Bipolar Disorder Research

 1: Am J Med Genet B Neuropsychiatr Genet. 2009 Jul 6. [Epub ahead of print]  Investigation of an epistastic effect between a set of TAAR6 and HSP-70 genes variations and major mood disorders.  Pae CU, Drago A, Forlani M, Patkar AA, Serretti A.  Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.  Epistasis, the interaction between genes, is a topic of current interest in molecular and quantitative genetics. We have further studied a previously investigated sample of 187 major depressive disorder (MDD) patients, 171 bipolar  disorder (BD) patients, and 288 controls, and tried to analyze the interaction between a set of variations of independent genes: the trace amine receptor 6 (rs4305745, rs8192625, rs7452939, rs6903874, and rs6937506) and the heat shock protein 70 (rs562047, rs1061581, rs2227956). The multifactor dimensionality reduction (MDR) method was applied and the covariates associated with diagnosis were also controlled. A significant predictive value of specific interactions between genotypes located in the investigated genes was found. We then report preliminary evidence that the epistasis between trace amine receptor 6 and heat shock protein 70 variations may compose a risk profile for major mood disorders.  The level of statistical significance (P < 0.001) and the testing balancing accuracy over 0.62 suggest a cautious optimism toward this result, although the possibility of false positivity warrants further analyses in independent samples. (c) 2009 Wiley-Liss, Inc.  PMID: 19582769 [PubMed - as supplied by publisher]  2: Am J Med Genet B Neuropsychiatr Genet. 2009 Jul 6. [Epub ahead of print]  Preliminary evidence of ubiquitin proteasome system dysregulation in schizophrenia and bipolar disorder: Convergent pathway analysis findings from two independent samples.  Bousman CA, Chana G, Glatt SJ, Chandler SD, Lucero GR, Tatro E, May T, Lohr JB, Kremen WS, Tsuang MT, Everall IP.  Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California.  Schizophrenia (SCZ) and bipolar disorder (BPD) are polygenic disorders with many  genes contributing to their etiologies. The aim of this investigation was to search for dysregulated molecular and cellular pathways for these disorders as well as psychosis. We conducted a blood-based microarray investigation in two independent samples with SCZ and BPD from San Diego (SCZ = 13, BPD = 9, control = 8) and Taiwan (SCZ = 11, BPD = 14, control = 16). Diagnostic groups were compared to controls, and subjects with a history of psychosis [PSYCH(+): San Diego (n = 6), Taiwan (n = 14)] were compared to subjects without such history [PSYCH(-): San Diego (n = 11), Taiwan (n = 14)]. Analyses of covariance comparing mean expression levels on a gene-by-gene basis were conducted to generate the top 100  significantly dysregulated gene lists for both samples by each diagnostic group.  Gene lists were imported into Ingenuity Pathway Analysis (IPA) software. Results  showed the ubiquitin proteasome pathway (UPS) was listed in the top ten canonical pathways for BPD and psychosis diagnostic groups across both samples with a considerably low likelihood of a chance occurrence (P = 0.001). No overlap in dysregulated genes populating these pathways was observed between the two independent samples. Findings provide preliminary evidence of UPS dysregulation in BPD and psychosis as well as support further investigation of the UPS and other molecular and cellular pathways for potential biomarkers for SCZ, BPD, and/or psychosis. (c) 2009 Wiley-Liss, Inc.  PMID: 19582768 [PubMed - as supplied by publisher]  3: Arch Gen Psychiatry. 2009 Jul;66(7):748-55.  Meta-analytic Evidence for Familial Coaggregation of Schizophrenia and Bipolar Disorder.  Van Snellenberg JX, de Candia T.  MA, MPhil, Department of Psychology, Columbia University, 406 Schermerhorn Hall,  1190 Amsterdam Ave, Mail Code 5501, New York, NY 10027. jared@psych.columbia.edu.  CONTEXT: Several data sources suggest a link between schizophrenia and bipolar disorder (BD); however, family studies have not revealed coaggregation of these disorders. OBJECTIVES: To systematically review family studies of probands with schizophrenia and BD and to determine whether these disorders coaggregate in families. DATA SOURCES: MEDLINE and PsycINFO databases. STUDY SELECTION: All family studies published from January 1, 1980, to December 31, 2006, reporting morbid risk or raw counts of schizophrenia or BD in first-degree relatives (FDRs) of a proband group with DSM-III or later; International Classification of Diseases, Ninth or Tenth Revision; or research diagnostic criteria schizophrenia  or BD were included. Of the original 2326 studies identified through the database search, 38 studies were used to investigate rates of BD in FDRs of probands with  schizophrenia, while 39 studies were used to examine rates of schizophrenia in FDRs of BD probands. DATA EXTRACTION: Data were analyzed with a novel random-effects bootstrapping technique that allows for the inclusion of studies lacking a patient or control group, which made up a substantial portion of the available data. Data were also blindly weighted for methodological quality. DATA  SYNTHESIS: The FDRs of probands with schizophrenia showed significantly (P = .01) increased rates of BD relative to control FDRs (odds ratio [OR] = 2.08). The FDRs of probands with BD showed marginally (P = .06) increased rates of schizophrenia  relative to control FDRs (OR = 2.10); this analysis was significant (P = .02) when studies that did not report morbid risk estimates were excluded (in this case, OR = 3.49). CONCLUSIONS: This meta-analysis provides direct evidence for familial coaggregation of schizophrenia and BD, a finding that argues against the view that these disorders are entirely discrete diagnostic entities. Rather, a continuum model is supported.  PMID: 19581566 [PubMed - in process]  4: Arch Gen Psychiatry. 2009 Jul;66(7):713-20.  Somatic hospital contacts, invasive cardiac procedures, and mortality from heart  disease in patients with severe mental disorder.  Laursen TM, Munk-Olsen T, Agerbo E, Gasse C, Mortensen PB.  National Centre for Register-Based Research, Aarhus University, Taasingegade 1, DK-8000 Aarhus C, Denmark. tml@ncrr.dk.  CONTEXT: Excess mortality from heart disease is observed in patients with severe  mental disorder. This excess mortality may be rooted in adverse effects of pharmacological or psychotropic treatment, lifestyle factors, or inadequate somatic care. OBJECTIVES: To examine whether persons with severe mental disorder, defined as persons admitted to a psychiatric hospital with bipolar affective disorder, schizoaffective disorder, or schizophrenia, are in contact with hospitals and undergoing invasive procedures for heart disease to the same degree as the nonpsychiatric general population, and to determine whether they have higher mortality rates of heart disease. Design, Setting, and PARTICIPANTS: A population-based cohort of 4.6 million persons born in Denmark was followed up from 1994 to 2007. Rates of mortality, somatic contacts, and invasive procedures  were estimated by survival analysis. MAIN OUTCOME MEASURES: Incidence rate ratios of heart disease admissions and heart disease mortality as well as probability of invasive cardiac procedures. RESULTS: The incidence rate ratio of heart disease contacts in persons with severe mental disorder compared with the rate for the nonpsychiatric general population was only slightly increased, at 1.11 (95% confidence interval, 1.08-1.14). In contrast, their excess mortality rate ratio from heart disease was 2.90 (95% confidence interval, 2.71-3.10). Five years after the first contact for somatic heart disease, the risk of dying of heart disease was 8.26% for persons with severe mental disorder (aged <70 years) but only 2.86% in patients with heart disease who had never been admitted to a psychiatric hospital. The fraction undergoing invasive procedures within 5 years  was reduced among patients with severe mental disorder as compared with the nonpsychiatric general population (7.04% vs 12.27%, respectively). CONCLUSIONS: Individuals with severe mental disorder had only negligible excess rates of contact for heart disease. Given their excess mortality from heart disease and lower rates of invasive procedures after first contact, it would seem that the treatment for heart disease offered to these individuals in Denmark is neither sufficiently efficient nor sufficiently intensive. This undertreatment may explain part of their excess mortality.  