Abu Minhajuddin

Prevalence of Major Depressive Episode in CKD

BACKGROUND Depression is prevalent in long-term dialysis patients and is associated with death and hospitalization. Whether depression is present through all chronic kidney disease (CKD) stages or appears after dialysis therapy initiation is not clear. We determined the prevalence of a major depressive episode and other psychiatric illnesses by using a structured gold-standard clinical interview and demographic and clinical variables associated with major depressive episode in patients with CKD. STUDY DESIGN Observational cross-sectional study using a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)-based structured interview administered by trained persons to 272 consecutive participants. Multivariable logistic regression was used to determine demographic and clinical variables associated with major depressive episode. SETTING & PARTICIPANTS Patients with stages 2 to 5 CKD not treated by using dialysis were consecutively approached and enrolled from a Veterans Affairs CKD clinic. PREDICTORS Demographic and clinical variables. OUTCOME Major depressive episode diagnosed by using a structured Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)-based interview, the Mini International Neuropsychiatric Interview. RESULTS The cohort had a mean age of 64.5 +/- 12.0 years. Thirty-eight percent were African American, and 55% had diabetes mellitus. Percentages of patients with stages 2, 3, 4, and 5 CKD were 6%, 38%, 41%, and 14%, respectively. Mean hemoglobin level was 12.5 +/- 2.0 g/dL. The prevalence of a major depressive episode was 21% and did not vary significantly among different CKD stages. Variables associated with a major depressive episode were diabetes mellitus, comorbid psychiatric illness, and history of drug or alcohol abuse. LIMITATIONS Single-center study composed of primarily male veterans. CONCLUSIONS One in 5 patients with CKD had a major depressive episode. Patients with CKD should be screened routinely for depression given this high prevalence and the independent association of depression with poor outcomes in patients with end-stage renal disease receiving maintenance dialysis.

Association Between Major Depressive Episodes in Patients With Chronic Kidney Disease and Initiation of Dialysis, Hospitalization, or Death

CONTEXT Patients with chronic kidney disease (CKD) experience increased rates of hospitalization and death. Depressive disorders are associated with morbidity and mortality. Whether depression contributes to poor outcomes in patients with CKD not receiving dialysis is unknown. OBJECTIVE To determine whether the presence of a current major depressive episode (MDE) is associated with poorer outcomes in patients with CKD. DESIGN, SETTING, AND PATIENTS Prospective cohort study of 267 consecutively recruited outpatients with CKD (stages 2-5 and who were not receiving dialysis) at a VA medical center between May 2005 and November 2006 and followed up for 1 year. An MDE was diagnosed by blinded personnel using the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. MAIN OUTCOME MEASURES The primary outcome was event-free survival defined as the composite of death, dialysis initiation, or hospitalization. Secondary outcomes included each of these events assessed separately. RESULTS Among 267 patients, 56 had a current MDE (21%) and 211 did not (79%). There were 127 composite events, 116 hospitalizations, 38 dialysis initiations, and 18 deaths. Events occurred more often in patients with an MDE compared with those without an MDE (61% vs 44%, respectively, P = .03). Four patients with missing dates of hospitalization were excluded from survival analyses. The mean (SD) time to the composite event was 206.5 (19.8) days (95% CI, 167.7-245.3 days) for those with an MDE compared with 273.3 (8.5) days (95% CI, 256.6-290.0 days) for those without an MDE (P = .003). The adjusted hazard ratio (HR) for the composite event for patients with an MDE was 1.86 (95% CI, 1.23-2.84). An MDE at baseline independently predicted progression to dialysis (HR, 3.51; 95% CI, 1.77-6.97) and hospitalization (HR, 1.90; 95% CI, 1.23-2.95). CONCLUSION The presence of an MDE was associated with an increased risk of poor outcomes in CKD patients who were not receiving dialysis, independent of comorbidities and kidney disease severity.

