Gender differences in unipolar depression: a general population survey of adults between age 18 to 64 of German nationality.

BACKGROUND: Several studies from different epidemiological backgrounds have shown that unipolar depression is more prevalent in females than in males. This study examines gender differences in depression in a sample of 4075 probands recruited representatively from the general population in the northern German epidemiological catchment area of Lübeck. METHODS: Probands were interviewed with M-CIDI by lay interviewers. RESULTS: Being married only seems to increase the female depression risk when having children, while higher education reduced female excess; both male and female risk for depression raised sharply in separated, divorced and widowed probands. Not being employed was associated with an increased risk in male depression whereas in females risk was nearly unchanged. The gender ratio increased with the minimum number of depressive symptoms. Female excess was not reduced by a higher degree of subjective impairment or melancholic features. Females also predominated in longer episode durations. Female excess in the total group emerged beginning from adolescence with a tendency for a male excess in the prepubescent ages. No birth cohort effect was observed. LIMITATIONS: The cross-sectional design of this study precluded causal analysis of reported associations and some retrospective assessments are error-prone because of recall bias. CONCLUSIONS: We support previous findings of variations in gender differences in depression, however observed social parameter influences underline the need for a more detailed analysis of subgroups and underlying psychological mechanisms.

A comparison of GMS-A/AGECAT, DSM-III-R for dementia and depression, including subthreshold depression (SD)--results from the Berlin Aging Study (BASE).

BACKGROUND: Empirical evaluation of the agreement between different diagnostic approaches is crucial for the understanding of epidemiological results in geriatric psychiatry. OBJECTIVES: In this paper, we analyse differences between widely used diagnostic approaches of dementia and depression and offer evidence that diagnostic thresholds vary substantially on quantitative dimensions, but that conceptual and other differences between approaches must also been taken into account. METHODS: In an epidemiological study of n = 516 persons, aged 70-103 years, we compared psychiatric diagnoses of dementia and depression obtained by GMS-A/HAS-AGECAT, DSM-III-R and clinician's diagnoses of subthreshold depression (SD). RESULTS: For depression, cumulative prevalence of clinician's diagnosis (including SD, GMS-A/HAS-AGECAT and DSM-III-R defined forms) was highest, followed by GMS-A/HAS-AGECAT-diagnosis and DSM-III-R, while for dementia DSM-III-R was followed by GMS-A/HAS-AGECAT. Overall agreement between DSM-III-R and GMS-A/HAS-AGECAT was moderate. Adapting thresholds for AGECAT resulted in slightly better diagnostic efficiency. Diagnostic disagreement was found predominantly for cases with intermediate symptom severity, supporting the hypothesis of differing thresholds between DSM-III-R and GMS-A/HAS-AGECAT, while cases with lower or higher symptom severity were similarly seen as cases or non-cases. CONCLUSION: Disagreement is not only caused by conceptual differences, but also different thresholds of diagnostic algorithms. Adaptation of threshold levels should be feasible, depending on the purpose of the analysis.

What do patients in a lithium outpatient clinic know about lithium therapy?

OBJECTIVE: To determine how much patients know about lithium therapy and to examine factors that might influence this knowledge. SETTING: Lithium outpatient clinic. PATIENTS: Patients (n = 123) affiliated with a lithium outpatient clinic (mean treatment duration of 12 years). Diagnoses, according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised, included bipolar disorder, recurrent unipolar depression and schizoaffective disorder. OUTCOME MEASURES: Quantitative assessment of lithium-related knowledge, obtained by responses to a questionnaire adapted from the Lithium Knowledge Test, and factors affecting this knowledge. RESULTS: Age was negatively correlated with lithium therapy knowledge scores, whereas duration of treatment, sex, education and diagnosis appeared to be unrelated to knowledge. CONCLUSION: Patient education about lithium treatment should be intensified, especially for older patients taking lithium because adverse drug reactions pose a greater risk to the elderly.

Further evidence of human leukocyte antigen-encoded susceptibility to clozapine-induced agranulocytosis independent of ancestry.

To further examine the human leukocyte antigen (HLA)-encoded genetic susceptibility to clozapine-induced agranulocytosis (CA) we performed HLA-genotyping in a sample of German schizophrenic patients, who suffered from this haematotoxic side-effect. Thirty-one schizophrenic patients with CA (17 women and 14 men) and 77 schizophrenic comparison subjects (40 women and 37 men) were included in the study. HLA-genotyping included identification of major histocompatibility complex (MHC) class I (HLA-A, B, Cw) and class II (HLA-DR, DQ) antigens. CA was significantly associated with HLA-Cw*7 (P<0.02), DQB*0502 (P<0.04), DRB1*0101 (P<0.03) and DRB3*0202 (P<0.02). These HLA-haplotypes are also partly linked to other diseases with a strong genetic background. All other antigens revealed no association to this haematotoxic reaction. In addition, we did not find gender-related effects, whereas age seemed to be a further major risk factor of CA (P<0.0003). Thus, HLA loci may serve as genetic marker to identify subjects of different ethnic subgroups prone to this severe idiosyncratic drug reaction of clozapine. Further studies are needed to investigate whether these associations with CA are due to causal involvement or linkage disequilibrium.

