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MotivationPolygenic risk score (PRS) methods based on genome-wide association studies (GWAS) have a potential for predicting the risk of developing complex diseases and are expected to become more accurate with larger training datasets... more
MotivationPolygenic risk score (PRS) methods based on genome-wide association studies (GWAS) have a potential for predicting the risk of developing complex diseases and are expected to become more accurate with larger training datasets and innovative statistical methods. The area under the ROC curve (AUC) is often used to evaluate the performance of PRSs, which requires individual genotypic and phenotypic data in an independent GWAS validation dataset. We are motivated to develop methods for approximating AUC of PRSs based on the summary level data of the validation dataset, which will greatly facilitate the development of PRS models for complex diseases.ResultsWe develop statistical methods and an R package SummaryAUC for approximating the AUC and its variance of a PRS when only the summary level data of the validation dataset are available. SummaryAUC can be applied to PRSs with SNPs either genotyped or imputed in the validation dataset. We examined the performance of SummaryAUC using a large-scale GWAS of schizophrenia. SummaryAUC provides accurate approximations to AUCs and their variances. The bias of AUC is typically <0.5% in most analyses. SummaryAUC cannot be applied to PRSs that use all SNPs in the genome because it is computationally prohibitive.Availability and implementation https://github.com/lsncibb/SummaryAUC.Supplementary information Supplementary data are available at Bioinformatics online.
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ABSTRACT In this paper, we explore the underlying dimensional structure of personality disorder, propose a novel approach to its diagnosis, and outline our concepts of its etiology and treatment based on the seven factor psychobiological... more
ABSTRACT In this paper, we explore the underlying dimensional structure of personality disorder, propose a novel approach to its diagnosis, and outline our concepts of its etiology and treatment based on the seven factor psychobiological model of temperament and character. Temperament and character traits were evaluated in a consecutive series of 109 psychiatric out-patients, with or without personality disorder and varying mood and anxiety states. Low scores on character dimensions consistently correlated with high symptom counts for personality disorder. Each subtype of personality disorder created a unique combination of correlations with the four temperament traits. Temperament and Character Inventory (TCI) temperament and character traits efficiently diagnose personality disorder and differentiate its individual subtypes. Character traits are used to diagnose the presence and the severity of personality disorder, whereas temperament traits are used for differential diagnosis. The distinction between temperament and character provides an attractive theoretical basis for etiological postulates and treatment of personality disorder.
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Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the... more
Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P &amp;amp;lt; .0001) and number of alleles per marker (9.2 vs. 8.4, P &amp;amp;lt; .0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P &amp;amp;lt; .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment.
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Research Interests: Philosophy and Hebrew
Specific personality traits have been proposed as a schizophrenia-related endophenotype and confirmed in siblings at risk for psychosis. The relationship of temperament and character with psychosis has not been previously investigated in... more
Specific personality traits have been proposed as a schizophrenia-related endophenotype and confirmed in siblings at risk for psychosis. The relationship of temperament and character with psychosis has not been previously investigated in Africa. The study was conducted in Kenya, and involved participants at clinical high-risk (CHR) for psychosis (n = 268) and controls (n = 251), aged 15–25 years. CHR status was estimated using the Structured Interview of Psychosis-Risk Syndromes (SIPS) and the Washington Early Psychosis Center Affectivity and Psychosis (WERCAP) Screen. Student’s t-tests were used to assess group differences on the Temperament and Character Inventory (TCI). Neurocognitive functioning, stress severity, and substance use were correlated with the TCI, correcting for psychosis severity. CHR participants were more impulsive (ie, higher novelty seeking [NS]) and asocial (ie, lower reward dependence) than controls. They were also more schizotypal (ie, high self-transcendenc...
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Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3)... more
Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are jointly organized and develop in an integrated manner. In three large independent genome-wide association studies from Finland, Germany, and Korea, we used a data-driven machine learning method to uncover joint...
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Human personality is 30-60% heritable according to twin and adoption studies. Hundreds of genetic variants are expected to influence its complex development, but few have been identified. We used a machine learning method for genome-wide... more
Human personality is 30-60% heritable according to twin and adoption studies. Hundreds of genetic variants are expected to influence its complex development, but few have been identified. We used a machine learning method for genome-wide association studies (GWAS) to uncover complex genotypic-phenotypic networks and environmental interactions. The Temperament and Character Inventory (TCI) measured the self-regulatory components of personality critical for health (i.e., the character traits of self-directedness, cooperativeness, and self-transcendence). In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified five clusters of people with distinct profiles of character traits regardless of genotype. Third, we found 42 SNP sets that identified 727 gene loci and were significantly associated with one or more of the character profiles...
