Research is an important and integral part of PEPP. Through research activities in the program, patients and their families benefit from new knowledge, resulting in state-of-the-art diagnostic and treatment methods for the early stages of psychosis.

Research aims at furthering our understanding of the nature of psychotic disorders, the impact of such disorders on patients and their families, and the development and evaluation of new approaches to treatment and prevention.

Research projects

PEPP-Montréal researchers come from various backgrounds and have strong collaborations with experts working in different disciplines at the Douglas Institute, across Canada and around the world.

1- Early case detection project

Ashok Malla , MD, FRCPC; Norbert Schmitz, PhD; Ross Norman, PhD; Joseph Rochford, PhD; Thomas G. Brown, PhD; Ridha Joober, MD, PhD

The project for early case identification of psychosis aims to reduce delay in treatment of psychosis by means of an initiative termed 'academic detailing'.

Academic detailing describes an intervention provided to primary health and education services in our jurisdiction (physicians, nurses, psychologists, social workers, counselors, teachers, and other health care providers and school staff working in primary care and education), that in the past have made referrals to the program.

The intervention consists of a film created by the program, depicting two scenarios of how a young person suffering from a First Episode of Psychosis (FEP) presents in a family context, followed by extensive discussions with the staff at the referral agency.

The 'academic detailing' presentations aim to educate health and education agency professionals to better identify potential patients presenting with FEP and to increase referral rates with less delay than encountered currently.

The effectiveness of the intervention to reduce delay in treatment is evaluated using a historical control design.

This is the first such initiative in Canada and the second one in the world (the other one is in Birmingham).

Funding: Canadian Institutes of Health Research (2006-2010)

2- Brain imaging in first episode psychosis patients with sustained negative symptoms: A two-year longitudinal study

Martin Lepage, PhD; Ashok Malla, MD, FRCPC; Jens Pruessner, PhD; Bruce Pike, PhD; Ridha Joober MD, PhD

Using functional Magnetic Resonance Imaging (MRI), the study compares brain activity for recognition memory (memory retrieval) in a group of subjects with First Episode of Psychosis (FEP) with sustained negative symptoms, in which memory retrieval dysfunction might be an important aspect of their symptomatology, and in healthy control subjects.

It is hypothesized that problems of memory in subjects with FEP are associated with abnormal activity in specific portions of the brain. In this longitudinal study, participants are scanned when they enter the study, and again at one year and two years following the initial scan.

3- An investigation of the factors relating to adherence to treatment in early psychosis and its relation to failure in achieving full remission

Ashok Malla, MD, FRCPC; Mark Rabinovitch, MD (MSc in Psychiatry Student)
Coordinator: Clifford Cassidy, MSc

The study seeks to understand the various factors that affect patients' adherence to medication and to what degree this affects the outcome of their illness. The main purpose of the study is to examine the impact of family and social support on patients' adherence to medication. Family members and patients are recruited after 3 months of being followed at PEPP, and participants are followed every month for a six-month period.

Funding: Janssen-Ortho Canada. Grant to Ashok Malla as an independent investigator project, including funding for fellowship.

4- Cortisol reactivity and its relationship to symptoms and hippocampal volume in first episode psychosis patients and individuals at ultra-high risk for psychosis

Marita Pruessner, PhD; Ashok Malla, MD, FRCPC; Jens Pruessner, PhD

Stress-vulnerability models of schizophrenia regard psychosocial stress as an important factor for the etiology and exacerbation of psychosis. Physical and mental challenges lead to increased secretion of a hormone called cortisol. The study investigates the cortisol responses to awakening and psychosocial stress and their relationship to the severity of psychotic symptoms and subthreshold psychotic symptoms, protective factors like self-esteem, social support and coping mechanisms and the volume of a brain structure called hippocampus in patients suffering from a first episode of psychosis (FEP) and individuals at ultra-high risk for psychosis (UHR).

Funding: NARSAD, Young Investigator Award to Marita Pruessner, PhD

5- Sub-study on genetics as part of the Brain imaging in First Episode Psychosis patients with Sustained Negative Symptoms: A one-year longitudinal study

Ridha Joober, MD, PhD; Martin Lepage, PhD; Ashok Malla, MD, FRCPC; Ferid Fathalli, MD (PhD Student)

The study seeks to understand how genetics might influence mental health. There is strong evidence that one or several disturbed genes (such as COMT, Glutamate receptor 3, BDNF) can lead to changes in behaviour that are typical for patients suffering from psychosis. Genes contain DNA which are molecules containing all the transmissible genetic information which control the activities of the body cells. DNA provides the instructions for determining the hereditary characteristics of a person such as eye colour and blood type. Genetic properties will be determined from a blood sample drawn from the participant’s arm.

