Maron E.,University of Tartu |
Maron E.,Imperial College London |
Hettema J.M.,Virginia Commonwealth University |
Shlik J.,University of Ottawa |
Shlik J.,Royal Ottawa Mental Health Center
Molecular Psychiatry | Year: 2010
The molecular genetic research on panic disorder (PD) has grown tremendously in the past decade. Although the data from twin and family studies suggest an involvement of genetic factors in the familial transmission of PD with the heritability estimate near 40%, the genetic substrate underlying panicogenesis is not yet understood. The linkage studies so far have suggested that chromosomal regions 13q, 14q, 22q, 4q31-q34, and probably 9q31 are associated with the transmission of PD phenotypes. To date, more than 350 candidate genes have been examined in association studies of PD, but most of these results remain inconsistent, negative, or not clearly replicated. Only Val158Met polymorphism of the catechol-O-methyltransferase gene has been implicated in susceptibility to PD by several studies in independent samples and confirmed in a recent meta-analysis. However, the specific role of this genetic variation in PD requires additional analysis considering its gender-and ethnicity-dependent effect and putative impact on cognitive functions. The recent advantages in bioinformatics and genotyping technologies, including genome-wide association and gene expression methods, provide the means for far more comprehensive discovery in PD. The progress in clinical and neurobiological concepts of PD may further guide genetic research through the current controversies to more definitive findings. © 2010 Macmillan Publishers Limited All rights reserved.
Lee E.K.,University of Ottawa |
Lee E.K.,Royal Ottawa Mental Health Center |
Douglass A.B.,University of Ottawa |
Douglass A.B.,Ottawa Health Research Institute
Canadian Journal of Psychiatry | Year: 2010
Although the precise function of sleep is unknown, decades of research strongly implicate that sleep has a vital role in central nervous system (CNS) restoration, memory consolidation, and affect regulation. Slow-wave sleep (SWS) and rapid eye movement (REM) sleep have been of significant interest to psychiatrists; SWS because of its putative role in CNS energy recuperation and cognitive function, and REM sleep because of its suggested involvement in memory, mood regulation, and possible emotional adaptation. With the advent of the polysomnogram, researchers are now beginning to understand some of the consequences of disrupted sleep and sleep deprivation in psychiatric disorders. The same neurochemistry that controls the sleep-wake cycle has also been implicated in the pathophysiology of numerous psychiatric disorders. Thus it is no surprise that several psychiatric disorders have prominent sleep symptoms. This review will summarize normal sleep architecture, and then examine sleep abnormalities and comorbid sleep disorders seen in schizophrenia, as well as anxiety, cognitive, and substance abuse disorders.
Qin Z.,Ottawa Hospital Research Institute |
Zhou X.,Ottawa Hospital Research Institute |
Pandey N.R.,Ottawa Hospital Research Institute |
Vecchiarelli H.A.,University of Calgary |
And 8 more authors.
Neuron | Year: 2015
Collapse of endocannabinoid (eCB) signaling in the amygdala contributes to stress-induced anxiety, but the mechanisms of this effect remain unclear. eCB production is tied to the function of the glutamate receptor mGluR5, itself dependent on tyrosine phosphorylation. Herein, we identify a novel pathway linking eCB regulation of anxiety through phosphorylation of mGluR5. Mice lacking LMO4, an endogenous inhibitor of the tyrosine phosphatase PTP1B, display reduced mGluR5 phosphorylation, eCB signaling, and profound anxiety that is reversed by genetic or pharmacological suppression of amygdalar PTP1B. Chronically stressed mice exhibited elevated plasma corticosterone, decreased LMO4 palmitoylation, elevated PTP1B activity, reduced amygdalar eCB levels, and anxiety behaviors that were restored by PTP1B inhibition or by glucocorticoid receptor antagonism. Consistently, corticosterone decreased palmitoylation of LMO4 and its inhibition of PTP1B in neuronal cells. Collectively, these data reveal a stress-responsive corticosterone-LMO4-PTP1B-mGluR5 cascade that impairs amygdalar eCB signaling and contributes to the development of anxiety. © 2015 Elsevier Inc.
