Department of Psychiatry, Umea University, S-901 85 Umea, Sweden
Over time, our knowledge has increased about the classification and delineation of the affective psychoses. A distinction between unipolar affective disorders and bipolar affective disorders has been suggested by Perris (12) and Angst (3). Di­agnostic criteria for major depression and bipolar disorders have been presented in DSM-III (2). As concerns the nonpsychotic depressive disorders, there are still many un­solved problems, and there are no generally accepted diagnostic criteria delin­eating specific diagnostic subgroups. At the Department of Psychiatry at Umea University, we have used an op­erational definition of a subgroup called neurotic-reactive depression. The di­agnostic criteria have been used in a series of studies over the last 15 years. According to the diagnostic definition, the patients must have shown a clear-cut depressive symptomatology of a neurotic, nonpsychotic dimension, i.e., with unimpaired evaluation of reality during the whole course of the depressive dis­order. Furthermore, the condition must have arisen as a reaction to external events or represent an acute breakdown in patients with unstable personalities and a tendency to react with depressive, anxious, or psychosomatic symptoms under the influence of stress in relatively ordinary life situations (5). This definition somewhat resembles the definition of neurotic depression used by the World Health Organization (23). A neurotic disorder characterized by disproportionate depression which has usually recognizably ensued on a distressing experience; it does not include among its features delusions or hallucinations, and there is often preoccupation with the psychic trauma Which preceded the illness, e.g., loss of a cherished person or possession. Anxiety is also frequently present and mixed states of anxiety and depression should be included ere. The distinction between depressive neuroses and psychosis should be made ot only upon the degree of depression but also on the presence or absence of other eurotic and psychotic characteristics and upon the degree of disturbance of the patient’s behaviour. (more…)

In our family studies, it is obvious that patients with neurotic-reactive depres­sion have a low morbidity risk of bipolar affective disorders in their first-degree relatives (Table 4) (13). Thus both neurotic-reactive depression and unipolar affective disorders seem to be distinct categories from bipolar affective disorders as concerns family studies. Furthermore, there is no significant difference in morbidity risk for alcoholism or schizophrenia between the first-degree relatives of patients with neurotic-reactive depression and patients with unipolar affective disorders. The only significant difference found is a significantly higher morbidity risk for nonbipolar affective disorders in the first-degree relatives of patients with unipolar affective disorders, as compared to the first-degree relatives of patients with neurotic-reactive depression. The results seem to indicate a higher genetic component in unipolar affective disorders than in patients with neurotic-reactive depression. The results are comparable to results from other studies presented earlier (Table 5) (13).

There are certain limitations in family studies, some of which may be overcome in twin studies. In an extensive twin study, Torgersen (19) concluded that: "The analysis of concordance rates indicates that hereditary factors may be important
the development of bipolar disorder and in major depression, except in non-psychotic, hysterical individuals. Furthermore, hereditary factors may not play any role in dysthymic disorder and depressive adjustment disorder." The results appear to be in line with those from our family studies in which there is no genetic relationship between neurotic-reactive depression and bipolar affective disorders and a higher morbidity risk for nonbipolar affective disorders in the relatives of patients with unipolar affective disorders than in the relatives of patients with neurotic-reactive depression. (more…)