PMID: 19581562 [PubMed - in process]  5: Br J Clin Psychol. 2009 Jul 3. [Epub ahead of print]  Autobiographical memory specificity, depression, and trauma in bipolar disorder.  Mowlds W, Shannon C, McCusker CG, Meenagh C, Robinson D, Wilson A, Mulholland C.  Objectives In a bipolar disorder (BD) sample, the present study investigated: (i) the prevalence of trauma; (ii) the specificity of autobiographical memory (AM); (iii) the influence of childhood trauma on AM specificity, current inter-episode  depressive mood, and BD severity; (iv) if AM specificity moderates the influence  of childhood trauma on current inter-episode depressive mood and BD severity. Methods Fifty-two participants were recruited from a geographically well-defined  mental health service in Northern Ireland. The AM test, self-report measures of lifetime experience of trauma, childhood trauma, and depression were administered. Severity of BD was estimated utilizing a systematic tool for reviewing all available clinical data of participants. Results A high prevalence  of trauma was found. A total of 94.2% (49/52) of participants reported experiencing a traumatic event in either childhood or adulthood. AM specificity was significantly lower than previous reports of such in major depression. However, whilst childhood trauma predicted current inter-episode depressive mood, childhood trauma was not predictive of BD severity or AM specificity. Moreover, the association between childhood trauma and depressed mood was not moderated by  AM specificity. Conclusions The findings of this study suggest a relationship between early psychosocial adversity and current inter-episode depressive mood in BD. In addition, levels of overgeneral AM are similar to that reported for depression, but are unrelated to childhood trauma, current inter-episode depressive mood, or BD severity. Clinical implications include the importance of  routine assessment of trauma in BD and the need for adjunctive evidenced-based psychological therapies.  PMID: 19580704 [PubMed - as supplied by publisher] 

 1: J Neural Transm. 2009 Jul 4. [Epub ahead of print]  The Val/Met functional polymorphism in COMT confers susceptibility to bipolar disorder: evidence from an association study and a meta-analysis.  Zhang Z, Lindpaintner K, Che R, He Z, Wang P, Yang P, Feng G, He L, Shi Y.  Bio-X Center, Shanghai Jiao Tong University, PO Box 501, Haoran Building, 1954 Huashan Road, 200030, Shanghai, People's Republic of China, zuogouquan@hotmail.com.  The COMT gene is considered as one of the prominent candidate genes for susceptibility to BP, and most studies focused a functional polymorphism in the gene: the Val/Met polymorphism (rs4680). However, results from these studies are  sometimes contradictory, due to small sample size or heterogeneity. In this study, we first investigate the possible association between the Val/Met polymorphism in COMT and bipolar disorder in the Han population, which has never  been done before. Then a systematic meta-analysis was conducted to determine if the low-activity allele (Met) increases the risk of BP in different ethnic groups. A total of 478 BP patients and 469 healthy subjects were recruited in our case/control study. MIX software package was employed to perform the meta-analysis on 19 studies after careful search and selection. We observed statistically-significant differences in allele (p = 0.00060) and genotype (p = 0.00203) frequencies between patients and controls in our samples. The meta-analysis also provided a significant pooled OR for association of the Met allele in rs4680 with BP in the total population (p = 0.0223) and in the Asian population (p = 0.0232). Although a significant pooled OR was also found for the  Caucasian population (p = 0.0409) after one of the studies as discussed below was removed, the role for Val/Met polymorphism in BP in Caucasian ethnicity was not yet to be confirmed. In conclusion, the low-activity allele (Met) of rs4680 in COMT gene possibly confers risk for bipolar disorder in the Han population, while it needs further evidence for concluding its association with BP in the Caucasian population.  PMID: 19578924 [PubMed - as supplied by publisher]  2: Adicciones. 2009;21(2):167-72.  [Concomitant lithium and methadone treatment in a bipolar patient: a case report.]  [Article in Spanish]  Roncero C, López-Ortiz C, Barral C, Sáez-Francàs N, Rovira M, Casas M.  Dual diagnosis requires complex therapeutic approaches to adapt treatment to the  dual nature of the problem. It is important to understand the drug effects and the drug interactions that may be observed during the integral treatment of these pathologies. Given the scarcity of data on the effects of lithium and methadone treatment, the aim of this clinical case report is to explain the interactions produced between methadone and lithium carbonate, in a female patient with medical multi-pathology, opioid-dependent and with comorbid bipolar disorder, who was treated with both drugs. The most common adverse effects for each drug are described. Drug interactions and temporal correspondence of the two drugs, as well as their dosages, are described through review of the retrospective chart and prospective follow-up of the patient. After oneyear of follow-up the patient  had experienced no interactions in the concomitant lithium and methadone treatment. It should be noted that treatment of bipolar patients with dual diagnosis is complex, and should only be carried out by experts.  Publication Types:      English Abstract  PMID: 19578734 [PubMed - in process]  3: Rev Bras Psiquiatr. 2009 Jun;31(2):191-2.  Specific language impairment in an adult with type I bipolar disorder: a case report.  Mattos P, Rabelo B, Gueiros F, Soares T, Coutinho G.  Centro de Neuropsicologia Aplicada, Rio de Janeiro, RJ, Brazil.  PMID: 19578699 [PubMed - in process]  4: Rev Bras Psiquiatr. 2009 Jun;31(2):183-5.  [Neuropsychological aspects of bipolar disorder.]  [Article in Portuguese]  Malloy-Diniz LF, Neves F, Corrêa H.  Departamento de Psicologia, Faculdade de Filosofia e Ciências Humanas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.  PMID: 19578694 [PubMed - in process]  5: Rev Bras Psiquiatr. 2009 Jun;31(2):171-80.  Facial emotion recognition in bipolar disorder: a critical review.  Rocca CC, Heuvel E, Caetano SC, Lafer B.  Psychology and Neuropsychology Unit, Institute of Psychiatry, Medical School, Universidade de São Paulo, São Paulo, SP, Brazil.  OBJECTIVE: Literature review of the controlled studies in the last 18 years in emotion recognition deficits in bipolar disorder. METHOD: A bibliographical research of controlled studies with samples larger than 10 participants from 1990 to June 2008 was completed in Medline, Lilacs, PubMed and ISI. Thirty-two papers  were evaluated. RESULTS: Euthymic bipolar disorder presented impairment in recognizing disgust and fear. Manic BD showed difficult to recognize fearful and  sad faces. Pediatric bipolar disorder patients and children at risk presented impairment in their capacity to recognize emotions in adults and children faces.  Bipolar disorder patients were more accurate in recognizing facial emotions than  schizophrenic patients. DISCUSSION: Bipolar disorder patients present impaired recognition of disgust, fear and sadness that can be partially attributed to mood-state. In mania, they have difficult to recognize fear and disgust. Bipolar  disorder patients were more accurate in recognizing emotions than depressive and  schizophrenic patients. Bipolar disorder children present a tendency to misjudge  extreme facial expressions as being moderate or mild in intensity. CONCLUSION: Affective and cognitive deficits in bipolar disorder vary according to the mood states. Follow-up studies re-testing bipolar disorder patients after recovery are needed in order to investigate if these abnormalities reflect a state or trait marker and can be considered an endophenotype. Future studies should aim at standardizing task and designs.  PMID: 19578691 [PubMed - in process] 

