Matthias Martin

Spectrum of binge eating symptomatology in patients treated with clozapine and olanzapine.

Summary. The authors explored the binge eating symptomatology in 74 patients receiving clozapine (N = 57) or olanzapine (N = 17), and compared body mass index (BMI, kg/m2) and weight gain in patients with and without binge eating symptomatology. Subjects who screened positively for binge eating were interviewed using a modified version of the Questionnaire on Eating and Weight Patterns (QEWP). Current BMIs were assessed cross-sectionally, BMIs at initiation of clozapine/olanzapine treatment retrospectively. Thirty-seven subjects (50%) screened positively. Taking clozapine and olanzapine together, 6/27 (22.2%) females and 3/47 (6.4%) males fulfilled criteria for binge eating disorder, 3/27 (11.1%) females and 2/47 (4.3%) males for bulimia nervosa. Patients who screened positively showed higher current BMIs (26.8 ± 3.9 vs. 24.7 ± 3.7 kg/m2) and higher BMI increments during clozapine/olanzapine treatment (3.9 ± 3.1 vs. 2.6 ± 3.4 kg/m2) than patients who screened negatively. We conclude that clozapine/olanzapine may induce binge eating and full blown eating disorders which may have predictive value for weight gain. For future research in this field we suggest a novel DSM-IV research classification “Medication-induced eating disorders”.

Lack of association between the -759C/T polymorphism of the 5-HT2C receptor gene and clozapine-induced weight gain among German schizophrenic individuals.

Weight gain is a major side effect of treatment with clozapine and other antipsychotics. Recent studies suggest an important role of the serotonin type 2C receptor gene (5-HT2CR) in antipsychotic-induced weight gain. However, investigations pertaining to a possible association between a –759C/T polymorphism (C allele) of the 5-HT2CR and weight gain induced by clozapine and/or other antipsychotics have yielded inconsistent results. We investigated the –759C/T polymorphism of the 5-HT2CR in relation to clozapine-induced change in body mass index (BMI) (kg/m2) in 97 German patients with schizophrenia and found no association between the –759C allele and weight gain after 12 weeks of clozapine treatment. In addition, confounding effects of initial BMI, age, sex and duration of illness on change in BMI could not be detected by multiple linear regression analysis. Our data do not support an involvement of the –759C/T polymorphism of the 5-HT2CR in clozapine-induced weight gain in German patients with schizophrenia. Further pharmacogenetic studies pertaining to antipsychotic-induced weight gain are warranted.

Prevalence of obesity in adolescent and young adult patients with and without schizophrenia and in relationship to antipsychotic medication

The prevalence of obesity in inpatients of a German psychiatric rehabilitation center for adolescents and young adults (mean age 19.5 years) is assessed and set into relationship to diagnosis and medication regimen. In a cross-sectional naturalistic study body weights and heights of 151 inpatients, 109 of whom presented with ICD-10 schizophrenia spectrum disorders, were measured for the calculation of body mass indices (BMI, kg/m2); current medication regimen including the duration of treatment was assessed from medical records. BMIs were plotted into gender- and age-specific BMI-percentiles representative for the German population. Among the whole study population, obesity (BMI > or =90th percentile) was apparent in 44/98 (45%) of the male and in 31/53 (59%) of the female inpatients (overall: 50%). With respect to schizophrenia spectrum disorders, 36/70 (51%) males and 25/39 (64%) females (overall: 56%) were obese in contrast to 14/42 (33%) among the individuals without schizophrenia. Set into relationship to the treatment groups, the prevalence rates of obesity were 64% in patients treated with clozapine (n=69), 56% for other atypical antipsychotics (olanzapine, sulpiride, risperidone; n=27), 30% for classic antipsychotics (haloperidol, flupentixol, perazine; n=20) and 28% for the currently drug-free group (n=25). Together with other published findings in adults, these results suggest an increased prevalence of obesity among young patients with schizophrenia and especially among patients chronically treated with atypical antipsychotics.

