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Sunday, 19.09.2021

W. Edwin Fann: A History of the Tennessee Neuropsychiatric Institute

David S. Janowsky’s comment
My time at the Tennessee Neuropsychiatric Institute (1970 – 1973)

 

 

            Dr. Tom Ban was kind enough to ask me to comment on Edwin W. Fann’s account of the founding and early years of the Tennessee Neuropsychiatric Institute (TNI). He also requested that I present my story and experiences of the time I was there, which was from the Fall of 1970 until the Summer of 1973.  I must say that I do not share Ed’s fantastic memory for details nearly 50 years later, but here goes, in free form, anyway. 

            First, I would like to comment on Ed’s essay.  I so much appreciate his giving a historical context to the development of the TNI.  I learned much about the TNI’s early development from reading his essay-information that had more or less bypassed me as a young professional.  Ed’s comments put into bold relief just how innovative and groundbreaking the TNI’s early development was and how much ingenuity, foresight and perseverance its founders, including, prominently, Ed Fann, had shown over the decade before John Davis’s and my arrival in 1970.   Those efforts, often done on a handshake by scientific luminaries, such as Fridolin Sulser, John Oates, Frank Luton, Alan Bass, Jim Dingell, Daniel Efron and a myriad of State administrators, seems almost quaint in today’s world.    To break from the hallowed halls of Vanderbilt University and to build a research center within the aged Central State Hospital, miles away, peopled in large part by chronic lifelong psychiatric patients, and to incorporate a preclinical and clinical research institute therein was truly revolutionary.  It was, by the way, something I had never heard of while the TNI was being developed.  Probably such news was masked by the conceit of the time that the heart of psychiatry and psychiatric research lay on the Eastern seaboard, especially at NIMH in Bethesda, possibly in the upper mid-west and, since I was from there, at UCLA.  This prejudice could have served as a filter of any good news to be had about the laid-back South.  

            As Ed Fann notes, by 1967 the basic scientists at the TNI were conducting preclinical psychopharmacological and psychobiologic research at the remodeled Cooper Building on the Central State campus. Clinical psychobiologic and psychopharmacological research was going on at Vanderbilt and at the Nashville Veterans Hospital under the TNI’s umbrella, but the clinical unit of the TNI had not yet been created.  That occurred later, in 1970. 

            I became a Clinical Associate at the NIMH Clinical Center in Bethesda, Maryland, in July, 1967, after two years of psychiatric residency at UCLA and one year of pediatric internship. I was selected to be a Clinical Associate at the NIMH Clinical Center, serving under the direction of Dr. William Bunney for one year and Fred Goodwin for a second. I served a two-year stint as a USPHS officer which met my military draft obligation, i.e., that kept me out of Vietnam and gave me a year of psychiatric residency credit in addition. I believe I was the only Clinical Associate who came from West of the Mississippi in my peer group.  I had been initially hired to run an open, basically equalitarian inpatient psychiatric unit- a therapeutic community to be carefully compared for outcome with a conventional more pyramidal unit.  However, the senior scientist who planned the study several weeks before my arrival was firedand I was assigned to Dr. Bunney’s psychobiologic unit.

            I met John Davis at NIMH when he was a post-Clinical Associate member of Dr. Bunney’s team, the equivalent of a faculty member. We began several research projects together.  We looked at the role of dopamine, norepinephrine and serotonin as these related to ovarian hormones in synaptosomal rat models, preclinical work related to the clinical studies I did investigating premenstrual tension as a resident at UCLA.   John was and is a dear friend and the best, and possibly only mentor I have ever had.  In the summer of 1969 I completed my USPHS “military” obligation and returned to California to start a psychiatric crisis-emergency room service at Harbor General Hospital in Torrance, a part of the UCLA Department of Psychiatry.  I had left NIMH under a slight cloud, at least in my own mind, having not been asked to remain there, and I thought my “research career” had ended. Yet, I was happy to be back in California.  About a year after returning, in mid-1970, John Davis called and told me about a job he was about to take in Nashville, Tennessee, at Vanderbilt.  He asked if I would join him in developing a clinical research ward, having seen me administrate Dr. Bunney’s research unit at NIMH while I was there.  My wife and I discussed this, thought about how interesting it would be to live in the South in a town like Nashville.  I agreed to go,in part because I wanted to make up for not having been asked to stay in Bethesda.  

