Rebekah Bradley

Association of FKBP5 Polymorphisms and Childhood Abuse With Risk of Posttraumatic Stress Disorder Symptoms in Adults

CONTEXT In addition to trauma exposure, other factors contribute to risk for development of posttraumatic stress disorder (PTSD) in adulthood. Both genetic and environmental factors are contributory, with child abuse providing significant risk liability. OBJECTIVE To increase understanding of genetic and environmental risk factors as well as their interaction in the development of PTSD by gene x environment interactions of child abuse, level of non-child abuse trauma exposure, and genetic polymorphisms at the stress-related gene FKBP5. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study examining genetic and psychological risk factors in 900 nonpsychiatric clinic patients (762 included for all genotype studies) with significant levels of childhood abuse as well as non-child abuse trauma using a verbally presented survey combined with single-nucleotide polymorphism (SNP) genotyping. Participants were primarily urban, low-income, black (>95%) men and women seeking care in the general medical care and obstetrics-gynecology clinics of an urban public hospital in Atlanta, Georgia, between 2005 and 2007. MAIN OUTCOME MEASURES Severity of adult PTSD symptomatology, measured with the modified PTSD Symptom Scale, non-child abuse (primarily adult) trauma exposure and child abuse measured using the traumatic events inventory and 8 SNPs spanning the FKBP5 locus. RESULTS Level of child abuse and non-child abuse trauma each separately predicted level of adult PTSD symptomatology (mean [SD], PTSD Symptom Scale for no child abuse, 8.03 [10.48] vs > or =2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs > or =4 types, 16.74 [12.90]; P < .001). Although FKBP5 SNPs did not directly predict PTSD symptom outcome or interact with level of non-child abuse trauma to predict PTSD symptom severity, 4 SNPs in the FKBP5 locus significantly interacted (rs9296158, rs3800373, rs1360780, and rs9470080; minimum P = .0004) with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. This gene x environment interaction remained significant when controlling for depression severity scores, age, sex, levels of non-child abuse trauma exposure, and genetic ancestry. This genetic interaction was also paralleled by FKBP5 genotype-dependent and PTSD-dependent effects on glucocorticoid receptor sensitivity, measured by the dexamethasone suppression test. CONCLUSIONS Four SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult PTSD symptoms. There were no main effects of the SNPs on PTSD symptoms and no significant genetic interactions with level of non-child abuse trauma as predictor of adult PTSD symptoms, suggesting a potential gene-childhood environment interaction for adult PTSD.

Influence of child abuse on adult depression: Moderation by the corticotropin-releasing hormone receptor gene

CONTEXT Genetic inheritance and developmental life stress both contribute to major depressive disorder in adults. Child abuse and trauma alter the endogenous stress response, principally corticotropin-releasing hormone and its downstream effectors, suggesting that a gene x environment interaction at this locus may be important in depression. OBJECTIVE To examine whether the effects of child abuse on adult depressive symptoms are moderated by genetic polymorphisms within the corticotropin-releasing hormone type 1 receptor (CRHR1) gene. DESIGN Association study examining gene x environment interactions between genetic polymorphisms at the CRHR1 locus and measures of child abuse on adult depressive symptoms. SETTING General medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia. PARTICIPANTS The primary participant population was 97.4% African American, of low socioeconomic status, and with high rates of lifetime trauma (n = 422). A supportive independent sample (n = 199) was distinct both ethnically (87.7% Caucasian) and socioeconomically (less impoverished). MAIN OUTCOME MEASURES Beck Depression Inventory scores and history of major depressive disorder by the Structured Clinical Interview for DSM-IV Axis I Disorders. RESULTS Fifteen single-nucleotide polymorphisms spanning 57 kilobases of the CRHR1 gene were examined. We found significant gene x environment interactions with multiple individual single-nucleotide polymorphisms (eg, rs110402, P = .008) as well as with a common haplotype spanning intron 1 (P < .001). Specific CRHR1 polymorphisms appeared to moderate the effect of child abuse on the risk for adult depressive symptoms. These protective effects were supported with similar findings in a second independent sample (n = 199). CONCLUSIONS These data support the corticotropin-releasing hormone hypothesis of depression and suggest that a gene x environment interaction is important for the expression of depressive symptoms in adults with CRHR1 risk or protective alleles who have a history of child abuse.

