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1.  Interpersonal and Social Rhythm Therapy for Adolescents with Bipolar Disorder: Treatment Development and Results from an Open Trial 
Depression and anxiety  2010;27(5):457-464.
In adolescents and adults, bipolar disorder (BD) is associated with significant morbidity, mortality, and impairment in psychosocial and occupational functioning. IPSRT is an empirically-supported adjunctive psychotherapy for adults with bipolar disorder which has been shown to help delay relapse, speed recovery from a bipolar depressive episode, and increase occupational and psychosocial functioning in adults with BD. The current study is designed to describe the adolescent-specific developmental adaptations made to IPSRT (i.e., IPSRT-A) and to report the results from an open trial of IPSRT-A with 12 adolescents with a bipolar spectrum disorder.
Interpersonal and Social Rhythm Therapy was adapted to be developmentally-relevant to adolescents with bipolar disorder. Twelve adolescents (mean age 16.5 ± 1.3 years) diagnosed with a bipolar spectrum disorder participated in 16–18 sessions of adjunctive IPSRT-A over 20 weeks. Manic, depressive, and general symptoms and global functioning were measured at baseline, monthly during treatment, and at post-treatment. Adolescent satisfaction with treatment was also measured.
Feasibility and acceptability of IPSRT-A were high; 11/12 participants completed treatment, 97% of sessions were attended, and adolescent-rated satisfaction scores were high. IPSRT-A participants experienced significant decreases in manic, depressive and general psychiatric symptoms over the 20 weeks of treatment. Participants’ global functioning increased significantly as well. Effect sizes ranged from medium-large to large.
IPSRT-A appears to be a promising adjunctive treatment for adolescents with bipolar disorder. A current randomized controlled trial is underway to examine effects of adjunctive IPSRT-A on psychiatric symptoms and psychosocial functioning.
PMCID: PMC4318681  PMID: 20186968
Bipolar Disorder; Adolescents; Interpersonal Psychotherapy
2.  [No title available] 
PMCID: PMC3900595  PMID: 23761021
3.  [No title available] 
PMCID: PMC4293038  PMID: 24254958
4.  Disorder-Specific Mental Health Service Use for Mood and Anxiety Disorders: Associations with Age, Sex, and Psychiatric Comorbidity 
Depression and anxiety  2011;29(3):234-242.
The objectives of this study are to examine the prevalence of disorder-specific mental health service use for mood and anxiety disorders, and relationships between helpseeking and age, sex, and psychiatric comorbidity.
The authors used Wave 2 data from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), which included 34,653 adults. Cross tabulations provided helpseeking prevalence rates for five anxiety disorders and three mood disorders by age and sex, as well as for individuals with and without comorbid anxiety and mood disorders. Logistic regression analyses explored the likelihood of helpseeking among younger and middle-aged adults in comparison to older adults.
The prevalence of helpseeking was highest for panic disorder (45.3%) and dysthymia (44.5%) and lowest for specific phobias (7.8%). For each condition except panic disorder service use was most likely among middle-aged adults and especially unlikely among older individuals. Sex differences in treatment seeking favoring women showed only modest variability with age. Finally, the prevalence of helpseeking was generally lower among individuals without comorbid anxiety or mood disorders, and the hill-shaped influence of age on service use was attenuated in this pure group.
The results of this study highlight the highest prevalence of disorder-specific service use among middle-aged adults and women, and among individuals with panic disorder and dysthymia. For purposes of identifying groups who are in need of targeted efforts to increase service use, helpseeking was especially unlikely among people suffering from specific phobia, as well as among men and older adults.
PMCID: PMC4284961  PMID: 22065571
mental health services; prevalence; mental disorders; aged; epidemiology
5.  Cortisol reactivity to experimentally-manipulated psychosocial stress in young adults at varied risk for depression 
Depression and anxiety  2013;31(1):10.1002/da.22125.
This study examined cortisol and affective reactivity to a psychosocial stress task in 102 young adults who varied in risk for depression (56 remitted-depressed, 46 never-depressed). Participants were randomly assigned to either a stress (i.e., social-evaluative threat) or control (i.e., no social-evaluative threat) condition. For never-depressed individuals, cortisol responses were significantly greater in the stress compared to the control condition. Moreover, cortisol responses were significantly greater for never-depressed than remitted-depressed individuals in the stress condition. For individuals with a history of depression, cortisol responses did not differ significantly between the stress and control conditions. Negative affective reactivity also was higher for never-depressed, but not remitted-depressed, individuals in the stress compared to the control condition. Moreover, cortisol responses were inversely related to negative affect during the recovery phase in both stress and control conditions. Findings indicate the lack of a robust cortisol response to social evaluation stress among remitted-depressed individuals as compared to that of never depressed controls. Future studies should investigate unique and interactive links between these hypothalamic-pituitary-adrenal and affective reactivity alterations and risk for subsequent depressive episodes.
