Bipolar Disorder: Licht RW

Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Moller HJ, Kasper S. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · World J Biol Psychiatry. · Pubmed #19347775 No free full text.

Abstract: These updated guidelines are based on a first edition that was published in 2003, and have been edited and updated with the available scientific evidence until end of 2008. Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute mania in adults. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from the clinical trial database clinicaltrials.gov, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into six levels of evidence (A-F). As these guidelines are intended for clinical use, the scientific evidence was finally asigned different grades of recommendation to ensure practicability.

Licht RW, Vestergaard P, Kessing LV, Larsen JK, Thomsen PH, Anonymous00236. · Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Risskov, Denmark. · Acta Psychiatr Scand Suppl. · Pubmed #12974784 No free full text.

Abstract: A subcommittee under the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark have recently developed national guidelines for the psychopharmacological treatment with lithium and antiepileptic drugs, and the present translation aims at contributing to the international discussion on the development of proper guidelines for the treatment of bipolar disorder. Among the antiepileptic drugs, the report deals with valproate, carbamazepine and lamotrigine and to a lesser extent with oxcarbazepine, gabapentin and topiramate. The various drugs will be reviewed, outlining the scientific evidence for mood-stabilizing properties and discussing major side effects, the most important interactions with other drugs and practical use. Special considerations during pregnancy and lactation, during treatment of children and adolescents and during treatment of the elderly will also be presented. Antidepressants and antipsychotics are beyond the scope of the report, but due to the mood-stabilizing properties of at least some of the atypical antipsychotics, these agents will be brought into some focus in connection with the overall treatment guidelines for the different phases of bipolar disorder given at the end of this report.

Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht RW, Vieta E, Möller HJ, Anonymous00027. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #12582971 No free full text.

Abstract: Identical to the preceding guidelines of this series, these practice guidelines for the biological, mainly pharmacological treatment of acute bipolar mania were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute mania. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was finally not only graded, but has also been commented by the experts of the task force to ensure practicability. Key words: bipolar disorder, mania, acute treatment, evidence-based guidelines, pharmacotherapy, antipsychotics, mood stabiliser, electroconvulsive therapy.

Rendell JM, Licht RW. · No affiliation provided · Acta Psychiatr Scand. · Pubmed #17430410 No free full text.

This publication has no abstract.

Licht RW, Gijsman H, Nolen WA, Angst J. · Mood Disorders Research Unit, Aarhus University Hospital, Risskov, Denmark. · Acta Psychiatr Scand. · Pubmed #18754834 No free full text.

Abstract: OBJECTIVE: To address whether switch of depression into hypomania or mania or cycle acceleration in patients with bipolar disorder is caused by antidepressants or whether this phenomenon is attributable to the natural history of bipolar disorder itself. METHOD: A critical review of the literature, pointing at sources of bias that have been previously overlooked. For examining the causation in question, the Bradford-Hill criteria were applied, i.e. specificity of the potential causative agent, strength of effect, consistency in findings, dose-response relation, temporal relation with exposure to agent preceding effect and biological plausibility. RESULTS: There is a scarcity of randomized studies addressing the question, and the available studies all suffer from various forms of bias. However, there is some evidence suggesting that antidepressants given in addition to a mood stabilizer are not associated with an increased rate of switch when compared with the rate associated with the mood stabilizer alone. CONCLUSION: When combined with a mood stabilizer, antidepressants given for acute bipolar depression seemingly do not induce a switch into hypomania or mania. Whether antidepressants may accelerate episode frequency and/or may cause other forms of destabilization in patients with bipolar disorder remain to be properly studied.

Vestergaard P, Licht RW. · Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Skovagervej 2, 8240 Risskov, Denmark. · World J Biol Psychiatry. · Pubmed #12587181 No free full text.

Abstract: Lithium has been used as a treatment for various psychiatric- and somatic-illnesses for more than 50 years. Today the main use of lithium is for the prevention of episode recurrences in bipolar disorder. The main emphasis of this review will be on the efficacy and effectiveness of lithium prophylaxis in bipolar disorder but the review will also discuss other indications for lithium treatment, the historical development, pharmacokinetic and -dynamic issues, unwanted effects of lithium and the organisation of treatment services. Finally, although not the main purpose of this review, a short description of alternative mood stabilizing drugs will also be presented.

