Institute of Clinical Psychiatry, Sc hool of Medicine, University of Milan, 20122 Milan, Italy
A positive global evaluation is certainly possible at the end of a thorough discussion on anxiety and depression in the four fields in which the workshops have been articulated, that is, family, biology, psychopathology, and treatment. What seems difficult if not impossible is to reach definite conclusions in a field that is almost exactly characterized by the continuous overlapping of con­trasting theoretical and pragmatical proposals and models. The word "anxiety" derives from the Latin "angere" (to constrain), that is probably the somatic implication of the affective state that the word describes. In common language, it is synonymous with preoccupation (pre-occupy) —to occupy oneself before any event, to be waiting for it, and it describes in other words an alerting signal, a feeling of danger, a danger almost impossible to face. On the contrary, the word "depression" originates from the Latin "deprimere," that is, to crush down, to diminish, to fall dynamically. It is finked to the antinomy "value/without value," implying the conception of loss of values, that is, contempt for oneself in the Latin sense of "without value" (pretium). This is, in the clinical sense, the condition of the depressed person —a person pervaded by feelings of unworthiness, unable to find his own values (dispretium), and who can reach the extreme condition of melancholy, the complete lack of any will to live. This is a condition in which the individual no longer has true values because he does not belong to the world of meanings of existence. In fact, we cannot have any real knowledge of this "death," but can only reach a hy­pothetical meaning that can be symbolized but not understood. As we have seen, common language already describes two affective ways of perceiving the life to which psychodynamics (primarily psychoanalysis) has given a scientific organization. In this field, we find the description of anxiety as an expression of the failure of the defense mechanisms against the unconscious drives; anxiety also points out the individual successive evolutional steps: fear of losing objects, castration, ego-superego conflicts, and then the feeling that indicates the exhaustion of the homeostatic mechanisms brought against a stimulus that one is unable to face. In all the conditions mentioned, both symbolic and real, anxiety is a danger signal that testifies to the activation of the mechanism (to face stimuli or conflicts) to maintain individual integrity (3). As we have already stated, depression points out the loss of values or depre­ciation of self. This inability to establish one’s own value is deeply rooted in primordial relationship in the personal evolution (2). In the mother-son relationship, when the difference between subject/object has been established, the individual/subject is unable to build his own indepen­dent value. The extreme condition of this is melancholy (1). Through a wide range of conditions, anxiety and depression trace a path from normality to pathology with continuous overlappings. Anxiety is experienced as an unbearable present linked to a future suffered completely in imperative and unknown terms, whereas depression is experienced as a guilty past, condi­tioning everything and transforming the present time only into expiation and punishment. Therefore, in anxiety, the time parameter is experienced as extremely accel­erated; in depression, we can observe the complete time collapse. This is revealed by the total psychomotorial slowing down of the depressed patient who only seems to react when facing the burden of guilt that has not received adequate punishment. This is when anxiety appears in depression as a signal of the above mentioned event. This increasingly complicates the problem of distinguishing between anxiety and depression. Psychopathology and treatment do not give any satisfactory answer to all the problems involved. However, we cannot consider this fact negatively; the active opposition of themes must continue to promote progress in the knowledge of two ubiquitous conditions of human experience. (more…)

We collected information on first- and second-degree relatives of 112 subjects (35 men and 77 women), diagnosed as having Major Depression, Recurrent (UP) (15 men and 41 women), and Bipolar Disorders (BP) (20 men and 36 women), according to DSM-III criteria (1). All the probands were patients being followed at the Institute of Clinical Psychiatry of the University of Milan. These patients represented an overlapping subset of those discussed in previous reports (4,14). Naturally, only subjects for whom complete information about second- degree relatives and tricyclic antidepressant drag treatment outcome was available could be included in the study. Each patient participated in at least one clinical trial, although most of them took part in several trials with different antidepressant drags of the classical tricyclic type only (chlorimipramine, imipramine, amitriptyline, and nortrip­tyline). Each trial consisted of 4 weeks of treatment with full dosages (3,12). Responders were the patients who always showed improvement under the tricyclic treatment. This group consisted of 63 probands, 18 men (UP = 6; BP = 12) and 45 women (UP = 29; BP = 16). We classified as nonresponders the patients who did not improve irrespective of the administered drag; they were 17 probands, 9 men (UP = 4; BP = 5) and 8 women (UP = 2; BP = 6). We defined as poor responders the patients who only showed a slight improvement and/or the patients who had poor outcome on treatment with one of the abovementioned tricyclics and a good outcome on treatment with another one. This last group