PMCID: PMC3735776  PMID: 23606237
Stress; depression; remission; cortisol; negative affect
Depression and anxiety  2013;30(8):709-715.
The current proposal for the DSM-5 definition of social anxiety disorder (SAD) is to replace the DSM-IV generalized subtype specifier with one that specifies fears in performance situations only. Relevant evaluations to support this change in youth samples are sparse.
The present study examined rates and correlates of the DSM-IV and proposed DSM-5 specifiers in a sample of treatment-seeking children and adolescents with SAD (N = 204).
When applying DSM-IV subtypes, 64.2% of the sample was classified as having a generalized subtype of SAD, with the remaining 35.2% classifying as having a nongeneralized subtype SAD. Youth with generalized SAD, relative to those with nongeneralized SAD, were older, had more clinically severe SAD, showed greater depressive symptoms, and were more likely to have a comorbid depressive disorder. No children in the current sample endorsed discrete fear in performance situations only in the absence of fear in other social situations.
The present findings call into question the meaningfulness of the proposed changes in treatment-seeking youth with SAD.
PMCID: PMC4258526  PMID: 23494954
anxiety disorders; children; classification; diagnosis; diagnostic and statistical manual of mental disorders; DSM-5
Depression and anxiety  2014;31(7):542-550.
Following the Boston Marathon attack, the extraordinary interagency manhunt and shelter-in-place made for a truly unprecedented experience for area families. Although research on Boston youth has found robust associations between manhunt-related experiences and post-attack functioning, such work does little to identify the specific needs of a particularly vulnerable population—i.e., children with a relative who participated in the manhunt. Understanding the adjustment of these youth is critical for informing clinical efforts.
Survey of Boston-area parents/caretakers (N = 460) reporting on their child’s attack/manhunt-related experiences, as well as psychosocial functioning in the first six post-attack months; analyses compared youth with and without a relative in law enforcement or the armed services who participated in the manhunt.
The proportion of youth with likely PTSD was 5.7 times higher among youth with relatives in the manhunt than among youth without. After accounting for child demographics, blast exposure, and children’s own exposure to manhunt events (e.g., hearing/seeing gunfire/explosions, having officers enter/search home), having a relative in the manhunt significantly predicted child PTSD symptoms, emotional symptoms, and hyperactivity/inattention. Fear during the manhunt that a loved one could be hurt mediated relationships between having a relative in the manhunt and clinical outcomes; living within the zone of greatest manhunt activity did not moderate observed relationships.
Children with relatives called upon to participate in the unprecedented interagency manhunt following the Boston Marathon attack carried a particularly heavy mental health burden. Continued research is needed to clarify the clinical needs of youth with relatives in high-risk occupations.
PMCID: PMC4258527  PMID: 24865569
disasters; terrorism; first responders; PTSD; child
Depression and anxiety  2012;29(12):1004-1013.
Anxiety disorder not otherwise specified (ADNOS) is one of the more common and impairing DSM-IV diagnoses assigned in child practice settings, but it is not clear what percentage of these assignments simply reflect poor diagnostic practices.
The present study evaluated patterns and correlates of child ADNOS in a large outpatient treatment seeking sample of anxious youth (N = 650), utilizing structured diagnostic interviewing procedures.
Roughly, 15% of youth met diagnostic criteria for ADNOS. Overall, these youth exhibited comparable levels of clinical problems relative to youth with DSM-IV–specified anxiety disorders (AD), and roughly two-thirds of ADNOS cases exhibited symptom presentations closely resembling generalized anxiety disorder (GAD). Among ADNOS presentations resembling GAD, those failing to meet the “worries more days than not” or “worries across multiple domains” criteria showed lower internalizing symptoms than GAD youth, but comparable anxious/depressed symptoms, somatic symptoms, social problems, externalizing problems, and total problems as measured by the Child Behavior Checklist.
Childhood ADNOS cases are prevalent and warrant clinical attention. In many cases there are only a couple, if any, clinical differences between these disorders and the ADs they closely resemble. Future work is needed to improve upon the current taxonomy of childhood ADs to specify a larger proportion of affected youth needing care.
PMCID: PMC4258529  PMID: 22807226
anxiety disorders; children; classification; diagnosis; diagnostic and statistical manual of mental disorders; DSM-5
9.  The Corticotropin Releasing Hormone Receptor 2 (CRHR-2) Gene is Associated with Decreased Risk and Severity of Posttraumatic Stress Disorder in Women 
Depression and anxiety  2013;30(12):10.1002/da.22176.
