His Excellency the Right Honourable David Johnston Governor General of Canada (right) presented Her Majesty’s Diamond Jubilee Medal to Dr. David Goldbloom, Senior Medical Advisor of the Centre of Addiction and Mental Health (CAMH) and Chair of the Mental Health Commission of Canada. Photo credit: Sgt Ronald Duchesne, Rideau Hall © 2012 Office of the Secretary to the Governor General of Canada

For Immediate Release – April 16, 2012 – (Toronto) - His Excellency the Right Honourable David Johnston Governor General of Canada presented Her Majesty’s Diamond Jubilee Medal to Dr. David Goldbloom, Senior Medical Advisor of the Centre of Addiction and Mental Health (CAMH) and Chair of the Mental Health Commission of Canada. The presentation occured during the Governor General’s visit to CAMH with his wife her Excellency Sharon Johnston on Friday April 13, 2012.

Their Excellencies toured the CAMH Brain Imaging Centre and laboratories, met with researchers and students to learn about the most up-to-date, advanced research on mental illness and addiction, and were briefed on CAMH’s bold Queen Street Redevelopment Project.

“I was completely gobsmacked by this honour,” said Dr. Goldbloom. “Our focus in touring Their Excellencies was the opportunity to showcase our terrific young researchers in brain imaging and genetics. All of us who tagged along were beaming with pride at the display of their intellectual capital and impressive technology. So the award came as a total surprise at the end of an enriching afternoon.”The new Diamond Jubilee commemorative medal was created to mark the 2012 celebrations of the 60th anniversary of Her Majesty Queen Elizabeth’s accession to the Throne as Queen of Canada.

“I know from my conversation with the Governor-General and his wife that they were deeply impressed by CAMH’s research staff, resources, and accomplishments,” Dr. Goldbloom added.

“This is a well-deserved honour for David, and I wish to congratulate him on behalf of all of his colleagues at CAMH,” said Dr. Catherine Zahn, CAMH President and CEO and leader of the Governor General’s tour.  “This is a very proud day.”

Dr. Goldbloom is a gifted psychiatrist, communicator and tireless advocate on behalf of people with mental illness and addictions. His activities have long been recognized and awarded by his peers and students. He has authored numerous scientific articles and book chapters and has provided talks and lectures to student, professional and public audiences.

Dr. Goldbloom was born in Montreal and raised in Quebec and Nova Scotia. He completed an honours degree, majoring in Government, at Harvard University and then attended the University of Oxford as a Rhodes Scholar where he obtained an M.A. in Physiological Sciences. He trained in medicine and psychiatry at McGill University and is a Professor of Psychiatry at the University of Toronto.

He maintains an active clinical and teaching role at the Centre for Addiction and Mental Health where he serves as Senior Medical Advisor. He was also recently appointed Chair of the Mental Health Commission of Canada. In addition to his professional activities, Dr. Goldbloom is Chair of the Board of Governors of the Stratford Shakespeare Festival of Canada.

“The combined results from these two studies mean that NSUN2 is among the most common causes of intellectual disability resulting from recessive genes,” says Dr. Vincent.

As a recessive disorder, a child must inherit one defective NSUN2 gene from each parent to develop intellectual disability. This gene, located on chromosome 5p, encodes a type of protein called an RNA methyltransferase.

At the cellular level, the researchers found that the mutated protein was prevented from reaching its target area within the nucleus of a cell. As a result, it was unable to perform its normal role in cell division and/or RNA methylation.

Collaborators from the Wellcome Trust Centre for Stem Cell Research in Cambridge, U.K., showed which type of brain cells were likely to be most affected by this mutation. They are called Purkinje cells, a type of neuron that responds to the neurotransmitter GABA. Purkinje cells also control motor coordination, which were affected in the Pakistani family.

“We speculate that the muscle effects may result from the accumulation of the NSUN2 protein outside its target area in the nucleus,” says Dr. Vincent.

To date, Dr. Vincent’s lab has identified five genes causing different forms of recessive intellectual disability.

This research was supported by grants from Pakistan’s Higher Education Commission and the Canadian Institutes of Health Research.

Bart Everson

“Gestational diabetes mellitus (GDM) typically develops in the second and third trimesters and is defined as glucose intolerance with onset or first recognition during pregnancy,” the authors write as background information in the article. “The prevalence of GDM has been rising for over 20 years, particularly among ethnic minorities and individuals with low socioeconomic status (SES), as have lifestyle changes that heighten risk including greater consumption of saturated fats, sugar, and processed foods, and sedentary working environments.”

