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Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
Mood and anxiety disorders co-occur and share symptoms, treatments and genetic risk, but it is unclear whether combining them into a single phenotype would better capture genetic variation. The contribution of common genetic variation to these disorders has been investigated using a range of measures; however, the differences in their ability to capture variation remain unclear, while the impact of rare variation is mostly unexplored.
Aims
We aimed to explore the contributions of common genetic variation and copy number variations associated with risk of psychiatric morbidity (P-CNVs) to different measures of internalising disorders.
Method
We investigated eight definitions of mood and anxiety disorder, and a combined internalising disorder, derived from self-report questionnaires, diagnostic assessments and electronic healthcare records (EHRs). Association of these definitions with polygenic risk scores (PRSs) of major depressive disorder and anxiety disorder, as well as presence of a P-CNV, was assessed.
Results
The effect sizes of both PRSs and P-CNVs were similar for mood and anxiety disorder. Compared to mood and anxiety disorder, internalising disorder resulted in higher prediction accuracy for PRSs, and increased significance of associations with P-CNVs for most definitions. Comparison across the eight definitions showed that PRSs had higher prediction accuracy and effect sizes for stricter definitions, whereas P-CNVs were more strongly associated with EHR- and self-report-based definitions.
Conclusions
Future studies may benefit from using a combined internalising disorder phenotype, and may need to consider that different phenotype definitions may be more informative depending on whether common or rare variation is studied.
The effect dietary FODMAPs (fermentable oligo-, di- and mono-saccharides and polyols) in healthy adults is poorly documented. This study compared specific effects of low and moderate FODMAP intake (relative to typical intake) on the faecal microbiome, participant-reported outcomes and gastrointestinal physiology. In a single-blind cross-over study, 25 healthy participants were randomised to one of two provided diets, ‘low’ (LFD) <4 g/d or ‘moderate’ (MFD) 14-18 g/d, for 3 weeks each, with ≥2-week washout between. Endpoints were assessed in the last week of each diet. The faecal bacterial/archaeal and fungal communities were characterised in 18 participants in whom high quality DNA was extracted by 16S rRNA and ITS2 profiling, and by metagenomic sequencing. There were no differences in gastrointestinal or behavioural symptoms (fatigue, depression, anxiety), or in faecal characteristics and biochemistry (including short-chain fatty acids). Mean colonic transit time (telemetry) was 23 (95% confidence interval: 15, 30) h with the MFD compared with 34 (24, 44) h with LFD (n=12; p=0.009). Fungal diversity (richness) increased in response to MFD, but bacterial richness was reduced, coincident with expansion of the relative abundances of Bifidobacterium, Anaerostipes, and Eubacterium. Metagenomic analysis showed expansion of polyol-utilising Bifidobacteria, and Anaerostipes with MFD. In conclusion, short-term alterations of FODMAP intake are not associated with symptomatic, stool or behavioural manifestations in healthy adults, but remarkable shifts within the bacterial and mycobiome populations were observed. These findings emphasise the need to quantitatively assess all microbial Domains and their interrelationships to improve understanding of consequences of diet on gut function.
Objectives/Goals: To explore the caregivers’ lived experiences related to facilitators of and barriers to effective primary care or neurology follow-up for children discharged from the pediatric emergency department (PED) with headaches. Methods/Study Population: We used the descriptive phenomenology qualitative study design to ascertain caregivers’ lived experiences with making follow-up appointments after their child’s PED visit. We conducted semi-structured interviews with caregivers of children with headaches from 4 large urban PEDs over HIPAA-compliant Zoom conferencing platform. A facilitator/co-facilitator team (JH and SL) guided all interviews, and the audio of which was transcribed using the TRINT software. Conventional content analysis was performed by two coders (JH and AS) to generate new themes, and coding disputes were resolved by team members using Atlas TI (version 24). Results/Anticipated Results: We interviewed a total of 11 caregivers (9 mothers, 1 grandmother, and 1 father). Among interviewees, 45% identified as White non-Hispanic, 45% Hispanic, 9% as African-American, and 37% were publicly insured. Participants described similar experiences in obtaining follow-up care that included long waits to obtain neurology appointments. Participants also described opportunities to overcome wait times that included offering alternative healthcare provider types as well as telehealth options. Last, participants described desired action while awaiting neurology appointments such as obtaining testing and setting treatment plans. Discussion/Significance of Impact: Caregivers perceived time to appointment as too long and identified practical solutions to ease frustrations while waiting. Future research should explore sharing caregiver experiences with primary care providers, PED physicians, and neurologists while developing plans to implement caregiver-informed interventions.