The corticotropin releasing hormone (CRH) system has been implicated in a variety of anxiety and mood-based symptoms and disorders. CRH receptor-2 (CRHR-2) plays a role in attenuating biological responses to stressful life events and trauma, making the CRHR-2 gene a strong candidate to study in relationship to posttraumatic stress disorder (PTSD).
The sample was 491 trauma-exposed white non-Hispanic veterans and their cohabitating intimate partners assessed via structured interview for lifetime DSM-IV PTSD; just over 60% met criteria for the disorder. Thirty-one single nucleotide polymorphisms (SNPs) in and near CRHR-2, obtained from an array of 2.5 million markers, were tested for association with PTSD diagnosis and symptom severity in the whole sample and in men and women separately.
Ten SNPs showed nominally significant evidence of association with PTSD in the full sample and two SNPs (rs8192496 and rs2190242) were significant after permutation-based multiple testing correction (uncorrected ps = .0004 and .0005, odds ratios = .60 and .58, respectively). Analyses stratified by sex revealed that the effect was specific to women, who comprised 35% of the sample (uncorrected ps = .0003 and .0002, odds ratios = .41 and .35, respectively). Two additional SNPs (rs2267715 and rs2284218) also showed significant association with PTSD in women (both uncorrected ps = .001, both odds ratios = .48).
Results suggest that CRHR-2 variants may affect risk for PTSD in women by attenuating the stress response and reducing symptoms of the disorder.
PMCID: PMC3855198  PMID: 24123648
PTSD; single nucleotide polymorphisms; rs8192496; rs2284218; women; veterans; latent variable
Depression and anxiety  2013;30(12):1211-1216.
Previous research has identified high rates of comorbid anxiety disorders among individuals presenting with primary CG. In the present study, we examined the prevalence of comorbid CG in bereaved primary anxiety disorder (AD) patients compared to bereaved healthy controls. We also examined the impairment associated with comorbid CG in AD.
Participants were 242 bereaved adults (mean (SD) age = 41.5 (13.1), 44.2% women) with a primary AD diagnosis, including generalized anxiety disorder (GAD; n = 57), panic disorder (PD; n = 49), posttraumatic stress disorder (PTSD; n = 29), and generalized social anxiety disorder (GSAD; n = 107), as well as 155 bereaved healthy controls with no current DSM-IV Axis I diagnosis (mean (SD) age = 43.0 (13.6), 51.0% women). CG symptoms were measured using the 19-item inventory of complicated grief (ICG), with threshold CG defined as an ICG score of ≥30. Quality of life and functional impairment were assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Range of Impaired Functioning Tool (LIFE-RIFT), respectively.
Participants with primary ADs had significantly higher rates of threshold CG symptoms than bereaved controls (12.0% vs. 0.65%; Fisher’s Exact P < 0.001). Rates of threshold CG were significantly elevated for each AD when compared to bereaved controls. After adjustment for age, sex, education, and comorbid major depressive disorder, threshold CG was associated with lower quality of life (β = −0.140, P = 0.023) and greater impairment (β = 0.141, P = 0.035) among individuals with AD.
Our findings suggest that threshold CG is of clinical relevance in bereaved individuals with a primary anxiety disorder. Screening for CG in patients with ADs may be warranted.
PMCID: PMC4038035  PMID: 23495105
Complicated grief; grief; bereavement; anxiety; comorbidity; quality of life
11.  Olfactory Reference Syndrome: Issues for DSM-V 
Depression and anxiety  2010;27(6):592-599.
The published literature on olfactory reference syndrome (ORS) spans more than a century and provides consistent descriptions of its clinical features. The core symptom is preoccupation with the belief that one emits a foul or offensive body odor, which is not perceived by others. This syndrome is associated with substantial distress and disability. DSM-IV and ICD-10 do not explicitly mention ORS but note convictions about emitting a foul body odor in their description of delusional disorder, somatic type. However, the fact that such symptoms can be non-delusional poses a diagnostic conundrum. Indeed, DSM-IV also mentions fears about the offensiveness of one’s body odor in the social phobia text (as a symptom of taijin kyofusho). There also appears to be phenomenological overlap with body dysmorphic disorder, obsessive-compulsive disorder, and hypochondriasis. This paper provides a focused review of the literature to address issues for DSM-V, including whether ORS should continue to be mentioned as an example of another disorder or should be included as a separate diagnosis. We present a number of options and preliminary recommendations for consideration for DSM-V. Because research is still very limited, it is unclear how ORS should best be classified. Nonetheless, classifying ORS as a type of delusional disorder appears problematic. Given this syndrome’s consistent clinical description across cultures for more than a century, substantial morbidity, and a small but growing research literature, we make the preliminary recommendation that ORS be included in DSM-V’s Appendix of Criteria Sets Provided for Further Study, and we suggest diagnostic criteria.
