VA Healthcare-VISN 4

BACKGROUND: Identifying, developing, and testing implementation strategies are important goals of implementation science. However, these efforts have been complicated by the use of inconsistent language and inadequate descriptions of implementation strategies in the literature. The Expert Recommendations for Implementing Change (ERIC) study aimed to refine a published compilation of implementation strategy terms and definitions by systematically gathering input from a wide range of stakeholders with expertise in implementation science and clinical practice. METHODS: Purposive sampling was used to recruit a panel of experts in implementation and clinical practice who engaged in three rounds of a modified Delphi process to generate consensus on implementation strategies and definitions. The first and second rounds involved Web-based surveys soliciting comments on implementation strategy terms and definitions. After each round, iterative refinements were made based upon participant feedback. The third round involved a live polling and consensus process via a Web-based platform and conference call. RESULTS: Participants identified substantial concerns with 31% of the terms and/or definitions and suggested five additional strategies. Seventy-five percent of definitions from the originally published compilation of strategies were retained after voting. Ultimately, the expert panel reached consensus on a final compilation of 73 implementation strategies. CONCLUSIONS: This research advances the field by improving the conceptual clarity, relevance, and comprehensiveness of implementation strategies that can be used in isolation or combination in implementation research and practice. Future phases of ERIC will focus on developing conceptually distinct categories of strategies as well as ratings for each strategy's importance and feasibility. Next, the expert panel will recommend multifaceted strategies for hypothetical yet real-world scenarios that vary by sites' endorsement of evidence-based programs and practices and the strength of contextual supports that surround the effort.

BACKGROUND: Poor terminological consistency for core concepts in implementation science has been widely noted as an obstacle to effective meta-analyses. This inconsistency is also a barrier for those seeking guidance from the research literature when developing and planning implementation initiatives. The Expert Recommendations for Implementing Change (ERIC) study aims to address one area of terminological inconsistency: discrete implementation strategies involving one process or action used to support a practice change. The present report is on the second stage of the ERIC project that focuses on providing initial validation of the compilation of 73 implementation strategies that were identified in the first phase. FINDINGS: Purposive sampling was used to recruit a panel of experts in implementation science and clinical practice (N = 35). These key stakeholders used concept mapping sorting and rating activities to place the 73 implementation strategies into similar groups and to rate each strategy's relative importance and feasibility. Multidimensional scaling analysis provided a quantitative representation of the relationships among the strategies, all but one of which were found to be conceptually distinct from the others. Hierarchical cluster analysis supported organizing the 73 strategies into 9 categories. The ratings data reflect those strategies identified as the most important and feasible. CONCLUSIONS: This study provides initial validation of the implementation strategies within the ERIC compilation as being conceptually distinct. The categorization and strategy ratings of importance and feasibility may facilitate the search for, and selection of, strategies that are best suited for implementation efforts in a particular setting.

Neuropsychiatric symptoms (NPS) are common in dementia and in predementia syndromes such as mild cognitive impairment (MCI). NPS in MCI confer a greater risk for conversion to dementia in comparison to MCI patients without NPS. NPS in older adults with normal cognition also confers a greater risk of cognitive decline in comparison to older adults without NPS. Mild behavioral impairment (MBI) has been proposed as a diagnostic construct aimed to identify patients with an increased risk of developing dementia, but who may or may not have cognitive symptoms. We propose criteria that include MCI in the MBI framework, in contrast to prior definitions of MBI. Although MBI and MCI can co-occur, we suggest that they are different and that both portend a higher risk of dementia. These MBI criteria extend the previous literature in this area and will serve as a template for validation of the MBI construct from epidemiologic, neurobiological, treatment, and prevention perspectives.

