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A dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p

Reliability and validity of the Quality of Life (QoL) construct were investigated in healthy controls (N=346), patients with depression (N=114) and patients with schizophrenia (N=91) using two different QoL instruments: the Short-Form 36 (SF-36), a well-established generic instrument measuring eight dimensions; and the Modular System for Quality of Life (MSQoL), a recently developed instrument measuring seven core dimensions and four specific modules (objective data, partnership, family, occupation). The MSQoL and the SF-36 were administered at three intervals (hospital admission, discharge and 4-month follow-up). Reliability, group profiles (clinical specificity), responsiveness, discriminant validity (with regard to sociodemographic, psychopathological, clinical and state variables) and convergent validity were tested. At admission, patients with depression had the lowest QoL level, patients with schizophrenia had an intermediate level, and controls had the highest QoL level. At discharge and follow-up, the two patient groups did not differ from each other, but still had lower levels than controls. Both patient groups improved significantly in QoL from admission to discharge. This improvement was confounded by improvement in depressive symptoms, but not in positive or negative symptoms. Current mood state influenced QoL assessments in all three samples substantially. In conclusion, QoL can be measured reliably and with sufficient responsiveness by the MSQoL and the SF-36 in psychiatric and non-clinical populations, although discriminant validity with regard to depression and current mood is questionable.

Prolactin (PRL) and Cortisol (CORT) responses to d,l-fenfluramine (FEN) challenge (60 mg) were examined in patients with affective disorders on two occasions under euthymic conditions: drug-free before admission to prophylactic treatment and after about 9 months of medication with lithium or carbamazepine. Response to treatment was assessed by a complex algorithm using continuous ratings in outpatient clinic over a period of 2 years. In general, treatment resulted in a delayed and diminished CORT release (n.s.); subgroup analysis revealed an attenuated CORT response (P0.05) in responders, whereas nonresponders showed no change in CORT secretion pattern except an enhanced CORT baseline value (P0.05). Cross-sectional comparison of responders with nonresponders under medication yielded a trend for greater CORT stimulation in nonresponders. This result was not affected by FEN/NorFEN or lithium/carbamazepine serum levels, baseline CORT values, age, sex, diagnostic distribution, number of appointments to the outpatient clinic or duration of medication at the time of FEN test session. Before onset of prophylactic medication responders and nonresponders could not be discriminated significantly regarding stimulated hormone release, probably due to the small sample size (n = 17). CORT response to FEN was increased in drugfree unipolar patients compared to bipolar (P0.05) and to schizoaffective patients (P0.1). In accordance with its well-documented presynaptic 5-HT-agonistic action lithium medication resulted in a significantly greater increase in CORT release than carbamazepine (P0.05). Evaluation of PRL stimulation showed patterns of secretion quite similar to those of CORT, without reaching statistical significance in most cases. Perhaps due to methodological differences in assessing treatment response, these data do not confirm former results, which supposed an enhanced 5-HT net activity in long-term prophylactic lithium treatment. Because of high interindividual variances of hormone parameters, the FEN-test procedure is not a useful tool for the prediction of therapeutical outcome in terms of clinical routine use. Relations of stimulated hormone response as a marker of central serotoninergic activity and clinical outcome are discussed.

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in 144 patients with bipolar disorder (74 vs. 70 patients; observation period: 2.5 years; lithium serum level: 0.63 +/- 0.12 mmol/l, carbamazepine dose: 621 +/- 186 mg/day). Hospitalisations, recurrences, need of psychotropic comedication and adverse effects prompting discontinuation were defined as treatment failures. Survival analyses regarding hospitalisations and recurrences showed no statistically significant differences between both drugs. Results were distinctly in favour of lithium, considering recurrences combined with comedication (P = 0.041) and/or adverse effects (P = 0.007). Whereas adverse effects prompting discontinuation were more frequent under carbamazepine (9 vs. 4, ns), lithium patients reported more often slight/moderate side effects (61% vs. 21% after 2.5 years; P = 0.0006). In completers, recurrences occurred in 28% (lithium) vs. 47% (carbamazepine) of the patients (P = 0.06). Lithium seems to be superior to carbamazepine in maintenance treatment of bipolar disorder, in particular when applying broader outcome criteria including psychotropic comedication and severe side effects.

