H(2)-histamine antagonist (famotidine) induced adverse CNS reactions with long-standing secondary mania and epileptic seizures.

We report on the case of a 65-year-old female who was treated for one week with famotidine, a reversible H(2)-histamine antagonist, due to gastric pain. Shortly after treatment began, she presented manic symptoms and developed two generalized seizures, after which famotidine was discontinued. Manic symptoms were present for three months; intermittent treatment with both carbamazepine and antipsychotic medication was necessary before her mental status was completely restored. While cimetidine and ranitidine are known to cause secondary mania, this symptom has not been described for famotidine. CNS side effects are usually short-lived and respond to discontinuation of the drug, which was not the case in our patient. During a follow-up period that has so far lasted four years, the patient has been stable without any psychiatric medication. Adjusting the maintenance dosage of H(2)-histamine antagonists has been recommended in elderly patients since age-related reduction in renal plasma flow, glomerular filtration rate and renal tubular function may be present, which can in turn elevate histamine levels in plasma and cerebrospinal fluid. Our patient, however, had normal renal function and was free of organic or psychiatric diseases, so what pathogenetic mechanism led to the remarkably long standing manic syndrome after a relatively short course of famotidine remained unknown; famotidine seems to cause the same spectrum of adverse central nervous system (CNS) reactions as other H(2)-histamine antagonists.

High sensitivity detection of JC-virus DNA in postmortem brain tissue by in situ PCR.

Opportunistic infection of the central nervous system by human polyomavirus JC can cause a devastating disease, progressive multifocal leukoencephalopathy (PML). To gain new neuropathological insights into JC-virus (JCV) infection patterns in PML at the light microscopic level, the highly sensitive indirect in situ polymerase chain reaction (in situ PCR) was employed in up to 15-year old formalin-fixed and paraffin-embedded postmortem brain tissue derived from nine AIDS patients with PML. In situ PCR, in which target DNA is amplified intracellularly and detected by a specific labelled probe in morphologically intact tissue, was compared with conventional in situ hybridization (ISH). Validity was ensured by the inclusion of 13 controls. JCV detection with in situ PCR proved to be highly sensitive since in all nine brain samples the number of positive cells exceeded the ISH results by 2-3-fold. Whereas by routine staining the brain tissue of each individual patient showed regions with severe, mild or no involvement by PML, improved detection of JCV DNA by in situ PCR allowed a regrading into five different degrees of JCV infection. Significant myelin staining was observed, suggesting that cell-to-cell contact may not be the only means of virus spread but that new cells could also be infected by virus released after cell lysis. Furthermore, using in situ PCR hitherto unreported intracellular distribution patterns of JCV DNA in oligodendro- and astrocytes were observed by light microscopy.

Asymptomatic pancreatitis associated with clozapine.

Besides the well-known adverse effects of clozapine, such as granulocytopenia, tiredness and hypersalivation, acute pancreatitis is known to be a very rare complication of the drug. In the literature a total of five case reports have been published so far. We report a case of asymptomatic pancreatitis subsequent to clozapine treatment at therapeutic doses in a 38-year-old male patient with chronic paranoid-hallucinatory schizophrenia. The patient was rehospitalized after an acute exacerbation of the psychosis subsequent to an attempt to change medication on an outpatient basis. Treatment with clozapine was initiated again. During phases of progressively increasing the clozapine dose, serum levels of amylase and lipase were increased; after maintaining daily doses of clozapine of 300 mg and/or 600 mg the pancreatic enzymes normalized quickly within a few days. The patient did not report any pancreas-related complaints, nor did specific diagnostic studies produce any indicative result, only a minor thickening of the head and body of the pancreas in the ultrasound. It is assumed that the phenomenon of subclinical, asymptomatic pancreatitis during increasing dosage of clozapine occurs more often than previously supposed. The monitoring of serum amylase levels during slow increase in clozapine is recommended; if leukocytosis or eosinophilia is present, the possibility of even a subclinical and asymptomatic pancreatitis should be considered.

Are psychoactive-drug-induced changes in plasma lipid and lipoprotein levels of significance for clinical remission in psychiatric disorders?

