Monday, 24.02.2020

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): 5c. Contributions of Interviewees

(Bulletin 65)


           Three of the interviewees (Cooper, Dahl and Glassman) from Volume Seven were engaged in pharmacokinetic research (Ban 2011; Blackwell 2011). Thomas B. Cooper contributed to the determination of plasma and tissue levels of various antipsychotics (including butaperazine,, loxapine, clozapine and fluphenazine), antidepressants (including mianserin and nortriptyline) and benzodiazepines (Cooper 1989, 1996; Cooper, Simpson, Haher et al. 1975; Katz, Simpson, Jethanandi et al. 1989; Koreen, Lieberman, Alvir et al. 1994; Simpson, Cooper and Lee 1978; Suckow, Cooper, Quitkin and Steward 1982). In 1973, in collaboration with Bergner and Simpson, Cooper demonstrated that a 24-hour serum lithium level is a good “prognosticator” of dose requirement in patients (Cooper, Bergner and Simpson 1973). Cooper was member of the team which reported in 1980 on the effect of antiparkinsonian medication on plasma levels of chlorpromazine (Simpson, Cooper, Cooper, Bark et al. 1980). He was also a member of the team that compared (in 2004) the pharmacodynamic and pharmacokinetic effects of d and d,l-threo-methylphenidate hydrochloride in children with attention deficit disorder (Quinn, Wigal, Swanson et al. 2004).

            While studying the relationship between plasma levels and therapeutic effect of imipramine, in the 1970s, Alexander H. Glassman and his associates found that patients with delusions (psychotic depression) did not respond to the drug (Glassman, Hurrik and Perel 1972; Glassman, Kantor and Shostak 1975; Glassman, Perel, Shostak et al. 1977; Perel, Stiller and Glassman 1978). They also revealed cardiac conductance changes with imipramine, similar to those seen with quinidine (Kantor, Biger, Glassman et al. 1978; Kantor, Glassman, Biger et al. 1978). During the 1980s the focus of Glassman’s research shifted to smoking. He was among the first to demonstrate that clonidine, an α-2 adrenergic agonist, reduced the severity of symptoms after “smoking cessation.” He had also shown the effects of smoking cessation on major depression.

            Svein G. Dahl was among the first in the mid-1970s to study the pharmacokinetics of chlorpromazine and methotrimeprazine after the administration of single and multiple doses (Dahl 1986; Dahl and Straandjord 1977). Ten years later, in the mid-1980s, he was again among the first to introduce plasma level monitoring of antipsychotic drugs (Dahl 1986). During the 1990s the focus of Dahl’s research shifted to the study of structure-activity relationships and to the modeling of neurotransmitter receptors (Dahl, Edwardsen and Sylte 1991; Dahl, Kollman, Ran and Singh 1992).

            Two of the interviewees (George and Lisanby) were involved in research with biophysical approaches to treatment. Mark S. George was first in the 1990s to employ transcranial magnetic stimulation in the treatment of depression (George, Nahas, Kozel et al. 1999; George, Wasserman, Kimbrell et al. 1997; George, Wasserman, Williams et al. 1995). He was also first to explore the utility of vagus nerve stimulation in the treatment of psychiatric disorders (George, Rush, Sackeim et al. 2003).

In the early years of the 21st century Sarah Hollingsworth Lisanby was instrumental in developing magnetic seizure therapy and repetitive transcranial magnetic stimulation in the treatment of depression (Lisanby, Lubeck, Finck et al. 2000; Lisanby, Lubeck, Schlaepfer and Sackeim 2003; Lisanby, Morales. Payne et al. 2003; Lisanby, Schlaepfer and Fisch 2001).  She also explored the possible augmentation of sertraline treatment with transcranial magnetic stimulation (Lisanby, Pascal-Leone, Sampson et al. 2001).  