Posttraumatic stress disorder (PTSD) is associated with regional alterations in brain structure and function that are hypothesized to contribute to symptoms and cognitive deficits associated with the disorder. We present here the first systematic meta-analysis of neurocognitive outcomes associated with PTSD to examine a broad range of cognitive domains and describe the profile of cognitive deficits, as well as modifying clinical factors and study characteristics. This report is based on data from 60 studies totaling 4,108 participants, including 1,779 with PTSD, 1,446 trauma-exposed comparison participants, and 895 healthy comparison participants without trauma exposure. Effect-size estimates were calculated using a mixed-effects meta-analysis for 9 cognitive domains: attention/working memory, executive functions, verbal learning, verbal memory, visual learning, visual memory, language, speed of information processing, and visuospatial abilities. Analyses revealed significant neurocognitive effects associated with PTSD, although these ranged widely in magnitude, with the largest effect sizes in verbal learning (d = -.62), speed of information processing (d = -.59), attention/working memory (d = -.50), and verbal memory (d =-.46). Effect-size estimates were significantly larger in treatment-seeking than community samples and in studies that did not exclude participants with attention-deficit/hyperactivity disorder, and effect sizes were affected by between-group IQ discrepancies and the gender composition of the PTSD groups. Our findings indicate that consideration of neuropsychological functioning in attention, verbal memory, and speed of information processing may have important implications for the effective clinical management of persons with PTSD. Results are further discussed in the context of cognitive models of PTSD and the limitations of this literature.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case–control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD—for both European- and African-American individuals—and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

CONTEXT: Existing evidence suggests that military veterans with mental health disorders have poorer family functioning, although little research has focused on this topic. OBJECTIVE: To test whether psychiatric symptoms are associated with family reintegration problems in recently returned military veterans. DESIGN: Cross-sectional survey of a clinical population. Respondents who were referred to behavioral health evaluation from April 2006 through August 2007 were considered for the survey. SETTING: Philadelphia Veterans Affairs Medical Center, Pa. PARTICIPANTS: 199 military veterans who served in Iraq or Afghanistan after 2001 and were referred for behavioral health evaluation from primary care (mean age = 32.7 years, SD = 9.1). MAIN OUTCOME MEASURES: Measures included the Mini-International Neuropsychiatric Interview for psychiatric diagnoses, the 9-item Patient Health Questionnaire for depression diagnosis and severity, and screening measures of alcohol abuse and illicit substance use. A measure of military family readjustment problems and a screening measure of domestic abuse were developed for this study. RESULTS: Three fourths of the married/cohabiting veterans reported some type of family problem in the past week, such as feeling like a guest in their household (40.7%), reporting their children acting afraid or not being warm toward them (25.0%), or being unsure about their family role (37.2%). Among veterans with current or recently separated partners, 53.7% reported conflicts involving "shouting, pushing, or shoving," and 27.6% reported that this partner was "afraid of them." Depression and posttraumatic stress disorder symptoms were both associated with higher rates of family reintegration problems. CONCLUSIONS: Mental health problems may complicate veterans' readjustment and reintegration into family life. The findings suggest an opportunity to improve the treatment of psychiatric disorders by addressing family problems.

Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are widespread and disabling. This has been known since Dr. Alois Alzheimer's first case, Frau Auguste D., presented with emotional distress and delusions of infidelity/excessive jealousy, followed by cognitive symptoms. Being cognizant of this, in 2010 the Alzheimer's Association convened a research roundtable on the topic of NPS in AD. A major outcome of the roundtable was the founding of a Professional Interest Area (PIA) within the International Society to Advance Alzheimer's Research and Treatment (ISTAART). The NPS-PIA has prepared a series of documents that are intended to summarize the literature and provide more detailed specific recommendations for NPS research. This overview paper is the first of these living documents that will be updated periodically as the science advances. The overview is followed by syndrome-specific synthetic reviews and recommendations prepared by NPS-PIA workgroups on depression, apathy, sleep, agitation, and psychosis.

A number of studies have indicated that antagonists of the N-methyl-d-aspartate subtypes of glutamate receptors can cause schizophrenia-like symptoms in healthy individuals and exacerbate symptoms in individuals with schizophrenia. These findings have led to the glutamate hypothesis of schizophrenia. Here we review the evidence for this hypothesis in postmortem studies of brain tissue from individuals affected by schizophrenia, summarizing studies of glutamate neuron morphology, of expression of glutamate receptors and transporters, and of the synthesizing and metabolizing enzymes for glutamate and its co-agonists. We found consistent evidence of morphological alterations of dendrites of glutamatergic neurons in the cerebral cortex of subjects with schizophrenia and of reduced levels of the axon bouton marker synaptophysin. There were no consistent alterations of mRNA expression of glutamate receptors, although there has been limited study of the corresponding proteins. Studies of the glutamate metabolic pathway have been limited, although there is some evidence that excitatory amino acid transporter-2, glutamine synthetase, and glutaminase have altered expression in schizophrenia. Future studies would benefit from additional direct examination of glutamatergic proteins. Further advances, such as selective testing of synaptic microdomains, cortical layers, and neuronal subtypes, may also be required to elucidate the nature of glutamate signaling impairments in schizophrenia.

