Susceptibility genes for schizophrenia have been hypothesised to mediate liability for the disorder at least partly by influencing cognitive performance. We investigated the association between genotype and cognitive performance for a Dysbindin risk haplotype which is associated with schizophrenia in our sample. Fifty-two patients with schizophrenia or schizoaffective disorder (24 risk haplotypes carriers versus 28 non-risk haplotype carriers) were assessed in areas of cognition showing evidence of familial deficits in schizophrenia. Verbal and spatial memory, working memory, and attentional control was assessed using selected measures from the Weschler memory scale (WMS), Cambridge automated test battery (CANTAB), continuous performance test (CPT), and a simple go/no-go task. Pre-morbid IQ was also assessed using the Weschler Test of Adult Reading (WTAR). Patients carrying the Dysbindin risk haplotype showed significantly lower spatial working memory performance than patients who were non-risk carriers, with genotype explaining 12% of variance in performance. Our study suggests that the increased risk for schizophrenia associated with dysbindin may be partly mediated by its influence on pre-frontal function.

No abstract

Building trust in science and evidence-based decision-making depends heavily on the credibility of studies and their findings. Researchers employ many different study designs that vary in their risk of bias to evaluate the true effect of interventions or impacts. Here, we empirically quantify, on a large scale, the prevalence of different study designs and the magnitude of bias in their estimates. Randomised designs and controlled observational designs with pre-intervention sampling were used by just 23% of intervention studies in biodiversity conservation, and 36% of intervention studies in social science. We demonstrate, through pairwise within-study comparisons across 49 environmental datasets, that these types of designs usually give less biased estimates than simpler observational designs. We propose a model-based approach to combine study estimates that may suffer from different levels of study design bias, discuss the implications for evidence synthesis, and how to facilitate the use of more credible study designs.

No abstract

Long-term weight-restored patients with anorexia nervosa (AN) have lower norepinephrine levels than controls. 1,2 Since this may reflect altered reuptake by the norepinephrine transporter (NET),The noradrenergic system is involved in regulating each of the neuroendocrine systems that become disrupted in AN. 5-7 AN patients at normal weight for 6-72 months have significantly lower blood and CSF levels of norepinephrine 1,2 and 3-methoxy-4-hydroxyphenylglycol 1 than normal controls, suggesting that reduced noradrenergic activity is associated with longterm weight restoration. It is not clear, however, whether alterations in metabolism, secretion, or NET reuptake of norepinephrine are responsible for this reduced activity. The NET gene has been cloned and sequenced 8 and polymorphisms have been identified in the coding and intronic regions 9-11 but not in the promoter. We hypothesised that DNA variation in the NET gene promoter was involved in the genetic susceptibility to develop AN.We observed tandem AAGG repeats from positions −4297 to −4282 (AAGG1 in Figure 1a) in the only published sequence of the far 5Ј end of the NET gene promoter reported earlier by Kim et al. 12 To investigate this repeat region, an expected 517-bp fragment was PCR-amplified from genomic DNA. However, gel sizing revealed a Ͼ800-bp band (data not shown) which was confirmed to be 860 bp after bidirectional DNA sequencing of the PCR product. Only the 860-bp fragment was observed in 50 anonymous (48 Caucasian: two East Asian) genomic DNA samples (data not shown). The 860 bp consisted of 517 bp from the Kim et al 12 sequence together with a novel 343-bp GA-rich sequence. Blast searches of GenBank with the novel sequence produced no matches with any known gene and only a single gene encoding the human NET is known to exist. 13 After we submitted our novel sequence to GenBank (accession number AF330628), The Human Genome Project working draft confirmed the existence of the novel sequence.To study the 343-bp novel sequence, primers were designed to amplify a 525-bp region including the novel sequence (Figure 1a). Bidirectional sequencing of the PCR product revealed six discrete islands of consensus AAGG tetranucleotide repeats which we desig- Figure 1 Organisation of the NETpPR, and NETpPR polymorphic variants. (a) 525-bp genomic DNA sequence from current study deposited in GenBank accession AF330628; numbering relates to the start site (+1) in GenBank sequence AF061198; 12 NETpPR located from −4297 to −3935; imperfect repeat sequences (RepeatA and RepeatB) are underlined; 343-bp novel sequence is in uppercase (−4277 to −3935); AAGG1-AAGG6 are boxed; identified polymorphisms are labelled L1, S1, L4, and S4; Elk-1 transcription factor sites lost in S1 and S4 are shown with core sequence in bold; primer sequences are shaded. (b), (c), and (d) Demonstrate detection of polymorphisms through heteroduplex (heterodup.) analysis: (b) and (c) electrophoresed using mini-PROTEAN II/III systems; (d) electrophoresed using Hoefer SE600.