Refining the Construct of Narcissistic Personality Disorder: Diagnostic Criteria and Subtypes

OBJECTIVE Narcissistic personality disorder has received relatively little empirical attention. This study was designed to provide an empirically valid and clinically rich portrait of narcissistic personality disorder and to identify subtypes of the disorder. METHOD A random national sample of psychiatrists and clinical psychologists (N=1,201) described a randomly selected current patient with personality pathology. Clinicians provided detailed psychological descriptions of the patients using the Shedler-Westen Assessment Procedure-II (SWAP-II), completed a checklist of axis II diagnostic criteria, and provided construct ratings for each axis II personality disorder. Descriptions of narcissistic patients based on both raw and standardized SWAP-II item scores were aggregated to identify, respectively, the most characteristic and the most distinctive features of narcissistic personality disorder. RESULTS A total of 255 patients met DSM-IV criteria for narcissistic personality disorder based on the checklist and 122 based on the construct ratings; 101 patients met criteria by both methods. Q-factor analysis identified three subtypes of narcissistic personality disorder, which the authors labeled grandiose/malignant, fragile, and high-functioning/exhibitionistic. Core features of the disorder included interpersonal vulnerability and underlying emotional distress, along with anger, difficulty in regulating affect, and interpersonal competitiveness, features that are absent from the DSM-IV description of narcissistic personality disorder. CONCLUSIONS These findings suggest that DSM-IV criteria for narcissistic personality disorder are too narrow, underemphasizing aspects of personality and inner experience that are empirically central to the disorder. The richer and more differentiated view of narcissistic personality disorder suggested by this study may have treatment implications and may help bridge the gap between empirically and clinically derived concepts of the disorder.

Affect regulation in borderline personality disorder.

Although difficulty with affect regulation is generally considered a core component of borderline personality disorder (BPD), surprisingly little research has focused on the nature of affect regulation and dysregulation in BPD. A random national sample of 117 experienced clinicians provided data on a randomly selected patient with BPD (N = 90) or dysthymic disorder (DD; N = 27). Clinicians described their patients using the Affect Regulation and Experience Q-sort-Questionnaire Version, a psychometric instrument designed for expert informants to assess affect and affect regulation. BPD and DD patients appear to differ in both the emotions they experience and the ways they regulate or fail to regulate them. Whereas DD patients are characterized by negative affect, BPD patients are characterized by both negative affect and affect dysregulation, which appear to be distinct constructs. BPD patients also show distinct patterns of affect regulation, and subtypes of BPD patients show distinct affect regulation profiles of potential relevance to treatment.

Etiology of Borderline Personality Disorder: Disentangling the Contributions of Intercorrelated Antecedents

A substantial body of research points to several variables relevant to the etiology of borderline personality disorder (BPD), notably childhood physical and sexual abuse, childhood family environment, and familial aggregation of both internalizing and externalizing disorders. However, these variables tend to be correlated, and few studies have examined them simultaneously. A national sample of randomly selected psychologists and psychiatrists described 524 adult patients with personality disorders. Family environment, parental psychopathology, and history of abuse all independently predicted BPD symptoms in multiple regression analyses. Sexual abuse contributed to the prediction of BPD symptoms over and above family environment, although family environmental factors such as instability partially mediated the effect. The results converge with recent studies using very different samples and methodologies.

Treatment barriers for low-income, urban African Americans with undiagnosed posttraumatic stress disorder

African Americans in low-income, urban communities are at high risk for exposure to traumatic events as well as for symptoms of posttraumatic stress disorder (PTSD). Approximately 22% of 220 participants recruited from urban hospital medical clinics met survey criteria for PTSD. Among the common traumas were having relatives/friends murdered (47%), being attacked with weapons (64% of men), and being sexually attacked (36% of women). Although desiring mental health services, only 13.3% of those with PTSD had prior trauma-focused treatment. Barriers to treatment included limited transportation and finances, family disapproval, and unfamiliarity with accessing treatment, among others. These data highlight the need for an awareness of the high prevalence of trauma and PTSD in this population.

