Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

To examine two hypotheses about the longitudinal relationship between night-time parenting behaviours in the first few postnatal weeks and infant night-time sleep-waking at five weeks, three months and six months of age in normal London home environments.

Most western infants develop long night-time sleep periods by four months of age. However, around 20–30% of infants in many countries continue to sleep for short periods and cry out on waking in the night: the most common type of infant sleep behaviour problem. Preventive interventions may help families and improve services. There is evidence that ‘limit-setting’ parenting, which is common in western cultures, supports the development of settled infant night-time behaviour. However, this evidence has been challenged. The present study measures three components of limit-setting parenting (response delay, feeding interval, settling method), examines their stability, and assesses the predictive relationship between each of them and infant sleep-waking behaviours.

Longitudinal observations comparing a General-Community (n=101) group and subgroups with a Bed-Sharing (n=19) group on infra-red video, diary and questionnaire measures of parenting behaviours and infant feeding and sleep-waking at night.

Bed-Sharing parenting was highly infant-cued and stable. General-Community parenting involved more limit-setting, but was less stable, than Bed-Sharing parenting. One element of General-Community parenting – consistently introducing a short interval before feeding – was associated with the development of longer infant night-time feed intervals and longer day-time feeds at five weeks, compared with other General-Community and Bed-Sharing infants. Twice as many General-Community infants whose parents introduced these short intervals before feeding in the early weeks slept for long night-time periods at three months of age on both video and parent-report measures, compared with other General-Community and Bed-Sharing infants. The findings’ implications for our understanding of infant sleep-waking development, parenting programmes, and for practice and research, are discussed.

To provide descriptive figures for infant distress and associated parenting at night in normal London home environments during the first three months of age.

Most western infants develop long night-time sleep periods by four months of age. However, 30% of infants in many countries sleep for short periods and cry out on waking in the night: the most common type of infant sleep behaviour problem. Preventive interventions may help families and improve services. There is evidence that ‘limit-setting’ parenting, which is common in western cultures, supports the development of settled infant night-time behaviour. However, a recent review has challenged this and argued that this form of parenting risks distressing infants. This study describes limit-setting parenting as practiced in London, compares it with ‘infant-cued’ parenting and measures the associated infant distress.

Longitudinal infrared video, diary and questionnaire observations comparing a General-Community (n=101) group and subgroups with a Bed-Sharing (n=19) group on measures of infant and parenting behaviours at night.

General-Community parents took longer to detect and respond to infant waking and signalling, and to begin feeding, compared with the highly infant-cued care provided by Bed-Sharing parents. The average latency in General-Community parents’ responding to infant night-time waking was 3.5 min, during which infants fuss/cried for around 1 min. Compared with Bed-Sharing parenting, General-Community parenting was associated with increased infant distress of around 30 min/night at two weeks, reducing to 12 min/night by three months of age. However, differences in infant distress between General-Community subgroups adopting limit-setting versus infant-cued parenting were not large or statistically significant at any age. The figures provide descriptive evidence about limit-setting parenting which may counter some doubts about this form of parenting and help parents and professionals to make choices.

To investigate the influence of a trial lifestyle intervention on participants’ preferences for a range of exercise and diet programmes and whether these differ between successful and unsuccessful participants.

Hypothetical scenarios that describe attributes of diet and exercise programmes were developed using an experimental design. Participants completed an online questionnaire at baseline, 16 weeks and 12 months where they chose their most preferred of three programmes in each of sixteen scenarios. Discrete choice modelling was used to identify which attributes participants emphasised at each time point.

Fifty-five individuals who exhibited symptoms of metabolic syndrome and who participated in a 16-week trial lifestyle intervention.

There was a clear shift in programme preferences from structure to flexibility over the intervention. At baseline, emphasis was on individually designed and supervised exercise, structured diets and high levels of support, with Gainers focusing almost exclusively on support and supervision. Losers tended to consider a wider range of programme attributes. After 16 weeks preferences shifted towards self-directed rather than organised/supervised exercise and support was less important (this depended on the type of participant and whether they were in the follow-up group). Cost became significant for Gainers following the end of the primary intervention.

The stated preference method could be a useful tool in identifying potential for success and specific needs. Gainers’ relinquishment of responsibility for lifestyle change to programme staff may be a factor in their failure and in their greater cost sensitivity, since they focus on external rather than internal resources.

There is compelling evidence for the existence of susceptibility genes for bipolar disorder. Association studies using functional DNA variations are an important approach for identifying these genes. The enzyme catechol-O-methyltransferase (COMT) plays a key role in the degradation of catecholamine neurotransmitters and is a candidate for involvement in bipolar disorder. Recently a common functional genetic polymorphism that underlies population variation in COM Tactivity has been elucidated and a simple assay developed.

In a collaboration involving seven European centres, we have undertaken an association study of this functional polymorphism in 412 unrelated West European caucasian DSM - III-R bipolar patients and 368 ethnically matched controls.

We found no evidence of allelic or genotypic association.

We can conclude that variation at this functional polymorphism does not make an important contribution to bipolar disorder in the Western European population. Future studies using this powerful experimental approach can be expected to contribute to identification of bipolar susceptibility genes.