PMCID: PMC4247225  PMID: 20533369
odor; smell; delusional disorder; hallucinations; olfactory; DSM-V
Depression and Anxiety  2013;31(7):566-573.
Our objective was to compare self- and parent-reported irritability in youths with anxiety disorders, healthy youths, and those with mood disorders characterized by irritability. Irritability is a common but relatively understudied psychiatric symptom in child and adolescent anxiety disorders. In anxious youths, little is known about the severity of irritability, its impact on functioning, or the effect of informant source on reports of irritability.
We compared parent- and self-report forms of the Affective Reactivity Index (ARI), a validated measure of irritability, in youths ages 8–17 years with no psychopathology (healthy comparison, HC; n = 38), anxiety disorders (ANX; n = 42), bipolar disorder (BD; n = 35), or severe mood dysregulation (SMD; n = 61; a phenotype characterized by chronic, severely impairing irritability).
Irritability was significantly higher in ANX than HC youths by both parent and self-report (partial η2 = 0.24 and 0.22, respectively, P’s < 0.001). Informant effects differed among ANX, BD, and SMD. Overall, parent-reported irritability was higher in BD with comorbid anxiety disorders and SMD with or without comorbid anxiety disorders than ANX (P’s < 0.007), but self-reported irritability was not significantly different among the three patient groups.
By both parent and self-report, youths with anxiety disorders exhibit significantly more irritability and associated impairment than healthy subjects. Self-reported irritability in youths with anxiety disorders is comparable to that observed in youths with severe mood disorders, although parental reports of irritability differ among the disorders. Future research should examine the pathophysiology of anxiety-associated irritability, as well as its prognostic and treatment implications.
PMCID: PMC3937265  PMID: 23818321
irritable mood; anxiety disorders; trait anger
Depression and Anxiety  2013;30(12):1185-1193.
Depression and anxiety co-occur with substance use and abuse at a high rate. Ascertaining whether substance use plays a causal role in depression and anxiety is difficult or impossible with conventional observational epidemiology. Mendelian randomisation uses genetic variants as a proxy for environmental exposures, such as substance use, which can address problems of reverse causation and residual confounding, providing stronger evidence about causality. Genetic variants can be used instead of directly measuring exposure levels, in order to gain an unbiased estimate of the effect of various exposures on depression and anxiety. The suitability of the genetic variant as a proxy can be ascertained by confirming that there is no relationship between variant and outcome in those who do not use the substance. At present, there are suitable instruments for tobacco use, so we use that as a case study. Proof-of-principle Mendelian randomisation studies using these variants have found evidence for a causal effect of smoking on body mass index. Two studies have investigated tobacco and depression using this method, but neither found strong evidence that smoking causes depression or anxiety; evidence is more consistent with a self-medication hypothesis. Mendelian randomisation represents a technique that can aid understanding of exposures that may or may not be causally related to depression and anxiety. As more suitable instruments emerge (including the use of allelic risk scores rather than individual single nucleotide polymorphisms), the effect of other substances can be investigated. Linkage disequilibrium, pleiotropy, and population stratification, which can distort Mendelian randomisation studies, are also discussed.
PMCID: PMC4235433  PMID: 23847157
instrumental variable; genetics; causal inference; substance use
14.  Comparative Outcomes among the Problem Areas of Interpersonal Psychotherapy for Depression 
Depression and anxiety  2010;27(5):434-440.
Although interpersonal psychotherapy (IPT) is an efficacious treatment for acute depression, the relative efficacy of treatment in each of the four IPT problem areas (grief, role transitions, role disputes, interpersonal deficits) has received little attention. We evaluated the specificity of IPT by comparing treatment success among patients whose psychotherapy focused on each problem area. Moreover, we sought to understand how the patient characteristics and interpersonal problems most closely linked to the onset of a patient’s current depression contributed to IPT success.
Patients meeting DSM-IV criteria for an episode of major depressive disorder (n=182) were treated with weekly IPT. Remission was defined as an average Hamilton Rating Scale for Depression 17-item score of 7 or below over 3 weeks. Personality disorders were diagnosed using the Structured Clinical Interview for DSM-IV Personality Disorders.
Contrary to our prediction that patients whose treatment was focused on interpersonal deficits would take longer to remit, survival analyses indicated that patients receiving treatment focused on each of the four problem areas did not differ in their times to remission. Nor were patients in the interpersonal deficits group more likely to have an Axis II diagnosis. Patients whose treatment focused on role transitions remitted faster than those whose treatment focused on role disputes, after controlling for covariates.