consisted of 32 probands, 8 men (UP = 5; BP = 3) and 24 women (UP = 10; BP = 14). The demographic and clinical information on the families of our patients such as sex, present age, presence of secondary cases of Affective Disorders, and age at onset was collected by direct interviews with the patients and their relatives. Data on secondary cases in families were confirmed by hospital records, in in­stances in which the subjects previously had been admitted to a psychiatric in­stitute, or by asking the psychiatrists for additional information. Relatives considered to have Major Affective Disorders were those meeting the DSM-III criteria for Major Depression, Recurrent, and Bipolar Disorder. Affective Spectrum Disorders were diagnosed in cases in which the relative met the DSM-III criteria for Dysthymic Disorder, Cyclothymic Disorder, or Atypical Depression. Since we were studying the segregation of susceptibility to Affective Disorders and not the segregation of the disorders themselves, we sought to identify families susceptible to Affective Disorders, regardless of their phenotypical manifestations (both Major Affective Disorders and Affective Spectrum Disorders were included). We submitted our data to segregation analyses, performed by means of Lalouel and Morton’s POINTER program (7). For purposes of the analysis, the nuclear family unit was broadened to include family members who have led to its as­certainment. This procedure introduces the use of the POINTER concept, that is, a relative of extreme phenotype (an affected relative) outside the nuclear family to which it points. The program assumes that each component of a nuclear family (father, mother, and their common offspring) may have only one pointer, a given pointer being assigned only to the closest component of the nuclear family. Information about a pointer includes its phenotype and relationship to the family members. We adopted conditional likelihoods to calculate the like­lihoods of sibships in nuclear families conditioned to pointers as well as on parents. The threshold model requires population prevalences so that liability thresholds can be defined. We incorporated separate prevalences for males and females. Since the probability of illness changes with age and assuming that age of onset is accurately recorded and does not affect ascertainment, we formulated a con­tinuous liability scale defined by 10 age categories, five for males and five for females. We subdivided the total population prevalence of the disorder according to the proportion of onset in these five classes of age (ranging between 10 and 14, 15 and 25, 26 and 37, 38 and 49, and more than 50 years). We assumed uniform risk distribution within each liability class. The analyses were performed on the SPERRY UNI VAC 1100/90 Computer of the University of Milan.

Data from three published reports (6,12,15) were retabulated to allow a direct comparison of the studies. Since Crowe et al. (6) and Noyes et al. (15) reported rates of secondary depression among relatives, it was possible to retabulate their data so that frequencies of diagnoses were obtained. These frequencies could then be compared to the results reported by Leckman et al. (12). For this chapter, the data presented in Crowe et al. (6) and Noyes et al. (15) were retabulated to obtain rates of the following diagnoses: major depressive disorder (MDD), panic disorder and/or generalized anxiety disorder (PD/GAD), and any anxiety disorder that included PD/GAD. The retabulation was accomplished by simply summing the rates for primary diagnoses and all secondary diagnoses for a specific mental disorder. For instance, the rate of MDD is equal to the rate of primary MDD plus all rates of secondary MDD. The data from the Leckman et al. study were retabulated to obtain similar diagnostic groupings for relatives of probands with MDD alone (MDD) and for relatives of probands with MDD and PD (MDD + PD). In addition, because the data from the Crowe et al. and Noyes et al. studies included families of probands with chronologically primary panic disorder or agoraphobia regardless of whether they had secondary depression, we combined the families from the Leckman et al. study in which the probands had major depression without anxiety and the families where the proband had primary major depression and secondary panic disorder. This combination allowed a comparison of rates of diagnoses among relatives of probands with primary major depression with and without panic disorder (MDD ± PD), primary panic disorder with and without major depression (PD ± MDD), and primary ago­raphobia with panic attacks with and without depression (Ag/PD ± MDD). Since some forms of MDD are familial, this retabulation of the Leckman et al. data could introduce a bias. For instance, if the rate of MDD is not elevated in the relatives of probands with PD or agoraphobia alone, then the rate of MDD among relatives in the MDD ± PD families should be higher than the rate of MDD among relatives in the PD ± MDD families. A more appropriate com­parison would be to contrast the rates of illness among the relatives of probands with chronologically primary MDD and secondary PD (MDD + PD) with the rates of illness among the relatives of probands with chronologically primary PD with secondary MDD (PD + MDD). Although the data for the MDD + PD probands were reported by Leckman and co-workers, it was not possible to extract the data for PD + MDD from the published reports of Crowe and Noyes. or this report, the control relatives collected by Leckman et al. were chosen for comparison because the probands were persons with no history of psychiatric illness. The control samples reported by Crowe et al. and Noyes et al. included probands with MDD.