Bipolar Disorder: Möller HJ

Grunze H, Kasper S, Goodwin G, Bowden C, Möller HJ, Anonymous00338. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #15346536 No free full text.

Abstract: As with the two preceding guidelines of this series, these practice guidelines for the pharmacological maintenance treatment of bipolar disorder 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 relating to maintenance treatment. The data used for these guidelines were extracted from a MEDLINE and EMBASE search, from recent proceedings from key conferences and various national and international treatment guidelines. The scientific justification of support for particular treatments was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was not only graded, but also reviewed by the experts of the task force to ensure practicality.

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.

Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht R, Vieta E, Möller HJ, Anonymous00265. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #12478876 No free full text.

Abstract: These practice guidelines for the biological, mainly pharmacological treatment of bipolar depression 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 bipolar depression. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, and from recent proceedings of key conferences and 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 not only graded, but also commented on by the experts of the task force to ensure practicability.

Möller HJ. · No affiliation provided · Eur Arch Psychiatry Clin Neurosci. · Pubmed #12938683 No free full text.

This publication has no abstract.

Severus WE, Kleindienst N, Seemüller F, Frangou S, Möller HJ, Greil W. · Department of Psychiatry, University of Munich, Munich, Germany. · Bipolar Disord. · Pubmed #18271901 No free full text.

Abstract: OBJECTIVES: There is substantial uncertainty about the most efficacious serum lithium level for the long-term treatment of bipolar disorder (BD). This review focuses on the available evidence taking into consideration the effects of previous lithium history, changes in lithium level and polarity of relapse or recurrence. METHODS: We conducted a MEDLINE search, using the MeSH Terms 'bipolar disorder' and 'lithium' together with 'randomized controlled trial' or 'controlled clinical trial' covering the time span from 1966 to March 2006. We only included studies reporting on the long-term treatment of mood disorders where patients with BD were examined as a separate group and were assigned to precisely specified target ranges of lithium level. RESULTS: The minimum efficacious serum lithium level in the long-term treatment of bipolar disorder was 0.4 mmol/L with optimal response achieved at serum levels between 0.6-0.75 mmol/L. Lithium levels >0.75 mmol/L may not confer additional protection against overall morbidity but may further improve control of inter-episode manic symptoms. Abrupt reduction of serum levels of more than 0.2 mmol/L was associated with increased risk of relapse. CONCLUSIONS: In the long-term treatment of bipolar disorder clinicians should initially aim for serum lithium levels of 0.6-0.75 mmol/L, while higher levels may benefit patients with predominantly manic symptoms.

Möller HJ, Curtis VA. · Psychiatric Department, University of Munich, Nussbaumstr 7, D-80336 Munich, Germany. · Expert Rev Neurother. · Pubmed #16279864 No free full text.

Abstract: Bipolar disorder represents a clinically challenging, episodic, lifelong medical illness that is both disabling and dangerous to the patient and is associated with a high risk of suicide. The prognosis for bipolar patients is likely to worsen with delays in accurate diagnosis and treatment as time is allowed for more extensive complications and morbidity to accrue and for alcohol or other substance use comorbidity to complicate the course of the illness. Physicians face several challenges when diagnosing bipolar disorder, including overlapping symptomatology and comorbidity with other disorders, as well as the somewhat restrictive and categorical approach taken by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the International Statistical Classification of Diseases, 10th Revision (ICD-10) diagnostic criteria. As a result, bipolar disorder is frequently unrecognized and misdiagnosed with considerable clinical and prognostic consequences for the patient. The accuracy of diagnosis of bipolar disorder could be improved through the introduction of a refined procedure for the identification and evaluation of a broader range of symptoms, and by careful attention to the presence of subthreshold symptomatology. A conceptual shift toward acceptance of a 'spectrum' model of bipolar disorder and the development of appropriate clinical diagnostic tools should assist physicians in differentiating bipolar disorder from other Axis I, Axis II, and personality disorders, as well as ensuring early diagnosis and therapeutic intervention.

Möller HJ, Grunze H, Broich K. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #16078087 No free full text.

Abstract: This conceptual review summarises the results of relevant studies on antidepressants, mood stabilisers such as lithium and anticonvulsants, and second generation antipsychotics in the indication of bipolar depression. Based on methodological and clinical considerations, the position of antidepressants and the possible alternatives in this indication are reviewed very carefully. In addition the regulatory requirements for licensing a drug for the indication "short-term treatment of bipolar depression" are described.