 1: Int J Geriatr Psychiatry. 2009 Jul 2. [Epub ahead of print]  fMRI activation in late-life anxious depression: a potential biomarker.  Andreescu C, Butters M, Lenze EJ, Venkatraman VK, Nable M, Reynolds CF 3rd, Aizenstein HJ.  Department of Psychiatry, The Advanced Center in Interventions and Services Research for Late-Life Mood Disorders, University of Pittsburgh School of Medicine and the John A. Hartford Center of Excellence in Geriatric Psychiatry, Pittsburgh, PA, USA.  OBJECTIVE AND METHODS: The neurobiology of late-life anxious depression (LLAD) is poorly characterized despite evidence that this is a common and severe subtype of late-life depression. To identify the neuroanatomical substrate of LLAD, we examined event-related fMRI data collected in eight subjects with late-life depression, half of whom had high levels of comorbid anxiety. Subjects were trained on the Preparing to Overcome Prepotency (POP) task, which is an executive control task that reliably activates the lateral prefrontal cortex-anterior cingulate cortex (ACC) cognitive control circuit. RESULTS: Time series analysis showed that, when compared with elderly depressed subjects, elderly subjects with anxious depression performing the POP task produced a significantly greater and more sustained signal in three regions: BA24 (dorsal anterior cingulate), BA31 (posterior cingulate), and BA6 (prefrontal cortex). While elderly subjects with pure depression presented a bimodal activation curve in the dorsal anterior cingulate and the posterior cingulate, elderly subjects with anxious depression presented a sustained unimodal activation pattern. CONCLUSIONS: Our preliminary results suggest specific activation patterns unique to anxious depression that may suggest greater and more sustained efforts of the ACC to carry out cognitive  control tasks. Further research is needed to clarify the neuroanatomical basis of LLAD. Copyright (c) 2009 John Wiley & Sons, Ltd.  PMID: 19575412 [PubMed - as supplied by publisher]  2: J Investig Med. 2009 Jun 1. [Epub ahead of print]  Fragile X-Associated Tremor/Ataxia Syndrome: Clinical Phenotype, Diagnosis, and Treatment.  Leehey MA.  From the Department of Neurology, University of Colorado Denver, Aurora, CO.  Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG repeat expansion in the premutation range (55-200) in the fragile X mental retardation 1 gene. Onset is typically in the early seventh  decade, and men are principally affected. The major signs are cerebellar gait ataxia, intention tremor, frontal executive dysfunction, and global brain atrophy. Other frequent findings are parkinsonism (mild), peripheral neuropathy,  psychiatric symptoms (depression, anxiety, and agitation), and autonomic dysfunction. The clinical presentation is heterogeneous, with individuals presenting with varied dominating signs, such as tremor, dementia, or neuropathy. Magnetic resonance imaging shows atrophy and patchy white matter lesions in the cerebral hemispheres and middle cerebellar peduncles. The latter has been designated the middle cerebellar peduncle sign, which occurs in about 60% of affected men, and is relatively specific for FXTAS. Affected females generally have less severe disease, less cognitive decline, and some symptoms different from that of men, for example, muscle pain. Management of FXTAS is complex and includes assessment of the patient's neurological and medical deficits, treatment of symptoms, and provision of relevant referrals, especially genetic counseling.  Treatment is empirical, based on anecdotal experience and on knowledge of what works for symptoms of other disorders that also exist in FXTAS. Presently, the disorder is underrecognized because the first published report was only in 2001 and because the presentation is variable and mainly consists of a combination of  signs common in the elderly. However, accurate diagnosis is critical for the patient and for the family because they need education regarding their genetic and health risks.  PMID: 19574929 [PubMed - as supplied by publisher]  3: Acad Psychiatry. 2009 Summer;33(3):204-211.  Student Experiences with Competency Domains During a Psychiatry Clerkship.  West DA, Nierenberg DW.  Dartmouth Medical School, Psychiatry, DHMC -Psychiatry Level 2, # 1 Medical Center Dr., Lebanon, NH 03756; donald.west@dartmouth.edu.  OBJECTIVES: The authors reviewed medical student encounters during 3 years of a required psychiatry clerkship that were recorded on a web-based system of six broad competency domains (similar to ACGME-recommended domains). These were used  to determine diagnoses of patients seen, clinical skills practiced, and experiences in interpersonal and communications skills, professionalism, practice-based learning and improvement, and system-based practice. The authors aim to understand how students are learning and growing in these domains and to modify the clerkship in an ongoing manner. METHODS: Data were collected from the  Dartmouth Medical Encounter Documentation System (DMEDS) for all student encounters in required third-year psychiatry clerkships during academic years 2004-2007, in which students had intensive involvement in patient care. RESULTS:  One hundred seventy three students reported a total of 4,676 patient encounters,  averaging 27.2 encounters per student and 1.8 psychiatric diagnoses per patient.  Students met "learning targets" for anxiety disorder, bipolar affective disorder, depression, personality disorder (borderline), posttraumatic stress disorder, psychosis, schizophrenia, and substance abuse (alcohol), but not for disorders more likely seen in outpatient settings. For the 10 counseling skills learning targets, students only met those for family issues. In the four "newer" competency domains, students reported struggling with issues in 0.3% to 12.6% of  encounters. Students documented being challenged by professionalism issues most often and recorded examples of how these competencies played out for them during  the clerkship. CONCLUSION: Use of a required web-based medical encounter reporting system for student-patient-faculty encounters during a psychiatry clerkship can be of significant value in assessing what students are seeing, doing, and learning on this required third-year experience. The results provide helpful current information to the clerkship director and data that help the director modify the clerkship on an ongoing basis to better meet students' educational needs.  PMID: 19574516 [PubMed - as supplied by publisher]  4: J Psychiatr Res. 2009 Jun 30. [Epub ahead of print]  Social defeat stress produces prolonged alterations in acoustic startle and body  weight gain in male Long Evans rats.  Pulliam JV, Dawaghreh AM, Alema-Mensah E, Plotsky PM.  Neuroscience Institute, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta, GA 30310, United States.  Individuals exposed to psychological stressors may experience a long-term resetting of behavioral and neuroendocrine aspects of their "stress response" so  that they either hyper or hypo-respond to subsequent stressors. These effects of  psychological or traumatic stressors may be mimicked in rats using the resident-intruder model of social defeat. The social defeat model has been characterized to model aspects of the physiology and behavior associated with anxiety and depression. The objective of this study was to determine if behaviors elicited following repeated social defeat can also reflect aspects of ethologically relevant stresses associated with existing post traumatic stress disorder (PTSD) models. Socially defeated rats displayed weight loss and an enhanced and prolonged response to acoustic startle which was displayed for up to 10days following repeated social defeat. These data indicate that the severe stress of social defeat can produce physiologic and behavioral outcomes which may reflect aspects of traumatic psychosocial stress.  PMID: 19573876 [PubMed - as supplied by publisher]  5: J Clin Psychiatry. 2009 Jun;70(6):817-828.  Pegylated interferon and ribavirin-induced depression in chronic hepatitis c: role of personality.  Castellvi P, Navinés R, Gutierrez F, Jiménez D, Márquez C, Subirà S, Solà R, Martín-Santos R.  