With skillful use of IPT strategies and tactics and with careful medication management where appropriate, patients in this study whose treatment focused on each problem area were treated with equal success by trained IPT clinicians.
PMCID: PMC4228685  PMID: 20099274
mood disorders; treatment outcome; personality disorders; specificity; pharmacotherapy
Depression and anxiety  2014;31(8):690-698.
Treatment-resistant depression (TRD) is a pervasive and difficult to treat condition for which deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCCwm) is an emerging therapeutic option. However, neuropsychological safety data for this novel treatment have only been published for a small number of subjects. Moreover, little is known regarding the neuropsychological profile present in TRD patients at baseline, prior to initiation of DBS therapy. This report describes the neuropsychological effects of TRD and acute and chronic DBS of the SCCwm in patients with unipolar and bipolar TRD.
Patients with TRD (N =17) were compared to a healthy control group (N = 15) on subtests from the Cambridge Neuropsychological Test Automated Battery and the Stroop Task. Patients were then tested again at subsequent time points of 1 and 6 months following the initiation of chronic DBS of the SCCwm.
Patients with TRD showed similar levels of performance to healthy controls on most neuropsychological measures, with the exception that the TRD group had slower processing speed. Patients with bipolar TRD, relative to those with unipolar TRD, obtained lower scores on measures of executive function and memory only at baseline. With acute and chronic SCCwm DBS, neuropsychological function improved in multiple domains including processing speed and executive function (planning, set shifting, response inhibition), and memory remained stable.
Patients with TRD show slowed processing speed but otherwise largely preserved neuropsychological functioning. DBS of the SCCwm does not result in worsening of any aspect of neuropsychological function and may improve certain domains. Future research is warranted to better understand the effects of TRD and DBS on neuropsychological function.
PMCID: PMC4226070  PMID: 24753183
deep brain stimulation; neuropsychology; subcallosal cingulate; treatment-resistant depression
16.  Generalized anxiety disorder and the proposed associated symptoms criterion change for DSM-5 in a treatment-seeking sample of anxious youth 
Depression and anxiety  2012;29(12):994-1003.
A current proposal for the DSM-5 generalized anxiety disorder (GAD) definition is to remove fatigue, difficulty concentrating, irritability, and sleep disturbance from the list of associated symptoms, and to require the presence of one of two retained symptoms (restlessness or muscle tension) for diagnosis. Relevant evaluations in youth to support such a change are sparse.
The present study evaluated patterns and correlates of the DSM-IV GAD associated symptoms in a large outpatient sample of anxious youth (N=650) to empirically consider how the proposed diagnostic change might impact the prevalence and sample composition of GAD in children.
Logistic regression found irritability to be the most associated, and restlessness to be the least associated, with GAD diagnosis. Fatigue, difficulty concentrating, and sleep disturbances—which have each been suggested to be nonspecific to GAD due to their prevalence in depression—showed sizable associations with GAD even after accounting for depression and attention problems. Among GAD youth, 10.9% would not meet the proposed DSM-5 associated symptoms criterion. These children were comparable to GAD youth who would meet the proposed criteria with regard to clinical severity, symptomatology, and functioning.
A substantial proportion of youth with excessive, clinically impairing worry may be left unclassified by the DSM-5 if the proposed GAD associated symptoms criterion is adopted. Despite support for the proposed criterion change in adult samples, the present findings suggest that in children it may increase the false negative rate. This calls into question whether the proposed associated symptoms criterion is optimal for defining childhood GAD.
PMCID: PMC4224948  PMID: 22952043
Anxiety disorders; Children; Classification; Diagnosis; Diagnostic and Statistical Manual of Mental Disorders; DSM-5
Depression and anxiety  2014;31(7):551-558.
Terrorist attacks have been shown to precipitate posttraumatic stress disorder (PTSD) symptomatology in children and adolescents, particularly among youths with high exposure to media coverage surrounding such events. Media exposure may be particularly likely to trigger PTSD symptoms in youths with high physiological reactivity to stress or with prior psychopathology or exposure to violence. We examined the interplay between media exposure, preattack psychopathology, autonomic nervous system (ANS) reactivity, and prior violence exposure in predicting PTSD symptom onset following the terrorist attack at the 2013 Boston Marathon.
A community sample of 78 adolescents (mean age = 16.7 years, 65% female) completed a survey about the bombings, including media exposure to the event and PTSD symptoms. All respondents participated in a study assessing psychopathology prior to the attack, and sympathetic and parasympathetic reactivity to a laboratory-based stressor was assessed in a subset (N = 44) of this sample. We examined the associations of media exposure, ANS reactivity, preattack psychopathology, and prior violence exposure with onset of PTSD symptoms related to the bombings.
