Gisela Gross

Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia

Circadian rhythm abnormalities have been described mostly with respect to manic-depressive illness; little information is available concerning circadian rhythms and schizophrenia or their influence on neuroleptic drugs. We showed previously that the MESOR of dopamine is higher in schizophrenic patients than in healthy subjects and that women who are drug-free schizophrenic have lower prolactin MESORs and lower amplitudes than healthy women. We now report the data of a cosinor analysis of tryptophan, serotonin, melatonin, and pituitary hormones in the blood of 34 healthy subjects, 90 drug-free schizophrenics, and 25 neuroleptic-treated schizophrenic patients. This data indicated a significant phase advance of serum tryptophan, prolactin, and melatonin concentrations, a trend toward a phase advance in serotonin. Thyroid stimulating hormone (TSH), and growth hormone concentrations, and decreases in the TSH MESORs among patients compared to healthy subjects. These results suggest that circadian changes, such as phase advances and alterations in MESOR, are not only present in depression but also in schizophrenia. Although neuroleptic treatment raised the prolactin MESOR and amplitude, it did not elicit any change in circadian rhythmicity among the other parameters.

Circadian rhythm of vital signs, norepinephrine, epinephrine, thyroid hormones, and cortisol in schizophrenia

Changes in the circadian rhythmicity in vital signs, catecholamines, thyroid hormones, and cortisol have been observed in psychiatric disorders, most notably in depression. With respect to schizophrenia, the literature is scanty. We report here on the circadian parameter estimates of the vital signs, epinephrine, norepinephrine, triiodothyronine, thyroxine, thyroid stimulating hormone, and cortisol in the blood of 34 healthy subjects, 89 drug-free schizophrenic patients, and 25 neuroleptic-treated schizophrenic patients. The analyses are based on the cosine model to fit the experimental data. The circadian profiles of heart rate, blood pressure, and oral temperature are similar among schizophrenic patients and healthy subjects. Neuroleptic-treated patients have significantly higher MESORs (the daily mean) of serum norepinephrine and epinephrine than healthy subjects. The TSH MESOR is significantly lower in schizophrenic patients; the MESOR of triiodothyronine also shows a tendency to be nonsignificantly lower in schizophrenic patients compared with control subjects. The circadian serum thyroxine and cortisol profiles are similar in the three groups. The data show that the circadian profiles of vital signs in drug-free chronic schizophrenic patients who are not chronically hospitalized are similar to those of healthy subjects and that the increase in serum catecholamines and the apparent lowering in some thyroid indices might induce a down-regulation in the noradrenergic receptor system that could contribute to the pathophysiology of schizophrenia.