Liver Section the Department of Adults, Adolescents and Child Psychopathology, Facultat de Psicologia, Institut Clínic de Neurociències, Hospital Clínic, IDIBAPS, Barcelona, Spain.  OBJECTIVE: Pegylated interferon (PegIFN) and ribavirin (RBV) treatment for the hepatitis C virus (HCV) infection can induce depressive episodes. Personality traits have been associated with mood disorders. The aim of this study was to evaluate the personality profile as a risk factor for induced depression by PegIFN and RBV treatment in patients with HCV. METHOD: In a prospective cohort study, 204 consecutive HCV outpatients who received PegIFN and RBV were assessed  using the Structured Clinical Interview for DSM-IV Axis I Disorders and the Temperament and Character Inventory-Revised (TCI-R). Moreover, the Patient Health Questionnaire and the Hospital Anxiety and Depression Scale were administered at  baseline and at 4, 12, 24, and/or 48 weeks of treatment. Patients were recruited  between September 2003 and December 2006. RESULTS: One hundred eighteen patients  (57.8%) were men. The mean (SD) age was 44.39 (10.4) years. The incidence of induced depression during the 48 weeks of antiviral treatment was 73 (42%). Low self-directedness dimension (HR = 0.63, 95% CI = 0.446 to 0.890, p = .009), baseline subclinical depression levels (HR = 1.113, 95% CI = 1.023 to 1.22, p = .013), and history of mood disorders (HR = 0.372, 95% CI = 0.220 to 0.629, p <.001) were independent predictive factors for induced depression during PegIFN and RBV treatment. Other predictive personality TCI-R subscales were enlightened  second nature (HR = 2.939, 95% CI = 1.423 to 6.071, p = .004), fatigability (HR = 0.421, 95% CI = 0.237 to 0.749, p = .01), and disorderliness (HR = 0.449, 95% CI  = 0.248 to 0.815, p = .008). CONCLUSION: Low self-directedness, depressive symptoms at baseline, and history of previous mood disorders may predict induced  depression by PegIFN and RBV in euthymic HCV patients. © Copyright 2009 Physicians Postgraduate Press, Inc.  PMID: 19573480 [PubMed - as supplied by publisher] 

 1: Acad Psychiatry. 2009 Summer;33(3):204-211.  Student Experiences with Competency Domains During a Psychiatry Clerkship.  West DA, Nierenberg DW.  Dartmouth Medical School, Psychiatry, DHMC -Psychiatry Level 2, # 1 Medical Center Dr., Lebanon, NH 03756; donald.west@dartmouth.edu.  OBJECTIVES: The authors reviewed medical student encounters during 3 years of a required psychiatry clerkship that were recorded on a web-based system of six broad competency domains (similar to ACGME-recommended domains). These were used  to determine diagnoses of patients seen, clinical skills practiced, and experiences in interpersonal and communications skills, professionalism, practice-based learning and improvement, and system-based practice. The authors aim to understand how students are learning and growing in these domains and to modify the clerkship in an ongoing manner. METHODS: Data were collected from the  Dartmouth Medical Encounter Documentation System (DMEDS) for all student encounters in required third-year psychiatry clerkships during academic years 2004-2007, in which students had intensive involvement in patient care. RESULTS:  One hundred seventy three students reported a total of 4,676 patient encounters,  averaging 27.2 encounters per student and 1.8 psychiatric diagnoses per patient.  Students met "learning targets" for anxiety disorder, bipolar affective disorder, depression, personality disorder (borderline), posttraumatic stress disorder, psychosis, schizophrenia, and substance abuse (alcohol), but not for disorders more likely seen in outpatient settings. For the 10 counseling skills learning targets, students only met those for family issues. In the four "newer" competency domains, students reported struggling with issues in 0.3% to 12.6% of  encounters. Students documented being challenged by professionalism issues most often and recorded examples of how these competencies played out for them during  the clerkship. CONCLUSION: Use of a required web-based medical encounter reporting system for student-patient-faculty encounters during a psychiatry clerkship can be of significant value in assessing what students are seeing, doing, and learning on this required third-year experience. The results provide helpful current information to the clerkship director and data that help the director modify the clerkship on an ongoing basis to better meet students' educational needs.  PMID: 19574516 [PubMed - as supplied by publisher]  2: Drug Alcohol Depend. 2009 Jun 30. [Epub ahead of print]  A "community-friendly" version of integrated group therapy for patients with bipolar disorder and substance dependence: A randomized controlled trial.  Weiss RD, Griffin ML, Jaffee WB, Bender RE, Graff FS, Gallop RJ, Fitzmaurice GM.  Department of Psychiatry, Harvard Medical School, Boston, MA 02115, United States; Division of Alcohol and Drug Abuse, McLean Hospital, Belmont, MA 02478, United States.  BACKGROUND: Integrated group therapy, a new treatment for patients with bipolar disorder and substance use disorder, has previously been found to be efficacious  in reducing substance use, but its length (20 sessions) and need for highly trained therapists may limit its adoption in substance use disorder community treatment programs. This paper compares a briefer (12 session) version of integrated group therapy, led by substance use disorder counselors without previous cognitive-behavioral training or bipolar disorder experience, to group drug counseling. METHODS: Sixty-one patients with bipolar disorder and substance  dependence, taking mood stabilizers, were randomized to 12 sessions of integrated group therapy (n=31) or group drug counseling (n=30). RESULTS: Analyses of primary outcomes showed trends favoring integrated group therapy, with greater reduction in substance use during follow-up and a greater decline in risk of mood episodes during treatment. Secondary analyses favored integrated group therapy, with a significantly greater likelihood of achieving total abstinence, a significantly shorter time to the first abstinent month, and a significantly greater likelihood of achieving a "good clinical outcome" (a composite measure encompassing both substance use and mood simultaneously). CONCLUSIONS: A shortened version of integrated group therapy can be delivered successfully by substance use disorder counselors, with better overall outcomes than those achieved with group drug counseling.  PMID: 19573999 [PubMed - as supplied by publisher]  3: J Clin Psychiatry. 2009 Jun 30. [Epub ahead of print]  Is psychopharmacologic treatment associated with neuropsychological deficits in bipolar youth?  Henin A, Mick E, Biederman J, Fried R, Hirshfeld-Becker DR, Micco JA, Miller KG,  Rycyna CC, Wozniak J.  Pediatric Psychopharmacology Unit, Massachusetts General Hospital, 185 Alewife Brook Pkwy, Suite 2000, Cambridge, MA 02138, USA. ahenin@partners.org.  OBJECTIVE: To evaluate the impact of psychopharmacologic treatments on neuropsychological functioning in bipolar youth. METHOD: Participants were 173 children (aged 6-17 years) with DSM-IV bipolar disorder. Participants were comprehensively assessed using structured diagnostic interviews (Schedule for Affective Disorders and Schizophrenia for School-Age Children) and neuropsychological measures (eg, subtests of the Wechsler Intelligence Scale for  Children-III and Wechsler Adult Intelligence Scale-III) during the years 2001-2006. Comparisons were made in neuropsychological functioning between medicated and unmedicated youth with bipolar disorder. RESULTS: Children who were treated with mood stabilizers performed significantly (P < .05) more poorly than  untreated children on measures of processing speed and working memory. Treatment  with other classes of medication, including second-generation antipsychotics, was not significantly associated with neuropsychological impairments. CONCLUSIONS: Treatment with mood stabilizers may be associated with specific neuropsychological impairments. Cognitive side effects may need to be considered  in selecting particular psychopharmacologic treatments for children with bipolar  disorder. © Copyright 2009 Physicians Postgraduate Press, Inc.  