Licht RW, Vestergaard P. · Forskningsafdeling for affektive sygdomme, Psykiatrisk Hospital i Arhus, Arhus Universitetshospital, DK-8240 Risskov. · Ugeskr Laeger. · Pubmed #12025705 No free full text.

Abstract: This paper gives an update on the psychopharmacological treatment of bipolar disorder. The antimanic efficacy of lithium is well documented. The same applies to valproate, which is also efficacious in mixed mania. Conventional antipsychotics act fast in mania and do not require blood tests, but they have considerable neurological side effects. The newer antipsychotics, olanzapine, risperidone, and ziprasidone, have also been shown to have antimanic efficacy. Clozapine is extremely effective, also when other treatment fails. For the treatment of bipolar depression, lithium, lamotrigine, and antidepressants all seem to work, but antidepressants may sometimes precipitate mania or worsen the course of illness. For prophylaxis, lithium is still to be considered the first drug of choice. However, for several reasons, for instance treatment failure or side effects, long-term treatment with antiepileptics may often be necessary. Among the antiepileptics, carbamazepine, valproate, and lamotrigine are the best studied.

Licht RW, Vestergaard P, Brodersen A. · Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Risskov, Denmark. · Bipolar Disord. · Pubmed #18199244 No free full text.

Abstract: OBJECTIVES: From placebo-controlled studies of up to two years duration, it has been established that lithium has preventive efficacy in bipolar disorder (BD). However, the effectiveness of lithium under routine conditions seems less pronounced. In the present study, the overall 15.3-year outcome in BD patients commenced on lithium is described. METHODS: Ninety-one patients with BD consecutively commenced on prophylactic lithium treatment during hospitalization at the Aarhus University Psychiatric Hospital from 1981 to 1983 were followed until death or censoring occurred during up to 15.3 years of observation. Register-based outcome measures, available for all patients, included accumulated duration of admission and number of admissions. In addition, serious attempts were made to collect detailed information on treatment during follow up. Simple descriptive statistics were applied; potential independent associations between baseline variables and outcome were examined using logistic regression models. RESULTS: Of the 91 patients, 27 patients died (six from suicide) during the observation period, which was an excess mortality compared to the general population. Fifty percent of the patients were admitted for more than one month per 20 months of observation and admitted more than once for each four years of observation. Only 19 (21%) patients were not admitted to hospital during the observation period. No statistically significant predictors of poor outcome could be identified. In addition to lithium prophylaxis given for variable lengths of time, the majority of the 36 (40%) patients, from whom treatment data were available, received various other drug treatments during follow-up. CONCLUSIONS: The overall outcome in patients beginning prophylactic treatment is unsatisfactory. However, due to the observational design and the lack of detailed treatment information during the long follow-up period, inferences about the efficacy of lithium cannot be made from this study.

Tohen M, Greil W, Calabrese JR, Sachs GS, Yatham LN, Oerlinghausen BM, Koukopoulos A, Cassano GB, Grunze H, Licht RW, Dell'Osso L, Evans AR, Risser R, Baker RW, Crane H, Dossenbach MR, Bowden CL. · Lilly Research Laboratories, Indianapolis, IN 46285, USA. · Am J Psychiatry. · Pubmed #15994710 links to  free full text

Abstract: OBJECTIVE: The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/recurrence. METHOD: Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score > or =20 entered the study and received open-label co-treatment with olanzapine and lithium for 6-12 weeks. Those meeting symptomatic remission criteria (Young Mania Rating Scale score < or =12; 21-item Hamilton depression scale score < or =8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5-20 mg/day (N=217), or lithium (target blood level: 0.6-1.2 meq/liter) (N=214). RESULTS: Symptomatic relapse/recurrence (score > or =15 on either the Young Mania Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapine-treated and 38.8% of lithium-treated patients. The noninferiority of olanzapine relative to lithium (primary objective) in preventing relapse/recurrence was met, since the lower limit of the 95% confidence interval on the 8.8% risk difference (-0.1% to 17.8%) exceeded the predefined noninferiority margin (-7.3%). Secondary results showed that compared with lithium, olanzapine had significantly lower risks of manic episode and mixed episode relapse/recurrence. Depression relapse/recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium-treated patients. Mean weight gain during open-label co-treatment was 2.7 kg; during double-blind monotherapy, weight gain was significantly greater with olanzapine (1.8 kg) than with lithium (-1.4 kg). CONCLUSIONS: These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium co-treatment. Both agents were comparable in preventing depression relapse/recurrence.

