Effect of Pharmacogenomic Testing for Drug-Gene Interactions on Medication Selection and Remission of Symptoms in Major Depressive Disorder: The PRIME Care Randomized Clinical Trial.

Importance: Selecting effective antidepressants for the treatment of major depressive disorder (MDD) is an imprecise practice, with remission rates of about 30% at the initial treatment. Objective: To determine whether pharmacogenomic testing affects antidepressant medication selection and whether such testing leads to better clinical outcomes. Design, Setting, and Participants: A pragmatic, randomized clinical trial that compared treatment guided by pharmacogenomic testing vs usual care. Participants included 676 clinicians and 1944 patients. Participants were enrolled from 22 Department of Veterans Affairs medical centers from July 2017 through February 2021, with follow-up ending November 2021. Eligible patients were those with MDD who were initiating or switching treatment with a single antidepressant. Exclusion criteria included an active substance use disorder, mania, psychosis, or concurrent treatment with a specified list of medications. Interventions: Results from a commercial pharmacogenomic test were given to clinicians in the pharmacogenomic-guided group (n = 966). The comparison group received usual care and access to pharmacogenomic results after 24 weeks (n = 978). Main Outcomes and Measures: The co-primary outcomes were the proportion of prescriptions with a predicted drug-gene interaction written in the 30 days after randomization and remission of depressive symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9) (remission was defined as PHQ-9 ≤ 5). Remission was analyzed as a repeated measure across 24 weeks by blinded raters. Results: Among 1944 patients who were randomized (mean age, 48 years; 491 women [25%]), 1541 (79%) completed the 24-week assessment. The estimated risks for receiving an antidepressant with none, moderate, and substantial drug-gene interactions for the pharmacogenomic-guided group were 59.3%, 30.0%, and 10.7% compared with 25.7%, 54.6%, and 19.7% in the usual care group. The pharmacogenomic-guided group was more likely to receive a medication with a lower potential drug-gene interaction for no drug-gene vs moderate/substantial interaction (odds ratio [OR], 4.32 [95% CI, 3.47 to 5.39]; P < .001) and no/moderate vs substantial interaction (OR, 2.08 [95% CI, 1.52 to 2.84]; P = .005) (P < .001 for overall comparison). Remission rates over 24 weeks were higher among patients whose care was guided by pharmacogenomic testing than those in usual care (OR, 1.28 [95% CI, 1.05 to 1.57]; P = .02; risk difference, 2.8% [95% CI, 0.6% to 5.1%]) but were not significantly higher at week 24 when 130 patients in the pharmacogenomic-guided group and 126 patients in the usual care group were in remission (estimated risk difference, 1.5% [95% CI, -2.4% to 5.3%]; P = .45). Conclusions and Relevance: Among patients with MDD, provision of pharmacogenomic testing for drug-gene interactions reduced prescription of medications with predicted drug-gene interactions compared with usual care. Provision of test results had small nonpersistent effects on symptom remission. Trial Registration: ClinicalTrials.gov Identifier: NCT03170362.

Fatigue - but not mTBI history, PTSD, or sleep quality - directly contributes to reduced prospective memory performance in Iraq and Afghanistan era Veterans.

OBJECTIVE: Memory problems that affect daily functioning are a frequent complaint among Veterans reporting a history of repetitive mild traumatic brain injury (mTBI), especially in cohorts with comorbid PTSD. Here, we test the degree to which subjective sleep impairment and daytime fatigue account for the association of PTSD and self-reported mTBI history with prospective memory. METHOD: 82 Veterans with and without personal history of repeated blast-related mTBI during deployment were administered the Clinician Administered PTSD Scale (CAPS), Memory for Intentions Test (MIST), Patient Health Questionnaire-9 (PHQ-9), Neurobehavioral Symptom Inventory (NSI), and the Pittsburgh Sleep Quality Index (PSQI). Relationships between self-reported mTBI, PTSD, self-reported poor sleep and daytime fatigue, and MIST performance were modeled using partial least squares structural equation modeling (PLS-SEM). RESULTS: Reported daytime fatigue was strongly associated with poorer prospective memory performance. Poor subjective sleep quality was strongly and positively associated with reported daytime fatigue, but had no significant direct effect on prospective memory performance. PTSD diagnosis and self-reported mTBI history were only associated with prospective memory via their impact on subjective sleep quality and daytime fatigue. CONCLUSIONS: Results suggest that daytime fatigue may be a mediating factor by which both mTBI and PTSD can interfere with prospective memory. Additional attention should be given to complaints of daytime fatigue, independent of subjective sleep quality, in the clinical care of those with a self-reported history of mTBI, and/or PTSD. Further research into whether interventions that decrease daytime fatigue lead to improvement in prospective memory and subjective cognitive functioning is warranted.