Validation of Depression Screening Scales in Patients With CKD

BACKGROUND Depressive symptoms, assessed by using self-report scales, are present at a striking rate of 45% in patients with chronic kidney disease (CKD) at dialysis therapy initiation. These scales may emphasize somatic symptoms of anorexia, sleep disturbance, and fatigue, which may coexist with chronic disease symptoms and lead to overestimation of depression diagnosis. No study has validated these scales in patients with CKD before dialysis therapy initiation. STUDY DESIGN We conducted a diagnostic test study in participants with CKD to investigate the screening characteristics of 2 depression self-report scales against a gold-standard structured psychiatric interview. SETTING & PARTICIPANTS 272 consecutively recruited outpatients with stages 2 to 5 CKD not treated by dialysis were studied. INDEX TESTS The Beck Depression Inventory (BDI) and the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR(16)) depression screening scales were administered to all participants. REFERENCE TEST A structured Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)-based interview, the Mini International Neuropsychiatric Interview, was administered by trained persons blinded to self-report scale scores. RESULTS 57 of 272 (21%) patients had major depression according to the reference test. The best cutoff scores by means of receiver/responder operating characteristic curves to identify a major depressive episode were 11 for the BDI and 10 for the QIDS-SR(16). Sensitivities were 89% (95% confidence interval [CI], 78 to 96; BDI) and 91% (95% CI, 80 to 97; QIDS-SR(16)), whereas specificities were 88% (95% CI, 83 to 92; BDI) and 88% (95% CI, 83 to 92; QIDS-SR(16)). The positive and negative likelihood ratios for these cutoff scores were 7.6 and 0.1 (BDI) and 7.5 and 0.1 (QIDS-SR(16)). LIMITATIONS Single-center study and a sample not representative of US demographics. CONCLUSIONS We found that a BDI score of 11 or higher was a sensitive and specific cutoff value for identifying a major depressive episode in patients with CKD not on dialysis therapy. Both the BDI and QIDS-SR(16) are effective screening tools.

Addictive-like behaviours to ultraviolet light among frequent indoor tanners

Background.  Frequent, purposeful exposure to ultraviolet (UV) light may induce a compulsive desire to tan despite the negative consequences being known, suggesting a behavioural complex similar to addictive disorders.

Association of Urinary Sodium/Potassium Ratio with Blood Pressure: Sex and Racial Differences

BACKGROUND AND OBJECTIVES Previous studies reporting an association between high BP and high sodium and low potassium intake or urinary sodium/potassium ratio (U[Na(+)]/[K(+)]) primarily included white men and did not control for cardiovascular risk factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This cross-sectional study investigated the association of U[Na(+)]/[K(+)] with BP in 3303 participants using robust linear regression. RESULTS Mean age was 43±10 years, 56% of participants were women, and 52% were African American. BP was higher in African Americans than in non-African Americans, 131/81±20/11 versus 120/76±16/9 mmHg (P<0.001). Mean U[Na(+)]/[K(+)] was 4.4±3.0 in African Americans and 4.1±2.5 in non-African Americans (P=0.002), with medians (interquartile ranges) of 3.7 (3.2) and 3.6 (2.8). Systolic BP increased by 1.6 mmHg (95% confidence interval, 1.0, 2.2) and diastolic BP by 1.0 mmHg (95% confidence interval, 0.6, 1.4) for each 3-unit increase in U[Na(+)]/[K(+)] (P<0.001 for both). This association remained significant after adjusting for diabetes mellitus, smoking, body mass index, total cholesterol, GFR, and urine albumin/creatinine ratio. There was no interaction between African-American race and U[Na(+)]/[K(+)], but for any given value of U[Na(+)]/[K(+)], both systolic BP and diastolic BP were higher in African Americans than in non-African Americans. The diastolic BP increase was higher in men than in women per 3-unit increase in U[Na(+)]/[K(+)] (1.6 versus 0.9 mmHg, interaction P=0.03). CONCLUSIONS Dietary Na(+) excess and K(+) deficiency may play an important role in the pathogenesis of hypertension independent of cardiovascular risk factors. This association may be more pronounced in men than in women.