Licht RW, Bysted M, Christensen H. · Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Risskov, Denmark. · Int Clin Psychopharmacol. · Pubmed #11236068 No free full text.

Abstract: The purpose of the study was to assess the efficacy and tolerance of risperidone in mania. Fourteen inpatients with a DSM-IV manic episode were treated with risperidone at a fixed daily dose of 6 mg for 4 weeks. Compliance was assured by weekly determinations of serum concentrations of risperidone. Ten out of the 14 patients completed all 4 weeks of treatment, and all of these achieved at least a 75% reduction on the Bech-Rafaelsen Mania Scale (MAS). On the other applied measures, a substantial improvement was also seen in most patients, and no worsening in any of the rating scales was observed in any patient. Five patients continued concomitant treatment with a mood stabilizer. When the results were compared with the results from a similar historic control group treated with the middle-potency typical antipsychotic zuclopenthixol at a daily dose of 20 mg under the same experimental conditions, a between group difference in mean percentage change (baseline versus endpoint) on the MAS was 34.7% (95% confidence interval = 7.9-61.6%) in favour of risperidone. Side-effect profiles were rather similar in the two treatment groups. Despite design limitations, these findings may justify the conduction of randomized controlled trials to investigate the use of risperidone in mania.

Licht RW, Straarup KN. · Arhus Universitetshospital, Klinik for Mani og Depression, Risskov. · Ugeskr Laeger. · Pubmed #17484845 No free full text.

Abstract: Due to the episodic nature of affective disorders, treatments that prevent relapses/recurrences have a high priority. The number of long-term studies is scarce, but for moderate and severe cases of recurrent depression and for most cases of bipolar disorder, there is enough evidence to recommend various psychological interventions in combination with long-term pharmacotherapy (mainly antidepressants for recurrent depression and mainly lithium for bipolar disorder). Even though none of the treatments cause dramatic risk reduction, it is often possible to improve the individual prognosis through integrated long-term management by specialized teams.

Øgendahl BK, Agerbo E, Byrne M, Licht RW, Eaton WW, Mortensen PB. · National Center for Register-based Research, University of Aarhus, Aarhus C, Denmark. · Psychol Med. · Pubmed #16836796 No free full text.

Abstract: BACKGROUND: Several studies have found an association between indicators of fetal growth and/or obstetric complications and schizophrenia but only a few studies have investigated the possible association between these factors and bipolar disorder. Furthermore, the results of these studies have been contradictory. The aim of this study was to investigate whether the risk of bipolar disorder is associated with exposure to indicators of fetal growth. METHOD: A national population nested case-control study based on Danish longitudinal register databases was carried out. Conditional logistic regression was used, controlling for potential confounding factors such as parental age at birth, socio-economic indicators and psychiatric history. We identified 196 cases, and each case was time-, age- and sex-matched with 25 normal population-based controls. All cases were between the ages of 12 and 26 years at the time of diagnosis, were born between 1973 and 1983 and were admitted and diagnosed between 1987 and 1999. RESULTS: During the study period 1973-1983, none of the individual variables available for analyses (birthweight, birth length, gestational age and number of previous pregnancies in the mother) was associated with receiving a diagnosis of bipolar disorder. CONCLUSIONS: None of the indicators of fetal growth under study could be identified as risk factors for bipolar disorder, suggesting that the etiologies of schizophrenia and bipolar disorder, at least in part, are different.