            We moved to Nashville in the early Fall of 1970, bought a lovely 3,000 square-foot house overlooking a beautiful valley on an acre plus of land for $65,000, at half the price of one we could have had in Los Angeles, and moved in with our sons, ages 2 and 4, all over a period of about two months. I was 31-years-old.   Nashville at that time was not Los Angeles in almost any way.  It had only one Chinese eatery and plenty of barbecue, and people generally appeared to be talking socially about their lawns and lawnmowers. On the positive side, there was a fabulous southern breakfast place, the Loveless Motel, where I learned to love country fried ham, grits and eggs.  This was only to be outdone by a “pig picking” in which a roasted pig was barbecued in the ground at a party for the Pharmacology department, given by Pharmacology Professor Dr.  Daniel Buxsbaum at his home in Nashville. 

            I had never heard of any of the principals who developed the TNI and had no strong preexisting idea about what the Department of Psychiatry was like, but I thought it would be a nice adventure and was greeted warmly by members of the departments of pharmacology and psychiatry during my recruitment. It also seemed exotic to think of such an endeavor in what was then was pretty much the deep South, at least to this California boy.  Some of my colleagues at UCLA, in part in jest, in part not, warned me that I would probably be lynched as a Jewish person living in the South.  Untrue, by the way— there was a strong and well-integrated and accepted Jewish community in Nashville. Also, by the way, there was a very nice interaction between the African American psychiatric faculty at Meharry Medical School and Vanderbilt’s psychiatric faculty.  Nashville was integrating and there were many very interesting currents going on, i.e., white flight to “segregation” academies. 

            We arrived in the early Fall of 1970.     It was a very heady time and I believe John Davis, Ed Fann and I felt a strong pull to get things rolling. I personally liked Dr. Marc Hollander, the new chair of psychiatry and felt he was supportive and welcoming, as was the Department of Psychiatry in general.   I didn’t know Dr. Orr, although I think he remained in the department.    I was aware that Dr. Fann thought Dr. Orr had been obstructionistic and I believe they clashed philosophically on the role of psychoanalysis in training and in psychiatry in general. The psychobiologic and psychopharmacological revolution was just kicking in widely and it threatened many.   I personally didn't care if Dr. Hollander focused on the group at the TNI since the major support   financially, logistically and in scientific focus came from Central State Hospital and from the department of pharmacology's Dr. John Oates, whose clinical pharmacology center grant paid most of my salary, from Dr. Alan Bass as Chair of Pharmacology and from Dr. Fridolin Sulser as director of the TNI.   Nevertheless, I was asked by the Department of Psychiatry to give a series of psychopharmacological lectures to the medical students, which I enjoyed.   However, I was startled during my first lecture to find that the medical students attending the lecture stood up when I entered the room to speak and I believe most were wearing coats and ties…. we were not in Kansas anymore,Toto.  With respect to my integration into the Department of Psychiatry, it didn’t hurt that I loved psychotherapy, having been a resident in the UCLA Department of Psychiatry, that heavily emphasized psychodynamics and psychoanalysis.  Hence, I was philosophically in tune with the direction of the Department of Psychiatry in Nashville. 

            My primary role at Central State Hospital was to be the new clinical research unit chief; run the unit day-to-day; in part to be the principal liaison to the clinical staff and unit chiefs of Central State Hospital; and to facilitate the research of the clinical unit.  As I alluded to above, I had trained in my first year of residency on an inpatient unit at UCLA which was designed as a “therapeutic community.” The therapeutic community at its extreme, and as written about, was a unit where patients had much more to say about their fates.   For example, they voted with some authority on whether the ward door would be locked on a given day and even voted/advised on passes for each other.  They openly discussed ward policies in group therapy and discussed which drugs they were on in groups and as individuals.    There was a generally equalitarian ethic in which nursing staff, trainees, MD’s and psychologists were treated more or less as equals, on a first name basis and wearing street clothes, including jeans and without white coats.  More or less, mostly more, the opinion of the janitor counted in the community meetings, if based on logic, as much as did that of any more professionally trained employee.  Many or most decisions were made by consensus.   This model very much fit my California pseudo hippie ultra-liberal image of myself.   I had tried to set up that model at the NIMH on Dr. Bunney’s unit with little success or support and wanted to try again.  John Davis was supportive.  I believe some of the nursing staff assigned to the clinical ward at the TNI, especially the older ones, and especially the assigned head nurse,was skeptical of the planned direction of the unit.   I believe this skepticism included the head of the TNI, Dr. Sulser. 

