Amin Azzam

Meta‐analysis of the association between the catecholamine‐O‐methyl‐transferase gene and obsessive‐compulsive disorder

Obsessive‐compulsive disorder (OCD) is a chronic, severely debilitating mental illness that affects approximately 1–2% of the population. Data from twin and family studies have shown that genetic factors contribute to the expression of the disease. The dopaminergic system has been implicated in the pathogenesis of OCD, and catecholamine‐O‐methyl‐transferase (COMT) is a key modulator of dopaminergic and noradrenergic neurotransmission. The gene for COMT has a common polymorphism that has been shown to be correlated with a three‐ to fourfold change in enzymatic activity. Several groups have searched for an association between the COMT gene polymorphism and the presence or absence of OCD, with contrasting results. We conducted a systematic review and meta‐analysis of both the published literature and unpublished data. Available data were stratified according to the original study design as either case‐control or family‐based, and two separate meta‐analyses were conducted, using both fixed‐effects and random‐effects models. These analyses showed insufficient evidence to support an association between the COMT gene polymorphism and OCD. Subgroup stratification based on gender generated no statistically significant associations. These results should be considered in any future work correlating the COMT gene with OCD.

ADHD Prevalence and Association with Hoarding Behaviors in Childhood-Onset OCD

Background: It has been suggested that attention‐deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD), both neurodevelopmental disorders with onset in childhood, are highly comorbid, but previous studies examining ADHD and OCD comorbidity have been quite variable, partly because of inconsistency in excluding individuals with tic disorders. Similarly, ADHD has been postulated to be associated with hoarding although this potential relationship is largely methodologically unexplored. This study aimed to examine the prevalence of ADHD among individuals with childhood‐onset OCD but without comorbid tic disorders, as well as to examine the relationship between clinically significant hoarding behaviors (hoarding) and ADHD. Method: ADHD prevalence rates and the relationship between ADHD and hoarding were examined in 155 OCD‐affected individuals (114 probands and 41 relatives, age range 4–82 years) recruited for genetic studies and compared to pooled prevalence rates derived from previously published studies. Results: In total, 11.8% met criteria for definite ADHD, whereas an additional 8.6% had probable or definite ADHD (total=20.4%). In total, 41.9% of participants with ADHD also had hoarding compared to 29.2% of participants without ADHD. Hoarding was the only demographic or clinical variable independently associated with ADHD (odds ratio=9.54, P<0.0001). Conclusion: ADHD rates were elevated in this sample of individuals with childhood‐onset OCD compared to the general population rate of ADHD, and there was a strong association between ADHD and clinically significant hoarding behavior. This association is consistent with recent studies suggesting that individuals with hoarding may exhibit substantial executive functioning impairments and/or abnormalities, including attentional problems. Depression and Anxiety, 2010.

Heritability and clinical features of multigenerational families with obsessive-compulsive disorder and hoarding.

To date, only one complete genome screen for obsessive‐compulsive disorder (OCD) has been published. That study identified a region of suggestive linkage (maximum lod score of 2.25) with a relatively small sample size (N = 56; 27 with OCD). Additional complete genome screens are needed to confirm this finding and identify other regions of linkage. We present the clinical characteristics and power to detect linkage of 11 multigenerational families with OCD and hoarding (N = 92; 44 with OCD), as well as heritability estimates for several quantitative traits. Families with at least two individuals with OCD were identified through probands with childhood‐onset OCD. Expected lod scores were calculated for simulated genetic marker data under an additive and two dominant models assuming a dense SNP marker map. All affected individuals had an early age of onset (18 or younger). Hoarding was present in 46% of subjects. Obsessive‐compulsive symptoms and hoarding were highly heritable. The maximum mean expected lod score was 3.31 for OCD and 1.39 for hoarding. We found reasonable power to detect regions of interest (lod = 2) for OCD in these families, but will need to expand our family collection to have adequate power to detect regions of interest for hoarding.

Skeletal muscle phosphatidylcholine fatty acids and insulin sensitivity in normal humans