Each of the remaining six interviewees (Arango, Costa, Kupfer, McKinney, Shooter and Weissman) was involved in a different are of research. Victoria Arango with her associates demonstrated an increase in serotonin 5HT2 and β-adrenergic receptor binding sites in the brains of suicide victims in the 1990s (Arango, Ernsberger, Maszuk et al. 1990). They localized the increase of serotonin receptor binding sites to the ventrolateral prefrontal cortex (Arango, Underwood, Gubbi et al. 1995). In 2002 Arrango was member of the team which reported on altered editing of serotonin 5HT2c receptor pre-mRNA in the prefrontal cortex in suicide and in 2006 she was member of the team that demonstrated lower serotonin transporter binding during major depressive episode (Gurevich, Tamur, Arango et al. 2002; Parsey, Hastings, Oquendo et al. 2006).

            Erminio Costa was first to demonstrate the differential expression of serotonin in various areas of the human brain in the late 1950s (Costa and Aprison 1958). His findings indicated multiple serotonin receptors with different sensitivity to inhibition by lysergic acid diethylamide (LSD) (Costa 1960, 2003). In the 1970s Costa and his associates demonstrated that potentiation of gabaminergic activity plays an important role in the mode of action of benzodiazepines (Costa, Guidotti, Mao and Suria 1975; Guidotti, Baraldi and Costa 1979). They also contributed to the characterization of benzodiazepine receptors (Guidotti, Toffano and Costa 1978). In the mid-1980s Costa was member of the team that discovered metabotropic glutamate receptors (Nicoletti, Meek, Iadarola et al. 1985). In the early years of the 21st century Costa and his associates found that reelin protein and mRNA was reduced in several brain areas in schizophrenia and manic-depressive disease and suggested that dendritic spine hypoplasticity with downregulation of reelin and GABAergic tone is a vulnerability factor for schizophrenia (Costa, Davis, Grayson et al. 2001). In 2002 they postulated that schizophrenia is a disease at the interface of the genome and the epigenome (Costa, Chen, Davis et al. 2002).   

             In the 1970s David J Kupfer reported on changed interval between the onset of sleep and rapid eye-movement sleep in depressed patients and suggested that shortened rapid eye movement (REM) latency was an indicator (“biological marker”) of primary depressive disease (Kupfer 1976; Kupfer and Foster 1972). Kupfer found a statistically significant relationship between the changes in the tonic component of REM sleep and therapeutic response to antidepressants. He also demonstrated that an increase in REM latency and REM suppression after a loading dose of 50 mg of amitriptyline was a predictor of favorable treatment outcome with the drug (Kupfer, Harris, Spiker et al. 1978, 1979). In other areas of research Kupfer contributed to knowledge on maintenance treatment in recurrent depression and on the management of insomnia (Kupfer, Frank, Perel et al. 1992; Kupfer and Reynolds 1997). 

Working with rhesus monkeys William T. McKinney was first in the 1970s to report on the effect of reserpine on social behaviour and on the effect of chlorpromazine on disturbed behavior (McKinney, Eising, Moran et al. 1972; McKinney, Young, Suomi and Davis 1873). In the 1980s he studied the effects of several drugs on the response to social isolation and published his monograph “Animal Models of Mental Disorders” (McKinney 1988; McKinney, Moran and Kraemer 1983).

            In 1976 Eric M. Shooter, in collaboration with Mobley and Schenker, succeeded with the isolation and characterization of “proteolytically modified nerve growth factor” (Mobley, Schenker and Shooter1976). Twenty-six years later, in 2002, Shooter, in collaboration with Cosgaya and Chan, reported that the neurotrophin receptor p75NTR is a positive modulator of myelinisation (Cosgaya, Chan and Shooter 2002).

