Major depression is a complex disorder with no single, direct causal mechanism. Morbidity has been linked to genetic processes, developmental history, and unique environmental exposures. Epigenetic mechanisms, especially DNA methylation, are also likely important factors in the pathogenesis of major depressive disorder (MDD). A community-based twin sample has many advantages for epigenetic studies, given the shared genetic and developmental histories of same-sex twin pairs. This article describes the rationale and study design for the Mood and Methylation Study in which 133 twin pairs (101 monozygotic and 32 dizygotic), both discordant and concordant for lifetime history of MDD, were evaluated on a large number of variables related to MDD. The twins also provided blood samples for an epigenome-wide association study of differentially methylated regions (DMR) relevant to MDD. Although MDD is typically considered a disorder of the central nervous system, it is unfeasible to obtain a large sample of brain tissues. However, epigenetic variation is not limited to the affected tissue but can also be detected in peripheral blood leukocytes. Thus, this study focused on monocytes for the major analyses. Additional plans for the study include gene expression analysis from the same set of twins using RNA-seq and validation of significant DMRs in postmortem brain tissues from a separate sample. Moreover, sufficient samples have been collected to perform future ‘multi-omic’ analyses, including metabolome, microbiome, and transcriptome. Our long-term goal is to understand how epigenomic and other ‘omic’ factors can be manipulated for diagnostic, preventive, and therapeutic purposes for MDD and its related conditions.

Collaborative care is a well-studied and effective model of integrating behavioural healthcare into primary care medical settings. Despite evidence of its effectiveness, it has been difficult to implement into the US healthcare system. The upcoming reorganisation of US healthcare will rely heavily on adaptations of this model to improve its uptake and cost-effectiveness.

Background. Panic disorder is a prevalent, often disabling, disorder among primary-care patients, but there are large gaps in quality of treatment in primary care. This study describes the incremental cost-effectiveness of a combined cognitive behavioral therapy (CBT) and pharmacotherapy intervention for patients with panic disorder versus usual primary-care treatment.

Method. This randomized control trial recruited 232 primary-care patients meeting DSM-IV criteria for panic disorder from March 2000 to March 2002 from six primary-care clinics from university-affiliated clinics at the University of Washington (Seattle) and University of California (Los Angeles and San Diego). Patients were randomly assigned to receive either treatment as usual or a combined CBT and pharmacotherapy intervention for panic disorder delivered in primary care by a mental health therapist. Intervention patients had up to six sessions of CBT modified for the primary-care setting in the first 12 weeks, and up to six telephone follow-ups over the next 9 months. The primary outcome variables were total out-patient costs, anxiety-free days (AFDs) and quality adjusted life-years (QALYs).

Results. Relative to usual care, intervention patients experienced 60·4 [95% confidence interval (CI) 42·9–77·9] more AFDs over a 12-month period. Total incremental out-patient costs were $492 higher (95% CI $236–747) in intervention versus usual care patients with a cost per additional AFD of $8.40 (95% CI $2.80–14.0) and a cost per QALY ranging from $14158 (95% CI $6791–21496) to $24776 (95% CI $11885–37618). The cost per QALY estimate is well within the range of other commonly accepted medical interventions such as statin use and treatment of hypertension.

Conclusions. The combined CBT and pharmacotherapy intervention was associated with a robust clinical improvement compared to usual care with a moderate increase in ambulatory costs.

Background. Excessive worry is required by DSM-IV, but not ICD-10, for a diagnosis of generalized anxiety disorder (GAD). No large-scale epidemiological study has ever examined the implications of this requirement for estimates of prevalence, severity, or correlates of GAD.

Method. Data were analyzed from the US National Comorbidity Survey Replication, a nationally representative, face-to-face survey of adults in the USA household population that was fielded in 2001–2003. DSM-IV GAD was assessed with Version 3.0 of the WHO Composite International Diagnostic Interview. Non-excessive worriers meeting all other DSM-IV criteria for GAD were compared with respondents who met full GAD criteria as well as with other survey respondents to consider the implications of removing the excessiveness requirement.

Results. The estimated lifetime prevalence of GAD increases by ~40% when the excessiveness requirement is removed. Excessive GAD begins earlier in life, has a more chronic course, and is associated with greater symptom severity and psychiatric co-morbidity than non-excessive GAD. However, non-excessive cases nonetheless evidence substantial persistence and impairment of GAD, high rates of treatment-seeking, and significantly elevated co-morbidity compared with respondents without GAD. Non-excessive cases also have sociodemographic characteristics and familial aggregation of GAD comparable to excessive cases.

