, and (iii) negative loadings on NPT extraversion and histrionic PD, and positive loadings on APT detachment and schizoid/avoidant PD. Unique environmental factors were dominated, by (i) high loadings on all PDs, (ii) high loadings on all APT dimensions and NPT neuroticism, and (iii) negative loadings on NPT extraversion and positive loadings on NPT detachment/avoidant PD. CONCLUSIONS: Two genetic and one environmental common factor were consistent with a high congruence model while one genetic and two environmental factors were more supportive of a low congruence model. The relationship between genetic and environmental influences on personality assessed by NPTs, APTs, and PDs is complex and does not fit easily into a low or high congruence model.

Relationships Among Avoidant Personality Disorder, Social Anxiety Disorder, and Normative Personality Traits: A Twin Study.

Avoidant personality disorder (AvPD) and social anxiety disorder (SAD) share risk factors to a substantial degree, and both are characterized by the experience of anxiety in social situations. The authors investigated whether these disorders are differentially related to the Big Five personality traits. They also examined the underlying genetic and environmental influences on these associations. A population-based sample of 1,761 female twins was interviewed at baseline, and 1,471 of these were re-interviewed 10 years later. Associations between AvPD, SAD, and personality traits were investigated with multivariate biometric analyses. The authors found that AvPD and SAD are differentially related to several personality traits at the phenotypic, genetic, and environmental level. The genetic and environmental liability to AvPD could be fully accounted for by the genetic and environmental factors influencing SAD and personality. The findings may increase current etiological understanding of these disorders and inform future classification and treatment efforts.

Personality characteristics below facets: A replication and meta-analysis of cross-rater agreement, rank-order stability, heritability, and utility of personality nuances.

Mõttus and colleagues (2017) reported evidence that the unique variance in specific personality characteristics captured by single descriptive items often displayed trait-like properties of cross-rater agreement, rank-order stability, and heritability. They suggested that the personality hierarchy should be extended below facets to incorporate these specific characteristics, called personality nuances. The present study attempted to replicate these findings, employing data from 6,287 individuals from 6 countries (Australia, Canada, Czech Republic, Denmark, Japan, and United States). The same personality measure-240-item Revised NEO Personality Inventory-and statistical procedures were used. The present findings closely replicated the original results. When the original and current results were meta-analyzed, the unique variance of nearly all items (i.e., items' scores residualized for all broader personality traits) showed statistically significant cross-rater agreement (median = .12) and rank-order stability over an average of 12 years (median = .24), and the unique variance of the majority of items had a significant heritable component (median = .14). These 3 item properties were intercorrelated, suggesting that items systematically differed in the degree of reflecting valid unique variance. Also, associations of items' unique variance with age, gender, and body mass index (BMI) replicated across samples and tracked with the original findings. Moreover, associations between item residuals and BMI obtained from one group of people allowed for a significant incremental prediction of BMI in an independent sample. Overall, these findings reinforce the hypotheses that nuances constitute the building blocks of the personality trait hierarchy, their properties are robust and they can be useful. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Genetically Informative Mediation Modeling Applied to Stressors and Personality-Disorder Traits in Etiology of Alcohol Use Disorder.

A statistical mediation model was developed within a twin design to investigate the etiology of alcohol use disorder (AUD). Unlike conventional statistical mediation models, this biometric mediation model can detect unobserved confounding. Using a sample of 1410 pairs of Norwegian twins, we investigated specific hypotheses that DSM-IV personality-disorder (PD) traits mediate effects of childhood stressful life events (SLEs) on AUD, and that adulthood SLEs mediate effects of PDs on AUD. Models including borderline PD traits indicated unobserved confounding in phenotypic path coefficients, whereas models including antisocial and impulsive traits did not. More than half of the observed effects of childhood SLEs on adulthood AUD were mediated by adulthood antisocial and impulsive traits. Effects of PD traits on AUD 5‒10 years later were direct rather than mediated by adulthood SLEs. The results and the general approach contribute to triangulation of developmental origins for complex behavioral disorders.

Joint factorial structure of psychopathology and personality.

