Testing the causal impact of amyloidosis on total Tau using a genetically informative sample of adult male twins.

Introduction: The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers.

Methods: Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative.

Collaborative study on the genetics of alcoholism: The strength of collaboration, team science, and longitudinal data.

This issue contains a series of articles describing the various resources, studies, results, and future directions for the collaborative study on the genetics of alcoholism (COGA). The collaborative and integrative approach initiated by this group ~30 years ago serves as an excellent example of the strength of team science. Individually, various aspects of COGA would be limited in their impact toward improved understanding of alcohol use disorder.

Do Rating and Task Measures of Control Abilities Assess the Same Thing?

The ability to control our thoughts and actions is broadly associated with health and success, so it is unsurprising that measuring self-control abilities is a common goal across many areas of psychology. Puzzlingly, however, different measures of control - questionnaire ratings and computerized cognitive tasks - show only weak relationships to each other. We review evidence that this discrepancy is not just a result of poor reliability or validity of ratings or tasks.

Joint linkage and association mapping of complex traits in shrub willow (Salix purpurea L.).

Background And Aims: Increasing energy demands and the necessity to reduce greenhouse gas emissions are key motivating factors driving the development of lignocellulosic crops as an alternative to non-renewable energy sources. The effects of global climate change will require a better understanding of the genetic basis of complex adaptive traits to breed more resilient bioenergy feedstocks, like willow (Salix spp.).

Evidence for Transdiagnostic Repetitive Negative Thinking and Its Association with Rumination, Worry, and Depression and Anxiety Symptoms: A Commonality Analysis.

Recent theoretical advances have emphasized the commonality between rumination and worry, often referred to as repetitive negative thinking. Although not studied extensively, repetitive negative thinking may not only account for a substantial overlap between depression and anxiety symptoms but also encapsulate other constructs including one's tendency to experience unwanted intrusive thoughts or have low levels of mindfulness. In this study, 643 college students completed self-report questionnaire measures of repetitive negative thinking (the Habit Index of Negative Thinking) and other relevant constructs including rumination, worry, depression and anxiety symptoms, intrusive thoughts, and mindfulness.

Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia.

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468).

Accumulation of Polyribosomes in Dendritic Spine Heads, But Not Bases and Necks, during Memory Consolidation Depends on Cap-Dependent Translation Initiation.

Translation in dendrites is believed to support synaptic changes during memory consolidation. Although translational control mechanisms are fundamental mediators of memory, little is known about their role in local translation. We previously found that polyribosomes accumulate in dendritic spines of the adult rat lateral amygdala (LA) during consolidation of aversive pavlovian conditioning and that this memory requires cap-dependent initiation, a primary point of translational control in eukaryotic cells.

Loss of the trpc4 gene is associated with a reduction in cocaine self-administration and reduced spontaneous ventral tegmental area dopamine neuronal activity, without deficits in learning for natural rewards.

Among the canonical transient receptor potential (TRPC) channels, the TRPC4 non-selective cation channel is one of the most abundantly expressed subtypes within mammalian corticolimbic brain regions, but its functional and behavioral role is unknown. To identify a function for TRPC4 channels we compared the performance of rats with a genetic knockout of the trpc4 gene (trpc4 KO) to wild-type (WT) controls on the acquisition of simple and complex learning for natural rewards, and on cocaine self-administration (SA). Despite the abundant distribution of TRPC4 channels through the corticolimbic brain regions, we found trpc4 KO rats exhibited normal learning in Y-maze and complex reversal shift paradigms.

Exposure to nicotine increases nicotinic acetylcholine receptor density in the reward pathway and binge ethanol consumption in C57BL/6J adolescent female mice.

Nearly 80% of adult smokers begin smoking during adolescence. Binge alcohol consumption is also common during adolescence. Past studies report that nicotine and ethanol activate dopamine neurons in the reward pathway and may increase synaptic levels of dopamine in the nucleus accumbens through nicotinic acetylcholine receptor (nAChR) stimulation.

Vulnerability to Stress-Related Sleep Disturbance and Insomnia: Investigating the Link with Comorbid Depressive Symptoms.

Greater sleep difficulty following a challenging event, or a vulnerability to stress-related sleep disturbance (i.e., sleep reactivity), is characteristic of insomnia.

Null mutation of the β2 nicotinic acetylcholine receptor subunit attenuates nicotine withdrawal-induced anhedonia in mice.

The anhedonic signs of nicotine withdrawal are predictive of smoking relapse rates in humans. Identification of the neurobiological substrates that mediate anhedonia will provide insights into the genetic variations that underlie individual responses to smoking cessation and relapse. The present study assessed the role of β2 nicotinic acetylcholine receptor (nACh receptor) subunits in nicotine withdrawal-induced anhedonia using β2 nACh receptor subunit knockout (β2(-/-)) and wildtype (β2(+/+)) mice.