Tattoos as a window to the psyche: How talking about skin art can inform psychiatric practice.

Tattooing the skin as a means of personal expression is a ritualized practice that has been around for centuries across many different cultures. Accordingly, the symbolic meaning of tattoos has evolved over time and is highly individualized, from both the internal perspective of the wearer and the external perspective of an observer. Within modern Western societies through the 1970s, tattoos represented a cultural taboo, typically associated with those outside of the mainstream such as soldiers, incarcerated criminals, gang members, and others belonging to marginalized and counter-cultural groups. This paper aims to review the more recent epidemiology of tattoos in Western culture in order to establish that tattooing has become a mainstream phenomenon. We then review psychological and psychiatric aspects of tattoos, with a goal of revising outmoded stigmas about tattooing and helping clinicians working with tattooed patients to facilitate an exploration of the personal meaning of skin art and self-identity. We suggest that as a kind of augmentation of the physical exam, looking at and talking to patients about their tattoos can provide a valuable window into the psyche, informing clinical practice.

Effects of an 8-week meditation program on mood and anxiety in patients with memory loss.

BACKGROUND: This study assesses changes in mood and anxiety in a cohort of subjects with memory loss who participated in an 8-week Kirtan Kriya meditation program. Perceived spirituality also was assessed. Previous reports from this cohort showed changes in cognitive function and cerebral blood flow (CBF). The purpose of this analysis was to assess outcome measures of mood and affect, and also spirituality, and to determine whether or not results correlated with changes in CBF. METHODS: Fifteen (15) subjects (mean age 62±7 years) with memory problems were enrolled in an 8-week meditation program. Before and after the 8-week meditation, subjects were given a battery of neuropsychologic tests as well as measures of mood, anxiety, and spirituality. In addition, they underwent single photon emission computed tomography scans before and after the program. A region-of-interest template obtained counts in several brain structures that could also be compared to the results from the affect and spirituality measures. RESULTS: The meditation training program resulted in notable improvement trends in mood, anxiety, tension, and fatigue, with some parameters reaching statistical significance. All major trends correlated with changes in CBF. There were nonsignificant trends in spirituality scores that did not correlate with changes in CBF. CONCLUSIONS: An 8-week, 12 minute a day meditation program in patients with memory loss was associated with positive changes in mood, anxiety, and other neuropsychologic parameters, and these changes correlated with changes in CBF. A larger-scale study is needed to confirm these findings and better elucidate mechanisms of change.

Meditation effects on cognitive function and cerebral blood flow in subjects with memory loss: a preliminary study.

This preliminary study determined if subjects with memory loss problems demonstrate changes in memory and cerebral blood flow (CBF) after a simple 8-week meditation program. Fourteen subjects with memory problems had an IV inserted and were injected with 250 MBq of Tc-99m ECD while listening to a neutral stimulus CD. They then underwent a pre-program baseline SPECT scan. Then subjects were guided through their first meditation session with a CD, during which they received an injection of 925 MBq ECD, and underwent a pre-program meditation scan. Subjects completed an 8-week meditation program and underwent the same scanning protocol resulting in a post-program baseline and meditation scan. A region of interest (ROI) template obtained counts in each ROI normalized to whole brain to provide a CBF ratio. Baseline and meditation scans and neuropsychological testing were compared before and after the program. The meditation program resulted in significant increases (p< 0.05) in baseline CBF ratios in the prefrontal, superior frontal, and superior parietal cortices. Scores on neuropsychological tests of verbal fluency, Trails B, and logical memory showed improvements after training. This preliminary study evaluated whether an 8-week meditation program resulted in improvements in neuropsychological function and differences in CBF in subjects with memory loss. While the findings are encouraging, there are a number of limitations that can be addressed in future studies with more participants and more detailed analyses.