Ventilatory capacity and risk for dementia.

BACKGROUND: Previous studies have found a relationship between single indicators of ventilatory capacity and measures of cognitive function, but have not addressed dementia specifically. This study examined the relationship between different indicators of ventilatory capacity and dementia, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, controlling for important confounding factors. METHODS: Cross-sectional data on participants (n = 437) of the Berlin Aging Study (BASE), which are representative of former West Berlin's living population aged 70 years and older, were analyzed. Ventilatory capacity was measured by spirometry as peak expiratory flow rate (PEF-R), forced expiratory volume in 1 second (FEV-1), maximal expiratory flow at 50% of forced vital capacity (MEF50%FVC), and maximal expiratory flow at 25% of forced vital capacity (MEF25%FVC). Odds ratios (OR) for dementia associated with ventilatory capacity were obtained by logistic regression, adjusting for age, gender, education, ApoE4 status, chronic obstructive pulmonary disease, smoking, heart failure, visual and auditory functioning, grip strength, and former physical activity. RESULTS: Separate analyses for PEF-R, FEV-1, MEF50%FVC, and MEF25%FVC revealed significantly increased odds for dementia among subjects in the lowest compared with the best functioning group in ventilatory testing. The OR associated with PEF-R > or = 2 l/s was found to be 20.4 (confidence interval [CI] 5.1-82.7). For FEV-1, MEF50%FVC, and MEF25%FVC ORs of 7.5 (CI 2.1-27.9), 4.3 (CI 1.5-12.5), and 4.7 (CI 1.3-17) were obtained, respectively. CONCLUSIONS: Ventilatory capacity, measured by spirometry in a representative sample of very elderly people, is cross-sectionally related to dementia. Taking evidence from longitudinal studies into account, this result suggests that decreased respiratory function may increase the risk for dementia, independent from already known risk factors.

Long-term therapeutic drug monitoring of clozapine and metabolites in psychiatric in- and outpatients.

RATIONALE: Clozapine is a unique antipsychotic drug, outstanding for its lack of extrapyramidal side-effects and its superior efficacy in refractory schizophrenia. However, an unambiguous concentration-response relationship has not yet been established. OBJECTIVE: We investigated serum concentrations of clozapine, norclozapine and clozapine-N-oxide in psychiatric in- and outpatients to identify particular metabolic patterns in clozapine responders and non-responders and putative threshold levels for clozapine response. METHODS: Psychiatric assessments, CYP2D6 genotype, and weekly serum concentrations of clozapine, norclozapine and clozapine-N-oxide were obtained in 34 adult schizophrenic in-and outpatients (18 men, 16 women) during 10 weeks of clozapine treatment with a naturalistic dose design. RESULTS: Responders (n=21) displayed significantly lower serum concentrations of clozapine corrected for dose compared to non-responders (n=13; P<0.05), while none of the other parameters (absolute clozapine concentration, metabolite ratios, gender) were different. Smokers had significantly lower dose-corrected clozapine concentrations. A positive correlation was observed between age and average steady state clozapine concentrations. CONCLUSIONS: These findings indicate a possible link between CYP activity and response to clozapine that is not mediated through differences in serum concentrations. No clinically meaningful pattern in serum parameters could be identified that differentiates responders from non-responders. Thus, clozapine TDM seems ineffective for predicting clinical response. Smoking behavior is a major determinant of clozapine clearance while CYP2D6 genotype does not impact clozapine disposition.

Anxiety and anxiety disorders in the old and very old--results from the Berlin Aging Study (BASE).