Preventing Depressive Relapse and Recurrence in Higher-Risk Cognitive Therapy Responders: A Randomized Trial of Continuation Phase Cognitive Therapy, Fluoxetine, or Matched Pill Placebo

IMPORTANCE Strategies to improve the course of recurrent major depressive disorder have great public health relevance. To reduce the risk of relapse/recurrence after acute phase cognitive therapy (CT), a continuation phase model of therapy may improve outcomes. OBJECTIVES To test the efficacy of continuation phase CT (C-CT) and fluoxetine for relapse prevention in a pill placebo (PBO)-controlled randomized trial and compare the durability of prophylaxis after discontinuation of treatments. DESIGN A sequential, 3-stage design with an acute phase (all patients received 12 weeks of CT); 8-month experimental phase (responders at higher risk were randomized to C-CT, fluoxetine, or PBO); and 24 months of longitudinal, posttreatment follow-up. SETTING Two university-based specialty clinics. PATIENTS A total of 523 adults with recurrent major depressive disorder began acute phase CT, of which 241 higher-risk responders were randomized and 181 subsequently entered the follow-up. INTERVENTIONS Cognitive therapy responders at higher risk for relapse were randomized to receive 8 months of C-CT (n = 86), fluoxetine (n = 86), or PBO (n = 69). MAIN OUTCOMES AND MEASURES Survival analyses of relapse/recurrence rates, as determined by blinded evaluators using DSM-IV criteria and the Longitudinal Interval Follow-up Evaluation. RESULTS As predicted, the C-CT or fluoxetine groups were significantly less likely to relapse than the PBO group across 8 months. Relapse/recurrence rates for C-CT and fluoxetine were nearly identical during the 8 months of treatment, although C-CT patients were more likely to accept randomization, stayed in treatment longer, and attended more sessions than those in the fluoxetine and PBO groups. Contrary to prediction, relapse/recurrence rates following the discontinuation of C-CT and fluoxetine did not differ. CONCLUSIONS AND RELEVANCE Relapse risk was reduced by both C-CT and fluoxetine in an enriched randomization sampling only CT responders. The preventive effects of C-CT were not significantly more durable than those of fluoxetine after treatment was stopped, suggesting that some higher-risk patients may require alternate longer-term interventions. TRIAL REGISTRATION clinicaltrials.gov Identifiers: NCT00118404, NCT00183664, and NCT00218764.

Implication of common and disease specific variants in CLU, CR1, and PICALM

Two recent genome-wide association studies (GWAS) for late onset Alzheimers disease (LOAD) revealed 3 new genes: clusterin (CLU), phosphatidylinositol binding clathrin assembly protein (PICALM), and complement receptor 1 (CR1). In order to evaluate association with these genome-wide association study-identified genes and to isolate the variants contributing to the pathogenesis of LOAD, we genotyped the top single nucleotide polymorphisms (SNPs), rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), and sequenced the entire coding regions of these genes in our cohort of 342 LOAD patients and 277 control subjects. We confirmed the association of rs3851179 (PICALM) (p = 7.4 × 10(-3)) with the disease status. Through sequencing we identified 18 variants in CLU, 3 of which were found exclusively in patients; 8 variants (out of 65) in CR1 gene were only found in patients and the 16 variants identified in PICALM gene were present in both patients and controls. In silico analysis of the variants in PICALM did not predict any damaging effect on the protein. The haplotype analysis of the variants in each gene predicted a common haplotype when the 3 single nucleotide polymorphisms rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), respectively, were included. For each gene the haplotype structure and size differed between patients and controls. In conclusion, we confirmed association of CLU, CR1, and PICALM genes with the disease status in our cohort through identification of a number of disease-specific variants among patients through the sequencing of the coding region of these genes.

