Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and b... more Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and bipolar affective disorder (BPAD) in comparison with control individuals have previously been reported, implying a possible etiological role for trinucleotide repeats in these diseases. Two unstable CAG/CTG repeats, SEF2-1B and ERDA1, have recently been cloned, and studies indicate that the majority of individuals with large repeats as detected by repeat-expansion detection (RED) have large repeat alleles at these loci. These repeats do not show association of large alleles with either BPAD or SCZ. Using RED, we have identified a BPAD individual with a very large CAG/ CTG repeat that is not due to expansion at SEF2-1B or ERDA1. From this individual's DNA, we have cloned a highly polymorphic trinucleotide repeat consisting of (CTA) n (CTG) n , which is very long (ā¼1,800 bp) in this patient. The repeat region localizes to chromosome 13q21, within 1.2 cM of fragile site FRA13C. Repeat alleles in our sample were unstable in 13 (5.6%) of 231 meioses. Large alleles (1100 repeats) were observed in 14 (1.25%) of 1,120 patients with psychosis, borderline personality disorder, or juvenile-onset depression and in 5 (.7%) of 710 healthy controls. Very large alleles were also detected for Centre d'Etude Polymorphisme Humaine (CEPH) reference family 1334. This triplet expansion has recently been reported to be the cause of spinocerebellar ataxia type 8 (SCA8); however, none of our large alleles above the disease threshold occurred in individuals either affected by SCA or with known family history of SCA. The high frequency of large alleles at this locus is inconsistent with the much rarer occurrence of SCA8. Thus, it seems unlikely that expansion alone causes SCA8; other genetic mechanisms may be necessary to explain SCA8 etiology.
Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2013
To examine the impact of anxiety disorders comorbid to bipolar disorder (BD) in a large, national... more To examine the impact of anxiety disorders comorbid to bipolar disorder (BD) in a large, nationally representative sample, to describe the sociodemographic and clinical profiles of Canadians living with BD and with or without comorbid anxiety disorders, to identify the characteristics uniquely associated with comorbid anxiety, and to examine treatment patterns. We analyzed data from the Canadian Community Health Survey: Mental Health and Well-Being, conducted among 38 492 Canadians. People meeting the criteria for BD (n = 808) were compared based on the presence or absence of an assessed anxiety disorder (that is, social phobia, panic disorder, and agoraphobia). People with BD and a comorbid anxiety disorder fare worse in terms of BD relapses, suicidality, and sleep disturbance, and are more likely to be taking psychiatric medication. They have more impairment in their work and social functioning and rate their health and life satisfaction lower. Despite the greater severity, they a...
Background: Comorbid anxiety disorders are extremely prevalent in bipolar disorder (BD) and have ... more Background: Comorbid anxiety disorders are extremely prevalent in bipolar disorder (BD) and have substantial impact on the course of illness. Limited evidence regarding treatment factors has led to a renewal of research efforts examining both the impact of treatments on comorbid anxiety and the impact of comorbid anxiety on treatments. The current study examines the impact of comorbid anxiety disorders on response to two psychosocial interventions for BD. Methods: A sample of 204 patients with BD took part in the study. Of them, 41.7% had a comorbid anxiety disorder. All participants received either individual cognitive-behavioral therapy or group psychoeducation for BD. Evaluations included complete pretreatment and 18-month follow-up assessments of mood and anxiety symptoms, functioning, medication compliance, dysfunctional attitudes, and coping style. Outcome was compared based on the presence or absence of a comorbid anxiety disorder. Results and discussion: The participants with comorbid anxiety disorders ranked more severe than those without on several measures. Despite more severe illness characteristics, the magnitude of their treatment gains was equivalent or superior to that of the participants without anxiety disorders on a variety of outcome measures. Although the treatments did not specifically target the anxiety disorder, the participants made significant improvements in anxiety symptoms. Despite greater illness severity, patients with comorbid anxiety disorders can make substantial gains from psychosocial interventions targeting BD. Even in the presence of an anxiety disorder, they are able to attend to the content of the psychosocial treatments and apply it to better manage their condition. The presence of a comorbid anxiety disorder should not be considered a deterrent to offering BDfocused psychosocial treatments.
Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2010
To review the overall clinical research findings from the Systematic Treatment Enhancement Progra... more To review the overall clinical research findings from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), the world's largest study of BD. STEP-BD was conducted from 1998 to 2005, enrolling participants (n = 4361) across 22 clinical sites in the United States. Each individual was followed for up to 2 years in naturalistic practice with blinded research assessments, while subgroups participated in randomized controlled trials (RCTs) for bipolar depression. The naturalistic database was used to examine the course of BD, comorbidity with other psychiatric disorders, and suicidality. Relevant studies in English, published from January 1, 1994, to May 31, 2009, were identified using computerized searches of electronic databases (PubMed, PsycINFO, and Cochrane Register of Clinical Trials), inspection of bibliographies, and review of other major reports. One large RCT involving the addition of either paroxetine or bupropion to mood stabilizers in acute depressi...
There is evidence for the involvement of glutamatergic transmission in the pathogenesis of major ... more There is evidence for the involvement of glutamatergic transmission in the pathogenesis of major psychoses. The two most commonly used mood stabilizers (ie lithium and valproate) have been found to act via the N-methyl-D-aspartate receptor (NMDAR), suggesting a specific role of NMDAR in the pathogenesis of bipolar disorder (BP). The key subunit of the NMDAR, named NMDA-1 receptor, is coded by a gene located on chromosome 9q34.3 (GRIN1). We tested for the presence of linkage disequilibrium between the GRIN1 (1001-G/C, 1970-A/G, and 6608-G/C polymorphisms) and BP. A total of 288 DSM-IV Bipolar I, Bipolar II, or schizoaffective disorder, manic type, probands with their living parents were studied. In all, 73 triads had heterozygous parents for the 1001-G/C polymorphism, 174 for the 1970-A/G, and 48 for the 6608-G/C. These triads were suitable for the final analyses, that is, the transmission disequilibrium test (TDT) and the haplotype-TDT. For the 1001-G/C and the 6608-G/C polymorphism...
Canadian journal of psychiatry. Revue canadienne de psychiatrie, 1997
To summarize the quality of evidence for the efficacy of different biological treatments in mania... more To summarize the quality of evidence for the efficacy of different biological treatments in mania, mixed state, and rapid cycling and to propose guidelines for treatment of these conditions. Articles published on treatment of acute mania, mixed states, and rapid cycling were reviewed and rated for quality of evidence using Periodic Health Examination guidelines. Lithium and divalproex sodium are effective in classical pure mania, whereas divalproex sodium and carbamazepine are likely more effective in mixed states. Divalproex sodium is likely more efficacious than carbamazepine and lithium when the mania is part of a rapid-cycling course. Typical neuroleptics are efficacious in acute mania, particularly in the presence of marked psychotic symptoms. Atypical neuroleptics can be useful in refractory mania. Some benzodiazepines do have antimanic effects, but they are increasingly being shown to have usefulness as adjuncts to mood stabilizers or neuroleptics rather than as primary antim...
To summarize the evidence for efficacy from published literature of biological treatments in the ... more To summarize the evidence for efficacy from published literature of biological treatments in the continuation and maintenance phases of bipolar disorder, as well as the recommendations about different treatment options made by the working group within the Bipolar Sub-Committee of the Canadian Network for Mood and Anxiety Treatments (CANMAT).
To understand the epidemiology and course of bipolar disorder; to outline the importance of accur... more To understand the epidemiology and course of bipolar disorder; to outline the importance of accurate and reliable diagnosis of bipolar disorder both on a cross-sectional and longitudinal basis; and to emphasize the value of a collaborative therapeutic relationship, psychoeducation, and psychotherapy.
BackgroundIn 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anx... more BackgroundIn 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008ā2009 to reflect advances in the field. There is renewed interest in refined approaches to brain stimulation, particularly for treatment resistant major
To review studies on treatments for bipolar depression and make recommendations for practising cl... more To review studies on treatments for bipolar depression and make recommendations for practising clinicians treating patients with bipolar depression. Studies that examined various treatments for bipolar depression were evaluated and rated for evidence of efficacy using Periodic Health Examination criteria. The rating for classification of recommendation for an intervention was made taking both the efficacy and the side effects into consideration. Mood stabilizers, cyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and electroconvulsive therapy (ECT) are all effective in treating bipolar depression. Almost all antidepressant treatments with the exception of mood stabilizers have been reported to induce a manic-hypomanic switch and rapid cycling. Mood stabilizers, lithium in particular, are recommended as the first-line treatment. Addition of a second mood stabilizer or a cyclic antidepressant would be an appropriate next step. Newer agents such as lamotrigine offer considerable promise in treating bipolar depressed patients.