Bardell A.,University of Ottawa |
Lau T.,University of Ottawa |
Fedoroff J.P.,University of Ottawa |
Fedoroff J.P.,Ottawa Health Research Institute |
Fedoroff J.P.,Royal Ottawa Mental Health Center
International Psychogeriatrics | Year: 2011
Inappropriate sexual behavior (ISB) is an important topic in geriatrics; etiologies remain unclear and evidence for the efficacy of treatment strategies is limited. The aims of this study were to provide a description of the phenomenology of ISB in the geriatric population, to identify potential contributing factors, and to review the efficacy of interventions aimed at reducing ISB. Methods: A retrospective chart review was conducted of ten patients admitted to an academic inpatient geriatric psychiatry ward because of their ISB (study group) and ten patients matched in age and gender (control group). A comprehensive chart review inventory was done to determine variables that may contribute to ISB. For the study group, effectiveness, adverse effects, and discontinuation due to adverse effects of interventions aimed at reducing ISB were reviewed. Results: A significant finding was the association of a history of right frontal lobe stroke with ISB (Fisher's Exact Probability Test p < 0.05). Also significant was performance on cognitive testing and the presence of dementia (Fisher's Exact Probability Test p < 0.05) in the study group. Citalopram was well tolerated but with minimal reduction of ISB. Atypical antipsychotics olanzapine and risperidone were effective in some cases but also had adverse effects. Medroxyprogesterone acetate was well tolerated and effective in all cases in which it was utilized (n = 5). Conclusions: This study suggests that ISB in the geriatric population is associated with a history of right frontal lobe stroke and with severity of dementia. Case examples of pharmacologic interventions are reviewed. © 2011 International Psychogeriatric Association.
Bourget D.,Royal Ottawa Mental Health Center |
Gagne P.,Royal Ottawa Mental Health Center
Behavioral Sciences and the Law | Year: 2012
Spousal homicide perpetrators are much more likely to be men than women. Accordingly, little research has focused on delineating characteristics of women who have committed spousal homicide. A retrospective clinical review of coroners' files containing all cases of spousal homicide occurring in Quebec over a 20-year period was carried out. A total of 276 spousal homicides occurred between 1991 and 2010, with 42 homicides by female spouses and 234 homicides by male spouses. Differences between homicides committed by female offenders and male offenders are discussed, and findings on spousal homicide committed by women are compared with those of previous studies. Findings regarding offenses perpetrated by females in the context of mental illness, domestic violence, and homicide-suicide are explored. The finding that only 28% of the female offenders in the Quebec sample had previously been subjected to violence by their victim is in contrast to the popular belief and reports that indicate that most female-perpetrated spousal homicide occurs in self-defense or in reaction to long-term abuse. In fact, women rarely gave a warning before killing their mates. Most did not suffer from a mental illness, although one-fifth were acutely intoxicated at the time of the killing. In the vast majority of cases of women who killed their mates, there were very few indicators that might have signaled the risk and helped predict the violent lethal behavior. © 2012 John Wiley & Sons, Ltd.
Paterniti S.,University of Ottawa |
Paterniti S.,Royal Ottawa Mental Health Center |
Bisserbe J.-C.,University of Ottawa
BMC Psychiatry | Year: 2013
Background: Many new approaches have been adopted for the treatment of bipolar disorder (BD) in the past few years, which strived to produce more positive outcomes. To enhance the quality of care, several guideline recommendations have been developed. For study purposes, we monitored the prescription of psychotropic drugs administered to bipolar patients who had been referred to tertiary care services, and assessed the degree to which treatment met specific guidelines.Methods: Between December 2006 and February 2009, we assessed 113 individuals suffering from BD who had been referred to the Royal Ottawa Mental Health Centre (ROMHC) Mood Disorders Program by physicians within the community, mostly general practitioners. The Structured Clinical Interview for DSM-IV-TR was used to assess diagnosis. The prescribed treatment was compared with specific Canadian guidelines (CANMAT, 2009). Univariate analyses and logistic regression were used to assess the contribution of demographic and clinical factors for concordance of treatment with guidelines.Results: Thirty-two subjects had BD type I (BD-I), and 81 subjects had BD type II (BD-II). All subjects with BD-I, and 90% of the BD-II group were given at least one psychotropic treatment. Lithium was more often prescribed for subjects with BD-I (62%) than those with BD-II (19%). Antidepressants were the most frequently prescribed class of psychotropics. Sixty-eight percent of subjects received treatment concordant with guidelines by medication and dose. The presence of a current hypomanic episode was independently associated with poorer concordance to guidelines. In more than half the cases, the inappropriate use of antidepressants was at the origin of the non concordance of treatment with respect to guidelines. Absence of psychotropic treatment in bipolar II patients and inadequate dosage of mood stabilizers were the two other main causes of non concordance with guidelines.Conclusions: The factors related to treatment not concordant with guidelines should be further explored to determine appropriate strategies in implementing the use of guidelines in clinical practice. © 2013 Paterniti and Bisserbe; licensee BioMed Central Ltd.