Computerized tomography studies on schizophrenic diseases

SummaryEarlier clinical pneumoencephalographic studies showed a subgroup of schizophrenics that have small and dysplastic cerebral ventricles as well as a subgroup with a “pure defect”, i. e., a slight internal brain atrophy. In echoencephalograms of pure and mixed residual schizophrenic syndrome patients, a significantly higher average transverse diameter of the third ventricle was demonstrated compared to that in patients with complete remissions. Correlations cannot be expected between certain groups of disease, e.g., epilepsy, multiple sclerosis, or schizophrenia on the whole, and pneumoencephalographic (PEG) and CT findings. Only schizophrenics with distinct signs of pure defect that had persisted for at least 3 years revealed deviations from normal by CT and PEG, but those with irreversible fixed deformations of personality structure (“Strukturverformungen“ [9, 10]) did not. In patients who were 50 years of age or less with psychic reactive and psychopathic personality disorders, CT showed an average third ventricle diameter of 4.2 mm (range 2–6 mm). Of 117 schizophrenics (average age 35.5 years), only 28% revealed pathological CT changes. However, of 36 schizophrenics with pure residual syndromes 69% showed pathological CT findings that always concerned the third ventricle, rarely the lateral ventricles, and in no case the cortex. The average transverse diameter of the third ventricle in this subgroup with pure defect was 7.6 mm, as compared to 4.6 mm in the subgroup of schizophrenics with complete remission. There was no increase in size with increasing years until the 50th year in schizophrenics, as well as in the control group of variations of psychic being (neuroses and psychopathic personality disorders).ZusammenfassungFrühere klinisch-pneumencephalographische Untersuchungen zeigten, daß Schizophrene teilweise konstitutionell kleine und dysplastische Hirnventrikel und eine Untergruppe mit „reinem Defekt“ eine geringgradige innere Hirnatrophie aufweisen („neuroradiologisches Basalgangliensyndrom“). Bei Schizophrenen mit reinen oder gemischten Residualsyndromen konnte im Echoencephalogramm ein signifikant höherer Mittelwert des Transversaldurchmessers des 3. Ventrikels gefunden werden als bei vollremittierten schizophrenen Kranken. Zwischen bestimmten Krankheitsgruppen, z. B. Epilepsie, multiple Sklerose oder Schizophrenie im ganzen, und PEG- und CT-Befunden können keine Korrelationen erwartet werden. Nur bei Schizophrenen mit zumindest seit 3 Jahren persistierenden deutlichen Zeichen der „reinen Defizienz“ ergeben sich Abweichungen von der Norm im CT (und PEG), nicht aber bei Schizophrenen mit irreversiblen Strukturverformungen. Bei einer Kontrollgruppe mit erlebnisreaktiven Entwicklungen und psychopathischen Persönlichkeitsstörungen fand sich bis zum 50. Lebensjahr im CT ein durchschnittlicher Mittelwert des Transversaldurchmessers des 3. Ventrikels von 4,2 mm mit einer Streuung von 2 bis 6 mm. Von 117 schizophrenen Kranken mit einem durchschnittlichen Lebensalter von 35,5 Jahren boten nur 28% pathologische CT-Veränderungen. Von 36 Schizophrenen, deren Psychose vollständig, ohne Hinterlassung eines Residuums remittierte, boten 3%, dagegen von 36 Schizophrenen mit reinen Residualzuständen 69% pathologische CT-Veränderungen, die ausnahmslos den 3. Ventrikel, selten die Seitenventrikel und in keinem Fall die Hirnrinde betrafen. Der durchschnittliche Mittelwert des 3. Ventrikels betrug in der Untergruppe mit leichten reinen Residuen 7,6 mm gegenüber 4,6 mm in der Gruppe mit vollständiger Remission. Eine Altersabhängigkeit dieses Wertes (Ansteigen mit zunehmendem Lebensalter) läßt sich bis zum 50. Lebensjahr in unserem Beobachtungsgut von Schizophrenen und Variationen seelischen Wesens nicht nachweisen.

Basic Symptoms in Schizophrenic and Affective Psychoses

The study compares schizophrenic and affective psychoses with regard to basic symptoms. 30 patients in schizophrenic pre-, intra-, and postpsychotic basic stages and 30 patients in endogenous-depressive phases were examined according to the Bonn Scale for the Assessment of Basic Symptoms. The most important result is that certain cognitive basic symptoms and cenesthesias which are decisive for the development of florid productive-psychotic phenomena are found more frequently in the group of schizophrenias.

Psychopathology of Basic Stages of Schizophrenia in View of Formal Thought Disturbances

Psychopathological, nosological, and prognostic aspects of basic stages and basic symptoms, in particular consideration of formal thought disorders, are outlined. In view of the far-reaching overlap of the psychopathological pictures of the pre- und postpsychotic basic stages a Bonn Scale for the Assessment of Basic Symptoms (BSABS) including all types of basic stages was constructed. Subjective cognitive thought disorders were recorded from 69% of the patients in pure defective states, from 78% in postpsychotic reversible basic stages and from 67% in prodromes. In contrast to incoherence of thoughts, including the symptoms of the endogenomorphic-schizophrenic axial syndrome (Berner), these thought disorders are registered only on the basis of the reports of the patients and not through observation by the investigator. The difference between subjective and objective thought disorders is presumably only conditioned primarily by differences in the degree and secondarily by the psychopathological quality of the disorders. If the criteria concerning formal thought disorders and affective blunting of the schizophrenic axial syndrome or of SANS (Andreasen) are fulfilled, as a rule the patient loses the ability of perceiving, communicating, and coping with the disorders, and at the same time there is a break from an only quantitative to a qualitative abnormal phenomenon. The presence or absence of subjective or objective formal thought disorders in the beginning of the disease had no significant influence on the long-term outcome in the main sample of the Bonn study. Proceeding from the initial psychopathological syndromes 54% of the female hebephrenics with the most unfavorable long-term prognosis showed incoherence of thoughts in the first 2 years of the illness; in contrast, incoherence was seen in only 16% of the male hebephrenics for whom the long-term outcome did not differ from that of the whole sample. This and other data of the Bonn schizophrenia study seem to argue in favor of the assumption that typical incoherence of thoughts might be valuated as a criterion of unfavorable prognosis only when the phenomenon appears within the context of a hebephrenic initial syndrome in the beginning of the schizophrenic disease.

