6431 articles - 08.09.10
1: Arch Gen Psychiatry. 2010 Sep;67(9):931-938.
Fazel S, Lichtenstein P, Grann M, Goodwin GM, Langstrom N.
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, England. seena.fazel@psych.ox.ac.uk.
CONTEXT: Although bipolar disorder is associated with various adverse health outcomes, the relationship with violent crime is uncertain. OBJECTIVES: To determine the risk of violent crime in bipolar disorder and to contextualize the findings with a systematic review. DESIGN: Longitudinal investigations using general population and unaffected sibling control individuals. SETTING: Population-based registers of hospital discharge diagnoses, sociodemographic information, and violent crime in Sweden from January 1, 1973, through December 31, 2004. PARTICIPANTS: Individuals with 2 or more discharge diagnoses of bipolar disorder (n = 3743), general population controls (n = 37 429), and unaffected full siblings of individuals with bipolar disorder (n = 4059). Main Outcome Measure Violent crime (actions resulting in convictions for homicide, assault, robbery, arson, any sexual offense, illegal threats, or intimidation). RESULTS: During follow-up, 314 individuals with bipolar disorder (8.4%) committed violent crime compared with 1312 general population controls (3.5%) (adjusted odds ratio, 2.3; 95% confidence interval, 2.0-2.6). The risk was mostly confined to patients with substance abuse comorbidity (adjusted odds ratio, 6.4; 95% confidence interval, 5.1-8.1). The risk increase was minimal in patients without substance abuse comorbidity (adjusted odds ratio, 1.3; 95% confidence interval, 1.0-1.5), which was further attenuated when unaffected full siblings of individuals with bipolar disorder were used as controls (1.1; 0.7-1.6). We found no differences in rates of violent crime by clinical subgroups (manic vs depressive or psychotic vs nonpsychotic). The systematic review identified 8 previous studies (n = 6383), with high heterogeneity between studies. Odds ratio for violence risk ranged from 2 to 9. CONCLUSION: Although current guidelines for the management of individuals with bipolar disorder do not recommend routine risk assessment for violence, this assertion may need review in patients with comorbid substance abuse.
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PMID: 20819987 [PubMed - as supplied by publisher]2: J Clin Psychiatry. 2010 Aug 10; [Epub ahead of print]
Swartz HA, Thase ME.
Western Psychiatric Institute and Clinic, 3811 O'Hara St, Pittsburgh, PA 15213, USA. swartzha@upmc.edu.
OBJECTIVE: Bipolar II disorder is a common, recurrent, and disabling psychiatric illness, and yet little is known about how best to treat it. The pressing clinical need for evidence-based approaches to the treatment of bipolar II disorder, coupled with recent publication of pertinent studies, calls for an updated review of this literature. This review focuses on a critical examination of the evidence supporting the efficacy of treatments for acute depressive episodes in bipolar II disorder. DATA SOURCES: A MEDLINE (via Ovid) search of journals, covering the period from January 1950 to January 2009, was performed to identify relevant studies. Keywords used were bipolar II disorder, bipolar disorder, bipolar depression, and pharmacotherapy. Studies were further limited to those that were in adult samples, published in peer-reviewed journals, and written in English. STUDY SELECTION: We examined all randomized trials evaluating the use of pharmacotherapy in the treatment of acute bipolar II depression. Studies with mixed samples of bipolar I and II or bipolar II and unipolar depression were examined as well. Twenty-one randomized trials were identified and reviewed. DATA EXTRACTION: Therapeutic agents were rated according to the quality of evidence supporting their efficacy as treatments for bipolar II depression. DATA SYNTHESIS: Ninety percent of relevant trials were published after 2005. Quetiapine was judged as having compelling evidence supporting its efficacy. Lithium, antidepressants, and pramipexole were judged as having preliminary support for efficacy. Lamotrigine was considered to have mixed support. CONCLUSIONS: Although progress has been made, further research on bipolar II depression is warranted. (c) Copyright 2010 Physicians Postgraduate Press, Inc.
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PMID: 20816033 [PubMed - as supplied by publisher]3: J Clin Psychiatry. 2010 Aug 10; [Epub ahead of print]
Surman CB, Monuteaux MC, Petty CR, Faraone SV, Spencer TJ, Chu NF, Biederman J.
Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, Ste 2000, 185 Alewife Brook Pkwy, Cambridge, MA 02138, USA. csurman@partners.org.