Epidemiologic research has demonstrated that the majority of mental illness in the community is n... more Epidemiologic research has demonstrated that the majority of mental illness in the community is not treated. Primary care physicians and the specialty mental health sector each have an important role in the provision of mental health services. Our goal is to clarify the extent of undertreatment of selected mental illnesses in Ontario and to examine how treatment is divided between the primary care and specialty sectors. In particular, we are interested in both the relative numbers and the types--based on sociodemographic and severity indicators--of patients found in each sector, as well as in confirming the key role of primary care in the provision of mental health services. Data were taken from the Mental Health Supplement to the Ontario Health Survey, a community survey of 9953 individuals. All subjects who met DSM-III-R criteria for a past year diagnosis of mood, anxiety, substance abuse, bulimic, or antisocial personality disorders were categorized by their use of mental health services in the preceding year--into nonusers, primary care only patients, specialty only patients, and both sector patients. The 3 groups utilizing services were then compared by demographic, clinical, and disability characteristics. Only 20.8% of subjects with a psychiatric diagnosis reported use of mental health services, but 82.9% of these same individuals used primary care physicians for general health problems. Among those who used mental health services, 38.2% used family physicians only for psychiatric treatment, compared with 35.8% who used only specialty mental health providers, and 26.0% who used both sectors. The 3 groups of users showed only modest differences on sociodemographic characteristics. Patients in the specialty only sector reported significantly higher rates of sexual and physical abuse. On specific disability measures, all 3 groups were similar. The vast majority of individuals with an untreated psychiatric disorder are using the primary care sector for general health treatment, allowing an opportunity for identification and intervention. Primary care physicians also treat the majority of those seeking mental health services, and individuals seen only by these primary care physicians are probably as ill as those seen exclusively in the specialty mental health sector. From a public health perspective, future policy interventions should aim to improve collaboration between the 2 sectors and enhance the ability of primary care physicians to deliver psychiatric services.
Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and b... more Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and bipolar affective disorder (BPAD) in comparison with control individuals have previously been reported, implying a possible etiological role for trinucleotide repeats in these diseases. Two unstable CAG/CTG repeats, SEF2-1B and ERDA1, have recently been cloned, and studies indicate that the majority of individuals with large repeats as detected by repeat-expansion detection (RED) have large repeat alleles at these loci. These repeats do not show association of large alleles with either BPAD or SCZ. Using RED, we have identified a BPAD individual with a very large CAG/ CTG repeat that is not due to expansion at SEF2-1B or ERDA1. From this individual's DNA, we have cloned a highly polymorphic trinucleotide repeat consisting of (CTA) n (CTG) n , which is very long (ā¼1,800 bp) in this patient. The repeat region localizes to chromosome 13q21, within 1.2 cM of fragile site FRA13C. Repeat alleles in our sample were unstable in 13 (5.6%) of 231 meioses. Large alleles (1100 repeats) were observed in 14 (1.25%) of 1,120 patients with psychosis, borderline personality disorder, or juvenile-onset depression and in 5 (.7%) of 710 healthy controls. Very large alleles were also detected for Centre d'Etude Polymorphisme Humaine (CEPH) reference family 1334. This triplet expansion has recently been reported to be the cause of spinocerebellar ataxia type 8 (SCA8); however, none of our large alleles above the disease threshold occurred in individuals either affected by SCA or with known family history of SCA. The high frequency of large alleles at this locus is inconsistent with the much rarer occurrence of SCA8. Thus, it seems unlikely that expansion alone causes SCA8; other genetic mechanisms may be necessary to explain SCA8 etiology.
Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2013
To examine the impact of anxiety disorders comorbid to bipolar disorder (BD) in a large, national... more To examine the impact of anxiety disorders comorbid to bipolar disorder (BD) in a large, nationally representative sample, to describe the sociodemographic and clinical profiles of Canadians living with BD and with or without comorbid anxiety disorders, to identify the characteristics uniquely associated with comorbid anxiety, and to examine treatment patterns. We analyzed data from the Canadian Community Health Survey: Mental Health and Well-Being, conducted among 38 492 Canadians. People meeting the criteria for BD (n = 808) were compared based on the presence or absence of an assessed anxiety disorder (that is, social phobia, panic disorder, and agoraphobia). People with BD and a comorbid anxiety disorder fare worse in terms of BD relapses, suicidality, and sleep disturbance, and are more likely to be taking psychiatric medication. They have more impairment in their work and social functioning and rate their health and life satisfaction lower. Despite the greater severity, they a...