Media exposure, preattack psychopathology, and prior violence exposure were associated with PTSD symptoms. Moreover, media exposure interacted with sympathetic reactivity to predict PTSD symptom onset, such that adolescents with lower levels of sympathetic reactivity developed PTSD symptoms only following high exposure to media coverage of the attack.
We provide novel evidence that physiological reactivity prior to exposure to an unpredictable traumatic stressor predicts PTSD symptom onset. These findings have implications for identifying youths most vulnerable to PTSD following wide-scale trauma.
PMCID: PMC4219737  PMID: 24995832
media exposure; sympathetic nervous system; terrorism; posttraumatic stress disorder; stress
18.  Retention and Attrition Among African Americans in the STAR*D Study: What Causes Research Volunteers to Stay or Stray? 
Depression and anxiety  2013;30(11):10.1002/da.22134.
High attrition rates among African-Americans (AA) volunteers are a persistent problem that makes clinical trials less representative and complicates estimation of treatment outcomes. Many studies contrast AA with other ethnic/racial groups, but few compare the AA volunteers who remain in treatment with those who leave. Here, in addition to comparing patterns of attrition between African Americans and whites, we identify predictors of overall and early attrition among African Americans.
Sample comprised non-Hispanic African-American (n=673) and white (n=2,549) participants in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Chi-square tests were used to examine racial group differences in reasons for exit. Multivariate logistic regression was used to examine predictors of overall attrition, early attrition (by Level 2) and top reasons cited for attrition among African Americans.
For both African-American and white dropouts, non-compliance reasons for attrition were most commonly cited during the earlier phases of the study while reasons related to efficacy and medication side effects were cited later in the study. Satisfaction with treatment strongly predicted overall attrition among African Americans independent of socioeconomic, clinical, medical or psychosocial factors. Early attrition among African American dropouts was associated with less psychiatric comorbidity, and higher perceived physical functioning but greater severity of clinician-rated depression.
The decision to drop out is a dynamic process that changes over the course of a clinical trial. Strategies aimed at retaining African Americans in such trials should emphasize engagement with treatment and patient satisfaction immediately following enrollment and after treatment initiation.
PMCID: PMC3818393  PMID: 23723044
Research Volunteers; Ethnic Groups; Blacks; Depression; Disparities; Treatment
19.  Trajectories of Change in Anxiety Severity and Impairment During and After Treatment with Evidence-Based Treatment for Multiple Anxiety Disorders in Primary Care 
Depression and anxiety  2013;30(11):1099-1106.
Coordinated Anxiety Learning and Management (CALM) is a model for delivering evidence-based treatment for anxiety disorders in primary care. Compared to usual care, CALM produced greater improvement in anxiety symptoms. However, mean estimates can obscure heterogeneity in treatment response. This study aimed to identify (1) clusters of participants with similar patterns of change in anxiety severity and impairment (trajectory groups); and (2) characteristics that predict trajectory group membership.
The CALM randomized controlled effectiveness trial was conducted in 17 primary care clinics in 4 US cities in 2006–2009. 1,004 English- or Spanish-speaking patients age 18–75 with panic, generalized anxiety, social anxiety, and/or posttraumatic stress disorder participated. The Overall Anxiety Severity and Impairment Scale was administered repeatedly to 482 participants randomized to CALM treatment. Group-based trajectory modeling was applied to identify trajectory groups and multinomial logit to predict trajectory group membership.
Two predicted trajectories, representing about two-thirds of participants, were below the cut-off for clinically significant anxiety a couple of months after treatment initiation. The predicted trajectory for the majority of remaining participants was below by nine months. A small group of participants did not show consistent improvement. Being sicker at baseline, not working, and reporting less social support were associated with less favorable trajectories.
There is heterogeneity in patient response to anxiety treatment. Adverse circumstances appear to hamper treatment response. To what extent anxiety symptoms improve insufficiently because adverse patient circumstances contribute to suboptimal treatment delivery, suboptimal treatment adherence, or suboptimal treatment response requires further investigation.
Clinical Trial Registration Identifier: NCT00347269
PMCID: PMC3902647  PMID: 23801589
Anxiety/anxiety disorders; CBT/cognitive behavior therapy; primary care; treatment; life events/stress
Depression and anxiety  2013;30(11):1114-1120.
Sleep quality may be an important, yet relatively neglected, predictor of treatment outcome in cognitive-behavioral therapy (CBT) for anxiety disorders. Specifically, poor sleep quality may impair memory consolidation of in-session extinction learning. We therefore examined sleep quality as a predictor of treatment outcome in CBT for social anxiety disorder and the impact of d-cycloserine (DCS) on this relationship.
