Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Education in the Field in the Post-Neuropsychopharmacology Era
Background to An Oral History of the First Fifty Years

Special Areas (Volume Seven): 5b. Contributions of Interviewees

(Bulletin 64)

 

           Seven of the interviewees from Volume Seven (Akiskal, Clayton, Dunner, Eichelman, Endicott, Halbreich and Halmi) were engaged in research related to diagnostic end-points in psychopharmacologic research (Ban 2011; Blackwell 2011). In the late 1960 Paula J Clayton was instrumental in introducing Karl Leonhard’s diagnostic concept of “bipolar disorder” in the United States and in the early 1980s in perpetuating Kasanin’s diagnostic concept of “schizoaffective disorder” (Clayton 1982; Clayton, Halikas and Maurive 1972; Kasanin 1933; Leonhard 1957; Winokur, Clayton and Reich 1969).One of the recurring themes in Clayton’s research was the separation of symptoms of bereavement from symptoms of depression (1979, 1990). In the 1970s Clayton was a member of a team which studied the relationship between nortriptyline plasma levels and therapeutic response (Ziegler, Clayton, Taylor et al. 1976). In the 1990s she co-authored paper with Jules Angst and his associates in Zurich on mortality of patients with mood disorders (Angst, Stansen, Clayton and Angst 2002).

In the mid-1970s Jean Endicott, in collaboration with Robert Spitzer and Eli Robins, developed Research Diagnostic Criteria (RDC) for a Selected Group of Functional Psychoses (Spitzer, Endicott and Robins 1975, 1978). In collaboration with Spitzer she also developed the Schedule of Affective Disorder and Schizophrenia (SADS) (Endicott and Spitzer 1978). The RDC and SADS, together with Feighner’s Research Diagnostic Criteria, provided the bridge between the DSM-II and the DSM-III (American Psychiatric Association 1968, 1980; Feighner, Robins, Guze, Woodroff, Winokur and Munoz 1972). During the 1980s and ’90s, Endicott contributed with her research to the recognition of “premenstrual dysphoric disorder” as a distinct diagnostic entity (Endikott, Amsterdam, Erikson et al. 1999).

Searching for a unifying hypothesis of affective disorders, Hagop Akiskal studied sub-affective disorders, such as dysthymia, cyclothymia, and bipolar II disorder, in the “borderline realm” (Akiskal 1981; Akiskal and McKinney 1978). In 1983 he critically reviewed the relationship between personality and affective disorder and presented his findings on the psychopathology of chronic depressive subtypes (Akiskal 1983a; Akiskal, Hirschfeld and Yerevenian 1983). In the 1990s, further pursuing the same line of research, he introduced the concept of “bipolar spectrum disorders”; provided evidence for switching from unipolar to bipolar II disorder; and described prototypes of bipolar I, II, III and IV disorders (Akiskal 1983a,b; Akiskal, Maser, Zeller et al. 1995; Akiskal and Pinto 1999).

            Studying the genetics of manic-depressive illness in collaboration with Elliot Gershon, David Dunner, in the late 1960s, identified what was to become known as “bipolar II disorder” (Dunner, Gershon and Goodwin 1976). Subsequently, studying factors which might be related to failure in responding to lithium, in collaboration with Ronald Fieve, Dunner was among the first to describe “rapid cycling” patients (Dunner 1987; Dunner and Fieve 1974; Dunner, Fleiss and Fieve 1976; Dunner, Patrick and Fieve 1877; Fieve, Kimbaracki and Dunner 1976; Goodnick, Dunner and Fieve 1981). They also proposed a classification of bipolar affective disorder (Dunner, Russek, Russek and Fieve 1982). During the 1980s and ’90s Dunner was involved in the clinical evaluation of several psychotropic drugs, including adinazolam, alprazolam, fluoxetine, citalopram, paroxetine, etc. (Dunner and Dunbar 1982; Dunner, Hendricksen, Bea et al. 2002; Dunner, Ishiki, Avery et al. 1986; Dunner, Myers, Khan et al. 1987: Dunner, Schmaling, Hendricksen et al. 1998).     

            Using a specially devised assessment form for the detection of premenstrual symptoms in the mid-1980s, Uriel Halbreich, in collaboration with Jean Endicott, found a diversity of premenstrual changes and linked these changes to gonadal hormone secretion (Halbreich Endicott, Goldberg and Nee 1986; Halbreich, Endicott, Schacht and Nee 1982).  They also revealed a relationship between premenstrual dysphoric changes and depression (Halbreich and Endicott 1985). In the 1990s Halbreich suggested that “menstrually related disorders” are valid diagnostic end points and embarked on studies on the relationship between gonadal hormones and these disorders (Halbreich 1990a, 1993). He also explored the use of progesterone antagonists and sertraline in the treatment of the premenstrual dysphoric syndrome (Halbreich 1990b; Halbreich and Smoller 1997). In his early research Halbreich found a difference in growth hormone response to dextroamphetamine between depressed patients and normal subjects and between postmenopausal women and normal young men (Halbreich, Asnis, Halpern et al. 1980; Halpern, Sachar, Asnis et al. 1982). In 1990 he reported on the effects of estrogen replacement in the treatment of postmenopausal disorders (Halbreich 1990c).

            Focusing on eating disorders in her research, Katherine A Halmi, in the late 1970s, reported on the effectiveness of cyproheptadine, a serotonin antagonist, in the treatment of “anorexia nervosa” (Goldberg, Halmi and Eckert 1979). She followed up her findings with a comparative study of cyproheptadine and amitriptyline, and by comparing the effectiveness of cyproheptadine in bulimic and non-bulimic anorexia nervosa patients (Eckert, Halmi and March 1986; Halmi, Eckert, La Du and Cohen 1986).  With the employment of biological measures during the 1980s Halmi found similarities between anorexia nervosa and depression (Halmi 1981, 1992). Halmi was a member of the team which identified in 2002 a susceptibility gene for anorexia nervosa on chromosome 1 (Grica, Halmi, Fichter et al. 2002).

            In a series of experiments conducted in the rat in the early 1970s, Burt Eichelman found that social setting influenced physiological response to electric shock (Williams and Eichelman 1971). Focusing on the pharmacology of aggression in his research he revealed the effect of sub-cortical lesions on shock-induced aggression (Eichelman 1979). He then demonstrated that 6-hydroxydopamine administration facilitated aggressive behaviour (Eichelman, Thoa and Ng 1982). In the mid-1980s Eichelman reported that combined treatment with tryptophan and trazodone has a favourable effect on aggressive behaviour (O’Neil, Page, Adkins and Eichelman 1986). In 1990, in recognition of the pharmacological heterogeneity of the population displaying aggressive and violent behaviour, Eichelman developed The Carolina Nosology of Destructive Behaviour (Eichelman 1988; Eichelman and Hartwig 1990).

 

References:

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Akiskal HS. The bipolar spectrum. New concepts in classification and diagnosis. In: Grinspoon L, editor. Psychiatry Update: The American Psychiatric Annual Review. Washington: American Psychiatric Association; 1983b. p. 271-92.

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Akiskal HS, Maser JD, Zeller P, Endicott J, Coryell W, Keller M, Warshaw M, Clayton P, Goodwin FK. Switching from unipolar to bipolar II. An 11 year prospective study of clinical and temperamental predictors in 559 patients. Arch Gen Psychiatry 1995; 52: 114-23. .

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Fieve RR, Kumbaracki T, Dunner DL. Lithium prophylaxis of depression in bipolar I, bipolar II and unipolar patients. Am J Psychiatry 1976; 133: 925-30. 

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April 4, 2019