PMID: 19573494 [PubMed - as supplied by publisher]  4: J Clin Psychiatry. 2009 Jun;70(6):e17.  Overview of managing medical comorbidities in patients with severe mental illness.  McIntyre RS.  Department of Psychiatry and Pharmacology, University of Toronto, and the Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.  Patients with severe mental disorders have increased mortality rates compared with the general population. The leading cause of death for individuals with psychotic illnesses or bipolar disorder is cardiovascular disease (CVD), which is often the result of patients' health problems associated with their psychiatric disorders, including, but not limited to, obesity, metabolic syndrome, and diabetes. Such problems occur more often and have worse outcomes in patients with serious mental illness than the general population because of a combination of factors such as inadequate access to quality care, poor lifestyle choices, and the association between some antipsychotic medications and weight gain. Coordinated somatic and psychiatric treatment, weight-neutral or weight-reducing  pharmaceuticals, and behavioral weight management programs may help lessen the burden of CVD in the mental health population. © Copyright 2009 Physicians Postgraduate Press, Inc.  PMID: 19573473 [PubMed - as supplied by publisher]  5: Br J Clin Psychol. 2009 Jul 1. [Epub ahead of print]  Defence and coping in bipolar affective disorder: Stability and change of adaptational processes.  Kramer U.  Objectives Defence mechanisms and coping have rarely been investigated from an integrative point of view. We are particularly interested in stability and change of these adaptational processes in clinical crisis situations of in-patients presenting with bipolar affective disorder. Design We conducted a controlled interview study including an in-patient and a matched control group; longitudinal data are provided by follow-up interviewing for all participants. Methods A total of N=18 participants per group (patients presenting with bipolar affective disorder and non-clinical controls) were recruited and interviewed twice. All interviews were transcribed and analysed according to observer-rater systems for  coping (Coping Action Patterns) and defence mechanisms (Defence Mechanism Rating  Scales). Symptom check list-90-R, as well as specific symptomatic measures, were  used for symptomatic assessment and hierarchical linear modelling was used for statistical computation. Results Overall, defensive functioning remains stable over a 3 month period, whereas overall, coping functioning increases over the same period in-patients, as they are discharged from in-patient treatment; no such effect was found in controls. Conclusions Overall, stability in adaptational processes may be attributed to defensive functioning, whereas change over short periods of time are related to coping concepts in in-patients presenting with bipolar affective disorder.  PMID: 19573282 [PubMed - as supplied by publisher] 

 1: J Clin Psychol. 2009 Jul 1. [Epub ahead of print]  Cognitive-behavioral therapy of delusions: mental imagery within a goal-directed  framework.  Serruya G, Grant P.  University of Pennsylvania.  Central to psychotic disorders, delusions are associated with disability and often respond inadequately to pharmacotherapy. Cognitive-behavioral treatments have been developed over the last 20 years that successfully address delusions. However, meta-analyses suggest only a modest improvement in psychotic symptoms. Because delusions share considerable overlap with anxiety, adapting principles and techniques that have demonstrated efficacy in the treatment of anxiety disorders might improve the impact of cognitive-behavioral treatment of delusions. We report a case illustrating a cognitive-behavioral approach to delusions with an emphasis on mental imagery techniques. A 25-year-old male diagnosed with paranoid schizophrenia whose clinical presentation was dominated by paranoid delusions received 6 months of treatment. At the end of the follow-up period, the patient's delusions were minimal and his negative symptoms had significantly improved. Mental imagery may be an important treatment tool for delusions. (c) 2009 Wiley Periodicals, Inc. J Clin Psychol: In Session 65:1-12, 2009.  PMID: 19572276 [PubMed - as supplied by publisher]  2: Eur Arch Psychiatry Clin Neurosci. 2009 Jul 2. [Epub ahead of print]  Type of residual symptom and risk of relapse during the continuation/maintenance  phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine.  Yang H, Chuzi S, Sinicropi-Yao L, Johnson D, Chen Y, Clain A, Baer L, McGrath PJ, Stewart JW, Fava M, Papakostas GI.  Department of Psychiatry, Depression Clinical and Research Program at Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, WACC 812, Boston, MA, 02114, USA, hyang7@partners.org.  Relapse of major depressive disorder (MDD) is a common clinical problem. Identifying relapse predictors could lead to strategies that reduce relapse risk. This study is designed to determine whether residual symptoms predict relapse risk during the continuation/maintenance treatment of MDD. 570 MDD patients received open-label fluoxetine for 12 weeks. Under double blind conditions, 262 patients who responded by week 12 were randomly assigned to continue fluoxetine or switch to placebo for 52 weeks or until relapse. Residual symptoms were measured using the Symptom Checklist-90 and the Symptom Questionnaire. The relationship between residual symptom severity and relapse risk was assessed. Without adjusting for overall residual symptom severity, a greater severity of residual obsessive-compulsive and phobic anxiety symptoms predicted greater relapse risk. After adjusting for overall residual symptom severity, only severity of phobic anxiety symptoms predicted relapse risk. The predictive value  of phobic anxiety symptoms with respect to relapse risk was independent of treatment assignment. The results indicated that there may be a specific pattern  of residual symptoms associated with depressive relapse during antidepressant continuation/maintenance, which is unrelated to treatment assignment. Future studies are needed to further explore the relationship between residual symptoms  and relapse risk in MDD. Clinical implications: (1) It is important to treat residual symptoms among antidepressant responders/remitters in order to decrease  relapse risk. (2) Clinicians should target residual phobic anxiety symptoms in order to decrease relapse risk. (3) Clinicians should target residual obsessive-compulsive symptoms in order to decrease relapse risk. Limitations: (1) limited generalizability due to inclusion/exclusion criteria; (2) lack of active  comparator treatment group; (3) post hoc analysis.  PMID: 19572158 [PubMed - as supplied by publisher]  3: Eur Neurol. 2009 Jul 1;62(3):130-136. [Epub ahead of print]  Relationship between Psychosocial Factors and Onset of Multiple Sclerosis.  Liu XJ, Ye HX, Li WP, Dai R, Chen D, Jin M.  Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.  Objective: The aim of this study was to investigate the influence of psychosocial variables on patients with multiple sclerosis (MS) and the relationship between these variables and the onset of MS. Background: The current evidence indicates that many types of psychosocial factors are involved in the development and relapse of MS, and it has been suggested that they could serve as predictors as well. So far, little has been reported on the effect of psychosocial factors on MS and the relationship between psychosocial factors and the onset of MS. Methods: Forty-one patients, 15 males and 26 females, average age 37.44 +/- 12.24 years (mean +/- SD), were evaluated by the Life Event Scale, Eysenck Personality  Questionnaire, Social Support Revaluate Scale and Symptom Check List 90 and compared with 41 equivalent healthy control subjects, 15 males and 26 females, average age 36.38 +/- 12.84 years (mean +/- SD). Disease, demographic, psychosocial and lifestyle factors were measured at baseline. Patients with MS were first diagnosed by 3 neurologists according to the Poser (1983) MS diagnostic criteria. Results: Significant differences were found between the MS and the control group in their negative emotions and symptoms such as depression, anxiety, obsession, phobia, tense interpersonal relationship and somatization disorder. Significant differences were found between the two groups in the total  number of negative life events, their family problems and the utilization of social support. The scores for various negative emotions in the MS group correlated positively with those for neuroticisms in personality type, and negatively with those for introverted and extroverted personality. Many kinds of  negative emotions in the MS group correlated positively with the total number of  life events, negative life events and family problems. Many kinds of negative emotions in the MS group correlated negatively with the utilization of social support. Conclusion: The psychosocial factors are closely associated with MS onset and may play important roles in the development of the disease. Copyright © 2009 S. Karger AG, Basel.  