Pub Date : 2001-06-01DOI: 10.1017/S1461145701002383
G. Emslie, G. Emslie, R. Armitage, W. Weinberg, A. Rush, T. Mayes, T. Mayes, R. Hoffmann
Adults with major depressive disorder (MDD) demonstrate certain sleep polysomnographic abnormalities, including sleep continuity disturbances, reduced slow-wave sleep, shortened rapid eye movement (REM) latency, and increased REM density. Findings of sleep EEG studies in depressed children and adolescents have yielded conflicting results, possibly because of methodological variations across the studies. Generally, however, studies have demonstrated that depressed children and adolescents exhibit less sleep continuity and non-REM sleep differences in comparison with control subjects than do adults. Thus, results from adult sleep polysomnography studies cannot necessarily be generalized to children and adolescents. Depressed adults who have reduced REM latency during the symptomatic episode appear more likely to have a relapse once treatment is discontinued than those with normal REM latency. No studies of the relationship between sleep polysomnographic variables and clinical course have been reported in depressed children and adolescents. Data for baseline clinical variables and 3 nights of sleep polysomnography were examined in 113 depressed children (< or = 12 yr; n = 51) and adolescents (> or = 13 yr; n = 62) (56 in-patients and 57 outpatients) where data was available on at least 1 yr of naturalistic follow-up. Subjects came from 2 studies of sleep polysomnography in children and adolescents with MDD. Clinical course was assessed using the Kiddie-Longitudinal Interval Follow-Up Evaluation (K-LIFE). This interview was used to define recovery from the index episode of MDD and recurrence, a new episode of meeting full criteria for MDD. Clinically, within 1 yr of initial evaluation 102/113 subjects had recovered from their index episode of depression (minimal or no symptoms for 60 d). Of the 102 subjects who recovered, 36 (35.3%) had a recurrence of MDD. The majority of subjects (55%) who had a recurrence were not on medication at the time of recurrence. Subjects who had a recurrence were more likely to report suicidal thoughts or attempts at baseline compared to those without a recurrence (67 vs. 37%; F = 8.77; p = 0.004). On baseline sleep polysomnography, subjects with a later recurrence had decreased sleep efficiency and delayed sleep onset (sleep latency > 10 min). Probability of recurrence at 12 months was 0.39 compared to 0.15 in subjects with non-delayed sleep onset (p = 0.005). Baseline suicidal ideation and sleep dysregulation on sleep polysomnography predicted recurrence in a large sample of depressed children and adolescents. Depression in children and adolescents is frequently a chronic, recurrent illness. Factors that can predict clinical course are important in increasing our understanding of depression in this age group.
{"title":"Sleep polysomnography as a predictor of recurrence in children and adolescents with major depressive disorder.","authors":"G. Emslie, G. Emslie, R. Armitage, W. Weinberg, A. Rush, T. Mayes, T. Mayes, R. Hoffmann","doi":"10.1017/S1461145701002383","DOIUrl":"https://doi.org/10.1017/S1461145701002383","url":null,"abstract":"Adults with major depressive disorder (MDD) demonstrate certain sleep polysomnographic abnormalities, including sleep continuity disturbances, reduced slow-wave sleep, shortened rapid eye movement (REM) latency, and increased REM density. Findings of sleep EEG studies in depressed children and adolescents have yielded conflicting results, possibly because of methodological variations across the studies. Generally, however, studies have demonstrated that depressed children and adolescents exhibit less sleep continuity and non-REM sleep