            Myrna M Weissman was among the first to use psychiatric research diagnostic criteria in epidemiological studies (Weissman and Klerman 1978). In the late 1970s she published her findings on affective disorder in an urban community of the United States and in 1980 she presented epidemiological findings on depression in New Haven (Klerman, DiMascio, Weissman et al. 1974; Weissman and Myers 1980). During the 1970s and ‘80s, Weissman, in collaboration with Gerald Klerman, studied the interaction between drugs and psychotherapy in the treatment of depression and developed short-term interpersonal psychotherapy. Subsequently, she became involved in molecular genetic research in psychiatry (Hamilton, Fyer, Durner et al. 2003; Holmans, Weissman, Zubenko et al. 2007; Klerman, Weissman, Rounsaville and Chevron 1984; Weissman, Pilowsky, Wickramaratne 2006; Weissman, Wickramaratne, Nomura et al. 2006).

The background of interviewees in Volume Seven varies widely. Their only common feature is that all 29 interviewees are members of ACNP.

Interviewees entered the field at different stages in the development of neuropsychopharmacology. Hence the volume covers 50 years of history.




Arango V, Ernsberger P, Maszuk PM, Chen JS, Tierney H, Stanley M, Mann JJ. Autoradiographic demonstration of increased serotonin 5HT2 and β-adrenergic receptor binding sites in the brain of suicide victims.  Arch Gen Psychiatry 1990; 47: 1036-47.

Arango V, Underwood MD, Gubbi AV, Mann JJ. Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims. Brain Res 1995; 688: 121-3.

Ban TA. Preface. In: Blackwell B, editor. Special Areas. (In: Ban TA, editor. An Oral History of Neuropsychopharmacology The First Fifty Years Peer Interviews. Volume Seven. Brentwood: American College of Neuropsychopharmacology; 2011, pp. ix –xxxiii.  

Blackwell B, editor. Special Areas. (In: Ban TA, editor. An Oral History of Neuropsychopharmacology The First Fifty Years Peer Interviews. Volume Seven.) Brentwood: American College of Neuropsychopharmacology; 2011.  

Cooper TB, Simpson GM, Haher EJ, Bergno PE. Butaperazine pharmacokinetics. Effect of drug regime on steady state plasma levels. Archives of General Psychiatry 1975; 32: 903-5.

Cooper TB. Gas liquid chromatography of antidepressants, antipsychotics and benzodiazepine drugs in plasma and tissues. Neuromethods 1989; 10: 65-98.

Cooper TB. Clozapine plasma level monitoring. Psychiatr Quarterly 1996; 67: 297-311.

Cooper TB, Bergner PE, Simpson GM. The 24-hour serum lithium level as a prognosticator of dosage requirement. Am J Psychiatry 1973; 30: 601- 3.

Cosgaya JM, Chan JR, Shooter EM. The neutrophin receptor p75NTR as a positive modulator of myelinization.  Science 2002; 298: 1245-8.

Costa E. The role of serotonin in neurobiology.  Int Rev Neurobiol 1960; 2: 175-227.

Costa E. An Early Attempt to Foster Neuroscience Globalization: An Autobiography.  Nashville: The Good Life Press; 2003. p. 14-5.

Costa E, Aprison MH. Studies on the 5-hydroxytryptamine (serotonin) content in human brain. J Nerv Ment Dis 1958; 126: 289-93.

Costa E, Chen Y, Davis J, Dong E, Noh JS, Tremolizzo L, Veldin M, Grayson DR, Guidotti A. Reelin in schizophrenia. A disease at the interface of the genome and the epigenome. Molecular Interventions 2002; 2: 147-57.

Costa E, Davis J, Grayson DR, Guidotti A, Pappas GD, Pesold C. Dendritic spine hypoplasticity and downregulation of reelin and GABAergic tone in schizophrenia vulnerability. Neurobiology of Disease 2001; 81: 72-42.

Costa E, Guidotti A, Mao CC, Suria A.  A new concept on the mechanism of`action of benzodiazepines. Life Sci 1975; 17: 167-86.

