Rebecca Harley

The Harvard Twin Study of Substance Abuse: What We Have Learned

The Harvard Twin Study of Substance Abuse was carried out with the members of the Vietnam Era Twin (VET) Registry. The VET Registry comprises over 8000 male twins who served in the United States military between 1965 and 1975 and were subsequently interviewed regarding their use of licit and illicit substances, as well as various types of psychopathology. Our research has demonstrated significant influences by genetic, shared environmental, and unique environmental factors on the abuse of illicit substances. Multivariate analyses have indicated that the co-occurrence of abuse of various types of illicit drugs reflects a common vulnerability, influenced by both genetic and environmental factors, that cuts across all categories of illicit drugs. We have also demonstrated that some drugs have unique determinants, both genetic and environmental, that are not shared with other drugs. In part, the genetic influence on marijuana abuse is mediated by genetic influence on subjective effects in response to the drug. The determinants of transitions from one stage of drug use to another differ depending on which drug or which transition is examined. We determined significant genetic influences on several aspects of nicotine and alcohol use separately, as well as genetic influences shared by both substances. We found that the co-occurrence of illicit drug abuse and major depression is due to unique environmental influences. The phenotypic association between symptoms of conduct disorder and alcohol and marijuana dependence is due largely to shared environmental influences. Our results, thus far, indicate a complex pattern of genetic and environmental influences on substance use and abuse.

A twin registry study of familial and individual risk factors for trauma exposure and posttraumatic stress disorder

This study examines the association of individual and familial risk factors with exposure to trauma and posttraumatic stress disorder (PTSD) in male twins (N = 6744) from the Vietnam Era Twin Registry. Independent reports of familial psychopathology from co-twins were used to avoid the potential biases of the family history method. Risk for exposure to traumatic events was increased by service in Southeast Asia, preexisting conduct disorder, preexisting substance dependence, and a family history of mood disorders whose effects appear to be partly genetic. Preexisting mood disorders in the individual were associated with decreased odds of traumatic exposure. Risk of developing PTSD following exposure was increased by an earlier age at first trauma, exposure to multiple traumas, paternal depression, less than high school education at entry into the military, service in Southeast Asia, and preexisting conduct disorder, panic disorder or generalized anxiety disorder, and major depression. Results suggest the association of familial psychopathology and PTSD may be mediated by increased risk of traumatic exposure and by preexisting psychopathology.

Adaptation of dialectical behavior therapy skills training group for treatment-resistant depression.

Treatment resistant depression is common, persistent, and results in substantial functional and social impairment. This study describes the development and preliminary outcome evaluation of a dialectical behavior therapy-based skills training group to treat depressive symptoms in adult outpatients for whom antidepressant medication had not produced remission. The 16-session, once-weekly group covered the 4 dialectical behavior therapy skill sets: mindfulness, interpersonal effectiveness, emotion regulation, and distress tolerance. Twenty-four patients with ongoing depressive symptoms despite stable, adequate medication treatment for major depressive disorder were randomly assigned to either the skills group or a wait-list condition. The depressive symptoms of participants who completed the study (9 wait-list participants, 10 skills group participants) were compared using a clinician-rated Hamilton rating scale for depression and then replicated using a self-report measure Beck depression inventory. Clinician raters were blind to each participant’s assigned study condition. Skills group participants showed significantly greater improvements in depressive symptoms compared with the control condition. Effect sizes were large for both measures of depression (Cohen’s d = 1.45 for Hamilton rating scale for depression and 1.31 for Beck depression inventory), suggesting that larger scale trials are warranted.