Conclusions. Individuals who meet all criteria for GAD other than excessiveness have a somewhat milder presentation than those with excessive worry, yet resemble excessive worriers in a number of important ways. These findings challenge the validity of the excessiveness requirement and highlight the need for further research into the optimal definition of GAD.

Background. Empirical findings suggest that psychiatric illness is associated with cardiovascular disease (CVD). The purpose of this study was to compare the strength of the association of lifetime post-traumatic stress disorder (PTSD) and lifetime major depression on CVD among Northern Plains American Indians.

Method. A total of 1414 participants aged 18–57 years completed a structured interview that assessed psychiatric diagnoses, alcohol abuse/dependence, self-reported CVD, and traditional CVD risk factors including age, sex, education, diabetes, high blood pressure, and smoking. Logistic regression analyses compared the odds ratios of CVD in participants with and without diagnosed PTSD or major depression.

Results. The rates of lifetime PTSD and major depression were 15% and 8% respectively. CVD was more commonly reported by participants with PTSD than by those without PTSD (12% v. 5%, p[les ]0·01). Likewise, more participants with major depression reported CVD than did their non-depressed counterparts (14% v. 6%, p[les ]0·05). PTSD was significantly associated with CVD even after controlling for traditional CVD risk factors and major depression (odds ratio 2·0, confidence interval 1·1–3·8). In contrast, the association of major depression with CVD was not significant after accounting for both traditional risk factors and PTSD.

Conclusions. Rates of PTSD are high in American Indian communities. Rising CVD rates in this population may be better understood if PTSD is considered along with other traditional risk factors. Future research should examine the association and mechanisms of PTSD and CVD prospectively. Such data could lead to more effective CVD prevention efforts for American Indians.

Background.Randomized clinical trials indicate a benefit from combining medications with cognitive behavioral therapy (CBT) relative to medication alone for panic disorder. Using an as-treated analysis, we evaluated whether the addition of CBT enhanced outcomes for panic disorder relative to medications alone in the primary-care setting.

Method.Primary-care patients with panic disorder reported on their receipt of CBT and medications over the 3 months following baseline assessment. The degree to which outcomes for those who used anti-panic medications were enhanced by the receipt of at least one component of CBT was analyzed using a propensity score model that took into account observable baseline patient characteristics influencing both treatment selection and outcomes.

Results.The addition of CBT resulted in statistically and clinically significant improvements at 3 months on anxiety sensitivity, social avoidance, and disability. Also, patients receiving CBT in the first 3 months of the study were more improved at 12 months than patients who took medications only during the first 3 months of the study.

Conclusions.The clinical utility of the findings are discussed in terms of the importance of primary-care physicians encouraging their panic disorder patients to receive CBT as well as medications.

Background. The proposed revisions of the ICD and DSM diagnostic systems have led to increased interest in evaluation of diagnostic criteria. This report focuses on the DSM-IV requirement that episodes of generalized anxiety disorder (GAD) must persist for at least 6 months. Community epidemiological data are used to study the implications of changing this requirement in the range 1–12 months for estimates of prevalence, onset, course, impairment, co-morbidity, associations with parental GAD, and sociodemographic correlates.

Method. Data come from the US National Comorbidity Survey Replication (NCS-R), a US household survey carried out during 2001–2003. Version 3.0 of the WHO Composite International Diagnostic Interview (WMH-CIDI) was used to assess DSM-IV anxiety disorders, mood disorders, substance disorders, and impulse-control disorders.

Results. Lifetime, 12-month, and 30-day prevalence estimates of DSM-IV GAD changed from 6·1%, 2·9%, and 1·8% to 4·2–12·7%, 2·2–5·5%, and 1·6–2·6% when the duration requirement was changed from 6 months to 1–12 months. Cases with episodes of 1–5 months did not differ greatly from those with episodes of [ges ]6 months in onset, persistence, impairment, co-morbidity, parental GAD, or sociodemographic correlates.

Conclusions. A large number of people suffer from a GAD-like syndrome with episodes of <6 months duration. Little basis for excluding these people from a diagnosis is found in the associations examined here.

The definition and clinical aspects of rapid cycling affective illness are reviewed and various factors associated with the onset and maintenance of rapid cycling enumerated. On the basis of this information and of reports of the response of rapid cycling patients to various treatment interventions, an approach is suggested to the evaluation and treatment of rapid cycling affective illness.