            Over a period of about two months we hired a group of enthusiastic young people, some college dropouts, some college graduates.  They were hired mostly based on their ability to relate, their flexibility and their interest in caring for the very sick—they were basically people with good hearts, now they would be said to have emotional intelligence.  One in particular was anAfrican American medic returning home from Vietnam who, on deplaning at the Nashville airport after his military service was up, was harassed by a group of local young men, talked back to them and was beaten. So, everything wasn’t roses in Nashville in 1970.  

            These new hires, highly enthused, joined the small cadre of professional psychiatric nurses and techs who in some cases didn’t like what was going on their unit, and either stayed and adapted or left. I tried to inculcate an ethic in which treatment and research were to be equally emphasized and analyzedfor their mutual impact, with the goal to improve the lot of the patients.  We tried to offer good care through group therapy, community meetings, and individual interactions, and to offer a humanistic slant to offset the vicissitudes of research.  I tried to overcome the attitude that these patients, chronic as they were, could not be helped very much, and tried to put forth a than definitely California attitude that there was some beauty in psychosis—  in line with the then popularity of hallucinogens as a way to self-enlightenment.  Credentials mattered very little on the unit, which was liberating to some and threatening to others. Somehow the system started and very quickly research began.  Over time, not a small number of difficult cases were referred from the community and nationally due to the unit's reputation. I think the unit was clinically quite successful.

            Once staff were hired and “trained” we filled the nine-bed unit with mostly long-term bipolar patients and schizophrenics and began studies and treatment, probably within two months of John Davis’ and my arrival. The structure I have described was the antithesis of the usual, accepted pyramidal structure of usual psychiatric units in the South, and for that matter throughout much of the country.   I do think all of this was somewhat of a shock to those at Vanderbilt, and the preclinical researchers at the TNI, including Dr. Sulser, and maybe Dr.  Fann, and I remember well many “conversations” with Dr. Sulser about what we were doing and why.  Somehow the system started and very quickly research began.  I think it was clinically quite successful.

            In part my role was to interact with the physicians who ran the units at Central State Hospital, often with 100 to 200 patients for each physician.   I believe many of these doctors were naturally suspicious of what they probably considered effete and snobbish doctors from Vanderbilt, who were there, at least in the state hospital doctors’ minds,to exploit their patients.  It was these doctors who held the key to our securing patients for our research. I remember two ward doctors in particular: the Forbush’s, a middle-aged German expat married couple; the husband had fought for the Germans in World War II.   I think both were initially ambivalent of our endeavoryet acknowledged that research was important.  They later became two of my very good friends and strong supporters of our unit.   I’m not sure how this evolved, possibly in part because they saw that our unit was very patient treatment oriented and that some patients got well and were discharged and rejoined the non-institutional world.  In any case, over a reasonably short time, they and other of the state hospital physicians became friends of our unit and were a rich source for us, for both research patients and clinical wisdom.    

            The unit ethic (re authorship) was an interesting and a very progressive one.  At that time, papers, their ideas and discoveries seemed to me to be the coin of the realm, rather than having grants or money be such a major emphasis, as it often seems to be the case now. I believe early on we considered ourselves a research team who worked together and enriched each other scientifically and, as such, put each other on each other’s papers and presentations.   Ed Fann was very generous in this way and put us on his papers, including some for which the research was accomplished before John Davis and I had arrived.  John Davis was equally generous in including us on those papers he was writing.  John was and is to this day, a very generous mentor and career booster of those who work with him. Furthermore, he was consistently willing to consider and put into action new and creative ideas, and, overall, served as and was the brains of the outfit. He consistently made those under his supervision co-authors or first authors when he could have claimed intellectual primacy —  that certainly included Ed Fann and myself and later included Khal El -Yousef when he joined our team,as well as pharmacologist-toxicologist Joseph Sekerke. 

            I was saddened to read and re-remember Ed Fann’s feelings of exclusion and rejection that led up to his leaving the TNI.  I was aware that tension existed between he and John Davis, and that he felt that he wasn’t integral to the planning of the clinical division.   I think that after all the energy he had put into the development of the TNI and the effort it took to learn research from John Oates and others so as to be a fine researcher, it would have been very hard to then not feel integral to a unit that he had had such a hand in developing.  Maybe the clashes were inevitable.  I hope I wasn’t a problem for Ed, too, but may have been.   In any case, around the time Ed Fann left the TNI in 1971 we hired a bright young scientist, Khaled El-Yousef, as a replacement.   “Khal”was hired in part to do research and in part to help me run the clinical aspects of the unit.  He was a very smart guy who had very interesting ideas.