The study explores whether minor symptoms of patients in recovery from a mood disorder have an impact on self-ratings of personality with special consideration of potential differences between diagnostic groups. 90 recovered DSM-III-R major unipolar depressives and 167 recovered bipolars were compared with respect to scale values of the Munich Personality Test (MPT). Major depressives showed significantly higher scores on the MPT scales Rigidity and Orientation towards Social Norms, and lower scores on Extraversion than the bipolar patients. Using a LISREL-model, psychopathology was found to have a significant impact on Neuroticism and Extraversion, but not on Rigidity and on Orientation towards Social Norms. Controlling for symptomatology, the differences in the MPT scale values of the two diagnostic groups remained significant and can hardly be sufficiently explained by residual symptomatology.

Neuropeptides appear to play a role in the pathophysiology of depression and electroconvulsive treatment and lithium affect these compounds in human cerebrospinal fluid (CSF) and rodent brain. Consequently, we investigated whether long-term treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram (Cit) would also affect neuropeptides in CSF of depressed patients. Changes in CSF monoamine metabolites were also explored. CSF concentrations of corticotropin-releasing hormone (CRH)-like immunoreactivity (-LI), neuropeptide Y (NPY)-LI, and Cit were determined in 21 patients with major depression. Lumbar puncture was performed in the morning at baseline and was repeated after at least 4 wk of Cit treatment (40 mg/d). The severity of depression was assessed by the Hamilton Rating Scale for Depression (HAMD). Cit treatment was associated with a significant increase in NPY-LI and decrease in CRH-LI. An evaluation of the relationship between changes in concentrations of NPY-LI, CRH-LI, and the clinical response showed significant correlations between these parameters. Significant NPY and CRH changes in CSF following treatment as well as correlations to changes in HAMD support the hypothesis that these two peptides play a role in affective disorders and are markers of therapeutic response.

Plasma and cerebrospinal fluid (CSF) concentrations of the enantiomers of citalopram (CIT), its N-demethylated metabolite demethylcitalopram (DCIT) and its deaminated metabolite citalopram propionic acid derivative (CIT-PROP) were measured in plasma and CSF in 22 depressed patients after a 4-week treatment with 40 mg/d citalopram, which was preceded by a 1-week washout period. CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured at baseline and after the 4-week CIT medication period. Patients were assessed clinically, using the Hamilton Depression Rating Scale (21-item HAM-D): at baseline and then at weekly intervals. CSF concentrations of S-CIT and R-CIT were 10.6 +/- 4.3 and 20.9 +/- 6 ng/mL, respectively, and their CSF/plasma ratios were 52% +/- 9% and 48% +/- 6%, respectively. The CIT treatment resulted in a significant decrease (28%) of 5-HIAA (P0.0001) and a significant increase (41%) of HVA in the CSF. Multiple linear regression analyses were performed to identify the impact of plasma and CSF CIT enantiomers and its metabolites on CSF monoamine metabolites and clinical response. There were 10 responders as defined by aor =50% decrease of the HAM-D score (DeltaHAM-D) after the 4-week treatment. DeltaHAM-D correlated (Spearman) significantly with CSF S-CIT (r = - 0.483, P0.05), CSF S-CIT-PROP (r = -0.543, P = 0.01) (a metabolite formed from CIT by monoamine oxidase [MAO]) and 5-HIAA decrease (Delta5-HIAA) (r = 0.572, P = 0.01). The demonstrated correlations between pharmacokinetic parameters and the clinical outcome as well as 5-HIAA changes indicate that monitoring of plasma S-CIT, CSF S-CIT and CSF S-CIT-PROP may be of clinical relevance.