BACKGROUND: Clinical trials have demonstrated that pharmacotherapies can safely treat attention-deficit/hyperactivity disorder (ADHD) in adulthood. Eligibility criteria in these trials may significantly limit their external validity by excluding a significant portion of adults with ADHD in the general population. In particular, exclusion criteria may frequently exclude individuals with comorbid mental health conditions, which are common in the adult ADHD population. METHOD: We addressed the representativeness of clinical trials by comparing 146 adult clinical trial participants with DSM-IV ADHD and a community sample composed of 124 adults with DSM-IV ADHD and 123 non-ADHD controls. Subjects were compared on socioeconomic status, Hollingshead occupational code, cognitive measures, lifetime psychopathology, and Global Assessment of Functioning (GAF) scale ratings. RESULTS: Adults with ADHD in the community sample had higher rates of lifetime psychiatric comorbidity, lower GAF scores, and lower occupational codes than those in the clinical trial. The clinical trial eligibility criteria would have excluded 61% of community sample adults with ADHD. This excluded portion of the community sample had higher rates of lifetime psychiatric comorbidity and lower GAF scores than clinical trial participants. CONCLUSIONS: Adults with ADHD participating in the clinical trial had less evidence of functional impairment and endorsed less psychiatric comorbidity than the majority of community sample subjects with ADHD. This suggests that findings from clinical trials may have limited external validity for adults with ADHD in the general population, particularly for those adults with ADHD with the greatest burden of comorbid psychopathology. (c) Copyright 2010 Physicians Postgraduate Press, Inc.
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PMID: 20816030 [PubMed - as supplied by publisher]4: J Clin Psychiatry. 2010 Aug 10; [Epub ahead of print]
Seemuller F, Moller HJ, Obermeier M, Adli M, Bauer M, Kronmuller K, Holsboer F, Brieger P, Laux G, Bender W, Heuser I, Zeiler J, Gaebel W, Schennach-Wolff R, Henkel V, Riedel M.
Department of Psychiatry, Ludwig-Maximilians-Universitat, Nussbaumstrasse 7, 80336 Munich, Germany florian.seemueller@med.uni-muenchen.de.
BACKGROUND: Because of strict inclusion and exclusion criteria, results drawn from placebo-controlled randomized antidepressant efficacy trials may not be transferable to real-world patients. METHOD: This study was performed from March 2000 to September 2005 as a prospective, multicenter follow-up. Patients were recruited from February 2000 to June 2005. All patients were hospitalized (N = 1,014) and met DSM-IV criteria for major depressive episode. Assessments with the 21-item Hamilton Depression Rating Scale were conducted biweekly until discharge. According to the most commonly applied exclusion criteria in randomized controlled antidepressant efficacy trials, patients were retrospectively divided into 2 groups: (1) patients not fulfilling exclusion criteria and therefore eligible for a randomized placebo-controlled trial, referred to as "efficacy sample," and (2) patients fulfilling at least 1 exclusion criterion, not being eligible for inclusion in an efficacy trial ("nonefficacy sample"). The efficacy sample was compared with the nonefficacy sample in terms of sociodemographic and clinical baseline variables and outcome measures, such as remission and response rates, 17-item Hamilton Depression Rating Scale mean scores, time to remission, and time to response. RESULTS: Significant differences were found, with the efficacy sample being older (P = .03) and being more often treated at a university hospital (P = .02). The efficacy sample demonstrated superior outcome only in significantly higher mean Global Assessment of Functioning scores at discharge (P = .03). There were no differences regarding remission (P = .68) and response (P = .06) rates, length of hospital stay (P = .49), 17-item Hamilton Depression Rating Scale total score at discharge (P = .13), or time to response (P = .39) or remission (P = .16). CONCLUSIONS: Both groups differed significantly in several baseline measures and final Global Assessment of Functioning scores but not in any other outcome measure. Challenging current beliefs, our findings show that results from efficacy antidepressant trials might be more generalizable than previously thought. (c) Copyright 2010 Physicians Postgraduate Press, Inc.
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PMID: 20816028 [PubMed - as supplied by publisher]5: Psychol Med. 2010 Sep 1;:1-8 [Epub ahead of print]
Kendler KS, Jablensky A.
Departments of Psychiatry, and Human and Molecular Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Emil Kraepelin fundamentally shaped our current psychiatric nosology. Although much has been written about his diagnostic formulations, less is known about his views on the fundamental nature of psychiatric illness and the goals of psychiatric nosology. We focus on his writings from 1896 to 1903 but also review his inaugural lecture in Dorpat in 1887 and his last two papers, published in 1919-1920. Kraepelin hoped for a 'natural' classification of psychiatric illness but realized that the level of etiologic knowledge required to undergird this effort was not feasible in his own lifetime. This did not stop him, however, from developing a pragmatic approach based on his clinical method of careful description with detailed follow-up, coupled with the available fallible tools of pathological anatomy and, by 1919, genetics and biochemistry. Kraepelin saw psychiatric disorders as multifactorial, arising from the difficult to untangle action and interaction of internal and external causes. He was aware of the problem of defining the boundaries of illness and health but knew this was not unique to psychiatry. Contrary to his stereotype, he was sensitive to the importance of personality factors in psychiatric illness and advocated for their investigation. He also recognized the limitations of his 'clinical method' and was especially critical of classifications based on single prominent symptoms. Ultimately, Kraepelin was a skeptical realist when it came to psychiatric nosology. His goal of developing a consistent 'natural' classification of the major mental disorders has yet to be attained, but his 'research agenda' remains central to psychiatry to the present day.