             In reading Ed Fann’s essay, I was reminded of how much the threads of research in the preclinical domain and the work done on the clinical unit were intertwined.   A concerted effort was made to work in areas that the preclinical researchers were exploring, i.e., serotonin, acetylcholine, dopamine, norepinephrine, neurophysiology, drug metabolism and drug mechanisms and the like.  Dr. Fann especially focused on drug metabolism and mechanisms which followed the lead of Dr. Oates’ pharmacologic center grant.   Although this integration was accomplished, the holy grail of what is now translational research, i.e., actually working hand-in-hand with the preclinical scientists to apply their specific   basic science discoveries clinically and vice versa, occurred incompletely as time went on.      In part, this represented a turn in the clinical unit’s focus from drug pharmacology/drug metabolism to psychobiology as a focus.   I believe this may have been a cause of some tensions between the clinical and preclinical scientists.

            The following outlines the main scientific accomplishments of the Clinical Unit of the TNI as occurred between 1970 and 1973. As described in Ed Fann’s article, a major focus of the TNI’s early clinical work involved Ed Fann studying underlying mechanisms as to how psychotropic drugs and their side effects occurred, i.e., psychotropic drug pharmacology.  Studies defining the effects of lithium on adrenergic function in man; determination that guanethidine’s hypotensive effects could be   blocked by chlorpromazine; and definition of doxepin’s and iprindol’seffects on biogenic amines were conducted and published. In addition, there was an early study of the prevalence of tardive dyskinesia and Parkinson’s symptoms in the Central State Hospital population by Dr. Fann and a study of amantadine as a treatment for tardive dyskinesia which seemed positive at firstbut ended up being a negative.  John Davis continued to write up review papers on which he included Ed Fann, Khaled El-Yousef, Joe Sekerke and me.

            We decided to pursue the dopamine hypothesis of schizophrenia, thus being in tune with the preclinical scientists’ interest in monoamines and John Griffith and Ed Fann’s earlier results.  The dopamine hypothesis was at the time a novel hypothesis which proposed that an overabundance of dopamine was a cause of schizophrenia, a hypothesis based largely on the anti-dopamine properties of antipsychotic medications.  A growing body of information supporting   this hypothesis was based on Vanderbilt’s John Griffith, Ed Fann’sand other’s work which showed that high dose amphetamine could cause normals to have a paranoid psychosis, very much resembling schizophrenia.  We decided to carry forward this hypothesis, giving the dopaminergic-noradrenergic psychostimulant methylphenidate to patients with various psychiatric diagnoses, especially schizophrenia, under controlleddouble-blind conditions.   We found that intravenous methylphenidate briefly activated preexisting psychotic symptoms in schizophrenics where these were marginally present at baseline. The relatively low doses of methylphenidate used did not activate those patients who had completely remitted nor cause symptoms in controls.   This finding had value in adding to the dopamine hypothesis, but also demonstrated the dangers of taking a psychostimulant if one had psychotic thoughts or hallucinations present. 

            The idea of using a centrally-active cholinesterase inhibitor, i.e., physostigmine, which increases central acetylcholine to treat tardive dyskinesia, was described in Ed Fann’s paper and reflected a dopaminergic-cholinergic balance hypothesis. That work, as such, did not actually come to fruition as far as I know, but was planned. However, we did give physostigmine to antagonize tricyclicand benztropine and combined drug confusional-hallucinatory states, postulating that this was due to anticholinergic side effects.  The physostigmine caused a clearing of confusion, thus suggesting a treatment and a causative anticholinergic mechanism.

            While we were conducting that study, I believe it was I who suggested that increasing central acetylcholine activity might   turn off manic symptoms, counteracting the increased noradrenergic activity, then presumed to occur in mania and shifting adrenergic-cholinergic balance to a cholinergic predominance.  We gave physostigmine to several manics and observed that the physostigmine rapidly and effectively turned off the manic symptoms over a period of minutes.   Expanding that work, we found that physostigmine induced depression in the manics, in patients with a depressive component to their psychiatric illness, as well as in a minority of normals.  Based on the above, we proposed an adrenergic cholinergic balance hypothesis of mania and depression   This has subsequently been widely studied and years later in 2006 led to the observation by scientists at NIMH in Bethesda that scopolamine is an effective antidepressant.

