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Aims: Depressive symptomatology can increase risk of development of alcohol problems in young people. Tension reduction and family interactional theories may explain the relationship between depression and problematic alcohol use in youth. This study addresses the nature of the longitudinal relationship between these two behaviours. The available literature is currently inconclusive about whether there are gender differences in these relationships; this is also examined., Design: The association between childhood depressive behaviours and adolescence problematic alcohol use was examined using ordered logistic regression models. Evidence of gender differences and the impact of relevant covariates on these relations were examined. Missing data were imputed using a Multiple Imputation by Chained Equation (MICE) approach., Settings: The Avon Longitudinal Study of Parents and Children (ALSPAC), a large UK population-based birth cohort., Participants: A total of 4220 British boys and girls., Measurements: Depressive symptomatology was assessed in childhood (mean age = 10.6, SD = 0.2) using the Short Mood and Feelings Questionnaire (SMFQ). Problematic alcohol use was assessed from several questions queried in adolescence (mean age = 13.8, SD = 0.2)., Findings: Childhood depressive symptoms were associated with increased risk of problematic alcohol use in early adolescence for girls [odds ratio (OR) = 1.14, P = 0.016] but not boys. This association for girls weakened (OR = 1.12, P = 0.058) when a priori selected covariates were taken into account, particularly the family and greater social environment., Conclusions: Problematic alcohol use in girls (but not boys) is associated with prior depressive symptoms. This association may be attributable to several family and social environment factors, suggesting that a family interactional theoretical model may explain these findings., (© 2011 Cardiff University.)

Background: Brain-derived neurotrophic factor (BDNF) influences neuronal survival, proliferation and plasticity. Three family-based studies have shown association of the common Valine (Val) allele of the Val66Met polymorphism of the BDNF gene with susceptibility to bipolar disorder., Aims: To replicate this finding., Method: We genotyped the Val66Met polymorphism in our UK White bipolar case-control sample (n=3062)., Results: We found no overall evidence of allele or genotype association. However, we found association with disease status in the subset of 131 individuals that had experienced rapid cycling at some time (P=0.004). We found a similar association on re-analysis of our previously reported family-based association sample (P < 0.03, one-tailed test)., Conclusions: Variation at the Val66Met polymorphism of BDNF does not play a major role in influencing susceptibility to bipolar disorder as a whole, but is associated with susceptibility to the rapid-cycling subset of the disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable, common psychiatric disorder that presents in childhood and that probably involves several genes. There are several lines of evidence suggesting that the nicotinic system may be functionally significant in ADHD: (a) nicotine promotes the release of dopamine and has been shown to improve attention in adults with ADHD, smokers and non-smokers; (b) ADHD is a significant risk factor for early initiation of cigarette smoking in children; (c) maternal cigarette smoking appears to be a risk factor for ADHD; (d) animal studies in rats and monkeys also suggest that nicotine may be involved in attentional systems and locomotor activity; and (e) a central nicotinic agonist, ABT-418, improves attention in both monkeys and ADHD adults. The current study examined the alpha 4 receptor, one of the sites of action of ABT-418. A known Cfol polymorphism within the nicotinic acetylcholine alpha 4 receptor gene, CHRNA4, was studied in 70 ADHD parent-proband trios from an ongoing sample collection of children aged 6-12 with ADHD, according to DSM-IV criteria. Children with known major medical or psychiatric conditions or mental retardation (IQ < 70) were excluded from the study. The Transmission Disequilibrium Test demonstrated no evidence that variation at the nicotinic acetylcholine alpha 4 receptor Cfol polymorphism influences susceptibility to ADHD (P > 0.35). The continuing sample collection will enable further study of other potential nicotinic system polymorphisms in ADHD in more powerful samples.

The dopaminergic system has been implicated in the aetiology of mood disorders. We conducted family-based association studies for polymorphisms at three genes involved in the metabolism of dopamine: dopamine transporter (DAT1), dopamine-beta-hydroxylase (DBH) and catechol-O-methyl transferase (COMT); and three dopamine receptors: DRD2, DRD3 and DRD5. We used a sample of 122 parent-offspring trios of British Caucasian origin where the proband had bipolar disorder I (BPI), and analysed the results with the transmission/disequilibrium test (TDT) which is robust to hidden population stratification. No statistically significant differences were found between transmitted and not transmitted alleles for any of the polymorphisms studied.

Since 1969, several classical linkage studies suggested an X-chromosome locus for bipolar affective disorder. However, methods using highly polymorphic DNA markers have provided conflicting evidence for linkage, and an X-chromosomal locus for bipolar disorder remains controversial. More recently, Pekkarinen et al. (1995) found a maximum LOD score of 3.54 at the marker DXS994 in a large bipolar Finnish kindred. In the present study, we attempted to replicate this finding using 43 families multiply affected by bipolar affective disorder. These families were selected for the absence of male-to-male transmission of the disease, and were genotyped for two microsatellte markers, DXS1227 and DXS1062 (which is about 2 cM telomeric to DXS994). Linkage to this region was excluded either using a two-point lod score method with two plausible genetic models, or by a model-free lod score analysis which does not require specification of a particular mode of transmission. We conclude that there is no evidence of a common major gene for bipolar affective disorder at Xq25-q27 in our set of families.

Tyrosine hydroxylase (TH) is the key enzyme in the synthesis of catecholamines and may therefore be of aetiological relevance in the development of psychiatric illness. Hipolar affective disorder association studies, with restriction fragment length polymorphisms located in flanking regions of the TH gene, have shown conflicting results. Alleles of a tetranucleotide repeat polymorphism (TH4) located in intron 1 of the gene were tested for association with bipolar affective disorder in a combined German and British sample of 183 bipolar patients and 209 healthy control probands. No differences in TH4 allele frequencies were found in the two groups. A subset of patients and controls was typed with the flanking markers Ty7/BglII and pJ4.7/TaqI and frequencies of two-locus haplotypes were estimated. Linkage disequilibrium was found between TH4-Ty7 and TH4-pJ4.7. Haplotype frequencies did not differ between patients and controls.