Support for allelic association of a polymorphic site in the promoter region of the serotonin transporter gene with risk for alcohol dependence.

OBJECTIVE: An association between the 5-HTTLPR short variant polymorphism in the promoter region of the serotonin transporter gene and risk for alcohol dependence has been reported from case-control studies that are, however, prone to chance findings related to artifacts of population structure. The authors sought additional evidence for this association from a family-based study. METHOD: Ninety-two alcohol-dependent probands and their parents were tested for nonrandom transmission of alleles from heterozygous parents to affected probands. RESULTS: Preferential transmission of the short allele was found (65 of 102 transmissions from heterozygous parents). CONCLUSIONS: The results suggest allelic association between a variant in the promoter region of the serotonin transporter gene and the risk for alcohol dependence. However, it remains to be seen whether the functional properties of this variant are directly responsible for the increased risk to alcohol dependence.

Differentiation between major and minor depression.

Though the concept of Major Depression was generated by clinicians using depressed inpatients as models, a polydiagnostic study in 600 psychiatric inpatients with heterogenous psychological disturbances revealed that all six competing operational definitions of Major Depression (including DSM-III-R and ICD-10) were too restrictive to serve as a general concept of depression. Another polydiagnostic study in 500 primary care outpatients showed that more than two-thirds of all non-chronic depressed cases were below the severity threshold of Major Depression: these patients are classified as Depression Not Otherwise Specified (NOS) by DSM-III-R. Loosening of the over-restrictive time criteria would broaden the concept of Major Depression so as to meet the requirements of a general concept of depression, while the definition of Minor Depression below the threshold of Major Depression would add to a reduction of cases of NOS Depression by more than 80%. For the evaluation of antidepressant drugs in outpatient samples, we propose that patients with these modified definitions of Major and Minor Depression be included, provided they meet a minimum severity criterion of 13 or more points on the Hamilton Depression Scale; four-fifths of the modified Major Depression group and one-third of the Minor Depression group do in fact meet this criterion.

Identification of minor affective disorders and implications for psychopharmacotherapy.

Five hundred general practice patients with functional complaints were studied with the Polydiagnostic Interview (PODI) to see whether DSM-IIIR criteria were able to specify affective disorders satisfactorily. Almost one third of the patients received the diagnosis of depression not otherwise specified (NOS). When Research Diagnostic Criteria were applied to these patients more than 70% received specific diagnoses. A modification of DSM-IIIR algorithms enabled us to further specify diagnoses in subjects with depression NOS. On the 17-item Hamilton Depression Scale many of these patients reached scores of 13 or more which is severe enough to justify a therapy trial with antidepressants.

The concept of major depression. I. Descriptive comparison of six competing operational definitions including ICD-10 and DSM-III-R.

All operationalized diagnostic systems contain a diagnostic category, which corresponds to the concept of major depression. Yet, these corresponding definitions are not identical. Up to now, no comprehensive comparisons of the competing diagnoses have been published. We will therefore present a series of studies, describing six different operational definitions of major depression according to their content and construction and empirically comparing them in large inpatient and outpatient samples. This first paper presents a descriptive comparison of the definitions given in the Feighner Diagnostic Criteria, the Research Diagnostic Criteria, the Diagnostic and Statistical Manual of Mental Disorders, third edition and third edition, revised, and in two developmental drafts of the ICD-10 diagnostic criteria for research (draft April 1987-I87; draft April 1989-I89). The descriptive comparison will demonstrate that there are many similarities, especially concerning the symptom-criteria of major depression. Classificatory relevance could only be assumed for those differences found for cut-offs, for time criteria and especially for exclusion criteria. Whether these differences are negligible and whether patients classified by different diagnostic systems are really comparable will be examined in subsequent publications.

The concept of major depression. II. Agreement between six competing operational definitions in 600 psychiatric inpatients.

Six operational definitions of the concept of major depression were submitted to empirical evaluation in 600 psychiatric inpatients. Special attention was given to the comparison of major depression in DSM-III-R and ICD-10. The data base created by a polydiagnostic interview revealed relevant classificatory differences between the six definitions under study. Sources of different diagnostic base rates were: inclusion or omission of anhedonia as an obligatory mood criterion; minimal number of syndrome criteria required for the syndrome diagnosis; different width and reference points of time criteria; exclusion rules for co-existing schizophrenic symptoms and for previous nonaffective and manic episodes. The empirically evaluated overlap between pairs of diagnostic definitions was less than excellent in most of the diagnostic definitions under study; only the DSM-III and DSM-III-R definitions agreed with each other to a highly comparable degree. The relatively good agreement of the 1989 draft definition of ICD-10 for major depression ("mild depression") with the other five operational definitions (kappa = 0.69) led us to expect that this definition should receive sufficient international acceptance.

The concept of major depression. III. Concurrent validity of six competing operational definitions for the clinical ICD-9 diagnosis.

The comparative validity of six operational diagnoses of major depression was evaluated in 600 psychiatric inpatients using the independently assessed clinical ICD-9 diagnoses as a yardstick. Agreement with, and positive predictive value for the ICD-9 categories of pure (endogenous and psychogenic) depression served as validation criteria; sensitivity of major depression diagnoses for detecting ICD-9 bipolar depressions was additionally used for examining the adequacy of width, time and exclusion criteria of the competing operational definitions. Three essential results were found. First, the "old" diagnostic definitions of RDC and FDC are superior to all newer definitions because they define the time criteria and the schizophrenic exclusion criteria more adequately than, for example, both DSM-III and DSM-III-R definition. Secondly, the current ICD-10 definition of 1989 ("mild", "moderate" or "severe" depression) comes closer to the concurrent validity of RDC and FDC than DSM-III, DSM-III-R and the previous ICD-10 definition of 1987. Thirdly, using the criterion of identifying a high proportion of ICD-9 bipolar depressions, all six competing diagnostic systems are too restrictive. Evaluations of predictive and criterion-related validity will be needed to substantiate these findings.