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PMID: 20809997 [PubMed - as supplied by publisher]6: Br J Psychiatry. 2010 Sep;197:174-9.
Singh SP, Singh V, Kar N, Chan K.
Step to Health, Mental Health Directorate, Wolverhampton City Primary Care Trust, Wolverhampton, WV10 9TH, UK. Dr.S.Singh@wlv.ac.uk.
BACKGROUND: Treatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue. AIMS: To analyse the efficacy of add-on antidepressants for the treatment of negative symptoms of chronic schizophrenia. METHOD: Systematic review and meta-analysis of randomised controlled trials comparing the effect of antidepressants and placebo on the negative symptoms of chronic schizophrenia, measured through standardised rating scales. Outcome was measured as standardised mean difference between end-of-trial and baseline scores of negative symptoms. RESULTS: There were 23 trials from 22 publications (n = 819). The antidepressants involved were selective serotonin reuptake inhibitors, mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other antidepressants were not available. The overall standardised mean difference was moderate (-0.48) in favour of antidepressants and subgroup analysis revealed significant responses for fluoxetine, trazodone and ritanserin. CONCLUSIONS: Antidepressants along with antipsychotics are more effective in treating the negative symptoms of schizophrenia than antipsychotics alone.
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PMID: 20807960 [PubMed - in process]7: J Clin Psychiatry. 2010 Aug;71(8):e1-e21.
Meyer RE, Salzman C, Youngstrom EA, Clayton PJ, Goodwin FK, Mann JJ, Alphs LD, Broich K, Goodman WK, Greden JF, Meltzer HY, Normand SL, Posner K, Shaffer D, Oquendo MA, Stanley B, Trivedi MH, Turecki G, Beasley CM Jr, Beautrais AL, Bridge JA, Brown GK, Revicki DA, Ryan ND, Sheehan DV.
Best Practice Project Management, Inc, PO Box 30219, Bethesda, MD 20824, USA. rmeyer@best-practice.net
OBJECTIVE: To address issues concerning potential treatment-emergent "suicidality," a consensus conference was convened March 23-24, 2009. PARTICIPANTS: This gathering of participants from academia, government, and industry brought together experts in suicide prevention, clinical trial design, psychometrics, pharmacoepidemiology, and genetics, as well as research psychiatrists involved in studies of major depression, bipolar disorder, schizophrenia, substance abuse/dependence, and other psychiatric disorders associated with elevated suicide risk across the life cycle. The process involved reviews of the relevant literature, and a series of 6 breakout sessions focused on specific questions of interest. EVIDENCE: Each of the participants at the meeting received references relevant to the formal presentations (as well as the slides for the presentations) for their review prior to the meeting. In addition, the assessment instruments of suicidal ideation/behavior were reviewed in relationship to standard measures of validity, reliability, and clinical utility, and these findings were discussed at length in relevant breakout groups, in the final plenary session, and in the preparation of the article. Consensus and dissenting views were noted. CONSENSUS PROCESS: Discussion and questions followed each formal presentation during the plenary sessions. Approximately 6 questions per breakout group were prepared in advance by members of the Steering Committee and each breakout group chair. Consensus in the breakout groups was achieved by nominal group process. Consensus recommendations and any dissent were reviewed for each breakout group at the final plenary session. All plenary sessions were recorded and transcribed by a court stenographer. Following the transcript, with input by each of the authors, the final paper went through 14 drafts. The output of the meeting was organized into this scholarly article, which has been developed by the authors with feedback from all participants at the meeting and represents a consensus view. Any areas of disagreement have been noted. CONCLUSIONS: The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's effort to promote standard definitions and definable expectations for investigators and industry sponsors by endorsing the terminology in the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to build upon its new authority to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk within informative large health care-related databases in the United States and abroad. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the current Agency requirement that all CNS clinical drug trials must include a C-CASA-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed, and they need to be included to enable premarket assessments of the risks and benefits of medications related to suicidal ideation, suicidal behavior, and suicide in such patients. Copyright 2010 Physicians Postgraduate Press, Inc.
Publication Types: Research Support, Non-U.S. Gov't
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PMID: 20797373 [PubMed - in process]8: Psychosom Med. 2010 Aug 17; [Epub ahead of print]
Pedersen A, Zachariae R, Bovbjerg DH.
