Psychobiology Of Major Affective Disorders
Overview Of History –
Personal History And Review Of Research –
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Publications: Bibliography
Overview Of History
Dr. Joseph J. Schildkraut is Professor of Psychiatry at Harvard Medical
School and Founding Director of the Neuropsychopharmacology/Psychiatric
Chemistry Laboratory at the Massachusetts Mental Health Center (MMHC)
in Boston. Dr. Schildkraut received his A.B. summa cum laude from Harvard
College in 1955, where he was elected to Phi Beta Kappa in his junior
year, and his M.D. cum laude from Harvard Medical School in 1959. He received
his residency training in psychiatry at the Massachusetts Mental Health
Center from 1960-1963, where he began his research on depression and catecholamines;
and he furthered his research training in neuropsychopharmacology at the
National Institute of Mental Health in Bethesda, Maryland from 1963-1967.
In 1967 Dr. Schildkraut returned to the MMHC and joined the faculty of
Harvard Medical School as an assistant professor of psychiatry. He became
an associate professor of psychiatry in 1970 and a professor of psychiatry
in 1974.
Dr. Schildkraut’s seminal paper, The Catecholamine Hypothesis of
Affective Disorders, published in 1965, set the agenda for biological
research on depression for the next 25 years. This paper, which crystallized
a new way of thinking about mood disorders and pushed forward a paradigmatic
shift in the understanding of their pathophysiology and putative etiology
(Healy, D. The Antidepressant Era, Harvard University Press, 1997, pp.
155-161), is the most frequently cited of all articles ever published
in The American Journal of Psychiatry and one of the most cited papers
in all of psychiatry. At the time it was published, The Catecholamine
Hypothesis captured the imagination of the field, demonstrating how pharmacology,
by providing a bridge linking neurochemistry and clinical psychiatry,
could offer a rational approach to research in clinical neurosciences.
Moreover, on a broader scale, these ideas eventually reached the popular
culture and helped lessen the stigma of psychiatric illness, emerging
as the view that depressions are medical illnesses and that many mental
disorders are related to “chemical imbalances.”
This article was selected as a “Classic Article in Neuropsychiatry”
and reprinted in the Journal of Neuropsychiatry and Clinical
Neuroscience in 1995 (Fall), the first year that this Series was
published in the Journal.
David Healy,
in his book, The Psychopharmacologists III (Oxford University Press, 2000,
page xxxiv) wrote: “More than any other paper, Joe Schildkraut’s
Catecholamine Hypothesis defined the psychopharmacological era. One may
quibble with the details of the hypothesis, but the paper was foundational
– the 1960’s equivalent to Freud’s The Interpretation
of Dreams.” (See also Healy, 2000, pp. 111-134.)
Upon returning to the Massachusetts Mental Health Center in 1967, Dr.
Schildkraut founded the Neuropsychopharmacology Laboratory (which some
years later developed a subcomponent, the Psychiatric Chemistry Laboratory,
which functioned as a clinical laboratory under the aegis of the Department
of Pathology at the New England Deaconess Hospital). In the course of
his pathfinding studies of mood disorders conducted in the Neuropsychopharmacology/Psychiatric
Chemistry Laboratory, Dr. Schildkraut and his collaborators, fellows,
and medical students elucidated the role of catecholaminergic neurotransmitters
in the mechanisms of action of antidepressant drugs and showed that subtypes
of depressive disorders could be differentiated biochemically on the basis
of measures of catecholamine metabolism. This research
was supported in part by a grant from NIMH (RO1MH15413) that was continuously
funded for 25 years.
In a recent aspect of his research, Dr. Schildkraut and his colleague,
Dr. John J. Mooney, developed a reconceptualization of the process of
inactivation and metabolism of norepinephrine released into the synapse.
This led to a reformulation of the mechanisms of action of norepinephrine
reuptake inhibitor antidepressant drugs. On this basis, they developed
a proposal for a rapidly acting antidepressant. Working through the Harvard
Medical School Office of Technology Licensing and Industry-Sponsored Research,
Drs. Schildkraut and Mooney filed a patent application, Antidepressant
Effect of Norepinephrine Uptake 2 Inhibitors and Combined Medications
Including Them, on March 16, 2001, and this patent was approved on June
11, 2002. Negotiations with major pharmaceutical companies are currently
underway.