Bernhard B, Schaub A, Kümmler P, Dittmann S, Severus E, Seemüller F, Born C, Forsthoff A, Licht RW, Grunze H. · Bipolar Disorder Program, Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80806 Munich, Germany. · Eur Psychiatry. · Pubmed #16380236 No free full text.

Abstract: BACKGROUND: In recent years, several controlled studies could show that psychoeducational interventions have been effective for relapse prevention in bipolar disorders. We therefore established a cognitive-psychoeducational group intervention with 14 sessions providing information about the illness, early warning signs, cognitive and behavioural strategies for stress management and social rhythm. Additionally we offered a group intervention for the patients' relatives. The objective of this study was to describe the outcome associated with our psychoeducational intervention in bipolar patients and their relatives. METHODS: Sixty-two bipolar patients attended 14 sessions (à 90 min) of cognitive-psychoeducational group therapy. Patients' knowledge of bipolar disorder and their satisfaction with the treatment were assessed using self-developed questionnaires before and after the group intervention. Additionally, 49 relatives of bipolar patients received two psychoeducational workshops of 4 hours each. We assessed demographic variables, burden, high expressed emotion and depressive symptoms of the relatives before and after the two workshops and at 1-year follow-up. RESULTS: Patients significantly improved their knowledge of bipolar disorder. They also have benefited from the discussions and the exchange of useful coping strategies. Burden and high expressed emotions showed no significant reductions at post-assessment, however they were significantly reduced at 1-year follow-up. Relatives also felt significantly better informed about the illness. CONCLUSIONS: These findings show that psychoeducational interventions in bipolar patients and their relatives improve patients' and their relatives' knowledge of the illness and the burden of the disorder as well as high expressed emotions are reduced in relatives at 1-year follow-up.

Laursen TM, Labouriau R, Licht RW, Bertelsen A, Munk-Olsen T, Mortensen PB. · National Centre for Register-Based Research, University of Aarhus, Taasingegade 1, DK-8000 Aarhus C, Denmark. · Arch Gen Psychiatry. · Pubmed #16061761 links to  free full text

Abstract: BACKGROUND: Schizoaffective disorder may be related to both schizophrenia and bipolar disorders, but no population-based studies, to our knowledge, have investigated this association in families. OBJECTIVES: To determine whether a psychiatric history of schizoaffective disorder, bipolar disorder, or schizophrenia among parents and siblings is a risk factor for developing a schizoaffective disorder, and whether a specific pattern of family history of psychiatric illness exists in persons with schizoaffective disorder compared with persons with bipolar disorder or schizophrenia. DESIGN: Register-based cohort study. SETTING: Denmark. COHORT: The 2.4 million persons born in Denmark after 1952. MAIN OUTCOME MEASURES: Relative risks of the 3 illnesses estimated by Poisson regression. RESULTS: In total, 1925 persons had a schizoaffective disorder, 3721 had a bipolar disorder, and 12 501 had schizophrenia. The relative risk of schizoaffective disorder was 2.76 (95% confidence interval, 2.49-3.06) if a first-degree relative had a history of mental illness compared with a person with no first-degree relatives with such a history. There was an additional risk (95% confidence interval) of 2.57 (2.11-3.13), 3.23 (2.63-3.95), or 1.92 (1.43-2.57) if the first-degree relative had schizophrenia, bipolar disorder, or schizoaffective disorder, respectively, compared with other psychiatric admissions. When bipolar disorder was the outcome, bipolar disorder in first-degree relatives was by far the significantly strongest risk factor. When schizophrenia was the outcome, the significantly strongest risk factor was schizophrenia among first-degree relatives. CONCLUSION: Schizoaffective disorder is not simply a subgroup of either bipolar disorder or schizophrenia but may be genetically linked to both, with schizoaffective disorder being a subtype of each or a genetic intermediate form.

Vieta E, Nolen WA, Grunze H, Licht RW, Goodwin G. · Bipolar Disorders Program, Hospital Clínic, University of Barcelona, IDIBAPS, Barcelona, Spain. · Bipolar Disord. · Pubmed #15952959 No free full text.

This publication has no abstract.

