Estimation of enteric methane emission factors for Ndama cattle in the Sudanian zone of Senegal.

Methane (CH4) emission estimations for cattle in Sub-Saharan Africa (SSA) reflect limited production levels and diets that are high in cellulose forage. However, data on these livestock systems is lacking for their accurate evaluation. To provide guidance for climate change mitigation strategies in Senegal, it is necessary to obtain reliable estimates of CH4 emissions from Ndama cattle reared in grazing systems, which is the predominant cattle system in the country. The objective of this study was to determine the annual methane emission factor (MEF) for enteric fermentation of Ndama cattle following the IPCC Tier 2 procedure. Our estimated annual MEF at the herd scale was 30.8 kg CH4/TLU (30.7 kg CH4/head/yr for lactating cows and 15.1 kg CH4/head/yr for other cattle). These values are well below the default IPCC emission factor (46 and 31 kg CH4/head/yr for dairy and other cattle, respectively) proposed in the Tier 1 method for Africa. Our study showed that feed digestibility values differ with season (from 46 to 64%). We also showed that cattle lose weight and adapt to lower feed requirements during the long dry season, with a resulting major reduction in methane emissions. The results of this work provide a new framework to re-estimate the contribution of grazing systems to methane emissions in Africa.

Association of ADHD and the Protogenin gene in the chromosome 15q21.3 reading disabilities linkage region.

Twin studies indicate genetic overlap between symptoms of attention deficit hyperactivity disorder (ADHD) and reading disabilities (RD), and linkage studies identify several chromosomal regions possibly containing common susceptibility genes, including the 15q region. Based on a translocation finding and association to two specific alleles, the candidate gene, DYX1C1, has been proposed as the susceptibility gene for RD in 15q. Previously, we tested markers in DYX1C1 for association with ADHD. Although we identified association for haplotypes across the gene, we were unable to replicate the association to the specific alleles reported. Thus, the risk alleles for ADHD are yet to be identified. The susceptibility alleles may be in a remote regulatory element, or DYX1C1 may not be the risk gene. To continue study of 15q, we tested a coding region change in DYX1C1, followed by markers across the gene Protogenin (PRTG) in 253 ADHD nuclear families. PRTG was chosen based on its location and because it is closely related to DCC and Neogenin, two genes known to guide migratory cells and axons during development. The markers in DYX1C1 were not associated to ADHD when analyzed individually; however, six markers in PRTG showed significant association with ADHD as a categorical trait (P = 0.025-0.005). Haplotypes in both genes showed evidence for association. We identified association with ADHD symptoms measured as quantitative traits in PRTG, but no evidence for association with two key components of reading, word identification and decoding was observed. These findings, while preliminary, identify association of ADHD to a gene that potentially plays a role in cell migration and axon growth.

Association study of the nicotinic acetylcholine receptor alpha4 subunit gene, CHRNA4, in attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood-onset psychiatric condition with a strong genetic component. Evidence from pharmacological, clinical and animal studies has suggested that the nicotinic system could be involved in the disorder. Previous studies have implicated the nicotinic acetylcholine receptor alpha4 subunit gene, CHRNA4, in ADHD. Particularly, a polymorphism in the exon 2-intron 2 junction of CHRNA4 has been associated with severe inattention defined by latent class analysis. In the current study, we used the transmission disequilibrium test (TDT) to investigate four polymorphisms encompassing this region of CHRNA4 for association with ADHD in a sample of 264 nuclear families from Toronto. No significant evidence of biased transmission was observed for any of the marker alleles for ADHD defined as a categorical trait (all subtypes included), although one haplotype showed marginal evidence of under-transmission. No association was found with the ADHD predominantly inattentive subtype or with symptom dimension scores of inattention. On the contrary, nominally significant evidence of association of individual markers was obtained for the ADHD combined subtype and with teacher-rated hyperactivity-impulsivity scores, with the same haplotype being under-transmitted. Based on our results and others, CHRNA4 may be involved in ADHD; however, its role in ADHD symptomatology remains to be clarified.

Association of the glutamate receptor subunit gene GRIN2B with attention-deficit/hyperactivity disorder.

The glutamatergic signaling pathway represents an ideal candidate susceptibility system for attention-deficit/hyperactivity disorder (ADHD). Disruption of specific N-methyl-D-aspartate-type glutamate receptor subunit genes (GRIN1, 2A-D) in mice leads to significant alterations in cognitive and/or locomotor behavior including impairments in latent learning, spatial memory tasks and hyperactivity. Here, we tested for association of GRIN2B variants with ADHD, by genotyping nine single nucleotide polymorphisms (SNPs) in 205 nuclear families identified through probands with ADHD. Transmission of alleles from heterozygous parents to affected offspring was examined using the transmission/disequilibrium test. Quantitative trait analyses for the ADHD symptom dimensions [inattentive (IA) and hyperactive/impulsive (HI)] and cognitive measures of verbal working memory and verbal short-term memory were performed using the fbat program. Three SNPs showed significantly biased transmission (P < 0.05), with the strongest evidence of association found for rs2,284,411 (chi(2)= 7.903, 1 degree of freedom, P= 0.005). Quantitative trait analyses showed associations of these markers with both the IA and the HI symptom dimensions of ADHD but not with the cognitive measures of verbal short-term memory or verbal working memory. Our data suggest an association between variations in the GRIN2B subunit gene and ADHD as measured categorically or as a quantitatively distributed trait.