In addition, Dr. Schildkraut was involved in the development and progress
of Harvard’s Commonwealth Research Center (CRC) based at the Massachusetts
Mental Health Center. For many years, in its initial phase of development,
Dr. Schildkraut served as the Chair of the CRC Scientific Advisory Board,
and he subsequently served as senior mentor and collaborator with Alan
I. Green, M.D. and other members of the CRC in their program of research
on schizophrenia. During the course of Dr. Green’s research on the
CRC, Dr. Schildkraut’s laboratory became an integral component of
the Commonwealth Research Center.
For the past fifteen years, Dr. Schildkraut also has been exploring the
inter-relatedness of depression, spirituality and artistic creativity,
and his papers on this subject have appeared in leading peer-reviewed
professional journals. Moreover, he is editor of the book, Depression
and the Spiritual in Modern Art: Homage to Miró, published by John
Wiley & Sons, Ltd. in 1996. This book is based on an international
symposium that Dr. Schildkraut organized and chaired in 1993 that was
held in Barcelona at the Joan Miró Foundation at the time of their
centenary celebration of the birth of Joan Miró.
Former Editor-in-Chief of the Journal of Psychiatric Research, Dr. Schildkraut
is the author of over 200 scientific publications. His pioneering research
on the neurochemistry and neuropharmacology of depressive disorders has
been recognized with many awards and prizes including: the Anna Monika
Foundation Prize for Research in Endogenous Depressions in 1967, the first
year that this international prize was awarded; the Hofheimer Prize for
Research from the American Psychiatric Association in 1971; the William
C. Menninger Memorial Award from the American College of Physicians in
1978; a Lifetime Achievement Award from the Society of Biological Psychiatry
in 1996, presented at the Society’s 50th Annual Meeting to “seminal
founding scientists in the field;” and The Award for Research in
Mood Disorders from The American College of Psychiatrists in 1999.
Personal History And Review Of Research
I came to the Massachusetts Mental Health Center (MMHC) in 1960, planning
to become a psychoanalyst. However, during my first year of residency, the
antidepressant drugs, phenelzine (a monoamine oxidase inhibitor) and imipramine
were just being introduced at MMHC for the treatment of depressed patients.
When I became aware of the remarkable clinical effects of these antidepressants
compared to psychotherapy alone (which, with the exception of electroconvulsive
treatment, had been the standard and only treatment for depressed patients
up until that time) it became clear to me that I had to learn more about
the possible mechanisms of action of these clinically effective antidepressant
drugs.
It was my good fortune that Milton Greenblatt, the Assistant Superintendent
at MMHC, who was in the process of developing a small research unit for
the study and treatment of depressed patients, asked me if I would be
willing to become the “chief”(and as it turned out the only) resident of this research ward.
This was a wonderful opportunity that I could not refuse. The ongoing
research on this unit enabled me to conduct a study comparing the effects
of phenelzine and imipramine on the excretion of VMA (a major metabolite
of norepinephrine) in depressed patients. Since the conversion of norepinephrine
to VMA requires the enzyme monoamine oxidase, the aim of this study was
to determine whether, in clinical use, phenelzine (the monoamine oxidase
inhibitor) would, in fact, decrease the urinary output of VMA. In addition
to a placebo comparison group, this study also included a comparison group
of patients treated with imipramine, which is not a monoamine oxidase
inhibitor, and which was, therefore, not expected to produce a change
in VMA.
While there was no change in VMA output in patients treated with placebo,
as we had hypothesized, VMA was markedly reduced in patients treated with
phenelzine. We were very surprised, however, to find that treatment with
imipramine also produced a decrease in VMA (Schildkraut et al., “Excretion
of 3-methoxy-4-hydroxymandelic Acid (VMA) in Depressed Patients Treated
with Antidepressant Drugs,” Journal of Psychiatric Research, 1964).
