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author:("Flory, canine")
1.  Context Processing in Schizotypal Personality Disorder: Evidence of Specificity of Impairment to the Schizophrenia Spectrum 
Journal of abnormal psychology  2008;117(2):342-354.
Working memory abnormalities, which are particularly pronounced on context processing tasks, appear relatively specific to schizophrenia spectrum illnesses compared with other psychotic disorders. However, the specificity of context processing deficits to schizotypal personality disorder (SPD), a prototype of schizophrenia, has not been studied. The authors administered 3 versions of the modified AX Continuous Performance Test and an N-back working memory test to 63 individuals with SPD and 25 with other personality disorders, as well as 42 healthy controls. For the AX Continuous Performance Test standard and degraded versions, there was a significant Trial Type × Delay × Group interaction, as SPDs made significantly more errors reflecting poor maintenance of context and fewer errors reflecting good maintenance of context. SPDs also demonstrated poor performance on the N-back, especially at the 2-back condition. Context processing errors and N-back accuracy scores were related to disorganization symptoms. These findings, which are quite similar to those previously reported in patients with schizophrenia, suggest that context processing deficits are specific to the schizophrenia spectrum and are not a reflection of overall psychopathology.
PMCID: PMC4176884  PMID: 18489210
schizotypal personality; context processing; cognition; schizophrenia spectrum; personality disorders
2.  Neural Correlates of Emotion Processing in Borderline Personality Disorder 
Psychiatry research  2009;172(3):192-199.
Emotional instability is a hallmark feature of borderline personality disorder (BPD), yet its biological underpinnings are poorly understood. We employed functional MRI to compare patterns of regional brain activation in BPD patients and healthy volunteers as they process positive and negative social emotional stimuli. fMRI images were acquired while 19 BPD patients and 17 healthy controls (HC) viewed emotion-inducing pictures from the IAPS set. Activation data were analyzed with SPM5 ANCOVA models to derive the effects of diagnosis and stimulus type. BPD patients demonstrated greater differences in activation than controls, when viewing negative pictures compared to rest, in the amygdala, fusiform gyrus, primary visual areas, superior temporal gyrus (STG), and premotor areas, while healthy controls showed greater differences than BPD’s in the insula, middle temporal gyrus and dorsolateral prefrontal cortex (BA46). When viewing positive pictures compared to rest, BPD patients showed greater differences in the STG, premotor cortex, and ventrolateral prefrontal cortex. These findings suggest that BPD patients show greater amygdala activity and heightened activity of visual processing regions than HC’s, when processing negative social emotional pictures compared to rest. They activate neural networks in emotion processing that are phylogenetically older and more reflexive than healthy controls.
PMCID: PMC4153735  PMID: 19394205
Affective Instability; Emotion; fMRI; Social-Emotional Cues; Borderline Personality Disorder
3.  Cigarette smoking and measures of impulsivity in a college sample 
An association between impulsivity and smoking has been consistently reported in the literature, but few studies have examined how distinct dimensions of impulsivity may relate differentially to smoking initiation versus persistent smoking. The aim of the current study was to examine the relationship between self-report and behavioral measures of impulsivity and smoking status in college students. Participants (n=243) completed a self-report history of tobacco use, two self-report measures of impulsivity (the Barratt Impulsiveness Scale and Zuckerman Sensation-Seeking Scale) and two behavioral measures (the Delay Discounting Task and Iowa Gambling Task). All participants were classified as never-smokers, triers, or smokers based on their smoking history, and between-group differences on the four measures were examined. On the self-report measures, all three groups differed on sensation seeking with the never-smokers reporting the lowest levels and the smokers reporting the highest. Furthermore, the smokers reported significantly higher disinhibitory impulsivity than the triers and never-smokers. The groups did not differ on the behavioral measures. Our results indicate that distinct dimensions of impulsivity characterize different smoking phenotypes. In particular, sensation seeking is associated with the initiation of smoking whereas disinhibitory impulsivity is associated with the transition to more persistent and regular use of cigarettes.
