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Turner N.E.,Center for Addiction and Mental Health | Turner N.E.,University of Toronto | Turner N.E.,The Center for Addiction and Mental Health | Paglia-Boak A.,Center for Addiction and Mental Health | And 16 more authors.
International Journal of Mental Health and Addiction | Year: 2012

Video game playing has become a very popular activity among adolescents. Its impact on the mental health and well-being of players is just beginning to be explored. This paper reports on the prevalence of problematic gaming in a representative sample of 2,832 Ontario students in grades 7 to 12. The survey included questions about the school grade, family and school related problems, frequency of video game playing and video game related problems as measured by the Problem Video Game Playing scale (PVP). Most of the students (85 %) reported playing video games in the past year and 18. 3 % reported playing video games daily. Slightly less then 1 in 10 of the students (9. 4 %) endorsed 5 or more of the PVP items (males 15. 1 %; females 3. 1 %). Further research is required to delineate the concept of excessive video game playing, its relation to other addictions, and the impact on adolescents' psychosocial functioning. © 2012 Springer Science+Business Media, LLC.


Carter M.,Holland Bloorview Kids Rehabilitation Hospital | Nikkel S.,Childrens Hospital of Eastern Ontario | Fernandez B.,Memorial University of Newfoundland | Marshall C.,Applied Genomics | And 14 more authors.
Clinical Genetics | Year: 2011

We describe the identification and clinical presentation of four individuals from three unrelated families with hemizygous deletions involving the DPYD gene at chromosome 1p21.3. DPYD encodes dihydropyrimidine dehydrogenase, which is the initial and rate-limiting enzyme in the catabolism of pyrimidine bases. All four individuals described met diagnostic criteria for autism spectrum disorder with severe speech delay. Patient 1's deletion was originally reported in 2008, and more detailed clinical information is provided. Subsequently, this male individual was found to have a missense mutation in the X-linked PTCHD1 autism susceptibility gene, which may also contribute to the phenotype. Patients 2 and 3 are siblings with a novel deletion encompassing the DPYD gene. In their mother, the genomic region deleted from chromosome 1p21.3 was inserted into chromosome 10. A fourth proband had a novel 10-kb intragenic deletion of exon 6 of the DPYD gene detected on a higher resolution microarray. Our study suggests that hemizygous deletions involving the DPYD locus present with variable phenotypes which can include speech delay and autistic features, and may also be influenced by additional mutations in other genes, issues which need to be considered in genetic counseling. © 2010 John Wiley & Sons A/S.


Rafiq M.A.,Campbell Family Mental Health Research Institute | Rafiq M.A.,Hospital for Sick Children | Leblond C.S.,Research Center Notre Dame Hospital | Leblond C.S.,Montreal Neurological Institute | And 44 more authors.
BMC Medical Genetics | Year: 2015

Background: Cohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits. Methods: Clinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations. Results: We identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population. Conclusion: We suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup. © 2015 Rafiq et al.


Rafiq M.A.,Hospital for Sick Children | Leblond C.S.,Research Center Notre Dame Hospital | Leblond C.S.,Montreal Neurological Institute | Saqib M.A.N.,Quaid-i-Azam University | And 41 more authors.
BMC Medical Genetics | Year: 2015

Background: Cohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits. Methods: Clinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations. Results: We identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population. Conclusion: We suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup. © 2015 Rafiq et al.


Guerin A.,The Hospital for Sick Children | Guerin A.,Kingston General Hospital | So J.,The Hospital for Sick Children | So J.,The Center for Addiction and Mental Health | And 5 more authors.
American Journal of Medical Genetics, Part A | Year: 2015

Ocular anomalies have been frequently reported in Noonan syndrome. Anterior segment anomalies have been described in 57% of PTPN11 positive patients, with the most common findings being corneal changes and in particular, prominent corneal nerves and cataracts. We report on a neonate with a confirmed PTPN11 mutation and ocular findings consistent with Axenfeld anomaly. The patient initially presented with non-immune hydrops and subsequently developed hypertrophic cardiomyopathy and dysmorphic features typical of Noonan syndrome. While a pathogenic mutation in PTPN11 was confirmed, prior testing for the two common genes associated with Axenfeld-Rieger syndrome, PITX2, and FOXC1 was negative. This finding expands the spectrum of anterior chamber anomalies seen in Noonan syndrome and perhaps suggests a common neural crest related mechanism that plays a critical role in the development of the eye and other organs. © 2014 Wiley Periodicals, Inc.