Department of Psychology (A.P., R.Z.), University of Aarhus, Aarhus, Denmark; Department of Oncology (R.Z.), Aarhus University Hospital, Arhus, Denmark; and the University of Pittsburgh Cancer Institute (D.H.B.), and Departments of Psychiatry, Psychology, and Behavioral and Community Health Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
Objective: To quantify the available evidence for the hypothesis that reduced resistance caused by psychological stress may influence the development of clinical disease in those exposed to an infectious agent. Methods: We conducted a systematic review and meta-analysis of 27 prospective studies examining the association between psychological stress and subsequent upper respiratory infection (URI). Results: The results revealed a significant overall main effect of psychological stress on the risk of developing URI (effect size correlation coefficient, 0.21; 95% confidence interval, 0.15-0.27). Further analyses showed that effect sizes for the association did not vary according to type of stress, how URI was assessed, or whether the studies had controlled for preexposure. Conclusions: The meta-analytical findings confirmed the hypothesis that psychological stress is associated with increased susceptibility to URI, lending support to an emerging appreciation of the potential importance of psychological factors in infectious disease.
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PMID: 20716708 [PubMed - as supplied by publisher]9: Biol Psychiatry. 2010 Aug 6; [Epub ahead of print]
Swardfager W, Lanctot K, Rothenburg L, Wong A, Cappell J, Herrmann N.
Department of Pharmacology and Toxicology, Toronto, Ontario, Canada; Department of Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
BACKGROUND: Studies suggest that inflammation is involved in the neurodegenerative cascade leading to Alzheimer's disease (AD) pathology and symptoms. This study sought to quantitatively summarize the clinical cytokine data. METHODS: Original English language peer-reviewed studies measuring cytokine concentrations in AD and healthy control subjects were included. Mean (+/-standard deviation) cytokine concentrations for AD and control subjects were extracted. RESULTS: Forty studies measuring peripheral blood cytokine concentrations and 14 measuring cerebrospinal fluid (CSF) cytokine concentrations were included. In peripheral blood, there were significantly higher concentrations (weighted mean difference [95% confidence interval]) of interleukin (IL)-6 (2.86 [1.68, 4.04] pg/mL, p < .00001, N[AD/control subjects] = 985/680, 14 studies), tumor necrosis factor (TNF)-alpha (3.25 [.76, 5.74] pg/mL, p = .01, N = 680/447, 14 studies), IL-1beta (.55 [.32, .78] pg/mL, p < .00001, N = 574/370, 10 studies), transforming growth factor (TGF)-beta (67.23 [28.62, 105.83] pg/mL, p = .0006, N = 190/158, 5 studies), IL-12 (7.60 [5.58, 9.62] pg/mL, p < .00001, N = 148/106, 5 studies), and IL-18 (15.82 [1.98, 29.66] pg/mL, p = .03, N = 131/94, 4 studies) but not of IL-4, IL-8, IL-10, interferon-gamma, or C-reactive protein in AD subjects compared with control subjects. There were significantly higher concentrations of TGF-beta (7.81 [2.27, 13.35] pg/mL, p =.006, N = 113/114, 5 studies) but not IL-6, TNF-alpha, and IL-1beta in the CSF of AD subjects compared with control subjects. CONCLUSIONS: These results strengthen the clinical evidence that AD is accompanied by an inflammatory response, particularly higher peripheral concentrations of IL-6, TNF-alpha, IL-1beta, TGF-beta, IL-12 and IL-18 and higher CSF concentrations of TGF-beta. Copyright (c) 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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PMID: 20692646 [PubMed - as supplied by publisher]10: Arch Gen Psychiatry. 2010 Aug;67(8):812-21.
Pyne JM, Fortney JC, Tripathi SP, Maciejewski ML, Edlund MJ, Williams DK.
Center for Mental Healthcare and Outcomes Research, Central Arkansas Veterans Healthcare System, North Little Rock, AR 72114, USA. jmpyne@uams.edu
CONTEXT: Collaborative care interventions for depression in primary care settings are clinically beneficial and cost-effective. Most prior studies were conducted in urban settings. OBJECTIVE: To examine the cost-effectiveness of a rural telemedicine-based collaborative care depression intervention. DESIGN: Randomized controlled trial of intervention vs usual care. SETTING: Seven small (serving 1000 to 5000 veterans) Veterans Health Administration community-based outpatient clinics serving rural catchment areas in 3 mid-South states. Each site had interactive televideo dedicated to mental health but no psychiatrist or psychologist on site. Patients Among 18 306 primary care patients who were screened, 1260 (6.9%) screened positive for depression; 395 met eligibility criteria and were enrolled from April 2003 to September 2004. Of those enrolled, 360 (91.1%) completed a 6-month follow-up and 335 (84.8%) completed a 12-month follow-up. Intervention A stepped-care model for depression treatment was used by an off-site depression care team to make treatment recommendations via electronic medical record. The team included a nurse depression care manager, clinical pharmacist, and psychiatrist. The depression care manager communicated with patients via telephone and was supported by computerized decision support software. MAIN OUTCOME MEASURES: The base case cost analysis included outpatient, pharmacy, and intervention expenditures. The effectiveness outcomes were depression-free days and quality-adjusted life years (QALYs) calculated using the 12-Item Short Form Health Survey standard gamble conversion formula. RESULTS: The incremental depression-free days outcome was not significant (P = .10); therefore, further cost-effectiveness analyses were not done. The incremental QALY outcome was significant (P = .04) and the mean base case incremental cost-effectiveness ratio was $85 634/QALY. Results adding inpatient costs were $111 999/QALY to $132 175/QALY. CONCLUSIONS: In rural settings, a telemedicine-based collaborative care intervention for depression is effective and expensive. The mean base case result was $85 634/QALY, which is greater than cost per QALY ratios reported for other, mostly urban, depression collaborative care interventions.
