To assess the associations among several anthropometric measures, as well as BMI trajectories and colorectal cancer (CRC) risk in older women.

Prospective cohort study.

Forty clinical centres in the USA.

Totally, 79 034 postmenopausal women in the Women’s Health Initiative Observational Study.

During an average of 15·8 years of follow-up, 1514 CRC cases were ascertained. Five BMI trajectories over 18–50 years of age were identified using growth mixture model. Compared with women who had a normal BMI at age 18, women with obesity at age 18 had a higher risk of CRC (HR 1·58, 95 % CI 1·02, 2·44). Compared with women who kept relatively low normal body size during adulthood, women who progressed from normal to obesity (HR 1·29, 95 % CI 1·09, 1·53) and women who progressed from overweight to obesity (HR 1·37, 95 % CI 1·13, 1·68) had higher CRC risks. A weight gain > 15 kg from age 18 to 50 (HR 1·20, 95 % CI 1·04, 1·40) and baseline waist circumference > 88 cm (HR 1·33, 95 % CI 1·19, 1·49) were associated with higher CRC risks, compared with stable weight and waist circumference ≤ 88 cm, respectively.

Women who have a normal weight in early adult life and gain substantial weight later, as well as those who are persistently heavy over adulthood, demonstrated a higher risk of developing CRC. Our study highlights the importance of maintaining a healthy body weight over the life course for reducing the risk of developing CRC in women.

Identification of treatment-specific predictors of drug therapies for bipolar disorder (BD) is important because only about half of individuals respond to any specific medication. However, medication response in pediatric BD is variable and not well predicted by clinical characteristics.

A total of 121 youth with early course BD (acute manic/mixed episode) were prospectively recruited and randomized to 6 weeks of double-blind treatment with quetiapine (n = 71) or lithium (n = 50). Participants completed structural magnetic resonance imaging (MRI) at baseline before treatment and 1 week after treatment initiation, and brain morphometric features were extracted for each individual based on MRI scans. Positive antimanic treatment response at week 6 was defined as an over 50% reduction of Young Mania Rating Scale scores from baseline. Two-stage deep learning prediction model was established to distinguish responders and non-responders based on different feature sets.

Pre-treatment morphometry and morphometric changes occurring during the first week can both independently predict treatment outcome of quetiapine and lithium with balanced accuracy over 75% (all p < 0.05). Combining brain morphometry at baseline and week 1 allows prediction with the highest balanced accuracy (quetiapine: 83.2% and lithium: 83.5%). Predictions in the quetiapine and lithium group were found to be driven by different morphometric patterns.

These findings demonstrate that pre-treatment morphometric measures and acute brain morphometric changes can serve as medication response predictors in pediatric BD. Brain morphometric features may provide promising biomarkers for developing biologically-informed treatment outcome prediction and patient stratification tools for BD treatment development.

Patients on dialysis are at high risk for severe COVID-19 and associated morbidity and mortality. We examined the humoral response to SARS-CoV-2 mRNA vaccine BNT162b2 in a maintenance dialysis population.

Single-center cohort study.

Adult maintenance dialysis patients at 3 outpatient dialysis units of a large academic center.

Participants were vaccinated with 2 doses of BNT162b2, 3 weeks apart. We assessed anti–SARS-CoV-2 spike antibodies (anti-S) ∼4–7 weeks after the second dose and evaluated risk factors associated with insufficient response. Definitions of antibody response are as follows: nonresponse (anti-S level, <50 AU/mL), low response (anti-S level, 50–839 AU/mL), and sufficient response (anti-S level, ≥840 AU/mL).

Among the 173 participants who received 2 vaccine doses, the median age was 60 years (range, 28–88), 53.2% were men, 85% were of Black race, 86% were on in-center hemodialysis and 14% were on peritoneal dialysis. Also, 7 participants (4%) had no response, 27 (15.6%) had a low response, and 139 (80.3%) had a sufficient antibody response. In multivariable analysis, factors significantly associated with insufficient antibody response included end-stage renal disease comorbidity index score ≥5 and absence of prior hepatitis B vaccination response.

Although most of our study participants seroconverted after 2 doses of BNT162b2, 20% of our cohort did not achieve sufficient humoral response. Our findings demonstrate the urgent need for a more effective vaccine strategy in this high-risk patient population and highlight the importance of ongoing preventative measures until protective immunity is achieved.

