The Depression Treatment Cascade in Primary Care: A Public Health Perspective

Major depressive disorder (MDD) is common and costly. Primary care remains a major access point for depression treatment, yet the successful clinical resolution of depression in primary care is uncommon. The clinical response to depression suffers from a “treatment cascade”: the affected individual must access health care, be recognized clinically, initiate treatment, receive adequate treatment, and respond to treatment. Major gaps currently exist in primary care at each step along this treatment continuum. We estimate that 12.5% of primary care patients have had MDD in the past year; of those with MDD, 47% are recognized clinically, 24% receive any treatment, 9% receive adequate treatment, and 6% achieve remission. Simulations suggest that only by targeting multiple steps along the depression treatment continuum (e.g. routine screening combined with collaborative care models to support initiation and maintenance of evidence-based depression treatment) can overall remission rates for primary care patients be substantially improved

Temporal order in memory and interval timing: An interference analysis

The effect of varying load in memory tasks performed during a time interval production was examined. In a first experiment, increasing load in memory search for temporal order affected concurrent time production more strongly than varying load in a spatial memory task of equivalent difficulty. This result suggests that timing uses some specific resources also required in processing temporal order in memory, resources that would not be used in the spatial memory task. A second experiment showed that the interference between time production and memory search involving temporal order was stronger when, during the timing task, a decision was made on the temporal position of a memory item, than when information on temporal order was retained throughout the interval to be produced. These results underscore the importance of considering the specific resources and processes involved when the interference between timing and concurrent nontemporal tasks is analyzed

Psychiatric comorbidity in depressed HIV-infected individuals: common and clinically consequential

To report on the prevalence of psychiatric comorbidity and its association with illness severity in depressed HIV patients

Changes in HIV Outcomes Following Depression Care in a Resource-Limited Setting: Results from a Pilot Study in Bamenda, Cameroon

BackgroundLittle is known about how improved depression care affects HIV-related outcomes in Africa. In a sample of depressed HIV patients in a low income, sub-Saharan country, we explored how implementing measurement-based antidepressant care (MBC) affected HIV outcomes over 4 months of antidepressant treatment.MethodsAs part of a project adapting MBC for use in Cameroon, we enrolled 41 depressed HIV patients on antiretroviral therapy in a pilot study in which a depression care manager (DCM) provided an outpatient HIV clinician with evidence-based decision support for antidepressant treatment. Acute depression management was provided for the first 12 weeks, with DCM contact every 2 weeks and HIV clinician appointments every 4 weeks. We measured HIV clinical and psychiatric outcomes at 4 months.ResultsParticipants were moderately depressed at baseline (mean Patient Health Questionnaire [PHQ] score = 14.4, range 13.1, 15.6). All HIV clinical outcomes improved by four month follow-up: mean (range) CD4 count improved from 436 (2, 860) to 452 (132, 876), mean (range) log-viral load decreased from 4.02 (3.86, 4.17) to 3.15 (2.81, 3.49), the proportion with virologic suppression improved from 0% to 18%, mean (range) HIV symptoms decreased from 6.4 (5.5, 7.3) to 3.1 (2.5, 3.7), the proportion reporting good or excellent health improved from 18% to 70%, and the proportion reporting any missed ARV doses in the past month decreased from 73% to 55%. Concurrently, psychiatric measures improved. The mean (range) PHQ score decreased from 14.4 (13.1, 15.6) to 1.6 (0.8, 2.4) and 90% achieved depression remission, while mean maladaptive coping style scores decreased and mean adaptive coping scores and self-efficacy scores improved.ConclusionIn this pilot study of an evidence-based depression treatment intervention for HIV-infected patients in Cameroon, a number of HIV behavioral and non-behavioral health outcomes improved over 4 months of effective depression treatment. These data are consistent with the hypothesis that better depression care can lead to improved HIV outcomes

Clinical outcomes and adverse events of bariatric surgery in adults with severe obesity in Scotland: the SCOTS observational cohort study