PMID: 19571540 [PubMed - as supplied by publisher]  4: Am J Psychiatry. 2009 Jul;166(7):762-7.  Diagnosis and treatment of PTSD-related compulsive checking behaviors in veterans of the Iraq war: the influence of military context on the expression of PTSD symptoms.  Tuerk PW, Grubaugh AL, Hamner MB, Foa EB.  Charleston VAMC, Mental Health 116, 109 Bee St., Charleston, SC 29401, USA. Tuerk@musc.edu  This case study presents an overview of the conceptualization and treatment of two veterans of the Iraq War who presented for combat-related treatment at a Veterans Administration Medical Center. In addition to posttraumatic stress disorder (PTSD) symptoms of reexperiencing, arousal, and avoidance, the veterans  exhibited compulsive checking behaviors that appear to be influenced by theater-specific combat duties and traumatic events. These cases represent what the authors believe to be an increasingly common expression of PTSD in veterans of the Iraq and Afghanistan wars. Both veterans were treated with prolonged exposure therapy, which includes imaginal and in vivo exposure to anxiety-provoking stimuli, processing of traumatic events, and self-assessment of anxiety. Treatment also included in vivo exposure with response prevention techniques borrowed from the literature on obsessive-compulsive disorder to address compulsive checking behaviors within the ecological context of each patient's symptom presentation. Measures related to PTSD and depression were obtained before, during, and after treatment. Treatment was associated with significant declines in symptom severity and improved functioning for both veterans. The unique nature of the conflict in the Middle East represents role challenges for soldiers that affect symptom presentation. Variations in symptom presentation can in turn complicate efforts to identify and appropriately address PTSD-related health concerns in this population. Thus, clinicians and researchers must remain cognizant of how theater-specific duties influence the manifestation  and treatment of PTSD in order to provide optimal care to a new generation of veterans.  Publication Types:      Research Support, Non-U.S. Gov't  PMID: 19570938 [PubMed - in process]  5: Am J Psychiatry. 2009 Jul 1. [Epub ahead of print]  Adult Outcomes of Youth Irritability: A 20-Year Prospective Community-Based Study.  Stringaris A, Cohen P, Pine DS, Leibenluft E.  Objective Irritability is a widely occurring DSM-IV symptom in youths. However, little is known about the relationship between irritability in early life and its outcomes in mid-adulthood. This study examines the extent to which youth irritability is related to adult psychiatric outcomes by testing the hypothesis that it predicts depressive and generalized anxiety disorders. Method The authors conducted a longitudinal community-based study of 631 participants whose parents  were interviewed when participants were in early adolescence (mean age=13.8 years [SD=2.6]) and who were themselves interviewed 20 years later (mean age=33.2 years [SD=2.9]). Parent-reported irritability in adolescence was used to predict self-reported psychopathology, assessed by standardized diagnostic interview at 20-year follow-up. Results Cross-sectionally, irritability in adolescence was widely associated with other psychiatric disorders. After adjustment for baseline emotional and behavioral disorders, irritability in adolescence predicted major depressive disorder (odds ratio=1.33, 95% confidence interval [CI]=1.00-1.78]), generalized anxiety disorder (odds ratio=1.72, 95% CI=1.04-2.87), and dysthymia (odds ratio=1.81, 95% CI=1.06-3.12) at 20-year follow-up. Youth irritability did  not predict bipolar disorder or axis II disorders at follow-up. Conclusions Youth irritability as reported by parents is a specific predictor of self-reported depressive and anxiety disorders 20 years later. The role of irritability in developmental psychiatry, and in the pathophysiology of mood and anxiety disorders specifically, should receive further study.  PMID: 19570932 [PubMed - as supplied by publisher] 

 1: Nature. 2009 Jul 1. [Epub ahead of print]  Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.  The International Schizophrenia Consortium; Manuscript preparation, Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P; Data analysis, Purcell Leader SM, Stone JL; GWAS analysis subgroup, Sullivan PF, Ruderfer DM, McQuillin A, Morris DW, O'Dushlaine CT, Corvin A, Holmans PA, O'Donovan MC, Sklar P; Polygene analyses subgroup, Wray NR, Macgregor S, Sklar P, Sullivan PF, O'Donovan MC, Visscher PM; Management committee, Gurling H, Blackwood DH, Corvin A, Craddock NJ, Gill M, Hultman CM, Kirov GK, Lichtenstein P, McQuillin A, Muir WJ, O'Donovan MC, Owen MJ, Pato CN, Purcell SM, Scolnick EM, St Clair D, Stone JL, Sullivan PF, Sklar Leader P; Cardiff University, O'Donovan  MC, Kirov GK, Craddock NJ, Holmans PA, Williams NM, Georgieva L, Nikolov I, Norton N, Williams H, Toncheva D, Milanova V, Owen MJ; Karolinska Institutet/University of North Carolina at Chapel Hill, Hultman CM, Lichtenstein  P, Thelander EF, Sullivan P; Trinity College Dublin, Morris DW, O'Dushlaine CT, Kenny E, Quinn EM, Gill M, Corvin A; University College London, McQuillin A, Choudhury K, Datta S, Pimm J, Thirumalai S, Puri V, Krasucki R, Lawrence J, Quested D, Bass N, Gurling H; University of Aberdeen, Crombie C, Fraser G, Leh Kuan S, Walker N, St Clair D; University of Edinburgh, Blackwood DH, Muir WJ, McGhee KA, Pickard B, Malloy P, Maclean AW, Van Beck M; Queensland Institute of Medical Research, Wray NR, Macgregor S, Visscher PM; University of Southern California, Pato MT, Medeiros H, Middleton F, Carvalho C, Morley C, Fanous A, Conti D, Knowles JA, Paz Ferreira C, Macedo A, Helena Azevedo M, Pato CN; Massachusetts General Hospital, Stone JL, Ruderfer DM, Kirby AN, Ferreira MA, Daly MJ, Purcell SM, Sklar P; Stanley Center for Psychiatric Research and Broad Institute of MIT and Harvard, Purcell SM, Stone JL, Chambert K, Ruderfer DM, Kuruvilla F, Gabriel SB, Ardlie K, Moran JL, Daly MJ, Scolnick EM, Sklar P.  [1] Psychiatric and Neurodevelopmental Genetics Unit, [2] Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.  Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%. We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands  of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.  PMID: 19571811 [PubMed - as supplied by publisher]  2: J Toxicol Sci. 2009;34(Special_):SP293-SP305.  Intrauterine environment-genome interaction and Children's development (4): Brain-behavior phenotypying of genetically-engineered mice using a comprehensive  behavioral test battery on research of neuropsychiatric disorders.  Takao K, Miyakawa T.  Division of Systems Medicine, Institute for Comprehensive Medical Science, Fujita Health University.  