The unexpected finding that treatment with imipramine decreased VMA led
to my thoroughly reviewing the rather modest basic pharmacological literature
pertaining to these antidepressants (at that time) and, thus, developing
an “expertise” in the emerging field of neuropsychopharmacology.
As a result, Seymour Kety invited me to become an associate in his Laboratory
of Clinical Science at the National Institute of Mental Health (NIMH)
upon completion of my residency in 1963. I went on to NIMH to spend the
next four years of my career (1963-67) extending my clinical research
in neuropsychopharmacology on Jack Durell’s unit, and beginning
my career in basic neuropharmacology, collaborating with Saul Schanberg
in Irv Kopin’s neuropharmacology laboratory.
The first study I performed at the NIMH was an attempt to replicate our
research on the effects of imipramine on VMA excretion and to extend it
to other aspects of norepinephrine metabolism. In that first study, we
confirmed that imipramine decreased VMA excretion. Moreover, we also observed
that normetanephrine (the O-methylated metabolite of norepinephrine),
which was thought to derive from norepinephrine that was released into
the synapse, was increased and that increase seemed to be related to the
clinical antidepressant effects of imipramine (Schildkraut et al., “Catecholamine
Metabolism in Affective Disorders: I. Normetanephrine and VMA Excretion
in Depressed Patients Treated with Imipramine,” Journal of Psychiatric
Research, 1965). This was of considerable interest, since Julie Axelrod
had previously discovered that the major mechanism for inactivating norepinephrine
released into the synapse was by reuptake of that norepinephrine into
the presynaptic neuron of origin, and that imipramine blocked this reuptake.
Early on in my career at NIMH I became aware that there was very little
cross-talk between the clinical psychiatrists and the basic neuropharmacologists,
and it appeared to me that there was a need for review of the psychiatric
implications emerging from ongoing neuropharmacological studies of norepinephrine
and other catecholamines. Thus, I came to write a paper entitled, “The
Catecholamine Hypothesis of Affective Disorders: A Review of Supporting
Evidence” that was published in The American Journal of Psychiatry
in 1965, and which came to be the most frequently cited paper ever published
in The American Journal of Psychiatry.
Following up on Julie Axelrod’s work, my colleagues and I (in Irv
Kopin’s laboratory) found that, in animals, a variety of tricyclic
antidepressant drugs blocked the reuptake of norepinephrine into the presynaptic
neuron of origin, while simultaneously increasing brain levels of normetanephrine.
Moreover, we found that acute administration of these drugs appeared to
slow the release of norepinephrine from the brain (Schanberg et al., “The
Effects of Psychoactive Drugs on Norepinephrine-H3 Metabolism in Brain,”
Biochemical Pharmacology, 1967; Schildkraut et al., “Norepinephrine
Metabolism and Drugs Used in the Affective Disorders: A Possible Mechanism
of Action,” The American Journal of Psychiatry, 1967. In further
studies (Schanberg et al., “Metabolism of Normetanephrine-H3 in
Rat Brain,” Biochemical Pharmacology, 1968), we went on to show
that the major metabolite of normetanephrine in rat brain was the sulfate
conjugate of 3-methoxy-4-hydroxyphelynglycol (MHPG).
In 1967, I returned to MMHC and established a neuropsychopharmacology
laboratory. One of the goals of this laboratory was to develop a program
of research to explore the mechanisms of action of antidepressant drugs.
Initially, I planned to study the neuropsychopharmacological effects of
long-term administration of tricyclic antidepressant drugs, since chronic
administration is required to achieve clinical antidepressant effects,
and virtually all of the previous studies of the neuropharmacology of
these antidepressants involved acute administration. Thus, after all laboratory
assays had been standardized, my first major study was to compare the
effects of acute and chronic (three weeks) administration of imipramine
on the turnover and metabolism of norepinephrine in rat brain.