To examine the association of gestational diabetes mellitus (GDM) and low socioeconomic status with neurodevelopment and attention-deficit/hyperactivity disorder (ADHD) outcomes, Yoko Nomura, M.D., Ph.D., of Queens College, City University of New York, Flushing, and colleagues, compared offspring of mothers with and without GDM in an economically diverse sample. The authors distributed the ADHD Rating Scale-IV to parents of 3- and 4-year-old children in preschools surrounding Queens College, and recruited 212 participants at a 2:1 ratio of “at risk” to “typically developing” children. At-risk children had at least six inattention or six hyperactive and impulsive symptoms as rated by parents, teachers, or both. “Typically developing” children had fewer than three symptoms in each domain.

The mean (average) inattention score at baseline for offspring exposed to mother’s GDM was significantly higher than for offspring unexposed, but there was no difference in hyperactivity/impulsivity scores between the two groups. Children in low SES families, compared to high SES families, had greater inattention and hyperactivity/impulsivity scores. The results showed no difference in the risk for ADHD at baseline, but a two-fold increased risk at age 6 years among children exposed to GDM compared with children who were not exposed. There was also a two-fold increased risk for ADHD at baseline and at age 6 years among children in low SES families.

Children exposed to both GDM and low SES showed compromised neurobehavioral functioning, including lower IQ, poorer language abilities and diminished behavioral and emotional functioning. When examining the relationship of both GDM and SES exposure on outcomes, the authors found a 14-fold increased risk of developing ADHD among children exposed to both GDM and low SES. Conversely, children exposed to maternal GDM alone or low SES alone had no significant increased risk for ADHD.

“This study demonstrates that children of mothers with GDM raised in lower SES households are at far greater risk for developing ADHD and showing signs of suboptimal neurocognitive and behavioral development,” the authors conclude. “Since ADHD is a disorder with high heritability, efforts to prevent exposure to environmental risks through patient education may help to reduce the nongenetic modifiable risk for ADHD and other developmental problems.”

Amika Singh, Ph.D., of the Vrije Universiteit University Medical Center, EMGO Institute for Health and Care Research, Amsterdam, the Netherlands, and colleagues reviewed evidence about the relationship between physical activity and academic performance because of concerns that pressure to improve test scores may often mean more instructional time for classroom subjects with less time for physical activity.

The authors identified 10 observational and four interventional studies for review. Twelve of the studies were conducted in the United States, plus one in Canada and one in South Africa. Sample sizes ranged from 53 to about 12,000 participants between the ages of 6 years and 18 years. Follow-up varied from eight weeks to more than five years.

“According to the best-evidence synthesis, we found strong evidence of a significant positive relationship between physical activity and academic performance. The findings of one high-quality intervention study and one high-quality observational study suggest that being more physically active is positively related to improved academic performance in children,” the authors comment.

Background information in the article suggests that exercise may help cognition by increasing blood and oxygen flow to the brain, increasing levels of norepinephrine and endorphins to decrease stress and improve mood, and increasing growth factors that help create new nerve cells and support synaptic plasticity.

Still, “relatively few studies of high methodological quality have explored the relationship between physical activity and academic performance,” the authors conclude. No study in their systematic review used an objective measure of physical activity.

“More high-quality studies are needed on the dose-response relationship between physical activity and academic performance and on the explanatory mechanisms, using reliable and valid measurement instruments to assess this relationship accurately,” the authors conclude.

Sagnik Bhattacharyya, M.B.B.S., M.D., Ph.D, at the Institute of Psychiatry, King’s College in London, and colleagues studied 15 healthy men, who were occasional marijuana users, to examine the effects of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) on regional brain function during salience processing, which is how people perceive things around them.

The authors used functional MRI images to study each participant on three occasions after administration of Δ9-THC, CBD or placebo. Study participants performed a visual oddball task of pressing buttons according to the direction arrows on a screen were pointing, as a measure of attentional salience processing.

“Pairwise comparisons revealed that Δ9-THC significantly increased the severity of psychotic symptoms compared with placebo and CBD whereas there was no significant difference between the CBD and placebo conditions,” the authors conclude.

Overall, findings revealed that Δ9-THC had a greater effect than placebo on reaction time to nonsalient relative to salient stimuli. This was associated with modulation of both prefrontal and striatal function by Δ9-THC, augmenting (increasing) activation in the former region and attenuating (weakening) it in the latter.

