H. Hecht

Increased sensitivity to agonist stimulation of the Ca2+ response in neutrophils of manic-depressive patients: effect of lithium therapy.

The agonist-stimulated increase of intracellular free-Ca2+ concentration, an indicator of the sensitivity of the inositol phospholipid second-messenger generating system, was measured in neutrophils from patients with manic-depressive disorder, and controls. Dose-response curves of the calcium response were determined by measuring the fluorescence of neutrophils loaded with fura-2 and stimulated with various concentrations of the chemotactic tripeptide formylmethionylleucylphenylalanine. EC50 values were obtained for 14 medication-free patients (5 acutely depressive, and 9 symptom free remitted patients with a history of manic-depression or recurrent major depression), 9 lithium-treated, euthymic manic-depressive patients and 10 drug-free healthy controls. The EC50 values of the untreated patients were significantly lower than in the controls. Lithium-treated patients had EC50 values significantly higher than controls. These results suggest that manic-depressive disorder is associated with an increased sensitivity of the inositol phospholipid second-messenger generating system, which is counteracted by lithium treatment.

An empirical comparison of diagnoses and reliabilities in ICD-10 and DSM-III-R.

SummaryThe psychiatric classification systems ICD-10 and DSM-III-R were compared by applying both sets of diagnostic criteria to the same sample of patients suffering from affective and psychotic disorders. Four independent raters assessed diagnoses according to both systems to 100 written case records which had been prepared in a traditional, standard format. The International Diagnostic Checklists (IDCL) were employed to rate relevant psychopathological signs and symptoms and to apply diagnostic decision rules. The results showed that ICD-10 yielded a generally higher reliability for all main disorders except for bipolar disorder. Overall reliability was κ=0.53 for diagnoses according to DSM-III-R and 0.59 for diagnoses according to ICD-10. Agreement was best for affective disorders, moderate for schizophrenia and inacceptable for schizoaffective disorder. Insufficient boundaries were found in both systems between schizoaffective disorder on one side and schizophrenia and bipolar disorder on the other side. The different duration criteria for schizophrenia of six months in DSM-III-R and one month in ICD-10 tend to have considerable consequences for frequency rates of schizophrenia in a typical clinical setting.

PREMORBID PERSONALITY IN PATIENTS WITH UNI- AND BIPOLAR AFFECTIVE DISORDERS AND CONTROLS : ASSESSMENT BY THE BIOGRAPHICAL PERSONALITY INTERVIEW (BPI)

The relationship between premorbid personality and subtypes of affective disorder was investigated by means of the Biographical Personality Interview (BPI) and by a self-rating scale. Interview and rater (BPI) were blind to diagnosis. A total of 52 patients with unipolar depression or bipolar II disorder (D/Dm), 32 bipolar-I patients (DM) and 39 control subjects (C) were examined. Expert rating of “typus melancholicus” features (BPI) were found to be more pronounced in D/Dm than in DM and C. “Typus manicus” features were also distinguished between both clinical groups, whereas anxious-insecure features were not significantly different between the groups of patients. In contrast to the expert-rated personality variants, self-rating of personality features did not reveal any significant differences between the two clinical groups. Potential sources of the discrepancies between the questionnaire data and the interview data are discussed. It is concluded that premorbid features of “typus manicus” and “typus melancholicus” predicted, respectively, a predominant manic and a predominant depressive course of an affective disorder.

Increased sensitivity of the inositol-phospholipid system in neutrophils from patients with acute major depressive episodes

Evidence from in vitro and in vivo studies suggests that the therapeutic and prophylactic effects of lithium in recurrent affective disorders are due to an attenuation of the inositol-phospholipid (IPL) second messenger system. An increased sensitivity of this signal transduction system might therefore constitute a risk factor for affective illness. The extent of the agonist-induced release of intracellular Ca2+ (Ca2+ response) can be used as an indicator of the sensitivity of the IPL system. Using this paradigm, we have measured the agonist-induced Ca2+ response in neutrophils of 17 unmedicated patients who were experiencing an acute major depressive episode. The neutrophils were stimulated by the chemotactic peptide formylmethionylleucylphenylalanine, which activates the IPL system in the cells. The sensitivity of the IPL system in these patients was significantly greater (dose-response curve shifted to the left) compared with its sensitivity in healthy age- and sex-matched control subjects. The results indicate that acute episodes of major depression are associated with an increased sensitivity of the IPL system.

Testing the comparability of psychiatric diagnoses in ICD-10 and DSM-III-R

The compatibility of the classification systems ICD-10 and DSM-III-R was investigated in a sample of 100 psychiatric inpatients with severe affective and psychotic disorders. Four independent raters assessed diagnoses by means of checklists from psychopathological descriptions of case records. Congruence between ICD-10 and DSM-III-R was good for depressive disorders with agreement rates above 80% and fair for bipolar disorders with rates above 60%. Less consistent findings were obtained for schizophrenia with rates of 57.5% for ICD-10 diagnoses and 82.6% for DSM-III-R diagnoses. Agreement for schizoaffective disorder was below 40% and thus insufficient. The results indicate that even small differences in the definitions of mental disorders may result in considerable inconsistencies.

Sensitivität des Inositolphosphat/Ca2+-second messenger Systems bei affektiven Störungen: Pathogenetischer Faktor und Angriffspunkt prophylaktischer Lithiumtherapie?

Signaltransduktionsmechanismen, also die biochemischen Prozesse, die das von einem Hormon oder Neurotransmitter an die Zelloberflache ubermittelte Signal in das Innere der Zelle weiterleiten, sind in den letzten Jahren ins Zentrum des Interesses biologisch-psychiatrischer Forschung geruckt (Ubersicht: Lachman et al. 1989, Baraban et al. 1989, Snyder 1992). Ausschlaggebend fur diese Entwicklung waren neuere Befunde der praklinischen Forschung, die nahelegten, das die therapeutischen und rezidivprophylaktischen Wirkungen von Lithiumsalzen bei affektiven Storungen wahrscheinlich auf einer lithiuminduzierten Hemmung eines biologisch besonders wichtigen Signaltransduktionssystems, des Inositolphosphat (IP)-Ca2+-Systems beruhen. Dieses System vermittelt die Signaltransduktion von Rezeptoren fur Noradrenalin, Acetylcholin und Serotonin (Ubersicht: Baraban et al. 1989), Neurotransmitter, deren Dysregulation fur das Auftreten depressiver und manischer Symptome verantwortlich zu sein scheint (Ubersicht: Bohus und Berger 1992).