PMCID: PMC3711662  PMID: 23844956
delay discounting; disinhibition; impulsivity; reward seeking; tobacco use
4.  Polymorphic variation in the dopamine D4 receptor predicts delay discounting as a function of childhood socioeconomic status: evidence for differential susceptibility 
Inconsistent or null findings among studies associating behaviors on the externalizing spectrum—addictions, impulsivity, risk-taking, novelty-seeking traits—with presence of the 7-repeat allele of a common length polymorphism in the gene encoding the dopamine D4 receptor (DRD4) may stem from individuals’ variable exposures to prominent environmental moderators (gene × environment interaction). Here, we report that relative preference for immediate, smaller rewards over larger rewards delayed in time (delay discounting), a behavioral endophenotype of impulsive decision-making, varied by interaction of DRD4 genotype with childhood socioeconomic status (SES) among 546 mid-life community volunteers. Independent of age, sex, adulthood SES and IQ, participants who were both raised in families of distinctly low SES (low parental education and occupational grade) and carried the DRD4 7-repeat allele discounted future rewards more steeply than like-reared counterparts of alternate DRD4 genotype. In the absence of childhood socioeconomic disadvantage, however, participants carrying the 7-repeat allele discounted future rewards less steeply. This bidirectional association of DRD4 genotype with temporal discounting, conditioned by participants’ early life circumstances, accords with a recently proposed developmental model of gene × environment interaction (‘differential susceptibility’) that posits genetically modulated sensitivity to both adverse and salubrious environmental influences.
PMCID: PMC3682430  PMID: 22345368
gene–environment interaction; differential susceptibility; delay discounting; DRD4; childhood socioeconomic status; impulsivity
5.  The Brain-Derived Neurotrophic Factor Val66Met Polymorphism Moderates an Effect of Physical Activity on Working Memory Performance 
Psychological science  2013;24(9):1770-1779.
Physical activity enhances cognitive performance, yet individual variability in its effectiveness limits its widespread therapeutic application. Genetic differences might be one source of this variation. For example, carriers of the methionine-specifying (Met) allele of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism have reduced secretion of BDNF and poorer memory, yet physical activity increases BDNF levels. To determine whether the BDNF polymorphism moderated an association of physical activity with cognitive functioning among 1,032 midlife volunteers (mean age = 44.59 years), we evaluated participants’ performance on a battery of tests assessing memory, learning, and executive processes, and evaluated their physical activity with the Paffenbarger Physical Activity Questionnaire. BDNF genotype interacted robustly with physical activity to affect working memory, but not other areas of cognitive functioning. In particular, greater levels of physical activity offset a deleterious effect of the Met allele on working memory performance. These findings suggest that physical activity can modulate domain-specific genetic (BDNF) effects on cognition.
PMCID: PMC3947596  PMID: 23907543
BDNF; physical activity; working memory; executive function; genetics; visual memory; episodic memory
6.  Hostile Mood and Social Strain during Daily Life: A Test of the Transactional Model 
Hostility is a multidimensional construct related to cardiovascular (CV) disease risk. Daily hostile mood and social interactions may precipitate stress-related CV responses in hostile individuals.
Determine whether trait cognitive hostility best predicts daily hostile mood and social interactions relative to other trait hostility factors and explore the temporal links between these daily measures.
171 participants completed assessments of 4 trait hostility scales. Participants completed an electronic diary across 3 days, assessing current hostile mood and social interaction quality.
Multiple regression analyses revealed both affective and cognitive hostility to be significant predictors of daily hostile mood, and cognitive hostility alone to predict daily social strain. Additional analyses revealed previous social strain to predict elevated subsequent hostile mood.
Episodes of social strain may give rise to elevated hostile mood. Trait cognitive hostility may be an important factor in predicting daily social strain.
PMCID: PMC3508292  PMID: 22899302
hostility; hostile mood; social strain; transactional model
7.  Epigenetic Biomarkers as Predictors and Correlates of Symptom Improvement Following Psychotherapy in Combat Veterans with PTSD 
Epigenetic alterations offer promise as diagnostic or prognostic markers, but it is not known whether these measures associate with, or predict, clinical state. These questions were addressed in a pilot study with combat veterans with PTSD to determine whether cytosine methylation in promoter regions of the glucocorticoid related NR3C1 and FKBP51 genes would predict or associate with treatment outcome. Veterans with PTSD received prolonged exposure (PE) psychotherapy, yielding responders (n = 8), defined by no longer meeting diagnostic criteria for PTSD, and non-responders (n = 8). Blood samples were obtained at pre-treatment, after 12 weeks of psychotherapy (post-treatment), and after a 3-month follow-up. Methylation was examined in DNA extracted from lymphocytes. Measures reflecting glucocorticoid receptor (GR) activity were also obtained (i.e., plasma and 24 h-urinary cortisol, plasma ACTH, lymphocyte lysozyme IC50-DEX, and plasma neuropeptide-Y). Methylation of the GR gene (NR3C1) exon 1F promoter assessed at pre-treatment predicted treatment outcome, but was not significantly altered in responders or non-responders at post-treatment or follow-up. In contrast, methylation of the FKBP5 gene (FKBP51) exon 1 promoter region did not predict treatment response, but decreased in association with recovery. In a subset, a corresponding group difference in FKBP5 gene expression was observed, with responders showing higher gene expression at post-treatment than non-responders. Endocrine markers were also associated with the epigenetic markers. These preliminary observations require replication and validation. However, the results support research indicating that some glucocorticoid related genes are subject to environmental regulation throughout life. Moreover, psychotherapy constitutes a form of “environmental regulation” that may alter epigenetic state. Finally, the results further suggest that different genes may be associated with prognosis and symptom state, respectively.