Dahl SG. Pharmacokinetics of methotrimeprazine after single and multiple doses. Clin Pharmacol Ther 1976; 19: 435-42.

Dahl SG. Plasma level monitoring of antipsychotic drugs. Clinical utility. Clin Phamacokinet 1986; 11: 36-61.

Dahl SG, Edwardsen O, Sylte J. Molecular dynamics of dopamine D2 receptor. Proc Natl Acad Sci (USA) 1991; 88: 8111-5.

Dahl SG, Kollman PA, Ran SN, Singh UC. Structural changes by sulfoxidation of phenothiazine drugs. J Computer Aided Molecular Des 1992: 6: 207-22.

Dahl SG, Straandjord RER. Pharmacokinetics of chlorpromazine after single and chronic dosages. Clin Pharmacol Ther 1977; 21: 437-8.

George MS, Nahas Z, Kozel PA, Goldman J, Mollow M, Oliver N. Improvement of depression following transcranial magnetic stimulation. Current Psychiatry Reports 1999; 1: 114 - 24.

George MS, Rush AJ, Sackeim HA, Marangell LB. Vagus nerve stimulation (VNS) utility in neuropsychiatric disorders.  Journal of Neuropsychopharmacology 2003; 6: 7383-4.

George MS, Wasserman EM, Kimbrell TA, Little JT, Williams WE, Danielson AC, Greenberg BD, Hellett M. Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation  in patients with depression. A placebo-controlled crossover trial. Am J Psychiatry 1997; 154: 1752-6.  

George MS, Wasserman EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (TMS) improves mood  in depression. Neuroreport 1995; 6: 1853-6.

Glassman AH, Covey LS, Stetner F, Rivelli S. Smoking cessation and the course of major depression. Lancet 2001; 357: 1546-9.

Glassman AH, Helzer JE, Covey LS, Cottler LB, Stetner F, Tip JE. Smoking cessation and major depression. JAMA 1990; 264: 1546-9.

Glassman AH, Hurvik MJ, Perel JM. Plasma binding properties of imipramine and clinical outcome. Am J Psychiatry 1973; 169: 1367-9.

Glassman AH, Kantor SJ, Shostak M. Depression, delusion and drug response. Am J Psychiatry 1975; 132; 711- 9.

Glassman AH, Perel JM, Shostak M, Kantor SJ, Fleiss L. Clinical implications of imipamine plasma levels on depressive illness. Arch Gen Psychiatry 1977; 34: 197-204.

Glassman AH, Stetner F, Walsh BT, Raizman L, Fleiss JL, Cooper TB, Covy LS. Heavy smokers, smoking cessation and clonidine. Results of a double-blind randomized trial. JAMA 1988; 254: 2863-6.

Glassman AH, Stetner F, Walsh BT, Raizman R, Rosenfeld B. Cigarette craving. Smoking withdrawal and clonidine. Science 1984; 226: 864-6.

Guidotti A, Baraldi M, Costa E. 1,4 Benzodiazepines and γ-aminobutyric acid: pharmacological and biochemical correlates.  Pharmacology 1979 19; 267-77.

Guidotti A, Toffano G, Costa E. An endogenous protein modulates the affinity of GABA and benzodiazepin receptors in rat brain.  Nature 1978; 257: 553-5.

Gurevich I, Tamir H, Arango V, Mann JJ, Dwork AJ, Schmauss C. Altered editing of serotonin HT2c receptor pre-mRNA in the prefrontal cortex of depressed suicide victims. Neuron 2002; 34: 349-56.

Hamilton SP, Fyer AJ, Durner M, Heiman GA, deLeon AB, Hodge SE, Knowles JA, Weissman MM. Further genetic evidence for a panic disorder syndrome mapping to chromosome 13q.  Proc Nat Acad Sciences  2003; 100: 2550-5.

