C. Robert Cloninger, MD, PhD is Director of the Anthropedia Institute, which is the research component of a non-profit working to promote health and well-being. He is Wallace Renard Professor Emeritus of Psychiatry, Genetics, and Psychological and Brain Sciences at Washington University in St. Louis.
Recent genomic, psychological, and developmental research shows that human personality is organiz... more Recent genomic, psychological, and developmental research shows that human personality is organized as a complex hierarchy that ascends from individual traits in many specific situations to multi-trait profiles in two domains that regulate emotional reactivity (temperament) or goals and values (character), and finally to three integrated temperament-character networks that regulate learning to maintain well-being in changing conditions. We carried out person-centered analyses of the components of subjective well-being (positive affect, negative affect, and life satisfaction) to personality in both adolescents (N = 1739) and adults (N = 897). Personality was considered at each level of its organization (trait, temperament or character profiles, and joint temperament-character networks). We show for the first time that negative affect and life satisfaction are dependent on the personality network for intentional self-control, whereas positive affect is dependent on the personality net...
Disorders of arousal (DOA) are Non-Rem Sleep (NREM) parasomnias that emerge from incomplete arous... more Disorders of arousal (DOA) are Non-Rem Sleep (NREM) parasomnias that emerge from incomplete arousal out of deep sleep and lead to a broad variety of emotional and motor behaviours. Increasing evidence supports the hypothesis that specific psychopathological traits contribute to the multifactorial origin of these phenomena. The aim of the current multicenter study was to compare the personality profile of children and adolescents with and without DOA using the Junior Temperament and Character Inventory (JTCI).We enrolled 36 patients with a diagnosis of DOA (mean age of 11 ± 3 years, 64% males), and 36 healthy age and gender matched control subjects (mean age of 11.2 ± 3.6, years, 67% males). Their parents completed the Paris Arousal Disorder Severity Scale (PADSS), the Sleep Disturbance Scale for Children (SDSC) and the JTCI.Patients with DOA reached significantly higher levels compared to their control group in total PADSS (p <.0001) and in total SDSC (p < 0.0001). They also d...
Objective(s) To fully understand the dynamics of Intimate Partner Violence (IPV) it is necessary ... more Objective(s) To fully understand the dynamics of Intimate Partner Violence (IPV) it is necessary to understand the role of personality. The current understanding of which personality characteristics are associated with IPV victimization is, however, far from comprehensive. Given this gap in the literature, our objective was to examine the associations between the dimensions of the psychobiological model of personality and psychopathological symptoms in women who had experienced IPV. Methods Using a case-control design, a group of women who had experienced IPV and who were living in shelters (n = 50) were compared to a group of control women who had not experienced IPV (n = 50). All women completed the Temperament and Character Inventory–Revised and the Brief Symptom Inventory. Results Victims of IPV showed significantly higher levels of Harm Avoidance and Self-Transcendence, and lower levels of Reward Dependence and Self-Directedness, than the non-IPV control group. Victims of IPV a...
The human brain’s resting-state functional connectivity (rsFC) provides stable trait-like measure... more The human brain’s resting-state functional connectivity (rsFC) provides stable trait-like measures of differences in the perceptual, cognitive, emotional, and social functioning of individuals. The rsFC of the prefrontal cortex is hypothesized to mediate a person’s rational self-government, as is also measured by personality, so we tested whether its connectivity networks account for vulnerability to psychosis and related personality configurations. Young adults were recruited as outpatients or controls from the same communities around psychiatric clinics. Healthy controls (n = 30) and clinically stable outpatients with bipolar disorder (n = 35) or schizophrenia (n = 27) were diagnosed by structured interviews, and then were assessed with standardized protocols of the Human Connectome Project. Data-driven clustering identified five groups of patients with distinct patterns of rsFC regardless of diagnosis. These groups were distinguished by rsFC networks that regulate specific biopsy...