            We also wondered if physostigmine could overcome a marijuana “high” since many of marijuana’s effects are anticholinergic in nature.  Under the leadership of Khaled El-Yousef, we gave physostigmine to two marijuana intoxicated pharmacology graduate students.  We were astonished to see that it caused profound depression, reversible by centrally-acting anticholinergic atropine.  We later showed that THC, given along with physostigmine to rats, increased physostigmine’s toxicity. We showed that physostigmine’s mood depressing effects could be counteracted by the dopamine-norepinephrine releasing effects of methylphenidate and vice versa, adding credence to the adrenergic-cholinergic balance hypothesis. We then showed this balance in rats given methylphenidate to induce stereotyped behavior.   

            In one extremely enjoyable experience we flew to New York to visit Sam Gershon, Baron Shopsin and their colleaguesat Belleview Hospital to demonstrate physostigmine’s effects. We demonstrated, in patients who were New York-style hyper-manics, that physostigmine turned off the mania. A few hours later, we observed a reboundphenomena, inwhich an even more exaggerated manic state occurred. This observation mirrored preclinical work done by others in previous years which  also showed hypoactivity followed by hyperactive rebound  after giving physostigmine to rats.

            At the TNI I continued my previous interest in ovarian hormone linked disorders, especially premenstrual tension.  As I mentioned, I had developed this as an area interest in my residency and later at NIMH where John Davis had worked with me to look at the effects of ovarian hormones on monoamines using rat brain synaptosomes.  At the TNI John Davis and I wrote up a clinical study we had done when we were at NIMH, showing that mood changes during the menstrual cycle correlated with mineralocorticoid activity, i.e., aldosterone and angiotensin, and postulated a renin angiotensin etiology for premenstrual tension.  We then wrote a paper proposing that monoamine perturbations by ovarian hormones could be the cause of premenstrual tension, a then novel hypothesis.  In that paper we set the groundwork for studies showing that later to-be-developed serotonergic antidepressants might alleviate premenstrual tension, a possibility years later proven by others to be true.  

            My colleagues and I had written a paper at NIMH entitled “Playing the Manic Game,” which outlined the disruptive and manipulative interpersonal interactions that manic patients demonstrate.  The TNI research team carried that work forward in our Central State Hospital patients.We showed that when treated with lithium, and when the mania decreased, the difficult interactions diminished proportionally, as did the classic symptoms of mania.  This work was important in showing that the interpersonal interactions we observed were illness related, rather than fixed as personality characteristics, and this work added to the spectrum of behaviors that manics show.

            In the summer of 1973 John Davis was recruited to become the director of the Illinois State Psychiatric Institute clinical unit, as part of the University of Illinois, and ultimately decided to take that job.  He invited me to join him in Chicago, but I declined, in part since Chicago is so windy and cold and in part because I wanted to either stay in Nashville or return to Los Angeles or San Diego.  There were discussions as to whether or not I would be the one to inherit John Davis’ role as director of the TNI clinical unit, but that remained uncertain and, like Ed Fann’s situation years earlier, I was offered a temporary leadership position, with the possibility of it becoming permanent.  I now realize that I was pretty young and “green” to take on an endeavor such as the clinical unit of the TNI but at the time I didn’t look at it that way.   I was being recruited to UCLA and UC San Diego's psychiatry departments and decided to return to San Diego where I had been born and raised and where I then served as a faculty member for the next 13 years until again moving to the South, to the University of North Carolina Chapel Hill.  I think I ultimately was actually offered the clinical directorship role of the TNI clinical unit, but by then "the train had left" and I was on my way to San Diego.

            We left Nashville in the fall of 1973 and briefly returned through the summer of 1974 to reconsider living in Nashville.   We realized what a great and interesting place Nashville was and how deep our roots had become.  I considered rejoining the Department of Psychiatry and was again offered a tenured position in it.  I believe the possibility of heading the TNI clinical unit, even temporarily, had passed and ultimately,and not necessarily for that reason, we returned to San Diego. 

            I believe Khaled El-Yousef was more or less offered the same deal as I was after I left in 1973, and he ultimately left to go to the Tampa Bay, Florida, area where he conducted a highly successful private practice.   When I left Nashville, Fridolin Sulser told me that I would never again be as productive as I had been at the TNI. We saw each other frequently at meetings over the years and developed a warm relationship.  Same with Ed Fann.   I now agree — the 1970-1973 period was the most creative and innovative time of my career and much of my subsequent research was based on my work at Central State Hospital and the TNI.  I cherish my experiences in Nashville to this day. 