In the present pilot study, our aim was to investigate whether associations could be demonstrated in psychiatric patients between the changes in plasma lipid and lipoprotein levels expected during treatment with psychoactive drugs and the changes in the patients' depressive and hostile behavior. One hundred and fourteen patients with various psychiatric disorders (depressive episode in bipolar affective disorder, depressive episode or recurrent depressive disorder, paranoid schizophrenia, and schizoaffective disorders) were included in the study. The following examinations were carried out in each patient on admission and at discharge: (1) the plasma lipid parameters total cholesterol (TC), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), high-density lipoprotein (HDL), and triglycerides (TRI) were determined, and (2) the psychopathological features were recorded employing the AMDP system and the AMDP Syndrome Scales. Within the context of a naturalistic clinical setting with a choice of psychoactive drugs available, patients were subdivided at the end of treatment into eight treatment groups, as follows: group 1, treatment with butyrophenones; group 2, treatment with tricyclics; group 3, treatment with butyrophenones and tricyclics; group 4, treatment with butyrophenones, tricyclics and selective serotonin reuptake inhibitors; group 5, treatment with butyrophenones and lithium; group 6, treatment with tricyclics and lithium; group 7, treatment with butyrophenones, tricyclics and lithium; and group 8, treatment with butyrophenones, tricyclics, selective serotonin reuptake inhibitors and lithium. To compare the changes in the eight treatment groups, mixed general linear models including diagnosis, gender, age, body mass index changes, and baseline values were applied using proc GLM of SAS. Butyrophenones induce an increase in TC, LDL, and TC/TRI ratio, whereas tricyclics lead to an increase in TC, LDL, VLDL, and TRI. In combined medication of butyrophenones and tricyclics the effects of tricyclics predominate. Comedication of lithium inhibits the increase in TC and LDL induced by butyrophenones and/or tricyclics. Treatment groups with lipid changes of the same type (decrease, no change, or increase) were combined in "lipid change groups". Analyses of variance or covariance (with psychopathological admission value as covariate where there were significant differences in psychopathological admission mean values between the groups) of these lipid change groups with regard to the changes in the Depressive Syndrome Scale and the Hostility Syndrome Scale gave results which are interpreted as follows: an increase in TC or LDL inhibits the remission of hostility, whereas an increase in TRI with concomitant decrease in TC, or else a relatively greater increase in TRI than in TC promotes the remission of hostility. A decrease in TRI or VLDL promotes the remission of depression. Our data and findings published in the literature may suggest that systemic changes in plasma lipid parameters, at the cellular level, induce changes in the fluidity of brain cell membranes. We hypothesize that an increase in plasma TC or LDL and/or a decrease in plasma TRI or VLDL may induce a relative decrease in brain cell membrane fluidity with decreased presynaptic serotonin reuptake and increased postsynaptic serotonin function. This proposed increase in brain serotonin function would finally result in an anti-depressive, aggression-promoting effect. Conversely, a decrease in plasma TC or LDL and/or an increase in plasma TRI or VLDL may induce a relative increase in brain cell membrane fluidity with increased presynaptic serotonin reuptake and decreased postsynaptic serotonin function. This proposed decrease in brain serotonin function would result in an anti-aggressive, depression-promoting effect.

[The personality of unipolar depressive and bipolar manic-depressive patients]. / Zur Persönlichkeit unipolar depressiver und bipolar manisch-depressiver Patienten.

Starting from central hypotheses on the relationship between personality and affective disorders, the profiles in the Freiburg Personality Inventory (FPI-A) of 23 unipolar depressives, 26 bipolar manic-depressives and 30 healthy controls of the standardization sample were analysed. Assessment by the Freiburg Personality Inventory was carried out at the time of discharge under the instruction to refer the answers to the time before the beginning of the illness. Parallel to the personality assessment the degree of remission was documented by the scales "Depressive Syndrome", "Apathetic Syndrome" and "Manic Syndrome" of the AMDP system and the d2 concentration test. In intraclass covariance analyses the following scales showed significant differences between unipolar depressives, bipolar manic-depressives and normal controls: FPI3 "Depressiveness", FPI8 "Inhibition" and FPIE "Extraversion". The differences cannot be explained by age or sex. In contrast to manic-depressives, unipolar depressives characterize themselves as more depressive, inhibited and introverted. The bipolar manic-depressives do not differ from the norms in any scale of the FPI. These findings are compared both with the starting hypotheses and with results reported in the literature.

