The aim
of this book is to highlight some of the findings and considerations that could be significant for studying the severity of anxiety and depression. It is quite clear that we must distinguish between symptoms and syndromes in this area, and between rating measures and clinical diagnoses. It is equally apparent that there is a great deal of heterogeneity in these disorders depending on the type of patients dealt with: community samples, symptomatic volunteers from the community, general medical practice patients, or patients already in psychiatric settings. It is essential to relate the symptoms to the population in which they are measured, if we wish to know the real meaning of each symptom. Both anxiety and depression have their roots in the psychology of the individual, and they can be experienced also by nonpatients. However, their feelings are quite different from those found in psychiatric syndromes. We must use whatever instruments we have to determine the borderline between normality and pathology in this area. The coexistence of anxiety and depression is not necessarily always the same. In some cases, it is a depressive reaction that appears during a real anxiety disorder that clearly maintains psychopathological pre-eminence. In other cases, excessive anxiety as a symptom of recurrent major depression sets up an anxious depressive syndrome. External factors can be useful to define its nature in these patients. In other cases, we may have no landmarks, and anxious depressive syndrome seems to represent a single intermediate situation between the two extremes. The DSM-III attributes a priori a diagnostic-interpretative prevalence to the affective aspect, including depressive neurosis among affective disorders, and it does not exhaust the problem. This is why operative criteria should be used in order to organize the information reliably and establish linkages between symptoms that are probable if not definite, such as depersonalization and self-confidence, both of which have different significance in anxiety when compared to depressive disorders. It emerges that there are at least several distinct conditions characterized by a mixture of anxiety and depression. One has been called anxious-melancholia, which is equivalent to endogenous depression with anxiety. Moreover, recent psychopathological studies do also recognize the coexistence of major affective disorder and panic attacks. In these patients both diagnosis of axis I of the DSM-III are present. This condition is different from the coexistence of depression and anxiety as simple symptoms in the same patients. The amount of anticipatory anxiety may even overwhelm the depressive component and obscure the limits between the two conditions. Another type of disorder appears to be a classical anxiety disorder with the complication of secondary depression, with tendencies toward different types of chronicity of the depression, but all relatively insensitive to drug treatment. Finally, the most difficult condition to consider is an undifferentiated disorder with features of both anxiety and depression that are usually milder. These are the subcases that are probably overrepresented in community samples and in symptomatic volunteers. Despite the great degree of overlap in anxiety and depressive symptoms and syndromes when looked at cross-sectionally, there is considerable evidence that the two disorders are indeed distinct. For instance, retardation is quite characteristic in depressive disorders but not in anxiety disorders. The cognitive differences, uncertainty, and threat of loss are the major themes in an anxiety disorder, and hopelessness and desire for death in depression. Periodicity and seasonality are quite uncharacteristic of anxiety disorders, agoraphobia is quite uncharacteristic in uncomplicated depression, and suicide is more characteristic of mood disorders. Long-term recovery is also quite different. In anxiety disorder it is not terribly good, but in mood disorders long-term recovery is usually quite good. However, when patients seem to have combined conditions, the outcome might be somewhat worse. There is much debate about genetic patterns in anxious depression, mainly because of the controversial findings of different groups. We still cannot reach a conclusion, and at least two alternative hypotheses have been proposed, a genetic and an environmental origin of anxious-depressive disorders. These different hypotheses indicate a dichotomy between "state" and "trait" pathologies. In this sense, apart from the particular case of panic attacks, several types of neurotic illness, such as generalized anxiety or separation anxiety, might be viewed as due to environmental factors, whereas personality traits referable to "anxiety liability" could be mainly genetic. This last point introduces another issue of discussion on what is inherited. In the classical approach, the structure inherited is the liability to a particular disease. Alternatively, it has been proposed that what is inherited are the milder aspects of the various diseases and not their overt forms. To detect a view of the inner mechanisms that, based on genetic properties, control the manifestation of psychic major symptomatologies, it is important to see whether a subject previously had a personality disorder. Unfortunately, this mode of thinking does not take into account the tremendous problem of heterogeneity in psychiatric genetics. In fact, it is well known that the so-called "phenotypic" similarities in psychiatry do not recognize common genetic backgrounds being related to various etiopathogenetic mechanisms. Neuropharmacological studies have shown that different neuronal systems are disturbed in both anxiety and depression in animals and humans. However, it emerges that the interactions among specific neurotransmitters, i.e., GABA, norepinephrine, and serotonin, seem to be of interest to explain the mechanisms of action of some pharmacological agents. Therefore, drugs that act on these neurons could manifest both antianxiety and antidepressant activity. Neuroendocrinological studies have not helped to differentiate between depression and anxiety disorders. Sleep data are preliminary, but there are studies suggesting that disorders can be distinguished on these bases. What do we need therefore to investigate? Special attention must be given to clinical measures. In addition to self-ratings, the psychiatrist must look at the effects on the patient. We need better measurements for psychomotor retardation and psychophysiologic responsivity. Moreover, cognitive features in depression anxiety and in combined syndromes must be considered. Early environment needs to be examined prospectively. Personality, as a subclinical expression of one or both disorders, needs to be studied more rigorously genetically. To make measurable what is not yet measurable is probably what is most needed in this particular area. Psychosocial functioning can be also looked at. Very elegant genetic models have been presented at this meeting, and they can be used to test spectrum models with larger sets of data. It might be useful to include personality functioning, personality disorders, and temperaments in these genetic models. Neuroendocrine and biological markers include urinary MHPG, platelet imipramine binding, 5-HT uptake, and sleep EEG. These variables should not be studied individually, as has been done so far, but as an entire complex of factors that underlie the clinical heterogeneity for both affective disorders and anxiety. This heterogeneity can never be overlooked, because it is the thoroughly established and productive aspect of our knowledge in this area. This is important because pharmacological response patterns should not be examined only as related to clinical features. It will be useful to include family history, personality, and biological measures in determining differences in the response patterns to various pharmacological agents. How should a clinician approach a pa
tient with a mixed syndrome? First of all, the possibility that the patient has a panic-agoraphobic type disorder must be excluded and that depression is not secondary to this illness; the next stage in evaluating a patient with a mixed syndrome would be to exclude that it is secondary depression or depression with anxiety symptoms. In this situation, it could be a mixed state, and clinical aspects of this were discussed in the meeting. This book will be of interest to psychiatrists, clinicians, and neuropharmacologists. It addresses issues for both the clinician and researcher regarding the importance of mixed syndromes versus single anxiety and depressive disorders in choosing appropriate pharmacological therapy. We think that it is clear that the interest in these particular clinical disorders is not only nosographical or theoretical, but is directly connected to both daily clinical practice and research.
Giorgio Racagni Enrico Smeraldi