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): 5a. Contributions of Interviewees
(Bulletin 63)

           Information in Bulletins 59, 60, 61 and 62 provides orientation points on the development of four major “special areas” in Volume Seven, in which interviewees were involved with: Child Psychiatry, Geriatric Psychiatry, Psychiatric Diagnosis and Pharmacokinetics (Ban 2011; Blackwell 2011).

           From the 29 interviewees, three (Costa, Eichelman, George) were MD/PhDs; 17 (Akiskal, Alexopoulos, Blazer, Chase, Clayton, Dunner, Fish, Glassman, Halbreich, Halmi, Jeste, Kupfer, Lisanby, McKinney, Reisberg, Rapoport and Wender) were MDs; eight (Arango, Conners, Dahl, Endicott, Kaufman, Klein, Shooter and Weissman) were PhDs; and one (Cooper) was an MA. From the 17 MDs, 16 were psychiatrists - one of the psychiatrists (Halmi) was also a qualified pediatrician - and one (Chase) was a neurologist. From the eight PhDs, three (Conners, Endicott and Klein) were psychologists and from the other five. each was qualified in a different discipline: Arango in neuroanatomy, Dahl in pharmacology, Kaufman in biochemistry, Shooter in chemistry and Weissman in epidemiology.

           All interviewees were affiliated with ACNP; two, Kupfer and Rapoport, were past presidents of the organization.   

           The interviews were conducted from 1996 to 2008 and, with the exception of one, Lisanby, who was interviewed at the CINP Congress in Paris, all were interviewed at ACNP’s annual meetings.

           The 29 interviewees were interviewed by 12 interviewers: one interviewee (Fish) was interviewed by two interviewers (Meldrum and Bromley). Nine of the interviewers were peers of the interviewees, knowledgeable in the same field, and three (Bromley, Meldrum and Tone) were medical historians. Eight of the interviewers (Angrist, Clayton, Koslow, Meldrum, Post, Regier, Schatzberg and Van Kammen) conducted one interview; two (Bromley and Healy) conducted two; and from the remaining two, one (Tone) conducted five and the other (Ban) conducted 13.

           By the time Volume Seven was completed, one of the interviewees (Schuster) passed away.

Contributions of Interviewees

           The 29 interviewees contributed to 11 areas of research. Six of the interviewees (Conners, Fish, Kaufman, Klein, Rapoport and Wender) were engaged in research related to child psychiatry.

           In the 1960s Seymour Kaufman described the structure of the phenylalanine cofactor and the physical properties of 3, 4 dihydroxyphenylalanine-β-hydroxylase (Kaufman 1963). He also defined the role of copper in the catalytic activity of the enzyme (Freedman and Kaufman 1965). In the 1970s Kaufman identified two new forms of phenylketonuria:  one (1975) due to deficiency of dihydropteridine release and the other (1978), due to biopterin deficiency (Kaufman, Berlow, Summer et al. 1978; Kaufman, Holzman, Milstein et al. 1978).

           In the 1960s and ’70s   Barbara Fish, contributed to the introduction of several psychotropic drugs, e.g., trifluoperazine, thiothixene, chlordiazepoxide, in child psychiatry (Fish, Campbell, Shapiro and Weinstein 1960; Fish, Shapiro and Campbell 1966; Petti, Fish, Shapiro et al. 1982). She also contributed to the development of a methodology for the detection of drug-induced changes in “an organism that is in the process of changing” (Fish 1964).

            C. Keith Conners contributed to the characterization of minimal brain dysfunction and to the development of rating scales for use in drug studies with children (Conners 1967; Werry, Sprague, Cohen and Conners1975). In a series of clinical investigations carried out in the 1960s he also contributed supportive information on the effectiveness of methylphenidate in disturbed children and of dextroamphetamine on the school behaviour of children with learning disabilities (Conners and Eisenberg 1963; Conners, Eisenberg and Barcai 1967). In 1980 Conners was among the first to discuss a possible relationship between food additives and hyperactivity in children. (Conners 1980).

           Paul H. Wender extended the diagnostic concept of “minimal brain dysfunction” from children to adults. He was first to explore systematically the pharmacology of minimal brain dysfunction (attention deficit hyperactivity disorder) in both children and adults. Wender presented his findings in his monographs on Minimal Brain Dysfunction in Children, published in 1971, and on Minimal Brain Dysfunction in Adults, published in 1995 (Wender 1971, 1995; Wender, Wood, Reinherr and Ward 1983). In the 1960s Wender, in collaboration with Seymour Kety and David Rosenthal, introduced a new methodology in epidemiologic genetic research by studying mental illness in the biological and adoptive families of adopted children with schizophrenia (Rosenthal, Kety, Wender, Schulsinger et al. 1968). They also introduced the concept of   ”schizophrenia spectrum disorders” (Kety, Rosenthal, Wender and Schulsinger 1968; Wender, Rosenthal and Kety 1968).       