PMCID: PMC3784793  PMID: 24098286
PTSD; veterans; epigenetics; methylation; promoter; glucocorticoid receptor; FK506 binding protein 5; psychotherapy
Preventive medicine  2012;54(0):229-233.
Background and Aims
Commuting by public transportation (PT) entails more physical activity and energy expenditure than by cars, but its biologic consequences are unknown.
In 2009-2010, we randomly sampled New York adults, usually commuting either by car (n=79) or PT (n=101). Measures comprised diet and physical activity questionnaires, weight and height, white blood cell (WBC) count, C reactive protein, (CRP) gene-specific methylation (IL-6), and global genomic DNA methylation (LINE-1 methylation).
Compared to the 101 PT commuters, the 79 car drivers were about 9 years older, 2 kg/m2 heavier, more often non-Hispanic whites, and ate more fruits and more meats. The 2005 guidelines for physical activity were met by more car drivers than PT users (78.5% vs. 65.0%). There were no differences in median levels of CRP (car vs. PT: 0.6 vs. 0.5 mg/dl), mean levels of WBC (car vs. PT: 6.7 vs. 6.5 cells/mm3), LINE-1 methylation (car vs. PT: 78.0% vs. 78.3%), and promoter methylation of IL-6 (car vs. PT: 56.1% vs. 58.0%).
PT users were younger and lighter than car drivers, but their commute mode did not translate into a lower inflammatory response or a higher DNA methylation, maybe because, overall, car drivers were more physically active.
PMCID: PMC3670595  PMID: 22313796
9.  Using Confirmatory Factor Analysis to Measure Contemporaneous Activation of Defined Neuronal Networks in Functional Magnetic Resonance Imaging 
Neuroimage  2012;60(4):1982-1991.
Functional neuroimaging often generates large amounts of data on regions of interest. Such data can be addressed effectively with a widely-used statistical technique based on measurement theory that has not yet been applied to neuroimaging. Confirmatory factor analysis is a convenient hypothesis-driven modeling environment that can be used to conduct formal statistical tests comparing alternative hypotheses regarding the elements of putative neuronal networks. In such models, measures of each activated region of interest are treated as indicators of an underlying latent construct that represents the contemporaneous activation of the elements in the network. As such, confirmatory factor analysis focuses analyses on the activation of hypothesized networks as a whole, improves statistical power by modeling measurement error, and provides a theory-based approach to data reduction with a robust statistical basis. This approach is illustrated using data on seven regions of interest in a hypothesized mesocorticostriatal reward system in a sample of 262 adult volunteers assessed during a card-guessing reward task. A latent construct reflecting contemporaneous activation of the reward system was found to be significantly associated with a latent construct measuring impulsivity, particularly in males.
PMCID: PMC3321108  PMID: 22348884
confirmatory factor analysis; functional neuroimaging; measurement theory; mesocorticostriatal reward system; impulsivity; sex differences
10.  Alcohol dependence, disinhibited behavior and variation in the prodynorphin gene 
Biological psychology  2011;88(1):51-56.
The results of the current analyses present preliminary evidence of an association between putatively functional variation in the prodynorphin (PDYN) gene and a dimensional measure of disinhibited behavior. A 68 bp sequence in the core promoter region of the PDYN gene was genotyped in a community sample of 1021 adults aged 30–54. Participants were interviewed for lifetime history of DSM-IV alcohol dependence and completed two self-report measures of sensation seeking and impulsiveness. Fifteen percent (n=151) of the sample met DSM-IV criteria for alcohol dependence and while results did not support an association between the PDYN polymorphism and the diagnosis of alcohol dependence, we did observe an association between the “low” expressing L allele of the PDYN gene and a preference for engaging in disinhibited behavior. Additionally, people who had both a history of alcohol dependence and higher scores on this Disinhibited Behavior scale were most likely to carry an L allele. These results indicate that variation in the PDYN gene is associated with a dimensional trait or intermediate phenotype that reflects a preference for heavy drinking and engaging in related risky behaviors (e.g., drug use, sexual activity).