Within the context of the Berlin Aging Study, we examined the distribution of anxiety symptoms and disorders in a representative community sample. The participants were beyond the age of 70 years, thereby extending results from other studies not covering this age range. Additionally, we analyzed the distribution of anxiety symptoms and syndromes not fulfilling specified diagnostic criteria. A sample of 258 old (70 to 84 years) and 258 very old (85 to 103 years) subjects were examined. Anxiety disorders as defined in DSM-III-R and according to clinical judgment (diagnoses termed NOS) were assessed. In addition, items from the Geriatric Mental State-A (GMS-A) covering a wide range of symptoms of anxiety were subjected to factor analysis. The raw score distributions of anxiety subscales obtained by this procedure are examined by age, gender, education, personal living situation, and psychiatric comorbidity. The weighted overall prevalence of anxiety in the elderly community is 4.5% (n = 17), including specified (n = 8) anxiety disorders according to the DSM-III-R and unspecified (n = 9) disorders. Prevalence rates in the younger old were 4.3% and in the older old 2.3%. Weighted prevalence rates for males were 2.9% and for females 4.7%. The most common comorbid disorders were affective disorders in both age groups as well as both genders. Independently of the nosological level, 52.3% reported one or more symptoms of anxiety. Factor analysis of anxiety-related symptoms yielded 5 independent subscales, reflecting hypochondriasis, panic, phobia, worries, and vegetative anxiety. There were more phobic symptoms in the younger age group (P < .001). Except for worries and hypochondriac symptoms, females showed significantly higher anxiety in all other anxiety dimensions. There was no relation between anxiety and cognitive status or socioeconomic status (SES). Only for subjects living alone was more phobic-type anxiety found. Anxiety disorders in old and very old persons are less frequent than other psychiatric disorders of old age, and do not increase with age. Gender differences can still be observed. The symptomatic structure of anxiety seems similar to that found in younger cohorts. Thus, anxiety disorders in old age do not seem substantially different from those in younger age. Their relative contribution to the spectrum of mental disorders seems to decrease, rather than increase, with age, while at the same time anxiety symptoms are an almost daily experience.

DHEA-S plasma levels and incidence of Alzheimer's disease.

BACKGROUND: Cross-sectional studies controlling for age and gender reported a relationship between Alzheimer's disease and low dehydroepiandrosterone sulphate (DHEA-S) plasma levels. Prospective data with sufficient control for confounding factors are lacking. METHODS: A nested case-control study examined baseline DHEA-S in participants of the Berlin Aging Study. Cases (n = 14) developed dementia of the Alzheimer type within 3 years. Control group A (n = 14) was matched for gender, age, multimorbidity, and immobility. Control group B (n = 13) was matched for gender and age and comprised participants free from multimorbidity, immobility, multimedication, need of help, incontinence, visual impairment, hearing impairment, and depression. RESULTS: The mean plasma DHEA-S concentration of case subjects was 1.02 +/- 0.61 mumol/L. Both control groups had higher mean DEHA-S levels, in control group A, it was 1.89 +/- 1.24 mumol/L (p = .012) and in control group B 1.70 +/- 1.38 mumol/L (p = .093). CONCLUSIONS: This population-based prospective study supports the role of DHEA-S as a risk factor for Alzheimer's disease.

The impact of psychosocial and clinical variables on duration of inpatient treatment for depression.

The duration of psychiatric hospital stays becomes increasingly important as economic pressures on medicine mount. Psychiatric hospitals, in particular, search for ways to cut costs without sacrificing efficiency. There is no doubt that clinical depression is one of the most important cost factors in psychiatry. Former studies have concentrated mainly on the influence of clinical variables such as the severity or subtype of depression on the length of stay (LOS). However, it can also be assumed that life situations or psychosocial variables in general might influence LOS. Data from 736 admissions between January 1983 and 1991 with a diagnosis of depression were examined to test the hypothesis that psychosocial and clinical variables influence LOS. Results showed a significant influence of age, marital status and gender, as well as severity and type of depression, on duration of inpatient treatment. Age, female gender, being widowed or divorced, the diagnosis of "endogenous depression" and severity were all associated with longer LOS. There was an interaction of gender, marital status and perceived loneliness, as well as an interaction of severity of depression with gender, both of which were associated with LOS.

[Multi-axial system of chapter V (F) of ICD-10. Initial results of a multicenter practicability and reliability study]. / Multiaxiales System des Kapitels V (F) der ICD-10. Erste Ergebnisse der multizentrischen Praktikabilitäts-und Reliabilitätsstudie.

