Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).

Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).

Smoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).

Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Research shows that highly educated individuals have at least 20 graphomotor features associated with clock drawing with hands set for '10 after 11' (Davoudi et al., 2021). Research has yet to understand clock drawing features in individuals with fewer years of education. In the current study, we compared older adults with < 8 years of education to those with > 9 years of education on number and pattern of graphomotor feature relationships in the clock drawing command condition.

Participants age 65+ from the University of Florida (UF) and UF Health (N= 10,491) completed both command and copy conditions of the digital Clock Drawing Test (dCDT) as a part of a federally-funded investigation. Participants were categorized into two education groups: < 8 years of education (n= 304) and > 9 years of education (n= 10,187). Propensity score matching was then used to match participants from each subgroup (n= 266 for each subgroup) on the following demographic characteristics: age, sex, race, and ethnicity (n= 532, age= 74.99±6.21, education= 10.41±4.45, female= 42.7%, non-white= 32.0%). Network models were derived using Bayesian Structure Learning (BSL) with the hill-climbing algorithm to obtain optimal directed acyclic graphs (DAGs) from all possible solutions in each subgroup for the dCDT command condition.

Both education groups retained 13 of 91 possible edges (14.29%). For the < 8 years of education group (education= 6.65±1.74, ASA= 3.08±0.35), the network included 3 clock face (CF), 7 digit, and 3 hour hand (HH) and minute hand (MH) independent, or “parent,” features connected to the retained edges (BIC= -7395.24). In contrast, the > 9 years of education group (education= 14.17±2.88, ASA= 2.90±0.46) network retained 1 CF, 6 digit, 5 HH and MH, and 1 additional parent features representing the total number of pen strokes (BIC= -6689.92). Both groups showed that greater distance from the HH to the center of the clock also had greater distance from the MH to the center of the clock [ßz(< 8 years)= 0.73, ßz(> 9 years)= 0.76]. Groups were similar in the size of the digit height relative to the distance of the digits to the CF [ßz(< 8 years)= 0.27, ßz(> 9 years)= 0.56]. Larger HH angle was associated with larger MH angle across groups [ßz(< 8 years)= 0.28, ßz(> 9 years)= 0.23].

Education groups differed in the ratio of dCDT parent feature types. Specifically, copy clock production in older adults with < 8 years of education relied more heavily on CF parent features. In contrast, older adults with > 9 years of education relied more heavily on HH and MH parent features. Individuals with < 8 years of education may more infrequently present the concept of time in the clock drawing command condition. This study highlights the importance of considering education level in interpreting dCDT scores and features.

Research shows that highly educated individuals have at least 20 graphomotor features associated with clock drawing with hands set for '10 after 11' (Davoudi et al., 2021). Research has yet to understand clock drawing features in individuals with fewer years of education. In the current study, we compared older adults with < 8 years of education to those with > 9 years of education on number and pattern of graphomotor feature relationships in the clock drawing copy condition.

Participants age 65+ from the University of Florida (UF) and UF Health (N= 10,491) completed command and copy digital Clock Drawing Tests (dCDT) as a part of a federally-funded investigation. Participants were categorized into two groups: < 8 years of education (n= 304) and > 9 years of education (n= 10,187). Propensity score matching was used to match participants from each subgroup (n= 266 for each subgroup) on the following: age, sex, race, and ethnicity (n= 532, age= 74.99±6.21, education= 10.41±4.45, female= 42.7%, non-white= 32.0%). Network models were derived using Bayesian Structure Learning (BSL) with the hill-climbing algorithm to obtain optimal directed acyclic graphs (DAGs) from all possible solutions in each subgroup for the dCDT copy condition.

The < 8 years of education group (education= 6.65±1.74, ASA= 3.08±0.35), retained 12 of 91 possible edges (13.19%, BIC= -7775.50). The network retained 2 clock face (CF), 5 digit, and 5 hour hand (HH) and minute hand (MH) independent, or “parent,” features connected to the retained edges. In contrast, the > 9 years of education group (education= 14.17±2.88, ASA= 2.90±0.46) network retained 15 of 91 possible edges (16.48%, BIC= -8261.484). The network retained 2 CF, 6 digit, 4 HH and MH, and an additional 3 total stroke parent features. Both groups showed that greater distance from the HH to the clock center also had greater distance from the MH to the clock center (ßz= 0.73, both). Groups were similar in digit width size relative to digit height [ßz(< 8 years)= 0.72, ßz(> 9 years)= 0.74]. Digit height size related to CF area [ßz(< 8 years)= 0.44, ßz(> 9 years)= 0.62] and CF area related to the digit distance to the CF across groups [ßz(< 8 years)= 0.39, ßz(> 9 years)= 0.46]. Greater distance from the MH to the clock center was associated with smaller MH angle [ßz(< 8 years)= -0.35, ßz(> 9 years)= -0.31], whereas greater digit misplacement was associated with larger MH angle across groups [ßz(< 8 years)= 0.14, ßz(> 9 years)= 0.29].

Education groups differed in the ratio of dCDT parent feature types. Specifically, copy clock production in older adults with < 8 years of education relied more evenly across CF, digit, and MH and HH parent features. In contrast, those with > 9 years of education differed in the additional reliance on total stroke parent features. Individuals with < 8 years of education may more heavily rely upon visual referencing when copying a clock. This study highlights the importance of considering education level in interpreting dCDT scores and features.

Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities.

We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8–18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities.

While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample.

Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.

Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence.

Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence.

No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value = 6.63 × 10−3); 5′-adenosine monophosphate-activated protein kinase signalling (P-value = 9.57 × 10−3); and apoptosis (P-value = 1.75 × 10−2) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status.

The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies.

Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.

Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.

Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.

This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.

Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.

Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).

Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.

This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.