“Moreover, in the present study, the magnitude of Δ9-THC’s effect on response times to nonsalient stimuli was correlated with its effect on activation in the right caudate, the region where the physiological effect of Δ9-THC was linked to its induction of psychotic symptoms,” the authors write.

They conclude that “collectively, these observations suggest that Δ9-THC may increase the aberrant attribution of salience and induce psychotic symptoms through its effects on the striatum and lateral prefrontal cortex.”

When the effects of CBD were contrasted with Δ9-THC and placebo with respect to the visual task there was a “significant effect” in the left caudate with CBD augmenting (increasing) the response and Δ9-THC attenuating (weakening) it.

“These effects suggest that CBD may also influence the effect of cannabis use on salience processing – and hence psychotic symptoms – by having an opposite effect, enhancing the appropriate response to salient stimuli,” the authors wrote.

The researchers note as background in the study that disease-modifying therapies, such as immunotherapy, are more likely to be successful if started in the early stages of the disease so there is a need to identify patients with Alzheimer disease before neurodegeneration is not too severe.

Peder Buchhave, M.D., Ph.D, who is affiliated with Lund University and Skane University, Sweden, and colleagues conducted an extended follow-up of the cohort from a previous study of 137 patients with mild cognitive impairment (MCI) at baseline. The median follow-up was 9.2 years.

During the follow-up, 72 patients (53.7 percent) developed AD and 21 (15.7 percent) progressed to other forms of dementia. At the baseline, cerebrospinal fluid Aβ42 levels were reduced and other biomarkers T-tau and P-tau levels were elevated in patients who converted to AD during follow-up compared with levels in patients who did not develop AD.

The study indicates baseline CSF Aβ42 levels were equally reduced in patients with MCI who converted to AD within five years (the early converters) compared to those who converted later between five and 10 years. However, T-tau and P-tau levels were significantly higher in early converters compared to later ones.

Researchers suggest that “approximately 90 percent of patients with MCI and pathologic CSF biomarkers at baseline will develop AD within 9.2 years.”

“Therefore, these markers can identify individuals at high risk for future AD least five to 10 years before conversion to dementia. Hopefully, new therapies that can retard or even halt progression of the disease will soon be available. Together with an early and accurate diagnosis, such therapies could be initiated before neuronal degeneration is too widespread and patients are already demented,” the authors conclude.

“Progressive loss of brain gray matter (GM) has been reported in childhood-onset schizophrenia; however, it is uncertain whether these changes are shared by pediatric patients with different psychoses,” the authors write as background information in the study.

Celso Arango, M.D., Ph.D., of the Hospital General Universitario Gregorio Marañón, Madrid, Spain, and colleagues, examined the progression of brain changes in first-episode early-onset psychosis and the relationship to diagnosis and prognosis at two-year follow-up among patients at six child and adolescent psychiatric units in Spain. The authors performed magnetic resonance imaging (MRI) of the brain for 61 patients (25 diagnosed with schizophrenia, 16 with bipolar disorder and 20 with other psychoses) and 70 healthy control participants. MRI scans were conducted at study baseline and after two years of follow-up.

Compared with control patients, those diagnosed with schizophrenia showed greater gray matter volume loss in the frontal lobe during the two-year follow-up. Patients with schizophrenia also showed cerebrospinal fluid increase in the left frontal lobe. Additionally, changes for total brain gray matter and left parietal gray matter were significantly different in patients with schizophrenia compared with patients in the control group.

Among patients with schizophrenia, progressive brain volume changes in certain areas were related to markers of poorer prognosis, such as more weeks of hospitalization during follow-up and less improvement in negative symptoms. Greater left frontal gray matter volume loss was related to more weeks of hospitalization whereas severity of negative symptoms correlated with cerebrospinal fluid increase in patients with schizophrenia.

The authors did not find any significant changes in patients with bipolar disorder compared to control patients, and longitudinal brain changes in the control group were consistent with the expected pattern described for healthy adolescents.

“In conclusion, we found progression of gray matter volume loss after a two-year follow-up in patients who ended up with a diagnosis of schizophrenia but not bipolar disease compared with healthy controls,” the authors write.

“Some of these pathophysiologic processes seem to be markers of poorer prognosis. To develop therapeutic strategies to counteract these pathologic progressive brain changes, future studies should focus on their neurobiological underpinnings.”