Kläning U, Laursen TM, Licht RW, Kyvik KO, Skytthe A, Mortensen PB. · Mood Disorder Research Unit of Clinical Psychiatric Research, Aarhus University Psychiatric Hospital, Skovagervej 2, 8240 Risskov, Denmark. · J Affect Disord. · Pubmed #15306139 No free full text.

Abstract: BACKGROUND: A previous study demonstrated a higher rate of schizophrenia in dizygotic twins than in the general population, and a higher rate of schizophrenia in siblings of dizygotic twins than in siblings of monozygotic twins and singletons, pointing to a common genetic predisposition for dizygotic twinning and schizophrenia. The aim of the present study was to investigate whether these findings also apply to bipolar disorder. METHODS: Through record linkage between The Danish Twin Register, The Danish Psychiatric Central Register and The Danish Civil Registration System, the rate of bipolar disorder (diagnosed for the first time during admission to hospital) in dizygotic and monozygotic twins was compared with the rate in singletons, and the rate in siblings and parents of twins was compared with the rate in siblings and parents of singletons. RESULTS: The rate of bipolar disorder was the same in dizygotic twins, monozygotic twins and singletons as well as for parents and siblings of dizygotic twins, monozygotic twins and singletons. LIMITATIONS: The study is a register-based study, only including hospitalized patients. CONCLUSION: This study shows that there is an equal rate of bipolar disorder in twins and in singletons. Assuming that DZ twinning is under some genetic influence, a differential relationship between schizophrenia and DZ twinning on one hand and bipolar disorder and DZ twinning on the other hand may suggest differences in the genetic basis of the two diseases. The finding that the rate of bipolar disorder in monozygotic twins is the same as the rate of bipolar disorder in singletons supports studies finding no association between bipolar disorder and obstetric complications.

Licht RW. · Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Risskov, Denmark. · Bipolar Disord. · Pubmed #12479682 No free full text.

Abstract: During recent years, the majority of drug trials in mania have been conducted for the purpose of drug approval. On this background, this paper addresses to what extent these trials may actually provide the practising clinician with useful information. One major point is that selection prior to the point of randomization in RCTs in mania may limit the applicability of study results to patients seen in ordinary clinical practice. Limitations in study credibility and study design are also discussed. The need for large scale pragmatic studies using broad inclusion criteria, comparing the various treatments, alone or in combination, is emphasized.

Licht RW. · Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Risskov, Denmark. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #11824841 No free full text.

Abstract: Considering the increasing number of drugs evaluated for mania in randomised controlled trials (RCTs) and the potential discrepancies between recommendations based on RCTs and the antimanic treatment given in clinical practice, this paper addresses some issues related to RCTs on drug effects in mania. One major question raised in the paper is to what extent selection prior to the point of randomisation in RCTs in mania may limit the applicability of study results to patients seen in ordinary clinical practice. Although such limitations in generalisability can be difficult to investigate empirically, it is emphasised that they should be openly discussed in the reports of RCTs. Another major focus is the issue of evaluation and interpretation of outcome, including a discussion of various response criteria based on mania rating scale scores. It is pointed out that essential criteria of dimensionality have only been sufficiently evaluated for the Bech-Rafaelsen Mania Rating Scale, although the fulfilment of such criteria are prerequisites for adding up the item scores to a total score reflecting the severity of mania. It is suggested that response defined as a decline in mania score below a certain limit may have some advantages over the commonly used 50% reduction criterion. The issues arising from the unusual high drop-out rates of around 50% are also addressed. Despite the fact that we need rigorous placebo-controlled trials to establish antimanic efficacy of new compounds, we also need large scale pragmatic studies using broad inclusion criteria, comparing the various treatments, alone or in combination, to investigate how they work in clinical practice. These studies maybe randomised but open and use simple but relevant outcome measures.

Brodersen A, Licht RW, Vestergaard P, Olesen AV, Mortensen PB. · Psykiatrisk Hospital, Arhus Universitetshospital, DK-8240 Risskov. · Ugeskr Laeger. · Pubmed #11816921 No free full text.

Abstract: INTRODUCTION: Lithium treatment is claimed to reduce mortality in patients with affective disorder, but the evidence is conflicting. The aim of this study was to estimate mortality rates from a cohort of such patients, who commenced treatment with lithium, over an observation period of 16 years. MATERIAL AND METHODS: The mortality rates of affectively ill patients, who commenced lithium treatment, were compared with the mortality rates in the general Danish population, standardised for age, sex, and a time to death from all causes, suicide, and cardiovascular death. Comparison of the time from a two-year follow-up to death from any cause between patients compliant and non-compliant with two years of lithium treatment was performed with the Cox regression analysis. RESULTS: Forty of the 133 patients who participated in the study died during the 16-year observational period; 11 from suicide. Mortality in the patients was twice that of the background population. This statistically significantly higher mortality was predominantly caused by the number of suicides, whereas mortality from all other causes was similar to the background population. Thirty-two patients died after the first two years of observation and were included in the analysis of association between death and two years of compliance with lithium. Suicide occurred more frequently in the lithium non-compliant patients than in the lithium compliant patients. DISCUSSION: Mortality, particularly death from suicide, was significantly increased in unselected affective disorder patients, who commenced lithium treatment, as compared with the background population.

Licht RW, Vestergaard P, Rasmussen NA, Jepsen K, Brodersen A, Hansen PE. · Mood Disorders Research Unit, Aarhus University Psychiatric Hospital, Skovagervej 2, DK-8240 Risskov, Denmark. · Acta Psychiatr Scand. · Pubmed #11722321 No free full text.

Abstract: OBJECTIVE: This paper describes the outcome for the first 148 patients referred to a lithium clinic. METHOD: Two-year follow-up data from treatment charts are reported for all patients entering a lithium clinic in the study period. RESULTS: Lithium was given as the only mood stabilizer in 132 (89.2%) of the cases. Thirty-two (21.6%) patients were readmitted with a new affective disorder episode. Twenty-nine (19.6%) patients discontinued treatment prematurely. Variables predicting the recurrence of new affective disorder episodes as well as premature discontinuation of treatment were identified. CONCLUSION: The majority of bipolar patients received lithium for prophylaxis against recurrent affective disorder episodes. The outcome was moderate but comparable to the 30-40% improvement usually reported in follow-up studies of bipolar patients given long-term prophylactic treatment with lithium. Better long-term treatment results for bipolar patients depend on both the development of more effective mood stabilizing drugs or drug combinations and the improvement of patients' adherence to treatment.

Duffy A, Turecki G, Grof P, Cavazzoni P, Grof E, Joober R, Ahrens B, Berghöfer A, Müller-Oerlinghausen B, Dvoráková M, Libigerová E, Vojtĕchovský M, Zvolský P, Nilsson A, Licht RW, Rasmussen NA, Schou M, Vestergaard P, Holzinger A, Schumann C, Thau K, Robertson C, Rouleau GA, Alda M. · Department of Psychiatry, Dalhousie University, Halifax. · J Psychiatry Neurosci. · Pubmed #11022400 links to  free full text

Abstract: OBJECTIVE: To test for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. DESIGN: Polymorphisms located in genes that code for GABRA3, GABRA5 and GABRB3 subunits of the GABAA receptor were investigated using association and linkage strategies. PARTICIPANTS: A total of 138 patients with bipolar 1 disorder with a clear response to lithium prophylaxis, selected from specialized lithium clinics in Canada and Europe that are part of the International Group for the Study of Lithium-Treated Patients, and 108 psychiatrically healthy controls. Families of 24 probands were suitable for linkage analysis. OUTCOME MEASURES: The association between the candidate genes and patients with bipolar disorder versus that of controls and genetic linkage within families. RESULTS: There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. CONCLUSIONS: This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder.

Vestergaard P, Licht RW. · Arhus Universitetshospital, Psykiatrisk Hospital, afdeling A. · Ugeskr Laeger. · Pubmed #10895597 No free full text.

This publication has no abstract.