In these studies, we confirmed the earlier findings that the release
of norepinephrine from rat brain was decreased after a single administration
of imipramine. During long-term administration (three weeks) of imipramine,
however, the release of norepinephrine from brain gradually increased
(“Schildkraut et al., “Norepinephrine Turnover and Metabolism
in Rat Brain After Long-Term Administration of Imipramine,” Science,
1970). In that paper, we suggested that these findings may help to explain
why antidepressant effects are observed clinically only after long-term
treatment with imipramine; and in further studies, we went on to confirm
and extend these findings (Schildkraut et al., “Changes in Norepinephrine
Turnover in Rat Brain During Chronic Administration of Imipramine and
Protriptyline: A Possible Explanation for the Delay in Onset of Clinical
Antidepressant Effects,” The American Journal of Psychiatry, 1971).
Another goal of our research was to determine whether various subtypes
of depressive disorders showed differences in the output and metabolism
of norepinephrine. Since our earlier studies had shown that MHPG was the
major metabolite of norepinephrine in rat brain, in a preliminary study
we compared levels of urinary MHPG in patients with manic-depressive depressions
(i.e., bipolar disorders) and patients with unipolar chronic characterological
depressions. In this preliminary study we observed that urinary MHPG levels
were significantly lower (p<.05) in patients with manic-depressive
depressions than in patients with chronic characterological depressions
(Schildkraut et al., “MHPG Excretion and Clinical Classification
in Depressive Disorders,” Lancet, 1973). The findings of this preliminary
study led us to develop a program of research that we called “Toward
a Biochemical Classification of Depressive Disorders”; the findings
from this research on the biochemical pathophysiology of depressive disorders
were reported in a series of ten papers published from 1978 to 1989.
In the first of these studies (Schildkraut et al., “Toward a Biochemical
Classification of Depressive Disorders I: Differences in Urinary MHPG
and Other Catecholamine Metabolites in Clinically Defined Subtypes of
Depressions,” Archives of General Psychiatry, 1978a), we examined
the differences in levels of urinary MHPG and other catecholamine metabolites
in 63 patients with various clinically defined subtypes of depressive
disorders: manic-depressive depressions, schizo-affective depressions
(see paper Schildkraut et al., Archives of General Psychiatry, 1978a cited
above for definition of schizo-affective depressions used in this study),
unipolar endogenous depressions, unipolar nonendogenous depressions, and
schizophrenia-related depressions. Urinary MHPG
levels were significantly lower in patients with bipolar manic-depressive
and schizo-affective depressions than in patients with unipolar non-endogenous
depressions. In patients with unipolar endogenous depressions, we observed
a wide range of MHPG levels with some patients showing levels comparable
to those seen in patients with bipolar manic-depressive depressions, and
others showing urinary MHPG levels that were higher than those seen in
patients with unipolar nonendogenous depressions. (It is possible that
some of those patients with low levels of urinary MHPG may, in fact, have
been patients with bipolar disorders who had not yet experienced their
first episode of mania.)
In addition to levels of urinary MHPG, we also measured urinary norepinephrine,
epinephrine, and various other metabolites of these catecholamines, including
VMA, normetanephrine, and metanephrine. Further biochemical discrimination
among these clinically defined subtypes of depressive disorders was obtained
using an empirically derived multivariate discrimination equation based
on these biochemical data (Schildkraut et al., “Toward A Biochemical
Classification of Depressive Disorders II: Application of Multivariate
Discriminant Function Analysis to Data on Urinary Catecholamines and Metabolites,”
Archives of General Psychiatry, 1978). Multivariate discriminant function
analysis was applied to the data on catecholamines and metabolites obtained
from an initial series of patients with bipolar manic-depressive depressions
and unipolar nonendogenous (chronic characterological) depressions. The
terms available for computer entry into this equation included: norepinephrine
(NE), normetanephrine (NMN), epinephrine (E), metanephrine (MN), vanillylmandelic
acid (VMA), 3-methoxy-4-hydroxyphenglycol (MHPG), and various sums and
ratios of these terms.
Based on these terms, a discrimination equation was developed in a stepwise
procedure where the variable selected by the computer for entry into the
equation at each step was the one with the largest contribution to discrimination
(when the information shared with items already entered was partialed
out). Thus, this equation was determined by an analytic procedure that
was not influenced by the investigators.