Objective Personality can influence how we interpret and react to our day-to-day life circumstanc... more Objective Personality can influence how we interpret and react to our day-to-day life circumstances. Temperament and character are the primary dimensions of personality, and both are influenced genetically. Temperament represents our emotional core, while character reflects our goals and values as we develop through life. Research shows that where people live, their social, economic, and physical environment can influence attitudes and behaviors, and these have links to variations in personality traits. There are few studies that focus on Australian personality as temperament and character. Using an Australian general population sample, we examined the psychometric properties of the Temperament and Character Inventory (TCIR140) and investigated the associations between TCIR140 traits with both sociodemographic variables and measures of well-being. In addition, we investigated differences in temperament and character between our Australian general population sample and published resu...
IntroductionExtant studies have examined the effect of psychological characteristics on clinical ... more IntroductionExtant studies have examined the effect of psychological characteristics on clinical features that define behavior problems. The purpose of this study was to analyze the effects of temperament and character as both individual factors and complex profiles on behavior problems in a community sample of adolescents.MethodsBehavior problems and personality of 670 Korean high school students were measured with the Youth Self-Report (YSR) and Junior version of the Temperament and Character Inventory (JTCI). Stepwise regression analysis analyzed the effects of JTCI character and temperament traits on YSR Total, Internalizing and Externalizing subscale scores, and Profile Analysis examined differences of JTCI personality profiles among three latent YSR subscale profiles acquired from Latent Profile Analysis.ResultsSeven subscales of the JTCI explained 38% of the YSR total degree of behavior problems, and JTCI Novelty-Seeking and Harm-Avoidance were found to account for vulnerabil...
Personality disorder (PD) is the primary psychiatric illness observed in most patients with psych... more Personality disorder (PD) is the primary psychiatric illness observed in most patients with psychosocial complaints, particularly young adults. PD is present in one sixth of people in the general population and more than half of all psychiatric patients. Reliable diagnosis of PD can be made in routine clinical practice by brief assessment of two essential features of a person’s character—low
Person-centered medical care, bioethical concepts fundamentally based on the notion of the person... more Person-centered medical care, bioethical concepts fundamentally based on the notion of the person, discussions of the importance of the person in medical curricula, and the many chapters of this book focused on the person all require some reference to the nature of persons. What they are, what they do or do not do, and what it means to speak of persons in the context of medicine. This chapter defines what a person is. To give an idea of the complexity of the subject we start with a summary statement. A person is an embodied being, purposeful, thinking, feeling, emotional, capable of choosing, reflective, relational, responsible, very complex human individual of a certain personality and temperament, existing through time in a narrative sense, whose life in all spheres points both outward and inward and who does things. Each of these terms is a dynamic function, constantly changing, and requiring action on the part of the person to be maintained—although generally the maintenance is habitual and unmediated by thought.
Genome-wide association studies of human personality have been carried out, but transcription of ... more Genome-wide association studies of human personality have been carried out, but transcription of the whole genome has not been studied in relation to personality in humans. We collected genome-wide expression profiles of adults to characterize the regulation of expression and function in genes related to human personality. We devised an innovative multi-omic approach to network analysis to identify the key control elements and interactions in multi-modular networks. We identified sets of transcribed genes that were co-expressed in specific brain regions with genes known to be associated with personality. Then we identified the minimum networks for the co-localized genes using bioinformatic resources. Subjects were 459 adults from the Young Finns Study who completed the Temperament and Character Inventory and provided peripheral blood for genomic and transcriptomic analysis. We identified an extrinsic network of 45 regulatory genes from seed genes in brain regions involved in self-regulation of emotional reactivity to extracellular stimuli (e.g., self-regulation of anxiety) and an intrinsic network of 43 regulatory genes from seed genes in brain regions involved in self-regulation of interpretations of meaning (e.g., production of concepts and language). We discovered that interactions between the two networks were coordinated by a control hub of 3 miRNAs and 3 protein-coding genes shared by both. Interactions of the control hub with proteins and ncRNAs identified more than 100 genes that overlap directly with known personality-related genes and more than another 4000 genes that interact indirectly. We conclude that the six-gene hub is the crux of an integrative network that orchestrates information-transfer throughout a multi-modular system of over 4000 genes enriched in liquid-liquid-phase-separation (LLPS)-related RNAs, diverse transcription factors, and hominid-specific miRNAs and lncRNAs. Gene expression networks associated with human personality regulate neuronal plasticity, epigenesis, and adaptive functioning by the interactions of salience and meaning in self-awareness.