Möller HJ. · Department of Psychiatry, Ludwig-Maximilians-Universität München, Nussbaumstrasse, 80336 Munich, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #15812601 No free full text.

Abstract: For a long time,in the context of depressive symptoms in schizophrenia traditional neuroleptics were mostly discussed with respect to possible depressiogenic side effects, although some studies argued that they may also have certain antidepressive effects. However, this was not proven at that time in placebo-controlled studies. Placebo-controlled studies performed in recent years have shown that second generation antipsychotics have antidepressive effects which are significantly stronger than those of the traditional neuroleptics. In addition, it was demonstrated that this antidepressive effect can only partially be explained as being secondary to the improvement of positive and negative symptoms, and is apparently predominantly due to a direct (primary) effect on depressive symptoms. It is of special relevance in this context that the antidepressive effect of second generation antipsychotics was recently demonstrated in depression. The positive results from some studies in bipolar depression are especially impressive and underline the antidepressive potencies of novel antipsychotics beyond the spectrum of schizophrenia.

Kleindienst N, Severus WE, Möller HJ, Greil W. · Psychiatric Hospital of the University of Munich, Nussbaumstr. 7, 80336 Munich, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #15711896 No free full text.

Abstract: BACKGROUND: Recently published data might indicate that the polarity of recurrence is related to lithium serum levels. To systematically test this hypothesis all published maintenance trials in bipolar disorders were examined with regard to this issue. METHOD: Maintenance studies were subdivided in trials with low (i. e. below 0.6 mEq/l),medium (i. e. 0.6 to 0.8 mEq/l) and high (i. e. above 0.8 mEq/l) lithium serum levels. Percentage of depressive vs. (hypo-)manic or mixed recurrences were compared for these three groups. RESULTS: The percentage of depressive recurrences in the groups with low, medium and high lithium levels differed in a clinically and statistically significant manner (12% vs. 38% vs. 64%, p < 0.0001). CONCLUSION: The results might indicate that low lithium levels are effective in preventing depression whereas higher blood levels are needed to prevent (hypo-)manic or mixed states.

Möller HJ. · Psychiatric Department of the University of Munich, Munich, Germany. · J Clin Psychiatry. · Pubmed #12720477 No free full text.

Abstract: Bipolar disorder continues to present complex diagnostic and therapeutic challenges. Originally considered 2 separate diseases (mania and depression), bipolar disorder is now recognized to be a single disorder characterized by different subtypes and degrees of severity. Despite the availability of official guidelines, such as the DSM-IV and ICD-10, diagnosis is still problematic. Traditionally, bipolar disorder has been considered a clinical entity distinct from schizophrenia, although that assumption is being increasingly challenged. Proponents of a bipolar continuum theory support the concept of an expanded psychiatric continuum ranging from unipolar to bipolar disorders all the way to schizophrenia. This notion is supported by various independent findings. Both bipolar disorder and schizophrenia demonstrate a high degree of genetic transmissibility. Some data reported in family and twin studies suggest hereditary overlap between the 2 disorders. Gene mapping for both diseases is in its early stages, but certain susceptibility markers appear to be located on the same chromosomes. Bipolar disorder and schizophrenia also demonstrate some similarities in neurotransmitter dysfunction. As further indirect evidence of a possible association, many newer atypical antipsychotic agents approved for the treatment of schizophrenia are also proving useful for bipolar disorder. Ongoing research should aid in the understanding of bipolar disorder and foster the development of more effective treatment.

Möller HJ, Nasrallah HA. · Psychiatric Department of University Munich, Munich, Germany. · J Clin Psychiatry. · Pubmed #12720475 No free full text.

Abstract: Management strategies for bipolar disorder often entail relatively long-term, complex medication regimens that combine primary mood stabilizers, antipsychotic agents, antidepressants, and other medications, such as benzodiazepines. New strategies for the management of bipolar disorder have recently been evaluated in controlled clinical trials, including using newer anticonvulsants, replacing conventional antipsychotics with atypical antipsychotics, and using novel combination treatments. This article provides an overview of current management strategies for patients with bipolar disorder and describes how these approaches can be incorporated into clinical practice.

Grunze H, Walden J, Dittmann S, Berger M, Bergmann A, Bräunig P, Dose M, Emrich HM, Gastpar M, Greil W, Krüger S, Möller HJ, Uebelhack R. · Psychiatrische Klinik der Universität München. · Nervenarzt. · Pubmed #11975062 No free full text.

Abstract: The broadening of the classification systems for manic-depressive illness towards a spectrum of bipolar disorders implicates a more differentiated use of pharmacotherapies. However, many questions still remain open. This implies that all consensus guidelines and recommendations have to be considered as preliminary. On the other hand, research in the last decade has developed many new treatment alternatives, both for mood stabilizers and antidepressants as well as antipsychotics. These recommendations, which have been developed in the process of two consensus meetings, try to consider the broadening of the concept of bipolar disorder by differentiating between subgroups according to acute symptomatology and characteristics of the long-term course, e.g., rapid cycling. In particular, the emerging role and new indications of mood stabilizing antiepileptic drugs, atypical antipsychotics, and new antidepressants will be discussed.

Möller HJ, Grunze H. · Psychiatrische Klinik der Ludwig-Maximilian-Universität, Munich, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #10853919 No free full text.

Abstract: This paper gives a critical review of recommendations concerning the drug treatment of acute bipolar depression. The suggestions of different guidelines and consensus papers, especially in US-American and Canadian psychiatry, have a strong tendency against antidepressants in bipolar depression; they prefer mono-therapy with mood stabilizers and, in the case of co-medication with mood stabilizers and antidepressants in severe depression, to withdraw the antidepressant as early as possible. The intention of this restrictive use is to avoid the risk of mania and the risk of rapid cycling induced by antidepressants. However, apparently the risk of suicidal acts, which is as prominent in bipolar depression as in unipolar depression, has been totally neglected. Furthermore, the fact that none of the mood stabilizers have proven their antidepressive efficacy leads not only to the risk of depression-related suicidal behavior but also to the risk of chronicity of depressive symptoms due to undertreatment. Altogether the view expressed in some guidelines and consensus papers appears not well balanced. Furthermore, the fact that apparently the selective serotonin re-uptake inhibitors and possibly some other modern antidepressants have only a low risk of inducing a switch to mania should stimulate a rewriting of the guidelines on drug treatment in acute bipolar depression in a less restrictive way concerning the use of antidepressants.

Kleindienst N, Greil W, Rüger B, Möller HJ. · Psychiatric Hospital of the University of Munich, Germany. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #10433128 No free full text.

Abstract: It has been reported recently that the prophylactic efficacy of lithium is a transient phenomenon in many patients. Other studies suggest sustained efficacy against affective recurrences for many years. As this issue is of major therapeutic relevance, published literature considering changes in lithium efficacy over time has been reviewed. The present review includes a critical evaluation of the data and the methodology which yielded these controversial results. Considering the published data discussed in this review, the balance of evidence does not indicate a general loss of lithium efficacy in the prophylaxis of major affective disorders. A supposed persistence of the prophylactic effects in general does not, however, exclude the reappearance of affective recurrences after years of successful treatment in individual cases. Possible reasons for this phenomenon are discussed.

Yatham LN, Vieta E, Young AH, Möller HJ, Paulsson B, Vågerö M. · Division of Mood Disorders, University of British Columbia, UBC Hospital, Vancouver, British Columbia, Canada. · Int Clin Psychopharmacol. · Pubmed #17519644 No free full text.

Abstract: The aim of this study was to evaluate the efficacy and tolerability of quetiapine combined with lithium or divalproex in the treatment of bipolar mania. Patients were randomized to 6 weeks of quetiapine (up to 800 mg/day) and lithium/divalproex (Li/DVP) (target trough serum concentrations of 0.7-1.0 mEq/L and 50-100 microg/mL, respectively) or placebo and lithium/divalproex. Quetiapine+lithium/divalproex treatment (n=104) showed a 2.0-point greater improvement on the primary outcome (change from baseline in Young Mania Rating Scale total score at day 21) compared with placebo+lithium/divalproex (n=96), and a 2.8-point greater difference by day 42, but the differences between groups were not statistically significant. Other efficacy measures, however, did show a statistically significant advantage in favor of quetiapine+lithium/divalproex over lithium/divalproex monotherapy at day 42. Improvement of mean Young Mania Rating Scale scores with quetiapine+lithium/divalproex was numerically but not statistically significantly greater than lithium/divalproex monotherapy in the treatment of bipolar mania. Potential reasons for the failure of quetiapine+lithium/divalproex to differentiate from placebo+lithium/divalproex treatment on the primary outcome measure and the implications of this for the treatment of mania and future studies are discussed. Overall, the combination of quetiapine with lithium or divalproex was well tolerated.

Bottlender R, Rudolf D, Strauss A, Möller HJ. · Department of Psychiatry, Ludwig Maximilians University, Munich, Germany. · Pharmacopsychiatry. · Pubmed #10761824 No free full text.

Abstract: Switching over from depression into states known an "maniform" in Germany ("expansive syndromes") been frequently, observed and appears to be partially related to the type of antidepressive medication. Apart from the medication, some evidence suggests that additional factors such as thyroid function may be relevant for the switchover. With this background, the aim of the present study was to evaluate the hypothesis that depressed bipolar patients with lower basal TSH serum levels (b-TSH) on admission at the hospital as inpatients are at a higher risk of switching from depression into "maniform" states than depressed bipolar patients with higher b-TSH. From a total of 158 bipolar depressed patients, 16 patients developed mania during their hospital stay. After dividing the sample of patients at the median b-TSH into one group with lower b-TSH (N = 78) and another group with higher b-TSH (N = 79), we found that the switchover rate to mania was significantly higher in the group of patients with lower b-TSH (15.4%) than in the group of patients with higher b-TSH (5.1 %). These findings suggest that lower b-TSH may be a risk factor for switching over from depression into "maniform" states in bipolar depressed patients.

Dittmann S, Hennig-Fast K, Gerber S, Seemüller F, Riedel M, Emanuel Severus W, Langosch J, Engel RR, Möller HJ, Grunze HC. · Department of Psychiatry and Psychotherapy, Ludwigs-Maximilians-University, Nussbaumstr. 7, Munich 80336, Germany. · Bipolar Disord. · Pubmed #19594503 No free full text.

Abstract: OBJECTIVE: There is growing evidence of cognitive impairment as a trait factor in bipolar disorder. The generalizability of this finding is limited because previous studies have either focussed exclusively on bipolar I disorder or have analysed mixed patient groups. Thus, it is still largely unknown whether bipolar II patients perform differently from bipolar I patients on measures of cognitive functioning. METHODOLOGY: A total of 65 patients with bipolar I disorder, 38 with bipolar II disorder, and 62 healthy controls participated in the study. Patients had to be euthymic for at least one month. Clinical and demographic variables were collected in a clinical interview and with the Structured Clinical Interview for DSM-IV. Cognitive functioning was assessed using a neuropsychological battery. Univariate and multivariate analyses of variance were conducted for analyzing possible differences between the groups. RESULTS: The multivariate analysis of covariance (MANCOVA) indicated overall differences in neuropsychological performance between the three groups (Pillai Spur: F 1.96, p = 0.003). Post hoc comparisons revealed that patients with bipolar I disorder showed significantly lower scores in psychomotor speed, working memory, verbal learning, delayed memory, and executive functions than healthy controls. Patients with bipolar II disorder showed significant deficits in psychomotor speed, working memory, visual/constructional abilities, and executive functions compared to controls, but not on verbal learning and delayed memory. The two patient groups did not differ significantly from each other on any domain tested. CONCLUSION: These results support a similar pattern of cognitive deficits in both subtypes of bipolar disorder.

Riedel M, Müller N, Strassnig M, Spellmann I, Severus E, Möller HJ. · Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Germany. · Neuropsychiatr Dis Treat. · Pubmed #19300555 links to  free full text

Abstract: Quetiapine was developed in 1985 by scientists at AstraZeneca (formerly Zeneca) Pharmaceuticals. It received official US Food and Drug Administration approval in September 1997 and approval in Germany in 2000. Since then, quetiapine has been used in the treatment of severe mental illness in approximately 70 countries including Canada, most Western European countries, and Japan. Quetiapine is a dibenzothiazepine derivative with a relatively broad receptor binding profile. It has major affinity to cerebral serotonergic (5HT(2A)), histaminergic (H1), and dopaminergic D(1) and D(2) receptors, moderate affinity to alpha(1)- und alpha(2)-adrenergic receptors, and minor affinity to muscarinergic M1 receptors; it demonstrates a substantial selectivity for the limbic system. This receptor occupancy profile with relatively higher affinity for the 5HT(2A) receptor compared with the D(2) receptor is in part responsible for the antipsychotic characteristics and low incidence of extrapyramidal side-effects of quetiapine. The efficacy of quetiapine in reducing positive and negative symptoms of schizophrenia has been proven in several clinical trials with placebo-controlled comparators. Quetiapine has also demonstrated robust efficacy for treatment of cognitive, anxious-depressive, and aggressive symptoms in schizophrenia. Long-term trials show sustained tolerability for a broad spectrum of symptoms. Quetiapine has also proven efficacy and tolerability in the treatment of moderate to severe manic episodes, and in the treatment of juveniles with oppositional-defiant or conduct disorders, and in the geriatric dementia population. Recent data indicate that quetiapine may also be effective in the treatment of bipolar depressive symptoms without increasing the risk of triggering manic episodes, and in borderline personality disorder. In comparison with other antipsychotics, quetiapine has a favorable side-effect profile. In clinical trials only small insignificant prolongations of the QT interval were observed. Weight-gain liabilities and new-onset metabolic side-effects occupy a middle-ground among newer antipsychotics. As a result of its good efficacy and tolerability profile quetiapine has become well established in the treatment of schizophrenia and manic episodes.

Egli S, Riedel M, Möller HJ, Strauss A, Läge D. · Institute of Psychology, Applied Cognitive Psychology, University of Zurich, Binzmühlestrasse 14/28, Zurich 8050, Switzerland. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #19165526 No free full text.

Abstract: BACKGROUND: In the current debate about the categorical or dimensional classification of mental disorders many fruitful methods to illustrate one or the other aspect are employed, and suggestions are made to combine the two perspectives. METHODS: We present such an approach to combine both perspectives at the same time. Based on psychopathological AMDP-symptom profiles, a map of psychiatric patients was calculated by robust nonmetric multidimensional scaling (NMDS). RESULTS: The sample from the Ludwig-Maximilians University in Munich included the records of patients, who were admitted and discharged in 2002 and 2003 with a diagnosis of either paranoid schizophrenia, (F20.00, N = 24), bipolar affective disorder, current episode manic without psychotic symptoms (F31.1, N = 32) or severe depressive episode without psychotic symptoms (F32.2, N = 78). In the resulting map of patients we found a clear categorical distinction according to the diagnostic groups, but also high regression values of AMDP-syndromes (manic syndrome: r = 0.83, depressive syndrome: r = 0.68, and paranoid-hallucinatory syndrome, r = 0.62). DISCUSSION: The map of psychiatric patients presents an approach to consider the categorical and dimensional aspects at the same time. We were able to identify meaningful delineations between diagnostic clusters as well as continuous transitions. This method allows the whole psychopathological profile of each individual patient to be considered and also to identify misdiagnosed cases at a glance.

Severus WE, Kleindienst N, Evoniuk G, Bowden C, Möller HJ, Bohus M, Frangou S, Greil W, Calabrese JR. · Department of Psychiatry, University of Munich, Munich, Germany. · J Affect Disord. · Pubmed #19019453 No free full text.

Abstract: BACKGROUND: Preliminary evidence suggests that the polarity of relapse/recurrence (depressive vs. hypomanic/manic/mixed) in bipolar patients on lithium might be related to serum lithium levels. METHODS: Polarity of episodes in 64 bipolar-I patients on lithium monotherapy during a prospective 18-month maintenance trial was predicted from (a) intra-individual oscillations of lithium levels over time and from (b) absolute lithium levels preceding relapse/recurrence. RESULTS: On an individual basis, depressive (vs. hypomanic/manic/mixed) episodes were mostly preceded by lithium levels above the individual means (p<0.001). Relapse/recurrence occurring at lithium levels above the overall mean serum level of 0.66 mmol/l was depressive (not hypomanic/manic/mixed) in most cases (odds-ratio=3.86, p=0.032). Lithium levels before depressive episodes were numerically higher than before hypomanic/manic/mixed episodes (0.769+/-0.242 vs. 0.675+/-0.262 mmol/l, p=0.13). Cox-regression including current lithium levels as time-dependent predictor essentially confirmed these results. LIMITATIONS: As patients were not randomized to specific lithium levels, potential confounders could not be completely ruled out. Furthermore, a closer than monthly assessment of both lithium levels and psychopathology would have been desirable to better understand the interplay between lithium levels and new mood episodes. CONCLUSIONS: The results indicate that within the currently accepted therapeutic range (0.4-1.1 mmol/l), the relative risk for depressive vs. hypomanic/manic/mixed relapses/recurrences may be associated with higher lithium levels. Therefore, lithium levels at the lower range of the therapeutic spectrum may be sufficient for the optimal prevention of depressive episodes whereas higher lithium levels within this range may be needed for optimal protection against manic/mixed episodes.

Scherk H, Backens M, Zill P, Schneider-Axmann T, Wobrock T, Usher J, Reith W, Falkai P, Möller HJ, Bondy B, Gruber O. · Department of Psychiatry and Psychotherapy, Georg-August-University Goettingen, von-Siebold-Str. 5, 37075, Göttingen, Germany. · J Neural Transm. · Pubmed #18726138 No free full text.

Abstract: The SNAP-25 gene is an integral part of the vesicle docking and fusion machinery that controls neurotransmitter release. Several post mortem studies revealed a reduction of SNAP-25 protein in the hippocampus of patients with schizophrenia and bipolar disorder (BD). Thirty-eight patients with schizophrenia, BD or obsessive-compulsive disorder and 17 healthy controls participated in the study. Proton magnetic resonance spectroscopy in left hippocampus was performed in each individual. Three single nucleotide polymorphisms (SNP) of the SNAP-25 gene were genotyped. Individuals with the homozygous CC genotype of the DdeI SNP presented a significantly higher ratio of N-acetyl-aspartate (NAA)/choline-containing compounds (Cho) in the left hippocampus compared to the group of individuals with the homozygous TT genotype. The SNAP-25 genotype may modulate synaptic plasticity and neurogenesis in the left hippocampus, and altered NAA/Cho ratio may be an indicator for this genetic modulation of neuronal function in the hippocampus.

O'Donovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V, Nikolov I, Hamshere M, Carroll L, Georgieva L, Dwyer S, Holmans P, Marchini JL, Spencer CC, Howie B, Leung HT, Hartmann AM, Möller HJ, Morris DW, Shi Y, Feng G, Hoffmann P, Propping P, Vasilescu C, Maier W, Rietschel M, Zammit S, Schumacher J, Quinn EM, Schulze TG, Williams NM, Giegling I, Iwata N, Ikeda M, Darvasi A, Shifman S, He L, Duan J, Sanders AR, Levinson DF, Gejman PV, Cichon S, Nöthen MM, Gill M, Corvin A, Rujescu D, Kirov G, Owen MJ, Buccola NG, Mowry BJ, Freedman R, Amin F, Black DW, Silverman JM, Byerley WF, Cloninger CR, Anonymous00094. · Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK. · Nat Genet. · Pubmed #18677311 No free full text.

Abstract: We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P = 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)).

Dittmann S, Seemüller F, Grunze HC, Schwarz MJ, Zach J, Fast K, Born C, Dargel S, Engel RR, Bernhard B, Möller HJ, Riedel M, Severus WE. · Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany. · J Clin Psychiatry. · Pubmed #18399726 No free full text.

Abstract: OBJECTIVE: Bipolar disorder is associated with cognitive impairment. High homocysteine levels seem to have a negative impact on cognition in the elderly. The aim of the present study was to investigate the potential relationship of elevated homocysteine levels and cognitive impairment in bipolar patients. METHOD: Cognitive functioning of DSM-IV bipolar disorder patients who were euthymic (Hamilton Rating Scale for Depression score < or = 5 and Young Mania Rating Scale score < or = 5) and healthy controls was assessed with the revised Wechsler Adult Intelligence Scale Information Subtest, the Wechsler Adult Intelligence Scale III Letter-Number Sequencing Subtest, the Trail Making Test, and the Repeatable Battery for the Assessment of Neuropsychological Status Form A to examine premorbid IQ, information processing speed, working memory, verbal learning, visuospatial/constructional abilities, delayed memory, and executive functions. Total homocysteine plasma concentration was measured by using high-performance liquid chromatography. Multivariate analyses of variance and multiple regression analyses were conducted to examine group differences and possible associations between cognitive functioning and homocysteine level. The study was conducted from 2002 through 2006. RESULTS: Seventy-five euthymic bipolar patients and 42 healthy controls participated in the study. Patients performed significantly worse than controls in all cognitive domains tested (Pillai Spur: F = 3.32, p = .038) except premorbid IQ (p = .068). The mean +/- SD homocysteine levels were 10.2 +/- 3.2 microM/L for patients and 8.9 +/- 2.8 microM/L for controls (p = .036). Stepwise regression analyses revealed a significant and independent association of homocysteine levels with verbal learning (p = .002), delayed memory (p = .030), and executive function (p = .011) in the patient group. About 11% of the variance was explained by only the homocysteine level. CONCLUSIONS: Elevated homocysteine levels may have a negative impact on verbal learning, delayed memory, and executive function in euthymic bipolar patients, but further studies are warranted.

Kawohl W, Giegling I, Mavrogiorgou P, Pogarell O, Mulert C, Möller HJ, Hegerl U, Rujescu D, Juckel G. · Research Group Clinical and Experimental Psychopathology, Psychiatric University Hospital Zurich, Zurich, Switzerland. · Int J Neuropsychopharmacol. · Pubmed #18257968 No free full text.

Abstract: Nitric oxide (NO) is a gaseous molecule with neurotransmitter properties that is involved in numerous functions in the central nervous system (CNS), the vascular system and also in macrophages. Haplotypes of NOS1 and NOS3 genes have been shown to be associated with different psychiatric disorders such as schizophrenia and bipolar disorder. Therefore, the detection of other characteristics of nitrinergic transmission is desirable. Because nitrinergic functioning influences serotonergic transmission, a functional marker of the serotonergic transmission, the loudness dependence of auditory evoked potentials (LDAEP), can be assumed to be influenced by nitrinergic changes as well. In order to clarify the relationship between nitrinergic transmission and LDAEP, 95 healthy subjects (41 males, 54 females) underwent electrophysiological recording and blood drawing for genotyping of single nucleotide polymorphisms (SNPs) and haplotypes of the NOS1 and NOS3 genes. Interestingly, two functional SNPs in both NOS1 (G-84A_exon 1c promoter polymorphism) and NOS3 (Glu298Asp) were associated with lower LDAEP. Further studies are needed to fully clarify the relationship between nitrinergic transmission, LDAEP and complex disorders such as schizophrenia and affective disorders.

Seemüller F, Riedel M, Wickelmaier F, Adli M, Mundt C, Marneros A, Laux G, Bender W, Heuser I, Zeiler J, Gaebel W, Jäger M, Möller HJ, Henkel V. · Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Nussbaumstrasse 7, 80336 Munich, Germany. · J Affect Disord. · Pubmed #18164767 No free full text.

Abstract: OBJECTIVE: The objective was (1) to assess the frequency of atypical depression (AD) in depressed inpatients; (2) to compare clinical features of patients with atypical and nonatypical depression (Non-AD) (3) to evaluate the meaning of single psychopathological symptoms with special respect to mood reactivity. METHOD: Diagnoses of 1073 inpatients were assessed according to DSM-IV using SCID (Structured Clinical Interview for the DSM-IV) and AMDP (Association for Methodology and Documentation). Diagnosis of atypical depression was defined according to criteria of the DSM-IV specifier for AD. All patients were rated using HAMD-21 (Hamilton Depression Scale). RESULTS: A high percentage of patients met criteria for AD (15.3%, 95% CI 13.0-17.9%). Women were more likely to suffer from AD (OR=1.54, p=0.037). There were no significant differences between AD and Non-AD patients regarding age, HAMD total baseline score, and diagnosis of any bipolar illness. In terms of psychopathology patients with AD were significantly more likely to suffer from somatic anxiety, somatic symptoms, guilt, genital symptoms, depersonalisation and suspiciousness as defined by HAMD-21 items. Interestingly, mood reactivity was not found to be significantly associated with the presence of two or more additional symptoms of AD. LIMITATIONS: Results were assessed by a post-hoc analysis, based on prospectively collected data. Compared to other inpatient samples with MDE, prevalence of bipolar disorder was rather low. CONCLUSION: (1) Frequency of AD may be underestimated, especially in inpatient samples. Further studies of inpatient samples are recommended. (2) Quality of distinct anxiety symptoms may be different in both groups, with AD patients being more likely to suffer from somatic symptoms and somatic anxiety. The presence of suspiciousness and even paranoid phenomena may not exclude a diagnosis of AD, but may be related to rejection sensitivity. (3) The mandatory presence of mood reactivity for the diagnosis of AD needs further consideration, regarding its validity for the concept.