Publication Types: Comparative Study Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, Non-P.H.S.
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PMID: 20679589 [PubMed - indexed for MEDLINE]11: Br J Psychiatry. 2010 Aug;197:91-5.
Poole NA, Wuerz A, Agrawal N.
St Bartholomew's Hospital, East London Foundation Trust, West Smithfield, London EC1A 7BE, UK. norman.poole@googlemail.com
BACKGROUND: The value of drug interviews in the treatment of conversion disorder is at present unknown. AIMS: To review all the available papers published in English that report on the use of drug interviews for treating conversion/dissociative disorder. METHOD: Databases (including EMBASE, MEDLINE and PsycINFO) were searched from 1920 to 2009. Selected publications had to report on the use of drug interviews in people diagnosed with a conversion/dissociative disorder. Qualitative and quantitative data were extracted. Predictors of a positive response were ascertained using meta-analytic techniques. RESULTS: Fifty-five papers meeting inclusion criteria were identified. No studies compared the intervention with a suitable control group. However, two studies reported high response rates when drug interview was used in individuals with treatment-resistant conversion disorder. In the meta-analysis, the use of suggestion and occurrence of emotional catharsis during the interview were positively associated with recovery. Combining two medications and comorbid psychiatric disorder were negatively associated with recovery. CONCLUSIONS: The evidence for effectiveness of drug interviews is of poor quality but it may be of benefit in the treatment of acute and treatment-resistant conversion disorder. A proactive approach during the interview, making suggestions the individual will respond, could influence outcome. Comorbid psychiatric disorder should be treated conventionally. Experimental studies to determine efficacy are required.
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PMID: 20679259 [PubMed - in process]12: Biol Psychiatry. 2010 Aug 15;68(4):314-9.
Bale TL, Baram TZ, Brown AS, Goldstein JM, Insel TR, McCarthy MM, Nemeroff CB, Reyes TM, Simerly RB, Susser ES, Nestler EJ.
Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania.
For more than a century, clinical investigators have focused on early life as a source of adult psychopathology. Early theories about psychic conflict and toxic parenting have been replaced by more recent formulations of complex interactions of genes and environment. Although the hypothesized mechanisms have evolved, a central notion remains: early life is a period of unique sensitivity during which experience confers enduring effects. The mechanisms for these effects remain almost as much a mystery today as they were a century ago. Recent studies suggest that maternal diet can program offspring growth and metabolic pathways, altering lifelong susceptibility to diabetes and obesity. If maternal psychosocial experience has similar programming effects on the developing offspring, one might expect a comparable contribution to neurodevelopmental disorders, including affective disorders, schizophrenia, autism, and eating disorders. Due to their early onset, prevalence, and chronicity, some of these disorders, such as depression and schizophrenia, are among the highest causes of disability worldwide according to the World Health Organization 2002 report. Consideration of the early life programming and transcriptional regulation in adult exposures supports a critical need to understand epigenetic mechanisms as a critical determinant in disease predisposition. Incorporating the latest insight gained from clinical and epidemiological studies with potential epigenetic mechanisms from basic research, the following review summarizes findings from a workshop on Early Life Programming and Neurodevelopmental Disorders held at the University of Pennsylvania in 2009. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
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PMID: 20674602 [PubMed - in process]13: Biol Psychiatry. 2010 Sep 15;68(6):568-77. Epub 2010 Jul 31.
Semkovska M, McLoughlin DM.
Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, St. Patrick's University Hospital, Ireland.