differences in comparison with control subjects than do adults. Thus, results from adult sleep polysomnography studies cannot necessarily be generalized to children and adolescents. Depressed adults who have reduced REM latency during the symptomatic episode appear more likely to have a relapse once treatment is discontinued than those with normal REM latency. No studies of the relationship between sleep polysomnographic variables and clinical course have been reported in depressed children and adolescents. Data for baseline clinical variables and 3 nights of sleep polysomnography were examined in 113 depressed children (< or = 12 yr; n = 51) and adolescents (> or = 13 yr; n = 62) (56 in-patients and 57 outpatients) where data was available on at least 1 yr of naturalistic follow-up. Subjects came from 2 studies of sleep polysomnography in children and adolescents with MDD. Clinical course was assessed using the Kiddie-Longitudinal Interval Follow-Up Evaluation (K-LIFE). This interview was used to define recovery from the index episode of MDD and recurrence, a new episode of meeting full criteria for MDD. Clinically, within 1 yr of initial evaluation 102/113 subjects had recovered from their index episode of depression (minimal or no symptoms for 60 d). Of the 102 subjects who recovered, 36 (35.3%) had a recurrence of MDD. The majority of subjects (55%) who had a recurrence were not on medication at the time of recurrence. Subjects who had a recurrence were more likely to report suicidal thoughts or attempts at baseline compared to those without a recurrence (67 vs. 37%; F = 8.77; p = 0.004). On baseline sleep polysomnography, subjects with a later recurrence had decreased sleep efficiency and delayed sleep onset (sleep latency > 10 min). Probability of recurrence at 12 months was 0.39 compared to 0.15 in subjects with non-delayed sleep onset (p = 0.005). Baseline suicidal ideation and sleep dysregulation on sleep polysomnography predicted recurrence in a large sample of depressed children and adolescents. Depression in children and adolescents is frequently a chronic, recurrent illness. Factors that can predict clinical course are important in increasing our understanding of depression in this age group.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"4 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130075673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-06-01DOI: 10.1017/S1461145701002395
Daniel A. Geller, Daniel A. Geller, J. Biederman, J. Biederman, S. Faraone, C. A. Bellordre, Grace S. Kim, Lisa Hagermoser, Kathleen Cradock, J. Frazier, J. Frazier, B. Coffey, B. Coffey
Although paediatric obsessive--compulsive disorder (OCD) is increasingly recognized as a putative developmental subtype of the disorder, it remains uncertain as to whether additional subtyping by age at onset in childhood or adolescence is warranted. Subjects included children and adolescents meeting DSM-III-R and DSM-IV criteria for OCD referred to a specialized OCD clinic. All youth were systematically evaluated with structured diagnostic interviews and clinical assessment by an OCD expert. Irrespective of current age, an earlier age at onset predicted increased risk for attention deficit hyperactivity disorder, simple phobia, agoraphobia and multiple anxiety disorders. In contrast, mood and psychotic disorders were associated with chronological age and were more prevalent in older subjects. Tourette's disorder showed associations with both chronological age and age at onset. Chronological age and age at onset predicted different patterns of comorbidity and dysfunction in children and adolescents with OCD. Considering the heterogeneity of OCD, age at onset may help identify meaningful developmental subtypes of the disorder beyond chronological age.
