C. Robert Cloninger

Common variants on chromosome 6p22.1 are associated with schizophrenia

Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5–1%, with high heritability (80–85%) and complex transmission. Recent studies implicate rare, large, high-penetrance copy number variants in some cases, but the genes or biological mechanisms that underlie susceptibility are not known. Here we show that schizophrenia is significantly associated with single nucleotide polymorphisms (SNPs) in the extended major histocompatibility complex region on chromosome 6. We carried out a genome-wide association study of common SNPs in the Molecular Genetics of Schizophrenia (MGS) case-control sample, and then a meta-analysis of data from the MGS, International Schizophrenia Consortium and SGENE data sets. No MGS finding achieved genome-wide statistical significance. In the meta-analysis of European-ancestry subjects (8,008 cases, 19,077 controls), significant association with schizophrenia was observed in a region of linkage disequilibrium on chromosome 6p22.1 (P = 9.54u2009×u200910-9). This region includes a histone gene cluster and several immunity-related genes—possibly implicating aetiological mechanisms involving chromatin modification, transcriptional regulation, autoimmunity and/or infection. These results demonstrate that common schizophrenia susceptibility alleles can be detected. The characterization of these signals will suggest important directions for research on susceptibility mechanisms.

Individual differences in personality traits reflect structural variance in specific brain regions.

Personality dimensions such as novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (PER) are said to be heritable, stable across time and dependent on genetic and neurobiological factors. Recently a better understanding of the relationship between personality traits and brain structures/systems has become possible due to advances in neuroimaging techniques. This Magnetic Resonance Imaging (MRI) study investigated if individual differences in these personality traits reflected structural variance in specific brain regions. A large sample of eighty five young adult participants completed the Three-dimensional Personality Questionnaire (TPQ) and had their brain imaged with MRI. A voxel-based correlation analysis was carried out between individuals personality trait scores and grey matter volume values extracted from 3D brain scans. NS correlated positively with grey matter volume in frontal and posterior cingulate regions. HA showed a negative correlation with grey matter volume in orbito-frontal, occipital and parietal structures. RD was negatively correlated with grey matter volume in the caudate nucleus and in the rectal frontal gyrus. PER showed a positive correlation with grey matter volume in the precuneus, paracentral lobule and parahippocampal gyrus. These results indicate that individual differences in the main personality dimensions of NS, HA, RD and PER, may reflect structural variance in specific brain areas.

Dimensional assessment of personality in an out-patient sample: Relations of the systems of Millon and Cloninger

The Cloninger Temperament and Character Inventory (TCI) and the Millon Clinical Multiaxial Inventory (MCMI-II) are both self-report inventories that can be used to assess personality reliably in clinical samples. Both instruments were administered to 103 consecutive psychiatric out-patients with or without personality disorders. The goals were to assess the convergent validity of the two instruments, to replicate the findings of Svrakic et al. (1993) Archives of General Psychiatry, 50, 991-999, about the differential diagnosis of Axis II disorders, and to analyse the relations of Millons measures of Axis I disorders with Cloningers measures. We observed a strong convergent validity between the instruments; the seven dimensions of the TCI accounted for most of the variance in MCMI-II measures of both Axis 1 and Axis 2 disorders. As reported by Svrakic et al. (1993) Archives of General Psychiatry, 50, 991-999, in in-patients, low self-directedness and low cooperativeness were confirmed to be the essential features of all personality disorders in out-patients. In addition, self-transcendence, the third of Cloningers character dimensions, was observed to be a strong correlate of severe Axis-1 psychopathology, including manic and delusional disorders.