Genetic and Environmental Influences on Transitions in Drug Use

Genetic and environmental factors influence drug abuse, but abuse represents the culmination of a sequence of events. Different levels of use may have different determinants and these determinants may differ across drug types. Approximately 3200 male–male twin pairs from the Vietnam Era Twin Registry were interviewed by telephone. Data were obtained regarding exposure to six categories of illicit drugs, initiation of use, continuation of use, regular usage, and diagnosis of drug abuse/dependence. Genetic, common environmental, and unique environmental influences on transitions of drug involvement, defined as movement from one level of drug use to the next, were investigated. Marijuana had the highest conditional probability for the transition from exposure to use, from use to use more than five times, and from use more than five times to regular use. The rate of transition to regular use of heroin was higher than the rate for amphetamine, cocaine, sedatives, and psychedelics. Cocaine had the highest conditional probability for the transition from regular use to abuse/dependence. Significant genetic influences were observed for a number of transitions in marijuana, amphetamine, and cocaine usage.

Concurrent Validity of the Personality Assessment Inventory Borderline Scales in Patients Seeking Dialectical Behavior Therapy

Abstract The purpose of this study was to explore the usefulness of the Personality Assessment Inventory (Morey, 1991) Borderline full scale (BOR) and subscales in the assessment of patients being evaluated for dialectical behavior therapy (DBT; Linehan, 1993). We administered 67 patients both the PAI and the Diagnostic and Statistical Manual of Mental Disorders(4th ed.; American Psychiatric Association, 1994) Structured Clinical Interview for Axis II disorders (SCID-II; First, Spitzer, Gibbon, Williams, & Benjamin, 1997). Point biserial correlations showed a significant relationship between the presence of borderline personality disorder (BPD) and scores on the BOR and Schizophrenia (SCZ) scales. A regression analysis showed that among the BOR subscales, those measuring identity disturbance, self-harming behavior, and negative relationships were significantly related to the total number of SCID-II BPD criteria. Diagnostic efficiency statistics between the BOR scale and the number of SCID-II BPD criteria indicated that a T score cutoff of 65 optimally differentiates patients who do and do not meet criteria for BPD. The relationship between BOR and SCID-II BPD demonstrates the concurrent validity of the PAI and shows its usefulness in this setting

Self-reported premenstrual exacerbation of depressive symptoms in patients seeking treatment for major depression

BACKGROUND Very little research has examined the frequency with which women with major depressive disorder experience premenstrual exacerbation (PME) of depression or the characteristics of those who report such worsening. The NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study provides a unique opportunity to evaluate PME in depressed women seeking treatment in primary care or psychiatric settings. METHOD This report presents data from the first 1500 participants enrolled in the STAR*D study. Premenopausal women with major depressive disorder were asked if they experienced a worsening of their depressive symptoms 5-10 days prior to menses. Those reporting PME were compared with those reporting no PME with regard to sociodemographic characteristics, course of illness features, symptom presentation, general medical co-morbidity, functional impairment, and quality of life. RESULTS Of 433 premenopausal women not taking oral contraceptives, 64% reported a premenstrual worsening of their depression. Women who reported PME had a longer duration of their current major depressive episode [30.7 (S.D. = 73.7) months versus 13.5 (S.D. = 13.2) months; p=0.001], as well as greater general medical co-morbidity. Women reporting PME were also more likely to endorse symptoms of leaden paralysis, somatic complaints, gastrointestinal complaints, and psychomotor slowing, and were less likely to endorse blunted mood reactivity. CONCLUSIONS PME is endorsed by the majority of premenopausal women with major depressive disorder and appears to be associated with a longer duration of depressive episode. PME is a common and important clinical issue deserving of further attention in both research and practice.

Change in emotional processing during a dialectical behavior therapy-based skills group for major depressive disorder.