{"title":"Disentangling chronological age from age of onset in children and adolescents with obsessive--compulsive disorder.","authors":"Daniel A. Geller, Daniel A. Geller, J. Biederman, J. Biederman, S. Faraone, C. A. Bellordre, Grace S. Kim, Lisa Hagermoser, Kathleen Cradock, J. Frazier, J. Frazier, B. Coffey, B. Coffey","doi":"10.1017/S1461145701002395","DOIUrl":"https://doi.org/10.1017/S1461145701002395","url":null,"abstract":"Although paediatric obsessive--compulsive disorder (OCD) is increasingly recognized as a putative developmental subtype of the disorder, it remains uncertain as to whether additional subtyping by age at onset in childhood or adolescence is warranted. Subjects included children and adolescents meeting DSM-III-R and DSM-IV criteria for OCD referred to a specialized OCD clinic. All youth were systematically evaluated with structured diagnostic interviews and clinical assessment by an OCD expert. Irrespective of current age, an earlier age at onset predicted increased risk for attention deficit hyperactivity disorder, simple phobia, agoraphobia and multiple anxiety disorders. In contrast, mood and psychotic disorders were associated with chronological age and were more prevalent in older subjects. Tourette's disorder showed associations with both chronological age and age at onset. Chronological age and age at onset predicted different patterns of comorbidity and dysfunction in children and adolescents with OCD. Considering the heterogeneity of OCD, age at onset may help identify meaningful developmental subtypes of the disorder beyond chronological age.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"53 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128582816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-06-01DOI: 10.1017/S1461145701002280
M. Buchsbaum, E. Hollander, M. Haznedar, Cheuk Y. Tang, J. Spiegel-Cohen, T. Wei, A. Solimando, B. Buchsbaum, D. Robins, C. Bienstock, C. Cartwright, S. Mosovich
The regional metabolic effects of fluoxetine were examined in patients with autism spectrum disorders. Six adult patients with DSM-IV and Autism Diagnostic Interview (ADI) diagnoses of autism (n = 5) and Asperger's syndrome (n = 1), entered a 16-wk placebo-controlled cross-over trial of fluoxetine. The patients received (18)F-deoxyglucose positron emission tomography with co-registered magnetic resonance imaging at baseline and at the end of the period of fluoxetine administration. After treatment, the patients showed significant improvement on the scores of the Yale--Brown Obsessive--Compulsive Scale -- Obsessions subscale and the Hamilton Anxiety Scale; Clinical Global Impressions -- Autism scores showed 3 of the patients much improved and 3 unchanged. Relative metabolic rates were significantly higher in the right frontal lobe following fluoxetine, especially in the anterior cingulate gyrus and the orbitofrontal cortex. Patients with higher metabolic rates in the medial frontal region and anterior cingulate when unmedicated were more likely to respond favourably to fluoxetine. These results are consistent with those in depression indicating that higher cingulate gyrus metabolic rates at baseline predict SRI response.
{"title":"Effect of fluoxetine on regional cerebral metabolism in autistic spectrum disorders: a pilot study.","authors":"M. Buchsbaum, E. Hollander, M. Haznedar, Cheuk Y. Tang, J. Spiegel-Cohen, T. Wei, A. Solimando, B. Buchsbaum, D. Robins, C. Bienstock, C. Cartwright, S. Mosovich","doi":"10.1017/S1461145701002280","DOIUrl":"https://doi.org/10.1017/S1461145701002280","url":null,"abstract":"The regional metabolic effects of fluoxetine were examined in patients with autism spectrum disorders. Six adult patients with DSM-IV and Autism Diagnostic Interview (ADI) diagnoses of autism (n = 5) and Asperger's syndrome (n = 1), entered a 16-wk placebo-controlled cross-over trial of fluoxetine. The patients received (18)F-deoxyglucose positron emission tomography with co-registered magnetic resonance imaging at baseline and at the end of the period of fluoxetine administration. After treatment, the patients showed significant improvement on the scores of the Yale--Brown Obsessive--Compulsive Scale -- Obsessions subscale and the Hamilton Anxiety Scale; Clinical Global Impressions -- Autism scores showed 3 of the patients much improved and 3 unchanged. Relative metabolic rates were significantly higher in the right frontal lobe following fluoxetine, especially in the anterior cingulate gyrus and the orbitofrontal cortex. Patients with higher metabolic rates in the medial frontal region and anterior cingulate when unmedicated were more likely to respond favourably to fluoxetine. These results are consistent with those in depression indicating that higher cingulate gyrus metabolic rates at baseline predict SRI response.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"113 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133379696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-06-01DOI: 10.1017/S1461145701002334
O. Alhassoon, R. Dupont, B. Schweinsburg, M. Taylor, T. Patterson, I. Grant
Although abuse of cocaine or methamphetamine usually takes place in the context of heavy drinking, there is little information on the effects of such substance use comorbidity on brain perfusion. We explored similarities and differences in the effects of these two drugs in combination with alcohol on brain function using SPECT. Global and regional cerebral blood flow (CBF) were examined in 7 abstinent cocaine-dependent alcoholics (CDA; mean age = 39.2 yr, S.D. = 9.2 yr), 7 abstinent methamphetamine-dependent alcoholics (MDA; mean age = 36.8 yr, S.D. = 5.0 yr), and 7 non-alcoholic/non-stimulant abusing controls (NAC; mean age = 37.3 yr, S.D. = 9.6 yr). MDA had significantly lower global CBF than CDA who, in turn, were significantly lower than NAC. In addition, CDA had abnormal perfusion in the superior posterior frontal region compared to NAC; while MDA did not display specific regional deficits. Therefore, it appears that cocaine alters the relationship between global and regional CBF in alcoholics, while methamphetamine does not.
