•Monoamine oxidases have been implicated in the pathophysiology of various neurological disorders.•Functional monoamine oxidase genetic polymorphisms are associated with neurological disorder risk, ...symptoms, and treatment response.•Rodents and primates display differences in monoamine oxidase function and developmental trajectory in the brain.•Monoamine oxidases are regulated by sex hormones via canonical and non-canonical pathways.•Monoamine oxidase inhibitors are promising therapeutic agents for preventing and slowing the progress of neurodegenerative disease.
Monoamine oxidase enzymes are responsible for the degredation of serotonin, dopamine, and norepinephrine in the central neurvous system. Although it has been nearly 100 years since they were first described, we are still learning about their role in the healthy brain and how they are altered in various disease states. The present review provides a survey of our current understanding of monoamine oxidases, with a focus on their contributions to neuropsychiatric, neurodevelopmental, and neurodegenerative disease. Important species differences in monoamine oxidase function and development in the brain are highlighted. Sex-specific monoamine oxidase regulatory mechanisms and their implications for various neurological disorders are also discussed. While our understanding of these critical enzymes has expanded over the last century, gaps exist in our understanding of sex and species differences and the roles monoamine oxidases may play in conditions often comorbid with neurological disorders.
•Conducted within a large prospective cohort of over 500,000 participants in the U.S.•Distance-, wind-, and toxicity-weighted emissions index to estimate dioxin exposure.•Exposure to the highest ...levels of dioxin emissions associated with risk of NHL.•NHL risk increased for those residing near coal-fired power plants.•Risks were highest for DLBCL and follicular lymphoma subtypes.
Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) are persistent organic pollutants emitted from industrial sources. Residential proximity to these emissions has been associated with risk of non-Hodgkin lymphoma (NHL) in a limited number of studies.
We evaluated associations between residential proximity to PCDD/F-emitting facilities and NHL in the NIH-AARP Diet and Health Study (N = 451,410), a prospective cohort enrolled in 1995–1996 in 6 states and 2 U.S. cities. We linked enrollment addresses with a U.S. Environmental Protection Agency database of 4,478 historical PCDD/F sources with estimated toxic equivalency quotient (TEQ) emissions. We evaluated associations between NHL and exposures during a historical period prior to enrollment (1980–1995) using an average emissions index, weighted by toxicity, distance, and wind direction (AEI-W g TEQ/km2) within 3-, 5- and 10 km of residences. We also evaluated proximity-only metrics indicating the presence/absence of one or more facilities within each distance, and metrics calculated separately for each facility type. We used Cox regression to estimate associations (hazard ratio, HR; 95 % confidence interval, 95 %CI) with NHL and major subtypes, adjusting for demographic, lifestyle, and dietary factors.
A total of 6,467 incident cases of NHL were diagnosed through 2011. Participants with an AEI-W ≥ 95th percentile had elevated risk of NHL compared to those unexposed at 3 km (HR = 1.16; 95 %CI = 0.89–1.52; p-trend = 0.24), 5 km (HR = 1.20;95 %CI = 0.99–1.46;p-trend = 0.05) and 10 km (HR = 1.15; 95 %CI = 0.99–1.34; p-trend = 0.04). We found a positive association at 5 km with follicular lymphoma (HR≥95vs.0 = 1.62; 95 %CI = 0.98–2.67; p-trend = 0.05) and a suggestive association for diffuse large B-cell lymphoma (HR≥95vs.0 = 1.40; 95 %CI = 0.91–2.14; p-trend = 0.11). NHL risk was also associated with high emissions from coal-fired power plants within 10 km (HR≥95vs.0 = 1.42; 95 %CI = 1.09–1.84; p-trend = 0.05).
Residential proximity to relatively high dioxin emissions from industrial sources may increase the risk of NHL and specific subtypes.
As COVID-19 halted traditional neuropsychological assessment due to infection risk, neuropsychologists considered alternative practice models. Cognitive stabilization intervention (CSI) via ...telehealth, was developed to stabilize cognition in advance of neuropsychological assessment. It incorporates elements of evidence-based treatments, including cognitive training, sleep training, and medication adherence training within a motivational interview framework. Two case vignettes are described. One vignette describes an elder man who received CSI to manage sleep difficulties, forgetfulness, and mood symptoms. Another vignette describes a woman who completed CSI following an autoimmune disorder episode to improve sleep, organization, and attention. The benefits and limitations of CSI are discussed.