[Personality of schizophrenic and schizoaffective patients]. / Zur Persönlichkeit schizophrener und schizoaffektiver Patienten.

At time of discharge 33 patients with ICD-9 schizophrenia and 16 patients with ICD-9 schizoaffective psychosis were assessed by the Freiburg Personality Inventory (FPI). Psychological profiles were analyzed individually and compared to controls. In addition, a hierarchical cluster analysis was carried out. Psychopathological findings at time of discharge were documented by the AMDP system. Impact of psychopathology on response behavior in the FPI was not evident. There were but few schizophrenic or schizoaffective patients without any abnormal FPI score. For the schizophrenics abnormal (high and low) scores could especially be found on the scales "Nervousness", "Depressiveness" and "Masculinity", for the schizoaffective patients on the scales "Nervousness", "Depressiveness", "Excitability", "Extraversion" and "Neuroticism". With regard to personality both groups turned out to be heterogenous. The schizophrenics differed significantly from the controls by higher means on the scales "Nervousness" and "Depressiveness" and a lower mean on the scale "Masculinity". The schizoaffective patients differed significantly from the controls by higher means on the scales "Depressiveness" and "Inhibition". Hierarchical cluster analysis resulted in 3 clusters for the schizophrenics: 1. introverted-schizoid type (42%), 2. extraverted-aggressive type (36%), 3. normal type (22%), and 2 clusters for the schizoaffective patients: 1. emotional labile type (56%), 2 normal type (44%). Results are compared to literature.

Judgement of the hypothalamic-pituitary-adrenocortical function in psychiatric patients by betamethasone-induced cortisol suppressibility.

Betamethasone induced cortisol suppressibility was examined in 62 drug free consecutively admitted psychiatric inpatients. Betamethasone was choosen instead of the commonly used dexamethasone, because its double half-life compared to dexamethasone and its higher tissue availability. After a base-line evaluation with blood samples drawn at 8 a.m., 4 p.m., and 11 p.m., 0.5 mg or 1.0 mg betamethasone was given orally at 11 p.m. Postbetamethasone cortisol as well as betamethasone blood levels were then measured at the same time points as on the baseline day. In the groups receiving 1.0 mg betamethasone non-depressed patients had significantly (p less than 0.05) lower postbetamethasone cortisol levels than depressed patients for each time point measured whereas 0.5 mg betamethasone did not differentiate depressed from non-depressed patients. Patients with other depressions like schizoaffective psychosis-depressive subtype- or organic brain syndrome with depressive symptomatology demonstrated similar postbetamethasone cortisol profiles as the group of patients with major depression. Betamethasone plasma concentrations differed significantly (p less than 0.001) with respect to the oral dosage with higher values for the 1.0 mg betamethasone groups.

Responsiveness of microcirculation and local cold vasodilation to capsaicin in the intact and chronically denervated canine tongue.

Lingual blood flow and its distribution were determined at rest and in response to local cooling of the tongue (32 degrees C) in 6 anaesthetized, paralyzed and artificially ventilated dogs before and after two intraarterial (i.a.) injections of capsaicin (2.5 mg) at an interval of about 40 min. In 3 dogs, the same protocol was performed after degeneration of the chorda-lingual and glossopharyngeal nerves due to prior transection. In general the first i.a. injection of capsaicin resulted in a marked and the second injection in a smaller decrease of lingual blood flow. Local cooling of the tongue induced significant increases in lingual blood flow before as well as after capsaicin treatment, regardless of whether sensory innervation was intact or degenerated. In both the untreated and capsaicin treated dogs the increase in lingual blood flow during local cooling of the tongue was solely due to an increase in blood flow through the arteriovenous anastomoses, while blood flow through the capillaries of the mucosa and muscles even decreased. The findings suggest that capsaicin-induced vasoconstriction of the tongue vessels is due to a direct effect on vascular receptors. It is further suggested that cold vasodilatation of the canine tongue is not mediated by axon collaterals releasing substance P. Direct thermal effects on the intramural ganglia and the postganglionic vasomotor efferents innervating the AVAs, or on AVAs basal tone itself are suggested as the underlying mechanism.