The relationship between resilience and personality traits in doctors: implications for enhancing well being

Objective. The health and well being of medical doctors is vital to their longevity and safe practice. The concept of resilience is recognised as a key component of well being and is an important factor in medical training to help doctors learn to cope with challenge, stress, and adversity. This study examined the relationship of resilience to personality traits and resilience in doctors in order to identify the key traits that promote or impair resilience. Methods. A cross sectional cohort of 479 family practitioners in practice across Australia was studied. The Temperament and Character Inventory measured levels of the seven basic dimensions of personality and the Resilience Scale provided an overall measure of resilience. The associations between resilience and personality were examined by Pearson product-moment correlation coefficients, controlling for age and gender (α = 0.05 with an accompanying 95% confidence level) and multiple regression analyses. Results. Strong to medium positive correlations were found between Resilience and Self-directedness (r = .614, p < .01), Persistence (r = .498, p < .01), and Cooperativeness (r = .363, p < .01) and negative with Harm Avoidance (r = .−555, p < .01). Individual differences in personality explained 39% of the variance in resilience [F(7, 460) = 38.40, p < .001]. The three traits which contributed significantly to this variance were Self-directedness (β = .33, p < .001), Persistence (β = .22, p < .001) and Harm Avoidance (β = .19, p < .001). Conclusion. Resilience was associated with a personality trait pattern that is mature, responsible, optimistic, persevering, and cooperative. Findings support the inclusion of resilience as a component of optimal functioning and well being in doctors. Strategies for enhancing resilience should consider the key traits that drive or impair it.

Somatization Disorder: Psychologic Symptoms, Social Disability, and Diagnosis

Abstract The authors examined 50 outpatient women with somatization disorder (Briquets syndrome) and 25 control women with primary major depression. Somatizers had many psychologic symptoms besides physical complaints and were often misdiagnosed. The somatizers were more socially disabled than the controls, particularly at work and as parents. The authors also review the history of somatization disorder, recent literature on psychological symptoms of somatization disorder, and make recommendations on the management, classification, and diagnosis of somatization disorder.

Anticipation in schizophrenia: Biology or bias?

Anticipation is a genetic phenomenon wherein age of disease onset decreases and/ or severity increases in successive generations. Anticipation has been demonstrated for several neuropsychiatric disorders with expanding trinucleotide repeats recently identified as the underlying molecular mechanism. We report here the results of an analysis of anticipation performed with multiplex families segregating schizophrenia. Thirty-three families were identified through the NIMH Genetics Initiative that met the following criteria: had at least two affected members in successive generations and were not bilineal. Affectation diagnoses included schizophrenia, schizoaffective disorder-depressed, and psychosis NOS. Additional analyses included the Cluster A personality disorders. Three indices of age of onset were used. Disease severity was measured by several different indices. Four sampling schemes as suggested by McInnis et al. were tested, as well as additional analysis using pairs ascertained through the parental generation. Anticipation was demonstrated for age of onset, regardless of the index or sampling scheme used (P<0.05). Anticipation was not supported for disease severity. Analyses that took into account drug use and diminished fecundity did not affect the results. While the data strongly support intergenerational differences in disease onset consistent with anticipation, they must be viewed cautiously given unavoidable biases attending these analyses.

The role of temperament in the etiopathogenesis of bipolar spectrum illness

Bipolar disorder constitutes a challenge for clinicians in everyday clinical practice. Our knowledge concerning this clinical entity is incomplete, and contemporary classification systems are unable to reflect the complexity of this disorder. The concept of temperament, which was first described in antiquity, provides a helpful framework for synthesizing our knowledge on how the human body works and what determines human behavior. Although the concept of temperament originally included philosophical and sociocultural approaches, the biomedical model is dominant today. It is possible that specific temperaments might constitute vulnerability factors, determine the clinical picture, or modify the course of illness. Temperaments might even act as a bridge between genes and clinical manifestations, thus giving rise to the concept of the bipolar spectrum, with major implications for mental health research and treatment. More specifically, it has been reported that the hyperthymic and the depressive temperaments are related to the more classic bipolar disorder, whereas cyclothymic, anxious, and irritable temperaments are related to more complex manifestations and might predict poor response to treatment, violent or suicidal behavior, and high comorbidity. Incorporating of the concept of temperament and the bipolar spectrum into the standard training of psychiatric residents might well result in an improvement of everyday clinical practice.