Research Interests: Genetics, Psychology, Personality, Biology, Medicine, and 15 moreCardiovascular Risk, Molecular Psychiatry, Biological Sciences, Behavioural Genetics, Heritability, Regulatory Network, Association, Snp, Single Nucleotide Polymorphism, Depressive Symptoms, Medicine and Health Sciences, Psychiatry and Psychology, cooperativeness, Psychology and Cognitive Sciences, and Medical and Health Sciences
We studied the pattern of personality development in a longitudinal population-based sample of 752 American adolescents. Personality was assessed reliably with the Junior Temperament and Character Inventory at 12, 14, and 16 years of age.... more
We studied the pattern of personality development in a longitudinal population-based sample of 752 American adolescents. Personality was assessed reliably with the Junior Temperament and Character Inventory at 12, 14, and 16 years of age. The rank-order stability of Junior Temperament and Character Inventory traits from age 12 to 16 was moderate (r = .35). Hierarchical linear modeling of between-group variance due to gender and within-group variance due to age indicated that harm avoidance and persistence decreased whereas self-directedness and cooperativeness increased from age 12 to 16. Novelty seeking, reward dependence, and self-transcendence increased from age 12 to 14 and then decreased. This biphasic pattern suggests that prior to age 14 teens became more emancipated from adult authorities while identifying more with the emergent norms of their peers, and after age 14 their created identity was internalized. Girls were more self-directed and cooperative than boys and maintain...
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Objective: This study was conducted to compare the profile of temperament and character dimensions in patients with major depressive disorder and bipolar mood disorder with a control group. Method: In this causal-comparative study, the... more
Objective: This study was conducted to compare the profile of temperament and character dimensions in patients with major depressive disorder and bipolar mood disorder with a control group. Method: In this causal-comparative study, the population consisted of 2 clinical groups (major depressive disorder and bipolar mood disorder) and a non-clinical group. The sample was 193 individuals (77 patients with major depressive disorder, 86 patients with bipolar mood disorder, and 30 controls), with an age range of 18 to 65 years and the mean age of 40.1. They were selected from Roozbeh psychiatric hospital using available sampling method. Tools used in this research included Temperament and Character Inventory-140 and General Health Questionnaire-28. Collected data were analyzed by independent t test and one-way analysis of variance using Statistical Package for the Social Sciences-22 software. Results: The results revealed a significant difference among groups in dimensions of novelty see...
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It is unclear why some individuals reporting psychotic experiences have balanced lives while others go on to develop mental health problems. The objective of this study was to test if the personality traits of harm avoidance,... more
It is unclear why some individuals reporting psychotic experiences have balanced lives while others go on to develop mental health problems. The objective of this study was to test if the personality traits of harm avoidance, self-directedness, and self-transcendence can be used as criteria to differentiate healthy from unhealthy schizotypal individuals. We interviewed 115 participants who reported a high frequency of psychotic experiences. The instruments used were the Temperament and Character Inventory (140), Structured Clinical Interview for DSM-IV, and the Oxford-Liverpool Inventory of Feelings and Experiences. Harm avoidance predicted cognitive disorganization (β = 0.319; t = 2.94), while novelty seeking predicted bipolar disorder (β = 0.136, Exp [β] = 1.146) and impulsive non-conformity (β = 0.322; t = 3.55). Self-directedness predicted an overall decrease in schizotypy, most of all in cognitive disorganization (β = -0.356; t = -2.95) and in impulsive non-conformity (β = -0.3...
