Reinhard Heun

Personality traits in subjects at risk for unipolar major depression : a family study perspective

Particular patterns of personality (e.g., introversion, neuroticism, obsessionality) have been found to be associated with unipolar depression by a large number of investigators; recent prospective studies have stressed neuroticism as a premorbid risk factor for depression. This study examines whether similar patterns of personality are found in relatives of affective disorder patients and of controls. First-degree relatives of normal controls and of subjects with primary unipolar depression were studied using the Munich Personality Test. Relatives in remission from an episode of unipolar depression had clearly higher levels of neuroticism and rigidity and lower levels of extraversion than controls; healthy relatives of controls had higher levels of rigidity (both sexes) and of neuroticism (males only) than controls. It is proposed that these traits are either risk factors for depression or attenuated forms of depression.

Unipolar depression in the aged: determinants of familial aggregation.

Late-onset depression (greater than or equal to 60 years) is believed to be less associated with a risk of depression in first-degree relatives than early-onset depression. However, family studies in elderly probands fitting the current methodological standards of family studies are not available. The reported family study in geriatric inpatients with unipolar major depression (n = 92) supported the proposed relationship between age at onset and the proposed familial loading. A comparison to families of age-matched controls (n = 33) revealed that relatives of probands with late-onset depression are still at an increased risk of depression. However, late-onset depression was not more common in families of probands with late-onset depression than in families of probands with early-onset depression. Besides the age at onset, the recurrence of depressive episodes defined distinct patterns of familial aggregation.

The efficacy of agomelatine in elderly patients with recurrent major depressive disorder: A placebo-controlled study

OBJECTIVE The present placebo-controlled study evaluated the efficacy, tolerability, and safety of 8-week treatment with agomelatine (25-50 mg/d by mouth) in elderly patients with major depressive disorder (MDD). METHOD Elderly outpatients aged ≥ 65 years with a primary diagnosis of moderate to severe episode of recurrent MDD (DSM-IV-TR) were recruited in 27 clinical centers in Argentina, Finland, Mexico, Portugal, and Romania from November 2009 to October 2011. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS17) total score. RESULTS A total of 222 elderly patients entered the study (151 in the agomelatine group, 71 in the placebo group), including 69 patients aged 75 years and older. Agomelatine improved depressive symptoms in the elderly population, as evaluated by the HDRS17 total score, in terms of last postbaseline value (agomelatine-placebo difference: mean estimate [standard error] = 2.67 [1.06] points; P = .013) and response to treatment (agomelatine, 59.5%; placebo, 38.6%; P = .004). The agomelatine-placebo difference according to the Clinical Global Impressions-Severity of Illness scale (CGI-S) score was 0.48 (0.19). The agomelatine-placebo difference (estimate [standard error]) for remission on the HDRS17 was 6.9% (4.7%) and did not achieve statistical significance (P = .179, post hoc analysis). Clinically relevant effects of agomelatine were confirmed on all end points in the subset of severely depressed patients (HDRS17 total score ≥ 25 and CGI-S score ≥ 5 at baseline). Agomelatine was well tolerated by patients, with only minimal distinctions from placebo. CONCLUSIONS The present study provides the first evidence that an 8-week treatment with agomelatine 25-50 mg/d efficiently relieves depressive symptoms and is well tolerated in elderly depressed patients older than 65 years. TRIAL REGISTRATION Controlled-Trials.com identifier: ISRCTN57507360.

The risk of minor depression in families of probands with major depression: Sex differences and familiality

SummaryCurrently it is not clear whether minor forms of unipolar depression not matching the criteria of “major depression” should be considered as a separate diagnostic category. A controlled family study examined the familial aggregation of minor depression among probands with unipolar major depression. In the families of these probands the relative risk for minor depression was elevated by a similar magnitude to the risk for major depression. Threrefore, the diagnostic category “minor depression” would not increase diagnostic sensitivity at the expense of diagnostic specificity as far as familiality is the criterion. In agreement with recent epidemiological studies, minor depression did not reveal a similar excess prevalence in females compared with males as major depression does. The variation of the sex ratio for any subtype of unipolar depression was not associated with the familiality of this disorder.

Selection bias during recruitment of elderly subjects from the general population for psychiatric interviews

The aim of the present study was to determine and assess a possible selection bias in an epidemiologic investigation in the elderly. A stratified sample of 1305 probands aged 60–99 years was initially contacted by mail and then by telephone to obtain their consent to participate in a psychiatric interview. A liberal recruitment procedure led to interview participation of only 291 subjects. The proportion of younger, male, and married subjects participating in the study was greater than that of elderly, female, and single or widowed subjects. Subjects without a psychiatric lifetime diagnosis were more cooperative than those with a psychiatric disorder. The latter finding demonstrates the need to determine and assess the selection bias in psychiatric epidemiologic studies in elderly subjects.

Selection biases during recruitment of patients and relatives for a family study in the elderly

The aim of the present study was to examine selection effects during recruitment of patients, controls and relatives for a family study in the elderly. The primary sample consisted of 368 in-patients (aged above 60 years) admitted in the years 1992 and 1993. One-hundred and eighty-four subjects (50%) suffering from dementia of Alzheimer type or major depression fulfilled the diagnostic inclusion criteria. Finally, 100 subjects participated in the family study. Demographic data of participants, ineligible subjects, uncooperative candidates, and control subjects from the general population was examined. Demographic parameters, reasons for refusal of personal interviews, and family history information were compared in first-degree relatives of participants and of 40 control subjects. According to demographic data, participants were representative for the whole sample of demented or depressed patients, and were comparable with the control sample. Demographic parameters of relatives were also equivalent in both groups. Rates of psychiatric disorders were equal in interviewed and unavailable relatives of patients (18.0% and 18.8%, respectively). However, interviewed relatives of controls had significantly fewer psychiatric disorders than unavailable relatives (7.8% vs 20%). This selection effect indicates the need for family history information on unavailable relatives in family studies on geriatric patients. Equivalence of demographic data alone was not a sufficient indicator of sample comparability. A second hospitalized comparison group might serve to increase the validity of conclusions resulting from comparative family studies.