The fatty acid composition of skeletal muscle membrane phospholipids (PL) is known to influence insulin responsiveness in humans. However, the contribution of the major PL of the outer (phosphatidylcholine, PC) and inner (phosphatidylethanolamine, PE) layers of the sarcolemma to insulin sensitivity is not known. Fatty acid composition of PC and PE from biopsies of vastus lateralis from 27 normal men and women were correlated with insulin sensitivity determined by the hyperinsulinemic euglycemic clamp technique at insulin infusion rates of 0.4, 1.0, and 10.0 mU . kg-1 . min-1. Significant variation in the half-maximal insulin concentration (ED50) was observed in the normal volunteers (range 24.0-146.0 microU/ml), which correlated directly with fasting plasma insulin (r = 0.75, P < 0.0001). ED50 was inversely correlated with the degree of membrane unsaturation (C20-C22 polyunsaturated fatty acids; r = 0. 58, P < 0.01) and directly correlated with fatty acid elongation (ratio of 16:0 to 18:0, r = 0.45, P < 0.05) in PC. However, no relationship between fatty acid composition and insulin sensitivity was observed in PE (NS). These studies suggest that the fatty acid composition of PC may be of particular importance in the relationship between fatty acids and insulin sensitivity in normal humans.The fatty acid composition of skeletal muscle membrane phospholipids (PL) is known to influence insulin responsiveness in humans. However, the contribution of the major PL of the outer (phosphatidylcholine, PC) and inner (phosphatidylethanolamine, PE) layers of the sarcolemma to insulin sensitivity is not known. Fatty acid composition of PC and PE from biopsies of vastus lateralis from 27 normal men and women were correlated with insulin sensitivity determined by the hyperinsulinemic euglycemic clamp technique at insulin infusion rates of 0.4, 1.0, and 10.0 mU ⋅ kg-1 ⋅ min-1. Significant variation in the half-maximal insulin concentration (ED50) was observed in the normal volunteers (range 24.0-146.0 μU/ml), which correlated directly with fasting plasma insulin ( r = 0.75, P < 0.0001). ED50 was inversely correlated with the degree of membrane unsaturation (C20-C22polyunsaturated fatty acids; r = 0.58, P < 0.01) and directly correlated with fatty acid elongation (ratio of 16:0 to 18:0, r = 0.45, P < 0.05) in PC. However, no relationship between fatty acid composition and insulin sensitivity was observed in PE (NS). These studies suggest that the fatty acid composition of PC may be of particular importance in the relationship between fatty acids and insulin sensitivity in normal humans.

Genome-Wide Linkage Analysis of Obsessive-Compulsive Disorder Implicates Chromosome 1p36

BACKGROUND Obsessive-compulsive disorder (OCD) has a complex etiology involving both genetic and environmental factors. However, the genetic causes of OCD are largely unknown, despite the identification of several promising candidate genes and linkage regions. METHODS Our objective was to conduct genetic linkage studies of the type of OCD thought to have the strongest genetic etiology (i.e., childhood-onset OCD), in 33 Caucasian families with ≥2 childhood-onset OCD-affected individuals from the United States (n = 245 individuals with genotype data). Parametric and nonparametric genome-wide linkage analyses were conducted with Morgan and Merlin in these families using a selected panel of single nucleotide repeat polymorphisms from the Illumina 610-Quad Bead Chip. The initial analyses were followed by fine-mapping analyses in genomic regions with initial heterogeneity logarithm of odds (HLOD) scores of ≥2.0. RESULTS We identified five areas of interest (HLOD score ≥2) on chromosomes 1p36, 2p14, 5q13, 6p25, and 10p13. The strongest result was on chromosome 1p36.33-p36.32 (HLOD = 3.77, suggestive evidence for linkage after fine mapping). At this location, several of the families showed haplotypes co-segregating with OCD. CONCLUSIONS The results of this study represent the strongest linkage finding for OCD in a primary analysis to date and suggest that chromosome 1p36, and possibly several other genomic regions, may harbor susceptibility loci for OCD. Multiple brain-expressed genes lie under the primary linkage peak (approximately 4 megabases in size). Follow-up studies, including replication in additional samples and targeted sequencing of the areas of interest, are needed to confirm these findings and to identify specific OCD risk variants.

From primary care to public health: using Problem-based Learning and the ecological model to teach public health to first year medical students.

We investigated whether a public health-oriented Problem-Based Learning case presented to first-year medical students conveyed 12 “Population Health Competencies for Medical Students,” as recommended by the Association of American Medical Colleges and the Regional Medicine-Public Health Education Centers. A public health-oriented Problem-Based Learning case guided by the ecological model paradigm was developed and implemented among two groups of 8 students at the University of California, Berkeley-UCSF Joint Medical Program, in the Fall of 2010. Using directed content analysis, student-generated written reports were coded for the presence of the 12 population health content areas. Students generated a total of 29 reports, of which 20 (69%) contained information relevant to at least one of the 12 population health competencies. Each of the 12 content areas was addressed by at least one report. As physicians-in-training prepare to confront the challenges of integrating prevention and population health with clinical practice, Problem-Based Learning is a promising tool to enhance medical students’ engagement with public health.

Why Medical Schools Should Embrace Wikipedia: Final-year Medical Student Contributions to Wikipedia Articles for Academic Credit at One School.

