Harald Krauss

Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder

Various polymorphisms of the X-chromosomal monoamine oxidase A (MAO-A) gene were investigated for association with affective disorders. However, none of the studied variants could consistently be associated with either major depressive or bipolar affective disorder. Recently, a positive association between panic disorder and a novel functional repeat polymorphism in the MAO-A gene promoter, with the longer alleles being more active, was reported. Since monoaminergic neurotransmission is supposed to play an important role in affective disorders, we investigated a potential association of this polymorphism with major depressive illness in a sample of 146 unrelated patients of German descent and a control group of 101 individuals with a negative life history for affective disorders. Similarly to the recent findings in panic disorder, we observed a significantly increased frequency of genotypes containing only long alleles in female patients with recurrent major depression in comparison with age- and sex-matched controls. Thus, our data suggest that an excess of high-activity MAO-A gene promoter alleles resulting in an elevated MAO-A activity is a risk factor for major depressive disorder in females. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:801-803, 2000.

Dopamine D3 receptor variant and tardive dyskinesia

Abstract In the search for genetic factors contributing to tardive dyskinesia, dopamine receptor genes are considered major candidates. The dopamine D3 receptor is of primary interest as dopamine D3 receptor knock-out mice show locomotor hyperactivation resembling extrapyramidal side-effects of neuroleptic treatment. Furthermore, Steen and colleagues (1997) recently reported an association between tardive dyskinesia and a dopamine D3 receptor gene variant.In the present study we tried to replicate this finding. We investigated 157 patients with schizophrenia or schizoaffective disorder receiving long-term neuroleptic medication who never or persistently displayed tardive dyskinesia. As advanced age is a main risk factor for tardive dyskinesia, we also compared older patients with a long duration of schizophrenia not displaying tardive dyskinesia to younger patients with a shorter duration of the illness displaying tardive dyskinesia. However, we found no evidence that the dopamine D3 receptor gene is likely to confer susceptibility to the development of tardive dyskinesia.

Further evidence for age of onset being an indicator for severity in bipolar disorder

Since the early report by Taylor and Abrams supported by Carlson et al. (1977). Moreover, McEl(1973) which suggested that age of onset might be roy et al. (1997) even found adolescent patients to used as a criterion to delineate subgroups in bipolar display a significantly lower rate of psychotic feaaffective disorder, several studies have tackled this tures than adult-onset bipolar patients. issue. However, consistent evidence for earlyand Further controversy surrounds the question of late-onset bipolar disorder representing two different whether age of onset might serve as a valid disphenotypes has not emerged so far. Studies by criminator between bipolar I and II disorder Ballenger et al. (1982), Rosen et al. (1983), Joyce (Peselow et al., 1982; Egeland et al., 1987; (1984), and Carlson et al. (2000) reported earlyMcMahon et al., 1994; Benazzi, 1999). In a very onset bipolar patients to suffer more often from recent approach, based on a large sample of consecu psychotic symptoms than patients with a late onset, tively recruited bipolar patients, Schurhoff et al. leading to a more severe clinical picture. These (2000) tested the hypothesis of whether the age of observations are partly supported by a study by onset in bipolar disorder might serve as an important McGlashan (1988), who found patients with adolesindicator for identifying more homogeneous clinical cent-onset mania to present with more psychotic subtypes. They compared clinical features, comorsymptoms and greater chronicity than adult-onset bidity and familial risk of 58 early-onset and 39 patients; however, the long-term outcome of the late-onset bipolar patients. For the early-onset group early-onset group was comparable or even better they observed a higher rate of psychotic sympthan that of the late-onset patients, a finding which is tomatology, elevated frequency of mixed episodes, greater comorbidity with panic disorder, and poorer prophylactic lithium responses. Furthermore, first*Corresponding author. Department of Psychiatry, University of degree relatives of early-onset patients also showed a Chicago, Jules F. Knapp Research Center, 924 East 57th Street, higher risk of affective disorder than relatives of Room R004, Chicago, IL 60637, USA. Tel.: 11-773-834-8920; patients with a late-onset bipolar illness. Thus, fax: 11-773-834-2970. E-mail address: schulze@uchicago.edu (T.G. Schulze). Schurhoff et al. (2000) concluded that an early age

Major psychoses symptomatology: factor analysis of 2241 psychotic subjects

Abstract Current nosography classifies major psychoses as separate disorders, but their symptomatological presentation during illness episodes largely overlaps and diagnoses may change during a lifetime. Few analyses of major psychoses symptomatology have been performed so far because of the large number of subjects needed to obtain stable factors. The purpose of this study was, therefore, to identify the symptomatologic structure common to major psychoses based on lifetime symptoms. Two thousand and forty-one inpatients affected by schizophrenic (n=1008), bipolar (n=563), major depressive (n=352), delusional (n=108) and psychotic not otherwise specified disorder (n=210) were rated for lifetime symptoms using the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and included in a factorial analysis. Four factors were obtained, the first consisted of excitement symptoms, the second comprised psychotic features (delusions and hallucinations), the third comprised depression and the fourth disorganization. When scored by the OPCRIT checklist, major psychoses symptomatology is composed of excitement, depressive, delusion and disorganization symptoms.

