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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.
This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care.
We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted.
Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3–4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3–4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions.
When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.
The Crunch&Sip programme is a school-based nutrition initiative designed to increase the fruit, vegetable and water intakes of primary-school children. In recognition of the notable deficits in children’s vegetable consumption, the present study explored the receptivity of school staff to a realignment of the Crunch&Sip programme to feature a primary focus on vegetable consumption. This involved investigating school staff members’ perceptions of relevant barriers, motivators and facilitators.
A multi-method approach was adopted that involved four focus groups and a survey (administered in paper and online formats) containing a mixture of open- and closed-ended items.
Staff from Western Australian schools participated in the focus groups (n 37) and survey (n 620).
School staff were strongly supportive of modifying the Crunch&Sip programme to focus primarily on children’s vegetable consumption and this was generally considered to be a feasible change to implement. Possible barriers identified included children’s taste preferences and a perceived lack of parental support. Suggested strategies to overcome these barriers were education sessions for parents and children, teachers modelling vegetable consumption for their students and integrating vegetable-related topics into the school curriculum.
School staff are likely to support the introduction of school-based nutrition programmes that specifically encourage the consumption of vegetables. Potential barriers may be overcome through strategies to engage parents and children.
Severe dementia is associated with frequent psychiatric and behavioural disturbances in addition to marked cognitive and functional deficits. Research to determine a neurochemical understanding of dementia over the last three decades has generated therapeutic strategies which improve patients' cognition and activities of daily living. Different key dementia syndromes have been shown to have distinct neurotransmitter biochemical patho-logy, with important implications for therapy. The current review focuses predominantly upon excitatory neurotransmitter systems.
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