Supplemental Digital Content is available in the text.

Evidence for a heritable unidimensional symptom factor underlying obsessionality

The division of obsessive‐compulsive symptoms (OCS) into specific factors is now widely accepted. However, the utility of these categories for genetic studies remains unclear, as studies examining their heritability have been inconsistent. Less attention has been paid to the possibility that clinically significant obsessionality is primarily determined by a “core” group of OCS that crosses the boundaries between symptom subgroups. The aim of this study is to determine whether such a core group exists, and to compare its heritability to that of the more traditionally derived symptom factors. We examined the properties and heritability of obsessive‐compulsive symptoms in college students, medical students, and obsessive‐compulsive disorder (OCD) families using the Leyton Obsessional Inventory. In each of the three samples, we identified a core group of symptoms that comprised a single unique construct and accounted for over 90% of the variation of the four more traditional symptom factors. This core construct was highly correlated with OCD in our families and had a heritability estimate of 0.19 when OCD was not included as a covariate and 0.49 when OCD was included as a covariate. In contrast, the four symptom factors were not heritable. There appears to be an underlying unidimensional component to obsessionality, both in non‐clinical and clinical samples. This component, which is heritable, accounts for the majority of the variation of the more traditionally derived symptom factors in our sample, and is composed of OCS that are not specific to any of the symptom subgroups.

Competency-based medical education and scholarship: Creating an active academic culture during residency

The competency-based medical education movement has been adopted in several medical education systems across the world. This has the potential to result in a more active involvement of residents in the educational process, inasmuch as scholarship is regarded as a major area of competency. Substantial scholarly activities are well within the reach of motivated residents, especially when faculty members provide sufficient mentoring. These academically empowered residents have the advantage of early experience in the areas of scholarly discovery, integration, application, and teaching. Herein, the authors review the importance of instituting the germinal stages of scholarly productivity in the creation of an active scholarly culture during residency. Clear and consistent institutional and departmental strategies to promote scholarly development during residency are highly encouraged.

Student near-peer co-tutors in PBL groups

Context and setting The practice of medicine in Pakistan is guided by expert opinion, giving rise to an environment defined by the dictum ‘the professor is always right’. Evidence-based medicine (EBM) has not been recognised as a competency in most Pakistani medical school curricula. As we have the benefit of being imbedded in an innovative institution, we designed an educational experience in EBM with the aim of encouraging students to use scientific inquiry to question common clinical practices. Why the idea was necessary The college mission clearly states its goal of graduating students who are ready to practise medicine in the 21st century. Although the importance of evidence-based practice has been well documented in the literature, formal teaching of EBM in our curricula was non-existent. What was done The strategy included a plan for educating both faculty and students. Four internal medicine faculty members, trained in EBM, conducted a small-group workshop for 12 interested clinical faculty staff. Subsequently, two of the original trainers provided two ‘EBM for Beginners’ workshops for 21 students each, prior to the students’ fifth (final) year clinical clerkships. Students learned to ‘ask a well-built, searchable clinical question’ and ‘acquire the appropriate evidence’ on MEDLINE using various search strategies – the first two steps of the four EBM practice model steps. The workshops were conducted in an informatics laboratory equipped with 20 online work stations. A student handbook was developed for quick reference. Evaluation of results and impact Gains in faculty’s knowledge of and skills in EBM were assessed by preand post-workshop Berlin questionnaires. During the EBM for Beginners workshops, students completed a questionnaire that assessed their baseline computer skills, knowledge about study designs, and perceptions about the use of evidence in patient care. Students also completed a preand post-workshop paper case that required them to search MEDLINE in order to answer items pertaining to developing a clinical question and acquiring appropriate evidence. At the end of the workshop, self-rated skills and attitudes were also recorded on a retrospective preand post-test. Five months post-workshop, students self-rated their EBM skills and attitudes. In the first year of implementation, we demonstrated that both faculty and students could learn relatively quickly to apply the first two steps of EBM. The workshops were welcomed by both students and faculty. After the workshop, students expressed concerns that doctors in Pakistan may not be familiar with the idea of EBM. In addition to these intended outcomes, there were several other ways that this educational intervention affected behaviour within and the environment of our institution. The workshops brought the word ‘evidence’ to the fore in an environment not generally conducive to the questioning of clinical practices. Informal observation of routine clinical teaching indicated that faculty and students began to request evidence for clinical practices in clinical teaching activities. The effect rippled on to the College of Nursing’s research module, internal medicine morning reports, generating interest in medical education projects and international recognition of the institution at medical education conferences at which several oral and poster presentations were made. The project was eventually incorporated into the newly implemented integrated medical curriculum.