One hundred sixty-nine participants with a primary diagnosis of DSM-IV generalized social anxiety disorder were recruited across three sites. Participants were enrolled in 12 weeks of group CBT. Participants randomly received 50 mg of DCS (n = 87) or pill placebo (n = 82) 1 hr prior to sessions 3–7. Participants completed a baseline measure of self-reported sleep quality and daily diaries recording subjective feelings of being rested upon wakening. Outcome measures including social anxiety symptoms and global severity scores were assessed at each session.
Poorer baseline sleep quality was associated with slower improvement and higher posttreatment social anxiety symptom and severity scores. Moreover, patients who felt more “rested” after sleeping the night following a treatment session had lower levels of symptoms and global severity at the next session, controlling for their symptoms and severity scores the previous session. Neither of these effects were moderated by DCS condition.
Our findings suggest that poor sleep quality diminishes the effects of CBT for social anxiety disorder and this relation is not attenuated by DCS administration. Therapeutic attention to sleep quality prior to initiation of CBT and during the acute treatment phase may be clinically indicated.
PMCID: PMC4043139  PMID: 24038728
sleep quality; cognitive behavioral therapy; psychotherapy; social anxiety disorder; social phobia; d-cycloserine
Depression and anxiety  2014;31(6):494-505.
The development of the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) and ICD-11 has led to reconsideration of diagnostic criteria for posttraumatic stress disorder (PTSD). The World Mental Health (WMH) Surveys allow investigation of the implications of the changing criteria compared to DSM-IV and ICD-10.
WMH Surveys in 13 countries asked respondents to enumerate all their lifetime traumatic events (TEs) and randomly selected one TE per respondent for PTSD assessment. DSMIV and ICD-10 PTSD were assessed for the 23,936 respondents who reported lifetime TEs in these surveys with the fully structured Composite International Diagnostic Interview (CIDI). DSM-5 and proposed ICD-11 criteria were approximated. Associations of the different criteria sets with indicators of clinical severity (distress-impairment, suicidality, comorbid fear-distress disorders, PTSD symptom duration) were examined to investigate the implications of using the different systems.
A total of 5.6% of respondents met criteria for “broadly defined” PTSD (i.e., full criteria in at least one diagnostic system), with prevalence ranging from 3.0% with DSM-5 to 4.4% with ICD-10. Only one-third of broadly defined cases met criteria in all four systems and another one third in only one system (narrowly defined cases). Between-system differences in indicators of clinical severity suggest that ICD-10 criteria are least strict and DSM-IV criteria most strict. The more striking result, though, is that significantly elevated indicators of clinical significance were found even for narrowly defined cases for each of the four diagnostic systems.
These results argue for a broad definition of PTSD defined by any one of the different systems to capture all clinically significant cases of PTSD in future studies.
PMCID: PMC4211431  PMID: 24894802
Posttraumatic stress disorder; World Mental Health Surveys; epidemiology; nosology; DSM-IV; DSM-5; ICD-10; ICD-11
22.  Toward an Account of Clinical Anxiety Predicated on Basic, Neurally-Mapped Mechanisms of Pavlovian Fear-Learning: The Case for Conditioned Overgeneralization 
Depression and anxiety  2012;29(4):257-263.
The past two decades have brought dramatic progress in the neuroscience of anxiety due, in no small part, to animal findings specifying the neurobiology of Pavlovian fear-conditioning. Fortuitously, this neurally mapped process of fear learning is widely expressed in humans, and has been centrally implicated in the etiology of clinical anxiety. Fear-conditioning experiments in anxiety patients thus represent a unique opportunity to bring recent advances in animal neuroscience to bear on working, brain-based models of clinical anxiety. The current presentation details the neural basis and clinical relevance of fear conditioning, and highlights generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of clinical anxiety. Studies testing such generalization across a variety of anxiety disorders (panic, generalized anxiety disorder, and social anxiety disorder) with systematic methods developed in animals will next be presented. Finally, neural accounts of over-generalization deriving from animal and human data will be described with emphasis given to implications for the neurobiology and treatment of clinical anxiety.
PMCID: PMC4194209  PMID: 22447565
anxiety disorders; Pavlovian fear-conditioning; stimulus generalization; neurobiology; fMRI; fear-potentiated startle
23.  Developmental timing of child maltreatment and symptoms of depression and suicidal ideation in young adulthood: Results from the National Longitudinal Study on Adolescent Health 
Depression and anxiety  2013;30(10):10.1002/da.22102.