The risk of antipsychotic-associated cardiovascular and metabolic events may differ among countries, and limited real-world evidence has been available comparing the corresponding risks among children and young adults. We, therefore, evaluated the risks of cardiovascular and metabolic events in children and young adults receiving antipsychotics.

We conducted a multinational self-controlled case series (SCCS) study and included patients aged 6–30 years old who had both exposure to antipsychotics and study outcomes from four nationwide databases of Taiwan (2004–2012), Korea (2010–2016), Hong Kong (2001–2014) and the UK (1997–2016) that covers a total of approximately 100 million individuals. We investigated three antipsychotics exposure windows (i.e., 90 days pre-exposure, 1–30 days, 30–90 days and 90 + days of exposure). The outcomes were cardiovascular events (stroke, ischaemic heart disease and acute myocardial infarction), or metabolic events (hypertension, type 2 diabetes mellitus and dyslipidaemia).

We included a total of 48 515 individuals in the SCCS analysis. We found an increased risk of metabolic events only in the risk window with more than 90-day exposure, with a pooled IRR of 1.29 (95% CI 1.20–1.38). The pooled IRR was 0.98 (0.90–1.06) for 1–30 days and 0.88 (0.76–1.02) for 31–90 days. We found no association in any exposure window for cardiovascular events. The pooled IRR was 1.86 (0.74–4.64) for 1–30 days, 1.35 (0.74–2.47) for 31–90 days and 1.29 (0.98–1.70) for 90 + days.

Long-term exposure to antipsychotics was associated with an increased risk of metabolic events but did not trigger cardiovascular events in children and young adults.

To compare therapeutic efficacy, social function, discontinue rate, relapse and recurrence rate of the depression outpatients with first episode between Venlafaxine extended release and Fluoxertine hydrochloride treatment. Methods In this 48 week natural parallel follow-up study, total 188 patients who meet ICD-10 criteria for a major depressive episode were admitted and assigned to receive either Venlafaxine Extended Release (Venlafaxine XR group) (n=89) or Fluoxertine hydrochloride(Fluoxertine group) (n=99).At baseline,week2,8,12,16,24,32,48,Hamilton Rating Scale for Depression (HAMD)-17 item was used to value disease severity, and Social Disability Screening Schedule(SDSS)for social disability, and the discontinue, relapse and recurrence rates were compared. Results (1) At week 24 Venlafaxine XR group had much lower HAMD17 total score than Fluoxertine group (P<0.05). (2)The remission rate and response rate between two groups had no statistical difference (P>0.05). (3) At week 12, Venlafaxine XR group had a higher SDSS score than Fluoxertine group (P<0.05).(4)At week 12, 16, 24, 32,48,Venlafaxine XR group displayed lower discontinue rates (P<0.05). Venlafaxine XR group had a longer treatment course than Fluoxertine did [(30.99±15.98) weeks vs. [(22.57±15.26) weeks] (P<0.01). (5) The relapse and recurrence rates of two groups had no statistical difference (P>0.05). Conclusions In the acute phase, Venlafaxine XR has a better effect for social function and treatment adherence than Fluoxertine hydrochloride. In the continued phase and sustained phase, Venlafaxine XR performs better for symptoms relief and treatment adherence.Venlafaxine XR has parallel performance with Fluoxertine hydrochloride by the terms of therapeutic efficacy, social function restore, relapse and recurrence rate.

Studies revealed that prenatal stress (PS) may increase the vulnerability to depression in their offspring, and ERK-CREB signal system might play a role in its mechanism.

The present study investigated the effect of MK-801 on depressive-like behavior and its impacts on ERK2, CREB, Bcl-2 mRNA expression in PS female rat offspring.

The pregnant rats were randomly divided into three groups, the control group (Con) was left undisturbed, the PS-saline group (PS-saline) and the PS-MK-801 group (PS-MK-801) were subjected to restraint stress on days 14–20 of pregnancy three times daily for 45 min, and received an i.p. administration of saline or MK-801(sigma, 0.2 mg/kg) 30 min before the first stress respectively. Forced swimming test was undertaken to assess depressive-like behavior in one month female offspring. ERK2, CREB, Bcl-2 mRNA in the hippocampus, frontal cortex, and striatum were detected by RT-PCR.