Additional file 1: Table S1. Correlations between the five lower order sub-scales that compose th... more Additional file 1: Table S1. Correlations between the five lower order sub-scales that compose the self-directedness (SD) scale of the temperament and character inventory (N = 2714). Table S2. Correlations between the five lower order sub-scales that compose the Cooperativeness (CO) scale of the temperament and character inventory (N = 2714). Table S3. Correlations between the three lower order sub-scales that compose the self-transcendence (ST) scale of the temperament and character inventory (N = 2714).
Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable disorders that share a signifi... more Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable disorders that share a significant proportion of common risk variation. Understanding the genetic factors underlying the specific symptoms of these disorders will be crucial for improving diagnosis, intervention and treatment. In case-control data consisting of 53,555 cases (20,129 BD, 33,426 SCZ) and 54,065 controls, we identified 114 genome-wide significant loci (GWS) when comparing all cases to controls, of which 41 represented novel findings. Two genome-wide significant loci were identified when comparing SCZ to BD and a third was found when directly incorporating functional information. Regional joint association identified a genomic region of overlapping association in BD and SCZ with disease-independent causal variants indicating a fourth region contributing to differences between these disorders. Regional SNP-heritability analyses demonstrated that the estimated heritability of BD based on the SCZ GWS regions...
Polygenic risk scores have shown great promise in predicting complex disease risk, and will becom... more Polygenic risk scores have shown great promise in predicting complex disease risk, and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves LD-pruning markers and applying a P-value threshold to association statistics, but this discards information and may reduce predictive accuracy. We introduce a new method, LDpred, which infers the posterior mean causal effect size of each marker using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the pruning/thresholding approach, particularly at large sample sizes. Accordingly, prediction R2 increased from 20.1% to 25.3% in a large schizophrenia data set and from 9.8% to 12.0% in a large multiple sclerosis data set. A similar relative improvement in accuracy was observed for three additional large disease data sets and when predicting in non-European schizophrenia samples. The advantage of LDpred ...
Regulatory and coding variants are known to be enriched with associations identified by genome-wi... more Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (hg(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg(2) from imputed SNPs (5.1× enrichment; p = 3.7 × 10(-17)) and 38% (SE = 4%) of hg(2) from genotyped SNPs (1.6× enrichment, p = 1...
This study explored the temporal limits of cognitive change from an intention-to-treat with group... more This study explored the temporal limits of cognitive change from an intention-to-treat with group music therapy. Elderly cognitively-impaired psychiatric inpatients (N = 28) participated in an 8-week randomized control trial using a crossover design. Once a week, subjects were assigned either to music therapy or a control treatment (age-appropriate movie). The Mini-Mental State Exam (MMSE) assessed cognition 3 times every week: prior to the intervention, immediately after the mid-afternoon intervention, and the morning following the intervention. Comparisons between conditions included weekly changes in individual subject&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s MMSE scores from weekly baseline to both the 2 follow-ups and the following week&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s baseline. Significant next morning improvements in MMSE scores were found within intent-to-treat music therapy cases as compared to control cases. While all the subjects in this study were cognitively impaired, only 17 had been formally diagnosed with dementia. Based on a Cochrane Collaboration suggestion that music therapy studies within geriatric populations look specifically at the treatment of dementia, a final generalized estimating equation model considered only the change within the 17 dementia-diagnosed subjects. Immediately after the intervention, MMSE scores in the dementia-diagnosed subjects assigned to music therapy improved 2.00 points compared to the dementia-diagnosed subjects assigned to the control group (Z = 1.99, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). Next-day MMSE test scores in the dementia-diagnosed subjects assigned to music therapy showed average improvements of 3.69 points compared to the control subjects (Z = 3.38, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). By the following week, no significant cognitive differences remained between the two groups. It was concluded that a reasonable music therapy intervention facilitated by a trained and accredited music therapist significantly improved next-morning cognitive functioning among dementia patients. With many music therapists working in geriatric settings, more research is justified to both replicate this study and provide better guidance into the effective use of music therapy in the treatment of dementia.