The equation for what we term the, “Depression-type” (D-type)
score was of the form:
D-type score = C1 (MHPG) – C2 (VMA) + C3 (NE) – C4 (NMN + MN)/VMA + C0
These four terms were selected from the terms available to the computer
because each made a statistically significant (p<.01) contribution
to the discrimination between bipolar manic-depressive depressions and
unipolar nonendogenous (chronic characterological) depressions. No other
terms added significantly to the discrimination obtained from these four
terms, and the overall accuracy of discrimination was highly significant.
In developing the metric for this equation, a value of 0 was assigned
to bipolar manic-depressive depressions and the value 1 was assigned to
unipolar nonendogenous depressions. Therefore, in the application of this
equation, D-type scores less than 0.5 are associated with bipolar manic-depressive
depressions and D-type scores greater than 0.5 are associated with unipolar
nonendogenous depressions.
This equation was then applied to data on urinary catecholamines and
metabolites in an independent series of 33 depressed patients who were
studied after the derivation of this equation, and whose biochemical data,
therefore, had not been used to derive the parameters of the equation.
In this validation sample all of the patients with clinical diagnoses
of bipolar manic-depressive or schizo-affective depressions had D-type
scores below 0.5. In contrast, all of the patients with diagnoses of unipolar
nonendogenous depressions, as well as all patients with schizophrenia-related
and unclassifiable depressions had D-type scores above 0.5.
The 9 patients with unipolar endogenous depressions had a wide range
of D-type scores, with several below 0.5 and, clearly, in the range observed
in bipolar manic-depressive or schizo-affective depressions. Thus, D-type
scores below 0.5 may conceivably help to identify from within the overall
group of unipolar endogenous depressions, those patients with a biochemical
similarity or predisposition to bipolar manic-depressive (or schizo-affective)
disorders, even though the patient may not have a history of prior overt
episodes of hypomania or mania.
The fourth term of the equation, which is the ratio (NMN + MN)/VMA, may
reflect differences in monamine oxidase (MAO) activity between the subtypes
of depressive disorders. Since NMN and MN can be converted to VMA (or
MHPG) by deamination, this ratio may be inversely related to MAO activity.
On the basis of measurements of platelet MAO activity, some investigators
have suggested that MAO activity may be reduced in patients with bipolar
manic-depressive disorders, and increased in patients with other types
of depressive disorders. This would be consistent with the fact that the
ratio (NMN + MN)/VMA appears in the equation with a negative coefficient.
D-type scores and platelet MAO activity data were obtained from patients
concurrently. Platelet MAO activity was significantly lower in depressed
patients with D-type scores less than 0.5 than in depressed patients with
D-type scores greater than 0.5. These findings, showing that patients
with low versus high D-type scores have a significant difference in an
independent biochemical measure, further suggests that D-type scores may
be discriminating among biologically meaningful subtypes of depressive
disorders. Moreover, these findings are consistent with the possibility
that the fourth term of the discrimination equation for D-type scores
may reflect MAO activity.
This D-type equation may provide an even more precise discrimination
among biologically meaningful subtypes of depressive disorders than does
the level of urinary MHPG alone. Thus, it is intriguing to speculate that
the discrimination equation, by including the contribution of various
urinary catecholamine metabolites of peripheral origin may be correcting
for the fraction of urinary MHPG that derives from the periphery, rather
than the brain.
In a further study (Schatzberg et al., “Toward a Biochemical Classification
of Depressive Disorders X: Urinary Catecholamines, Their Metabolites,
and D-type Scores in Subgroups of Depressive Disorders,” Archives
of General Psychiatry, 1989), data on 24-hour urinary levels of catecholamines
and metabolites were determined in 114 depressed patients. For each patient,
a D-type score was calculated from the previously derived D-type equation.
Of all biochemical measures obtained, D-type scores provided the highest
sensitivity and specificity for separating bipolar manic-depressive/schizo-affective
depressed patients from all remaining patients.