6- A Randomized Controlled Evaluation of "Extended Specialized Early Intervention Service" vs. "Regular care" for Management of Early Psychosis over the Five year Critical Period

Ashok Malla, MD, FRCPC; Ridha Joober, MD, PhD; Thomas Brown, PhD; Eric Latimer, PhD; Norbert Schmitz, PhD; David Bloom, MD; Amal Abdel-Baki, MD; Ross Norman, PhD; Merete Nordentoft, PhD; Nicolas Cascalanda, MD
Coordinator: Aldanie Rho

"Early intervention" in psychosis is a relatively new concept in mental health. It is designed to improve outcome in schizophrenia through earlier detection of untreated psychosis and provision of effective, phase specific treatments. Whilst the results of an early intervention approach to treatment of first episode psychosis are encouraging it remains to be seen how long such specialized interventions should be sustained to produce a longer lasting beneficial effect on the long-term course of illness. Therefore, a pilot randomized controlled study is being conducted to compare long-term effectiveness of continued specialized treatment (using the PEPP-Montreal model of modified assertive case management treatment) with the alternative routine/standard follow-up care in a sample of first-episode patients who have achieved remission of symptoms following a minimum of one year of treatment in PEPP-Montreal. Study subjects are first-episode psychosis patients who have received a minimum of one year of treatment in PEPP-Montreal and have been in remission for at least 6 months. The project is coordinated by Sherezad Abadi, M.Sc, CCRP

This study aims to establish a link between genes that may be involved in psychosis and brain structures that are often considered abnormal in people with these types of disorders.

7- Comparative effectiveness of two different long-term treatment programs following initial intervention for first episode psychosis (Pilot study)

Ashok Malla, MD; Ridha Joober, MD, PhD; Thomas Brown, PhD; Eric Latimer, PhD; Norbert Schmitz, PhD; David Bloom, MD; Vania Jimenez, MD
Coordinator: Sherezad Abadi

While the results of an early intervention approach to treatment of first episode psychosis are encouraging, it remains to be seen how long such specialized interventions should be sustained to produce a longer lasting beneficial effect on the long-term course of the illness.

Therefore, a pilot randomized-controlled study is being conducted to compare long-term effectiveness of continued specialized treatment (using the PEPP-Montréal model of modified assertive case management treatment) with the alternative routine/standard follow-up care in a sample of first-episode patients who have achieved remission of symptoms.

Study subjects are first-episode psychosis patients who have received a minimum of one year of treatment in PEPP-Montréal and have been in remission for at least 6 months.

8- Effects of antipsychotic treatment on marijuana craving amongst marijuana using patients with First Episode Psychosis Protocol RIS-SCH-3005

Ashok Malla, MD, FRCPC; Kia Faridi, MD

Substance use disorders (SUD) are extremely prevalent amongst patients suffering from a first episode of psychosis (FEP), and are known to impact outcome during the early years of psychotic illnesses. This pilot study proposes to examine the evolution of cued-craving for marijuana from baseline and through the first three months of treatment with atypical antipsychotic medications. Further objectives are: to evaluate the effect of antipsychotic treatment on initiation or maintenance of substance-use disorders; and to evaluate interactions with medication adherence. Marijuana consuming subjects newly referred to a specialized FEP program, PEPP-Montreal, will be initiated in a non-randomized, open-label fashion on one of four antipsychotics, risperidone, olanzapine, quetiapine, and ziprasidone. Their cued marijuana craving and recent self-reported marijuana use will be evaluated at baseline and at monthly for the first three months of treatment. In addition, as per the usual PEPP Montreal protocols, monthly symptom evaluations, side-effect evaluations, and adherence measures shall be performed. Analyses shall focus on the changes in levels of marijuana use and marijuana craving over time, and any interaction with medication adherence.

9- Outcome in First-Episode Psychosis: The Role of Self-Esteem, Parenting Style, and Childhood Trauma

Ashok Malla, MD, FRCPC; Nadia Vracotas, MSc Candidate

Self-esteem is an important construct in psychiatric disorders. We hypothesize that in patients with first onset of a psychotic disorder, self-esteem will be associated with outcome and it will, in turn, be influenced by early life experiences.
Methods: The Self-Esteem Rating Scale, The Parental Bonding Instrument (PBI), the Measure of Parental Style (MOPS) and The Childhood Trauma Questionnaire (CTQ) were administered to individuals with first-episode psychosis. Symptoms and the GAF were assessed at entry to the program and at six months.
Results: Self-esteem was positively correlated with the GAF, but not with remission status at six months. Self-esteem was negatively correlated with the PBI Overprotection, MOPS Overcontrol and Abuse subscales, in relation to mothers and also negatively with Emotional Neglect, Emotional Abuse and Sexual Abuse subscales of the CTQ. Conclusion: Self-esteem influences outcome in early psychosis and is in turn, influenced by early life experiences. This may have implications for designing special interventions to improve outcome.