Despite massive research efforts, the exact pathogenesis and pathophysiology of psychiatric disorders, such as schizophrenia and bipolar disorder, remain largely unknown. Animal models can serve as essential tools for investigating the etiology and treatment of such disorders. Some mutant mouse strains were found to exhibit behavioral abnormalities reminiscent of human psychiatric disorders. Here we outline our unique approach of extrapolating findings in mice to humans, and present studies on alpha-CaMKII heterozygous knockout (alpha-CaMKII+/-) mice as examples. Alpha-CaMKII+/- mice have profoundly dysregulated behaviorbehaviours and impaired neuronal development in the dentate gyrus (DG). The behavioral abnormalities include a severe working memory deficit and an exaggerated infradian rhythm, which are similar to symptoms seen in schizophrenia, bipolar mood disorder and other psychiatric disorders. By conducting a series of experiments, we discovered that almost all the neurons in the mutant DG were very similar to the immature DG neurons of normal rodents. In other words, alpha-CaMKII+/- mice have an "immature DG". We proposed that an "immature DG" in  adulthood might induce alterations in behavior and serve as a promising candidate endophenotype* of schizophrenia and other human psychiatric disorders. The impact of a large-scale mouse phenotyping on studies of psychiatric disorders and the potential utility of an "animal-model-array" of psychiatric disorders for the development of suitable therapeutic agents is also discussed.  PMID: 19571483 [PubMed - as supplied by publisher]  3: Am J Psychiatry. 2009 Jul 1. [Epub ahead of print]  Adult Outcomes of Youth Irritability: A 20-Year Prospective Community-Based Study.  Stringaris A, Cohen P, Pine DS, Leibenluft E.  Objective Irritability is a widely occurring DSM-IV symptom in youths. However, little is known about the relationship between irritability in early life and its outcomes in mid-adulthood. This study examines the extent to which youth irritability is related to adult psychiatric outcomes by testing the hypothesis that it predicts depressive and generalized anxiety disorders. Method The authors conducted a longitudinal community-based study of 631 participants whose parents  were interviewed when participants were in early adolescence (mean age=13.8 years [SD=2.6]) and who were themselves interviewed 20 years later (mean age=33.2 years [SD=2.9]). Parent-reported irritability in adolescence was used to predict self-reported psychopathology, assessed by standardized diagnostic interview at 20-year follow-up. Results Cross-sectionally, irritability in adolescence was widely associated with other psychiatric disorders. After adjustment for baseline emotional and behavioral disorders, irritability in adolescence predicted major depressive disorder (odds ratio=1.33, 95% confidence interval [CI]=1.00-1.78]), generalized anxiety disorder (odds ratio=1.72, 95% CI=1.04-2.87), and dysthymia (odds ratio=1.81, 95% CI=1.06-3.12) at 20-year follow-up. Youth irritability did  not predict bipolar disorder or axis II disorders at follow-up. Conclusions Youth irritability as reported by parents is a specific predictor of self-reported depressive and anxiety disorders 20 years later. The role of irritability in developmental psychiatry, and in the pathophysiology of mood and anxiety disorders specifically, should receive further study.  PMID: 19570932 [PubMed - as supplied by publisher]  4: Schizophr Res. 2009 Jun 29. [Epub ahead of print]  Serotonergic hyperinnervation and effective serotonin blockade in an FGF receptor developmental model of psychosis.  Klejbor I, Kucinski A, Wersinger SR, Corso T, Spodnik JH, Dziewiątkowski J, Moryś J, Hesse RA, Rice KC, Miletich R, Stachowiak EK, Stachowiak MK.  Department of Pathology and Anatomical Sciences, SUNY, Buffalo, NY, USA; Department of Anatomy and Neurobiology, Medical University of Gdańsk, Poland.  The role of fibroblast growth factor receptors (FGFR) in normal brain development has been well-documented in transgenic and knock-out mouse models. Changes in FGF and its receptors have also been observed in schizophrenia and related developmental disorders. The current study examines a transgenic th(tk-)/th(tk-)  mouse model with FGF receptor signaling disruption targeted to dopamine (DA) neurons, resulting in neurodevelopmental, anatomical, and biochemical alterations similar to those observed in human schizophrenia. We show in th(tk-)/th(tk-) mice that hypoplastic development of DA systems induces serotonergic hyperinnervation  of midbrain DA nuclei, demonstrating the co-developmental relationship between DA and 5-HT systems. Behaviorally, th(tk-)/th(tk-) mice displayed impaired sensory gaiting and reduced social interactions correctable by atypical antipsychotics (AAPD) and a specific 5-HT2A antagonist, M100907. The adult onset of neurochemical and behavioral deficits was consistent with the postpubertal time course of psychotic symptoms in schizophrenia and related disorders. The spectrum of abnormalities observed in th(tk-)/th(tk-) mice and the ability of AAPD to correct the behavioral deficits consistent with human psychosis suggests that midbrain 5-HT2A-controlling systems are important loci of therapeutic action. These results may provide further insight into the complex multi-neurotransmitter etiology of neurodevelopmental diseases such autism, bipolar disorder, Asperger's Syndrome and schizophrenia.  PMID: 19570652 [PubMed - as supplied by publisher] 

 1: J Psychiatry Neurosci. 2009 Jul;34(4):263-271.  3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder.  Andreazza AC, Kapczinski F, Kauer-Sant'anna M, Walz JC, Bond DJ, Gonçalves CA, Young LT, Yatham LN.  Andreazza, Kauer-Sant'Anna, Bond, Young, Yatham - Department of Psychiatry, University of British Columbia, Vancouver, BC; Andreazza, Gonçalves - Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul; Kapczinski, Kauer-Sant'Anna, Walz - Laboratório de Psiquiatria Molecular, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.  BACKGROUND: There has been an increasing interest in the role of oxidative stress in the pathophysiology of bipolar disorder. To explore this further, we evaluated the activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST), as well as 3-nitrotyrosine levels and carbonyl content in patients in the early (within 3 years of illness onset) and late (a minimum of 10 years of illness) stages of bipolar disorder. METHODS: We matched 30 patients in the early stage and 30 patients in the late stage of bipolar disorder, diagnosed according to DSM-IV criteria, with 60 healthy controls (30 matched for each group of patients). We measured symptomatic status using the Hamilton Rating Scale for Depression and the Young Mania Rating Scale. RESULTS: We found a significant increase in 3-nitrotyrosine levels among patients in the early (p < 0.010) and late (p < 0.010) stages of bipolar disorder. The activity of GR and GST was increased only among patients in the late stage of illness. Glutathione peroxidase activity and carbonyl content did not differ among the groups. LIMITATIONS: Limitations of our study include its cross-sectional design, which did not allow us to examine direct causative mechanisms or the effects of progression of illness, and the potential environmental bias introduced by comparing patient groups recruited from different regions of the world. CONCLUSION: Our data indicate a possible tyrosine nitration-induced damage in patients with bipolar disorder that is present from the early stage of illness. Our data also indicate that patients in the late stage of illness demonstrate enhanced activity of GR and GST, which could suggest the involvement of a compensatory system in bipolar disorder.  PMID: 19568477 [PubMed - as supplied by publisher]  2: Br J Psychiatry. 2009 Jul;195(1):67-72.  Patterns of neurocognitive impairment in first-episode bipolar disorder and schizophrenia.  Barrett SL, Mulholland CC, Cooper SJ, Rushe TM.  