Language Difficulties in School-Age Children With Developmental Dyslexia.

Developmental dyslexia (DD) is a common reading disability, affecting 5% to 11% of children in North America. Children classified as having DD often have a history of early language delay (ELD) or language impairments. Nevertheless, studies have reported conflicting results as to the association between DD-ELD and the extent of current language difficulties in children with DD. To examine these relationships, we queried the parents of school-age children with reading difficulties on their child's early and current language ability. Siblings were also examined. Children were directly assessed using quantitative tests of language and reading skills. To compare this study with the literature, we divided the sample (N = 674) into three groups: DD, intermediate readers (IR), and skilled readers (SR). We found a significant association between DD and ELD, with parents of children in the DD/IR groups reporting their children put words together later than the SR group. We also found a significant association between DD and language difficulties, with children with low reading skills having low expressive/receptive language abilities. Finally, we identified early language predicted current language, which predicted reading skills. These data contribute to research indicating that children with DD experience language difficulties, suggesting early recognition may help identify reading problems.

Tagging SNP association study of the IL-1beta gene (IL1B) and childhood-onset mood disorders.

Given substantial evidence for IL-1beta involvement in the etiology of depression, the IL1B gene is a strong candidate for involvement in susceptibility to depressive disorders. However, association studies investigating this, to date, have been limited to just two polymorphisms (rs1143627[-31T/C] and rs16944[-511C/T]) that constitute only a fraction of the genetic variation that is actually present across this gene in the population. Here, in a family-based association study of childhood-onset mood disorders (COMD), characterized by onset of depression before the age of 15, we have used a gene-wide approach, employing a panel of five tagging SNPs spanning the entire gene. Based on TDT analyses of both individual alleles and haplotypes, in a study sample of 646 families (with 782 affected children), none of the SNPs, including those implicated in transcriptional regulation of the gene, showed evidence for association with COMD. This is the largest and most comprehensive study of IL1B in relation to mood disorders that has been carried out, to date. The results do not support the involvement of IL1B as a major factor in genetic risk for early-onset mood disorders.

Relations between multi-informant assessments of ADHD symptoms, DAT1, and DRD4.

Researchers conducting candidate gene studies of attention-deficit/hyperactivity disorder (ADHD) typically obtain symptom ratings from multiple informants (i.e., mothers, fathers, and teachers) and use a psychologist's best estimate or a simple algorithm, such as taking the highest symptom ratings across informants, to construct diagnostic phenotypes for estimating association. Nonetheless, these methods have never been empirically validated in the context of a molecular genetic study. In the current study, the authors systematically evaluated several methods of operationalizing phenotypes and the resulting evidence for association between ADHD and the candidate genes: dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4). Use of symptom scores as continuous scales in regression analysis suggested that the combination of mother and teacher ratings yielded the strongest evidence for association between hyperactive-impulsive ADHD symptoms and DAT1 and between inattentive ADHD symptoms and DRD4. Teacher ratings alone were sufficient for evaluating the association between inattentive symptoms and DAT1. Further, this regression-based method consistently yielded stronger evidence for association among ADHD symptoms, DAT1, and DRD4 than did three simple algorithms (i.e., the and, or, and averaging rules). The implications of these results for future molecular genetic studies of ADHD are discussed.

Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes.

AIM: TSPO is a neuroinflammatory biomarker and emerging therapeutic target in psychiatric disorders. We evaluated whether TSPO polymorphisms contribute to interindividual variability in schizophrenia, antipsychotic efficacy and antipsychotic-induced weight gain. PATIENTS & METHODS: We analyzed TSPO polymorphisms in 670 schizophrenia cases and 775 healthy controls. Gene-gene interactions between TSPO and other mitochondrial membrane protein-encoding genes (VDAC1 and ANT1) were explored. Positive findings were evaluated in two independent samples (Munich, n = 300; RUPP, n = 119). RESULTS: TSPO rs6971 was independently associated with antipsychotic-induced weight gain in the discovery (puncor = 0.04) and RUPP samples (p = 3.00 × 10(-3)), and interacted with ANT1 rs10024068 in the discovery (p = 1.15 × 10(-3)) and RUPP samples (p = 2.76 × 10(-4)). CONCLUSION: Our findings highlight TSPO as a candidate for future investigations of antipsychotic-induced weight gain, and support the involvement of mitochondrial membrane components in this serious treatment side effect.

Bipolar disorder and diabetes mellitus: epidemiology, etiology, and treatment implications.

INTRODUCTION: Bipolar disorder (BD) is a highly prevalent and disabling condition with significant mortality risk from suicide and other unnatural causes. This ignominious description is alongside recent observations that the majority of excess deaths in BD are secondary to medical comorbidity. The medical burden in BD is associated with a clustering of risk factors (e.g., obesity, smoking, unhealthy dietary habits) and inadequate utilization of preventative and primary healthcare. Diabetes mellitus (DM) is also a prevalent multifactorial disease which imparts substantial illness burden. Preliminary investigations indicate that patients who suffer from BD with comorbid DM have a more severe course and outcome, lower quality of life, higher prevalence of medical comorbidity and higher cost of illness. METHODS: We conducted a MedLine search of all English-language articles 1966-2004 using the key words: bipolar disorder, major depressive disorder, diabetes mellitus, glucose metabolism, mortality, overweight, obesity, body mass index. The search was supplemented with manual review of relevant references. Priority was given to randomized controlled data, when unavailable; studies of sufficient sample size are presented. RESULTS: Subpopulations of BD patients should be considered at high risk for DM. The prevalence of DM in BD may be three times greater than in the general population. CONCLUSIONS: Bipolar disorder populations may be an at-risk group for glucose metabolic abnormalities. Opportunistic screening and vigilance for clinical presentations suggestive of DM is encouraged.

Replication test for association of the IL-1 receptor antagonist gene, IL1RN, with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has a strong genetic basis, and aberrant brain dopaminergic and noradrenergic activity is implicated in its etiology. Interleukin-1 (IL-1), its antagonist, IL-1Ra, and IL-1 receptors are all present in the brain, and IL-1 has been shown to influence both dopaminergic and noradrenergic function. Recently, Segman et al. [1] tested the IL-1Ra gene, IL1RN, as a candidate for involvement in ADHD. Using the transmission/disequilibrium test (TDT) to examine 77 nuclear ADHD families for the inheritance of alleles of an intronic 86-bp VNTR polymorphism, they found significant evidence for biased transmission of the 4-repeat allele (p=0.04) and non-transmission of the 2-repeat allele (p=0.03). Here, we sought to replicate this in an independent sample of families. In contrast to the previous findings, our analysis of 178 ADHD families showed no evidence for biased transmission of these alleles (p=0.81 and p=1.00, respectively). Our lack of evidence for association of this IL1RN polymorphism with ADHD, based on a much larger sample of families, suggests that the original finding may have been a spurious (i.e. false-positive) result. These findings highlight the need for further investigations of this marker, in additional independent ADHD samples, in the future.