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in schizoaffective disorder. A total of 90 ICD-9 schizoaffective patients were included in the maintenance phase (2.5 years). They were also diagnosed according to RDC and DSM-III-R and classified into subgroups. Mean serum levels were 0.58 +/- 0.12 mmol/l for lithium and 6.4 +/- 1.5 micrograms/ml for carbamazepine (mean dose 643 +/- 179 mg/d). Outcome criteria were hospitalisation, recurrence, concomitant psychotropic medication and adverse effects leading to discontinuation. There were more non-completers under carbamazepine than under lithium (p = 0.02). Survival analyses demonstrated no significant differences between lithium and carbamazepine in treatment outcome. Patient's ratings of side effects (p = 0.003) and treatment satisfaction (p = 0.02) favoured carbamazepine. Following the RDC criteria, patients of the schizodepressive and non-classifiable type did better under carbamazepine (p = 0.055 for recurrence), whereas in the schizomanic patients equipotency of both drugs was found. Applying DSM-III-R, carbamazepine demonstrated a superiority in the patient group with more schizophrenia-like or depressive disorders (p = 0.040 for recurrence), but not in patients fulfilling the DSM-III-R criteria of bipolar disorder. Lithium and carbamazepine seem to be equipotent alternatives in the maintenance treatment of broadly defined schizoaffective disorders. However, in subgroups with depressive or schizophrenia-like features and regarding its long-term tolerability carbamazepine seems to be superior.

Die gesundheitsbezogene Lebensqualitatsforschung, die sich insbesondere aus dem Bedurfnis nach einem „weichen“ Therapieeffizienzkriterium motiviert, ist zur Zeit durch einen Zustand begrifflicher und empirischer Unklarheit charakterisiert, fur den das Motto der anarchistischen Erkenntnistheorie „anything goes“ (Feyerabend, 1983) eine adaquate Beschreibung liefert: Bereits nach Durchsicht weniger Standardwerke (Bowling, 1991; Walker und Rosser, 1988; Wenger et al., 1984) sowie des Programmes zum letzten „Quality of life “-Kongres in Wien (Association of European Psychiatrists, 1994) stost man auf nicht weniger als 104 Mesinstrumente, die alle in irgendeiner Weise vorgeben, Lebensqualitat (LQ) erheben zu konnen. Daruberhinaus scheint die Konzeptualisierung des Konstruktes LQ weitgehend der definitorischen Willkur eines jeden Autors uberlassen mit der Folge eines vorwiegend atheoretischen Aktivismus mit ebenso vielen in- und expliziten Modellierungen wie Operationalisierungen.

The paper reports on the process of patient recruitment for a controlled clinical multicenter study on the treatment of affective disorders. Two thirds of the patients screened did not participate because prophylactic treatment was either unnecessary or not justified for medical reasons. Further, a number of patients equal to that eventually allocated to the trial refused to participate for personal, idiosyncratic reasons. In spite of this, the patients in the trial were very similar to those not participating with respect to relevant variables such as age, sex, number of and intervals between previous episodes or severity of the present episode.

Eine definitorische Abgrenzung der Begriffe „Einsamkeit“, „Alleinsein“ und „Vereinsamung“ unter philosophischem und soziologischem Aspekt wird anhand entsprechender Aussagen der Literatur — vor allem auch im Hinblick auf eine wertende Einstellung — versucht. In der mit dem Polaritatenprofil gemessenen wertenden Einstellung zur Einsamkeit ergeben sich bei unserem Normal-Personenkollektiv deutliche Unterschiede im Vergleich zur Einstellungsattitudenposition des deutschen Hofstatterschen Kollektivs von 1957 einerseits bzw. eine Angleichung an die von ihm zum gleichen Zeitpunkt gemessene amerikanische Einstellung andererseits. Dieses Ergebnis wird auf dem zeitgeschichtlichen Hintergrund als Hinweis einer Anpassung an den Zeitgeist interpretiert. Des weiteren wurde nicht nur die Einstellung gegenuber der Einsamkeit, sondern auch das Einsamkeitserleben sowohl bei gesunden (112) Versuchspersonen als auch bei neurotischen (56) Versuchspersonen untersucht. Anhand der Klassifizierung der Einsamkeitsproblematik schien eine eindeutige Abgrenzung zwischen Gesunden und Neurotikem moglich. Es zeigt sich, das Neurotiker hochst signifikant starker unter Einsamkeit leiden und sich einsamer fuhlen, jedoch weniger kommunikationswillig und kontaktfreudig sind als Gesunde. Hinsichtlich der nosologischen Zuordnung ergab sich anhand der Einsamkeitsvariablen eine diagnostische Trefferwahrscheinlichkeit von 78%, was dafur spricht, das sich die Einsamkeitsproblematik als ein fur das Ereignis Neurose relevanter Aspekt erweist.

