Revisiting The Major Mental Disorders


                                        An updating  synthesis

Objective:  Incorporating recent findings in the current concepts of  Major Mental Disorders (MMDs) . Namely; bipolar disorder  schizophrenia, OCD, the anxieties, and ADHD.

Method: Enumerate and  consider the  collective significance of recent findings from  molecular genetics, evolutionary biology in conciliation with empirical clinical evidence.

Results:  Conciliating findings, point to:  Common neural-developmental origin for all MMDs. Genetic loci associated with schizophrenia, do not directly lead to the disorder; they code for the expression of lopsided temperamental variants in individuals, originating from mainly one part of our human nature. These individuals, contribute to the flexibility, robustness, and creative input to our species, concomitantly, incur vulnerability for developing a MMD as an evolutionary trade off.  MMDs initially, are expressed as  periodic epiphenomena on the underlying temperamental extreme variant – The expression tends to become permanent.  Underlying aberrant traits remain unaltered. The clinical expressions are characterized by “either-or” antithetical substitutes, in addition to the co-occurring psychosis.  (The latter common is for other assaults on the brain function.)  These characteristic symptoms are the result of a disturbed overall coordinating property of brain function, normally responsive for the smooth synchronizing expression of all higher mental faculties.

Conclusion: The findings point to the need of modifying the current schema, -to better reflect genetic, clinical, and evolutionary biological findings in their collective significance, thus providing robust working hypotheses guiding research to new promising directions, for elucidating the nature of MMDs variability, the triggers of their occurrence and their mechanisms of their development, opening new horizons for therapy.

Evolutionary  Biology:  Temperamental  Variability in Human Nature 

The normally occurring temperamental variability (i.e., inborn behavioral propensities), confers flexibility and robustness not necessarily to an individual  or to him alone, but to entire  species.  As social animals our evolutionary success depends on it among other factors.11  It is proposed on the evidence to be addressed that a particular temperamental clustering creates a pool of vulnerable individuals, some of who may develop major mental disorders but, at a much  higher rate to that of general population. This clustering originates mainly, albeit in it’s extreme form  for this particular group, from evolutionary pressures on the individual. E.O. Wilson and his co-workers discovered that such clusters of traits normally compose  one part of human nature. The second, originates from evolutionary pressures on the social aspects of human experience such as empathy, connectedness, altruism, mutuality cooperativeness and tribalism (i.e collective aggressive territoriality and tribal exclusivity) fulfilling mainly the phenomenon of Eusociality for our species.11-13  These social aspects are deficient in various combinations or lacking in individuals vulnerable for schizophrenia as well as to a various degree for other MMDs. Such deficits are often masked by learned civility. Preexisting prominent traits for these individuals include; self-absorption, dearth of empathy, aloofness, tendency to be and act alone, a felt  void/boredom, and an aversion to connect with others— all characteristic of the premorbid personality. Normally, as he explains, we balance traits that are un-amalgamated, chimera-like. This makes us successful but, conflicted social animals. E.O. Wilson further stated that we exist in unstable compromises between ourselves and those close to us within our own tribe and adjoining ones.11-13, 16

The Significance of the Cluster of Gene Loci-Variants Associated with Schizophrenia

Based on recent findings the cluster of gene loci-variants associated with schizophrenia 1,16 do not directly lead to the disorder. The implicated genes may actually express themselves in lopsided, phenotypic traits comprising the  premorbid personality. Such expression creates a pool of vulnerable individuals, some of whom will develop a MMD but at higher rate to those of the general population. Such occurrence is amenable to prediction only by statistical methods.3,5

 Extreme Temperamental Variance and Society

Extreme lopsidedness in variability at the edge of the temperamental spectrum, creates a group of mismatched individuals for the prevailing, social zeitgeist of the society in which they live. They are labeled as character disorders, or whatever the particular era they live in, decides to call them.15 These individuals, in addition to having personal dysphorics — often severe above and beyond that which are normally felt by all humans — such as a void felt from within or boredom, dysthymia, irritability, aloofness, an aversion to social interaction and possibly others, there also exists a dissonance between themselves and the prevailing but ever changing, circumstances, rules, and ethos of the social zeitgeist, compromising their everyday ability to function and often placing them in conflict with the prevailing social rules. These dysfunctional individuals while  variably labeled “behaviorally troubled” or outright “character disorders,” never the less, if also intelligent tenacious and curious, they can now express significant  creativity.29,19,20 Their particular temperamental variance, acts as an enabling factor. For instance, an impulsive, periodically explosive, intense, fearless, ambitious, and intelligent man will be prized as a great warrior, like Alexander the Great.21 Conversely, Steve Jobs an intense, compulsive, tenacious visionary, created and shaped the future in information technology. In spite of it , he was kicked out for a time from his own company.22 The gifted mathematician but socially odd ,writer Lewis Carroll, author of Alice in Wonderland was merely deemed an eccentric scholar by the real Alice’s family for his obsessive habit of photographing the eleven-year-old in the nude!23  Today  L. Carroll would be labeled as a pedophile and recommended for treatment if not arrest. Michelangelo, Leonardo Da Vinci,25 Isaac Newton and from our times Nicola Tesla, R. Feynman,26 Albert Einstein,27  shared similar temperamental peculiarities. The list is long. Conversely, individuals rich in social attributes and traits, while contributing to the cohesiveness and harmony of the tribe, would not advance without the significant and fundamental creative contributions from those lacking in these same traits.29