PMCID: PMC3171516  PMID: 21736916
11.  Citalopram Improves Metabolic Risk Factors Among High Hostile Adults: Results of a Placebo-Controlled Intervention 
Psychoneuroendocrinology  2011;36(7):1070-1079.
Hostility is associated with a number of metabolic risk factors for cardiovascular disease, including waist-hip ratio, glucose, and triglycerides. Along with hostility, many of these measures have also been shown to be associated with reduced central serotonergic function. We have previously reported that a citalopram intervention was successful in reducing hostility by self-report assessment (Kamarck, et al., 2009). Here we examine the effects of this serotonergic intervention on metabolic risk factors in the same sample. 159 healthy adults with elevated hostility scores were randomized to citalopram or placebo for a 2-month period. Citalopram favorably changed metabolic risk factors, including waist circumference (p = .003), glucose (p=.02), HDL cholesterol (p= .04), triglycerides (p=.03), insulin sensitivity (p = .045) and diastolic blood pressure by automated assessment (p = .0021). All of these metabolic changes were significantly mediated by treatment-related changes in body mass index (in most cases, p < .01). In addition, the changes in blood glucose were significantly mediated by treatment-related changes in hostility (p < .05). Mechanisms accounting for these associations remain to be explored.
PMCID: PMC3118402  PMID: 21306829
hostility; citalopram; metabolic syndrome; randomized clinical trial; ssri; glucose
12.  Joint Effect of Childhood Abuse and Family History of Major Depressive Disorder on Rates of PTSD in People with Personality Disorders 
Objective. Childhood maltreatment and familial psychopathology both lead to an increased risk of the development of posttraumatic stress disorder (PTSD) in adulthood. While family history of psychopathology has traditionally been viewed as a proxy for genetic predisposition, such pathology can also contribute to a stress-laden environment for the child. Method. Analyses were conducted to evaluate the joint effect of childhood abuse and a family history of major depressive disorder (MDD) on diagnoses of PTSD and MDD in a sample of 225 adults with DSM-IV Axis II disorders. Results. Results showed that the rate of PTSD in the presence of both childhood abuse and MDD family history was almost six-fold (OR = 5.89, P = .001) higher relative to the absence of both factors. In contrast, the rate of MDD in the presence of both factors was associated with a nearly three-fold risk relative to the reference group (OR = 2.75, P = .01). Conclusions. The results from this observational study contribute to a growing understanding of predisposing factors for the development of PTSD and suggest that joint effects of family history of MDD and childhood abuse on PTSD are greater than either factor alone.
PMCID: PMC3335173  PMID: 22577531
13.  Reported Early Family Environment Covaries with Menarcheal Age as a Function of Polymorphic Variation in Estrogen Receptor-α (ESR1) 
Age at menarche, a sentinel index of pubertal maturation, was examined in relation to early family relationships (conflict, cohesion) and polymorphic variation in the gene encoding estrogen receptor-α (ESR1) in a midlife sample of 455 European American women. Consistent with prior literature, women who reported being raised in families characterized by close interpersonal relationships and little conflict tended to reach menarche at a later age than participants reared in families lacking cohesion and prone to discord. Moreover, this association was moderated by ESR1 variation, such that quality of the family environment covaried positively with menarcheal age among participants homozygous for minor alleles of the two ESR1 polymorphisms studied here (rs9304799, rs2234693), but not among women of other ESR1 genotypes. In addition, a) family relationship variables were unrelated to ESR1 variation, and b) genotype-dependent effects of childhood environment on age at menarche could not be accounted for by personality traits elsewhere shown to explain heritable variation in reported family conflict and cohesion. These findings are consistent with theories of differential susceptibility to environmental influence, as well as the more specific hypothesis (by Belsky) that girls differ genetically in their sensitivity to rearing effects on pubertal maturation.