Background: Comorbid anxiety disorders are extremely prevalent in bipolar disorder (BD) and have ... more Background: Comorbid anxiety disorders are extremely prevalent in bipolar disorder (BD) and have substantial impact on the course of illness. Limited evidence regarding treatment factors has led to a renewal of research efforts examining both the impact of treatments on comorbid anxiety and the impact of comorbid anxiety on treatments. The current study examines the impact of comorbid anxiety disorders on response to two psychosocial interventions for BD. Methods: A sample of 204 patients with BD took part in the study. Of them, 41.7% had a comorbid anxiety disorder. All participants received either individual cognitive-behavioral therapy or group psychoeducation for BD. Evaluations included complete pretreatment and 18-month follow-up assessments of mood and anxiety symptoms, functioning, medication compliance, dysfunctional attitudes, and coping style. Outcome was compared based on the presence or absence of a comorbid anxiety disorder. Results and discussion: The participants with comorbid anxiety disorders ranked more severe than those without on several measures. Despite more severe illness characteristics, the magnitude of their treatment gains was equivalent or superior to that of the participants without anxiety disorders on a variety of outcome measures. Although the treatments did not specifically target the anxiety disorder, the participants made significant improvements in anxiety symptoms. Despite greater illness severity, patients with comorbid anxiety disorders can make substantial gains from psychosocial interventions targeting BD. Even in the presence of an anxiety disorder, they are able to attend to the content of the psychosocial treatments and apply it to better manage their condition. The presence of a comorbid anxiety disorder should not be considered a deterrent to offering BDfocused psychosocial treatments.
Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2010
To review the overall clinical research findings from the Systematic Treatment Enhancement Progra... more To review the overall clinical research findings from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), the world's largest study of BD. STEP-BD was conducted from 1998 to 2005, enrolling participants (n = 4361) across 22 clinical sites in the United States. Each individual was followed for up to 2 years in naturalistic practice with blinded research assessments, while subgroups participated in randomized controlled trials (RCTs) for bipolar depression. The naturalistic database was used to examine the course of BD, comorbidity with other psychiatric disorders, and suicidality. Relevant studies in English, published from January 1, 1994, to May 31, 2009, were identified using computerized searches of electronic databases (PubMed, PsycINFO, and Cochrane Register of Clinical Trials), inspection of bibliographies, and review of other major reports. One large RCT involving the addition of either paroxetine or bupropion to mood stabilizers in acute depressi...
There is evidence for the involvement of glutamatergic transmission in the pathogenesis of major ... more There is evidence for the involvement of glutamatergic transmission in the pathogenesis of major psychoses. The two most commonly used mood stabilizers (ie lithium and valproate) have been found to act via the N-methyl-D-aspartate receptor (NMDAR), suggesting a specific role of NMDAR in the pathogenesis of bipolar disorder (BP). The key subunit of the NMDAR, named NMDA-1 receptor, is coded by a gene located on chromosome 9q34.3 (GRIN1). We tested for the presence of linkage disequilibrium between the GRIN1 (1001-G/C, 1970-A/G, and 6608-G/C polymorphisms) and BP. A total of 288 DSM-IV Bipolar I, Bipolar II, or schizoaffective disorder, manic type, probands with their living parents were studied. In all, 73 triads had heterozygous parents for the 1001-G/C polymorphism, 174 for the 1970-A/G, and 48 for the 6608-G/C. These triads were suitable for the final analyses, that is, the transmission disequilibrium test (TDT) and the haplotype-TDT. For the 1001-G/C and the 6608-G/C polymorphism...
