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Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values

Objective. This open-label study examined the safety and efficacy of ziprasidone intramuscular with geriatric patients experiencing psychosis or agitation.Design. During an inpatient stay, consenting subjects who became acutely psychotic or agitated received ziprasidone intramuscular 10mg q 6 to 8 hours, up to a maximum dose of 20mg/24 hours. A within-group repeated measures design was employed to study whether the use of ziprasidone over the 24-hour observation period contributed to decreased agitation or to extrapyramidal side effects. The data were analyzed using an Analysis of Variance with trend analysis.Setting. The study was conducted on the geriatric psychiatry inpatient unit at the University of Toledo Medical Center, Toledo, Ohio.Participants. Fourteen patients, six men and eight women with mean age 77+/-8 years, participated in this study. Each patient had a diagnosis of dementia, co-occurring with one of the following: delirium, major depressive disorder with psychotic features, schizophrenia, bipolar disorder, or schizoaffective disorder.Measurements. The Brief Psychiatric Rating Scale, Delirium Rating Scale, and the Behavioral Activity Rating Scale were obtained at baseline and at 0.5, 2, and 24 hours after the first dose of ziprasidone intramuscular.Results. Overall, physiologic measures that would indicate undesirable side effects, including QTc intervals, remained unchanged pre- and post-study. However, there were significant improvements in scores on a variety of measures assessing agitation or psychosis.Conclusion. This study suggests that ziprasidone intramuscular may be a safe and effective short-term treatment for agitated or psychotic geriatric patients, and, therefore, additional studies should be conducted to confirm these findings.

Background: Nonadherence to antidepressant medication significantly contributes to the undertreatment of depression in primary care populations. The purpose of this study was to survey primary care patients' adherence to antidepressant medication to better understand factors associated with nonadherence., Method: Participants with a history of being prescribed an antidepressant for at least 4 weeks were recruited from a primary care research network. Subjects completed a demographic survey, the Patient Health Questionnaire (PHQ), the Beck Depression Inventory-II (BDI-II), the Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey, the Interpersonal Support Evaluation List, the Stages of Change Scale, the Medication Adherence Scale, and the MOS measure of adherence. Differences between adherent and nonadherent patients were compared using chi(2) for discrete variables, independent t tests for continuous variables, and Mann-Whitney U tests for rank-ordered data. Data were collected from April 1, 2001 to April 1, 2004., Results: Approximately 80% (N = 148) of individuals approached for this study agreed to participate. The overall sample was primarily white and female. The PHQ diagnoses at study entry were dysthymic disorder (8.8%, n = 13), major depressive disorder (31.8%, n = 47), "double depression" (both dysthymic disorder and major depressive disorder, 29.7%, n = 44), and no depression (16.2%, n = 24.) The mean BDI-II score for the total sample was 19.9. Nonadherent patients reported being more careless about taking their medications, were more worried about side effects, were less satisfied with their physicians, were under the age of 40 years, and were more likely to have asked for a specific antidepressant. Nonadherent patients also indicated being at lower stages of change., Conclusions: Individually tailoring education to patient preference and stage of change is recommended to promote adherence.