PMCID: PMC3077552  PMID: 21262040
Pubertal Timing; Menarche; Family Environment; Estrogen Receptor-α; Gene-Environment Interaction; Differential Susceptibility
14.  Psychometric properties of a short form of the Affective Lability Scale (ALS-18) 
Psychometric properties of a short form of the Affective Lability Scale (ALS) that was developed in a nonclinical sample (i.e., undergraduate students) were examined in a sample of people diagnosed with Cluster B DSM-IV Axis II personality disorders (n=236), other personality disorders (n=180), and healthy comparison participants (n=164). The total score of the ALS-18 score correlated strongly with the original 54-item scale (r = .97) and aspects of convergent and discriminant validity of the ALS-18 subscales (Anxiety/Depression, Depression/Elation, and Anger) were evaluated using self-report measures of affective and psychosocial functioning in the domains of affect intensity, anxiety, anger, and minimization/denial. Clinical utility of the scale was also demonstrated; participants diagnosed with Cluster B personality disorders reported higher affective lability scores, and healthy control participants reported lower scores, relative to individuals with Cluster A or Cluster C personality disorders (p’s < .001). Confirmatory factor analyses were conducted and demonstrated reasonably good fit to the data but future research is needed to test the three factor substructure of the ALS-18 against alternative factor models in samples that include clinical and non-clinical participants.
PMCID: PMC2893358  PMID: 20606710
affective lability scale; affect dysregulation; cluster B personality
15.  Neural Correlates of Using Distancing to Regulate Emotional Responses to Social Situations 
Neuropsychologia  2010;48(6):1813-1822.
Cognitive reappraisal is a commonly used and highly adaptive strategy for emotion regulation that has been studied in healthy volunteers. Most studies to date have focused on forms of reappraisal that involve reinterpreting the meaning of stimuli and have intermixed social and non-social emotional stimuli. Here we examined the neural correlates of the regulation of negative emotion elicited by social situations using a less studied form of reappraisal known as distancing. Whole brain fMRI data were obtained as participants viewed aversive and neutral social scenes with instructions to either simply look at and respond naturally to the images or to downregulate their emotional responses by distancing. Three key findings were obtained accompanied with the reduced aversive response behaviorally. First, across both instruction types, aversive social images activated the amygdala. Second, across both image types, distancing activated the precuneus and posterior cingulate cortex (PCC), intraparietal sulci (IPS), and middle/superior temporal gyrus (M/STG). Third, when distancing one’s self from aversive images, activity increased in dorsal anterior cingulate (dACC), medial prefrontal cortex (mPFC), lateral prefrontal cortex, precuneus and PCC, IPS, and M/STG, meanwhile, and decreased in the amygdala. These findings demonstrate that distancing from aversive social cues modulates amygdala activity via engagement of networks implicated in social perception, perspective-taking, and attentional allocation.
PMCID: PMC2905649  PMID: 20226799
Emotion; Cognitive Reappraisal; Social Cognitive Neuroscience; Emotional Distancing; Emotion Regulation; fMRI
16.  Pergolide Treatment of Cognitive Deficits Associated with Schizotypal Personality Disorder: Continued Evidence of the Importance of the Dopamine System in the Schizophrenia Spectrum 
Neuropsychopharmacology  2010;35(6):1356-1362.
Cognitive deficits observed in schizophrenia are also frequently found in individuals with other schizophrenia spectrum disorders, such as schizotypal personality disorder (SPD). Dopamine appears to be a particularly important modulator of cognitive processes such as those impaired in schizophrenia spectrum disorders. In a double-blind, placebo-controlled clinical trial, we administered pergolide, a dopamine agonist targeting D1 and D2 receptors, to 25 participants with SPD and assessed the effect of pergolide treatment, as compared with placebo, on neuropsychological performance. We found that the pergolide group showed improvements in visual-spatial working memory, executive functioning, and verbal learning and memory. These results suggest that dopamine agonists may provide benefit for the cognitive abnormalities of schizophrenia spectrum disorders.
PMCID: PMC3055340  PMID: 20130535
schizotypal personality; schizotypy; schizophrenia spectrum; cognition; pergolide; dopamine; Schizophrenia/Antipsychotics; Dopamine; Cognition; Clinical Pharmacology/Trials; schizotypal personality; pergolide
17.  The Role of Genes in Defining a Molecular Biology of PTSD 
Disease markers  2011;30(2-3):67-76.