Moreover, a further study (Mooney et al., “Urinary 3-Methoxy-4-hydroxyphenylglycol
and the Depression-Type Score as Predictors of Differential Responses
to Antidepressants,” 1991) examined pretreatment 24-hour urinary
MHPG levels and the D-type score as possible predictors of antidepressant
responses to either imipramine or alprazolam. In the case of imipramine,
the responders had significantly lower pretreatment urinary MHPG levels
(p=.002) and D-types scores (p<.001) than did nonresponders. In contrast,
responders to the antidepressant effects of alprazolam had significantly
higher pretreatment urinary MHPG levels (p<.05) and D-type scores (p=.001)
than did nonresponders. For each antidepressant treatment, D-type scores
appeared to provide a better separation of responders from nonresponders
than did urinary MHPG levels. These findings show that D-type scores,
which were initially derived to separate bipolar manic-depressive depressions
from other subgroups of depressive disorders, also appear to predict differential
responses to certain antidepressant drugs in patients with unipolar depressions.
Thus, this observation extends the potential clinical utility of the D-type
equation and enhances the heuristic value of this empirically derived
equation as a theoretical model that may provide clues concerning the
underlying biochemical pathophysiology of catecholaminergic neuronal systems
in patients with depressive disorders.
On June 11, 2002, Drs. Schildkraut and Mooney were awarded a United States
patent (Patent No.: US 6,403,645 B2) entitled, Antidepressant Effect of
Norepinephrine Uptake 2 Inhibitors and Combined Medications Including
Them, concerning a rapidly acting antidepressant. This patent proposed
that normetanephrine or other inhibitors of the extraneuronal monoamine
transporter (uptake 2) in brain would speed up the clinical antidepressant
effects of norepinephrine reuptake inhibitor antidepressant drugs.
In recent years, collaborating with Dr. Alan I. Green, Dr. Schildkraut
and members of the Neuropsychopharmacology/Psychiatric Chemistry Laboratory
focused their research on the neuropsychopharmacology of clozapine (Green
et al., “Clozapine Response and Plasma Catecholamines and Their
Metabolites,” Psychiatry Research, 1993; Green and Schildkraut,
“Should Clozapine be a First Line Treatment for Schizophrenia?:
The Rationale for a Double-Blind Clinical Trial in First Episode Patients,”
Harvard Review of Psychiatry, 1995; Green et al.,
“Clozapine for Comorbid Substance Use Disorder and Schizophrenia:
Do Patients with Schizophrenia Have a Reward-Deficiency Syndrome that
Can Be Ameliorated by Clozapine?,” Harvard Review of Psychiatry,
1999).
Over the years, in another aspect of the research of the Neuropsychopharmacology/Psychiatric
Chemistry Laboratory, Dr. John J. Mooney has spearheaded a series of studies
concerning biochemical methodologies and basic neuropsychopharmacological
studies. This work includes Mooney et al., “An Improved Method for
the Homogenization of Human Platelets Using Colchicine and Nitrogen Decompression,”
Biochemical Medicine, 1981; Mooney et al, “Platelet Monoamine Oxidase
Activity in Psychiatric Disorders. The Application of a Technique for
the Isolation of Free Platelet Mitochondria from Relatively Small Blood
Samples,” Journal of Psychiatric Research, 1981; Mooney et al.,
“Sodium Inhibits Both Adenylate Cyclase and High-Affinity [3H]-p-aminoclonidine
Binding to Alpha-Adrenergic Receptors in Purified Human Platelet Membranes,”
Molecular Pharmacology, 1982; Mooney et al., “Enhanced Signal Transduction
by Adenylate Cyclase in Platelet Membranes of Patients Showing Antidepressant
Responses to Alprazolam: Preliminary Data,” Journal of Psychiatric
Research, 1985; “Mooney et al., “Rapid Antidepressant Response
to Alprazolam in Depressed Patients with High Catecholamine Output and
Heterologous Desensitization of Platelet Adenylate Cyclase,” Biological
Psychiatry, 1988; and Mooney et al., “Mooney et al., “Signal
Transduction by Platelet Adenylate Cyclase: Alterations in Depressed Patients
May Reflect Impairment in the Coordinated Integration of Cellular Signals
(Coincidence Detection),” Biological Psychiatry, 1998.
For the past fifteen to twenty years, Dr. Schildkraut also has been exploring
the inter-relatedness of depression, spirituality and artistic creativity,
and his papers on this subject have appeared in leading professional journals.
