Depression with above-normal plasma vasopressin: validation by relations with family history of depression and mixed anxiety and retardation.

An anxious-retarded subtype of depression has been derived from the DSM-IV category of melancholia. It is defined by combined high scores for anxiety and retardation, and is related to family history of depression and increased plasma vasopressin (AVP) levels. Central problems concerning this hypothesized subcategory are whether elevated plasma AVP is related to family history, whether it would be better operationalized by a cut-off level for plasma AVP than as continuous variable, and whether the anxious-retarded phenotype would be better described in terms that account for full variability of mixed anxiety and retardation. A previous study suggested that above-normal plasma AVP was a more useful endophenotypic parameter than plasma AVP as a continuous variable. To answer these and related questions, 81 patients were investigated. Receiver Operating Characteristic analyses yielded a cut-off value of 5.56 pg/ml for above-normal plasma AVP, log-transformed plasma AVP (ln (AVP)) was used as continuous variable, and the correlation between anxiety and retardation was used to account for full variability of the anxious-retarded phenotype. Family history was related to above-normal plasma AVP (n = 16) and non-significantly to ln (AVP). Depression with above-normal plasma AVP, as well as familial depression with above-normal plasma AVP, showed a high correlation between anxiety and retardation, and this correlation was significantly higher than that found in the depressed patient control groups. The data support the delimitation of a largely familial depression with above-normal plasma AVP, vasopressinergic activation of the hypothalamus-pituitary-adrenal axis and a variable anxious-retarded phenotype.