Because environmental exposure to trauma is the sine qua non for the development of Post Traumatic Stress Disorder (PTSD), the recent focus on genetic studies has been noteworthy. The main catalyst for such studies is the observation from epidemiological studies that not all trauma survivors develop this disorder. Furthermore, neuroendocrine findings suggest pre-existing hormonal alterations that confer risk for PTSD. This paper presents the rationale for examining genetic factors in PTSD and trauma exposure, but suggests that studies of genotype may only present a limited picture of the molecular biology of this disorder. We describe the type of information that can be obtained from candidate gene and genomic studies that incorporate environmental factors in the design (i.e., gene – environment interaction and gene-environment correlation studies) and studies that capitalize on the idea that environment modifies gene expression, via epigenetic or other molecular mechanisms. The examination of epigenetic mechanisms in tandem with gene expression will help refine models that explain how PTSD risk, pathophysiology, and recovery is mediated by the environment. Since inherited genetic variation may also influence the extent of epigenetic or gene expression changes resulting from the environment, such studies should optimally be followed up by studies of genotype.
PMCID: PMC3825239  PMID: 21508511
18.  Maternal Exposure to the Holocaust and Health Complaints in Offspring 
Disease markers  2011;30(2-3):133-139.
Although the link between chronic stress and the development of cardiovascular and metabolic diseases of adulthood has been known for some time, there is growing recognition that early environmental influences may result in developmental programming via epigenetic mechanisms, thereby affecting the developmental trajectory of disease progression. Previous studies support the idea that offspring of Holocaust survivors may have been subjected to early developmental programming. We evaluated the relationship between parental exposure to the Holocaust and self-reported health ratings and disorders made by their adult offspring (i.e., second generation Holocaust survivors). A total of 137 subjects were evaluated. Regression analyses demonstrated that maternal but not paternal exposure to the Holocaust was related to poorer subjective impressions of emotional and physical health. This relationship was diminished when the offspring’s own level of trait anxiety was considered. Offspring with maternal, but not paternal, Holocaust exposure also reported greater use of psychotropic and other medications, including medications for the treatment of hypertension and lipid disorders. The mechanism linking these health outcomes and maternal exposure deserves further investigation, including the possibility that fetal or early developmental programming is involved.
PMCID: PMC3825248  PMID: 21508517
19.  Subjective Socioeconomic Status and Presence of the Metabolic Syndrome in Midlife Community Volunteers 
Psychosomatic medicine  2009;72(1):35-45.
Objective indices of socioeconomic status (SES) predict diverse sources of morbidity and mortality, as well as numerous biological and behavioral risk factors for disease. Here we examine whether subjective SES may be similarly associated with measured risk factors, including the metabolic syndrome and its components of elevated blood pressure, high fasting glucose, dyslipidemia, and central adiposity.
Observations were based on a community sample of 981 adults (30–54 years of age; 52% female; 84% white, 16% African American). Subjective SES was measured using the nationally referenced (U.S.) MacArthur Scale of Subjective Social Status, and objective SES indexed by composite of years of education and family income.
Likelihood of meeting criteria for presence of the metabolic syndrome varied inversely with subjective SES (Odds Ratio [OR] =0.75; 95% CI: 0.64, 0.88, for a 1 SD increase in subjective SES, adjusted for age, sex, and race), and this association persisted on further adjustment for objective SES (OR = 0.82; 95% CI: 0.68, 0.99). Subjective SES was also associated inversely with blood pressure, waist circumference, and serum triglycerides, and positively with HDL cholesterol. Level of physical activity and smoking status were predicted by subjective SES as well, but adjusting for these health behaviors did not appreciably reduce associations of subjective SES with metabolic syndrome and syndrome components.
These findings support speculation that perceived social standing is associated with prominent cardiovascular risk factors and may prove a useful adjunct to conventional socioeconomic indicators in epidemiological research.
PMCID: PMC2807361  PMID: 19933505
socioeconomic status; subjective social status; metabolic syndrome; blood pressure; central adiposity; dyslipidemia
20.  Salivary Testosterone and a Trinucleotide (CAG) Length Polymorphism in the Androgen Receptor Gene Predict Amygdala Reactivity in Men 
Psychoneuroendocrinology  2010;35(1):94-104.