Child maltreatment is a potent risk factor for psychopathology. Although the developmental timing of first exposure to maltreatment is considered important in shaping risk of future psychopathology, no consensus exists on whether earlier or later exposures are more deleterious. This study examines whether age at first exposure to abuse is associated with subsequent depression and suicidal ideation.
Data were drawn from the National Longitudinal Study on Adolescent Health (n=15,701). Timing of first maltreatment exposure was classified using: (1) a crude measure capturing early childhood (0–5), middle childhood (6–10), or adolescence (11–17); and (2) a refined measure capturing infancy (0–2), preschool (3–5), latency (6–8), prepubertal (9–10), pubertal (11–13), or adolescence (14–17). We examined whether timing of first exposure was associated with depression and suicidal ideation in early adulthood in the entire sample and among those exposed to maltreatment.
Respondents exposed to physical abuse at any age had a higher odds of depression and suicidal ideation in young adulthood than non-maltreated respondents. Among maltreated respondents, exposure during early childhood (0–5), particularly pre-school (3–5), was most strongly associated with depression. Respondents first exposed to physical abuse during preschool had a 77% increase in the odds of depression and those first exposed to sexual abuse during early childhood had a 146% increase in the odds of suicidal ideation compared to respondents maltreated as adolescents.
Developmental timing of first exposure to maltreatment influences risk for depression and suicidal ideation. Whether these findings are evidence for biologically-based sensitive periods requires further study.
PMCID: PMC3873604  PMID: 23592532
developmental timing; sensitive period; child maltreatment; depression; suicidal
Depression and anxiety  2013;30(10):940-946.
Genetics of Recurrent Early-Onset Depression study (GenRED II) data were used to examine the relationship between posttraumatic stress disorder (PTSD) and attempted suicide in a population of 1,433 individuals with recurrent early-onset major depressive disorder (MDD). We tested the hypothesis that PTSD resulting from assaultive trauma increases risk for attempted suicide among individuals with recurrent MDD.
Data on lifetime trauma exposures and clinical symptoms were collected using the Diagnostic Interview for Genetic Studies version 3.0 and best estimate diagnoses of MDD, PTSD, and other DSM-IV Axis I disorders were reported with best estimated age of onset.
The lifetime prevalence of suicide attempt in this sample was 28%. Lifetime PTSD was diagnosed in 205 (14.3%) participants. We used discrete time-survival analyses to take into account timing in the PTSD-suicide attempt relationship while adjusting for demographic variables (gender, race, age, and education level) and comorbid diagnoses prior to trauma exposure. PTSD was an independent predictor of subsequent suicide attempt (HR = 2.5, 95% CI: 1.6, 3.8; P < .0001). Neither assaultive nor nonassaultive trauma without PTSD significantly predicted subsequent suicide attempt after Bonferroni correction. The association between PTSD and subsequent suicide attempt was driven by traumatic events involving assaultive violence (HR = 1.7, 95% CI: 1.3, 2.2; P < .0001).
Among those with recurrent MDD, PTSD appears to be a vulnerability marker of maladaptive responses to traumatic events and an independent risk factor for attempted suicide. Additional studies examining differences between those with and without PTSD on biological measures might shed light on this potential vulnerability
PMCID: PMC4026925  PMID: 23893768
25.  Potentially Traumatic Events and the Risk of Six Physical Health Conditions in a Population-Based Sample 
Depression and anxiety  2013;30(5):451-460.
Potentially traumatic events (PTEs) are common in the population, yet, the impact of total burden and specific types of PTEs on physical health has not been systematically investigated.
Data were drawn from the Detroit Neighborhood Health Study, a community sample of predominately African Americans living in Detroit, Michigan, interviewed in 2008–2009 (N = 1,547) and in 2009–2010 (N = 1,054). Kaplan–Meier and Cox proportional hazards models were used.
Respondents with the highest levels of PTE exposure (8+ events) had an average age of adverse physical health condition diagnosis that was 15 years earlier than respondents with no exposure. There was a monotonic relation between number of PTEs and arthritis risk. Compared to those who reported no lifetime events, respondents with 1–2, 3–4, 5–7, and 8+ traumatic events had 1.06, 1.12, 1.73, and 2.44 times the hazard of arthritis. Assaultive violence (HR = 1.7; 95% CI 1.2–2.3) and other threats to physical integrity (HR = 1.5, 95% CI 1.1–2.1) were particularly strong risk factors for arthritis.
These results provide novel evidence linking PTEs, particularly those involving violence and threat to life, to elevated risk for arthritic conditions. Efforts to prevent or mitigate traumatic event exposures may have a broad range of benefits for health.
PMCID: PMC4180235  PMID: 23495094
trauma; traumatic events; chronic disease; arthritis; physical health; African Americans

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