[Examinations by psychological tests in basic stages and pure residual syndromes of schizophrenic diseases (author's transl)].

SummaryThree groups of schizophrenic diseases which cannot be differentiated with regard to psychopathological cross-section syndromes were investigated by psychological tests: one group (22 cases) of reversible postpsychotic basic stages and two groups of pure residual syndromes with an average duration of disease of 9.3 years (20 cases) and 17.5 years (21 cases). All three groups revealed findings deviating significantly from the norm. The pathological values were most marked in the performance scale of HAWIE (Hamburg-WAIS), which in all groups showed a significant lowering of performance compared with verbal scale (which corresponds approximately to the premorbid intelligence level), in “KVT” and in measures of sensory-motor reaction time by “Wiener Reaktionsgerät”, less in “Benton test” and in examination with “Schreibdruckwaage”.Reversible postpsychotic asthenic basic stages could not be significantly differentiated in psychological tests from pure residual syndromes which were comparable with regard to sex and age at the onset of the disease and—in the pure residues group of 1980—with regard to age and school success. The decrease of performance in the reaction test, in the concentration test of Abels, and in the averbal part of HAWIE correlated with symptoms and factors which were found with the help of “Frankfurter Beschwerdefragebogen” in the same patients. This positive correlation was more distinct in the reversible postpsychotic basic stages than in pure residues.The findings support the global hypothesis that the deficiencies of schizophrenic stages with a component of reversible or irreversible pure potential reduction are based on disturbances of perception and interpretation of information. Also that there are no fundamental differences between cerebro-organic or psychosyndromes of schizophrenic diseases determined by the dynamic and cognitive disorders of pure deficiency.ZusammenfassungDrei testpsychologisch untersuchte Gruppen reversibler postpsychotischer Basisstadien und reiner Residuen schizophrener Erkrankungen mit kürzerer (9,3 Jahre) und längerer (17,5 Jahre) durchschnittlicher Krankheitsdauer unterscheiden sich in verschiedenen Leistungsbereichen, vor allem im Handlungsteil des HAWIE, im Konzentrations-Verlaufstest und im Reaktionsversuch signifikant gegenüber der Norm. Weniger ausgeprägt sind die Leistungsbeeinträchtigungen im visuellen Merkfähigkeitstest (Benton), nur noch unerheblich bei Untersuchungen mit der Schreibwaage.Reversible asthenische Basisstadien schizophrener Erkrankungen unterscheiden sich testpsychologisch im Leistungsbereich nicht signifikant von hinsichtlich Geschlecht, Erkrankungsalter und — bei der Gruppe der reinen Residuen von 1980 — auch hinsichtlich Lebensalter und Schulbildung vergleichbaren reinen Residualzuständen. Auch eine Diskriminanzanalyse (nach SPSS 8) ergab keine Unterschiede zwischen reversiblen Basisstadien und irreversiblen reinen Residualsyndromen in den testpsychologisch nachweisbaren Leistungsbeeinträchtigungen.Die Minderleistungen bei der Reaktionsprüfung, im Konzentrations-Verlaufstest und im Handlungsteil des HAWIE stehen in korrelativem Zusammenhang mit den im Frankfurter Beschwerdefragebogen erfaßten Beschwerden bzw. Faktoren. Dies gilt in erster Linie für die Gruppe der reversiblen Basisstadien, nur noch in geringerem Maße für die reinen Residualzustände. Ob sich hinter dieser Abschwächung der intraindividuellen Korrelationen eine Gesetzmäßigkeit verbirgt, müssen weitere Untersuchungen zeigen.