He is editor of the book, Depression and the Spiritual in Modern Art:
Homage to Miro, published by John Wiley & Sons, Ltd. in August, 1996.
These studies include: Schildkraut, “Miró and the Mystical
in Modern Art: Problems for Research in Metapsychiatry,” The American
Journal of Social Psychiatry, 1982; Schildkraut et al., “Mind and
Mood in Modern Art II: Depressive Disorders, Spirituality and Early Deaths
in the Abstract Expressionist Artists of the New York School,” The
American Journal of Psychiatry, 1994; and Schildkraut and Hirshfeld, “Mind
and Mood in Modern Art I: Miró and ‘Melancolie’,”
Creativity Research Journal, 1995. Moreover, in 1993, Dr. Schildkraut
organized and chaired a symposium on “Depression and the Spiritual
in Modern Art: Homage to Miró that was held at the Miró
Foundation in Barcelona. John Wiley & Sons, Ltd. published the proceedings
of this symposium in 1996 in a volume entitled, Depression and the Spiritual
in Modern Art: Homage to Miró. This book was edited by Joseph J. Schildkraut, M.D. and Aurora Otero, M.D. Dr. Schildkraut’s papers in
this symposium included “’Rain of Lyres Circuses of Melancholy:’
Homage to Miró” in collaboration with Alissa J. Hirshfeld
and “Depressive Disorders, Spirituality, and Early Deaths in the
Abstract Expressionist Artists of the New York School” in collaboration
with Alissa J. Hirshfeld and Jane M. Murphy.
Current Research
- Promotion of patent and exploration of the development of inhibitors
of the extraneuronal monoamine transporter (uptake 2) - Continued analyses of data on catecholamines and adenylate cyclase
in study of depressed patients treated with desipramine - Exploration of the hypothesis that Rembrandt experience a period of
depression at midlife (This study is being done in collaboration with
Marjorie B. Cohn, Carl A. Weyerhaeuser, Curator of Prints at Harvard’s
Fogg Art Museum, and Acting Director of Harvard University Art Museums.)
Faculty And Staff
Joseph J. Schildkraut, M.D.
Professor of Psychiatry Harvard Medical School and Senior Psychiatrist
Massachusetts Mental Health Center
John J. Mooney, M.D.
Assistant Professor of Psychiatry Harvard Medical School
Contact Us
Joseph J. Schildkraut, M.D. 617-731-2921
John J. Mooney, M.D. 617-731-2921
Patsy Kuropatkin 617-626-9463
Publications: Bibliography
Patent: Schildkraut JJ, Mooney JJ, inventors;
President and Fellows of Harvard College assignee. Antidepressant effect
of norepinephrine uptake 2 inhibitors and combined medications including
them. US patent 6,403,645. 2002 June 11.
Posener JA, Schatzberg AF, Williams GH, Samson JA, McHale NL, Bessette
MP, Schildkraut JJ. Hypothalamic-pituitary-adrenal axis effects on plasma
homovanillic acid in man. Biological Psychiatry 1999;45(2):222,228.
Green AI, Zimmet SV, Strous RD, Schildkraut JJ. Clozapine for comorbid
substance use disorder and schizophrenia: do patients with schizophrenia
have a reward-deficiency syndrome that can be ameliorated by clozapine?
Harvard Review of Psychiatry 1999;6:287-296.
Green AI, Drake RE, Zimmet SV, Strous RD, Burgess E, Xie H, McHugo G,
Khonstamm S, Schildkraut JJ. Alcoholism and schizophrenia: effects of
clozapine. Schizoprenia Research 1999;36(1-3):280-281.
Schildkraut JJ. The catecholamine hypothesis, interview by David Healy,
in
The Psychopharmacologists, Vol III, Oxford University Press, London, New
York,
2000, pp 111-134.
Canuso CM, Goldstein JM, Wojcik J, Dawson R, Brandman D, Klibanski A,
Schildkraut
JJ, Green AI. Antipsychotic medication, prolactin elevation, and ovarian
function in
women with schizophrenia and schizoaffective disorder. Psychiatry Research
2002; 111:11-20.