Forty-two-years later: the outcome of childhood-onset schizophrenia

SummaryThis paper describes the long-term course of 76 patients who had been consecutively admitted to the Department of Child and Adolescent Psychiatry, Philipps University, between 1920 and 1961 with a suspected diagnosis of childhood-onset schizophrenia. By means of a consensus analysis of available data in accordance with ICD-10 criteria, the diagnosis of schizophrenia was confirmed in only 50% of the original sample (n = 38, childhood-onset schizophrenia group); whereas the rest of the sample were allotted other diagnoses (n = 38, non-schizophrenia group). A follow-up investigation was conducted, interviewing all available patients, if possible, or their first-degree relatives or doctors. In the childhood-onset schizophrenia group, age at onset (mean ± S.D.) was 12.7 ± 2.5 (range 5–14) years and age at follow-up was 55.0 ± 4.8 (range 42–62) years. The outcome of this group was poor. According to the Global Assessment Scale (GAS), only 16% had a good (GAS score 71–100) and 24% had a moderate (GAS score 41–70) outcome. In the 16 childhood-onset schizophrenia patients who could be personally investigated at follow-up, 10 (62.5%) displayed severe or moderate depressive symptoms according to the BPRS depressive score. The death rate (including suicide) was significantly higher in the schizophrenia group (n = 15; 39.5%) than in the non-schizophrenia group (n = 7; 18.4%). A comparison of the life-time diagnoses of the total sample (n = 76) at follow-up with the ICD-10 diagnoses made retrospectively revealed a diagnostic stability in 69 (91%) and a change of diagnosis in 7 (9%) cases, among them 4 who were originally diagnosed as having childhood-onset schizophrenia.

Cognitive functions and psychopathological symptoms in early-onset schizophrenia

Abstract Type and extent of objectively tested cognitive impairments (attention, verbal fluency, nonverbal reasoning) and their association with self-ratings (Paranoia Depression Scale; Frankfurt Complaint Questionnaire) and clinical assessments (Brief Psychiatric Rating Scale, Scales for the Assessment of Positive Symptoms and Negative Symptoms) of psychopathological symptoms were studied in a sample of 74 adolescents primarily suffering from chronic schizophrenia (DSM-III-R; mean duration of illness = 3.4 years), including 15 patients with a very early onset (<14 years). Special consideration was given to the differentiation between positive and negative symptoms. In cross-sectional analyses, the schizophrenic adolescents were remarkably impaired in both cognitive functions (attention, reasoning) and psychopathological measures (BPRS, SANS, SAPS). However, factor analysis yielded orthogonal factors for cognitive and psychopathological parameters, and canonical correlation analyses did not find a significant correlation between these two areas. As the degree of objectively measured cognitive impairment in chronic schizophrenic adolescents cannot be predicted by the severity of individual psychopathological symptoms, a multidimensional evaluation of the symptomatology seems to be appropriate. Moreover, premorbid disturbances (motor and/or language developmental disorders) and onset characteristics (age, pattern, subdiagnosis), and their relationship to cognitive impairments were investigated. Premorbid disturbances were confirmed as risk factors for the subsequent occurrence of cognitive impairments.

Clozapin in der Kinder- und Jugendpsychiatrie

Die Inzidenz schizophrener Psychosen zeigt in der Altersgruppe adoleszenter Patienten einen sprunghaften Anstieg der Ersterkrankungen. Das Erstmanifestations-alter der schizophrenen Psychosen liegt dabei zu 22,1 % zwischen dem 15.–19. Lebensjahr (Remschmidt u. Martin 1992).