Personality as an intermediate phenotype for genetic dissection of alcohol use disorder

Genetic and environmental interactive influences on predisposition to develop alcohol use disorder (AUD) account for the high heterogeneity among AUD patients and make research on the risk and resiliency factors complicated. Several attempts have been made to identify the genetic basis of AUD; however, only few genetic polymorphisms have consistently been associated with AUD. Intermediate phenotypes are expected to be in-between proxies of basic neuronal biological processes and nosological symptoms of AUD. Personality is likely to be a top candidate intermediate phenotype for the dissection of the genetic underpinnings of different subtypes of AUD. To date, 38 studies have investigated personality traits, commonly assessed by the Cloninger’s Tridimensional Personality Questionnaire (TPQ) or Temperament and Character Inventory (TCI), in relation to polymorphisms of candidate genes of neurotransmitter systems in alcohol-dependent patients. Particular attention has been given to the functional polymorphism of the serotonin transporter gene (5-HTTLPR), however, leading to contradictory results, whereas results with polymorphisms in other candidate monoaminergic genes (e.g., tryptophan hydroxylase, serotonin receptors, monoamine oxidases, dopamine receptors and transporter) are sparse. Only one genome-wide association study has been performed so far and identified the ABLIM1 gene of relevance for novelty seeking, harm avoidance and reward dependence in alcohol-dependent patients. Studies investigating genetic factors together with personality could help to define more homogenous subgroups of AUD patients and facilitate treatment strategies. This review also urges the scientific community to combine genetic data with psychobiological and environmental data to further dissect the link between personality and AUD.

Toward a Global Understanding of Students Who Participate in Rural Primary Care Longitudinal Integrated Clerkships: Considering Personality Across 2 Continents

PURPOSEnMedical schools worldwide have developed rural primary care immersive experiences to nurture students interest in future rural careers and address workforce shortages. Few studies have looked at the students who participate in these programs. This study explores personality traits in US and Australian students who undertake rural-focused medical training.nnnMETHODSnA cross-sectional cohort design used the Temperament and Character Inventory to identify levels of the 7 basic dimensions of personality. Data were collected in successive cohorts over 2007-2011. Multivariate analysis compared trait levels between groups and by demographic variables.nnnFINDINGSnThe majority of the 302 students (US-167; Australia-135) were female, aged 20-29 years and single. A greater proportion of US students reported being partnered, living longest in a small rural/remote community and having a rural background. Significant differences between groups were detected in several traits but effect sizes were small. The personality pattern of the combined sample indicates students with a mature and stable personality high in Self-Directedness, Persistence, and Cooperativeness. Rural background and marital status enhanced this pattern.nnnCONCLUSIONSnDespite coming from different educational and societal backgrounds, similar personality patterns are evident in US and Australian students who pursue rural medical education. Data provide support for a pattern of traits associated with a rural background and its predictive influence on interest in rural practice. Considering the international expansion of rural longitudinal integrated clerkships, understanding student attributes may assist in identifying strategies to enhance the rural workforce that are relevant across cultures and continents.

Rethinking registrar attributes for Australian rural general practice training

OBJECTIVEnDespite increases in Commonwealth funded general practice (GP) Registrar training positions, workforce trends continue to show geographical maldistribution. This study aimed to identify Registrar attributes which describe a cohort choosing to work in rural practice.nnnDESIGNnCross-sectional self-report questionnaire for socio-demographics, prior training, current training pathway, measures of personality and resilience.nnnPARTICIPANTS AND SETTINGnGP Registrars (N = 452) training in either the general or rural pathways of three Registered Training Providers in three states, or training through the Australian College of Rural and Remote Medicines independent pathway.nnnMAIN OUTCOME MEASUREnOrdinal logistic regression tested the impact of key variables on the likelihood that Registrars would settle in rural practice. Univariate analysis explored differences between groups and effects of variables.nnnRESULTSnA significantly increased interest in rural practice was to found to exist among registrars who were male, identified themselves as being rural, had a partner who identified as being rural, were enrolled in a rural training pathway and had high levels of Cooperativeness.nnnCONCLUSIONnWe present a discriminating model combining socio-demographics, prior training and personality variables which challenges Australia to rethink Registrar attributes when training for rural general practice. With significant changes about to occur to GP training in Australia, this paper highlights the need for a more holistic approach which considers personal attributes such as Cooperativeness, rural identity and provision of geographically focused rural training pipelines to encourage Registrars to bond to individual rural communities and further develop their personal connectedness to country life and rural medical practice.