BACKGROUND: Patients using cholinesterase inhibitors (ChEIs) have a delay in nursing home (NH) admission compared with those who were not using the medication. There are no long-term studies of the effects of memantine in combination with ChEIs use in Alzheimer disease (AD). This study was conducted to examine the effects of ChEIs and memantine on time to death and time to NH admission. METHODS: Time to NH admission and death was examined in 943 probable AD patients who had at least a 1-year follow-up evaluation. Of these patients, 140 (14.9%) used both ChEIs and memantine, 387 (41%) [corrected] used only ChEIs, and 416 (44.1%) [corrected] used neither. The mean (SD) follow-up time was 62.3 (35.8) months. The analysis was conducted with multivariable Cox proportional hazard models controlling for critical covariates (ie, age, education level, gender, severity of the dementia, hypertension, diabetes mellitus, heart disease, psychiatric symptoms and use of psychotropic medications). RESULTS: Compared with those who never used cognitive enhancers, patients who used ChEIs had a significant delay in NH admission (HR: 0.37, 95% CI 0.27 to 0.49); this effect was significantly augmented with the addition of memantine (HR: 0.29, 95% CI 0.11 to 0.72) (memantine+ChEI vs ChEI alone). ChEIs alone, or in combination with memantine had no significant association on time to death. CONCLUSIONS: This observational study revealed that the addition of the NMDA receptor antagonist memantine to the treatment of AD with ChEI significantly altered the treated history of AD by extending time to nursing home admission.

IMPORTANCE: Alcohol dependence comorbid with posttraumatic stress disorder (PTSD) has been found to be resistant to treatment. In addition, there is a concern that prolonged exposure therapy for PTSD may exacerbate alcohol use. OBJECTIVE: To compare the efficacy of an evidence-based treatment for alcohol dependence (naltrexone) plus an evidence-based treatment for PTSD (prolonged exposure therapy), their combination, and supportive counseling. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, randomized clinical trial of 165 participants with PTSD and alcohol dependence conducted at the University of Pennsylvania and the Philadelphia Veterans Administration. Participant enrollment began on February 8, 2001, and ended on June 25, 2009. Data collection was completed on August 12, 2010. INTERVENTIONS: Participants were randomly assigned to (1) prolonged exposure therapy plus naltrexone (100 mg/d), (2) prolonged exposure therapy plus pill placebo, (3) supportive counseling plus naltrexone (100 mg/d), or (4) supportive counseling plus pill placebo. Prolonged exposure therapy was composed of 12 weekly 90-minute sessions followed by 6 biweekly sessions. All participants received supportive counseling. MAIN OUTCOMES AND MEASURES: The Timeline Follow-Back Interview and the PTSD Symptom Severity Interview were used to assess the percentage of days drinking alcohol and PTSD severity, respectively, and the Penn Alcohol Craving Scale was used to assess alcohol craving. Independent evaluations occurred prior to treatment (week 0), at posttreatment (week 24), and at 6 months after treatment discontinuation (week 52). RESULTS: Participants in all 4 treatment groups had large reductions in the percentage of days drinking (mean change, -63.9% [95% CI, -73.6% to -54.2%] for prolonged exposure therapy plus naltrexone; -63.9% [95% CI, -73.9% to -53.8%] for prolonged exposure therapy plus placebo; -69.9% [95% CI, -78.7% to -61.2%] for supportive counseling plus naltrexone; and -61.0% [95% CI, -68.9% to -53.0%] for supportive counseling plus placebo). However, those who received naltrexone had lower percentages of days drinking than those who received placebo (mean difference, 7.93%; P = .008). There was also a reduction in PTSD symptoms in all 4 groups, but the main effect of prolonged exposure therapy was not statistically significant. Six months after the end of treatment, participants in all 4 groups had increases in percentage of days drinking. However, those in the prolonged exposure therapy plus naltrexone group had the smallest increases. CONCLUSIONS AND RELEVANCE: In this study of patients with alcohol dependence and PTSD, naltrexone treatment resulted in a decrease in the percentage of days drinking. Prolonged exposure therapy was not associated with an exacerbation of alcohol use disorder. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006489.