Eine Universitätsklinik als psychiatrisches Versorgungszentrum für Kinder und Jugendliche

Zusammenfassung: Berichtet wird uber ein von einer Universitatsklinik gestaltetes und seit dem Jahr 1980 zunehmend erweitertes und ausgebautes Versorgungssystem fur psychisch kranke Kinder und Jugendliche, das, in einer landlichen Region gelegen, ein Pflichtversorgungsgebiet von drei Landkreisen mit insgesamt 807 000 Einwohnern umfasst. Von groser Bedeutung fur diese Entwicklung war das Modellprogramm der Bundesregierung zur «Reform der Versorgung im psychiatrischen und psychotherapeutisch/psychosomatischen Bereich», unter dessen 14 Regionen die Region «Marburg und umliegende Landkreise» die einzige war, die sich auf psychisch kranke Kinder und Jugendliche konzentrierte. Mit Hilfe dieses «Modellprogramms» konnte sowohl eine umfassende Evaluation vorhandener Dienste fur diesen Personenkreis durchgefuhrt werden als auch die Einrichtung neuer Dienste (u.a. eines Mobilen kinder- und jugendpsychiatrischen Dienstes und einer Tagesklinik) und vor allem der Ausbau eines vollstandigen Versorgungsnetzes mit vielfal...

Zur Diagnostik und Therapie bei schizophrenen Psychosen des Kindes- und Jugendalters

Psychosen sind im Kindesalter selten auftretende Erkrankungen, die einer sehr genauen differentialdiagnostischen Abklarung bedurfen. Ungefahr 0,5 bis 1% aller schizophrenen Psychosen beginnen vor dem 10. und etwa 4% vor dem 15. Lebensjahr. Im Jugendalter und der Adoleszenz kommt es dann zu einem bemerkenswerten Haufigkeitsanstieg, wobei sich ca. 22% aller Ersterkrankungen mit einer Schizophrenie zwischen dem 15. und 19. Lebensjahr manifestieren (Remschmidt 1993).

Etiology of Schizophrenia: Perspectives from Childhood Psychoses

Schizophrenic psychoses in childhood were delineated as specific psychotic disorders only in the late 1930s (Lutz 1937/1938). But the history of childhood schizophrenia starts earlier. Hermann Emminghaus, who wrote the first textbook of child psychiatry in 1887 with the title Psychic Disturbances of Childhood, describes childhood psychoses as “cerebral neurasthenia” and defines these disorders as “neuroses of the brain characterized by a reduction of cognitive abilities, mood changes, sleep disturbances and manyfold anomalies of innervation with a subacute or chronic course and different states of outcome” (Emminghaus 1887, p. 134). Emminghaus was also the first who introduced the developmental perspective into child psychiatry with special focus on psychoses. After Emil Kraepelin, at the end of the past century, first described dementia praecox (Kraepelin 1886) and Eugen Bleuler (1911) introduced the term “schizophrenia”, August Homburger stated, in his famous textbook (Homburger 1926), that childhood schizophrenia really exists and may be characterized by the following features: (a) A predominant change of the personality of the children in the direction of withdrawal, negativism, and strange and unexpected behavior.

Clozapin in der Kinder- und Jugendpsychiatrie Klinische Erfahrung und neue Befunde

Clozapin hat sich auch im Jugendalter als wirksame und klinisch gut praktikable Medikation bei schizophrenen Erkrankungen erwiesen. Seit Beginn der achtziger Jahre haben wir uns klinisch und wissenschaftlich mit dieser Substanz beschaftigt. In unserer ersten Publikation (Siefen u. Remschmidt 1986) konnten wir bei uber der Halfte der Patienten eine deutliche Besserung oder ein Schwinden der meisten noch bestehenden psychopathologischen Symptome bei 21 schizophrenen Jugendlichen feststellen. Die Indikation fur die Umstellung von einem konventionellen Neuroleptikum auf Clozapin waren damals entweder ungenugendes Ansprechen auf andere Neuroleptika, drohende Chronifizierung der psychotischen Symptomatik oder ausgepragte extrapyramidale Begleitwirkungen. Wir kamen seinerzeit zu dem Schluss, dass Clozapin eine hilfreiche Erganzung der medikamentosen Behandlung schizophrener Storungen im Kindes- und Jugendalter darstellt. Dies wurde mittlerweile durch eine Reihe von Studien bestatigt (Tabelle 1.1). In der Zwischenzeit haben wir weitere Untersuchungen durchgefuhrt, die in Tabelle 1.2 wiedergegeben sind.