{"title":"Regional cerebral blood flow in cocaine- versus methamphetamine-dependent patients with a history of alcoholism.","authors":"O. Alhassoon, R. Dupont, B. Schweinsburg, M. Taylor, T. Patterson, I. Grant","doi":"10.1017/S1461145701002334","DOIUrl":"https://doi.org/10.1017/S1461145701002334","url":null,"abstract":"Although abuse of cocaine or methamphetamine usually takes place in the context of heavy drinking, there is little information on the effects of such substance use comorbidity on brain perfusion. We explored similarities and differences in the effects of these two drugs in combination with alcohol on brain function using SPECT. Global and regional cerebral blood flow (CBF) were examined in 7 abstinent cocaine-dependent alcoholics (CDA; mean age = 39.2 yr, S.D. = 9.2 yr), 7 abstinent methamphetamine-dependent alcoholics (MDA; mean age = 36.8 yr, S.D. = 5.0 yr), and 7 non-alcoholic/non-stimulant abusing controls (NAC; mean age = 37.3 yr, S.D. = 9.6 yr). MDA had significantly lower global CBF than CDA who, in turn, were significantly lower than NAC. In addition, CDA had abnormal perfusion in the superior posterior frontal region compared to NAC; while MDA did not display specific regional deficits. Therefore, it appears that cocaine alters the relationship between global and regional CBF in alcoholics, while methamphetamine does not.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121547557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-06-01DOI: 10.1017/S1461145701002346
John S. March, B. Vitiello
This Special Section of Int J Neuropsychopharmacol highlights current progress in paediatric neuropsychopharmacology. Combining critical reviews and, in some cases, new data, specific topics include: biological findings in major depression, sleep dysregulation in depressed youth, cardiovascular and ventilatory dysregulation in panic disorder, paediatric autoimmune neuropsychiatric disorder associated with strep (PANDAS), age of onset as a subtype marker in tic and obsessive--compulsive disorders (OCD), functional and pharmaconeuroanatomy of OCD and the behavioural pharmacokinetics of methylphenidate. In this introductory section, these articles are placed in the context of the state-of-the field and, more specifically, within the framework of recent NIMH initiatives in paediatric neuropsychopharmacology.