RATIONALE: Home portable monitor testing is increasingly being used to diagnose patients with obstructive sleep apnea (OSA) and to initiate them on continuous positive airway pressure (CPAP) treatment. OBJECTIVES: To compare functional outcome and treatment adherence in patients who receive ambulatory versus in-laboratory testing for OSA. METHODS: Veterans with suspected OSA were randomized to either home testing or standard in-laboratory testing. Home testing consisted of a type 3 portable monitor recording followed by at least three nights using an automatically adjusting positive airway pressure apparatus. Participants diagnosed with OSA were treated with CPAP for 3 months. MEASUREMENTS AND MAIN RESULTS: We measured the change in Functional Outcomes of Sleep Questionnaire score, with an a priori noninferiority delta of -1, and the mean daily hours of objectively measured CPAP adherence, with an a priori noninferiority delta of -0.75 hour/day. Of the 296 subjects enrolled, 260 (88%) were diagnosed with OSA, and 213 (75%) were initiated on CPAP. Mean ± SD functional outcome score improved 1.74 ± 2.81 in the home group (P < 0.001) and 1.85 ± 2.46 in the in-laboratory group (P < 0.0001). The lower bound of the one-sided 95% noninferiority confidence interval was -0.54. Mean ± SD hours of daily CPAP adherence were 3.5 ± 2.5 hours/day in the home group and 2.9 ± 2.3 hours/day in the in-laboratory group (P = 0.08). The lower bound of the one-sided 95% noninferiority confidence interval was 0.03. CONCLUSIONS: Functional outcome and treatment adherence in patients evaluated according to a home testing algorithm is not clinically inferior to that in patients receiving standard in-laboratory polysomnography.

BACKGROUND: Identifying feasible and effective implementation strategies that are contextually appropriate is a challenge for researchers and implementers, exacerbated by the lack of conceptual clarity surrounding terms and definitions for implementation strategies, as well as a literature that provides imperfect guidance regarding how one might select strategies for a given healthcare quality improvement effort. In this study, we will engage an Expert Panel comprising implementation scientists and mental health clinical managers to: establish consensus on a common nomenclature for implementation strategy terms, definitions and categories; and develop recommendations to enhance the match between implementation strategies selected to facilitate the use of evidence-based programs and the context of certain service settings, in this case the U.S. Department of Veterans Affairs (VA) mental health services. METHODS/DESIGN: This study will use purposive sampling to recruit an Expert Panel comprising implementation science experts and VA mental health clinical managers. A novel, four-stage sequential mixed methods design will be employed. During Stage 1, the Expert Panel will participate in a modified Delphi process in which a published taxonomy of implementation strategies will be used to establish consensus on terms and definitions for implementation strategies. In Stage 2, the panelists will complete a concept mapping task, which will yield conceptually distinct categories of implementation strategies as well as ratings of the feasibility and effectiveness of each strategy. Utilizing the common nomenclature developed in Stages 1 and 2, panelists will complete an innovative menu-based choice task in Stage 3 that involves matching implementation strategies to hypothetical implementation scenarios with varying contexts. This allows for quantitative characterizations of the relative necessity of each implementation strategy for a given scenario. In Stage 4, a live web-based facilitated expert recommendation process will be employed to establish expert recommendations about which implementations strategies are essential for each phase of implementation in each scenario. DISCUSSION: Using a novel method of selecting implementation strategies for use within specific contexts, this study contributes to our understanding of implementation science and practice by sharpening conceptual distinctions among a comprehensive collection of implementation strategies.

Appropriate use of language in the field of addiction is important. Inappropriate use of language can negatively impact the way society perceives substance use and the people who are affected by it. Language frames what the public thinks about substance use and recovery, and it can also affect how individuals think about themselves and their own ability to change. But most importantly, language intentionally and unintentionally propagates stigma: the mark of dishonor, disgrace, and difference that depersonalizes people, depriving them of individual or personal qualities and personal identity. Stigma is harmful, distressing, and marginalizing to the individuals, groups, and populations who bear it. For these reasons, the Editorial Team of Substance Abuse seeks to formally operationalize respect for personhood in our mission, our public relations, and our instructions to authors. We ask authors, reviewers, and readers to carefully and intentionally consider the language used to describe alcohol and other drug use and disorders, the individuals affected by these conditions, and their related behaviors, comorbidities, treatment, and recovery in our publication. Specifically, we make an appeal for the use of language that (1) respects the worth and dignity of all persons ("people-first language"); (2) focuses on the medical nature of substance use disorders and treatment; (3) promotes the recovery process; and (4) avoids perpetuating negative stereotypes and biases through the use of slang and idioms. In this paper, we provide a brief overview of each of the above principles, along with examples, as well as some of the nuances and tensions that inherently arise as we give greater attention to the issue of how we talk and write about substance use and addiction.