 

Publications Generated From the1970-1973 TNI Clinical Research Unit

 

Refereed Publications:

 

Decker BL, Davis JM, Janowsky DS, El-Yousef MK, SekerkeHJ.Amantadine hydrochloride treatment of tardive dyskinesia.  New England Journal of Medicine. 1971;285:860 (letter).

 

Fann WE, Janowsky DS, Davis JM, Oates JA.  Chlorpromazine reversal of the antihypertensive action of guanethidine.  Lancet. 1971;2:436-437 (letter).

 

Janowsky DS, Fann WE, Davis JM.  Monoamines and ovarian hormone-linked sexual and emotional changes:  A review.  Archives of Sexual Behavior. 1971;1:205-218.

 

Fann WE, Cavanaugh JH, Kaufmann JS, Griffith JD, Davis JM, Janowsky DS, Oates JA.  Doxepin:  Effects on transport of biogenic amines in man.  Psychopharmacologia (Berlin). 1971;22:111-125.

 

Fann WE, Davis JM, Janowsky DS, Kaufmann JS, Griffith JD, Oates JA.  Effect of iprindole on amine uptake in man.  Archives of General Psychiatry. 1972;26:158-162.

 . 

Janowsky DS, Davis JM, Fann WE, Freeman J, Nixon R, Michelakis AA.  Angiotensin effect on uptake of norepinephrine by synaptosomes.  Life Sciences. 1972;11:1-11.

 

 Fann WE, Davis JM, Janowsky DS, Cavanaugh JH, Kaufmann JS, Griffith JD, Oates JA.  Effects of lithium on adrenergic function in man.  Clinical Pharmacology and Therapeutics. 1972;13:71-77.

 

FannWE, Davis JM, Janowsky DS.  The prevalence of tardive dyskinesias in mental hospital patients.  Diseases of the Nervous System. 1972;33:182-186.

 

 Christoph GW, Schmidt DE, Davis JM, Janowsky DS.  A method for determination of chlorpromazine in human blood serum.  Clinica Acta. 1972;38:265-270.

 

Rosenblatt JE, Janowsky DS, Davis JM, El-Yousef MK.  The augmentation of physostigmine toxicity in the rat by delta-9-tetrahydrocannabinol.  Research Communications in Chemical Pathology and Pharmacology. 1972;3:479-482.

 

Janowsky DS, El-Yousef MK, Davis JM, Sekerke HJ.  A cholinergic-adrenergic hypothesis of mania and depression.  Lancet. 1972;2:632-635.

 

Janowsky DS, El-Yousef MK, Davis JM, Sekerke HJ.  Cholinergic antagonism of methylphenidate-induced stereotyped behavior.  Psychopharmacologia (Berlin). 1972;27:295-303.

 

Janowsky DS, El-Yousef MK, Davis JM, Fann WE, Oates JA.  Guanethidine antagonism by antipsychotic drugs.  Journal of the Tennessee Medical Association. 1972;65:620-622.

 

El-Yousef MK, Janowsky DS, Davis JM, Fann WE.  Reversal of benztropine toxicity by physostigmine.  Journal of the American Medical Association. 1972;220:125 (letter).

 

El-Yousef MK, Davis JM, Janowsky DS, Fann WE.  Central atropine-like toxicity in combined psychotropic drug administration.  Journal of the Tennessee Medical Association. 1972;65:719.

 

Janowsky DS, El-Yousef MK, Davis JM, Fann WE.  Chlorpromazine – Another guanethidine antagonist.  Journal of the American Medical Association. 1972;220:1288-1289 (medical news).

 

Janowsky DS, El-Yousef MK, Davis JM, SekerkeHJ, Morris DR, Decker B.  Effects of amantadine on tardive dyskinesia and pseudo-parkinsonism.  New England Journal of Medicine. 1972;286:785 (letter).

 

Janowsky DS, El-Yousef MK, Davis JM, Hubbard B, Sekerke HJ.  Cholinergic reversal of manic symptoms.  Lancet. 1972;1:1236-1237 (letter).

 

Janowsky DS, Davis JM, El-Yousef MK, Sekerke HJ.  Combined anticholinergic agents and atropine-like delirium.  American Journal of Psychiatry. 1972;129:360-361 (letter).

 

Janowsky DS, El-Yousef MK, Davis JM, Sekerke HJ.  Provocation of schizophrenic symptoms by intravenous administration of methylphenidate.  Archives of General Psychiatry. 1973;28:185-191.