{"title":"Advances in paediatric neuropsychopharmacology: an overview.","authors":"John S. March, B. Vitiello","doi":"10.1017/S1461145701002346","DOIUrl":"https://doi.org/10.1017/S1461145701002346","url":null,"abstract":"This Special Section of Int J Neuropsychopharmacol highlights current progress in paediatric neuropsychopharmacology. Combining critical reviews and, in some cases, new data, specific topics include: biological findings in major depression, sleep dysregulation in depressed youth, cardiovascular and ventilatory dysregulation in panic disorder, paediatric autoimmune neuropsychiatric disorder associated with strep (PANDAS), age of onset as a subtype marker in tic and obsessive--compulsive disorders (OCD), functional and pharmaconeuroanatomy of OCD and the behavioural pharmacokinetics of methylphenidate. In this introductory section, these articles are placed in the context of the state-of-the field and, more specifically, within the framework of recent NIMH initiatives in paediatric neuropsychopharmacology.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130631240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-06-01DOI: 10.1017/S1461145701002371
H. Leonard, S. Swedo
The evidence to date, both published and unpublished, which addresses the validity of the proposed unique subgroup of children with early and abrupt onset of obsessive--compulsive disorder (OCD) and/or tic disorders subsequent to streptococcal infections was reviewed. The aetiology of OCD and tic disorders is unknown, although it appears that both disorders may arise from a variety of genetic and environmental factors. Post-streptococcal autoimmunity has been postulated as one possible mechanism for some. The acronym PANDAS (for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been given to a subgroup of paediatric patients who meet five inclusionary criteria: presence of OCD and/or tic disorder, pre-pubertal symptom onset, sudden onset or episodic course of symptoms, temporal association between streptococcal infections and neuropsychiatric symptom exacerbations, and associated neurological abnormalities. The proposed model of pathophysiology provides for several unique treatment strategies, including the use of antibiotic prophylaxis to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory interventions (such as intravenous immunoglobulin or therapeutic plasma exchange) in the treatment severe neuropsychiatric symptoms. For the latter study group, long-term (2--5 yr) follow-up revealed continued symptom improvement for the majority of patients, particularly when antibiotic prophylaxis had been effective in preventing recurrent streptococcal infections. In addition, the episodic nature of the subgroup's illness provides for opportunities to study brain structure and function during health and disease, as well as allowing for investigations of the aetiologic role of anti-neuronal antibodies and neuroimmune dysfunction in both OCD and tic disorders. Although much research remains to be done, an increasing body of evidence provides support for the postulate that OCD and tic disorders may arise from post-streptococcal autoimmunity. The unique clinical characteristics of the PANDAS subgroup, the presence of volumetric changes in the basal ganglia, and the dramatic response to immunomodulatory treatments, suggest that symptoms arise from a combination of local, regional and systemic dysfunction. Ongoing research is directed at understanding the nature of the abnormal immune response, as well as identifying at-risk children, in order to provide for novel strategies of prevention and treatment.
{"title":"Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS).","authors":"H. Leonard, S. Swedo","doi":"10.1017/S1461145701002371","DOIUrl":"https://doi.org/10.1017/S1461145701002371","url":null,"abstract":"The evidence to date, both published and unpublished, which addresses the validity of the proposed unique subgroup of children with early and abrupt onset of obsessive--compulsive disorder (OCD) and/or tic disorders subsequent to streptococcal infections was reviewed. The aetiology of OCD and tic disorders is unknown, although it appears that both disorders may arise from a variety of genetic and environmental factors. Post-streptococcal autoimmunity has been postulated as one possible mechanism for some. The acronym PANDAS (for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been given to a subgroup of paediatric patients who meet five inclusionary criteria: presence of OCD and/or tic disorder, pre-pubertal symptom onset, sudden onset or episodic course of symptoms, temporal association between streptococcal infections and neuropsychiatric symptom exacerbations, and associated neurological abnormalities. The proposed model of pathophysiology provides for several unique treatment strategies, including the use of antibiotic prophylaxis to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory interventions (such as intravenous immunoglobulin or therapeutic plasma exchange) in the treatment severe neuropsychiatric symptoms. For the latter study group, long-term (2--5 yr) follow-up revealed continued symptom improvement for the majority of patients, particularly when antibiotic prophylaxis had been effective in preventing recurrent streptococcal infections. In addition, the episodic nature of the subgroup's illness provides for opportunities to study brain structure and function during health and disease, as well as allowing for investigations of the aetiologic role of anti-neuronal antibodies and neuroimmune dysfunction in both OCD and tic disorders. Although much research remains to be done, an increasing body of evidence provides support for the postulate that OCD and tic disorders may arise from post-streptococcal autoimmunity. The unique clinical characteristics of the PANDAS subgroup, the presence of volumetric changes in the basal ganglia, and the dramatic response to immunomodulatory treatments, suggest that symptoms arise from a combination of local, regional and systemic dysfunction. Ongoing research is directed at understanding the nature of the abnormal immune response, as well as identifying at-risk children, in order to provide for novel strategies of prevention and treatment.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125041666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-06-01DOI: 10.1017/S1461145701002401
D. Rosenberg, Shauna MacMillan, G. Moore
Obsessive--compulsive disorder (OCD) is a severe, highly prevalent and often chronically disabling illness with frequent onset in childhood and adolescence. This underscores the importance of studying the illness during childhood near the onset of illness to minimize potential confounds of long-term illness duration and treatment intervention as well as to examine the developmental underpinnings of the illness. In this review, the authors focus on an integrated series of brain-imaging studies in paediatric OCD suggesting a reversible glutamatergically mediated thalamo-cortical--striatal dysfunction in OCD and their relevance for improved diagnosis and treatment of the condition. Developmental neurobiological models for OCD are presented and particular attention is devoted to evaluating neuroimaging studies designed to test these models and how they may help predict treatment response in paediatric OCD.