Holmans P, Weissman MM, Zubenko GS, Scheftner WS, Crowe RR, Depaulo JR, Knowles JA, Zubenko WN, Murphy-Eberenz K, Marta DH, Boutelle S, McInnis MG, Adams P, Gladis M, Thomas J, Chellis J, Miller E, Potash JB, MacKinnon D, Levinson DF. Genetics of recurrent early-onset major depression (GenRED): Final genome scan report.  American Journal of Psychiatry   2007; 164: 248-58.

Kantor SJ, Biger ST, Glassman AH, Macken DL, Perel JS. Imipramine-induced heart block. N Engl J Med 1975; 23: 1364-6.

Kantor SJ, Glassman AH, Biger  ST, Perel SM, Giardina EV. The cardiac effects of therapeutic concentration  of imipramine. Am J Psychiatry 1978; 135: 534-8.

Katz IR, Simpson GM, Jethanandi V, Cooper T, Muhly C. Steady state pharmacokinetics of nortiptyiline in the frail elderly. Neuropsychopharmacology 1989; 2: 229-36.

Klerman GL, DiMascio A, Weissman MM, Prusoff B, Paykel ES. Treatment of depression by drug and psychotherapy. Am J Psychiatry 1874; 131: 186-91.

Klerman GL, Weissman MM, Rounsaville BJ, Chevron E. Short-term Interpersonal Psychotherapy (IPT) for Depression. New York: Basic Books; 1984. 

Koreen R, Lieberman J, Alvir J, Chakos M, Loebel A, Cooper TB, Kane J. Relation of plasma fluphenazine levels to treatment response and extrapyramidal side effects. Am J Psychiatry 1994; 151: 15- 39.

Kupfer DJ. A psychobiological marker for primary depressive disease. Biol Psychiatry 1976; 11: 159-74.

Kupfer DJ, Frank E, Perel JM, Ciornes C, Mollinger AG, Thase ME, McEachan AB, Grochocinski VJ. Five-year outcome for maintenance therapies  in recurrent depression. Arch Gen Psychiatry 1992; 49: 769-73.

Kupfer DJ, Foster G. Interval between onset of sleep and rapid eye movement sleep as an indicator of depression. Lancet 1972; 2: 684-6.

Kupfer DJ, Hanin I, Spiker D, Neil J, Coble P, Grau T, Nevar C. Amitriptyline plasma levels and clinical response in primary depression: II. Communications in Psychopharmacology 1978; 2: 441-50.

Kupfer DJ, Hanin I, Spiker DG, Neil J, Coble P. EEG sleep and tricyclic plasma levels in primary depression. Communications in Psychopharmacology 1979; 3: 73-80.

Kupfer DJ, Reynolds CF. Management of insomnia. N Engl J Med 1997; 336: 341-6.

Lisanby SH, Luber B, Finck AD, Schroeder C, Sackeim HA. Deliberate seizure induction with repetitive transcranial magnetic stimulation in nonhuman primates. Archives of General Psychiatry 58: 199-200.

Lisanby SH, Luber B, Schlaepfer TE, Sackeim HA. Safety and feasibility of magnetic seizure therapy (MST) in major depression: randomized within subject comparison with electroconvulsive therapy.  Neuropsychopharmacology 2003; 28: 1852-65.

Lisanby SH, Morales O, Payne N, Kwon E, Fitzsimmons L, Luber B, Nobler MS, Sackeim  HA. New developments in electroconvulsive therapy and magnetic seizure therapy. CNS Spectrum 2003; 8: 529-36.

Lisanby SH, Pascal-Leone A, Sampson SM, Boylan LS, Burt T, Sackeim HA. Augmentation of sertraline antidepressant treatment with transcranial magnetic stimulation.  Biological Psychiatry 2001; 49:  815-6. 

Lisanby SH, Schlaepfer TE, Fisch HU. Magnetic seizure therapy of major depression. Archives of General Psychiatry. 2001; 58:  303-5.

McKinney WT. Animal Models of Mental Disorders. A New Comparative Psychiatry.  New York: Plenum Press; 1988.