Je 32 endogen Depressive und Schizophrene wurden im akuten Stadium ihrer Erkrankung und kurz vor der Entlassung aus der stationaren Behandlung hinsichtlich ihres Einsamkeitserlebens untersucht. Depressive fuhlen sich intrapsychotisch sehr signifikant einsamer und leiden mehr unter ihrer Einsamkeit als Schizophrene. Postpsychotisch besteht kein Unterschied zwischen den Krankheitsgruppen. Die Kontaktfahigkeit und der aktive Umweltbezug der Depressiven ist wahrend der Erkrankung sehr signifikant geringer als bei Schizophrenen, bei denen sich wiederum keine Anderung dieses Erlebnisaspektes intraoder postpsychotisch ergibt.

The effect of longstanding therapy using lithium salts compared to other psychotropic drugs in combination with lithium salts or other psychotropic drugs alone, on the human EEG is examined and compared with the literature. We found in our sample of 56 patients under lithium therapy: (1) that lithium salts – like other psychotropic drugs – evoke a significant increase in paroxysmal dysrhythmic activity and EEG abnormalities collectively; (2) that lithium salts cause an increase in rhythmical patterns and abnormalities in vigilance; and that (3) the combination of lithium salts with other psychotropic drugs leads to a significant augmentation of focal abnormalities of the left brain area and epileptic potentials, while EEG recordings without abnormalities are significantly diminished under this therapy. It results from this investigation that the risk for central decompensation in relation to the individual disposition seems to be especially high for the combination therapy.

Anhand von Beobachtungen an 6 Fallen — von denen einer ausfuhrlich mitgeteilt wird — sollte versucht werden, die Personlichkeitsstruktur und Phanomenologie der sog. „primaren Thalamusschwache“ mit ihren unterschiedlichen Verlaufsformen — angefangen bei Normvarianten primar sensibler Menschen, wie sie auch in der modernen Literatur ihren Niederschlag gefunden haben, uber Zustandsbilder bis zu krisenhaften und prozeshaften Verlaufstypen — herauszuarbeiten, was uns besonders hinsichtlich der differentialdiagnostischen Abgrenzung und der damit zusammenhangenden prognostischen Uberlegungen wunschenswert und notwendig erschien.

The purpose of this paper is to test the hypothesis that hormones secreted by the ovaries are responsible for a “protective mechanism” of blood pressure regulation of the woman. Under physiologic conditions, there was a distinct correlation between the degree of estrogenic activity and the blood pressure response. This was true for normotensive women at rest and under stress. This protective mechanism was also demonstrated in pharmacologic experiments when estrogens were administered to ovariectomized women. An additional activity of progestins caused a slight alteration of the systolic blood pressure response to stress but did not abolish the effect of estrogens.

Wenn man die hier uberpruften Parameter des kardiovaskularen Systems gemeinsam betrachtet, so hebt sich sowohl die Gruppe der endogen Depressiven als auch die Gruppe der Agitierten beider diagnostischer Zuordnungen zunachst einmal mit einem hoheren Ausgangsniveau von den ubrigen Gruppen ab, was am deutlichsten bei den agitiert endogen Depressiven sichtbar wird.

Wie der Uberblick uber die bisher referierte Literatur zur Frage pathophysiologischer, biochemischer und neuroendokrinologischer Veranderungen bei Depressionen zeigt, last sich keine allgemeingultige, die einzelnen Bereiche umgreifende Theorie der den Depressionen evtl. zugrundeliegenden oder zumindest begleitenden Dysfunktionen schlussig belegen.

In den vorangehenden Kapiteln wurde immer wieder auf die Schwierigkeit und zugleich Notwendigkeit der Zuordnung der einzelnen depressiven Syndrome zu bestimmten diagnostisch-„nosologischen“, syndromatologischen und symptomatologischen Gruppierungen verwiesen.