{"title":"Brain anatomy and chemistry may predict treatment response in paediatric obsessive--compulsive disorder.","authors":"D. Rosenberg, Shauna MacMillan, G. Moore","doi":"10.1017/S1461145701002401","DOIUrl":"https://doi.org/10.1017/S1461145701002401","url":null,"abstract":"Obsessive--compulsive disorder (OCD) is a severe, highly prevalent and often chronically disabling illness with frequent onset in childhood and adolescence. This underscores the importance of studying the illness during childhood near the onset of illness to minimize potential confounds of long-term illness duration and treatment intervention as well as to examine the developmental underpinnings of the illness. In this review, the authors focus on an integrated series of brain-imaging studies in paediatric OCD suggesting a reversible glutamatergically mediated thalamo-cortical--striatal dysfunction in OCD and their relevance for improved diagnosis and treatment of the condition. Developmental neurobiological models for OCD are presented and particular attention is devoted to evaluating neuroimaging studies designed to test these models and how they may help predict treatment response in paediatric OCD.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128882703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-06-01DOI: 10.1017/S1461145701002310
Lawrence Friedhoff, Edward I. Cullen, Neil S. M. Geoghagen, Joseph D. Buxbaum
The deposition of beta-amyloid (A beta) in neuronal plaques is believed to be crucial for the initiation and progression of Alzheimer's disease (AD). Studies in vitro have shown that inhibiting cholesterol metabolism with lovastatin, or its active metabolite lovastatin acid, lowers A beta production. To examine the effects of lovastatin on A beta in vivo, human subjects who had elevated low-density lipoprotein cholesterol were treated during a double-blind, randomized, placebo-controlled study with 10, 20, 40 or 60 mg once-daily doses of a controlled-release formulation of lovastatin, or matching placebo. Serum A beta concentrations were measured before and after up to 3 months of treatment. Mean and median changes from baseline in serum A beta concentrations showed a dose-dependent decrease, and analysis of variance indicated that treatment was statistically significant (p < 0.0348). Differences between the 40- and 60-mg dose groups and placebo were statistically significant (Dunnett's p < or = 0.05).