PS-saline spent significantly more immobile time compared to Con and PS-MK-801 (P < 0.05). ERK2 and CREB mRNA expression in hippocampus and frontal cortex was significantly decreased in PS-saline compared to Con and PS-MK-801 (P < 0.05), while in striatum CREB mRNA expression in PS-saline was lower than Con (P < 0.05). Bcl-2 mRNA expression in hippocampus and striatum was significantly decreased in PS-saline (P < 0.05), and in frontal cortex, its expression was significantly lower in PS-saline and PS-MK-801 (P < 0.05).

PS may suppress ERK-CREB signal pathway in female offspring rats, which could be partly prevented by MK- 801. (Supported by National Natural Science Foundation of China, No: 30970952).

Brain-derived neurotrophic factor (BDNF) has an important role in learning, motivation and regulation of mood. A body of research indicates that dysregulation of BDNF is found in post-traumatic stress disorder (PTSD). The aim of this study was to investigate the association of baseline plasma BDNF and follow-up PTSD symptoms in Chinese motor vehicle accident survivors.

Motor vehicle accident (MVA) survivors were recruited from one Emergency Room of Shanghai. BDNF plasma levels were measured in 24 hours after motor vehicle accident. The Clinician-Administered PTSD Scale (CAPS) was used to evaluated PTSD symptoms one month after accident. Totally, 60 MVA survivors participated in this study and 49 of them completed follow-up evaluation.

In the one month follow-up interview, 14 of the MVA survivors met the PTSD diagnosis. The PTSD MVA survivors shown lower baseline BDNF plasma level when compare with non-PTSD participants (p < 0.05).

People who show lower plasma BDNF after traumatic event may be more susceptible to PTSD, and plasma BDNF could be a predictor of PTSD.

The debates about depressive disorder and cognition impairment are supported by controversial data.

We launched the study to investigate cognitive change in first onset depressive patients over a 6 year period.

A prospective cohort was performed. Participants included 206 cases of first onset depressive Chinese outpatient aged from 17 to 60 year old and followed from Apr. 2003-Feb. 2004 to Apr. 2009-Feb. 2010 in Shanghai. During the first 48 weeks, case management service was delivered. Participants were assessed by 17-HAMD and HAMA scale at baseline, week 12, week 32, week 48, and year 6. Cognitive changes were assessed using the WMS-RC, WAIS-RC, and WCST at baseline (n = 116), week 12 (n = 80) and year 6 (n = 24), 41 normal participants as control.

1. (1) During the first depressive onset, cognitive performance deteriorated comparing with those of control group (P < 0.01).

2. (2) At week 12,effective medication could relieve symptom and improve cognition function (P < 0.05), cognitive performance compared between patient and control with no obvious difference (P > 0.05). While patient group had a significantly larger proportion (whose Memory Quotient below 85) than control group did (χ2 = 5.66, P < 0.05).

3. (3) Using a general linear mixed model to estimate cognitive change,patients with more severe depressive retardation and lower education had a worse short-term memory over 6 years (estimate = -1.65, SE = 0.80, P < 0.05;estimate=1.63, SE = 0.30, P < 0.01), adjusting for demographics and medical status.

The first onset depressive patient has cognitive defects. Memory does not full recovery after symptom relief. Short-term memory impairment persists over 6 years with relative factors.

With the widespread of atypical antipsychotics used among children and adolescents, the treatment effectiveness has been of great interest alongside with the efficacy and safety in this population. The study was designed to assess whether second-generation antipsychotics (SGAs) are associated with lower service costs in the real world. Factors associated with service costs were also examined.

The claim data (PIMC) of 1996-2008 from the National Insurance Plan of Taiwan was used. Patients aged less than 20 with an incident use of antipsychotics and last for 12 months during this period were included for analysis. Comparisons were made between 8 SGAs and 2 first-generation antipsychotics (FGAs). Changes in service costs were examined with 95% confidence interval. Multivariate regressions with propensity scores adjustment were performed to explore factors associated with psychiatric service costs.

A total of 343 treatment encounters were included and results showed no difference in psychiatric services costs in the SGAs group as the total service costs were offset to high antipsychotics costs of SGAs, though antiparkinsonian costs were not different between two groups. Factor positively associated with service costs were relapse (RR=4.0, p< 0.0001) and EPS incidence (RR=1.6, p< 0.008), while types of antipsychotics and diagnoses were not significant factors after adjusting for covariates.

Service costs were not different between FGAs and SGAs groups and medication costs were significantly higher in the SGAs group. Relapse and EPS incidence were factors of high costs among children and adolescents psychiatric patients treated with antipsychotics in Taiwan.

Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.

We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.

In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).

AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.