BACKGROUND: Normative and pathological personality traits have rarely been integrated into a joint large-scale structural analysis with psychiatric disorders, although a recent study suggested they entail a common individual differences continuum. METHODS: We explored the joint factor structure of 11 psychiatric disorders, five personality-disorder trait domains (DSM-5 Section III), and five normative personality trait domains (the 'Big Five') in a population-based sample of 2796 Norwegian twins, aged 19‒46. RESULTS: Three factors could be interpreted: (i) a general risk factor for all psychopathology, (ii) a risk factor specific to internalizing disorders and traits, and (iii) a risk factor specific to externalizing disorders and traits. Heritability estimates for the three risk factor scores were 48% (95% CI 41‒54%), 35% (CI 28‒42%), and 37% (CI 31‒44%), respectively. All 11 disorders had uniform loadings on the general factor (congruence coefficient of 0.991 with uniformity). Ignoring sign and excluding the openness trait, this uniformity of factor loadings held for all the personality trait domains and all disorders (congruence 0.983). CONCLUSIONS: Based on our findings, future research should investigate joint etiologic and transdiagnostic models for normative and pathological personality and other psychopathology.

Genetics, personality and wellbeing. A twin study of traits, facets and life satisfaction.

Human wellbeing is influenced by personality traits, in particular neuroticism and extraversion. Little is known about which facets that drive these associations, and the role of genes and environments. Our aim was to identify personality facets that are important for life satisfaction, and to estimate the contribution of genetic and environmental factors in the association between personality and life satisfaction. Norwegian twins (N = 1,516, age 50-65, response rate 71%) responded to a personality instrument (NEO-PI-R) and the Satisfaction With Life Scale (SWLS). Regression analyses and biometric modeling were used to examine influences from personality traits and facets, and to estimate genetic and environmental contributions. Neuroticism and extraversion explained 24%, and personality facets accounted for 32% of the variance in life satisfaction. Four facets were particularly important; anxiety and depression in the neuroticism domain, and activity and positive emotions within extraversion. Heritability of life satisfaction was 0.31 (0.22-0.40), of which 65% was explained by personality-related genetic influences. The remaining genetic variance was unique to life satisfaction. The association between personality and life satisfaction is driven mainly by four, predominantly emotional, personality facets. Genetic factors play an important role in these associations, but influence life satisfaction also beyond the effects of personality.

Current Knowledge on Gene-Environment Interactions in Personality Disorders: an Update.

PURPOSE OF REVIEW: We review the existing literature on gene-environment interactions (G×E) and epigenetic changes primarily in borderline personality disorder (BPD) but also in antisocial, schizotypal, and avoidant personality disorders. RECENT FINDINGS: Research supports that susceptibility genes to BPD or its underlying traits may be expressed under certain environmental conditions such as physical or childhood sexual abuse. Epigenetic modifications of neurodevelopment- and stress-related genes are suggested to underlie the relationship between early life adversary and borderline personality disorder. Only limited studies have investigated the role of gene-environment interactions and epigenetic changes in the genesis of antisocial, schizotypal, and avoidant personality disorders. Considering the lack of pharmacological treatment for most personality disorders, the emerging evidence on the critical role of G×E and epigenetic changes in the genesis of personality disorders could help develop more biologically oriented therapeutic approaches. Future studies should explore the potential of this new therapeutic dimension.

Maladaptive personality traits and romantic relationship satisfaction: A monozygotic co-twin control analysis.

The recent inclusion of an alternative model for personality disorders in the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5; American Psychiatric Association, 2013a) highlights the importance of extreme variants of personality for psychopathology. The maladaptive personality traits described in the alternative model comprise 5 higher-order domains and 25 lower-order facets that capture pathological levels of personality. The present report adds to a growing body of research on the implications of maladaptive personality traits for functioning by demonstrating significant associations between each of the higher-order domains (Negative Affect, Detachment, Antagonism, Disinhibition, and Psychoticism) and most of the lower-order facets and lower romantic relationship satisfaction in a population-based sample of 284 monozygotic (MZ) adult twins. We further capitalized upon co-twin differences in levels of personality pathology in a causally informative approach, the MZ co-twin control study design. Co-twin control analyses indicated that higher levels of Negative Affect, Detachment, Disinhibition, and Psychoticism, as well as several lower-order facets, were associated with lower romantic relationship satisfaction even after accounting for the genetic and environmental factors shared by twins that confer liability toward personality pathology and psychosocial dysfunction. The present results lend support to the potentially causal implications of personality pathology for interpersonal functioning, even in a community sample unlikely to be evidencing clinical levels of pathology, by suggesting that extreme variants of personality, manifested by comparably extreme deviations in thinking, feeling, behaving, and interacting with others, may lead to impaired functioning in important domains. (PsycINFO Database Record