Reliability and validity of the Premorbid Adjustment Scale (PAS) in a German sample of schizophrenic and schizoaffective patients

Abstract Premorbid functioning seems to be a phenomenological marker that possibly distinguishes a subtype of schizophrenia. The Premorbid Adjustment Scale (PAS) is an instrument for measuring premorbid functioning. It has gained international acceptance, although little is known about the reliability and validity of the test. Here data on the reliability and validity of the test derived from a German sample of schizoaffective and schizophrenic subjects (n = 86) and their healthy parents (n = 38) is presented. The DSM-IV diagnosis, PAS and Positive and Negative Syndrome Scale (PANSS) data were used as well as data on the course of the disorder. The estimation of the reliability per scale by internal consistency showed high positive values of Cronbach’s α between 0.809 and 0.931. High scores in PAS representing a bad premorbid social adjustment correlated significantly with a low age of onset, high PANSS scores, an insidious onset and a long period of hospitalisation. The disorganised DSM-IV subtype of schizophrenia showed a trend towards higher mean PAS scores. In the presented sample, the threshold between schizophrenics and healthy individuals is at 0.23. The PAS values higher than 0.53 appeared in patients with an unfavourable course of the disorder. These findings correspond with previous reports in the literature.

Zur Reliabilität und Validität der deutschen Version der Prämorbiden Anpassungsskala (PAS)

ZusammenfassungDie von Cannon-Spoor et al. 1982 für Forschungszwecke entwickelte Prämorbide Anpassungsskala (PAS) hat international Bedeutung erlangt. Sie soll messen, bis zu welchem Grad soziale Entwicklungsziele prämorbide erreicht wurden. In dieser Arbeit wird mit ersten Daten zur Reliabilität und Validität die deutsche Version vorgelegt. Bei einer Stichprobe schizophrener und schizoaffektiver Patienten (n=86) und gesunden Eltern der Patienten (n=38) wurden neben der DSM-IV-Diagnose PAS- und PANSS-Daten sowie Angaben zum Krankheitsverlauf erhoben. Die Reliabilitätsschätzung mittels Cronbachs α lag auch für die Subskalen zwischen 0,809 und 0,931. Hohe PAS-Scores, die eine schlechte prämorbide Anpassung repräsentieren, korrelierten jeweils signifikant mit niedrigem Alter bei Krankheitsbeginn, hohen PANSS-Werten, schleichendem Krankheitsbeginn, langer Dauer der stationären Behandlung und schwerem Krankheitsverlauf. Der PAS-Schwellenwert lag zwischen gesunden und kranken Probanden bei 0,23, ein eher ungünstiger Krankheitsverlauf zeichnete sich bei PAS-Werten > 0,53 ab. Die Vorhersagewahrscheinlichkeit für die Schizophrenie lag bei PAS-Werten > 0,23 bei OR=27,9 (95% CI 9,39–82,89). Die vorgelegten Befunde stimmen mit der bisherigen Literatur überein.SummaryThe Premorbid Adjustment Scale (PAS) was developed by Cannon-Spoor et al. 1982 for research use and has gained importance internationally. This scale is designed to measure the extent of attaining developmental goals premorbidly. The German version is presented here, with first data on the reliability and validity of the scale. In a sample of schizophrenic and schizoaffective patients (n=86) and healthy parents of the patients (n=38), DSM-IV diagnosis was made and PAS and Positive and Negative Syndrome Scale (PANSS) data were taken along with information on the course of the disorder. Using Cronbachs α, the estimated reliability for the scale and subscales lay between 0.809 and 0.931. High PAS scores, representing poor premorbid adjustment, correlated significantly with low age of onset, high PANSS scores, insidious onset, long hospitalisation, and serious course of the disorder. The threshold of PAS scores between healthy and sick probands was at 0.23. Patients with scores > 0.53 appeared to have an unfavourable course. With test results > 0.23, an odds ratio of 27.9 was ascertained (95% CI 9.39–M82.89). The findings presented correspond with those from previous reports in literature.

Affective symptomatology in schizophrenia: a risk factor for tardive dyskinesia?

Affective symptomatology has repeatedly been suggested to confer susceptibility to tardive dyskinesia (TD). In our sample of 174 schizophrenic patients a history of depressive symptoms was not associated with the occurrence of TD, whereas manic symptomatology was significantly associated with the absence of TD. Thus, our data suggest that affective symptomatology cannot unambiguously be considered to predispose to TD.

Familial occurrence of tardive dyskinesia: Familial tardive dyskinesia

Objective:  Familial occurrence of tardive dyskinesia (TD) and schizophrenia has been hypothesized to confer risk to the development of TD. We investigated these hypotheses in a large patient sample applying standardized methods for phenotype characterization.