“Since migraine is a highly genetic disorder, our study suggests that infant colic may be an early sign that a child may be predisposed toward migraine headache later in life,” said study author Dr. Amy Gelfand, child neurologist with the Headache Center at the University of California, San Francisco.

“Colic may be another example of a childhood periodic syndrome, which is often a precursor to migraine.”

Dr. Amy Gelfand added that we have known about colic for a really long time, but despite this fact, no one really knows why these babies are crying.

Colicky babies and migraineur mothers

 This investigation consisted of a cross-sectional study of infant colic and parental migraine history in general pediatric clinics inSan Francisco. During the screening period, 154 infant-mother pairs were surveyed about their babies’ crying patterns and their own history of migraine, and those responses were analyzed to make sure the reported crying did indeed fit the clinical definition of colic.

In order to minimize recall bias, mothers were surveyed at their infants’ two-month-old well-child visit, as this is the age when infant colic is most prevalent, researchers reported.

Findings revealed that infants with a maternal history of migraine were 2.6 times as likely to have colic as infants without a maternal history of migraine (28.6% vs. 11.1%, prevalence ratio 2.6 (1.2-5.5); p=0.02). In all, there was no difference in the accuracy with which migraineur mothers perceived their infants’ colic status compared to non-migraineur mothers. Data on paternal history of migraine was available for 93 of the infants. Infants with a paternal history of migraine had a trend toward higher prevalence of colic (22.2% vs. 9.5%, prevalence ratio 2.3 (0.6-9.4), p=0.24).

“This knowledge may be helpful in more accurately identifying children who have childhood periodic syndromes by asking about a history of infant colic. In addition, this study helps to advance our understanding about the different expressions of migraine across a person’s lifetime,” Dr. Gelfand concluded.

“This is one of the first large studies to examine the association between migraine and the development of depression over time,” said Tobias Kurth, MD, ScD, with Brigham and Women’s Hospital in Boston and Inserm in France and a Fellow of the American Academy of Neurology.

Studies have shown cross-sectional relationships between migraine and depression. However, few studies have been able to evaluate the association between migraine and incident depression, researchers wrote in a report released by the American Academy of Neurology.

During the study, researchers classified 36,154 women without depression who were enrolled in the Women’s Health Study and had provided information about migraine. Women were classified as either having active migraine with aura, active migraine without aura, past history of migraine (but not within the last year) or no history of migraine. Women also provided information about diagnoses of depression.

At baseline, 6,456 women reported any history of migraine, of whom 1815 (28.1%) reported active migraine with aura. During a mean of 14.3 years of follow-up, 3,971 incident cases of depression occurred. Women with any history of migraine had 1.36 times the risk of developing depression compared to women without a history of migraine (95% CI: 1.27, 1.47). Presence of migraine aura did not modify this association (RR=1.43, 95% CI: 1.26, 1.62 for migraine with aura compared to RR=1.29, 95% CI: 1.16, 1.44 for migraine without aura). Women with a past history of migraine had 1.41 times the risk of developing depression (95% CI: 1.24, 1.59).

“We hope our findings will encourage doctors to speak to their migraine patients about the risk of depression and potential ways to prevent depression,” Dr. Kurth concluded.

During the study investigators followed 23,752 people with an average age of 64 years who were free of stroke and cognitive problems at the start of the study. Participants underwent a Framingham Stroke Risk Profile, which is used to determine a person’s risk of stroke by measuring their age, blood pressure, education level, history of heart disease, smoking and diabetes status, and whether they have left ventricular hypertrophy and an abnormal heart rhythm.

After an average of four years of follow-up, 1,907 people had developed memory and thinking problems.

Findings revealed that the higher a person’s score on the Stroke Risk Profile, the greater the chance of developing cognitive problems four years later. Fifteen per cent of people who scored among the highest 25% on the Stroke Risk Profile test (greater than 11.99 points) had cognitive problems compared to 3% of those who scored among the bottom 25% with a score below 3.4 points.

“Overall, it appears that the total Stroke Risk Profile score, while initially created to predict stroke, is also useful in determining the risk of cognitive problems,” said study author Frederick Unverzagt, PhD, of Indiana University School of Medicine in Indianapolis.

The study found older age and the presence of thickening in the heart muscle, which is a result of long-term high blood pressure, were the only Stroke Risk Profile factors independently associated with future cognitive problems.