 

El-Yousef MK, Janowsky DS, Davis JM, Rosenblatt JE.  Induction of severe depression by physostigmine in marijuana intoxicated individuals.  British Journal of Addiction. 1973;68:321-325.

 

El-Yousef MK, Janowsky DS, Davis JM, Sekerke HJ.  Reversal of antiparkinsonian drug toxicity by physostigmine:  A controlled study.  American Journal of Psychiatry. 1973;130:141-145.

 

Janowsky JS, El-Yousef MK, Davis JM, Sekerke HJ.  Parasympathetic suppression of manic symptoms by physostigmine.  Archives of General Psychiatry. 1973;28:542-547.

 

Janowsky DS, Berens SC, Davis JM.  Correlations between mood, weight, and electrolytes during the menstrual cycle:  A renin-angiotensin-aldosterone hypothesis of premenstrual tension.  Psychosomatic Medicine. 1973;35:143-154.

 

Janowsky DS, El-Yousef MK, Davis JM, Fann WE.  Antagonism of guanethidine by chlorpromazine.  American Journal of Psychiatry. 1973;130:808-812.

 

Davis JM, Janowsky DS.  Psychopharmacology of methylphenidate in man:  Advances in neuropsychopharmacology.  Avicenum Czechoslovak Medical Press. 1973;511-125.

 

Davis JM, Fann WE, El-Yousef MK, Janowsky DS.  Clinical problems in treating the aged with psychotropic drugs.  Advances in Behavioral Biology. 1973;7:111-125.

 

Janowsky DS, El-Yousef MK, Davis JM, Sekerke HJ.  Antagonistic effects of physostigmine and methylphenidate in man.  American Journal of Psychiatry. 1973;130:1370-1376.

 

Fann WE, Davis JM, Janowsky DS, Sekerke HJ, Schmidt DM.  Chlorpromazine:  Effects of antacids on its gastrointestinal absorption.  Journal of Clinical Pharmacology. 1973;13:388-390.

 

Janowsky DS, El-Yousef MK, Davis JM.  Interpersonal maneuvers of manic patients.  American Journal of Psychiatry. 1974;131:250-255.

 

Janowsky DS, El-Yousef MK, Davis JM.  Acetylcholine and depression.  Psychosomatic Medicine. 1974;36:248-257. 

 

Davis JM, Janowsky DS.  Recent advances in the treatment of depression.  British Journal of Hospital Medicine. 1974;11:219-228.

 

Fann WE, Davis JM, Janowsky DS, Kaufman JF, Cavanaugh JH, Oates JA.  Effect of antidepressant and antimanic drugs on amine uptake in man.  Journal of Nervous Mental Disorders. 1974;158:361-368.

 

Davis JM, Sekerke HJ, Janowsky DS.  Drug interactions involving the drugs of abuse.  Drug Intelligence and Clinical Pharmacy. 1974;8:120-142.

 

Davis JM, Janowsky DS, Sekerke HJ, El-Yousef MK.  The psychotropic drugs--Cost effectiveness and clinical pharmacological studies.  Annals of Internal Medicine. 1974;11:219-228.

 

Shopsin B, Janowsky DS, Davis J, Gershon S.  Rebound phenomena in manic patients following physostigmine.  Neuropsychobiology. 1975;1:180-187.

 

Chapters and Books:

 

Janowsky DS, El-Yousef MK, Davis JM.  The elicitation of psychotic symptomatology by methylphenidate.  In: Cole J, ed. Drugs and Psychopathology. Baltimore, MD: Johns Hopkins University Press; 1973.

 

Davis JM, Janowsky DS, El-Yousef K.  Pharmacology - The biology of lithium.  In: Gershon S, Shopsin B, eds.  Lithium: Its Role in Psychiatric Research. New York: Plenum Publishing Company; 1973.

 

Fann WE, Davis JM, Janowsky DS, Oates JA.  Amine uptake in the pharmacology of affective disorders.  In: Gershon S, Bunney W, eds. Biogenic Amines in Psychiatry. New York: Plenum Publishing Company; 1973.

 

Davis JM, Janowsky DS.  Catecholamines and psychosis.  In: Friedhoff A ed. Catecholamines and Behavior. New York: Plenum Press; 1973.

 

Davis JM, Janowsky DS, Sekerke HJ, Manier H, El-Yousef MK.  The pharmacokinetics of butaperazine in serum.  In: Forrest, Carr, Usdin, eds. Phenothiazines and Structurally Related Compounds. New York: Raven Press; 433-443,1973.