The number of research groups studying the pupil is increasing, as is the number of publications. Consequently, new standards in pupillography are needed to formalize the methodology including recording conditions, stimulus characteristics, as well as suitable parameters of evaluation. Since the description of intrinsically photosensitive retinal ganglion cells (ipRGCs) there has been an increased interest and broader application of pupillography in ophthalmology as well as other fields including psychology and chronobiology. Color pupillography plays an important role not only in research but also in clinical observational and therapy studies like gene therapy of hereditary retinal degenerations and psychopathology. Stimuli can vary in size, brightness, duration, and wavelength. Stimulus paradigms determine whether rhodopsin-driven rod responses, opsin-driven cone responses, or melanopsin-driven ipRGC responses are primarily elicited. Background illumination, adaptation state, and instruction for the participants will furthermore influence the results. This standard recommends a minimum set of variables to be used for pupillography and specified in the publication methodologies. Initiated at the 32nd International Pupil Colloquium 2017 in Morges, Switzerland, the aim of this manuscript is to outline standards in pupillography based on current knowledge and experience of pupil experts in order to achieve greater comparability of pupillographic studies. Such standards will particularly facilitate the proper application of pupillography by researchers new to the field. First we describe general standards, followed by specific suggestions concerning the demands of different targets of pupil research: the afferent and efferent reflex arc, pharmacology, psychology, sleepiness-related research and animal studies.

For more than half a century, since the beginning of formal diagnostics, our psychiatric nosology has compartmentalized the compulsive pursuit of substance (e.g., alcohol, cocaine, heroin, nicotine) from nonsubstance (e.g., gambling, food, sex) rewards. Emerging brain, behavioral, and genetic findings challenge this diagnostic boundary, pointing to shared vulnerabilities underlying the pathological pursuit of substance and nonsubstance rewards. Working groups for the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), are thus considering whether the nosologic boundaries of addiction should be redrawn to include nonsubstance disorders, such as gambling. This review discusses how neurobiological data from problem gambling, obesity, and "normal" states of attachment (romantic infatuation, sexual attraction, maternal bonds) may help us in the task of carving addictions "at a new joint." Diagnostic recarving may have a positive effect on addiction research, stimulating discovery of "crossover" pharmacotherapies with benefit for both substance and nonsubstance addictions.

OBJECTIVE We compared the short-term efficacy of home telemonitoring coupled with active medication management by a nurse practitioner with a monthly care coordination telephone call on glycemic control in veterans with type 2 diabetes and entry A1C > or =7.5%. RESEARCH DESIGN AND METHODS Veterans who received primary care at the VA Pittsburgh Healthcare System from June 2004 to December 2005, who were taking oral hypoglycemic agents and/or insulin for > or =1 year, and who had A1C > or =7.5% at enrollment were randomly assigned to either active care management with home telemonitoring (ACM+HT group, n = 73) or a monthly care coordination telephone call (CC group, n = 77). Both groups received monthly calls for diabetes education and self-management review. ACM+HT group participants transmitted blood glucose, blood pressure, and weight to a nurse practitioner using the Viterion 100 TeleHealth Monitor; the nurse practitioner adjusted medications for glucose, blood pressure, and lipid control based on established American Diabetes Association targets. Measures were obtained at baseline, 3-month, and 6-month visits. RESULTS Baseline characteristics were similar in both groups, with mean A1C of 9.4% (CC group) and 9.6% (ACM+HT group). Compared with the CC group, the ACM+HT group demonstrated significantly larger decreases in A1C at 3 months (1.7 vs. 0.7%) and 6 months (1.7 vs. 0.8%; P < 0.001 for each), with most improvement occurring by 3 months. CONCLUSIONS Compared with the CC group, the ACM+HT group demonstrated significantly greater reductions in A1C by 3 and 6 months. However, both interventions improved glycemic control in primary care patients with previously inadequate control.

Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysis of three genome-wide association studies (GWASs) to identify loci that (1) increase susceptibility to an AD and subsequent psychotic symptoms; or (2) modify risk of psychotic symptoms in the presence of neurodegeneration caused by AD. In all, 1299 AD cases with psychosis (AD+P), 735 AD cases without psychosis (AD-P) and 5659 controls were drawn from Genetic and Environmental Risk in AD Consortium 1 (GERAD1), the National Institute on Aging Late-Onset Alzheimer's Disease (NIA-LOAD) family study and the University of Pittsburgh Alzheimer Disease Research Center (ADRC) GWASs. Unobserved genotypes were imputed to provide data on >1.8 million single-nucleotide polymorphisms (SNPs). Analyses in each data set were completed comparing (1) AD+P to AD-P cases, and (2) AD+P cases with controls (GERAD1, ADRC only). Aside from the apolipoprotein E (APOE) locus, the strongest evidence for association was observed in an intergenic region on chromosome 4 (rs753129; 'AD+PvAD-P' P=2.85 × 10(-7); 'AD+PvControls' P=1.11 × 10(-4)). SNPs upstream of SLC2A9 (rs6834555, P=3.0 × 10(-7)) and within VSNL1 (rs4038131, P=5.9 × 10(-7)) showed strongest evidence for association with AD+P when compared with controls. These findings warrant further investigation in larger, appropriately powered samples in which the presence of psychotic symptoms in AD has been well characterized.

A variety of psychological and physical phenomena elicit variations in the diameter of pupil of the eye. Changes in pupil size are mediated by the relative activation of the sphincter pupillae muscle (decrease pupil diameter) and the dilator pupillae muscle (increase pupil diameter), innervated by the parasympathetic and sympathetic branches, respectively, of the autonomic nervous system. The current guidelines are intended to inform and guide psychophysiological research involving pupil measurement by (1) summarizing important aspects concerning the physiology of the pupil, (2) providing methodological and data-analytic guidelines and recommendations, and (3) briefly reviewing psychological phenomena that modulate pupillary reactivity. Because of the increased ease and tractability of pupil measurement, the goal of these guidelines is to promote accurate recording, analysis, and reporting of pupillary data in psychophysiological research.

BACKGROUND: Alcohol dependence (AD) is a complex psychiatric disorder and a significant public health problem. Twin and family-based studies have consistently estimated its heritability to be approximately 50%, and many studies have sought to identify specific genetic variants associated with susceptibility to AD. These studies have been primarily linkage or candidate gene based and have been mostly unsuccessful in identifying replicable risk loci. Genome-wide association studies (GWAS) have improved the detection of specific loci associated with complex traits, including AD. However, findings from GWAS explain only a small proportion of phenotypic variance, and alternative methods have been proposed to investigate the associations that do not meet strict genome-wide significance criteria. METHODS: This review summarizes all published AD GWAS and post-GWAS analyses that have sought to exploit GWAS data to identify AD-associated loci. RESULTS: Findings from AD GWAS have been largely inconsistent, with the exception of variants encoding the alcohol-metabolizing enzymes. Analyses of GWAS data that go beyond standard association testing have demonstrated the polygenic nature of AD and the large contribution of common variants to risk, nominating novel genes and pathways for AD susceptibility. CONCLUSIONS: Findings from AD GWAS and post-GWAS analyses have greatly increased our understanding of the genetic etiology of AD. However, it is clear that larger samples will be necessary to detect loci in addition to those that encode alcohol-metabolizing enzymes, which may only be possible through consortium-based efforts. Post-GWAS approaches to studying the genetic influences on AD are increasingly common and could greatly increase our knowledge of both the genetic architecture of AD and the specific genes and pathways that influence risk.

Psychiatric and neurodegenerative disorders, including intellectual disability, autism spectrum disorders (ASD), schizophrenia (SZ), and Alzheimer's disease, pose an immense burden to society. Symptoms of these disorders become manifest at different stages of life: early childhood, adolescence, and late adulthood, respectively. Progress has been made in recent years toward understanding the genetic substrates, cellular mechanisms, brain circuits, and endophenotypes of these disorders. Multiple lines of evidence implicate excitatory and inhibitory synaptic circuits in the cortex and hippocampus as key cellular substrates of pathogenesis in these disorders. Excitatory/inhibitory balance--modulated largely by dopamine--critically regulates cortical network function, neural network activity (i.e. gamma oscillations) and behaviors associated with psychiatric disorders. Understanding the molecular underpinnings of synaptic pathology and neuronal network activity may thus provide essential insight into the pathogenesis of these disorders and can reveal novel drug targets to treat them. Here, we discuss recent genetic, neuropathological, and molecular studies that implicate alterations in excitatory and inhibitory synaptic circuits in the pathogenesis of psychiatric disorders across the lifespan.