Early Cannabis Use, Polygenic Risk Score for Schizophrenia and Brain Maturation in Adolescence

French, Leon; Gray, Courtney; Leonard, Gabriel; Perron, Michel; Pike, G. Bruce; Richer, Louis; Séguin, Jean R.; Veillette, Suzanne; Evans, John; Artiges, Éric; Banaschewski, Tobias; Bokde, Arun L.W.; Bromberg, Uli; Bruehl, Ruediger; Büchel, Christian; Cattrell, Anna; Conrod, Patricia J.; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Lemaître, Hervé; Martinot, Jean Luc; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Pangelinan, Melissa M.; Poustka, Luise; Rietschel, Marcella; Smolka, Michael N.; Walter, Henrik; Whelan, Robert; Timpson, Nicholas J.; Schumann, Günter; Smith, George Davey; Pausová, Zdenka; Paus, Tomáš

doi:10.1001/jamapsychiatry.2015.1131

Cited by 153 publications

(126 citation statements)

References 60 publications

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“…A clear benefit of this approach is that, unlike smaller single studies designed to explicitly address a single research question, such broad spectrum studies allow for the accumulation of a large well-powered dataset that can be used to address multiple different research questions, including expected small effects of common genetic variation. Further, because many other studies use similar methodology (e.g., HCP; (Barch et al, 2013); Brain Genomics Superstruct Project; (Holmes et al, In press); IMAGEN; (French et al, 2015), results can be readily integrated into prior literature with an increased likelihood that additional data may become available for replication attempts. However, alongside these clear benefits, there are also limitations that must be considered.…”

Section: 0 Discussionmentioning

confidence: 99%

Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function

Iorio

Carey

Michalski

et al. 2017

Psychoneuroendocrinology

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Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear.

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Section: 0 Discussionmentioning

confidence: 99%

Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function

Iorio

Carey

Michalski

et al. 2017

Psychoneuroendocrinology

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“…Two other MRI studies have reported that cannabis users had smaller hippocampal volumes than non-users, but that this was not evident in cannabis users with hair samples that were positive for CBD 40,41 . However, the extent to which cannabis use is associated with neuroanatomical changes remains controversial: studies that have matched participants on alcohol use, or have accounted for heritable and genetic risk, have failed to find an association between cannabis use and brain structure [42][43][44] .…”

Section: Psychosismentioning

confidence: 99%

Can we make cannabis safer?

Englund

Freeman

Murray

et al. 2017

The Lancet Psychiatry

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“…This mapping principle has been used to bring gene-expression data contained in the Allen Brain Atlas into a FreeSurfer-based anatomical parcellation of the cerebral cortex 155 . This allowed us, for example, to show that regional differences in cortical thickness associated with early cannabis use follow a regional gradient in the expression of CNR1 156 . Box 3: developmental structural neuroimaging Our first major longitudinal insight into the dynamics of in vivo human brain development came from a structural neuroimaging study 157 , which revealed that the maturational trajectory of human gray matter volume follows a curvilinear "inverted-U", rather than showing a linear progression to adult values.…”

Section: Box 2: Population Neurosciencementioning

confidence: 99%

Studying neuroanatomy using MRI

et al. 2017

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The study of neuroanatomy using imaging enables key insights into how our brains function, are shaped by genes and environment, and change with development, aging, and disease. Developments in MRI acquisition, image processing, and data modelling have been key to these advances. However, MRI provides an indirect measurement of the biological signals we aim to investigate. Thus, artifacts and key questions of correct interpretation can confound the readouts provided by anatomical MRI. In this review we provide an overview of the methods for measuring macro-and mesoscopic structure and inferring microstructural properties; we also describe key artefacts and confounds that can lead to incorrect conclusions. Ultimately, we believe that, though methods need to improve and caution is required in its interpretation, structural MRI continues to have great promise in furthering our understanding of how the brain works.

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Early Cannabis Use, Polygenic Risk Score for Schizophrenia and Brain Maturation in Adolescence

Abstract: assisted with recruitment and testing of the participants, technical assistance, and coordination of the imaging project in the ALSPAC.

Cited by 153 publications

References 60 publications

Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function

Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function

Can we make cannabis safer?

Studying neuroanatomy using MRI

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