BACKGROUND: Electroconvulsive therapy (ECT) is the most acutely effective treatment for depression, but is limited by cognitive side effects. However, research on their persistence, severity, and pattern is inconsistent. We aimed to quantify ECT-associated cognitive changes, specify their pattern, and determine progression. METHODS: MEDLINE, EMBASE, PsycArticles, PsychINFO, PsychLIT, and reference lists were systematically searched through January 2009. We included all independent, within-subjects design studies of depressed patients receiving ECT where cognition was assessed using standardized tests. Main outcome was change in performance after ECT relative to pretreatment scores with respect to delay between finishing ECT and cognitive testing. We explored potential moderators' influence, e.g., electrode placement, stimulus waveform. RESULTS: Twenty-four cognitive variables (84 studies, 2981 patients) were meta-analyzed. No standardized retrograde amnesia tests were identified. Significant decreases in cognitive performance were observed 0 to 3 days after ECT in 72% of variables: effect sizes (ES) ranging from -1.10 (95% confidence interval [CI], -1.53 to -.67) to -.21 (95% CI, -.40 to .01). Four to 15 days post-ECT, all but one CI included zero or showed positive ES. No negative ES were observed after 15 days, with 57% of variables showing positive ES, ranging from .35 (95% CI, .07-.63) to .75 (95% CI, .43-1.08). Moderators did not influence cognitive outcomes after 3 days post-ECT. CONCLUSIONS: Cognitive abnormalities associated with ECT are mainly limited to the first 3 days posttreatment. Pretreatment functioning levels are subsequently recovered. After 15 days, processing speed, working memory, anterograde memory, and some aspects of executive function improve beyond baseline levels. 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Publication Types: Research Support, Non-U.S. Gov't
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PMID: 20673880 [PubMed - in process]14: Biol Psychiatry. 2010 Jul 29; [Epub ahead of print]
Li T, Li Z, Chen P, Zhao Q, Wang T, Huang K, Li J, Li Y, Liu J, Zeng Z, Feng G, He L, Shi Y.
Bio-X Center and Affiliated Changning Mental Health Center, Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, People's Republic of China.
BACKGROUND: Schizophrenia is a complex major psychiatric disorder affecting approximately 1% of the world population. Recently, in a genome-wide association study and a follow-up in Caucasians, Stefansson et al. examined 7662 schizophrenic cases and 29053 normal control subjects and reported seven common single nucleotide polymorphisms (SNPs) that were significantly (>10(-8)) associated with schizophrenia. METHODS: To investigate whether these risk SNPs were significantly associated in Han Chinese, we analyzed the seven SNPs in 2496 schizophrenia patients and 5184 normal control subjects. Because only three of the seven SNPs were polymorphic in Han Chinese, we genotyped two additional common SNPs from the same risk regions. RESULTS: Three SNPs, rs6932590 (p = .00096), rs3131296 (p = 1.29 x 10(-6)), and rs3130375 (p = 1.76 x 10(-5)), mapping to the major histocompatibility complex region and one SNP rs2958182 (p = 3.64 x 10(-6)) located in the TCF4 gene were significant in our sample set. A meta-analysis using published genome-wide association study results also supported our findings. CONCLUSIONS: Our results confirm that common risk factors in the major histocompatibility complex region and TCF4 gene are associated with schizophrenia in Han Chinese, but our results fail to show an association with SNP rs12807809 in the NRGN gene. Copyright (c) 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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PMID: 20673877 [PubMed - as supplied by publisher]15: Biol Psychiatry. 2010 Jul 29; [Epub ahead of print]
Kegeles LS, Slifstein M, Xu X, Urban N, Thompson JL, Moadel T, Harkavy-Friedman JM, Gil R, Laruelle M, Abi-Dargham A.
Department of Psychiatry, Columbia University College of Physicians and Surgeons, and New York State Psychiatric Institute, New York, New York; Department of Radiology, Columbia University, College of Physicians and Surgeons, New York, New York.
BACKGROUND: Alterations in dopamine D(2)/D(3) receptor binding have been reported in schizophrenia, and a meta-analysis of imaging studies has shown a modest elevation in striatum. Newer radioligands now allow the assessment of these receptors in extrastriatal regions. We used positron emission tomography with [(18)F]fallypride to evaluate D(2)/D(3) receptors in both striatal and extrastriatal regions in schizophrenia. METHODS: Twenty-one patients with schizophrenia and 22 matched healthy control subjects were scanned with an ECAT EXACT HR+ camera. Two-tissue compartment modeling and the reference tissue method gave binding potentials relative to nondisplaceable uptake, total plasma concentration, and free plasma concentration. These were compared between groups in five striatal and eight extrastriatal regions. Several regional volumes were lower in the patient group, and positron emission tomography data were corrected for partial volume effects. RESULTS: Binding potential values differed in three regions between groups. Values for binding potential relative to nondisplaceable uptake from two-tissue compartment modeling in patients and control subjects, respectively, were 28.7 +/- 6.8 and 25.3 +/- 4.3 in postcommissural caudate, 2.9 +/- .7 and 2.6 +/- .4 in thalamus, and 1.8 +/- .5 and 2.1 +/- .7 in uncus. Loss of D(2)/D(3) receptors with age was found in striatal and extrastriatal regions and was greater in neocortex. CONCLUSIONS: Our study found selective alterations in D(2)/D(3) receptors in striatal and extrastriatal regions, consistent with some but not all previously published reports. As previously shown for the striatum, a more sensitive imaging approach for studying the role of dopamine in the pathophysiology of schizophrenia might be assessment of neurotransmitter levels rather than D(2)/D(3) receptor levels in extrastriatal regions. Copyright (c) 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20673873&dopt=ExternalLink
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PMID: 20673873 [PubMed - as supplied by publisher]16: J Clin Psychiatry. 2010 Jun 29; [Epub ahead of print]
Lepping P, Delieu J, Mellor R, Williams JH, Hudson PR, Hunter-Lavin C.