In studies employing functional magnetic resonance imaging (fMRI), reactivity of the amygdala to threat-related sensory cues (viz., facial displays of negative emotion) has been found to correlate positively with interindividual variability in testosterone levels of women and young men and to increase on acute administration of exogenous testosterone. Many of the biological actions of testosterone are mediated by intracellular androgen receptors (ARs), which exert transcriptional control of androgen-dependent genes and are expressed in various regions of the brain, including the amygdala. Transactivation potential of the AR decreases (yielding relative androgen insensitivity) with expansion a polyglutamine stretch in the N-terminal domain of the AR protein, as encoded by a trinucleotide (CAG) repeat polymorphism in exon 1 of the X-chromosome AR gene. Here we examined whether amygdala reactivity to threat-related facial expressions (fear, anger) differs as a function of AR CAG length variation and endogenous (salivary) testosterone in a mid-life sample of 41 healthy men (mean age = 45.6 yr, range: 34–54 yr; CAG repeats, range: 19–29). Testosterone correlated inversely with participant age (r = −0.39, p = 0.012) and positively with number of CAG repeats (r = 0.45, p = 0.003). In partial correlations adjusted for testosterone level, reactivity in the ventral amygdala was lowest among men with largest number of CAG repeats. This inverse association was seen in both the right (rp = −0.34, p<0.05) and left (rp = −0.32, p<0.05) hemisphere. Activation of dorsal amygdala, correlated positively with individual differences in salivary testosterone, also in right (r = 0.40, p<0.02) and left (r = 0.32, p<0.05) hemisphere, but was not affected by number of CAG repeats. Hence, androgenic influences on threat-related reactivity in the ventral amygdala may be moderated partially by CAG length variation in the AR gene. Because individual differences in salivary testosterone also predicted dorsal amygdala reactivity and did so independently of CAG repeats, it is suggested that androgenic influences within this anatomically distinct region may be mediated, in part, by non-genomic or AR-independent mechanisms.
PMCID: PMC2825741  PMID: 19493626
testosterone; androgen receptor; CAG repeat polymorphism; fMRI; amygdala; facial expressions of emotion
21.  Laboratory Induced Aggression: A PET Study of Aggressive Individuals with Borderline Personality Disorder 
Biological psychiatry  2009;66(12):1107-1114.
Borderline personality disorder (BPD) is often associated with symptoms of impulsive aggression, which pose a threat to patients themselves and to others. Preclinical studies show that orbital frontal cortex (OFC) plays a role in regulating impulsive aggression. Prior work has found OFC dysfunction in BPD.
We employed a task to provoke aggressive behavior, the Point Subtraction Aggression Paradigm (PSAP), which has never previously been used during functional brain imaging. Thirty-eight BPD patients with impulsive aggression (BPD-IED) and 36 age-matched healthy controls (HC) received 18FDG-PET on two occasions with a provocation and non-provocation version of the PSAP. For each participant, we measured mean relative glucose metabolism in cortical Brodmann areas (BAs) in each hemisphere; difference scores (Provoked–Non-provoked) were calculated. A whole brain exploratory analysis for the double difference of BPD-IED–HC for Provoked–Non-provoked was also conducted.
BPD-IED patients were significantly more aggressive than HC on the PSAP. BPD-IED patients also increased relative glucose metabolic rate (rGMR) in OFC and amygdala when provoked, while HC decreased rGMR in these areas. However, HC increased rGMR in anterior, medial, and dorsolateral prefrontal regions during provocation more than BPD-IED patients.
Patients responded aggressively and showed heightened rGMR in emotional brain areas, including amygdala and OFC in response to provocation, but not in more dorsal brain regions associated with cognitive control of aggression. In contrast, HC increased rGMR in dorsal regions of PFC during aggression provocation, brain regions involved in top-down cognitive control of aggression and, more broadly, of emotion.
PMCID: PMC2788117  PMID: 19748078
brain imaging; Point Subtraction Aggression Paradigm; PSAP; emotion
22.  Parental Education is Related to C-Reactive Protein among Female Middle Aged Community Volunteers 
Brain, behavior, and immunity  2009;23(5):677-683.
Growing evidence suggests that socioeconomic attributes of both childhood and adulthood confer risk for cardiovascular morbidity and mortality. In this study, we examine the association of both parental and individual educational attainment with C-reactive protein (CRP), an inflammatory mediator relevant to cardiovascular pathophysiology, in a midlife community sample. Subjects were 811 men and women (394 men/417 women; 87 % European-American/13 % African American), 30–54 years of age. Plasma concentrations of CRP were determined from blood samples obtained at a single session following an overnight fast. Regression analyses adjusting for age and race showed both parental education and individual education to be associated inversely with CRP in women, but not men. The relationship of parental education with CRP in women persisted on multivariable adjustment for both lifestyle risk factors (smoking, alcohol consumption, sleep, exercise, body mass index) and individual SES. Independent of reported personal educational attainment, mid-life adult women whose parents achieved fewer years of educational attainment exhibit higher levels of circulating CRP than women with higher parental education. This association may help explain the increased risk of atherosclerotic cardiovascular morbidity and mortality conferred by low childhood socioeconomic status.