           In the 1970s Judith Rapoport contributed to knowledge on the use of methylphenidate in attention deficit hyperactivity disorder (Rapoport, Quinn, Bradhard and Riddle 1974; Zamotkin and Rapoport 1987). She was first to demonstrate that dextroamphetamine produced a marked decrease in reaction time and motor activity in normal pre-pubertal boys (Rapoport, Buchsbaum, Zahn et al. 1978). In the 1980s Rapoport ‘s research shifted to the study of the pharmacology of obsessive-compulsive disorder (OCD) in children (Rapoport 1989a,b). In the early 1990s she was a member of the team which showed the differential effect of desipramine and clomipramine in children and adolescents with OCD (Leonard, Swedo, Rapoport et al. 1989).

           Rachel Gittelman Klein was first in the 1990s to show the effectiveness of imipramine in the treatment of separation anxiety disorder (Klein, Kopewicz and Kanner 1992). She was also among the first to extend the use of methylphenidate to conduct disorders (Klein, Abikoff, Klass et al. 1997). Klein was member of the team which explored the use of pemoline in conduct disorders (Shah, Seese, Abikoff and Klein 1994). In 1997 in collaboration with Abikoff, Klein had shown that behaviour therapy gives no added benefit to treatment with methylphenidate in attention deficit hyperactivity disorder (Klein and Abikoff 1997).

            Five of the interviewees (Alexopoulos, Blazer, Chase, Jeste and Reisberg) were engaged in research related to geriatric psychiatry.

           Dan G. Blazer was involved in studying the epidemiology and genetics of melancholia in the aged. He was among the first to report on a decrease of depressive illness in the elderly (Blazer 2001a,b, 2005; Blazer, Burchett and Fillenbaum 2002).

           In the early 1980s Barry Reisberg developed assessment instruments which were to be used extensively in clinical studies with psychotropic drugs in the aged, e.g., Global Deterioration Scale, Brief Cognitive Rating Scale (Reisberg 1981, 1983; Reisberg, Ferris, de Leon and Crook  1982; Reisberg, Schneck, Ferris et al. 1982). Reisberg was among the first to study Memantine, a substance synthesized in 1963 that blocks glutamatergic N-methyl - aspartic acid (NMDA) receptors in elderly patients. He led the team which reported in 2003 on favourable effects of Memantine in moderate to severe Alzheimer’s disease (AD) (Reisberg, Doody, Stoffler et al. 2003).  

            In the 1980s, Thomas N. Chase studied cortical abnormalities in AD with the employment of glucose utilization (Chase, Burrows and Mohr 1987; Foster, Chase, Mansi et al. 1984).  He was among the first to explore gamma-butyric acid GABA agonist therapy for AD (Mohr, Bruno, Foster et al. 1986). Shifting the focus of his research from AD to Parkinson’s disease (PD) in the 1990s, Chase with his associates demonstrated the significance of continuous dopaminergic stimulation treatment of PD (Blanchot, Metman and Chase 1998; Chase 1998; Juncos, Fabbrini, Moaradian et al. 1982). In 2003 Chase was first to report on the use of an A_2A receptor agonist in the treatment of PD (Bara –Jimenez, Starzai, Dimitrova et al. 2003). 

           In the 1990s Dilip V. Jeste contributed to knowledge on late onset schizophrenia (Heaton, Gladsio, Palmer et al. 2001; Jeste, Symonds, Harris et al. 1997).   In a prospective study he also demonstrated the difference in the risk factor for tardive dyskinesia in old and young patients with schizophrenia (Jeste, Caligiuri, Paulsen et al. 1995). Jeste was a member of the team which reported in 2000 on the incidence and risk factors for hallucinations and delusions in probable AD (Paulsen, Salmon, Thal et al 2000).

           George S. Alexopoulos contributed to knowledge on late onset depression (Alexopoulos 2005; Alexopoulos, Klossen, Heo et al. 2005). He studied the relationship between: (1) brain changes and depression in geriatric patients; (2) late-life depression and neurological disease; and (3) depressive symptoms, vascular disease and cognitive impairment (Alexopoulos 1989; Alexopoulos, Meyers, Young et al. 1988; Barnes, Alexopoulos, Lopez et al. 2006). In the early years of the 21^st century Alexopoulos extended his research to the study of the difference in placebo response between old and young patients (Alexopoulos, Kanellopoulos, Murphy et al. 2007). In 2008 he reported on a negative correlation between micro-structural white matter abnormalities and remission in geriatric depression (Alexopoulos, Murphy, Gunning-Dixon et al. 2008).

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March 28, 2019