Zonisamide (1-(1,2-Benzoxazol-3-yl)methanesulphonamide) is a sulphonamide derivative with a molecular weight of 212.2 and a molecular formula of C8H8N2O3S.
Fludrocortisone acetate (9α-fluoro-11β,17α,21-trihydroxypregn-4-ene-3,10-dione 21-acetate) is a synthetic adrenal steroid. It has a molecular weight of 422.5 and a molecular formula of C23H31FO6.
Amitriptyline hydrochloride (3-(10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-ylidene)-N,N-dimethylpropan-1-amine; hydrochloride) has a molecular weight of 313.9 and a molecular formula of C20H23N,HCl. Amitriptyline is usually given as the hydrochloride and doses are expressed in terms of this salt. Amitriptyline hydrochloride 75 mg is equivalent to about 66.3 mg of the base.
Oxybutynin (4-diethylaminobut-2-ynyl 2-cyclohexyl-2-phenylglycolate; 4-(diethylamino)-2-butynyl α-phenylcyclohexaneglycolic acid ester) has a molecular weight of 357.5 and a molecular formula of C22H31NO3.
Nortriptyline hydrochloride (3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl(methyl)amine hydrochloride) is a dibenzocycloheptadiene tricyclic antidepressant with a molecular weight of 299.8 and an empirical formula of C19H21N,HCl.
Droxidopa ( (–)-threo-3-(3,4-dihydroxyphenyl)-l-serine) is an odourless, tasteless, white to off-white crystalline powder, which is slightly soluble to water. It has a molecular weight of 213.2 and a molecular formula of C9H11NO5.
Citalopram (1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3H-2-benzofuran-5-carbonitrile) is a fine white to off-white powder with a molecular weight of 324.4 and an empirical formula of C20H21FN2O. Citalopram 20 mg is equivalent to 24.99 mg citalopram hydrobromide.
Amantadine (tricyclo[3.3.1.1]decan-1-amine, 1-adamantanamine, 1-aminoadamantane) is a white or nearly white crystalline, odourless, and bitter-tasting powder, with a molecular weight of 151.25 and an empirical formula of C10H17N. Amantadine is a tricyclic amine with two available preparations, amantadine hydrochloride, which is given orally, and the salt amantadine sulphate, which is administered either orally or IV.
Melatonin (N-acetyl-5-methoxytryptamine or N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide) is a tryptophan-derived hormone and an antioxidant, produced primarily in the pineal gland. Exogenous melatonin is an amphiphilic, white–cream to yellowish crystalline powder, unchanged in the entire pH range. It has a molecular weight of 232.28 and an empirical formula of C13H16N2O2, while its chemical structure resembles serotonin.
Istradefylline (8-[(1E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-dethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione) is a xanthine derivative with a molecular weight of 384.4 and an empirical formula of C20H24N4O4.
Apomorphine hydrochloride (6aβ-aporphine-10,11-diol hydrochloride hemihydrate; (R)-10,11-dihydroxy-6a-aporphine hydrochloride hemihydrate; (6aR)-5,6,6a,7-tetrahydro-6-methyl-4H-dibenzo[de,g]quinoline-10,11-diol hydrochloride hemihydrate) has a molecular weight of 303.8 and a molecular formula of C17H18ClNO2.
Midodrine hydrochloride (2-amino-N-(β-hydroxy-2,5-dimethoxyphenethyl)acetamide hydrochloride or (RS)-N-(β-hydroxy-2,5-dimethoxyphenethyl)glycinamide hydrochloride), molecular weight 290.74 and a molecular formula of C12H18N2O4,HCl.