神经元斑块中β -淀粉样蛋白(A β)的沉积被认为对阿尔茨海默病(AD)的发生和发展至关重要。体外研究表明，用洛伐他汀或其活性代谢物洛伐他汀酸抑制胆固醇代谢可降低A β的产生。为了检验洛伐他汀对体内A β的影响，在一项双盲、随机、安慰剂对照研究中，对低密度脂蛋白胆固醇升高的人类受试者进行治疗，分别给予每日一次剂量为10,20,40或60mg的洛伐他汀控释制剂或匹配的安慰剂。在治疗前后3个月测量血清A β浓度。与基线相比，血清A β浓度的平均值和中位数变化呈剂量依赖性降低，方差分析显示治疗具有统计学意义(p < 0.0348)。40mg和60mg剂量组与安慰剂组的差异有统计学意义(Dunnett’s p < or = 0.05)。
{"title":"Treatment with controlled-release lovastatin decreases serum concentrations of human beta-amyloid (A beta) peptide.","authors":"Lawrence Friedhoff, Edward I. Cullen, Neil S. M. Geoghagen, Joseph D. Buxbaum","doi":"10.1017/S1461145701002310","DOIUrl":"https://doi.org/10.1017/S1461145701002310","url":null,"abstract":"The deposition of beta-amyloid (A beta) in neuronal plaques is believed to be crucial for the initiation and progression of Alzheimer's disease (AD). Studies in vitro have shown that inhibiting cholesterol metabolism with lovastatin, or its active metabolite lovastatin acid, lowers A beta production. To examine the effects of lovastatin on A beta in vivo, human subjects who had elevated low-density lipoprotein cholesterol were treated during a double-blind, randomized, placebo-controlled study with 10, 20, 40 or 60 mg once-daily doses of a controlled-release formulation of lovastatin, or matching placebo. Serum A beta concentrations were measured before and after up to 3 months of treatment. Mean and median changes from baseline in serum A beta concentrations showed a dose-dependent decrease, and analysis of variance indicated that treatment was statistically significant (p < 0.0348). Differences between the 40- and 60-mg dose groups and placebo were statistically significant (Dunnett's p < or = 0.05).","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126674913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-06-01DOI: 10.1017/S146114570100236X
C. Monk, Pavel Kovelenko, L. Ellman, R. Sloan, E. Bagiella, J. Gorman, D. Pine
The aim was to clarify the developmental nature of associations between psychiatric illness and risk for cardiovascular disease by investigating differences in cardiac functioning between youth with anxiety disorders and healthy controls. Twenty-two children meeting DSM-IV criteria for either separation anxiety disorder, overanxious disorder, panic disorder/panic attacks, or social phobia and 12 healthy controls underwent continuous electrocardiogram and respiration rate monitoring during a 15 min baseline period and 15 min of exposure to 5% CO(2). Heart rate (HR) and high frequency heart rate variability (HRV), a non-invasive measure of cardiac parasympathetic control, were calculated. Youth with anxiety disorders had higher and less fluctuating HR during baseline. Data also suggested that probands showed diminished overall changes in HRV during baseline and CO(2) inhalation relative to controls. However, as respiration rate affects HRV, these findings were confounded by changes in respiration elicited by CO(2) inhalation. The data suggest that youth with anxiety disorders experience an elevated and less fluctuating HR in the face of a novel situation, possibly due to a failure to appropriately modulate HRV. In adults, sustained elevations in HR in conjunction with deficient vagal modulation predicts risk for future cardiovascular disease. As such, the current data suggest that the presence of an anxiety disorder may identify youth who exhibit autonomic profiles that place them at risk for cardiac disease.