Platelet MAO activity in patients with affective psychosis and their first-degree relatives.

26 patients with affective psychoses, 11 with the unipolar and 15 with the bipolar form of the disease, 102 first-degree relatives and healthy controls matched for age and sex were examined for their platelet MAO activity. For evaluation of enzyme activity kinetic parameters as well as activities under saturation conditions were determined. The degree of depression was estimated by two standard self-rating depression scales. Intrafamilial correlation of MAO was found. MAO activities of patients did not differ from controls, and there was no consistent difference in MAO between the relatives and their controls. Neither among patients nor among relatives or controls were there indications for a relationship between MAO and the degree of depression. Reduced MAO activity cannot be regarded as a genetic marker of vulnerability to affective psychosis.

Urinary free cortisol excretion in endogenously depressed and schizophrenic patients.

In 8 endogenously depressed and 9 schizophrenic patients, the excretion of urinary free cortisol was measured. The endogenous depressives exhibited a significantly (p less than 0.01) higher excretion of free cortisol (X = 122 microgram/24 h or X = 68 microgram/24 h) when compared to schizophrenics. This finding, earlier reported by others, suggests a hypothalamic-pituitary-adrenocortical activation in endogenously depressed patients.

[Investigations of the plasma cortisol in psychiatric diagnostic groups (author's transl)]. / Untersuchungen des Plasma-Cortisols bei psychiatrischen Krankheitsgruppen.

In 23 endogenous depressives, 24 schizophrenics, 15 manics, 23 depressed neurotics, 23 nondepressed neurotics and 29 nonpsychiatric patients as controls, the plasma cortisol in the morning (7:30 a.m.) and the evening (7:30 p.m.) was measured with radioimmunoassay. Comparing the means of the groups, significant differences were found. In the morning the means of the nondepressed neurotics (-x = 16.6 microgram/100 ml), the endogenous depressives (-x = 14.8 microgram/100 ml), and the depressed neurotics (-x = 14.4 microgram/100 ml) are greater than that of the controls (-x = 10.0 microgram/100 ml). In the evening the means of the nondepressed neurotics (-x = 8.8 microgram/100 ml), the manics (-x = 6.4 microgram/100 ml), and the endogenous depressives (-x = 7.0 microgram/100 ml) are greater than that of the controls (-x = 3.6 microgram/100 ml); also, the mean of the nondepressed neurotics (-x = 8.8 microgram/100 ml) is greater than those of the depressped neurotics (-x = 4.9 microgram/100 ml) and the schizophrenics (-x = 4.4 microgram/100 ml). The results are compared with the literature. The interpretation of the findings is problematic: probably unspecific factors of stress and specific factors of illness--at least in depressive illness of the endogenomorphic type--are relevant.

[Investigations on the change of diagnosis in the course of illness in cases with initial respectively final diagnosis 'schizophrenia', 'endogenous depression' or 'psychopathia' (author's transl)]. / Objektivierende Untersuchungen zur Diagnosennderung im Krankheitsverlauf von Fällen mit der Anfangs- bzw. Enddiagnose "Schizophrenie", "endogene Depression" oder "Psychopathie".