Objective: Relative spending on substances (vs. alternatives) is predictive of several substance use outcomes, but it can be challenging to assess. We examined a novel method of assessing relative ...resource allocation through the use of a hypothetical lottery task wherein participants assume they collected $100,000 United States dollars in lottery winnings and were tasked with allocating their winnings across spending categories (e.g., savings, leisure, alcohol, cannabis). We hypothesized relative allocation of funds toward alcohol and cannabis would be positively associated with more use and problems of each substance. Method: College students (N = 479; Mage = 19.9 SD = 2.2) reported on their substance use and problems, alcohol and cannabis demand, and the hypothetical lottery task. Results: Relative resource allocation toward alcohol and cannabis on the lottery task positively correlated with alcohol and cannabis demand indices (intensity, breakpoint, Omax, and elasticity negatively), respectively. Using zero-inflated modeling, greater relative allocation toward alcohol positively related to alcohol use and problems in models that controlled for alcohol demand indices. For cannabis, relative resource allocation was also positively associated with cannabis use, but not problems, independently from cannabis demand indices. Conclusions: Results provide initial support for the hypothetical lottery task as an indicator of relative resource allocation toward substances. Generally, these results extend previous behavioral economic research demonstrating the utility of relative resource allocation as a unique predictor of clinically relevant outcomes.
Public Health Significance Statement
This study investigated relative resource allocation (i.e., proportion of available money allocated) toward alcohol and cannabis versus other discretionary spending using a new, hypothetical lottery task. Relative amount of discretionary spending allocated to alcohol and cannabis was related to self-reported alcohol and cannabis use and problems, respectively, above and beyond measures of behavioral economic demand. Operationalizing relative resource allocation using this lottery task may help capture unique processes related to substance use and problems.
The genus Macaca is an ideal model for investigating the biological basis of primate social behavior from an evolutionary perspective. A significant amount of behavioral diversity has been reported ...among the macaque species, but little is known about the neural substrates that support this variation. The present study compared neural cell density and serotonergic innervation of the amygdala among four macaque species using histological and immunohistochemical methods. The species examined included rhesus (Macaca mulatta), Japanese (M. fuscata), pigtailed (M. nemestrina), and moor macaques (M. maura). We anticipated that the more aggressive rhesus and Japanese macaques would have lower serotonergic innervation within the amygdala compared to the more affiliative pigtailed and moor macaques. In contrast to our prediction, pigtailed macaques had higher serotonergic innervation than Japanese and moor macaques in the basal and central amygdala nuclei when controlling for neuron density. Our analysis of neural cell populations revealed that Japanese macaques possess significantly higher neuron and glia densities relative to the other three species, however we observed no glia‐to‐neuron ratio differences among species. The results of this study revealed serotonergic innervation and cell density differences among closely related macaque species, which may play a role in modulating subtle differences in emotional processing and species‐typical social styles.
A high degree of behavioral variation has been observed among macaque species. To investigate the neural basis of this variation, we used stereological methods to compare neural cell density and serotonin transporter‐immunoreactive axon density in the amygdala among four species that differ in social style. We hypothesized that significantly greater serotonergic innervation would be observed in the amygdala of the most socially tolerant species in our sample, the moor macaque. Instead, the pigtailed macaque, which is considered moderately tolerant, possessed significantly greater serotonergic innervation in the amygdala relative to Japanese and moor macaques. Our findings provide insight on the neural substrates of primate sociality from an evolutionary perspective.
Abstract
Background
Ethylene oxide (EtO) is a carcinogenic gas used in chemical production and to sterilize medical equipment that has been linked to risk of breast and lymphohematopoietic cancers in ...a small number of occupational studies. We investigated the relationship between environmental EtO exposure and risk of these cancers.
Methods
Using the US Environmental Protection Agency’s Toxics Release Inventory, we estimated historical exposures for National Institutes of Health–AARP Diet and Health Study participants enrolled in 1995-1996. We constructed 2 metrics at 3, 5, and 10 km: 1) distance between residences and EtO-emitting facilities, weighted by the proportion of time the home was downwind of each facility, and 2) distance-weighted, wind direction–adjusted average airborne emissions index (AEI=∑lbs EtO/km2). We estimated risk (hazard ratio HR, 95% confidence interval CI) of incident breast cancer (in situ and invasive) among postmenopausal women (n = 173 670) overall and by tumor estrogen receptor status and non-Hodgkin lymphoma in the full cohort (n = 451 945).
Results
We observed an increased risk of breast cancer associated with EtO-emitting facilities within 10 km (HR≤10vs>10 = 1.05, 95% CI = 1.00 to 1.10) that appeared stronger for in situ (HR≤10vs>10 = 1.13, 95% CI = 1.00 to 1.27) than invasive (HR≤10vs>10 = 1.03, 95% CI = 0.97 to 1.09) disease. Risk of breast cancer in situ was also increased in the top AEI quartiles, and associations weakened with larger distances (HRQ4vs0 = 1.60, 95% CI = 0.98 to 2.61; HRQ4vs0 = 1.28, 95% CI = 0.92 to 1.79; HRQ4vs0 = 1.25, 95% CI = 1.02 to 1.53 at 3, 5, and 10 km, respectively). No differences in breast cancer risk were observed by estrogen receptor status. We found no clear pattern of increased non-Hodgkin lymphoma risk.
Conclusions
A novel potential association between EtO emissions and risk of in situ, but not invasive, breast cancer warrants additional evaluation.
