Research Hightlights - Research Annual Report 2005

Research highlights

Drs. Anne Bassett, Eva Chow and colleagues, in collaboration with Dr. Linda Brzustowicz at Rutgers University, reported that the CAPON (carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase) gene on chromosome 1 is linked to an inherited form of schizophrenia in Canadian families. CAPON is an appealing candidate for schizophrenia susceptibility because of its activities, which include formation of synapses in the developing brain and involvement in the glutamate neurotransmitter system, consistent with prevailing models of schizophrenia development.

Dr. Ray Blanchard published a meta-analysis of data from 10,143 male subjects, which confirmed that homosexuality in human males is predicted by higher numbers of older brothers, but not by higher numbers of older sisters, younger brothers or younger sisters.

In one of the first studies to characterize people dependent on  prescription opioids in a methadone maintenance treatment program, Dr. Bruna Brands showed that those dependent only on prescription opioids were less likely to use illicit non-opioid drugs or to be  associated with injection drug use; those who used prescription opioids only or initially were more likely to have ongoing pain  problems and to be involved in psychiatric treatment.

Dr. John Cairney of the Health Systems Research and Consulting Unit and his research team released data showing that mental health care services in Ontario appear to adequately target the mental health needs of single mothers.

Dr. Tony Cohn and colleagues published a paper characterizing  the coronary heart disease risk profile of people with chronic  schizophrenia. Compared with a matched reference population, men and women with chronic schizophrenia showed double the rate of metabolic syndrome. This finding -consistent with increased coronary heart disease mortality reported in schizophrenia -has  led this group to establish a protocol for monitoring metabolic and cardiac risk factors in people treated with clozapine.

An NIH-funded study, looking at the effectiveness of the Strengthening Families intervention for children of alcohol-abusing parents (co-led by Dr. David J. DeWit) identified punitive parenting as a mechanism to account for the relationship between parent psychopathology and child social skill deficits.

A study, led by Dr. Peter Farvolden, to assess the use and effectiveness of web-based self-help cognitive-behavioural therapy for panic disorder and agoraphobia showed that such programs hold promise as effective, accessible treatment for anxiety.

Dr. Benedikt Fischer, with collaborator Dr. John Farley and colleagues, studied interferon - ribavirin combination treatment for hepatitis C virus (HCV). This study, which looked at people infected with HCV who were inmates of federal correctional institutions in British Columbia, showed that two-thirds of the sample achieved a "sustained virological response" and thus were considered cured. Given that the majority of HCV infections occur in marginalized populations, the  key implication of this study is that state-of-the-art treatment is  feasible in the high-risk correctional setting and produces outcomes comparable to patient samples in the general community.

The Ontario Tobacco Research Unit, under the direction of Dr. Roberta Ferrence, released a major report on monitoring the Ontario Tobacco Strategy. The report includes extensive information, based on CAMH surveys as well as federal sources, on tobacco use and problems in Ontario and also includes recommendations for the Ministry of Health and Long-Term Care and the tobacco control community.

A project led by Dr. Susan George found that dopamine D1 and D2 receptor co-activation triggered a novel calcium signal in brain. This has significant implications for understanding schizophrenia and drug addiction and provides a new target for designing medications for these conditions.

Apelin peptide, a neurotransmitter, is the natural chemical that activates the apelin receptor; this receptor was first discovered in the Molecular Pharmacology laboratory, under the direction of Dr. George. The lab designed an analogue that can interfere with and block the actions of apelin, in order to decipher its role in the brain-this work may lead to a better understanding of higher brain functions, such as learning, mood regulation, stress responses and appetite.

A study to assess the influence of various factors in developing im-paired driving policy in the United States and Canada, led by Dr. Norman Giesbrecht and Dr. Linda Degutis (Yale University), showed that research evidence, victims' stories, societal factors and advocacy groups such as MADD played a major role in preventing drinking and driving.

Dr. Louis Gliksman completed the first Canadian research on drug treatment courts. The results indicated success with specific types of clients, but that drug treatment court is not a panacea. The research included recommendations for client retention, treatment requirements, court processes, cost implications and client process for other drug treatment courts that are starting across Canada.

As cannabis has entered mainstream culture, Dr. Andy Hathaway has found that people's cannabis use practices appear to be evolving. Based on interviews with 104 people in Toronto who had used cannabis long-term, illicit drug experience was largely limited to cannabis, and the law was not a problem for most people who use the drug. Rather, their emphasis was on informal rules for managing risk and stigma within their social circles.

Dr. Lorne Korman led a randomized controlled study evaluating an emotion- and behaviourally based treatment for concurrent gambling, substance use and anger. Results showed that an integrated  treatment was more effective at reducing gambling, substance  use and anger problems, and at retaining clients in treatment, than  a gambling-only treatment.

Dr. Peter Li reported that elevated levels of the signalling G protein, Gas, increases vulnerability of neuronal cells to cellular stressors. This finding extends his group's earlier observation implicating abnormalities of Gas-mediated signalling as another link in the molecular chain involved in bipolar disorder.

In response to an invitation by the Hospital Report Collaborative, a team led by Drs. Elizabeth Lin and Janet Durbin developed the first province-wide mental health Hospital Report Card. The report provided provincial and regional benchmarks for 24 performance  indicators of inpatient mental health care. The team developed  new data sources to provide critical province-wide information  on patient satisfaction, information management practices and  use of evidence-based practices.