Altered Neural Cholinergic Receptor Systems in Cocaine-Addicted Subjects

Changes in the brains cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimers disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1- to 6-week abstinent, cocaine- (and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (p<0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula. Group differences in the right dorsolateral prefrontal cortex, posterior cingulate, and middle temporal gyrus were also evident. Scopolamine also revealed group differences in the left hippocampus and right insula as well as the posterior cingulate and middle temporal gyrus. Cocaine addicted and controls differ in their subcortical, limbic, and cortical response to cholinergic probes in areas relevant to craving, learning, and memory. Cholinergic systems may offer a pharmacologic target for cocaine addiction treatment.

Predictors of Abstinence: National Institute of Drug Abuse Multisite Buprenorphine/Naloxone Treatment Trial in Opioid-Dependent Youth.

OBJECTIVE To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth. METHOD Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly individual and group drug counseling. Logistic regression models were constructed to identify baseline and during-treatment predictors of opioid-positive urine (OPU) at week 12. Predictors were selected based on significance or trend toward significance (i.e., p < .1), and backward stepwise selection was used, controlling for treatment group, to produce final independent predictors at p ≤ .05. RESULTS Youth presenting to treatment with previous 30-day injection drug use and more active medical/psychiatric problems were less likely to have a week-12 OPU. Those with early treatment opioid abstinence (i.e., weeks 1 and 2) and those who received additional nonstudy treatments during the study were less likely to have a week-12 OPU and those not completing 12 weeks of treatment were more likely to have an OPU. CONCLUSIONS Youth with advanced illness (i.e., reporting injection drug use and additional health problems) and those receiving ancillary treatments to augment study treatment were more likely to have lower opioid use. Treatment success in the first 2 weeks and completion of 12 weeks of treatment were associated with lower rates of OPU. These findings suggest that youth with advanced illness respond well to Bup/Nal treatment and identify options for tailoring treatment for opioid-dependent youth presenting at community-based settings. CLINICAL TRIAL REGISTRATION INFORMATION Buprenorphine/Naloxone-Facilitated Rehabilitation for Opioid Dependent Adolescents; http://www.clinicaltrials.gov; NCT00078130.

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

OBJECTIVE Currently, no valid measures inform treatment selection for depressed patients. Whether C-reactive protein (CRP) in particular and two other acute phase reactants (inflammatory markers) could differentiate between patients responding to either of two treatments with different mechanisms of action was assessed. METHOD Subjects included Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants randomly assigned to either escitalopram plus placebo (SSRI monotherapy, n=51) or bupropion plus escitalopram combination (bupropion-SSRI combination, n=55) with baseline plasma samples. CRP, serum amyloid P component, and alpha-2-macroglobulin were measured using the Bioplex Pro™ human acute-phase 4-plex panel. We conducted mixed model analyses of depressive symptom (Quick Inventory of Depressive Symptomatology Self-Report) and side-effect burden (Frequency, Intensity, and Burden of Side-Effects Rating Scale) obtained weekly or every other week over the 12-week acute-phase of CO-MED trial to evaluate the relationship between these outcomes and baseline CRP and other acute-phase reactants. RESULTS The treatment arms did not differ in depressive symptom or side effect outcomes. Most participants (69.8%, 74/106) had baseline CRP levels greater than 1mg/L (indicative of systemic inflammatory activity). Higher baseline CRP levels were associated lower depression severity (correlation coefficient=-0.63) with bupropion-SSRI combination but not with SSRI monotherapy (correlation coefficient=0.40). The overall remission rate was 41.5%. The estimated remission rate with CRP threshold based assignment (SSRI monotherapy for <1mg/L and Bupropion-SSRI for ≥1mg/L) was 53.1%, with a number needed to treat of 8.6. Side effect burden was unrelated to any baseline inflammatory marker. CONCLUSIONS Baseline CRP levels relate differentially to antidepressant treatment outcomes in persons with major depressive disorder. Clinicaltrials.gov identifier: NCT00590863.