One hundred and fifty-two cases of changes in diagnosis of 'schizophrenia', 'endogenous depression' and 'psychopathia' in the course of illness, are statistically analyzed in regard to tendency of changes of diagnosis, sex, symptomatics and syndromatics, age of onset and duration of cycles. The changes of diagnosis show a clear tendency in favour of the diagnosis of 'schizophrenia' as opposed to 'psychopathia'. Among the cases with changed diagnoses, women are significantly over-represented. On the level of symptomatics, few significant changes of symptom frequencies can be found. More information can be obtained in the analysis on syndromatics: four out of six groups show significant changes in the intensity of syndromes; on the basis of similarities in syndrome profiles, derived from materials which are diagnostically homogeneous, the actual diagnostic components can be evaluated. The analysis of the age of onset shows significant differences of means corresponding to the expectations of the hypothetic diagnostic components. Regarding duration of cycles, significant differences of means between the groups are not to be found.

[Statistical investigations of nosological parameters (sex distribution, diagnosis, age of onset) in 120 pairs of endogenous psychotic parent-child and sibling relationships (author's transl)]. / Statistische Untersuchungen nosologischer Parameter (Geschlechtsverteilung, Diagnostik, Ersterkrankungsalter) bei 120 endogen psychotischen Elter-Kind- und Geschwister-Paaren

120 pairs of parent-child and sibling relationships with endogenous psychoses--registered through 60 schizophrenic and manic-depressive probands each--are statistically investigated with regard to the nosologically and biologically relevant parameters of sex distribution, diagnosis and age of onset.

[The distribution of blood groups (ABO, Rh-factor, MNS) in psychic disorders (author's transl)]. / Zur Blutgruppenverteilung (ABO, Rh-Faktor, MNS) bei psychischen Störungen

1. 942 resp. 821 patients with psychic disorders (843 resp. 339 patients with neurotic disorders, 443 resp. 191 patients with manic-depressive psychoses, 436 resp. 193 patients with schizophrenic psychoses, 220 resp. 98 patients with organic syndromes) are compared with regard to the distribution of the ABO blood groups and the Rh-Factor with 5.000 normal controls and of the MNS blood group with the expected distribution respectively. Significant differences are demonstrated: AB (-2.63%, P less than 0.10) in organic syndromes; Rh+ (+3.65%, P less than 0.02) in neurotic disorders; Rh+ (+3.10%, P less than 0.005) in all diagnoses; 0, Rh+ (+4.31%, P less than 0,05) in neurotic disorders; AB, Rh+ (+2.29%, P less than 0.05) in manic-depressive psychoses; A, Rh- (-1.59%, P less than 0.05) in all diagnoses; AB, Rh- (-0.58%, P less than 0.05) in all diagnoses; MNS (Ms +2.26%, MS +2.10%, MNs -3.65%, MNS -0.35%, Ns +0.52%, NS -0.88%, P less than 0.05) in all diagnoses. The results are compared with the literature, and methodical problems are discussed.

[Investigations of fasting blood glucose in endogenous depressive, schizophrenic, and neurotic patients (author's transl)]. / Untersuchungen zum Nüchternblutzucker von endogen Depressiven, Schizophrenen und Neurotikern

Fasting blood glucose was estimated in endogenous depressive, schizophrenic, and neurotic patients. Mean fasting blood glucose levels were found to be significantly increased in endogenous depressive patients as compared with schizophrenics and neurotics. This finding is thought to be a sensitive symptom for a decrease in glucose tolerance in endogenous depression. No correlation could be detected to sex, body weight: body height ratio or age. Several hypothetical explanations of the finding are discussed.

[Leukocyte count in manics, endogenous depressive, schizophrenics and neurotics]. / Untersuchungen zum weissen Blutbild von Manikern, endogen Depressiven, Schizophrenen und Neurotikern.

Manic, endogenous depressive, schizophrenic and neurotic patients, 80 (40 females, 40 males) in each diagnostic group, are compared with regard to the white blood count with one another and with normal controls. Significant differences of means were found (1) between some groups of patients concerning the total number of leucocytes (micrometer +/- microseconds, micronD), the number of neutrophil granulocytes (micrometer +/- microsecond, micronN), the number of eosinophil granulocytes (micrometer +/- microseconds, micronD; micronN +/- microseconds, micronD) and the number of lymphocytes (micronN +/- micronD), and (2) between all groups of patients and normal controls concerning the number of monocytes (micronD, micronN, micrometer, microsecond +/- micronK). The findings are discussed.