Dr. Scott Macdonald and his colleagues found that convictions for driving while impaired by alcohol were significantly elevated among those assessed in treatment for cocaine-only problems but not among those who had problems with cannabis only. The results suggest that cross-dependence of alcohol and cocaine is common, and problematic drinking among people seeking help for cocaine dependence can go undetected when clients are being diagnosed  for treatment.

A project led by Dr. Brian O'Dowd discovered that the apelin receptor, one of the G protein coupled receptors, goes to the nucleus of human brain cells. The lab then created a novel screening method-based on modifying other receptors of this type so that they, too, can go to the nucleus of brain cells-to discover compounds that target G protein coupled receptors. These receptors are very important therapeutically, as many drugs target them.

G protein coupled receptors occur as complexes, or oligomers, in the human brain; these complexes have novel properties in the brain. Dr. Brian O'Dowd observed these complexes in living cells and achieved their disruption for the first time. Receptor oligomers undergo a strict quality control check of their structure before being sent to the cell surface to ensure that they are in the correct conformation for activation; if abnormal receptors are made, they will be detected by the cell. Understanding these receptor complexes better has implications for discoveries about diseases and medications.

Analyses for the World Bank and WHO by Drs. Jürgen Rehm and  Dan Chisholm showed that, for most parts of the world, taxation and other regulatory policies are the most effective and cost-effective ways to lessen the burden of alcohol-related disease, including alcohol dependence.

Dan Rootman, Dr. Robert Mann, Rania Shuggi and colleagues examined the proportion of clients who completed Back on Track (BOT), Ontario's Remedial Measures Program for those convicted of drinking and driving. Program completion rates are important  indicators of program success. BOT's completion rate was found  to be over 97 per cent, the highest rate reported in the literature.

The PREGNETS (Network for the Prevention of Gestational and Neonatal Exposure to Tobacco Smoke) project, led by Dr. Peter Selby, aimed to increase capacity among health care professionals who work with women who smoke during pregnancy and postpartum. The project also trained staff in two provincial resources, Smokers Helpline and Motherisk, and provided counselling to pregnant women who smoke. As a result, the website www.pregnets.org was established.

The Neighbour at Work project, led by Drs. Martin Shain and Helen Suurvali, identified the "Neighbour at Work Effect," an outcome obtained when employees and their managers enter into a particular process to improve the quality of employment relationships. In the process, a survey allows an exchange of perspectives on conditions of work that enables the parties to see the others' points of view. Results show that the process leads to an overall greater perception of fairness in the immediate working environment. This  perception, in turn, is known to be a positive influence on mental health, leading to reduced symptoms of anxiety and depression.

Dr. Beth Sproule and colleagues conducted a study to assess community pharmacists' attitudes and professional interactions toward people who use mental health medications; results showed that, despite generally positive attitudes, pharmacists felt uncomfortable discussing mental health symptoms and related medications with clients. Adequate training in mental health may be key in improving the professional interactions of community pharmacists with these clients.

An initial low-level response in ethanol sensitivity may help predict risk for developing alcohol abuse and dependence in humans, although this has not been consistently shown in clinical studies. Drs. Denise Tomkins and Anh Dzung Le, using rats selectively bred at CAMH for binge-like drinking, suggest that one possible factor  for these inconsistencies is the preferred drinking profile; that is, binge drinking versus continuous alcohol consumption. High initial response to alcohol was a better predictor of a binge drinking profile. These results highlight the importance of considering genetic and behavioural factors when interpreting research findings.

A placebo-controlled study of the efficacy of naltrexone for concurrent problem gambling and alcohol dependence, led by Drs. Tony Toneatto, Bruna Brands and Peter Selby, found naltrexone and placebo to be equally effective in reducing gambling behaviour and alcohol consumption.

Dr. Tony Toneatto found that a one-session minimal intervention for problem gambling was as effective as more intensive treatments in reducing the frequency of gambling and the amount wagered.

A study to assess the link between being an aggressive person and people's reactions to hostile, ambiguous and accidental provocations, led by Dr. Paul Tremblay, showed that the role of an aggressive disposition in a provoking situation depends on the intent of the instigator. This suggests that people who tend to be aggressive would benefit from intervention that addresses their perceptions  of the other person's intent in provoking situations.

Drs. Nigel Turner and John Macdonald presented findings from an evaluation of a prevention-oriented high-school curriculum on problem gambling. Their results suggest that the curriculum significantly improved the students' understanding of random chance and  coping skills.

Building on their recent discoveries into the role of altered intracellular calcium signalling dynamics as an important factor causing bipolar disorder, Dr. Jerry Warsh and his research team have now uncovered two calcium-permeable transient receptor potential channel proteins, TRPC3 and TRPM2, as a specific target of lithium and a genetic risk factor for bipolar disorder, respectively. Collectively, the findings create a compelling case that genetic and molecular  disturbances in a network of interacting calcium channel systems are a cause of illness in a substantial subgroup of people with bipolar disorder. Equally important, they have identified key targets for developing new medications to treat bipolar disorders.

Dr. Albert Wong's project, "Immunological mechanisms affecting  cortical neurodevelopment," complements ongoing work with  several other animal models related to psychosis, in which the analysis of global brain mRNA transcription patterns may help to identify molecular pathways and genes involved in schizophrenia.

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