Project description:Background: Personalized medicine is predicated on the notion that individual biochemical and genomic profiles are relatively constant in times of good health and to some extent predictive of disease or therapeutic response. We report a pilot study quantifying gene expression and methylation profile consistency over time, addressing the reasons for individual uniqueness, and its relation to N=1 phenotypes. Methods: Whole blood samples from 4 African American women, 4 Caucasian women, and 4 Caucasian men drawn from the Atlanta Center for Health Discovery and Well Being study at three successive 6-month intervals were profiled by RNASeq, miRNASeq, and Illumina Methyl-450 arrays. Standard regression approaches were used to evaluate the proportion of variance for each type of omic measure that is among individuals, and to quantify correlations among measures and with clinical attributes related to wellness. Results: Longitudinal omic profiles are in general highly consistent over time, with an average of 67% of the variance in transcript abundance, 42% of CpG methylation level (but 88% for the most differentiated CpG per gene), and 50% of miRNA abundance among individuals, which are all comparable to 74% of the variance among individuals for 74 clinical traits. One third of the variance can be attributed to differential blood cell type abundance, which is also fairly stable over time, and a lesser amount to eQTL effects, whereas seven conserved axes of covariance that capture diverse aspects of immune function explain over half of the variance. These axes also explain a considerable proportion of individually extreme transcript abundance, namely approximately 100 genes that are significantly up- or down-regulated in each person and are in some cases enriched for relevant gene activities that plausibly associate with clinical attributes. A similar fraction of genes have individually divergent methylation levels, but these do not overlap with the transcripts, and fewer than 20% of genes have significantly correlated methylation and gene expression. Conclusions: People express an “omic personality” consisting of peripheral blood transcriptional and epigenetic profiles that are constant over the course of a year and reflect various types of immune activity. Baseline genomic profiles can provide a window into the molecular basis of traits that might be useful for explaining medical conditions or guiding personalized health decisions. Whole blood samples from 12 subjects drawn from the Atlanta Center for Health Discovery and Well Being study at three successive 6-month intervals were profiled by RNASeq, miRNASeq, and Illumina Methyl-450 arrays.

Project description:The present study examined the association between personality pathology (PP) and alcohol dependence (AD; both lifetime and in the past 12 months) among middle-aged to older adults incorporating three sources of assessment, specifically, diagnostic interviews as well as self- and informant reports. We collected data from a representative sample of community participants (N = 1,630; ages 54-65 years) and their informants (N = 1,462). Measures employed were the substance use disorder sections of the Mini-International Neuropsychiatric Interview Schedule for Mental Disorders, the Structured Interview for DSM-IV Personality (American Psychiatric Association, 2000, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text rev.; DSM-IV-TR SIDP) and the NEO-Personality Inventory-Revised (Costa, P. T., & McCrae, R. R., Revised NEO-Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI) manual, 1992, Odessa, FL, Psychological Assessment Resources; self-report and informant versions). To complement the diagnostic interview for personality disorders (PDs), we utilized a PD-count technique derived from the five-factor model (FFM), which provided an index of PP liability. Factors representing lifetime and past-12 month AD were regressed on each of the 10 PP factors constructed from the SIDP interview, as well as self-report and informant FFM-count scores. Lifetime diagnosis of AD was positively associated with higher scores on several PP measures, including paranoid, schizotypal, antisocial, borderline, histrionic, and narcissistic PP. There was an inverse relation between lifetime AD and the factor score for obsessive-compulsive PP. With regard to AD in the past 12 months, antisocial, borderline, histrionic, and narcissistic PP factors were significantly associated with increased risk for AD, whereas the obsessive-compulsive and schizoid PP factors were associated with decreased risk for AD. The present data indicate that features of antisocial and borderline PP continue to exhibit a relatively strong association with risk for AD in later middle age.

Project description:BackgroundDespite the introduction of dimensional conceptualisations of personality functioning in the latest classification systems, such as Criterion A of the Alternative Model of Personality Disorders in the DSM-5, heterogeneous clinical presentation of personality pathology remains a challenge. Relatedly, the latent structure of personality pathology as assessed by the Semi-Structured Interview for Personality Functioning DSM-5 (STiP-5.1) has not yet been comprehensively examined in adolescents. Therefore, this study aimed to examine the latent structure of the STiP-5.1, and, based on those findings, to describe any unique clinical profiles that might emerge.MethodsThe final sample comprised 502 participants aged 11-18 years consecutively recruited from a specialised personality disorder outpatient service, as well as general day clinic and inpatient wards at the University Hospital University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Bern, Switzerland. Participants were assessed using the STiP-5.1, as well as a battery of other psychological measures by clinical psychologists or trained doctoral students. Variations of Factor Analysis, Latent Class Analysis and Factor Mixture Models (FMM) were applied to the STiP-5.1 to determine the most appropriate structure.ResultsThe best fitting model was an FMM comprising four-classes and two factors (corresponding to self- and interpersonal-functioning). The classes differed in both overall severity of personality functioning impairment, and in their scores and clinical relevance on each element of the STiP-5.1. When compared to the overall sample, classes differed in their unique clinical presentation: class 1 had low impairment, class 2 had impairments primarily in self-functioning with high depressivity, class 3 had mixed levels of impairment with emerging problems in identity and empathy, and class 4 had severe overall personality functioning impairment.ConclusionsA complex model incorporating both dimensional and categorical components most adequately describes the latent structure of the STiP-5.1 in our adolescent sample. We conclude that Criterion A provides clinically useful information beyond severity (as a dimensional continuum) alone, and that the hybrid model found for personality functioning in our sample warrants further attention. Findings can help to parse out clinical heterogeneity in personality pathology in adolescents, and help to inform early identification and intervention efforts.

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Understanding personality pathology in a clinical sample of youth: study protocol for the longitudinal research project 'APOLO'.

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