Hector Warnes’ comment

Janusz Rybakowski: The Faces of Manic-Depressive Illness
Reviewed by Janusz Rybakowski

            I congratulate Professor Rybakowski for this 154-page, most impressive book which reveals an unusual spirit of synthesis, a bridge between science and the humanities, a large number of ancient and modern historical data recognizing minute clinical observations on this illness throughout the centuries and a sober, critical and objective clinical stand. The book is comprised of 14 chapters, each written with clarity and precision. Some of the chapters deal with neuroscience, neuropharmacology, genetics, the evolutionary perspective, creativity in the bipolar population and research and treatment perspectives. There are 300 citations in the bibliography and excellent figures in each chapter, including the engravings by Albrecht Dürer, Lucas Cranach, Jacek Malczewski and Tadeusz Pruszkowski that depict Melancholic states. 

            Sophocles's "Ajax," published by Cambridge University Press in 2001, is an accurate description of the hero madness: manic excitement with hallucinations followed by depression and suicide. Winston Churchill called his episodes of depression "the black dog" and William Styron, in an autobiographical account of his depressive illness, called it "Darkness Visible. A Memoir of Madness.” The author in Chapter 10 (Creativity and Manic-Depressive Illness) focuses on the question of whether the use of Lithium would affect the creativity of outstanding artists.  Mogens Schou was the first to address this issue and wrote: “From 24 artists treated with lithium due to bipolar disorder 12 reported an increase in their artistic productivity, 6 a slight decrease and 6 noted no change at all" (p.140).

            The first chapter pays tribute to FK Goodwin and KR Jamison’s book on Manic-Depressive Illness, first published in 1990 and updated on 2007 (Oxford University Press). The second author, Kay Redfield Jamison, is a psychologist who herself suffered from Manic Depressive Illness and in 1996 wrote an autobiographical book: “An Unquiet Mind. A Memoir of Moods and Madness.” She also studied the profiles of outstanding artists of the visual arts, musicians, poets and writers in her book “Touched with Fire. Manic-Depressive Illness and the Artistic Temperament” and the topic of suicide in her book “Night Falls Fast. Understanding Suicide.” The reason for quoting the writings of Kay Redfield Jamison is because she had a very productive and creative life, acknowledging herself that it was largely due to the beneficial effects of Lithium. In this vein, NC Andreasen has updated the relationship between creativity and neuroscience in her book published in 2005: “The Creating Brain. The Neuroscience of Genius.”

            Professor Rybakowski asserts that modern pharmacological treatment of Manic-Depressive Disorders began in 1949 with the publication of John F. Cade: “Lithium salts in the treatment of psychotic excitement” in the Medical Journal of Australia (36:349-352), 50 years after the 6th edition of Kraepelin’s book which was published in 1899.

            On page 138, Professor Rybakowski writes: “The group of excellent lithium responders, involving about 1/3 of all bipolar patients, currently presents a focus of special attention of researchers. Patients from this group show complete recovery under Lithium monotherapy. Specific clinical traits and some molecular-genetic markers of these patients have been identified.” The concomitant use of other mood stabilizers has improved the responsiveness to Lithium in most cases up to 45-50%. In the 1970s, a group of French psychiatrists led by Pierre Lambert called the mood stabilizer’s effect "thymoregulatrice," which principally included valproic acid, carbamazepine and later lamotrigine. In the 1980s, valproic acid was shown by Stanislaw Puzynski from Warsaw to have beneficial effects in patients who were non-responders to Lithium (p.118). Since 1980, Mogens Schou's publication of “Lithium Treatment of Manic-Depressive Illness” is a classic on the use of Lithium and has been reprinted six times. 

            Rybakowski listed the many researchers of Lithium besides Cade, Geoffrey Hartigan (1963), Christian Baastrup (1964), Paul Grof (1999), Claude de Montigny (1981) and the author himself who followed up for five years 61 patients on Lithium treatment and concluded that: "Comparing the analysis of these periods, submitted to global inspection among all 61 patients,  showed that in the period of using Lithium the number of recurrences decreased by 71% and the number of hospitalizations decreased by 72%. Among 44% of patients’ recurrences of illness while using lithium were not observed" (p.111). In other research, Rybakowski and Matkowski showed that Lithium effectiveness was better in bipolar than unipolar disorders. In chapter 8, the author writes: "excellent Lithium responders may be considered a specific clinical subgroup (endophenotype) of manic depressive illness, useful in genetic-molecular research," basing his comments on the research of Paul Grof. 