Association of the calcyon gene (DRD1IP) with attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is a childhood-onset disorder characterized by marked inattention, hyperactivity and impulsivity. The dopaminergic system has been hypothesized to be involved in the development of ADHD. Positive associations have been found for the dopamine receptors D1 and D5 genes, suggesting that other genes involved in D1/D5 signalling may also contribute to ADHD. In this study, we tested the calcyon gene (DRD1IP), which encodes a brain-specific D1-interacting protein involved in D1/D5 receptors calcium signalling, for association with ADHD. The inheritance of nine polymorphisms in the calcyon gene was examined in a sample of 215 nuclear families, with 260 affected children, using the transmission/disequilibrium test. The most common haplotype, designated C1, demonstrated significant evidence for excess transmission. Quantitative trait analyses of this haplotype showed significant relationships with both the inattentive (parent's rating, P=0.006; teacher's rating, P=0.003) and hyperactive/impulsive (parent's rating, P=0.004) dimensions of the disorder. Two of the nine marker alleles included in haplotype C1, rs4838721A located approximately 10 kb 5' of the gene and rs2275723C located 10 bp upstream of the exon 5 acceptor splice site, also showed significant evidence for association when analysed individually. As these two variants are not predicted to alter calcyon function, we screened the gene exons by sequencing. No variation in the coding region was identified, suggesting that a causal variant allele resides elsewhere in a regulatory sequence of the gene. These findings support the proposed involvement of the calcyon gene in ADHD and implicate haplotype C1 as containing a risk allele.

The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder.

The synaptosomal-associated protein of 25 kDa gene (SNAP25) has been suggested as a genetic susceptibility factor in attention-deficit hyperactivity disorder (ADHD) based on the mouse strain coloboma. This strain is hemizygous for the SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but not to methylphenidate. Previously, we reported association of SNAP25 and ADHD using two polymorphisms. To further investigate this gene, we screened the exons for DNA variation and genotyped ten additional polymorphisms in an expanded sample of families from Toronto and a second sample of families collected in Irvine, CA. Significant results were observed in the Toronto sample for four markers, although not in the Irvine sample. The paper discusses the possible influence of the selection criteria on these differential results. The Irvine sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25. Our findings continue to support SNAP25 in the susceptibility to ADHD.

Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region.

The glutamate system may be involved in the development of attention-deficit/hyperactivity disorder (ADHD) based on animal models and the role of N-methyl-D-aspartate receptors (NMDAR) in cognition and motor processes. A follow-up study of the first genome scan for ADHD identified significant evidence for linkage to the 16p13 region. The glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the NMDA receptor, resides in this region and a recent study has reported an association between this gene and ADHD. We tested for linkage between the alleles and haplotypes of four polymorphisms at the GRIN2A locus and ADHD in our sample of 183 nuclear families with 229 affected children. In contrast to previous findings, we did not identify any evidence for a relationship of these markers and ADHD. Owing to the role of GRIN2A in aspects of cognition, we investigated the relationship of this gene to the cognitive phenotypes of inhibitory control, verbal short-term memory and verbal working memory. There was no significant evidence of linkage between GRIN2A and these phenotypes. While the results were not significant in our sample, the previous association finding suggests that further study of this gene is warranted.

Linkage of the dopamine receptor D1 gene to attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has a strong genetic basis, and evidence from human and animal studies suggests the dopamine receptor D1 gene, DRD1, to be a good candidate for involvement. Here, we tested for linkage of DRD1 to ADHD by examining the inheritance of four biallelic DRD1 polymorphisms [D1P.5 (-1251HaeIII), D1P.6 (-800HaeIII), D1.1 (-48DdeI) and D1.7 (+1403Bsp1286I)] in a sample of 156 ADHD families. Owing to linkage disequilibrium between alleles at the four markers, only three haplotypes are common in our sample. Using the transmission/disequilibrium test (TDT), we observed a strong bias for transmission of Haplotype 3 (1.1.1.2) from heterozygous parents to their affected children (P=0.008). Furthermore, using quantitative trait TDT analyses, we found significant and positive relationships between Haplotype 3 transmission and the inattentive symptoms, but not the hyperactive/impulsive symptoms, of ADHD. These findings support the proposed involvement of DRD1 in ADHD, and implicate Haplotype 3, in particular, as containing a potential risk factor for the inattentive symptom dimension of the disorder. Since none of the four marker alleles comprising Haplotype 3 is predicted to alter DRD1 function, we hypothesize that a functional DRD1 variant, conferring susceptibility to ADHD, is on this haplotype. To search for such a variant we screened the DRD1 coding region, by sequencing, focusing on the children who showed preferential transmission of Haplotype 3. DNA from 41 children was analysed, and no sequence variations were identified, indicating that the putative DRD1 risk variant for ADHD resides outside of the coding region of the gene.