Canadian journal of psychiatry. Revue canadienne de psychiatrie, 1997
To summarize the quality of evidence for the efficacy of different biological treatments in mania... more To summarize the quality of evidence for the efficacy of different biological treatments in mania, mixed state, and rapid cycling and to propose guidelines for treatment of these conditions. Articles published on treatment of acute mania, mixed states, and rapid cycling were reviewed and rated for quality of evidence using Periodic Health Examination guidelines. Lithium and divalproex sodium are effective in classical pure mania, whereas divalproex sodium and carbamazepine are likely more effective in mixed states. Divalproex sodium is likely more efficacious than carbamazepine and lithium when the mania is part of a rapid-cycling course. Typical neuroleptics are efficacious in acute mania, particularly in the presence of marked psychotic symptoms. Atypical neuroleptics can be useful in refractory mania. Some benzodiazepines do have antimanic effects, but they are increasingly being shown to have usefulness as adjuncts to mood stabilizers or neuroleptics rather than as primary antim...
To summarize the evidence for efficacy from published literature of biological treatments in the ... more To summarize the evidence for efficacy from published literature of biological treatments in the continuation and maintenance phases of bipolar disorder, as well as the recommendations about different treatment options made by the working group within the Bipolar Sub-Committee of the Canadian Network for Mood and Anxiety Treatments (CANMAT).
To understand the epidemiology and course of bipolar disorder; to outline the importance of accur... more To understand the epidemiology and course of bipolar disorder; to outline the importance of accurate and reliable diagnosis of bipolar disorder both on a cross-sectional and longitudinal basis; and to emphasize the value of a collaborative therapeutic relationship, psychoeducation, and psychotherapy.
BackgroundIn 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anx... more BackgroundIn 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008ā2009 to reflect advances in the field. There is renewed interest in refined approaches to brain stimulation, particularly for treatment resistant major
To review studies on treatments for bipolar depression and make recommendations for practising cl... more To review studies on treatments for bipolar depression and make recommendations for practising clinicians treating patients with bipolar depression. Studies that examined various treatments for bipolar depression were evaluated and rated for evidence of efficacy using Periodic Health Examination criteria. The rating for classification of recommendation for an intervention was made taking both the efficacy and the side effects into consideration. Mood stabilizers, cyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and electroconvulsive therapy (ECT) are all effective in treating bipolar depression. Almost all antidepressant treatments with the exception of mood stabilizers have been reported to induce a manic-hypomanic switch and rapid cycling. Mood stabilizers, lithium in particular, are recommended as the first-line treatment. Addition of a second mood stabilizer or a cyclic antidepressant would be an appropriate next step. Newer agents such as lamotrigine offer considerable promise in treating bipolar depressed patients.
Epidemiologic research has demonstrated that the majority of mental illness in the community is n... more Epidemiologic research has demonstrated that the majority of mental illness in the community is not treated. Primary care physicians and the specialty mental health sector each have an important role in the provision of mental health services. Our goal is to clarify the extent of undertreatment of selected mental illnesses in Ontario and to examine how treatment is divided between the primary care and specialty sectors. In particular, we are interested in both the relative numbers and the types--based on sociodemographic and severity indicators--of patients found in each sector, as well as in confirming the key role of primary care in the provision of mental health services. Data were taken from the Mental Health Supplement to the Ontario Health Survey, a community survey of 9953 individuals. All subjects who met DSM-III-R criteria for a past year diagnosis of mood, anxiety, substance abuse, bulimic, or antisocial personality disorders were categorized by their use of mental health services in the preceding year--into nonusers, primary care only patients, specialty only patients, and both sector patients. The 3 groups utilizing services were then compared by demographic, clinical, and disability characteristics. Only 20.8% of subjects with a psychiatric diagnosis reported use of mental health services, but 82.9% of these same individuals used primary care physicians for general health problems. Among those who used mental health services, 38.2% used family physicians only for psychiatric treatment, compared with 35.8% who used only specialty mental health providers, and 26.0% who used both sectors. The 3 groups of users showed only modest differences on sociodemographic characteristics. Patients in the specialty only sector reported significantly higher rates of sexual and physical abuse. On specific disability measures, all 3 groups were similar. The vast majority of individuals with an untreated psychiatric disorder are using the primary care sector for general health treatment, allowing an opportunity for identification and intervention. Primary care physicians also treat the majority of those seeking mental health services, and individuals seen only by these primary care physicians are probably as ill as those seen exclusively in the specialty mental health sector. From a public health perspective, future policy interventions should aim to improve collaboration between the 2 sectors and enhance the ability of primary care physicians to deliver psychiatric services.
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Papers by Sagar Parikh