            I was not aware until I read this concise encyclopedia of Manic Depressive illness that in 1896 Carl Lange published a paper on Periodic Depression and its pathogenesis in the abnormal metabolism of uric acid ("brain gout”) (p.107)

            The most complete updated research on the subject was published in the journal “Personalized Medicine in Psychiatry” in 2017 and includes all the possible mechanisms of action of Lithium salts and other proven treatments for bipolar or unipolar disorders. There is considerable research on the factors predicting Lithium responsiveness or non-responsiveness, most of them covered in Professor Rybakowski's book (gene expression, brain derived neurotrophic factor, growth factors, mitochondrial function Inflammatory cytokines, vascular endothelial growth factor A, glial derived growth factor, endocrine factors, chronic stress response and so on). Besides these ongoing researches there are three genes associated with bipolarity: the MAO-A, the Catechol-O-methyltransferase (COMT) and the serotonin transporter genotype. Professor Rybakowski and his team published a research on “Prophylactic effect of lithium in bipolar affective illness may be related to serotonin transporter genotype” (2005). The author also published on the treatment of refractory depression with carbamazepine and lamotrigine particularly the latter.

            On page 112, the author cited Ross Baldessarini (2006) and his team from Harvard University who published an extensive review paper on the issue of suicide among Bipolar Disorders and noted that: "the risk of committing suicide was five times lower among patients taking lithium than those subjected to other forms of treatment." Another interesting finding of researchers from the University of Birmingham showed that Lithium inhibits replication of the herpes simplex virus and led to remission of labial herpes while being used.  

Another development first noticed by Karl Kleist and by Karl Leonhard was the finding of a genetic difference demonstrated independently by genetic research carried out by Jules Angst from Switzerland and Carlos Perris from Sweden. Further studies have shown that about 3 to 5 % of the population may be affected by Bipolar Spectrum Disorder (p.12). Further, Karl Leonhard introduced the group of cycloid psychoses and phasic psychoses for those disorders with a periodic course that belong neither to the group of schizophrenias nor to the group of affective psychoses (p.23).

            Kraepelin's classification was further questioned particularly because of his finding that "many genes influencing the predisposition to mental disorders may increase the risk of both schizophrenia and manic-depressive illness. Second, the new generation of neuroleptic drugs have a therapeutic effect in schizophrenia in which they influence a wider spectrum of symptoms than the so-called neuroleptic drugs, as well as in mania, and sometimes also in depression, and they prevent recurrence of these symptoms in manic-depressive illness" (p.23). The term “dysthymia” was first used by Hippocrates and later Karl Kahlbaum used it in the sense of a depressive character of mild intensity. Endoreactive depression was a term meaning a more intense depression between endogenous and reactive type.  Cyclothymia and typus melancholicus were personalities described by Ernst Kretschmer and Hubertus Tellenbach, respectively. The term “hyperthymic personality” was first used by Kurt Schneider in his 1950 book, "Clinical Psychopathology." The word “hypomania” was first used by the German psychiatrist and neurologist Emanuel Mendel in his book "Die Manie" published in 1881 (p.30). The Spanish psychiatrists F. Colom and E. Vieta proposed the term “anastrophic” thinking, in contrast to the catastrophic one occurring in depression, in their paper, "Sudden glory revisited: cognitive contents of hypomania" (p.32). A disciple of Kraepelin, Wilhelm Weygandt published the first monograph on mixed states (depression and mania occurring at the same time, Mischzustände) (p.51).

            The “Mad Hatter syndrome,” named after a character from Alice in Wonderland, was a toxic manic state due to mercury poisoning and later identified with overstimulation of the dopaminergic transmission, e.g., by amphetamine or levodopa. In chapter 7, entitled "What is going on in the brain?", the author addresses the latest neurobiological findings of this disorder. It is widely accepted that Lithium’s mechanism of action is via " an intracellular step in the process of information transmission. Most studies on intracellular signaling have concentrated on the phosphoinositide (PI), cyclic adenosine monophosphate (cAMP) and protein kinase C (PKC) pathways” (p.72).

            I congratulate Professor Rybakowski for an excellent overview on Manic Depressive Illness and particularly for his attempt to bring together science and the humanities.  


Gonzalez, SD, Williams AJ, Blacker, CJ. et al. Putative biological predictors of treatment response in bipolar disorders. Personalized Medicine in Psychiatry. 2017; 1 & 2: 39-58.

Rybakowski J, Suwalska A, Czerski M, Dmitrzak-Weglarz, M. Prophylactic effect of lithium in bipolar affective illness may be related to serotonin transporter genotype. Pharmacological Report 2005; 57:124-7.


December 7, 2017