Division of Psychiatry and Neuroscience, Queens University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, UK. s.l.barrett@qub.ac.uk  BACKGROUND: Researching psychotic disorders in unison rather than as separate diagnostic groups is widely advocated, but the viability of such an approach requires careful consideration from a neurocognitive perspective. AIMS: To describe cognition in people with bipolar disorder and schizophrenia and to examine how known causes of variability in individual's performance contribute to any observed diagnostic differences. METHOD: Neurocognitive functioning in people with bipolar disorder (n = 32), schizophrenia (n = 46) and healthy controls (n =  67) was compared using analysis of covariance on data from the Northern Ireland First Episode Psychosis Study. RESULTS: The bipolar disorder and schizophrenia groups were most impaired on tests of memory, executive functioning and language. The bipolar group performed significantly better on tests of response inhibition, verbal fluency and callosal functioning. Between-group differences could be explained by the greater proclivity of individuals with schizophrenia to experience global cognitive impairment and negative symptoms. CONCLUSIONS: Particular impairments are common to people with psychosis and may prove useful as endophenotypic markers. Considering the degree of individuals' global cognitive impairment is critical when attempting to understand patterns of selective impairment both within and between these diagnostic groups.  Publication Types:      Research Support, Non-U.S. Gov't  PMID: 19567899 [PubMed - in process]  3: Br J Psychiatry. 2009 Jul;195(1):23-9.  Genetic utility of broadly defined bipolar schizoaffective disorder as a diagnostic concept.  Hamshere ML, Green EK, Jones IR, Jones L, Moskvina V, Kirov G, Grozeva D, Nikolov I, Vukcevic D, Caesar S, Gordon-Smith K, Fraser C, Russell E, Breen G, St Clair D, Collier DA, Young AH, Ferrier IN, Farmer A, McGuffin P; Wellcome Trust Case Control Consortium, Holmans PA, Owen MJ, O'Donovan MC, Craddock N.  Biostatistics and Bioinformatics Unit and Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.  BACKGROUND: Psychiatric phenotypes are currently defined according to sets of descriptive criteria. Although many of these phenotypes are heritable, it would be useful to know whether any of the various diagnostic categories in current use identify cases that are particularly helpful for biological-genetic research. AIMS: To use genome-wide genetic association data to explore the relative genetic utility of seven different descriptive operational diagnostic categories relevant to bipolar illness within a large UK case-control bipolar disorder sample. METHOD: We analysed our previously published Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder genome-wide association data-set, comprising  1868 individuals with bipolar disorder and 2938 controls genotyped for 276 122 single nucleotide polymorphisms (SNPs) that met stringent criteria for genotype quality. For each SNP we performed a test of association (bipolar disorder group  v. control group) and used the number of associated independent SNPs statistically significant at P<0.00001 as a metric for the overall genetic signal in the sample. We next compared this metric with that obtained using each of seven diagnostic subsets of the group with bipolar disorder: Research Diagnostic  Criteria (RDC): bipolar I disorder; manic disorder; bipolar II disorder; schizoaffective disorder, bipolar type; DSM-IV: bipolar I disorder; bipolar II disorder; schizoaffective disorder, bipolar type. RESULTS: The RDC schizoaffective disorder, bipolar type (v. controls) stood out from the other diagnostic subsets as having a significant excess of independent association signals (P<0.003) compared with that expected in samples of the same size selected randomly from the total bipolar disorder group data-set. The strongest association in this subset of participants with bipolar disorder was at rs4818065 (P = 2.42 x 10(-7)). Biological systems implicated included gamma amniobutyric acid (GABA)(A) receptors. Genes having at least one associated polymorphism at P<10(-4) included B3GALTS, A2BP1, GABRB1, AUTS2, BSN, PTPRG, GIRK2 and CDH12. CONCLUSIONS: Our findings show that individuals with broadly defined bipolar schizoaffective features have either a particularly strong genetic contribution or that, as a group, are genetically more homogeneous than the other phenotypes tested. The results point to the importance of using diagnostic approaches that recognise this group of individuals. Our approach can be applied to similar data-sets for other psychiatric and non-psychiatric phenotypes.  Publication Types:      Research Support, Non-U.S. Gov't  PMID: 19567891 [PubMed - in process]  4: Psychiatry Clin Neurosci. 2009 Jun;63(3):401-9.  Comorbidity of cardiovascular diseases with mood and anxiety disorder: a population based 4-year study.  Huang KL, Su TP, Chen TJ, Chou YH, Bai YM.  Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.  AIMS: Accumulating evidence from Caucasian patients has shown that depression, bipolar and anxiety disorders are associated with an increased risk of cardiovascular diseases (CVD), but reports in the Asian population are limited, and age effect is rarely investigated. This population-based study was carried out to examine and compare the CVD comorbidities among patients with mood and anxiety disorders in different age groups. METHOD: A 4-year cross-sectional survey was carried out using the Taiwan National Health Insurance Research Database from 2000 to 2003. RESULTS: An average total of 1,031,557 patients with  mood and anxiety disorders were enrolled as study participants, including 76,430  cases of major depressive disorder, 41,557 cases of bipolar disorder, and 913,570 cases of anxiety disorder. When compared with the insured population without mood or anxiety disorders (average 21,356,304 people), the average relative risk (RR)  of developing ischemic heart disease and hypertensive disorders in 1,031,557 study participants was 2.0 and 2.05, respectively. The highest RR was found in the age group under 20 years (RR = 4.74 and 4.08, respectively), and the lowest RR in the age group equal to or older than 65 years (RR = 0.47 and 0.58, respectively). CONCLUSIONS: Taiwanese patients with mood and anxiety disorders experience high cardiovascular morbidity, especially patients with anxiety disorders. Age acted as an important modifier variable that influenced the relationship between mood, anxiety disorder and CVD. This study highlights the need for future research in different age groups, in order to elucidate the causality and the trajectory of developing CVD among patients with mental disorders.  PMID: 19566773 [PubMed - in process]  5: Psychiatry Clin Neurosci. 2009 Jun;63(3):385-91.  Risk factors for obstructive sleep apnea syndrome screening in mood disorder patients.  Hattori M, Kitajima T, Mekata T, Kanamori A, Imamura M, Sakakibara H, Kayukawa Y, Okada T, Iwata N.  Department of Psychiatry, Okehazama Hospital, Fujita Health University School of  Medicine, Aichi, Japan.  AIMS: Previous studies have reported that the incidence of obstructive sleep apnea syndrome (OSAS) in patients with depression is higher than in the general population. We examined the risk factors to predict OSAS in mood disorder patients with depressive symptoms. METHOD: We conducted polysomnography for patients who satisfied the following criteria: (i) diagnosis of major depressive  disorder or bipolar disorder according to the Mini-International Neuropsychiatric Interview (MINI); (ii) a score of > or =10 on the Hamilton Rating Scale for Depression (HAM-D); (iii) fulfillment of either (a) or (b) below: (a) at least one of the following: severe snoring, witnessed apnea during sleep, excessive daytime sleepiness; (b) at least one of the following plus an oxygen desaturation index of 4% > or =5 times/h by pulse oximeter: mild snoring, sleep disturbance, headache, high blood pressure. The patients with apnea hypopnea index > or =5 were diagnosed with OSAS. RESULTS: Of the 32 mood disorder patients who met the subject conditions, 59.4% had OSAS. The diagnosis rate with our criteria was significantly higher than the previously reported incidence of OSAS in patients with depression. There was no significant difference among diagnosis rates as to  individual risk factors or the number of risk factors. A multiple regression test showed no significant association between apnea-hypopnea index and other clinical factors including depression severity. CONCLUSION: The present results showed that OSAS can be detected at a remarkably higher rate by considering appropriate  OSAS risk factors in mood disorder patients, and suggested that there is a high rate of undetected and therefore untreated OSAS among mood disorder patients.  PMID: 19566771 [PubMed - in process]