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1.
R Soc Open Sci ; 6(3): 181133, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31031995

ABSTRACT

Individuals appraise events as a consequence of their own actions (i.e. internal locus of control, LoC) or as the outcome of chance or others' will (i.e. external LoC). We hypothesized that having a more external LoC would be associated with higher risk of tobacco and alcohol use. Few studies have examined this association using large prospective data. We evaluated within the Avon Longitudinal Study of Parents and Children (ALSPAC) the associations between LoC at 16 and tobacco and alcohol consumption at 17 and 21 years using logistic regression. A more external LoC at age 16 (N = 4656) was associated with higher odds of being a weekly smoker at age 17 (OR 1.18, 95% CI 1.10-1.25) and 21 (OR 1.14, 95% CI 1.07-1.21) and with dependence measured using the Fagerström Test of Nicotine Dependence at age 17 (OR 1.26, 95% CI 1.05-1.51) and 21 (OR 1.25, 95% CI 1.05-1.49). Individuals with external LoC at age 16 were more likely to be hazardous drinkers according to the Alcohol Use Disorders Identification Test at age 17 (OR 1.09, 95% CI 1.04-1.15) but not at 21 (OR 1.01, 95% CI 0.96-1.06). Having a more external LoC at age 16 is associated with increased tobacco consumption at age 17 and 21 and alcohol consumption at 17 years. LoC may represent an intervention target for preventing substance use and dependence.

2.
Mol Psychiatry ; 23(3): 713-722, 2018 03.
Article in English | MEDLINE | ID: mdl-28373692

ABSTRACT

Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.


Subject(s)
Katanin/genetics , Katanin/metabolism , Adenosine Triphosphatases/metabolism , Animals , Cilia/genetics , Cilia/physiology , Circadian Rhythm/genetics , Ependyma/metabolism , Humans , Mice , Mice, Inbred C57BL , Microcephaly , Microtubules/metabolism , Mutation , Mutation, Missense , Neurons/metabolism , Neurons/pathology , Phenotype , Sleep/genetics
3.
Genes Brain Behav ; 16(6): 612-618, 2017 07.
Article in English | MEDLINE | ID: mdl-28421709

ABSTRACT

Attachment styles are established soon after birth and form the basis for a healthy psychological life during adulthood. Here, we investigated whether genetic background (i.e. isogenic strains: C57BL/6N and BALB/c) and parent-of-origin (i.e. reciprocal hybrids) epigenetic effects influence attachment-like styles in mice. We discovered that a specific genetic and epigenetic assortment exerts a role on the development of a secure or insecure attachment-like style. In particular, when biological mothers raise their pups, the attachment-like style is mainly secure, independently of the genetic background. However, when foster mothers raise pups, the attachment-like style can be either secure or insecure, depending on the particular genetic background, and this effect is paternally transmitted. Finally, we observed that secure attachment-like in mice leads to greater sociability during adulthood, while insecure attachment-like leads to reduced sociability. Our study sheds light on gene-environment interactions that shape the attachment-like style early in development and pave the way for a healthy psychological life.


Subject(s)
Gene-Environment Interaction , Object Attachment , Animals , Brain/growth & development , Brain/physiology , Epigenesis, Genetic , Female , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL
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