Delineation of cryptogenic Lennox-Gastaut syndrome and myoclonic astatic epilepsy using multiple correspondence analysis.

PURPOSE: To distinguish various types of childhood severe cryptogenic/idiopathic generalised epilepsy on the basis of reproducible diagnostic criteria, using multiple correspondence analysis (MCA). METHODS: We applied MCA to a series of 72 children with no evidence of brain damage, starting epilepsy between 1 and 10 years, with two or more types of generalised seizures. We excluded patients with infantile spasms or typical absences. MCA was performed on all clinical and EEG parameters, first throughout follow-up, then restricted to the first year of the disease. RESULTS: When including all follow-up variables, there were three groups: (1) Thirty-seven children with male predominance, familial history of epilepsy, simple febrile convulsions, massive myoclonus, tonic-clonic fits. Outcome was favourable, with no seizures and mildly affected cognitive functions. Interictal EEG showed short sequences of irregular 3-Hz spike-waves. (2) In 18 children, clinical characteristics were similar to those of the first group at the early stage, but 95% exhibited myoclonic status and vibratory tonic seizures, with persisting seizures on follow-up. EEG showed long sequences of generalised irregular spike and slow waves. Those two groups meet the characteristics of childhood onset myoclonic-astatic epilepsy (MAE) with respectively, favourable and unfavourable outcome. (3) Eleven children had later onset, atypical absences, tonic and partial seizures, and no myoclonus, or vibratory tonic seizures. All had mental retardation and persisting seizures. EEG showed long sequences of slow spike-wave activity and half the patients had spike and slow wave foci. These patients met the major characteristics of Lennox-Gastaut syndrome. Initial parameters failed to distinguish the first two groups, but Lennox-Gastaut syndrome (the third group) was distinct from both groups of myoclonic astatic epilepsy from the onset. Within MAE groups combined, clinical and EEG risk factors for mental retardation could be identified. CONCLUSION: It is possible to validate statistically the distinction between discrete epileptic syndromes. Myoclonic astatic epilepsy is therefore distinct from Lennox-Gastaut syndrome, and the distinction appears from the first year of the disorder.

Differential effects of methylphenidate on working memory in ADHD children with and without comorbid anxiety.

OBJECTIVE: To examine the effects of methylphenidate (MPH) on working memory and behavior in anxious and nonanxious children with attention-deficit hyperactivity disorder (ADHD). METHOD: A total of 40 ADHD children (22 nonanxious, 18 anxious) completed a randomized, double-blind, placebo-controlled, crossover trial with three doses (0.3, 0.6, 0.9 mg/kg) of MPH. A serial addition task was used to assess working memory; direct observation of motor activity indexed behavior. RESULTS: MPH improved working memory in the nonanxious ADHD group but not in the comorbidity anxious group. By contrast, MPH reduced activity level in both groups. The presence of concurrent learning disabilities did not influence stimulant response. CONCLUSIONS: The presence of comorbid anxiety in children with ADHD predicts a less robust response to stimulant treatment and suggests that ADHD with anxiety may constitute a distinct and clinically meaningful subtype of ADHD.

Psychogeriatric consultation. General Hospital versus home for the aged.

As more elderly persons are institutionalized in long-term care settings, there will be an increasing need for psychiatric consultation-liaison (C/L) services. An understanding of how patterns of C/L service provision differ in these settings from those in the general hospital is important for efficient use of resources. In this study, certain characteristics of psychiatric consultations for the elderly patients in a general hospital were compared to consultations in a home for the aged. Three groups of 30 patients were examined: patients age 60 and over in a general hospital (GH), patients under age 60 in a general hospital (GHY), and patients in a home for the aged (HA). GH and GHY shared many characteristics, but there were significant differences between HA and GH: Consultations for HA were less likely to be urgent and more likely to be for management. Dementia was diagnosed in 70% of HA versus 27% in GH. Types of interventions were similar in GH and HA except that more psychotherapy was done in HA. In HA more contact was made with allied health professionals, while in GH there was more contact with medical personnel. GH patients were seen more intensively during the first 2 weeks following referral. We conclude that the major part-time attendance of a psychiatrist skilled in both the behavioral management of demented patients and liaison with allied health professionals is likely to be sufficient in long-term care institutions for elderly patients. However, the psychiatrist must also be proficient in the education of the staff of the institution so as to encourage the referral of all those patients who require psychiatric attention.