Differential roles of α6β2* and α4β2* neuronal nicotinic receptors in nicotine- and cocaine-conditioned reward in mice.

Mesolimbic α6* nicotinic acetylcholine receptors (nAChRs) are thought to have an important role in nicotine behavioral effects. However, little is known about the role of the various α6*-nAChRs subtypes in the rewarding effects of nicotine. In this report, we investigated and compared the role of α6*-nAChRs subtypes and their neuro-anatomical locus in nicotine and cocaine reward-like effects in the conditioned place preference (CPP) paradigm, using pharmacological antagonism of α6β2* nAChRs and genetic deletion of the α6 or α4 subunits in mice.

Genetic matters: thirty years of progress using mouse models in nicotinic research.

This research update summarizes thirty years of studies on genetic influences on responses to the acute or chronic administration of nicotine. Early studies established that various inbred mice are differentially sensitive to the effects of the drug. Classical genetic analyses confirmed that nicotine effects on locomotion, body temperature and seizures are heritable.

Control over stress, but not stress per se increases prefrontal cortical pyramidal neuron excitability.

Behavioral control over a stressful event reduces the negative consequences of not only that event, but also future stressful events. Plasticity in the prelimbic (PL) medial prefrontal cortex is critical to this process, but the nature of the changes induced is unknown. We used patch-clamp recording to measure the intrinsic excitability of PL pyramidal neurons in acute slices from rats exposed to either escapable stress (ES), for which rats had behavioral control over tail-shock termination, or inescapable stress (IS) without control.

Naturally occurring genetic variability in the nicotinic acetylcholine receptor alpha4 and alpha7 subunit genes and phenotypic diversity in humans and mice.

Through the use of pharmacological and molecular strategies, the identities of the nicotinic acetylcholine receptor (nAChR) subtypes that modulate different behaviors and physiological measures are being revealed. However, little is known with respect to how naturally occurring genetic variability in the genes that encode the members of the neuronal nAChR family contribute to phenotypic diversity in humans and research organisms. Because behavior, physiology and disease susceptibility in humans and other species are influenced to some extent by genetic factors and nAChRs contribute to a wide range of phenotypes, it is likely that polymorphisms in the genes that encode the nAChR subunit family contribute to phenotypic variability among individuals in a population.

alpha7 nicotinic receptor gene promoter polymorphisms in inbred mice affect expression in a cell type-specific fashion.

Inbred mouse strains display significant differences in their levels of brain alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) expression, as measured by binding of the alpha7-selective antagonist alpha-bungarotoxin. Variations in alpha-bungarotoxin binding have been shown to correlate with an animal's sensitivity to nicotine-induced seizures and sensory gating. In two inbred mouse strains, C3H/2Ibg (C3H) and DBA/2Ibg (DBA/2), the inter-strain binding differences are linked to a restriction length polymorphism in the alpha7 nAChR gene, Chrna7.

A genome-wide search for quantitative trait Loci that influence antisocial drug dependence in adolescence.

Background: Among adolescents, externalizing problem behavior and substance use disorders are often comorbid. Familial influences, including shared genetic risk factors, may account for part of this comorbidity. Previously we reported 2 chromosomal regions (3q24-3q25 and 9q34) likely to contain genes that influence substance dependence vulnerability (DV) in adolescence.

The relation between sluggish cognitive tempo and DSM-IV ADHD.

To test the relation between sluggish cognitive tempo (SCT) and DSM-IV ADHD symptoms, parent and teacher ratings of the 18 DSM-IV ADHD items and five potential SCT items were obtained in a community sample of 8-18 year-old twins that was overselected for ADHD and learning disabilities (n = 296). Confirmatory factor analyses revealed that a three-factor model provided the best fit to the data for both parent and teacher ratings. DSM-IV inattention and hyperactivity-impulsivity symptoms loaded on two factors consistent with the DSM-IV model, and five SCT symptoms loaded primarily on a third factor.

Genetic analysis of low-dose ethanol-induced activation (LDA) in inbred long sleep (ILS) and inbred short sleep (ISS) mice.

Ethanol-induced activation (LDA) is a measure of alcohol action on behavior and a predictor of future human alcoholism. Previous studies have shown that the long sleep (LS) and short sleep (SS) selected lines of mice differ in LDA and that two to five genes specify this phenotypic difference. The current study examines the genetic components of LDA in the ILS and ISS mice that are inbred derivatives of LS and SS and examines the effects of inbreeding on LDA.