Clinical Assessment of Attachment Patterns and Personality Disorder in Adolescents and Adults

The relevance of attachment theory and research for practice has become increasingly clear. The authors describe a series of studies with 3 aims: (a) to validate measures of attachment for use by clinicians with adolescents and adults, (b) to examine the relation between attachment and personality pathology, and (c) to ascertain whether factor analysis can recover dimensions of attachment reflecting both interpersonal and narrative style. In 3 studies, experienced clinicians provided psychometric data using 1 of 4 attachment questionnaires (2 adolescent and 2 adult samples). Attachment dimensions predicted both personality pathology and developmental experiences in predictable ways. Factor analysis identified 4 dimensions that replicated across adolescent and adult samples on the basis of a combination of interpersonal and narrative indicators: secure, dismissing, preoccupied, and incoherent/disorganized.

Empirically Supported Complexity Rethinking Evidence-Based Practice in Psychotherapy

Over the last 10 years, evidence-based practice in psychology has become synonymous with a particular operationalization of it aimed at developing a list of empirically supported therapies. Although much has been learned since the emergence of the empirically supported therapies movement, its restrictive definition of evidence (excluding, for example, basic science as a source of evidence to be used by clinicians) is problematic, and the assumptions inherent in its nearly exclusive focus on brief, focal treatments for specific disorders are themselves not generally supported by the available data. Recent meta-analytic data support a more nuanced view of treatment efficacy than one that makes dichotomous judgments of empirically supported or unsupported, suggesting the need for a more refined concept of evidence-based practice in psychology.

The external validity of controlled clinical trials of psychotherapy for depression and anxiety: A naturalistic study

Psychotherapy researchers have increasingly called for clinical practice and training to focus on empirically supported therapies tested in randomized controlled clinical trials (RCTs). In this paper, we report data from a naturalistic study of successful treatments in clinical practice that bear on the external validity of ESTs for three disorders. Participants were 242 experienced doctoral-level clinicians who reported on their last successfully treated patient seeking treatment for clinically significant depression, panic, or anxiety without panic. Successful treatments typically take substantially longer than the 8-16 sessions characteristic of efficacy trials for these disorders, even for the briefest treatments (cognitive-behavioural). Of particular relevance for generalizability from RCTs, most patients in clinical practice present with multiple problems other than a single Axis I disorder, which clinicians of all theoretical orientations recognize and treat, and these co-occurring conditions have a substantial impact on treatment length in everyday practice. The data suggest the importance of effectiveness research in bridging research and practice. They also point to the utility of distinguishing two complementary ways in which effectiveness research can be understood and implemented: by starting with efficacy trials and then testing treatments with promising results in the laboratory using broader community samples; or by starting with everyday clinical practice, examining patterns of covariation between specific interventions and outcomes at clinically meaningful follow-up intervals with diverse and ecologically valid samples and using these data to generate prototypes of treatments that can be used to guide the next generation of experimental studies.

The psychodynamics of borderline personality disorder: A view from developmental psychopathology

This article provides a contemporary view of the psychodynamics of borderline personality disorder (BPD) from a developmental psychopathology perspective. We first briefly describe the evolution of the borderline construct in psychoanalysis and psychiatry. Then we provide clinically and empirically informed model of domains of personality function and dysfunction that provides a roadmap for thinking about personality pathology from a developmental psychopathology standpoint and examine the nature and phenomenology of BPD in terms of these domains of functioning. Next, we describe prominent dynamic theories of etiology of BPD and examine these in relation to the available research. Finally, we describe psychodynamic conceptions of treatment and the way BPD phenomena manifest in treatment, followed again by consideration of relevant research, particularly on transference-countertransference constellations empirically identified in the treatment of patients with BPD.