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The goal of this study was to investigate the utility of the Temperament and Character Inventory (TCI) in predicting antidepressant response to repetitive transcranial magnetic stimulation (rTMS). Although rTMS of the dorsolateral... more
The goal of this study was to investigate the utility of the Temperament and Character Inventory (TCI) in predicting antidepressant response to repetitive transcranial magnetic stimulation (rTMS). Although rTMS of the dorsolateral prefrontal cortex is an established antidepressant treatment, little is known about predictors of response. The TCI measures multiple personality dimensions (harm avoidance, novelty seeking, reward dependence, persistence, self-directedness, self-transcendence, and cooperativeness), some of which have predicted response to pharmacotherapy and cognitive-behavioral therapy. A previous study suggested a possible association between self-directedness and response to rTMS in melancholic depression, although this was limited by the fact that melancholic depression is associated with a limited range of TCI profiles. Nineteen patients with a major depressive episode completed the TCI before a clinical course of rTMS over the dorsolateral prefrontal cortex. Treatme...
Research Interests: Psychology, Transcranial Magnetic Stimulation, Medicine, Humans, Major Depressive Disorder, and 14 moreCharacter, Female, Male, Temperament, Clinical Sciences, Aged, Middle Aged, Adult, Harm Avoidance, Novelty Seeking, Temperament and Character Inventory (TCI), Personality Inventory, cooperativeness, and Outcome assessment (Health care)
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The heritability of schizophrenia and most personality traits has been well established, but the role of personality in susceptibility to schizophrenia remains uncertain. The aim of this study was to test for an association between... more
The heritability of schizophrenia and most personality traits has been well established, but the role of personality in susceptibility to schizophrenia remains uncertain. The aim of this study was to test for an association between personality traits and Neurological Soft Signs (NSS), a well-known biological marker of schizophrenia, in non-psychotic relatives of patients with schizophrenia. For this purpose, we evaluated the NSS scale and personality measured by the Temperament and Character inventory (TCI-R) in three groups of subjects: 29 patients with schizophrenia, 24 unaffected relatives and 37 controls. The results showed that patients with schizophrenia were more asocial (higher harm avoidance and lower reward dependence), more perseverative (higher persistence), and more schizotypal (lower self-directedness and cooperativeness, higher self-transcendence). The unaffected relatives showed higher harm avoidance, lower self-directedness and cooperativeness than the healthy contr...
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Research Interests: Mathematics, Computer Science, Schizophrenia, Diffusion Tensor Imaging, Medicine, and 15 moreAnisotropy, Diffusion MRI, Humans, Corpus Callosum, Female, Neuroimage, Male, Cluster Analysis, Middle Aged, Adult, Fractional Anisotropy, Fornix, internal capsule, Psychology and Cognitive Sciences, and Medical and Health Sciences
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A general theory of personality and its development is described in terms of four quantitative dimensions of temperament and three quantitative dimensions of character. The four temperament dimensions (harm avoidance, novelty seeking,... more
A general theory of personality and its development is described in terms of four quantitative dimensions of temperament and three quantitative dimensions of character. The four temperament dimensions (harm avoidance, novelty seeking, reward dependence, and persistence) are moderately heritable, moderately stable throughout life, and invariant despite sociocultural influences. The three character dimensions (self-directedness, cooperativeness, and self-transcendence) mature in a stepwise manner from early childhood throughout adulthood. Transitions between levels of maturity are nonlinear functions of temperament, specific genetic influences, social learning, and random life events. Personality development is quantitatively formulated in terms of nonlinear dynamics of a complex adaptive system. The psychosocial interpretation of personality as a fitness-optimizing process is described and illustrated in terms of available data about the development of different personality configura...
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Research Interests: Clinical Psychology, Personality, Personality Assessment, Medicine, Harm Reduction, and 15 moreHumans, Major Depressive Disorder, Female, Male, Beck Depression Inventory, Clinical Sciences, Comprehensive, Adult, Age Factors, Harm Avoidance, Neurosciences, Novelty Seeking, Psychiatric Status Rating Scales, Hamilton Depression Rating Scale, and cooperativeness
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Background: Drug addiction and alcoholism involve a complex etiopathogenesis with a variable degree of risk contributions from the host (person), environment, and addictive substances. In this work, temperament and character features of... more
Background: Drug addiction and alcoholism involve a complex etiopathogenesis with a variable degree of risk contributions from the host (person), environment, and addictive substances. In this work, temperament and character features of individuals addicted to opiates or alcohol are compared with normal controls to study personality factors in the overall risk for drug addiction. Methods: The study was done in a permissive environment, with easy access to alcohol and heroin, which facilitated analyses of personality factors in drug choice. Participants included 412 consecutive patients (312 opiate addicts, 100 alcohol addicts) treated at the Specialized Hospital for Chemical Dependency in Belgrade, Serbia, and a community sample of 346 controls. Results: Opiate addicts manifested antisocial temperament configuration (high Novelty Seeking, low Reward Dependence) coupled with high Self‐transcendence (ie, susceptibility to fantasy and imagination). Alcohol addicts manifested sensitive ...
