Hagop S. Akiskal

Depressive Disorders: Toward a Unified Hypothesis Clinical, experimental, genetic, biochemical, and neurophysiological data are integrated

Our scientific understanding of psychiatric syndromes, including the phenomena of depression, has been hampered because of: (i) the use of metapsychological concepts that are difficult to test; (ii) methodological and linguistic barriers that prevent communication among psychoanalysts, behaviorists, experimental psychologists, and psychiatrists; and (iii) the reluctance of psychiatrists to accept animal models as possible approximations of certain aspects of human psychopathology. We have attempted to demonstrate that the animal models simulate some of the central features of clinical depression (for example, helplessness and object loss), thereby allowing one to rigorously investigate them from developmental, behavioral, and biochemical perspectives. The object loss model, as a concrete version of a metapsychological-psychoanalytic concept, has enabled primatologists to study the disruption of an attachment bond. The behavioral model accommodates this concept to a broader generalization: loss of reinforcement or loss of control over reinforcement. We have reviewed the evidence that these processes involve the diencephalic centers of reward or reinforcement, thereby permitting integration of the psychoanalytical and behavioral formulations with the biochemical hypotheses. Also, we have presented data strongly suggesting that the breaking of an attachment bond in the primate represents significant loss of reinforcement that induces helplessness and disrupts motivated behavior. Finally, we have argued that the depressive syndrome could be caused by interactions of genetic, chemical, developmental, and interpersonal factors, all of which impinge on the diencephalic centers of reinforcement.

Anxious Depressions Clinical, Family History, and Naturalistic Outcome -- Comparisons with Panic and Major Depressive Disorders

Patients with anxiety and depressive states were divided into 4 groups: those with panic attacks only, those with panic disorder and secondary depression, those with depression and secondary panic attacks, and those with depression only. Clinical and familial differences between the groups are described. Patients with both depression and panic attacks had the poorest outcome, and were most likely to be chronically depressed.

The manic-depressive mixed state: familial, temperamental and psychopathologic characteristics in 108 female inpatients.

SummaryData on 108 hospitalized bipolar I women were analyzed to characterize those whose course was marked with at least one mixed episode (i.e. an episode with concomitant manic and depressed features) on the basis of various anamnestic and cross-sectional clinical features in comparison with those without mixed episodes. Our data revealed a later age of appearance of the first mixed episode in the course of bipolar illness with a tendency to recur true to type; greater prevalence of mood incongruent psychotic features; lower frequency of hyperthymic temperament; and familial depressive, rather than bipolar, disorders. These characteristics tend to identify the mixed state as a distinct longitudinal pattern of manic-depressive illness.

Immune Cell Imbalance in Major Depressive and Panic Disorders

We investigated subsets of peripheral immunologic cells in 12 drug-free patients affected by major depression according to DSM-III-R criteria, and who had recent evidence of somatic diseases. They were compared with 10 drug-free depressives, with 10 patients with panic disorder, and with 12 healthy volunteers, all without somatic disease. The immune subsets were measured by flow cytometry. The results showed that both groups of depressives had the same abnormalities in immune cells compared with the healthy volunteers or the panic disorder patients; in particular they presented a lower number of CD3+, CD8+ and HLA-DR+. The patients with panic attacks did not differ from healthy controls, except for CD4+ cells which were significantly lowered, even in comparison with the depressive groups. These data, although preliminary and in a small sample, suggest that some immune parameters may be influenced by the presence of a major psychiatric disorder.

Differential changes in areas of social adjustment from depressive episodes through recovery

The findings of the present short-term prospective study of 99 depressed outpatients further support previous cross-sectional observations to the effect that the course of depressive illness is often complicated by fluctuating social disturbances manifested by uneasiness in the work area, by disagreements with colleagues, and by difficulty in maintaining conflict-free relationships with significant others. By contrast, the incapacity to enjoy and use leisure time appeared less related to the symptomatologic variation in depression. Although we favor the hypothesis that impairment in leisure activity may represent a trait marker of depression, the hypothesis of it being a residual complication of repeated depressive episodes cannot be ruled out in view of short follow-up.

Mental Status Examination

The Mental Status Examination represents the most important step in the clinical evaluation of individuals suffering from or suspected of having mental disorders. The evaluation is based on observations of a patient’s overt and verbal behavior as well as on his or her subjective experiences. Patients’ presenting problems dictate both the types of questions asked and the depth of inquiry necessary for a coherent and complete assessment of the mental status. In general, the more deviant and severely disturbed the patient, the more probing the mental status examination should be.

The role of psychotherapy in chronic depressions: A proposal

Abstract Chronic depressions which account for about 15% of depressive disorders, have been recently subdivided into early-onset characterologic and late-onset unipolar depressions. In both conditions chronic mild depressive symptoms become ingrained in the personality and impair social functioning; the treating physician may easily overlook the underlying affective disturbance and consider these patients as having anxiety or personality disorder. The late onset group of patients with unresolved, partially remitted acute depression, appears most promising for clinical trials testing the efficacy of brief psychotherapies aimed at symptom reduction and improved social functioning. The indirect evidence that psychotherapy may be useful for such patients is reviewed. Psychotherapeutic strategies are outlined.

Acompanhamento polissonográfico das apnéias do sono após uvulopalatofaringoplastia

Uvulopalatopharyngoplasty (UPPP) was performed in 12 patients with obstructive sleep apnea. Pre-surgical clinical and polysomnographic data were compared with those one to three months after surgery. Excessive daytime sleepiness was partially improved in 4 cases and completely abolished in 8. Total sleep time, sleep efficiency, number of arousals and sleep latency were similar in both evaluations. REM latency to stage 2 markedly increased on the follow-up. Stage distributions were similar in both nights except for stage 4 which was more frequently absent on the first recording. SaO2 levels below 80% were seen in 10 cases before UPPP and in 4 after it. Apnea index decreased in all cases but it reached normal levels only in 4.

Toward a Psychobiological Integration: Affective Illness as a Final Common Path to Adaptive Failure

In the late 1930s the philanthropist William T. Grant provided the financial means to study a group of male university students through the normal life cycle.2 Many of these men are now in their early 60s. Initially individuals were included in the study because they appeared healthy, and although all have experienced challenge and disappointment, many have stayed so. Reviewing something of what has been learned through study of the lives of these men, George Vaillant has observed that the most striking feature has been their ability to adapt to changing circumstance. Psychological health, Vaillant concludes, is realistic adaptation, orchestrating life’s demands so that they fall within one’s ability to manage. Adapting with some degree of success, or at least struggling on reasonably equal terms with one’s environment, may be termed coping. Consistent coping brings mastery.

Implications for Clinical Practice, Training, and Research

In this book we have tried to present a pluralistic and integrative view of the psychobiology of mood disorders. Our goal has been to present a holistic paradigm for understanding mood disorders, but the approach can serve equally well for understanding other major psychiatric syndromes. Despite the significant advances made over the last two decades, we are only just beginning to understand the affective psychoses. Undoubtedly, our present limited understanding of the monoaminergic and endocrine mechanisms that underlie the various types of depression will give way to more sophisticated theories. Likewise, the mechanisms by which attachment in early development influences mood and depression later in life will become clearer. Most importantly, the mechanisms whereby psychologically defined events such as developmental deprivation, specific characterological traits, and adult loss interact with predisposing heredity and concurrent physiological stressors will be elucidated.