With the introduction of operationalized diagnostic systems the multiaxial approach became a more important issue. The proposed multiaxial system of ICD-10 consists of three axes: on axis I psychiatric diagnoses are made according to the ICD-10 Clinical Guidelines or Diagnostic Criteria for Research. Axis II (Disability Diagnostic Scale, DDS) deals with impairment of psychosocial functioning. On axis III environmental/circumstantial and personal lifestyle management factors are rated. As part of the WHO international field trial, applicability and inter-rater reliability of the system were examined in seven German-speaking centers. In addition axis II was compared with the corresponding axis of DSM-III-R (Global Assessment of Functioning Scale). 45 German clinicians rated 12 case histories written in English (provided by WHO) with 488 ratings altogether. Diagnoses on axis I with an average percentage agreement of 65.6% and a mean kappa of 0.50 showed a moderate inter-rater reliability. For axis II the intraclass coefficient was 0.62, and that for the corresponding DSM-III axis was 0.65: both these axes thus also had a moderate inter-rater reliability. There was a close correlation between the subscales and the global assessment of axis II there was. Wide variation was found in the psychosocial circumstances on axis III, the mean kappa value being 0.16. In the discussion proposals for the revision process for the multiaxial ICD-10 system are made.

The multiaxial system of ICD-10: evaluation of a preliminary draft in a multicentric field trial.

The multiaxial system (MAS) of ICD-10, chapter V (F) consists of three axes: axis I, clinical syndromes (psychiatric disorders including personality disorders and somatic diseases); axis II, disabilities; axis III, environmental/circumstantial and personal life-style/life management factors. Results of a multicentric field trial evaluating a preliminary draft of the MAS are presented. 45 raters in seven German centers made 488 ratings on 12 written case histories. With a mean kappa of 0.50 for 3-character diagnoses interrater reliability for axis I was moderate although lower than expected from previous field trials. On axis II the WHO Disability Diagnostic Scale (WHO-DDS) was compared to the Global Assessment of Functioning (GAF) used in DSM-III-R and DSM-IV. For both scales the intraclass correlation coefficient showed a moderate interrater reliability (WHO-DDS = 0.62; GAF = 0.65). On axis III the number of relevant psychosocial circumstances coded by the different raters varied greatly. Interrater reliability was very poor with kappa values ranging from 0.03 to 0.55 for the different categories and an overall kappa of 0.16.

Normal ageing, impaired cognitive functioning and senile dementia--a mixture distribution analysis.

Dementia scores in the population of very old subjects (70 to > 95) do not demonstrate an obviously bimodal distribution. Heterogeneity analysis shows that the assumption of two distributions explains the data significantly better than a one-distribution model. The first distribution component can be regarded as representing the normal range of scores and the second the pathological range. An additional finding shows the normal range distribution shifting to the pathological range with increasing age.

Schizophrenia, schizotypal and delusional disorders (F2). Results from the ICD-10 field trial of the Diagnostic Criteria for Research in German-speaking countries.

The results of the ICD-10 field trial of the Diagnostic Criteria for Research in German-speaking countries concerning section F2, "Schizophrenia, schizotypal and delusional disorders', are presented. From a total of 39 cases (written case reports and video tapes) 5 met the criteria for schizophrenia (F20) with 201 ratings. The majority of clinicians rated the ease of diagnosis, confidence of diagnosis, and goodness of fit positive. The reliability of the 2-character diagnoses was excellent (F2; kappa = 0.88), as was the case for the category schizophrenia (F20; kappa = 0.89) and was higher than in the comparable study concerning the Clinical Diagnostic Guidelines.

Myoclonus in patients treated with clozapine: a case series.

BACKGROUND: Various types of movement disorder have been reported to occur rarely in patients treated with clozapine. This paper describes five cases in which these phenomena appeared to be clearly associated with clozapine medication and discusses possible pharmacologic mechanisms and treatment options. METHOD: Inpatients receiving clozapine were investigated for the presence of movement disorders. We present five patients with clozapine-induced myoclonus, describe their patterns, and compare clinical features. RESULTS: Five patients treated with clozapine developed a similar pattern of movement disorder that can be described as myoclonus. The neurologic symptoms improved after the treatment was discontinued, the clozapine dose reduced, or concomitant carbamazepine administered. CONCLUSION: Clozapine can induce dose-dependent myoclonus. However, these symptoms can be relieved by reducing the dose of clozapine or giving carbamazepine so that discontinuation of clozapine treatment can be avoided.

Quality assurance in psychiatric care--the example of routine use of the AMDP system.

Quality assurance and continuous monitoring of the quality of delivered care in mental health are going to become a topic of increasing importance. There are several reasons for this process, including increased costs for medical treatment, enhanced possibilities of comparing treatment and outcome success by reimbursement agencies, but also evidence from clinical and epidemiological research of differences in clinical practice that cannot be explained by the current state of psychiatric knowledge. The definition of standards of care and of criteria to indicate the quality of delivered care is a topic of current debate. It is shown that indicators for continuous quality assurance monitoring can be derived from systematized routine psychiatric documentation of patients as in the AMDP system, although this system does not provide comprehensive information to cover the full range of indicators necessary to establish sufficient control for quality of care. Future developments are discussed.