The nucleus accumbens (NAc) is central to motivation and action, exhibiting one of the highest densities of neuropeptide Y (NPY) in the brain. Within the NAc, NPY plays a role in reward and is ...involved in emotional behavior and in increasing alcohol and drug addiction and fat intake. Here, we examined NPY innervation and neurons of the NAc in humans and other anthropoid primates in order to determine whether there are differences among these various species that would correspond to behavioral or life history variables. We quantified NPY-immunoreactive axons and neurons in the NAc of 13 primate species, including humans, great apes, and monkeys. Our data show that the human brain is unique among primates in having denser NPY innervation within the NAc, as measured by axon length density to neuron density, even after accounting for brain size. Combined with our previous finding of increased dopaminergic innervation in the same region, our results suggest that the neurochemical profile of the human NAc appears to have rendered our species uniquely susceptible to neurophysiological conditions such as addiction. The increase in NPY specific to the NAc may represent an adaptation that favors fat intake and contributes to an increased vulnerability to eating disorders, obesity, as well as alcohol and drug dependence. Along with our findings for dopamine, these deeply rooted structural attributes of the human brain are likely to have emerged early in the human clade, laying the groundwork for later brain expansion and the development of cognitive and behavioral specializations.
Per- and polyfluoroalkyl substances (PFAS) are widespread and environmentally persistent chemicals with immunotoxic properties. Children are prenatally exposed through maternal transfer of PFAS to ...cord blood, but no studies have investigated the relationship with childhood leukemia.
We measured maternal serum levels of 19 PFAS in first-trimester samples collected in 1986-2010 and evaluated associations with acute lymphoblastic leukemia in full-term offspring (aged younger than 15 years) for 400 cases and 400 controls in the Finnish Maternity Cohort, matched on sample year, mother's age, gestational age, birth order, and child's sex. We analyzed continuous and categorical exposures, estimating odds ratios (ORs) and 95% confidence intervals (CIs) via conditional logistic regression adjusted for maternal smoking and correlated PFAS (ρ ≥ ±0.3). We also stratified by calendar period, mean diagnosis age, and the child's sex.
N-methyl-perfluorooctane sulfonamidoacetic acid was associated with acute lymphoblastic leukemia in continuous models (per each doubling in levels: ORperlog2 = 1.22, 95% CI = 1.07 to 1.39), with a positive exposure-response across categories (OR>90th percentile = 2.52, 95% CI = 1.33 to 4.78; Ptrend = .01). Although we found no relationship with perfluorooctane sulfonic acid overall, an association was observed in samples collected in 1986-1995, when levels were highest (median = 17.9 µg/L; ORperlog2 = 4.01, 95% CI = 1.62 to 9.93). A positive association with perfluorononanoic acid was suggested among first births (Pinteraction = .06). The N-methyl-perfluorooctane sulfonamidoacetic acid association was mainly limited to children diagnosed before age 5 years (Pinteraction = .02). We found no consistent patterns of association with other PFAS or differences by sex.
These novel data offer evidence of a relationship between some PFAS and risk of the most common childhood cancer worldwide, including associations with the highest levels of perfluorooctanesulfonic acid and with a precursor, N-methyl-perfluorooctane sulfonamidoacetic acid.
Insulin is fundamental in two conditions that are epidemic in the United States and globally: obesity and type II diabetes. Given insulin's established mechanistic involvement in energy balance and ...glucose tolerance, we examined its relationship to common health-related endpoints in a large population-based sample.
The National Health and Nutrition Examination Survey is a cross-sectional study that uses a complex multistage probability design to obtain a representative sample of the United States population. Adult participants were included from 8 successive 2-year data waves (1999-2014), including 9,224 normal individuals, 7,699 prediabetic, and 3,413 diabetic subjects. The homeostatic model for insulin resistance (HOMA-IR) was available for 20,336 participants and its relationship with demographic, anthropometric, and clinical data was analyzed. We examined the relationship of HOMA-IR to 8 groups of outcome variables: general health, anthropometric/metabolic waist size, body mass index (BMI), cardiovascular (blood pressure), lipid triglycerides, high-density lipoprotein (HDL), hepatic alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), hematologic white blood cells (WBC), hemoglobin (Hgb), platelets, inflammatory (C-reactive protein), and nutritional (vitamins D and C, serum folate, and pyridoxine) variables.
HOMA-IR was generally strongly, monotonically, and highly significantly associated with adjusted outcomes in normal subjects, although clinical laboratory values were generally within normal bounds across insulin quartiles. In the normal subset, the odds ratio and 95% confidence interval for a quartile change in HOMA-IR for obesity (BMI > 30) was 3.62 (3.30-3.97), and for the highest quintile for the triglyceride/HDL the ratio was 2.00 (1.77-2.26), for GGT it was 1.40 (1.24-1.58), and for WBC it was 1.28 (1.16-1.40). The relationship of HOMA-IR to the various outcomes was broadly similar to that observed in prediabetics and diabetics with a few exceptions.
HOMA-IR levels in a large sample of normal individuals are associated with poorer general health and adverse changes across a wide range of markers. A similar pattern of alterations is observed in prediabetic and diabetic samples.
Clinically, checking insulin levels may be helpful to identify patients that merit further observation and are candidates for early interventions.
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