10- Dopamine release in relatives of patients with first episode psychosis

G.A. O'Driscoll, PhD; A Dagher, MD; C Benkelfat, MD; J. Pruessner, PhD
Coordinator: Ava-Ann Allman

An influential model of schizophrenia posits that there is low tonic DA activity and high phasic in ventral striatum (Grace,1991) and that these physiological abnormalities the eventual development of negative and positive symptoms. There is evidence in support of this theory in both schizophrenia and populations at high risk for the disorder. First-degree relatives of schizophrenic patients have a highly elevated risk of schizophrenia (i.e. 10x as high as the general population) (Kety et al, 1994). Measures of DA transmission are under at least partial genetic control suggesting that the abnormalities in schizophrenic patients may be found as well in their first degree relatives, and may be a component of genetic risk for the disorder. No study to date has examined DA release in first degree relatives. The objective of this study is to use PET and 11C-raclopride to measure striatal binding potential (BP) in no-stress (tonic DA) and stress (phasic DA) conditions in first-degree relatives of schizophrenic patients. Researchers hypothesize that healthy relatives of schizophrenic patients will show increased 11C-raclopride baseline BP (i.e. low tonic DA) compared to controls, and will show greater stress-induced DA release than controls.

11- Understanding the decision to take anti-psychotic medications: A Qualitative Pilot Study Examining the Evolution of the Decision-Making Process

Kate Steger, MD; Ashok Malla MD, FRCPC

The purpose of this study is to better understand how people make decisions about the medications they are prescribed. The reason for studying this topic is to improve communication and make the decisions easier: if health professionals understood which factors seemed most important to people who are prescribed medications, they could provide the information or support that would be the most useful. How the process changes over time will also be explored, therefore patients who have been prescribed these medications for both short and long periods will be included. This project will involves a single one-on-one interview asking questions about factors that influence the decisions about taking medications. Ended in Feb 2009.

12- A study of ethnicity and treated incidence of psychotic disorders

Ashok Malla, MD, FRCPC; Francois Bourque, MD
Others involved: Elsje van der Ven

A primary objective is to examine whether the incidence rates of first-episode psychosis of immigrants differ from that of the native-born Canadian population, and also whether second-generation migrants have a higher than first-generation migrants. A secondary objective is to determine whether the pathways to care and service utilizations among migrants differ from those of the comparative population.
Additional objectives are to shed further insight into the relationship between migration and psychopathology, and into the social determinants of psychosis.

13- Bilingual Language Processing in Schizophrenia

Debra Titone, PhD; Ridha Joober, MD, PhD; Maya Libben, PhD Candidate
Collaborator: Veronica Whitford

This research project investigates bilingual language processing in people who are diagnosed with schizophrenia. All participants will engage in a computer task designed to help us better understand language function in schizophrenia. This research project does not involve the administration of any medication or the use of any therapeutic treatments. In this study, participants with schizophrenia are recruited from the Douglas Hospital psychiatry outpatient services.

14- A Canadian Multicentre, open-label, prospective long-term Study evaluating the clinical benefit effectiveness of Quetiapine fumurate Extended-release tablets (SEROQUEL XR) in subjects with schizophrenia

This study is being carried out to assess whether the problems that some clients may experience with current treatment of antipsychotic medications can be decreased by switching to treatment with extended-release tablets of Quetiapine. Quetiapine is an "atypical antipsychotic" drug made by AstraZeneca. Under the brand name of Seroquel®., quetiapine has been approved by Health Canada (TPD) since 1997 and many other countries to help people who suffer from schizophrenia. The extended-release (XR) tablet is a new type of tablet, but contains the same medication as the conventional tablet. Quetiapine in this formulation is absorbed more slowly and steadily into the body and therefore needs to be taken only once a day. SEROQUEL XR® was approved by Health Canada in September 2007 to treat patients with schizophrenia.

15- First Episode Psychosis in South India

Ashok Malla, MD, FRCPC; Ridha Joober, MD, PhD; Srividya Iyer; Thara Rangaswamy
Others involved: R. Mangala, R. Sushma, Alessandra Miklavcic and Elsje van der Ven

PEPP has been collaborating with the Schizophrenia Research Foundation (SCARF) since 2003, to set up a clinical-research FEP program similar to PEPP at the SCARF premises in Chennai, India. Recently, we have been awarded a R21 by NIH-CIHR to further this collaborative program of research. Over the proposed two-year funding period, a well characterized sample of patients with previously untreated first-episode psychosis will be followed in India and Canada and treatment interventions will be clearly defined. The premise of the studies to be undertaken is that family factors positively impact the course of schizophrenia in India, buffering the toxic effects of untreated psychosis prior to detection and reinforcing the effects of treatment after detection.

16- Patterns of Health Services Utilization by First-Episode Psychosis Patients

Kelly K. Anderson; Rebecca Fuhrer; Ashok Malla, MD, FRCPC

The objective of this study is to examine the determinants of health services utilization for patients with a first episode of psychosis. A mixed-methods study design will be used, which will consist of a small qualitative study to generate hypotheses for further investigation, followed by a quantitative analysis of data from the Prevention and Early Intervention for Psychoses Program (PEPP) in Montreal and from the Régie de L’assurance Maladie du Québec (RAMQ).