Background: Bariatric surgery is a common procedure worldwide for the treatment of severe obesity and associated comorbid conditions but there is a lack of evidence as to medium-term safety and effectiveness outcomes in a United Kingdom setting. Objective: To establish the clinical outcomes and adverse events of different bariatric surgical procedures, their impact on quality of life and the effect on comorbidities. Design: Prospective observational cohort study. Setting: National Health Service secondary care and private practice in Scotland, United Kingdom. Participants: Adults (age >16 years) undergoing their first bariatric surgery procedure. Main outcome measures: Change in weight, hospital length of stay, readmission and reoperation rate, mortality, diabetes outcomes (HbA1c, medications), quality of life, anxiety, depression. Data sources: Patient-reported outcome measures, hospital records, national electronic health records (Scottish Morbidity Record 01, Scottish Care Information Diabetes, National Records Scotland, Prescription Information System). Results: Between December 2013 and February 2017, 548 eligible patients were approached and 445 participants were enrolled in the study. Of those, 335 had bariatric surgery and 1 withdrew from the study. Mean age was 46.0 (9.2) years, 74.7% were female and the median body mass index was 46.4 (42.4; 52.0) kg/m2. Weight was available for 128 participants at 3 years: mean change was −19.0% (±14.1) from the operation and −24.2% (±12.8) from the start of the preoperative weight-management programme. One hundred and thirty-nine (41.4%) participants were readmitted to hospital in the same or subsequent 35 months post surgery, 18 (5.4% of the operated cohort) had a reoperation or procedure considered to be related to bariatric surgery gastrointestinal complications or revisions. Fewer than five participants (<2%) died during follow-up. HbA1c was available for 93/182 and diabetes medications for 139/182 participants who had type 2 diabetes prior to surgery; HbA1c mean change was −5.72 (±16.71) (p = 0.001) mmol/mol and 65.5% required no diabetes medications (p < 0.001) at 3 years post surgery. Physical quality of life, available for 101/335 participants, improved in the 3 years post surgery, mean change in Rand 12-item Short Form Survey physical component score 8.32 (±8.95) (p < 0.001); however, there was no change in the prevalence of anxiety or depression. Limitations: Due to low numbers of bariatric surgery procedures in Scotland, recruitment was stopped before achieving the intended 2000 participants and follow-up was reduced from 10 years to 3 years. Conclusions: Bariatric surgery is a safe and effective treatment for obesity. Patients in Scotland, UK, appear to be older and have higher body mass than international comparators, which may be due to the small number of procedures performed. Future work: Intervention studies are required to identify the optimal pre- and post surgery pathway to maximise safety and cost-effectiveness. Study registration: This study is registered as ISRCTN47072588. Funding details: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 10/42/02) and is published in full in Health Technology Assessment; Vol. 28, No. 7. See the NIHR Funding and Awards website for further award information

Hyperactivity and Hypermotivation Associated With Increased Striatal mGluR1 Signaling in a Shank2 Rat Model of Autism

Mutations in the SHANK family of genes have been consistently identified in genetic and genomic screens of autism spectrum disorder (ASD). The functional overlap of SHANK with several other ASD-associated genes suggests synaptic dysfunction as a convergent mechanism of pathophysiology in ASD. Although many ASD-related mutations result in alterations to synaptic function, the nature of those dysfunctions and the consequential behavioral manifestations are highly variable when expressed in genetic mouse models. To investigate the phylogenetic conservation of phenotypes resultant of Shank2 loss-of-function in a translationally relevant animal model, we generated and characterized a novel transgenic rat with a targeted mutation of the Shank2 gene, enabling an evaluation of gene-associated phenotypes, the elucidation of complex behavioral phenotypes, and the characterization of potential translational biomarkers. The Shank2 loss-of-function mutation resulted in a notable phenotype of hyperactivity encompassing hypermotivation, increased locomotion, and repetitive behaviors. Mutant rats also expressed deficits in social behavior throughout development and in the acquisition of operant tasks. The hyperactive phenotype was associated with an upregulation of mGluR1 expression, increased dendritic branching, and enhanced long-term depression (LTD) in the striatum but opposing morphological and cellular alterations in the hippocampus (HP). Administration of the mGluR1 antagonist JNJ16259685 selectively normalized the expression of striatally mediated repetitive behaviors and physiology but had no effect on social deficits. Finally, Shank2 mutant animals also exhibited alterations in electroencephalography (EEG) spectral power and event-related potentials, which may serve as translatable EEG biomarkers of synaptopathic alterations. Our results show a novel hypermotivation phenotype that is unique to the rat model of Shank2 dysfunction, in addition to the traditional hyperactive and repetitive behaviors observed in mouse models. The hypermotivated and hyperactive phenotype is associated with striatal dysfunction, which should be explored further as a targetable mechanism for impairment in ASD

Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes

Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases. Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease