Die Suche nach potentiellen Kandidatengenen für die Schizophrenie und die Bipolare Störung ist ein stark umforschtes Feld der modernen Psychiatrie. Das Fzd3-Gen findet sich auf dem Chromosom 8p21 und liegt auf einem Hotspot für Schizophrenien und bipolare Psychosen. Nach positiven, aber auch negativen Assoziationsanalysen für Einzelmarker und deren Haplotyp in asiatischen Populationen, untersuchten wir in einer Fall-Kontroll-Studie drei SNPs und deren Haplotyp bei 192 Patienten mit einer chronischen Schizophrenie, sowie bei 56 Patienten die an einer Bipolaren Störung litten. Als Vergleichsgruppe dienten 284 gesunde Blutspender. In vorliegender Studie ließen sich die Befunde der asiatischen Untersuchungen weder auf der Ebene der Einzelmarker, noch auf der Ebene der Haplotypen replizieren. / Polymorphisms in the human Fzd3 gene have been associated with schizophrenia and bipolar disease in several investigations in asian population. These findings could not be confirmed in following studies. After negative associations shown in a caucasian sample in the UK, we performed a case-control-study in a sample of 192 chronically ill schizophrenic and 56 bipolar subjects and 284 healthy controls in a German population. We tested 3 SNPs and their calculated haplotypes - we couldn't find any associations between Fzd3 and schizophrenia and bipolar disorder in our sample.

Despite an abundance of older and more recent retrospective and considerably fewer prospective-longitudinal studies in bipolar disorders I and II, there are still remarkable deficits with regard to our knowledge about the natural course and burden. The considerable general and diagnosis-specific challenges posed by the nature of bipolar disorders are specified, highlighting in particular problems in diagnostic and symptom assessment, shifts in diagnostic conventions and the broadening of the diagnostic concept by including bipolar spectrum disorders. As a consequence it still remains difficult to agree on several core features of bipolar disorders, such as when they begin, how many remit spontaneously and how many take a chronic course. On the basis of clinical and epidemiological findings this paper summarizes (i) a significant need to extend the study of the natural course of bipolar disorder in clinical samples beyond the snapshot of acute episodes to the study of the mid-term and long-term symptom course, associated comorbidities and the associated burden of the disease. (ii) In terms of epidemiological studies, that are also of key importance for resolving the critical issues of threshold definitions in the context of the bipolar spectrum concept, there is a clear need for identifying the most relevant risk factors for the first onset and those for the further illness progression in early stages. Since there are some indications that these critical processes might start as early as adolescence, such studies might concentrate on young cohorts and clearly before these prospective patients come to clinical attention. (iii) The value of both types of studies might be enhanced, if beyond the use of standardized diagnostic interview, special attempts are made to use prospective life- and episode-charting methods for bipolar illnesses.

Objective: To explore the measurement of subsyndromal mood symptoms in relation to studies of maintenance therapy for bipolar disorder. Methods: Literature review of the Medline database using the following selection criteria: (1) ‘bipolar disorder’ plus ‘inter-episode or interepisode or subsyndromal or subclinical or residual or subthreshold’ and (2) ‘bipolar disorder’ plus ‘maintenance or prophylaxis or longitudinal’. Studies of children or adolescents and non-English-language reports were excluded. Results: Of the studies published between 1987 and October 2007, 77 articles about subsyndromal mood symptoms and 257 studies of maintenance therapy agents were found. Only 11 of the 257 studies of maintenance therapy agents discussed subsyndromal mood symptoms. Of the 77 articles, two thirds were published after 2000. Inconsistent definitions of subsyndromal mood symptoms and different evaluation tools and methodologies were used in the studies. Conclusions: There is a need to standardize definitions and validate measuring approaches for subsyndromal mood symptoms. However, when measured in both naturalistic studies and clinical trials, subsyndromal mood symptoms were frequently reported by patients receiving maintenance therapy and were associated with poor functioning. As with other chronic illnesses, knowledge of the patient’s perspective of daily morbidity is important for improving the clinical outcome. Studies of maintenance therapy for bipolar disorder, regardless of the approach, should measure subsyndromal mood symptoms as an additional outcome. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Despite an abundance of older and more recent retrospective and considerably fewer prospective-longitudinal studies in bipolar disorders I and II, there are still remarkable deficits with regard to our knowledge about the natural course and burden. The considerable general and diagnosis-specific challenges posed by the nature of bipolar disorders are specified, highlighting in particular problems in diagnostic and symptom assessment, shifts in diagnostic conventions and the broadening of the diagnostic concept by including bipolar spectrum disorders. As a consequence it still remains difficult to agree on several core features of bipolar disorders, such as when they begin, how many remit spontaneously and how many take a chronic course. On the basis of clinical and epidemiological findings this paper summarizes (i) a significant need to extend the study of the natural course of bipolar disorder in clinical samples beyond the snapshot of acute episodes to the study of the mid-term and long-term symptom course, associated comorbidities and the associated burden of the disease. (ii) In terms of epidemiological studies, that are also of key importance for resolving the critical issues of threshold definitions in the context of the bipolar spectrum concept, there is a clear need for identifying the most relevant risk factors for the first onset and those for the further illness progression in early stages. Since there are some indications that these critical processes might start as early as adolescence, such studies might concentrate on young cohorts and clearly before these prospective patients come to clinical attention. (iii) The value of both types of studies might be enhanced, if beyond the use of standardized diagnostic interview, special attempts are made to use prospective life- and episode-charting methods for bipolar illnesses.

Involviert in Netzwerke für das episodische Gedächtnis sowie als Bestandteil des Hypothalamus und des limbischen Systems stellen sich die im Zwischenhirn gelegenen Mamillarkörper als Zielstruktur im Kontext affektiver Störungen dar. Bislang waren die Mamillarkörper diesbezüglich lediglich in einer postmortem durchgeführten Studie Gegenstand der Forschung; es liegen keine Untersuchungen mit Hilfe der 7 Tesla-Magnetresonanztomografie vor. Um diese neuen Möglichkeiten der in vivo-Volumetrie im Submillimeterbereich auszuschöpfen, wurde auf Grundlage einer farbkodierten Darstellung ein detaillierter Algorithmus entwickelt, der sich als Hauptergebnis der vorliegenden Arbeit als hoch reliabel erwies. In der vorliegenden Pilotstudie wurde darüber hinaus das Mamillarkörper-Volumen von 14 Patientinnen und Patienten mit einer Bipolaren Störung und 20 gesunden Kontrollpersonen anhand von hochaufgelösten T1-gewichteten MRT-Bildern bestimmt. Ein signifikanter Unterschied zwischen den beiden Gruppen konnte nicht nachgewiesen werden, ebenso kein Unterschied zwischen den Geschlechtern. Es konnte gezeigt werden, dass das Volumen der Mamillarkörper signifikant invers mit dem Alter der ProbandInnen korreliert. Des Weiteren wurde eine signifikante positive Korrelation mit dem Gesamthirnvolumen der ProbandInnen festgestellt. Krankheitsschwere und Episodenzahl hingegen hatten keinen Einfluss auf das Mamillarkörper-Volumen. Die Ergebnisse dieser Pilotstudie sollten anhand einer größeren Stichprobe überprüft werden.

Background: Reported rates of bipolar syndromes are highly variable between studies because of age differences, differences in diagnostic criteria, or restriction of sampling to clinical contacts. Method: In 1395 adolescents aged 14–17 years, DSM-IV (hypo)manic episodes (manic and hypomanic episodes combined), use of mental health care, and five ordinal subcategories representing the underlying continuous score of (hypo)manic symptoms (‘mania symptom scale’) were measured at baseline and approximately 1.5, 4 and 10 years later using the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI). Results: Incidence rates (IRs) of both (hypo)manic episodes and (hypo)manic symptoms (at least one DSM-IV core symptom) were far higher (714/105 person-years and 1720/105 person-years respectively) than traditional estimates. In addition, the risk of developing (hypo)manic episodes was very low after the age of 21 years [hazard ratio (HR) 0.031, 95% confidence interval (CI) 0.0050–0.19], independent of childhood disorders such as attention deficit hyperactivity disorder (ADHD). Most individuals with hypomanic and manic episodes were never in care (87% and 62% respectively) and not presenting co-morbid depressive episodes (69% and 60% respectively). The probability of mental health care increased linearly with the number of symptoms on the mania symptom scale. The incidence of the bipolar categories, in particular at the level of clinical morbidity, was strongly associated with previous childhood disorders and male sex. Conclusions: This study showed, for the first time, that experiencing (hypo)manic symptoms is a common adolescent phenomenon that infrequently predicts mental health care use. The findings suggest that the onset of bipolar disorder can be elucidated by studying the pathway from non-pathological behavioural expression to dysfunction and need for care.

A literature search, supplemented by an expert survey and selected reanalyses of existing data from epidemiological studies was performed to determine the prevalence and associated burden of bipolar I and II disorder in EU countries. Only studies using established diagnostic instruments based on DSM-III-R or DSM-IV, or ICD-10 criteria were considered. Fourteen studies from a total of 10 countries were identified. The majority of studies reported 12-month estimates of approximately 1% (range 0.5–1.1%), with little evidence of a gender difference. The cumulative lifetime incidence (two prospective-longitudinal studies) is slightly higher (1.5–2%); and when the wider range of bipolar spectrum disorders is considered estimates increased to approximately 6%. Few studies have reported separate estimates for bipolar I and II disorders. Age of first onset of bipolar disorder is most frequently reported in late adolescence and early adulthood. A high degree of concurrent and sequential comorbidity with other mental disorders and physical illnesses is common. Most studies suggest equally high or even higher levels of impairments and disabilities of bipolar disorders as compared to major depression and schizophrenia. Few data are available on treatment and health care utilization.

Objective: To explore the measurement of subsyndromal mood symptoms in relation to studies of maintenance therapy for bipolar disorder. Methods: Literature review of the Medline database using the following selection criteria: (1) ‘bipolar disorder’ plus ‘inter-episode or interepisode or subsyndromal or subclinical or residual or subthreshold’ and (2) ‘bipolar disorder’ plus ‘maintenance or prophylaxis or longitudinal’. Studies of children or adolescents and non-English-language reports were excluded. Results: Of the studies published between 1987 and October 2007, 77 articles about subsyndromal mood symptoms and 257 studies of maintenance therapy agents were found. Only 11 of the 257 studies of maintenance therapy agents discussed subsyndromal mood symptoms. Of the 77 articles, two thirds were published after 2000. Inconsistent definitions of subsyndromal mood symptoms and different evaluation tools and methodologies were used in the studies. Conclusions: There is a need to standardize definitions and validate measuring approaches for subsyndromal mood symptoms. However, when measured in both naturalistic studies and clinical trials, subsyndromal mood symptoms were frequently reported by patients receiving maintenance therapy and were associated with poor functioning. As with other chronic illnesses, knowledge of the patient’s perspective of daily morbidity is important for improving the clinical outcome. Studies of maintenance therapy for bipolar disorder, regardless of the approach, should measure subsyndromal mood symptoms as an additional outcome. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: Current screening recommendations for early detection of lithium-associated hyperparathyroidism propose an exclusive measurement of serum albumin-adjusted calcium (Aac) concentration as a single first step. However, longitudinal data in patients with recurrent affective disorders suggest that increases in serum intact parathyroid hormone (iPTH) levels in lithium-treated patients may not necessarily be accompanied by a parallel increase in the concentration of Aac. If true, patients with an isolated increase in iPTH concentration above the reference range might be missed following current screening recommendations. Therefore, this study set out to examine key parameters of calcium metabolism, including iPTH and 25-hydroxycholecalciferol concentrations in patients with bipolar disorder that was or was not managed with lithium. Methods: Sixty patients with bipolar disorder according to DSM-IV were enrolled, 30 of whom had received long-term lithium treatment (lithium group), whereas the other 30 patients were on psychopharmacological treatment not including lithium (non-lithium group) at the time of the study. Owing to exclusion criteria (e.g., lithium < 6 months, laboratory results indicative of secondary hyperparathyroidism), 23 bipolar patients composed the final lithium group, whereas 28 patients remained in the non-lithium group for statistical analyses. Results: Patients in the lithium group showed a significantly higher concentration of iPTH compared to the non-lithium group (p < 0.05). Similarly, Aac concentrations were significantly increased in the lithium group compared to the non-lithium group (p < 0.05). However, in a multivariate linear regression model, group affiliation only predicted iPTH concentration (p < 0.05). In line with this, none of the four patients in the lithium group with an iPTH concentration above the reference range had an Aac concentration above the reference range. Discussion: This study suggests that the biochemical characteristics between primary hyperparathyroidism and lithium-induced hyperparathyroidism differ substantially with regard to regulation of calcium homeostasis. As such, current screening practice does not reliably detect iPTH concentrations above the reference range. Therefore, further research is needed to elucidate the consequences of an isolated iPTH concentration above the reference range in order to develop the most appropriate screening tools for hyperparathyroidism in lithium-treated patients with bipolar disorder.

Background: Current screening recommendations for early detection of lithium-associated hyperparathyroidism propose an exclusive measurement of serum albumin-adjusted calcium (Aac) concentration as a single first step. However, longitudinal data in patients with recurrent affective disorders suggest that increases in serum intact parathyroid hormone (iPTH) levels in lithium-treated patients may not necessarily be accompanied by a parallel increase in the concentration of Aac. If true, patients with an isolated increase in iPTH concentration above the reference range might be missed following current screening recommendations. Therefore, this study set out to examine key parameters of calcium metabolism, including iPTH and 25-hydroxycholecalciferol concentrations in patients with bipolar disorder that was or was not managed with lithium. Methods: Sixty patients with bipolar disorder according to DSM-IV were enrolled, 30 of whom had received long-term lithium treatment (lithium group), whereas the other 30 patients were on psychopharmacological treatment not including lithium (non-lithium group) at the time of the study. Owing to exclusion criteria (e.g., lithium < 6 months, laboratory results indicative of secondary hyperparathyroidism), 23 bipolar patients composed the final lithium group, whereas 28 patients remained in the non-lithium group for statistical analyses. Results: Patients in the lithium group showed a significantly higher concentration of iPTH compared to the non-lithium group (p < 0.05). Similarly, Aac concentrations were significantly increased in the lithium group compared to the non-lithium group (p < 0.05). However, in a multivariate linear regression model, group affiliation only predicted iPTH concentration (p < 0.05). In line with this, none of the four patients in the lithium group with an iPTH concentration above the reference range had an Aac concentration above the reference range. Discussion: This study suggests that the biochemical characteristics between primary hyperparathyroidism and lithium-induced hyperparathyroidism differ substantially with regard to regulation of calcium homeostasis. As such, current screening practice does not reliably detect iPTH concentrations above the reference range. Therefore, further research is needed to elucidate the consequences of an isolated iPTH concentration above the reference range in order to develop the most appropriate screening tools for hyperparathyroidism in lithium-treated patients with bipolar disorder.