Wrexham Academic Unit, Croesnewydd Rd, Wrexham, LL13 7TY, Wales, UK. peter.lepping@wales.nhs.uk.
OBJECTIVE: To look at (1) the association between antipsychotics and cell stress, (2) whether first-generation antipsychotics may show different effects than second-generation antipsychotics, and (3) whether recommendations can be made regarding medication. DATA SOURCES: We conducted a systematic review of 5 databases for all articles published until December 31, 2007: PubMed, Ovid MEDLINE, EMBASE, PsycINFO, and EBM Reviews. Under specific headings (eg, "heat shock proteins" and "oxidative stress"), a systematic search of these databases included such terms as HSP70 and homocysteine, and specific search strings were constructed. No limits were placed on the year or language of publication. References from pertinent articles or books were retrieved. STUDY SELECTION: We included 42 articles of human studies from 2,387 references originally retrieved. We included only articles that (1) were quantitative; (2) referred only to human tissue, in vivo, or in vitro; (3) stated what tissue was examined; (4) identified what metabolites were measured; and (5) had references. DATA EXTRACTION: All articles were assessed by 2 authors, which ensured that the inclusion criteria were met. The selected studies were too heterogeneous to be combined for any useful meta-analysis. Three authors, therefore, independently interpreted the data, using specified criteria to judge whether each study showed a beneficial, detrimental, or no effect on the markers measured. DATA SYNTHESIS: The analysis revealed no conclusive association with direct or indirect markers of oxidative cell stress and antipsychotics. For every reviewed antipsychotic, we revealed differing research results showing a beneficial, detrimental, or no effect. This was true for in vivo as well as in vitro studies. CONCLUSIONS: It remains unclear whether antipsychotics increase or reduce cell stress. Claims of neuroprotective properties of antipsychotics seem premature. (c) Copyright 2010 Physicians Postgraduate Press, Inc.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20673558&dopt=ExternalLink
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PMID: 20673558 [PubMed - as supplied by publisher]17: J Clin Psychiatry. 2010 Aug;71(8):1040-6. Epub 2010 Jul 13.
Meyer RE, Salzman C, Youngstrom EA, Clayton PJ, Goodwin FK, Mann JJ, Alphs LD, Broich K, Goodman WK, Greden JF, Meltzer HY, Normand SL, Posner K, Shaffer D, Oquendo MA, Stanley B, Trivedi MH, Turecki G, Beasley CM Jr, Beautrais AL, Bridge JA, Brown GK, Revicki DA, Ryan ND, Sheehan DV.
Best Practice Project Management, Inc, PO Box 30219, Bethesda, MD 20824, USA. rmeyer@best-practice.net
OBJECTIVE: To address issues concerning potential treatment-emergent "suicidality," a consensus conference was convened March 23-24, 2009. PARTICIPANTS: This gathering of participants from academia, government, and industry brought together experts in suicide prevention, clinical trial design, psychometrics, pharmacoepidemiology, and genetics, as well as research psychiatrists involved in studies in studies of psychiatric disorders associated with elevated suicide risk across the life cycle. The process involved reviews of the relevant literature, and a series of 6 breakout sessions focused on specific questions of interest. EVIDENCE: Each of the participants at the meeting received references relevant to the formal presentations (as well as the slides for the presentations) for their review prior to the meeting. In addition, the assessment instruments of suicidal ideation/behavior were reviewed in relationship to standard measures of validity, reliability, and clinical utility, and these findings were discussed at length in relevant breakout groups, in the final plenary session, and in the preparation of the article. Consensus and dissenting views were noted. CONSENSUS PROCESS: Discussion and questions followed each formal presentation during the plenary sessions. Approximately 6 questions per breakout group were prepared in advance by members of the Steering Committee and each breakout group chair. Consensus in the breakout groups was achieved by nominal group process. Consensus recommendations and any dissent were reviewed for each breakout group at the final plenary session. All plenary sessions were recorded and transcribed by a court stenographer. Following the transcript, with input by each of the authors, the final paper went through 14 drafts. The output of the meeting was organized into this brief report and the accompanying full article from which it is distilled. The full article was developed by the authors with feedback from all participants at the meeting and represents a consensus view. Any areas of disagreement at the conference have been noted in the text. CONCLUSIONS: The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's encouragement of standard definitions and definable expectations for investigators and industry sponsors. Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the requirement that all central nervous system clinical drug trials must include a Columbia Classification Algorithm of Suicide Assessment (C-CASA)-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed. Copyright 2010 Physicians Postgraduate Press, Inc.