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Research Interests: Genetics, Neuroscience, Psychology, Biology, Medicine, and 15 moreMolecular Psychiatry, Episodic Memory, Biological Sciences, Temperament, Heritability, Regulatory Network, Personality Traits, Association, Novelty, Snp, Single Nucleotide Polymorphism, Medicine and Health Sciences, Harm Avoidance, Psychology and Cognitive Sciences, and Medical and Health Sciences
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The Tridimensional Personality Questionnaire is a self-report personality inventory measuring three major personality dimensions: Novelty Seeking, Harm Avoidance, and Reward Dependence. Normative data, based on a U.S. national probability... more
The Tridimensional Personality Questionnaire is a self-report personality inventory measuring three major personality dimensions: Novelty Seeking, Harm Avoidance, and Reward Dependence. Normative data, based on a U.S. national probability sample of 1,019 adults, are presented and the psychometric properties of the questionnaire are discussed.
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Assessment of health status as a holistic approach to the whole person is being reintegrated in clinical medicine because of the pressing needs created by chronic diseases and needs for more effective preventive approaches. The need for... more
Assessment of health status as a holistic approach to the whole person is being reintegrated in clinical medicine because of the pressing needs created by chronic diseases and needs for more effective preventive approaches. The need for person-centered assessment has been recognized since ancient times and has been emphasized in the definition of health inscribed in the World Health Organization (WHO) constitution. As a result of the prevalence and burden of chronic disease, there is a strong need for models that highlight health restoration and enhance prevention, recovery, and wellbeing. Measures of health status such as Health-related Quality of Life (HRQOL) have been found to be consistent predictors of outcome and have also been linked to prevention of chronic diseases and to common risk factors. Unfortunately, these assessments have not been incorporated yet into regular clinical practice and care, and, as a result, chronic illnesses have become all too prevalent across the world. The Person-centered Integrative Diagnosis (PID) approach, embodying the vision of Person-centered Psychiatry and Medicine as expressed to a large extent in the various Geneva Declarations and proceedings of the International College of Person-centered Medicine (ICPCM) (http://www.personcenteredmedicine.org/), provides an overarching conceptual framework for an assessment of the health status in an integrated and dynamic manner converging on the person in context as the center and goal of care and public health.
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The NIMH Genetics Initiative is a multi-site collaborative study designed to create a national resource for genetic studies of complex neuropsychiatric disorders. Schizophrenia pedigrees have been collected at three sites: Washington... more
The NIMH Genetics Initiative is a multi-site collaborative study designed to create a national resource for genetic studies of complex neuropsychiatric disorders. Schizophrenia pedigrees have been collected at three sites: Washington University, Columbia University, and Harvard ...