McKinney WT, Eising RG,  Moran EC,  Suomi SJ, Harlow HF. Effects of reserpine  on the social  behavior of rhesus monkeys. Dis Nerv System 1971; 32: 308-13.

McKinney WT, Moran EC, Kraemer GY. Effects of drugs on the response to social separation in rhesus monkeys. In: Steklis HD, King AS, editors. Hormones, Drugs and Social Behavior.  New York: Spectrum Press; 1983. p. 249-70.

McKinney WT, Young LD, Suomi SJ, Davis JM. Chlorpromazine treatment of disturbed monkeys.  Arch Gen Psychiatry 1973; 29:  490-4.

Mobley WC, Schenker A, Shooter EM. Characterization and isolation of proteolytically modified  nerve growth factor. Biochemistry 1976; 25: 5542-52.

Nicoletti  F, Meek JL, Iadarola  MJ, Chuang DM, Roth BL, Costa E. Coupling of inositol  phospholipid metabolism with excitatory amino acid  recognition sites  in rat hippocampus. J Neurochem 1985; 46:40-5. 

Parsey RV, Hastings RS, Oquendo MA, Huang YY, Ogden RT, Van Heertum RL, Arango V, Mann JJ. Lower serotonin transporter binding in the human brain during major depressive episode. Am J Psychiatry 2006; 163: 52-8.

Perel JM, Stiller RL, Glassman AH. Studies on plasma level/effect relationship in imipramine therapy. Commun Psychopharmacol 1978; 2: 1429-39.

Quinn D, Wigal S, Swanson J, Hirsch S, Ottolini Y, Dariani M, Roffman M, Zelds J, Cooper T. Comparative pharmacodynamics and plasma concentrations of d-threo-methylphenidate hydrochloride after single doses of d-threo-methylphenidate hydrochloride and d,l-threo-methylphenidate hydrochloride in a double-blind, placebo-controlled, crossover laboratory school study in children with attention-deficit/hyperactivity disorder. Child and Adolescent Psychiatry 2004; 413: 1422-9.

Simpson GM, Cooper TB, Bark N, Sut I, Lee HJ. Effect of antiparkinsonian medication on plasma levels of chlorpromazine. Archives of General Psychiatry 1980; 37: 205-8.

Simpson GM, Cooper TB, Lee JH, Young MA. Clinical and plasma level characterization of intramascular and oral loxapine. Psychopharmacology 1978; 58: 225-32. 

Suckow RF, Cooper TB, Quitkin FM, Steward JW. Determination of mianserin and metabolites in plasma by liquid chromatography with electrochemical detector. Journal of Pharmaceutical Sciences 1982; 71: 889-92.

Weissman MM, Klerman GL. Epidemiology of mental disorders. Merging trends in the United States. Arch Gen Psychiatry 1978; 35: 7-5-12.

Weissman MM, Myers JK. Affective disorders in a United States urban community; the use of research diagnostic criteria in an epidemiological survey. Arch Gen Psychiatry 1978; 35:  1304-11.

Weissman MM, Myers JK. Depression in New Haven. 1975-76. An epidemiological study. The Yale Journal of Biology and Medicine 1980; 53: 117-26.

Weissman MM, Pilowsky DJ, Wickramaratne PJ, Talati A, Wisniewski SR, Fava M, Hughes CW, Garber J, Malloy E, King CA, Cerda G, Sood AB, Alpert JE, Trivedi MH, Rush AJ; STAR*D-Child Team. Remission of maternal depression is associated with reductions in psychopathology in their children: A Star*D-Child Report.  JAMA   2006; 295: 1389-98.

Weissman MM, Wickramaratne P, NomuraY, Warner V, Pilowsky D, Verdeli H. Offspring of depressed parents: 20 years later. Am J Psychiatry   2006; 163: 1001-8.


April 11, 2019