Publication Types: Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20673551&dopt=ExternalLink
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PMID: 20673551 [PubMed - in process]18: J Clin Psychiatry. 2010 Jul 13; [Epub ahead of print]
Leon AC.
Weill Cornell Medical College, Department of Psychiatry, Box 140, 525 East 68th St, New York, NY 10065, USA. acleon@med.cornell.edu.
The National Institute of Mental Health Strategic Plan calls for the development of personalized treatment strategies for mental disorders. In an effort to achieve that goal, several investigators have conducted exploratory analyses of randomized controlled clinical trial (RCT) data to examine the association between baseline subject characteristics, the putative moderators, and the magnitude of treatment effect sizes. Exploratory analyses are used to generate hypotheses, not to confirm them. For that reason, independent replication is needed. Here, 2 general approaches to designing confirmatory RCTs are described that build on the results of exploratory analyses. These approaches address distinct questions. For example, a 2 x 2 factorial design provides an empirical test of the question, "Is there a greater treatment effect for those with the single-nucleotide polymorphism than for those without that polymorphism?" and the hypothesis test involves a moderator-by-treatment interaction. In contrast, a main effects strategy evaluates the intervention in subgroups and involves separate hypothesis-testing studies of treatment for subjects with the genotypes hypothesized to have enhanced and adverse response. These designs require widely disparate sample sizes to detect a given effect size. The former could need as many as 4-fold the number of subjects. As such, the choice of design impacts the research costs, clinical trial duration, and number of subjects exposed to risk of an experiment, as well as the generalizability of results. When resources are abundant, the 2 x 2 design is the preferable approach for identifying personalized interventions because it directly tests the differential treatment effect, but its demand on research funds is extraordinary. (c) Copyright 2010 Physicians Postgraduate Press, Inc.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20673550&dopt=ExternalLink
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PMID: 20673550 [PubMed - as supplied by publisher]19: J Clin Psychiatry. 2010 Jul;71(7):e15.
Gelenberg AJ.
Department of Psychiatry, Penn State College of Medicine, Hershey, Pennsylvania, USA.
A variety of American and European guidelines are available for clinicians treating major depressive disorder and depressive subtypes. Major Western guidelines published since 2000 make similar recommendations for all stages of treatment for depression, including a reliance on measurement-based care. First-line treatment is usually a serotonin reuptake inhibitor, psychotherapy, or a combination of pharmacotherapy and psychotherapy. Next-step treatment recommendations are switching or augmentation, depending on patient response to the initial treatment. Maintenance therapy continues the approach that led to remission. The American Psychiatric Association will release a new treatment guideline to offer information on developments made since the last guidelines were published in 2000. Despite progress made during the last decade, no major breakthroughs in the treatment of depression have occurred, and genetic testing developments allowing for personalized care remain the goal of research. (c) Copyright 2010 Physicians Postgraduate Press, Inc.
Publication Types: Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20667285&dopt=ExternalLink
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PMID: 20667285 [PubMed - indexed for MEDLINE]20: Psychol Med. 2010 Jul 21;:1-14 [Epub ahead of print]
Bourque F, van der Ven E, Malla A.
Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Canada.
BACKGROUND: There is increasing acceptance of migration as a risk factor for schizophrenia and related disorders; however, the magnitude of the risk among second-generation immigrants (SGIs) remains unclear. Generational differences in the incidence of psychotic disorders among migrants might improve our understanding of the relationship between migration, ethnicity and psychotic disorders. This meta-analysis aimed at determining the risk of psychotic disorders among SGIs in comparison with non-migrants and first-generation immigrants (FGIs).MethodMedline, EMBASE and PsycINFO databases were searched systematically for population-based studies on migration and psychotic disorders published between 1977 and 2008. We also contacted experts, tracked citations and screened bibliographies. All potential publications were screened by two independent reviewers in a threefold process. Studies were included in the meta-analysis if they reported incidence data, differentiated FGIs from SGIs and provided age-adjusted data. Data extraction and quality assessment were conducted for each study. RESULTS: Twenty-one studies met all inclusion criteria. A meta-analysis of 61 effect sizes for FGIs and 28 for SGIs yielded mean-weighted incidence rate ratios (IRRs) of 2.3 [95% confidence interval (CI) 2.0-2.7] for FGIs and 2.1 (95% CI 1.8-2.5) for SGIs. There was no significant risk difference between generations, but there were significant differences according to ethno-racial status and host country. CONCLUSIONS: The increased risk of schizophrenia and related disorders among immigrants clearly persists into the second generation, suggesting that post-migration factors play a more important role than pre-migration factors or migration per se. The observed variability suggests that the risk is mediated by the social context.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20663257&dopt=ExternalLink
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PMID: 20663257 [PubMed - as supplied by publisher]