71 ‘ subgroups of patients. By means of our operational definition of neurotic-reactive depression, we have been able to delineate a subgroup of patients that at least seems to be different from patients with unipolar and bipolar affective psychoses, furthermore, in long-term follow-up studies, these patients do not seem to de­velop clear-cut unipolar or bipolar affective disorders. In this subgroup of patients with neurotic-reactive depression, there are no supports in family studies, twin studies, or adoption studies for a specific genetic transmission. On the other hand, there seems to be a subgroup of patients with nonpsychotic depressive disorders, characterized by low platelet MAO activity. These subjects seem to be sensitive to stressful life events and seem to have a tendency to react with neurotic-reactive depression and alcohol and drug abuse, and in their relatives, there is an increased frequency of neurotic-reactive depres­sion, alcoholism, and attempted suicides. Because the clinical symptomatology of the patients with affective disorders accompanied by low platelet MAO activity is nonspecific, a variable number of these subjects could be included under any diagnostic category in the field of nonpsychotic depressive disorders. In family studies, this would be reflected as an increased unspecific vulnerability, and an increased frequency of a variety of psychiatric disorders in first-degree relatives. Since low platelet MAO activity has also consistently been found in subgroups of alcoholism (11), a coexistence of neurotic depression and alcoholism would be expected in some families, as suggested by Winokur (21).
REFERENCES
1. Akiskal H. S., Bitar A. H., Puzantian V. R., Rosenthal T. L., and Walker, P. W. (1978): The nosological status of neurotic depression. Arch. Gen. Psychiatry, 35:756-766. 2. American Psychiatric Association. (1980): Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. American Psychiatric Association, Washington, D.C. 3. Angst, J. (1966): Zur Atiologie un Nosologie endogener depressiver Psychosen. Springer Verlag, Berlin. 4. Buchsbaum, M. S., Coursey, R. D., and Murphy, D. L. (1976): The biological highrisk paradigm: Behavioral and familial correlates of low platelet monoamine oxidase activity. Science, 194:339-341. 5. d’Elia, G., von Knorring, L., and Perns, C. (1974): Non-psychotic depressive disorders: A ten year follow up. Acta Psychialr. Scand. (Suppl), 255:173-186. 6.Gershon, E. S., Baron, M., and Leckam, J. F. (1975): Genetic model of the transmission of affective disorders. J. Psychiatr. Res., 12:301-317. 7. von Knorring, A. L. (1983): Adoption Studies on Psychiatric Illness. Umea University Medical Dissertations. New Series No. 101, Umea. 8. von Knorring, L., Oreland, L., and von Knorring, A. L. (1986): Personality traits and psycho-pathology related to platelet MAO activity. In: Biological Psychiatry 1985, edited by С Shagass, R.- С Josiassen, W. H. Bridger, K. J. Weiss, D. Stoff, and G. M. Simpson, pp. 530-532. Elsevier Science Publishing Co., Inc., New York. 9. von Knorring, L., Penis, C, Oreland, L., Eisemann, M., Holgrem, S., and Penis, H. (1985): Morbidity risk for psychiatric disorders in families of probands with affective disorders divided according to levels of platelet MAO activity. Psychiatry Res., 15:271-279. 10. von Knorring, L., Penis, C, Oreland, L., Eisemann, M., and Perris H. (1987): Platelet MAO activity in affective disorders. Relationship to diagnostic subgroup. Biol. Psychiatry, (submitted). 11. Oreland, L., von Knorring, L., von Knorring, A. L., and Bohman, M. (1985): Studies on the connection between alcoholism and low platelet monoamine oxidase activity. In: Progress in Alcohol Research, Vol. 1, edited by Parvez et al., pp. 83-117. VNU Science Press. 12. Perns, С (1966): A study of bipolar (manic-depressive) and unipolar recurrent depressive psychoses. Acta Psychiatr. Scand. (Suppl), 194. 13. Perris, C, Perris, H., Ericsson, U., and von Knorring, L. (1982): The genetics of depression. A family study of unipolar and neurotic-reactive depressed patients. Arch. Psychiatr. Nervenkr 232:137-155. 14. Perris, H., von Knorring, L., Oreland, L., and Perris, С (1984): Life events and biological vul­nerability: A study of life events and platelet MAO activity in depressed patients. Psychiatry Res., 12:111-120. 15. Rasmussen, S., Sorensen, Т ., and Wildshiodtz, G. (1978): Neurosis depressive, en efterundersogelse Nord. Psykiatr. Tidskr., 321-331. 16. Revely, M. A., Revely, A. M., Clifford, R. M., and Murray, R. M. (1983): Genetics of platelet MAO activity in discordant schizophrenic and normal twins. Br. J. Psychiatry, 142:560-565. 17. Smeraldi, E., Negri, F., and Melica, A. M. (1977): A genetic study of affective disorders. Acta Psychiatr. Scand., 56:382-398. 18. Stenstedt, A. (1966): Genetics of neurotic depression. Acta Psychiatr. Scand., 42:392-409. 19. Torgersen, S. (1986): Genetic factors in moderately severe and mild affective disorders. Arch Gen. Psychiatry, 43:222-226. 20. Tzerebietowska. (1976): Unpublished paper. Quoted in: Smeraldi, E., Negri, F., and Melica, A. M. (1977): A genetic study of affective disorders. Acta Psychiatr. Scand., 56:382-398. 21. Winokur, G. (1979): Familial (genetic) subtypes of pure depressive disease. Am. J. Psychiatry, 136:911-913. 22. Winokur, G, Cadoret, R., Dorzab, J., and Baker, M. (1971): Depressive disease: A genetic study. Arch. Gen. Psychiatry, 24:135-144. 23. World Health Organization. (1978): Mental Disorders: Glossary and Guide to the Classification of Mental Disorders in Accordance with the Ninth Revision of the International Classification of Diseases. WHO, Geneva. 24. Zuckerman, M. (1984): Sensation seeking: A comparative approach to a human trait. The Be­havioral and Brain Sciences, 7:413-471. Anxious Depression: Assessment and Treatment, edited by G. Racagni and E. Smeraldi. Raven Press, New York © 1987. (more…)