We examined the role of common genetic variation in schizophrenia in a genome-wide association st... more We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals a...
Recent genomic, psychological, and developmental research shows that human personality is organiz... more Recent genomic, psychological, and developmental research shows that human personality is organized as a complex hierarchy that ascends from individual traits in many specific situations to multi-trait profiles in two domains that regulate emotional reactivity (temperament) or goals and values (character), and finally to three integrated temperament-character networks that regulate learning to maintain well-being in changing conditions. We carried out person-centered analyses of the components of subjective well-being (positive affect, negative affect, and life satisfaction) to personality in both adolescents (N = 1739) and adults (N = 897). Personality was considered at each level of its organization (trait, temperament or character profiles, and joint temperament-character networks). We show for the first time that negative affect and life satisfaction are dependent on the personality network for intentional self-control, whereas positive affect is dependent on the personality net...
Disorders of arousal (DOA) are Non-Rem Sleep (NREM) parasomnias that emerge from incomplete arous... more Disorders of arousal (DOA) are Non-Rem Sleep (NREM) parasomnias that emerge from incomplete arousal out of deep sleep and lead to a broad variety of emotional and motor behaviours. Increasing evidence supports the hypothesis that specific psychopathological traits contribute to the multifactorial origin of these phenomena. The aim of the current multicenter study was to compare the personality profile of children and adolescents with and without DOA using the Junior Temperament and Character Inventory (JTCI).We enrolled 36 patients with a diagnosis of DOA (mean age of 11 ± 3 years, 64% males), and 36 healthy age and gender matched control subjects (mean age of 11.2 ± 3.6, years, 67% males). Their parents completed the Paris Arousal Disorder Severity Scale (PADSS), the Sleep Disturbance Scale for Children (SDSC) and the JTCI.Patients with DOA reached significantly higher levels compared to their control group in total PADSS (p <.0001) and in total SDSC (p < 0.0001). They also d...
Objective(s) To fully understand the dynamics of Intimate Partner Violence (IPV) it is necessary ... more Objective(s) To fully understand the dynamics of Intimate Partner Violence (IPV) it is necessary to understand the role of personality. The current understanding of which personality characteristics are associated with IPV victimization is, however, far from comprehensive. Given this gap in the literature, our objective was to examine the associations between the dimensions of the psychobiological model of personality and psychopathological symptoms in women who had experienced IPV. Methods Using a case-control design, a group of women who had experienced IPV and who were living in shelters (n = 50) were compared to a group of control women who had not experienced IPV (n = 50). All women completed the Temperament and Character Inventory–Revised and the Brief Symptom Inventory. Results Victims of IPV showed significantly higher levels of Harm Avoidance and Self-Transcendence, and lower levels of Reward Dependence and Self-Directedness, than the non-IPV control group. Victims of IPV a...
The human brain’s resting-state functional connectivity (rsFC) provides stable trait-like measure... more The human brain’s resting-state functional connectivity (rsFC) provides stable trait-like measures of differences in the perceptual, cognitive, emotional, and social functioning of individuals. The rsFC of the prefrontal cortex is hypothesized to mediate a person’s rational self-government, as is also measured by personality, so we tested whether its connectivity networks account for vulnerability to psychosis and related personality configurations. Young adults were recruited as outpatients or controls from the same communities around psychiatric clinics. Healthy controls (n = 30) and clinically stable outpatients with bipolar disorder (n = 35) or schizophrenia (n = 27) were diagnosed by structured interviews, and then were assessed with standardized protocols of the Human Connectome Project. Data-driven clustering identified five groups of patients with distinct patterns of rsFC regardless of diagnosis. These groups were distinguished by rsFC networks that regulate specific biopsy...
Objective Personality can influence how we interpret and react to our day-to-day life circumstanc... more Objective Personality can influence how we interpret and react to our day-to-day life circumstances. Temperament and character are the primary dimensions of personality, and both are influenced genetically. Temperament represents our emotional core, while character reflects our goals and values as we develop through life. Research shows that where people live, their social, economic, and physical environment can influence attitudes and behaviors, and these have links to variations in personality traits. There are few studies that focus on Australian personality as temperament and character. Using an Australian general population sample, we examined the psychometric properties of the Temperament and Character Inventory (TCIR140) and investigated the associations between TCIR140 traits with both sociodemographic variables and measures of well-being. In addition, we investigated differences in temperament and character between our Australian general population sample and published resu...