Xiao Y.,Montreal Neurological Institute | Fonov V.,Montreal Neurological Institute | Beriault S.,Montreal Neurological Institute | Subaie F.A.,McGill University | And 5 more authors.
International Journal of Computer Assisted Radiology and Surgery | Year: 2015

Purpose : Parkinson’s disease (PD) is the second leading neurodegenerative disease after Alzheimer’s disease. In PD research and its surgical treatment, such as deep brain stimulation (DBS), anatomical structural identification and references for spatial normalization are essential, and human brain atlases/templates are proven highly instrumental. However, two shortcomings affect current templates used for PD. First, many templates are derived from a single healthy subject that is not sufficiently representative of the PD-population anatomy. This may result in suboptimal surgical plans for DBS surgery and biased analysis for morphological studies. Second, commonly used mono-contrast templates lack sufficient image contrast for some subcortical structures (i.e., subthalamic nucleus) and biochemical information (i.e., iron content), a valuable feature in current PD research.Methods : We employed a novel T1–T2* fusion MRI that visualizes both cortical and subcortical structures to drive groupwise registration to create co-registered multi-contrast (T1w, T2*w, T1–T2* fusion, phase, and an R2* map) unbiased templates from 15 PD patients, and a high-resolution histology-derived 3D atlas is co-registered. For validation, these templates are compared against the Colin27 template for landmark registration and midbrain nuclei segmentation.Results : While the T1w, T2*w, and T1–T2* fusion templates provide excellent anatomical details for both cortical and subcortical structures, the phase and R2* map contain the biochemical features. By one-way ANOVA tests, our templates significantly (p<0.05) outperform the Colin27 template in the registration-based tasks.Conclusion : The proposed unbiased templates are more representative of the population of interest and can benefit both the surgical planning and research of PD. © 2014, CARS.


da Silva T.L.,King's College | da Silva T.L.,The Center for Addiction and Mental Health | da Silva T.L.,University of Toronto | Ravindran A.V.,King's College | And 2 more authors.
Asian Journal of Psychiatry | Year: 2015

Female patients with schizophrenia tend to have a more benign course and better outcomes than males. One proposed explanation is the differential influence of male and female sex hormones, including estrogen, progesterone, testosterone, and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). Such benefit may be mediated by their effects on neurotransmitters and neuroprotection. Besides altered estrogen and DHEA/DHEAS levels in female patients, data is equivocal on hormonal differences between patients and controls. However, several reports note a mostly negative correlation between estrogen levels and symptom severity in both genders, and a positive correlation between estrogen levels and neurocognition but mainly in females. Adjunctive estrogen appears to improve symptoms in both genders. Progesterone levels have inconsistent links to symptom severity in both genders, and correlate positively with neurocognition but only in males. Estrogen-progesterone combination shows preliminary benefits as augmentation for both symptoms and neurocognition in females. Testosterone levels correlate inversely with negative symptoms in males and have inconsistent associations with neurocognition in both genders. Testosterone augmentation reduced negative symptoms in male patients in a pilot investigation, but has not been evaluated for neurocognition in either gender. DHEA/DHEAS have mixed results for their association with, and clinical utility for, symptoms and neurocognition in both genders. Overall, data on the impact of sex hormones on clinical course or as treatment for schizophrenia is limited, but estrogen has most evidence for positive influence and clinical benefit. The possibly greater tolerability and broader impact of these hormones versus existing medications support further exploration of their use. © 2015 Elsevier B.V.


Lee D.K.,University of Toronto | Ferguson S.S.G.,Robarts Research Institute | George S.R.,University of Toronto | George S.R.,The Center for Addiction and Mental Health | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2010

Internalization of the apelin receptor by apelin-13 is characterized by dissociation from β-arrestins and rapid recycling to the cell surface. Paradoxically, the apelin receptor internalized by apelin-36 was sequestered intracellularly. The specific pathways involved in apelin receptor trafficking were resolved using β-arrestin1 and constitutively active and dominant negative Rab proteins following activation by apelin-13 or apelin-36. β-Arrestin1 dissociated from the apelin-13-internalized receptor while the apelin-36-internalized receptor was trafficked with β-arrestin1 to intracellular compartments. The apelin-13-internalized receptor was rapidly recycled to the cell surface through a Rab4-dependent mechanism while Rab7 targeted the receptor to lysosomes. The internalized receptor co-expressed with dominant negative Rab4 were trafficked to lysosomes. These observations revealed a novel ligand-dependent targeting of the apelin receptor to β-arrestin-associated and -dissociated trafficking pathways and a role for different Rab proteins to direct these pathways. © 2010 Elsevier Inc. All rights reserved.

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