Sochocky N.,Royal Ottawa Mental Health Center
Current clinical pharmacology | Year: 2013
Second generation antipsychotics (SGA) have gained increased evidence for the treatment of irritability and aggression in children and adolescents with lower functioning autistic disorder. Individuals with Asperger's Disorder (AD) and High Functioning Autism (HFA) experience significant emotional and behavioral problems and psychiatric comorbidity. There is a need to review the published literature on SGA treatment efficacy in the AD and HFA populations to provide more effective treatment choices for these subgroups. We conducted a systematic review and meta-analysis of the recent English literature on SGA use in children and adolescents (ages 0-24 years) with AD and HFA using the Medline/PubMed and PsychINFO computerized databases. Key search words were 'Asperger', 'high functioning autism', 'autism spectrum disorders (ASD)', and 'pervasive developmental disorder (PDD)' in combination with 'second generation antipsychotics', 'aripiprazole; 'olanzapine', 'quetiapine', 'risperidone', or 'ziprasidone'. Our search yielded 214 citations, however only open-label or randomized-controlled trials (RCT) with ≥25% of their subjects having an IQ≥71 were included in our review. Eleven original studies met our inclusion parameters for review; eight studies for the meta-analysis. These studies, although limited in methodological rigor, and the meta-analytic results suggest that SGAs provide improvement in behavioral symptoms associated with AD and HFA. The majority of the studies reported weight gain as a potentially concerning adverse effect. There is a lack of robustly conducted trials on the use of SGAs in the management of AD and HFA. More research in pharmacological and psychosocial treatments is warranted. Clinicians are cautioned to approach pharmacological treatment prudently balancing benefit with potential cardiometabolic risk.
Dulude L.,University of Ottawa |
Labelle A.,Ottawa Health Research Institute |
Labelle A.,Royal Ottawa Mental Health Center |
Knott V.J.,Ottawa Health Research Institute |
Knott V.J.,Royal Ottawa Mental Health Center
Journal of Clinical Psychopharmacology | Year: 2010
Context: Patients with schizophrenia have a high rate of cigarette smoking and also exhibit profound deficits in sensory processing, which may in part be ameliorated by the acute actions of smoke-inhaled nicotine. The mismatch negativity (MMN), a preattentive event-related potential index of auditory sensory memory, is diminished in schizophrenia. The MMN is increased in healthy controls with acute nicotine. Objective: To utilize the MMN to compare auditory sensory memory in minimally tobacco-deprived (3 hours) patients and matched tobacco-deprived smoking controls and to assess the effects of acute nicotine on MMN-indexed sensory memory processing in the patients. DESIGN:: Event-related potentials were recorded in 2 auditory oddball paradigms, one involving tone frequency changes (frequency MMN) and one involving tone duration changes (duration MMN). Controls were assessed once under nontreatment conditions, and patients were assessed twice under randomized double-blind treatment conditions involving placebo and nicotine (8 mg) gum. SETTING:: Outpatient mental health center. PATIENTS:: Twelve smokers with schizophrenia and twelve control smokers. RESULTS:: Compared with the controls, the patients showed reduced frequency-MMN (P < 0.001) and duration-MMN (P < 0.04) amplitudes. In addition to prolonging peak latency in duration MMN (P < 0.01), nicotine, relative to placebo, increased the amplitude of the patients' duration MMN (P < 0.01), but not their frequency MMN, to a level comparable with that seen in the controls. Conclusions: These preliminary findings demonstrate for the first time that acute nicotine can normalize temporal aspects of sensory memory processing in patients with schizophrenia, an effect that may be mediated by activation of α7 nicotinic acetylcholine receptors, the function of which is diminished in schizophrenia. These ameliorating actions of nicotine may have implications for understanding the close relationship between tobacco smoking and schizophrenia and for developing nicotinic pharmacotherapies to alleviate sensory memory impairments in schizophrenia. © 2010 Lippincott Williams & Wilkins.