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Research Interests: Psychology, Clinical Psychology, Psychiatry, Psychosis, Schizophrenia, and 15 moreRisk, Argentina, Medicine, Schizotypy, Population, Humans, Female, Male, Adult, Chi Square Distribution, Indigenous, Subclinical Infection, population groups, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Research Interests: Family, Biology, Medicine, Multidisciplinary, Linear models, and 15 moreComorbidity, Amyotrophic Lateral Sclerosis, Humans, Correlation, Journal Article, Odds ratio, Linkage Disequilibrium, European Continental Ancestry Group, Genetic Association, Genetics Research, Nature Communications, HUMAN MEDICINE, Case Control Studies, Cohort Studies, and Motor neuron disease
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Research Interests: Genetics, Mathematics, Computer Science, Psychiatry, Multiple sclerosis, and 15 moreSchizophrenia, Biology, Medicine, Biological Sciences, Humans, Disequilibrium, Phenotype, Genotype, Sample Size Determination, Prognosis, Linkage Disequilibrium, Quantitative Trait Loci, Pruning, polygenic risk score, and Medical and Health Sciences
Research Interests: Neuroscience, Psychology, Cognitive Science, Neuroimaging, Schizophrenia, and 15 morePolymorphism, Magnetic Resonance Imaging, Research Support, Endophenotypes, Brain, Humans, Journal Article, Nature Neuroscience, Heritability, Meta Analysis, Linkage Disequilibrium, Genetic Architecture, Neurosciences, Proof of Concept, and brain size
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Research Interests: Psychiatry, Psychosis, Biology, Risk, Medicine, and 15 moreGene expression, Biological Sciences, Brain, Humans, Childhood, Genome Wide Association Studies, Mouse, Association, Disorder, Genotype, Quantitative Trait Loci, Cognitive Deficits, HUMAN MEDICINE, Case Control Studies, and Medical and Health Sciences
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Our aim was to investigate the prevalence of resilience personality profiles in a sample of Swedish long‐term unemployed in relation to the general Swedish population. We found that only 1.50% (vs. 26% in the general population) in the... more
Our aim was to investigate the prevalence of resilience personality profiles in a sample of Swedish long‐term unemployed in relation to the general Swedish population. We found that only 1.50% (vs. 26% in the general population) in the long‐term unemployed sample had a resilient personality profile, that is, low in harm avoidance (e.g., relaxed and optimistic), high in persistence (e.g., hard‐working), and high in self‐directedness (i.e., goal‐oriented and resourceful).
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BackgroundPolygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies (GWASs). PGS methods differ in which DNA... more
BackgroundPolygenic scores (PGSs), which assess the genetic risk of individuals for a disease, are calculated as a weighted count of risk alleles identified in genome-wide association studies (GWASs). PGS methods differ in which DNA variants are included and the weights assigned to them; some require an independent tuning sample to help inform these choices. PGSs are evaluated in independent target cohorts with known disease status. Variability between target cohorts is observed in applications to real data sets, which could reflect a number of factors, e.g., phenotype definition or technical factors.MethodsThe Psychiatric Genomics Consortium working groups for schizophrenia (SCZ) and major depressive disorder (MDD) bring together many independently collected case- control cohorts. We used these resources (31K SCZ cases, 41K controls; 248K MDD cases, 563K controls) in repeated application of leave-one-cohort-out meta-analyses, each used to calculate and evaluate PGS in the left-out ...
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Global inequalities contribute to marked disparities in health and wellness of human populations. Many opportunities now exist to provide health care to all people in a person- and people-centered way that is effective, equitable, and... more
Global inequalities contribute to marked disparities in health and wellness of human populations. Many opportunities now exist to provide health care to all people in a person- and people-centered way that is effective, equitable, and sustainable. We review these opportunities and the scientific, historical, and philosophical considerations that form the basis for the International College of Person-centered Medicine’s 2014 Geneva Declaration on Person- and People-centered Integrated Health Care for All. Using consistent time-series data, we critically examine examples of universal healthcare systems in Chile, Spain, and Cuba.
In a person-centered approach to public health, people are recognized to have intrinsic dignity and are treated with respect to encourage their developing health and happiness. A person-centered approach supports the freedom and the responsibility to develop one’s life in ways that are personally meaningful and that are respectful of others and the environment in which we live together. Evidence suggests that health care organizations function well when they operate in a person-and people-centered way because that stimulates better coordination, cooperation, and social trust.
Health care coverage must be integrated at several interconnected levels in order to be effective, efficient, and fair. To reduce the burden of disease, integration is needed between the people seeking and delivering care, within the social network of each person, across the trajectory of each person’s life, among primary caregivers and specialists, and across multiple sectors of society. For integration to succeed across all these levels, it must foster common values and a shared vision of the future.
In a person-centered approach to public health, people are recognized to have intrinsic dignity and are treated with respect to encourage their developing health and happiness. A person-centered approach supports the freedom and the responsibility to develop one’s life in ways that are personally meaningful and that are respectful of others and the environment in which we live together. Evidence suggests that health care organizations function well when they operate in a person-and people-centered way because that stimulates better coordination, cooperation, and social trust.
Health care coverage must be integrated at several interconnected levels in order to be effective, efficient, and fair. To reduce the burden of disease, integration is needed between the people seeking and delivering care, within the social network of each person, across the trajectory of each person’s life, among primary caregivers and specialists, and across multiple sectors of society. For integration to succeed across all these levels, it must foster common values and a shared vision of the future.