IntroductionExtant studies have examined the effect of psychological characteristics on clinical ... more IntroductionExtant studies have examined the effect of psychological characteristics on clinical features that define behavior problems. The purpose of this study was to analyze the effects of temperament and character as both individual factors and complex profiles on behavior problems in a community sample of adolescents.MethodsBehavior problems and personality of 670 Korean high school students were measured with the Youth Self-Report (YSR) and Junior version of the Temperament and Character Inventory (JTCI). Stepwise regression analysis analyzed the effects of JTCI character and temperament traits on YSR Total, Internalizing and Externalizing subscale scores, and Profile Analysis examined differences of JTCI personality profiles among three latent YSR subscale profiles acquired from Latent Profile Analysis.ResultsSeven subscales of the JTCI explained 38% of the YSR total degree of behavior problems, and JTCI Novelty-Seeking and Harm-Avoidance were found to account for vulnerabil...
Personality disorder (PD) is the primary psychiatric illness observed in most patients with psych... more Personality disorder (PD) is the primary psychiatric illness observed in most patients with psychosocial complaints, particularly young adults. PD is present in one sixth of people in the general population and more than half of all psychiatric patients. Reliable diagnosis of PD can be made in routine clinical practice by brief assessment of two essential features of a person’s character—low
Person-centered medical care, bioethical concepts fundamentally based on the notion of the person... more Person-centered medical care, bioethical concepts fundamentally based on the notion of the person, discussions of the importance of the person in medical curricula, and the many chapters of this book focused on the person all require some reference to the nature of persons. What they are, what they do or do not do, and what it means to speak of persons in the context of medicine. This chapter defines what a person is. To give an idea of the complexity of the subject we start with a summary statement. A person is an embodied being, purposeful, thinking, feeling, emotional, capable of choosing, reflective, relational, responsible, very complex human individual of a certain personality and temperament, existing through time in a narrative sense, whose life in all spheres points both outward and inward and who does things. Each of these terms is a dynamic function, constantly changing, and requiring action on the part of the person to be maintained—although generally the maintenance is habitual and unmediated by thought.
Genome-wide association studies of human personality have been carried out, but transcription of ... more Genome-wide association studies of human personality have been carried out, but transcription of the whole genome has not been studied in relation to personality in humans. We collected genome-wide expression profiles of adults to characterize the regulation of expression and function in genes related to human personality. We devised an innovative multi-omic approach to network analysis to identify the key control elements and interactions in multi-modular networks. We identified sets of transcribed genes that were co-expressed in specific brain regions with genes known to be associated with personality. Then we identified the minimum networks for the co-localized genes using bioinformatic resources. Subjects were 459 adults from the Young Finns Study who completed the Temperament and Character Inventory and provided peripheral blood for genomic and transcriptomic analysis. We identified an extrinsic network of 45 regulatory genes from seed genes in brain regions involved in self-regulation of emotional reactivity to extracellular stimuli (e.g., self-regulation of anxiety) and an intrinsic network of 43 regulatory genes from seed genes in brain regions involved in self-regulation of interpretations of meaning (e.g., production of concepts and language). We discovered that interactions between the two networks were coordinated by a control hub of 3 miRNAs and 3 protein-coding genes shared by both. Interactions of the control hub with proteins and ncRNAs identified more than 100 genes that overlap directly with known personality-related genes and more than another 4000 genes that interact indirectly. We conclude that the six-gene hub is the crux of an integrative network that orchestrates information-transfer throughout a multi-modular system of over 4000 genes enriched in liquid-liquid-phase-separation (LLPS)-related RNAs, diverse transcription factors, and hominid-specific miRNAs and lncRNAs. Gene expression networks associated with human personality regulate neuronal plasticity, epigenesis, and adaptive functioning by the interactions of salience and meaning in self-awareness.