Horton J.,Health Integrated |
Millar A.,University of Ottawa |
Labelle A.,Royal Ottawa Mental Health Center |
Knott V.J.,Ottawa Health Research Institute
Schizophrenia Research | Year: 2011
Event-related potential (ERP) probing of abnormal sensory processes in schizophrenia with the mismatch negativity (MMN) has shown impairments in auditory change detection, but knowledge of the acoustic features leading to this deficit is incomplete. Changes in the duration and frequency properties of sound stimuli result in diminished MMNs in schizophrenia but it is unclear as to whether this reduced responsiveness is seen with more subtle changes in sound frequency. In a sample of 19 healthy controls and 21 patients with chronic schizophrenia treated with clozapine, MMN was assessed in response to tone frequency changes of 5%, 10% and 20%, and to tone duration changes. Patients exhibited reduced amplitudes and shorter latencies than controls to all frequency changes, and attenuated amplitudes to tone duration increments and decrements. Clozapine dose was related to MMN, with increasing dose being positively associated with frequency-MMN amplitudes (10% Δf, 20% Δf) and negatively associated with the amplitude and latency of duration-MMNs. These data support the well-established findings of auditory sensory abnormality in schizophrenia and underscore the sensitivity of MMN to relatively small auditory change detection deficits that may appear to characterize chronic schizophrenia. © 2010 Elsevier B.V.
News Article | February 12, 2017
Mental disorders such as depression and anxiety disorders aren't just difficult to endure — there's also currently no specific cure that works for all patients. In some cases, patients do not respond to the drugs at all. But startup company NeuroQore hopes to find a way to treat mental disorders, such as depression, without the use of drugs or psychotherapy. NeuroQore claims to have found a way to cure depression through the use of magnetic pulses. The company is still in its early stages, but the group is confident that the method is effective, with a higher remission rate compared to the existing therapeutic methods for drug-resistant depression. "We have an 87.5 percent remission success rate over drug-resistant depression," said Mehran Talebinjad, co-founder of NeuroQore, in an interview with TechCrunch. The company's method isn't exactly a new concept. It builds on the current Neurofeedback therapy which has been in existence since the mid-90's. Neurofeedback therapy entails stimulating parts of the brain to send a positive signal in the form of a pleasant tone through the ears. This happens each time a desirable mood is achieved by the subject. The process is repeated over time in hopes of eventually achieving a permanently positive and healthy pattern, and has been used in clinics that did not rely on drugs as a primary treatment. Aside from depression, neurofeedback has also been used to help sufferers of PTSD, ADHD, addiction and certain impulse control disorders. NeuroQore's Repetitive Transcranial Magnetic Stimulation (rTMS) works in a similar way, but with a slight difference. Instead of sending positive tones through the ears, they transmit the tones directly into the brain through magnetic pulses. The company claims that the process does not have any side effects but still may not work with everyone. The installed system at the Royal Ottawa Mental Health Center in 2015 was successful in the first round of testing and is being prepared for the next. NeuroQore is already approved in Canada, with headquarters set up in Ontario. It is currently planning for FDA approval. The National Institute of Mental Health estimates that an estimated 17 million Americans suffer from depression during any one year period. It is a real mental illness that affects the different aspects of a sufferer's life. The American Psychological Association stresses that depression is a treatable disorder when patients receive proper care from licensed mental health professionals, and that any person or family member suspected to be suffering from depression should be recommended to immediately seek professional help. In many cases, a combination of psychotherapy and medication are given to patients to reduce the symptoms of depression. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.