{"title":"Enhanced stress reactivity in paediatric anxiety disorders: implications for future cardiovascular health.","authors":"C. Monk, Pavel Kovelenko, L. Ellman, R. Sloan, E. Bagiella, J. Gorman, D. Pine","doi":"10.1017/S146114570100236X","DOIUrl":"https://doi.org/10.1017/S146114570100236X","url":null,"abstract":"The aim was to clarify the developmental nature of associations between psychiatric illness and risk for cardiovascular disease by investigating differences in cardiac functioning between youth with anxiety disorders and healthy controls. Twenty-two children meeting DSM-IV criteria for either separation anxiety disorder, overanxious disorder, panic disorder/panic attacks, or social phobia and 12 healthy controls underwent continuous electrocardiogram and respiration rate monitoring during a 15 min baseline period and 15 min of exposure to 5% CO(2). Heart rate (HR) and high frequency heart rate variability (HRV), a non-invasive measure of cardiac parasympathetic control, were calculated. Youth with anxiety disorders had higher and less fluctuating HR during baseline. Data also suggested that probands showed diminished overall changes in HRV during baseline and CO(2) inhalation relative to controls. However, as respiration rate affects HRV, these findings were confounded by changes in respiration elicited by CO(2) inhalation. The data suggest that youth with anxiety disorders experience an elevated and less fluctuating HR in the face of a novel situation, possibly due to a failure to appropriately modulate HRV. In adults, sustained elevations in HR in conjunction with deficient vagal modulation predicts risk for future cardiovascular disease. As such, the current data suggest that the presence of an anxiety disorder may identify youth who exhibit autonomic profiles that place them at risk for cardiac disease.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"82 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126995530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-03-01DOI: 10.1017/S146114570100222X
G. Chen, L. Huang, W. Zeng, H. K Manji
Manic depressive illness (MDI) is a common, severe, chronic and often life-threatening illness. Despite well-established genetic diatheses and extensive research, the biochemical abnormalities underlying the predisposition to, and the pathophysiology of, these disorders remain to be clearly established. Despite formidable obstacles in our attempts to understand the underlying neurobiology of this illness, there is currently considerable excitement about the progress that is being made using novel strategies to identify changes in gene expression that may have therapeutic relevance in the long-term treatment of MDI. In this paper, we describe our recent research endeavours utilizing newer technologies, including a concerted series of mRNA RT-PCR studies, which has led to the identification of novel, hitherto completely unexpected targets for the long-term actions of mood stabilizers - the major cytoprotective protein bcl-2, a human mRNA binding (and stabilizing) protein, AUH, and a Rho kinase. These results add to the growing body of data suggesting that mood stabilizers may bring about some of their long-term benefits by enhancing neuroplasticity and cellular resilience. These results are noteworthy since recent morphometric brain imaging and post-mortem studies have demonstrated that MDI is associated with the atrophy and/or loss of neurons and glia. The development of novel treatments which more directly target molecules involved in critical CNS cell survival and cell death pathways have the potential to enhance neuroplasticity and cellular resilience, and thereby modulate the long-term course and trajectory of these devastating illnesses.
{"title":"Mood stabilizers regulate cytoprotective and mRNA-binding proteins in the brain: long-term effects on cell survival and transcript stability.","authors":"G. Chen, L. Huang, W. Zeng, H. K Manji","doi":"10.1017/S146114570100222X","DOIUrl":"https://doi.org/10.1017/S146114570100222X","url":null,"abstract":"Manic depressive illness (MDI) is a common, severe, chronic and often life-threatening illness. Despite well-established genetic diatheses and extensive research, the biochemical abnormalities underlying the predisposition to, and the pathophysiology of, these disorders remain to be clearly established. Despite formidable obstacles in our attempts to understand the underlying neurobiology of this illness, there is currently considerable excitement about the progress that is being made using novel strategies to identify changes in gene expression that may have therapeutic relevance in the long-term treatment of MDI. In this paper, we describe our recent research endeavours utilizing newer technologies, including a concerted series of mRNA RT-PCR studies, which has led to the identification of novel, hitherto completely unexpected targets for the long-term actions of mood stabilizers - the major cytoprotective protein bcl-2, a human mRNA binding (and stabilizing) protein, AUH, and a Rho kinase. These results add to the growing body of data suggesting that mood stabilizers may bring about some of their long-term benefits by enhancing neuroplasticity and cellular resilience. These results are noteworthy since recent morphometric brain imaging and post-mortem studies have demonstrated that MDI is associated with the atrophy and/or loss of neurons and glia. The development of novel treatments which more directly target molecules involved in critical CNS cell survival and cell death pathways have the potential to enhance neuroplasticity and cellular resilience, and thereby modulate the long-term course and trajectory of these devastating illnesses.","PeriodicalId":394244,"journal":{"name":"The International Journal of Neuropsychopharmacology","volume":"18 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2001-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114106493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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