Additional file 1: Table S1. Correlations between the five lower order sub-scales that compose th... more Additional file 1: Table S1. Correlations between the five lower order sub-scales that compose the self-directedness (SD) scale of the temperament and character inventory (N = 2714). Table S2. Correlations between the five lower order sub-scales that compose the Cooperativeness (CO) scale of the temperament and character inventory (N = 2714). Table S3. Correlations between the three lower order sub-scales that compose the self-transcendence (ST) scale of the temperament and character inventory (N = 2714).
Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable disorders that share a signifi... more Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable disorders that share a significant proportion of common risk variation. Understanding the genetic factors underlying the specific symptoms of these disorders will be crucial for improving diagnosis, intervention and treatment. In case-control data consisting of 53,555 cases (20,129 BD, 33,426 SCZ) and 54,065 controls, we identified 114 genome-wide significant loci (GWS) when comparing all cases to controls, of which 41 represented novel findings. Two genome-wide significant loci were identified when comparing SCZ to BD and a third was found when directly incorporating functional information. Regional joint association identified a genomic region of overlapping association in BD and SCZ with disease-independent causal variants indicating a fourth region contributing to differences between these disorders. Regional SNP-heritability analyses demonstrated that the estimated heritability of BD based on the SCZ GWS regions...
Polygenic risk scores have shown great promise in predicting complex disease risk, and will becom... more Polygenic risk scores have shown great promise in predicting complex disease risk, and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves LD-pruning markers and applying a P-value threshold to association statistics, but this discards information and may reduce predictive accuracy. We introduce a new method, LDpred, which infers the posterior mean causal effect size of each marker using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the pruning/thresholding approach, particularly at large sample sizes. Accordingly, prediction R2 increased from 20.1% to 25.3% in a large schizophrenia data set and from 9.8% to 12.0% in a large multiple sclerosis data set. A similar relative improvement in accuracy was observed for three additional large disease data sets and when predicting in non-European schizophrenia samples. The advantage of LDpred ...
Regulatory and coding variants are known to be enriched with associations identified by genome-wi... more Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (hg(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg(2) from imputed SNPs (5.1× enrichment; p = 3.7 × 10(-17)) and 38% (SE = 4%) of hg(2) from genotyped SNPs (1.6× enrichment, p = 1...
This study explored the temporal limits of cognitive change from an intention-to-treat with group... more This study explored the temporal limits of cognitive change from an intention-to-treat with group music therapy. Elderly cognitively-impaired psychiatric inpatients (N = 28) participated in an 8-week randomized control trial using a crossover design. Once a week, subjects were assigned either to music therapy or a control treatment (age-appropriate movie). The Mini-Mental State Exam (MMSE) assessed cognition 3 times every week: prior to the intervention, immediately after the mid-afternoon intervention, and the morning following the intervention. Comparisons between conditions included weekly changes in individual subject&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s MMSE scores from weekly baseline to both the 2 follow-ups and the following week&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s baseline. Significant next morning improvements in MMSE scores were found within intent-to-treat music therapy cases as compared to control cases. While all the subjects in this study were cognitively impaired, only 17 had been formally diagnosed with dementia. Based on a Cochrane Collaboration suggestion that music therapy studies within geriatric populations look specifically at the treatment of dementia, a final generalized estimating equation model considered only the change within the 17 dementia-diagnosed subjects. Immediately after the intervention, MMSE scores in the dementia-diagnosed subjects assigned to music therapy improved 2.00 points compared to the dementia-diagnosed subjects assigned to the control group (Z = 1.99, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). Next-day MMSE test scores in the dementia-diagnosed subjects assigned to music therapy showed average improvements of 3.69 points compared to the control subjects (Z = 3.38, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). By the following week, no significant cognitive differences remained between the two groups. It was concluded that a reasonable music therapy intervention facilitated by a trained and accredited music therapist significantly improved next-morning cognitive functioning among dementia patients. With many music therapists working in geriatric settings, more research is justified to both replicate this study and provide better guidance into the effective use of music therapy in the treatment of dementia.
We examined the role of common genetic variation in schizophrenia in a genome-wide association st... more We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals a...
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