PMCID: PMC2695412  PMID: 19486653
C-Reactive Protein; Parental Education
23.  Impulsiveness and cigarette smoking 
Psychosomatic medicine  2009;71(4):431-437.
Varying aspects of impulsive personality have been associated with tobacco use in cross-sectional and prospective studies, including novelty seeking and (low) constraint but most studies have not examined more than one tobacco use phenotype (e.g., any tobacco use versus dependence) or considered more than one variety of impulsiveness simultaneously.
The current study was conducted to evaluate the association of impulsive personality features with multiple tobacco use phenotypes including smoking status, lifetime tobacco consumption and dependence in a sample of 1284 adults between the ages of 30 and 54. Participants completed multiple self-report measures of impulsive personality and were interviewed regarding lifetime tobacco use.
Results revealed that reward seeking and disinhibitory traits were both associated with smoking status but only disinhibition was associated with tobacco dependence, after controlling for reward seeking.
The results reported here may aid investigations aimed at identifying neurobiological, including genetic, correlates of tobacco use and dependence by providing potential behavioral correlates of the diversity of tobacco use phenotypes. Moreover, successful efforts to prevent tobacco-related disease through prevention or cessation programs will be facilitated by the identification of factors that are differentially associated with different smoking phenotypes.
PMCID: PMC2713002  PMID: 19251874
disinhibition; impulsiveness; reward seeking; tobacco use
24.  Evaluation of behavioral impulsivity and aggression tasks as endophenotypes for borderline personality disorder 
Journal of psychiatric research  2009;43(12):1036-1048.
Borderline personality disorder (BPD) is marked by aggression and impulsive, often self-destructive behavior. Despite the severe risks associated with BPD, relatively little is known about the disorder’s etiology. Identification of genetic correlates (endophenotypes) of BPD would improve the prospects of targeted interventions for more homogeneous subsets of borderline patients characterized by specific genetic vulnerabilities. The current study evaluated behavioral measures of aggression and impulsivity as potential endophenotypes for BPD. Subjects with BPD (N = 127), a non cluster B personality disorder (OPD N = 122), or healthy volunteers (HV N = 112) completed self report and behavioral measures of aggression, motor impulsivity and cognitive impulsivity. Results showed that BPD subjects demonstrated more aggression and motor impulsivity than HV (but not OPD) subjects on behavioral tasks. In contrast, BPD subjects self-reported more impulsivity and aggression than either comparison group. Subsequent analyses showed that among BPD subjects behavioral aggression was associated with self-reported aggression, while behavioral and self-report impulsivity measures were more modestly associated. Overall, the results provide partial support for the use of behavioral measures of aggression and motor impulsivity as endophenotypes for BPD, with stronger support for behavioral aggression measures as an endophenotype for aggression within BPD samples.
PMCID: PMC2853811  PMID: 19232640
Borderline personality disorder; Endophenotype; Aggression; Impulsivity
25.  Citalopram Intervention for Hostility: Results of a Randomized Clinical Trial 
Hostility is associated with an increased risk for cardiovascular disease (CVD). Because central serotonin may modulate aggression, we might expect selective serotonin reuptake inhibitors (SSRIs) to be effective in reducing hostility. Such effects have never been examined in individuals scoring high on hostility who are otherwise free from major DSM-IV Axis I psychopathology. 159 participants (ages 30–50, 50 % female) scoring high on 2 measures of hostility and with no current major Axis I diagnosis were randomly assigned to 2 months of citalopram (40 mg, fixed flexible dose) or placebo. Adherence was assessed by electronic measurement and by drug exposure assessment. Treated subjects showed larger reductions in state anger (condition-by-time p = .01), hostile affect (p = 02), and, among women only, physical and verbal aggression (p = .005) relative to placebo controls. Treatment was also associated with relative increases in perceived social support (p = .04). Findings have implications for understanding the CNS correlates of hostility, its associations with other psychosocial risk factors for CVD, and, potentially, for the design of effective interventions.
PMCID: PMC2745900  PMID: 19170463
SSRIs; hostility; treatment; cardiovascular disease; social support

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