The activity of platelet MAO seems to be under strong genetic control. The hereditability has been estimated at 70% to 80%, according to twin studies (16). Within the individual, the activity of the enzyme seems to be stable over time, and thus it seems possible to regard this enzyme activity as a genetic marker (11). Low activity of platelet MAO has consistently been related to certain person­ality traits as sensation seeking, monotony avoidance, and extraversion (11,24). It was also demonstrated early on that subjects with low platelet MAO activity seemed to have an increased vulnerability with more psychopathology, more antisocial behavior, more experimentation with drugs, and more attempted sui­cides in their relatives (4). In patients with affective disorders, the results have been conflicting. In patients with unipolar or bipolar affective disorders, high, normal, and low platelet MAO activity has been reported (Table (10). In our own series, we tend to find
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All patients hospitalized at the Department of Psychiatry, Umea University, during the years 1960-1963 with the clinical diagnosis of neurotic-reactive depression were reevaluated and followed for 10 years. At the reevaluation of the records, it was found that the clinical diagnosis neurotic-reactive depression was used in a very imprecise way. Only 83 of the 146 patients with the clinical diagnosis of neurotic-reactive depression fulfilled our research criteria for neu­rotic-reactive depression (Table 2). When the 83 patients fulfilling our research criteria were followed over 10 years, the diagnosis was only changed in 2 (4%) of the patients (Table 3). Our results are in line with the findings of Rasmussen et al. (15); in their study only 2 of 23 patients with neurotic-reactive depression developed an affective psychosis during a 15-year follow-up period. However, the results are contradictory to the results obtained by Akiskal et al. (1). In their study 40% of the patients with neurotic-reactive depression developed a unipolar or bipolar affective disorder during a 3 to 4-year follow-up period. The discrepancy is probably owing to the differences in the diagnostic criteria used. If we had accepted the clinical diagnosis of neurotic-reactive depression and followed the whole group, our results would have been much more similar to the ones achieved by Akiskal et al. (1). However,
if our diagnostic criteria are followed strictly, we seem to be able to delineate a subgroup that at least is clearly distinct from unipolar and bipolar affective dis­orders. (more…)

In an adoption study performed at the Department of Child Psychiatry, Umea University, it was demonstrated that the biological parents of adoptees with neurotic-reactive depression did not differ significantly from the biological parents of control adoptees in regard to the prevalence of total psychiatric morbidity (Table 6) (7). After a subdivision of the psychiatric morbidity in the biological relatives of adoptees without psychiatric illness and those with neurotic-reactive depression, no certain relationship was found between any specific affective disorder in the biological parents and the disorders in the adoptees (Table 7) (7).

If the DSM-III diagnostic criteria (2) are applied to patients classified as neu­rotic-reactive depressives according to our research diagnostic criteria, it is obvious that there is no diagnostic category in DSM-III that is directly comparable to our subgroup of patients (Table 1). This finding must be kept in mind when our results are compared with results obtained by means of other diagnostic criteria. As many as 50% of our patients with neurotic-reactive depression fulfill the DSM-III criteria for major depression, a finding that has direct relevance when family studies are discussed.
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Thus, in the family studies, twin studies, and adoption studies presented so far, there is no strong support for a specific genetic factor in neurotic-reactive depression. However, there are some results from studies concerning biological markers under genetic control, indicating that genetic factors may still be of some importance, at least in subgroups of patients with neurotic-reactive depres­sion. It should also be kept in mind that as long as there is no generally accepted subclassification of patients with nonpsychotic depressive disorders, a genetic contribution in one of the subgroups may well be recognized in family studies, twin studies, and adoption studies. One biological marker that has been of certain interest in relation to affective disorders is the main degrative enzyme in the monoamine turnover —monoamine oxidase (MAO). MAO exists in two forms, A and B. Form A is only present in the brain, whereas form В is present in the brain and in platelets. Because of the easier access to MAO in platelets and based on the assumption of a relationship between brain and platelet MAO activities, a series of studies have been performed on platelet MAO activity in patients with affective disorders. In general, the results have been disappointing, but there are some results indicating a genetic component in a subgroup of patients with neurotic-reactive depression.