 

Janowsky DS, El-Yousef MK, Davis JM.  Side effects associated with psychotropic drugs.  In: Fann WE, Maddox GL, eds. Drug Issues in Geropsychiatry. Baltimore, MD: Williams & Wilkins; 28, 1974.

 

Janowsky DS, Davis JM.  Dopamine, psychomotor stimulants, and schozophrenia: Effects of methylphenidate and the stereoisomers of amphetamine in schizophrenics.  In: Usdin E, ed.

Neuropsychopharmacology of Monoamines and Their Regulatory Enzymes. New York: Raven Press; 1974:317-323.

 

Davis JM, Janowsky D.  Cholinergic and adrenergic balance in mania and schizophrenia.  In: Domino EF, Davis JM, eds. Neurotransmitter Balances Regulating Behavior. Ann Arbor, Michigan; 1975:135-148.

 

Shopsin B, Janowsky D, Davis J, Gershon S.  Rebound phenomena in manic patients following physostigmine:  Towards an understanding of the aminergic mechanisms underlying affective disorders.  In: Domino EF, Davis JM, eds. Neurotransmitter Balances Regulating Behavior. Ann

Arbor, MI; 1975:149-158.

 

Davis JM, Janowsky D.  Clinical Pharmacological Strategies.  In: Mendels V, ed. The Psychobiology of Depression. Spectrum Publications,Inc; 1975:133-142.

 

Davis J, Janowsky DS, Casper R.  Acetylcholine and mental disease.  In: Usdin E, Barchas, eds. NeuroRegulators in Psychiatric Disorders. England: Oxford University Press; 1976:450-457.

 

Janowsky DS, El-Yousef MK, Davis JM, Sekerke HJ.  A cholinergic-adrenergic hypothesis of mania and depression. In: Segal DS, Yager J, Sullivan JL, eds. Foundations of Biochemical Psychiatry. Woburn, MA: Butterworth Publishers, Inc; 1976:230-236.

 

Janowsky DS, Davis JM.  Pharmacological challenge tests in psychiatric diagnosis:  Physostigmine and methylphenidate.  In: Psychiatric Diagnosis: Exploration of Biological Predictors. Spectrum Publications; 1978:263-27819.

 

Davis JM, Janowsky D, El-Yousef MK.  The effect of drug treatment on interpersonal styles of manic patients.  Neuro-Psychopharmacologicum: Tenth CollegicumInternationale Neuro-Psychopharmacologicum. Oxford, England: Pergamon Press; 1978;1:91-96.

 

Davis JM, Janowsky D, Tamminga C, Smith RC.  In: Jenden D, ed.  Cholinergic mechanisms in schizophrenia, mania and depression.  In: Cholinergic Mechanisms in Psychopharmacology. New York: Plenum Press; 1978:805-815.

 

Janowsky DS, Davis JM.  Psychologic effects of cholinomimetic agents.  In: Davis K, Berger P, eds. Brain Acetylcholine and Neuropsychiatric Disease. New York: Plenum Publishing Corp; 1979:3-14.

 

Non-Refereed Journals:

 

Curry SH, Davis JM, Janowsky DS, Marshall JHL.  Interpatient variation in physiological availability of chlorpromazine as a complicating factor in correlation studies of drug metabolism and clinical effect, Proceedings of the Sixth International Congress of the C.I.N.P., 1969:72-76.

 

Fann WE, Oates JA, Janowsky DS, Davis JM.  The effects of lithium and iprindole on adrenergic function in man.  Psychopharmacology Bulletin. 1972;8:32.

 

Davis JM, Janowsky DS, El-Yousef MK.  The use of lithium in clinical psychiatry.  Psychiatric Annals. 1973;3:78-99.

 

Janowsky DS, Sekerke HJ, Davis JM.  Differential affects of amantadine on pseudoparkinsonism and tardive dyskinesia.  Psychopharmacology Bulletin. 1973;9:37-38.

 

Davis JM, Sekerke HJ, Janowsky DS.  Drug interactions involving drugs of abuse.  Drugs of America, Problems in Perspective, Vol. 1, 181-208, U.S. Govt. Printing Office,1973.

 

Janowsky DS, El-Yousef MK, Davis JM.  Effects of intravenous d-amphetamine, l-amphetamine and methylphenidate in schizophrenics. Psychopharmacology Bulletin. 1974;10:15-24.

 

July 19, 2018