Across studies, paying attention to and analyzing ones emotions has been found to be both positively and negatively correlated with depression symptoms. One way of reconciling these seemingly contradictory findings is the possibility that attending to emotions in a skillful manner may help to reduce depression whereas attending to emotions with limited skill may be counterproductive. Dialectical behavior therapy (DBT) is a clinical intervention designed to foster adaptive awareness, expression, regulation, tolerance, and acceptance of emotions. Results of the present report come from a pilot study of a 16-week DBT-based skills training group for treatment-resistant major depressive disorder (MDD) as an adjunctive treatment to pharmacotherapy. Patients were randomized to treatment or a waitlist control group. A significant interaction revealed that increases in emotional processing were associated with decreases in depression symptoms in the DBT-based skills group; however, increases in emotional processing in the waitlist condition were associated with increases in depression. Results offer preliminary support for the idea that participating in DBT-based skills training may help individuals with treatment-resistant MDD to develop skills that facilitate processing emotions in a way that helps to reduce rather than exacerbate depression symptoms.

Use of dialectical behavior therapy skills training for borderline personality disorder in a naturalistic setting

Abstract This nonrandomized, naturalistic study describes a modified outpatient dialectical behavior therapy (DBT) program for borderline personality disorder (BPD) in which some patients receive the comprehensive, empirically supported DBT package and others receive DBT skills group therapy with non-DBT individual therapy. Patients who completed one skills group cycle showed significant improvements in BPD, depression, and suicidal ideation as measured by the Personality Assessment Inventory. Fifty-one percent of patients dropped out of skills group, but patients with in-system individual therapy were significantly more likely to complete group therapy. Although causal conclusions cannot be drawn, this report demonstrates that a modified DBT program can be implemented successfully in settings in which a full DBT package for all patients may not be feasible and suggests that BPD patients receiving non-DBT individual therapy may benefit from DBT skills group.

Continuation cognitive-behavioural therapy maintains attributional style improvement in depressed patients responding acutely to fluoxetine

BACKGROUND Little is known about how continuation and maintenance cognitive-behavioural therapy (CBT) influences important psychological constructs that may be associated with long-term outcome of major depressive disorder. The goal of this study was to examine whether CBT would help maintain attributional style changes experienced by patients during acute phase fluoxetine treatment. METHOD Three hundred and ninety-one patients with major depressive disorder were enrolled in an open, fixed-dose 8 week fluoxetine trial. Remitters to this acute phase treatment (N= 132) were randomized to receive either fixed-dose fluoxetine (meds only) or fixed-dose fluoxetine plus cognitive-behavioural therapy (CBT+meds) during a 6-month continuation treatment phase. The Attributional Style Questionnaire (ASQ) was completed by patients at three time points - acute phase baseline, continuation phase baseline and continuation phase endpoint. Analysis of covariance was used to compare continuation phase ASQ composite score changes between groups. RESULTS Patients in both treatment groups experienced significant gains in positive attributional style during the acute phase of treatment. Continuation phase ASQ composite change scores differed significantly between treatment groups, with the CBT + meds group maintaining acute phase positive attributional style changes, and the meds only group exhibiting a worsening of attributional style. The two treatment groups did not significantly differ in rates of relapse and final continuation phase visit HAMD-17 scores. CONCLUSIONS In this sample, the addition of CBT to continuation psychopharmacological treatment was associated with maintenance of acute treatment phase attributional style gains. Further research is needed to evaluate the role of such gains in the long-term course of depressive illness.

Trauma-related psychophysiological reactivity in women exposed to war-zone stress.

Women are at particular risk for Posttraumatic Stress Disorder (PTSD), but surprisingly little is known about their objective manifestations of the disorders hallmark symptoms. Although research suggests that people with PTSD exhibit physiological reactivity to the presentation of trauma-related cues, the majority of studies to date have focused on men. We assessed the physiological reactions of three groups of trauma-exposed female Vietnam veterans (those with current PTSD, lifetime PTSD, or no PTSD) to war-related stimuli. Responses of women with current PTSD differed significantly from those without PTSD on skin conductance and systolic blood pressure, and mean levels of reactivity for women with lifetime PTSD fell between the other two groups. Although symptom severity was correlated with physiologic reactivity overall, results suggested differential relationships at the symptom cluster level. Study results replicate earlier findings with men and extend knowledge of autonomic reactivity to an important group of female survivors.