Demenzscreening im klinischen Alltag Eine vergleichende Analyse von MMSE, SIDAM und ADAS

ZusammenfassungFür ein Demenzscreening im klinischen Alltag sind kurze, sensitive und spezifische Tests erforderlich. Hierfür stehen einige standardisierter Verfahren zur Verfügung. In der vorliegenden Arbeit wurde der Zusammenhang von Testumfang und diagnostischer Güte an 3 beispielhaften Demenzscreeninginstrumenten untersucht. Die Mini-Mental-State-Untersuchung (MMSE), das Strukturierte Interview für die Diagnose einer Demenz vom Alzheimer-Typ, der Multiinfarktdemenz und Demenzen anderer Ätiologie nach ICD-10 und DSM-III-R (SIDAM) und die Alzheimer’s Disease Assessment Scale (ADAS) wurden bei 71 Patienten mit Demenz vom Alzheimer-Typ und 73 nichtdementen Kontrollprobanden durchgeführt. Eine ROC-Analyse zeigte, daß weder SIDAM noch ADAS besser zwischen dementen Patienten und nichtdementen Kontrollprobanden unterschieden, als der MMSE-Testwert. Dies galt auch für Patienten mit leichter Demenz. Auch bei der Abgrenzung verschiedener Schweregrade der Demenz waren die umfangreicheren Instrumente dem Kurztest MMSE nicht überlegen. Für den klinischen Alltag stellt die MMSE wegen ihrer Kürze das geeignetste Screeninginstrument dar.SummaryDementia-screening in clinical routine requires short, sensitive and specific tools. A number of standardized instruments are available for this purpose. The present study analysed the relationship between size of three examplary dementia-screening tests and their diagnostic accuracy.The Mini-Mental-State-Examination (MMSE), the Structured Interview for the Diagnosis of Dementia of the Alzheimer-type, Multiinfarct Dementia and Dementias of other Aetiologies according to ICD-10 and DSM-III-R (SIDAM) and the Alzheimer’s Disease Assessment Scale (ADAS) were applied to 71 patients with dementia of the Alzheimer-type and 73 non-demented controls.A ROC-analysis revealed that neighter SIDAM nor ADAS differentiated better between demented and non-demented probands than the MMSE. This was also true for patients with mild dementia. In dementia staging the more comprehensive instruments did not surpass the MMSE, too.Due to it’s brevity, the MMSE is the preferential screening-instrument for clinical routine.

Serial Position Effects in Dementia of the Alzheimer Type

Background: The aim of the present study was to analyse serial position effects for immediate and delayed free recall in patients with dementia of the Alzheimer type and controls. Experiment 1: 44 patients with dementia of the Alzheimer-type and 24 non-demented controls were asked for immediate and delayed free recall of 12 schematic drawings of common objects presented at the rate of 10 s/picture. Steep primacy effects were obtained at all delays in controls. By contrast, primacy effects were significantly impaired in patients with dementia at all delays of recall. Small immediate and delayed recall recency effects were found in both, patients and controls. Experiment 2: 19 patients with dementia of the Alzheimer type and 21 controls were asked for immediate and delayed free picture recall with presentation rates of 10, 5 and 1 s/picture. Again, primacy effects were significantly impaired in demented patients versus controls. With shorter presentation times, immediate recall recency effects were more pronounced than with longer presentation times, and no delayed recall recency effects were found. Conclusions: Primacy effect is impaired for immediate and delayed recall in dementia of the Alzheimer type. By contrast, immediate recall recency effect and possibly also long-term recency effect are preserved. The loss of the primacy effect contributes to the impairment of episodic memory in dementia of the Alzheimer type. Therefore further research is warranted into pharmacological and psychological interventions that might re-establish the primacy effect. Possibly, the orientation of demented patients might be improved by psychological techniques that rely on long-term recency effect.

Bipolar II disorders in six first-degree relatives

As proposed by Dunner et al (1976), the distinction of bipolar !! disorder from other effective disorders has been included in Research Diagnostic Criteria (RDC) (Spitzer et al 1978) but not in DSM-IiI-R or ICD 10 (APA 1987, WHO 1991). Family studies indicate that bipolar 1I disorder might represent a distinct diagnostic entity with a common genetic background (Gershon et al 1982; Dunner 1983; Endicott et al 1985; Andreasen et al 1987). Familial aggregation, diagnostic stability, and course of illness represent external validators for nosologic classifications (Kendler 1990). Therefore, pedigrees with multiple cases of diagnostically stable bipolar Ii disorder without cases of bipolar 1 disorder or unipolar depression would argue for a distinct nosologic category. To our knowledge, this is the third pedigree with multiple bipolar I1 family members to be published (DePaulo et al 1990; Kuyler 1988).

Concordance for gender in sib pairs affected with schizophrenia and related disorders

An excess concordance by sex among siblings affected with schizophrenia has been proposed by some previous and recent investigators. However, this hypothesis has not been supported by some recent studies having complete ascertainment of probands and relatives. The present report is based on sibships with multiple affected members derived from a family study of systematically recruited inpatients (146 probands with schizophrenia and 132 probands with other psychotic disorders). Evidence for an excess concordance rate for gender among proband-sibling pairs with both members affected is suggested under a broad definition of illness.