Hyperdopaminergia in schizophreniform psychosis: A chronobiological study

Circadian rhythm abnormalities have been described in various psychiatric disorders, but they have not received much attention in studies of schizophrenia and schizophreniform psychosis. The present study used the cosine model to determine the circadian patterns of amino acids, dopamine, and prolactin concentrations, which were analyzed over a 24-hour period in serum of healthy subjects, drug-free schizophrenic patients, and neuroleptic-treated schizophrenic patients. The mesor (the daily mean) of phenylalanine was lower in drug-free schizophrenic women than in healthy women. The mesors of the ratio of phenylalanine or tyrosine to competing amino acids were similar in healthy subjects and patients. The ratio of phenylalanine/competing amino acids showed a phase advance (i.e., earlier onset of the time of highest concentration) in drug-free patients compared with healthy subjects. Schizophrenic patients displayed a higher dopamine mesor than healthy subjects. Female drug-free schizophrenic patients had lower prolactin mesors and lower amplitudes (i.e., half of the total predictable change in rhythm) than healthy women. Compared with healthy subjects, schizophrenic patients showed a phase advance of circadian prolactin concentrations. Neuroleptics raised the prolactin mesor and amplitudes but did not elicit any phase change in amino acids, dopamine, or prolactin. These data confirm the indirect pharmacologic evidence of increased dopaminergic activity in schizophrenic patients that relates to dopamines precursors and to the neuroendocrine regulation of prolactin.

Altered interrelationship of dopamine prolactin thyrotropin and thyroid hormone in schizophrenic patients

SummaryIncreased dopaminergic activity has been postulated to be one of the main causes of schizophrenia. To evaluate this hypothesis further, the interrelation between dopamine, prolactin, thyrotropin (TSH) and l-thyroxine was studied by determining their concentrations in the serum of ten acutely ill schizophrenic patients exhibiting distinct stages of process activity and ten healthy subjects. The level of dopamine was elevated in the sera of schizophrenic patients, whereas the levels of prolactin, TSH and l-thyroxine were decreased. On the basis of these results we hypothesize that 1. increased dopaminergic activity affects pituitary secretory function, and 2. decreased β-adrenergic activity may be a consequence of decreased thyroid hormone concentration in plasma.

Classification Prognosis of Schizophrenic Disorders in Light of the Bonn Foliow-Up Studies

In the Bonn Schizophrenia Study ( Huber et al, Monogr. Gesamtgebiete Psychiat., vol. 21, Springer, Berlin 1979) 113 cases fulfilled the criteria for four types of schizo-affective an

Sind selbst wahrnehmbare neuropsychologische Defizite bei Patienten mit Neurose- oder Persönlichkeitsstörungs- diagnosen für spätere schizophrene Erkrankungen prädiktiv?

ZusammenfassungDiese Studie überprüft erstmals die mögliche prädiktive Aussagekraft früher selbst wahrgenommener neuropsychologischer Defizite für die spätere Entwicklung einer Schizophrenie. 96 Fälle mit DSM-III-R-Diagnosen vorwiegend aus dem Bereich der Neurosenachfolgebestimmungen und Persönlichkeitsstörungen, die bei der Indexuntersuchung zu 81 % solche Basisstörungen geboten hatten und deshalb gemäß der Prüfhypothese als stark psychosegefährdete Patientengruppe einzustufen waren, wurden im Hinblick auf schizophrene Symptombildungen nachuntersucht. Nach einer Follow-up-Periode von durchschnittlich ca. 8 Jahren hatte mehr als die Hälfte dieser Patienten nach DSM-III-R-Kriterien eine schizophrene Störung entwickelt. Die Outcome-Alternative Schizophrenie vs. keine Schizophrenie wurde durch den Unterschied, ob die Betroffenen bei der Indexuntersuchung selbst erlebte Wahrnehmungs-, Denk-, Sprach- und Handlungsstörungen angegeben hatten oder nicht, in 77 % der Fälle korrekt vorhergesagt.SummeryFor the first time, the present study assessed the achievable predictive value of early self-experienced neuropsychological deficits for the fater development of schizophrenia. Ninety-six patients with DSM-III-R diagnoses mainly of the formerly neurotic or personality disordered field, of whom 81 % had shown such basic disorders at the time of the index examination and therefore were classified as persons at high risk of developing schizophrenia, were re-examined for schizophrenia. After an average follow-up period of about 8 years, more than half of the re-examined sample had developed a schizophrenic disorder according to DSM-III-R. The outcome of schizophrenia versus no schizophrenia was predicted correctly in 77 % of cases by the presence or absence of self-experienced disturbances of perception, thought, speech or action.