Alda M, Turecki G, Grof P, Cavazzoni P, Duffy A, Grof E, Ahrens B, Berghöfer A, Müller-Oerlinghausen B, Dvoráková M, Libigerová E, Vojtĕchovský M, Zvolský P, Joober R, Nilsson A, Prochazka H, Licht RW, Rasmussen NA, Schou M, Vestergaard P, Holzinger A, Schumann C, Thau K, Rouleau GA. · Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. · Am J Med Genet. · Pubmed #10893493 No free full text.

Abstract: Corticotropin-releasing hormone (CRH) and proenkephalin (PENK) are hypothalamic peptides involved in the stress response and hypothalamic-pituitary axis regulation. Previous research has implicated these peptides in the pathogenesis of affective disorders. In this study we investigated two polymorphisms located in the genes that code for CRH and PENK by means of association and linkage analyses. A total of 138 bipolar patients and 108 controls were included in the association study. In addition, 24 families were available for linkage analysis, including six families of probands with documented periodic positivity of dexamethasone suppression tests (DST) during remission. We found no association of bipolar disorder with either gene. Similarly, we did not find any evidence of linkage (P = 0.56 for CRH and 0.52 for PENK) in the entire sample or in the subsample of families of DST positive probands. In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribute to the genetic susceptibility to bipolar disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:178-181, 2000.

Turecki G, Alda M, Grof P, Joober R, Lafrenière R, Cavazzoni P, Duffy A, Grof E, Ahrens B, Berghöfer A, Müller-Oerlinghausen B, Dvoráková M, Libigerová E, Vojtechovský M, Zvolský P, Nilsson A, Prochazka H, Licht RW, Rasmussen NA, Schou M, Vestergaard P, Holzinger A, Schumann C, Thau K, Rouleau GA. · Centre for Research in Neuroscience, The Montreal General Hospital, McGill University, 1650 Cedar Ave, Montreal, Canada. · J Affect Disord. · Pubmed #10760559 No free full text.

Abstract: BACKGROUND: Several studies have suggested that expanded trinucleotide repeats, particularly CAG, may have a role in the etiology of BD. Results obtained with the repeat expansion detection technique (RED) have indicated that bipolar patients have an excess of expanded CAG repeats. However, it is not clear which loci account for this difference. METHODS: Using lithium-responsive bipolar patients in order to reduce heterogeneity, we investigated five loci that are expressed in the brain and contain translated CAG repeats. A sample of 138 cases and 108 controls was studied. Genotypes were coded quantitatively or qualitatively and repeat distributions were compared. RESULTS: No difference was found in allele distribution between cases and controls for any of the loci studied. In one locus - L10378 - patients had a tendency to present shorter alleles (28.1 versus 27.9 repeats; t=2.55, df=205, P=0.011), however, this difference disappeared after correction for multiple testing. LIMITATIONS: The study has limitations common to most candidate gene association studies, that is, limited number of loci investigated and limited power to detect loci that account for a small proportion of the total genetic variability. CONCLUSIONS: Our results suggest that the loci investigated have no major role in the genetic predisposition to bipolar disorder.

Turecki G, Grof P, Cavazzoni P, Duffy A, Grof E, Ahrens B, Berghöfer A, Müller-Oerlinghausen B, Dvoráková M, Libigerová E, Vojtechovsky M, Zvolsky P, Joober R, Nilsson A, Prochazka H, Licht RW, Rasmussen NA, Schou M, Vestergaard P, Holzinger A, Schumann C, Thau K, Rouleau GA, Alda M. · Centre for Research in Neuroscience, Montreal General Hospital, McGill University, Canada. · Psychiatr Genet. · Pubmed #10335547 No free full text.

Abstract: A number of association studies have investigated the role of the monoamine oxidase A (MAOA) gene in the susceptibility to bipolar disorder. Although some studies have reported positive findings, there remains some controversy, because results from different studies have not been consistent. A common explanation for inconsistencies between studies is genetic heterogeneity. We have focused on lithium responsive bipolar disorder as a way to reduce heterogeneity. In this study, we investigated the role of MAOA in lithium responsive bipolar patients using association and linkage study designs. The investigation used 138 patients and 108 normal controls. In addition, 25 families were also studied. Our results were not supportive of a major role of MAOA in the predisposition to bipolar disorder.