The Significance of Extreme Temperamental Variance in MMDs 

Individuals who are lopsided in temperament, creative or not, as mentioned, significantly also make up a pool of vulnerable individuals some of whom will develop major mental disorder at a much greater rate than the general population.1,16  Their aberrant traits are now renamed “premorbid personality” or “residual” following remission.9,28  The occurrence of a MMD for these individuals is probabilistic and amenable to prediction only by statistical methods. The rate for the general population is 3-6% worldwide irrespective of culture for all three types combined.29

The clinical expression of MMDs should be considered as a periodic phenomenon superimposed on a patient’s lopsided temperament.  They are characterized with frequent remissions and relapses, at least upon onset, while later becoming permanent, akin to the occurrence of atrial fibrillation which becomes also permanent later on.30,31

Significantly, symptoms of MMDs, in addition to the presence of a generic psychosis with its delusions and hallucinations -to be addressed later-are made up of antithetical substitutes with an  “either-or” character.32,33,34  

Importantly, compelling evidence accumulated from disparate fields indicates that in reality, there exists only one major mental disorder.5,7 It is expressed in three main embodiments with their own variability. These embodiments frequently overlap or even alternate, resulting in a messy clinical picture, rarely, if ever, conforming to the categorical guidelines of the DSM. This is particularly evident in the case of ADHD, which later is often expressed as bipolar disorder. This phenomenon is traditionally termed co-morbidity, instead of being considered —as the clinical evidence suggests— another manifestation of the same MMD. These embodiments include schizophrenia involving the coordination of thinking, feeling and behavior and  appropriateness of social interactions. Bipolar affective disorder involving mood modulation, and Obsessive compulsive disorder (OCD) involving the algorithmic faculty (responsible for scheduling, sequencing, fore-planing future actions, routines, and habits).32,35 In addition, the anxiety disorders and phobias are also often a commonly shared symptom of all MMDs.40 The symptoms of all of these syndromes are, as mentioned, characterized by antithetical substitutes, i.e., the manic-depressive oscillation characteristic of bipolar affective disorder, the ambivalence of schizophrenia (the rapid attitudinal oscillations towards a person or object), – the either-or concrete-tistic  and non-sequitur thinking, inability to accommodate ambiguity ,apathy punctuated by explosive outrage  and  mismatched responses to a given social situation. In the case of OCD, over-diligence, switches to slovenliness along with the equivocation and inability to bring closure to a decision, replacing obsessive tenacity32,39 as well as entrainment of thoughts. Significantly, in the case of  an intermittent, major, depression, the presence of a manic phase is overlooked occurring usually as an unnoticed, transient, emotional rush—readily recounted by the patient when asked. All pointing to  disturbed coordination in the expression of  the higher faculties.

The Significance of the Overall Synchronizing Mode of Brain Function.

Actually, all of the aforementioned, clinical expressions manifest themselves as a kind of “psychic-Parkinsonism,”6,43 reflecting an abrupt switch from the normal phase of the overall coordinating mode of brain function,insuring   smoothness elegance and subtlety ,  to that of black and white -either -or ,entrained character in their expressions.  The  normally present, over-all synchronizing faculty of the expression of all higher mental faculties is rarely taken into account.  However, it is responsible for the elegant expression, characteristic of normal humans in action, true for  all higher mental faculties, including the mentioned areas of thinking, feeling, coordination of thinking with feelings, mood modulation and the algorithmic one responsible for scheduling, sequencing, and routine habit  formation.42,43  During the onset of a MMD or during a relapse, this mode switches to “pathologically ordered state“ with familiar symptoms characterized by  antithetical substitutes mentioned above. -This phenomenon is particularly startling  during clinical interactions in a flare up of the borderline disorder (a possible  variant of bipolar disorder -); the clinician witness within minutes rapid antithetical expressions of feelings, attitudes and utterances by the sufferer 35,44,45  – It is akin to the cacophony ensued by a performing orchestra following the sudden departure of its conductor. Importantly, the co-occurrence of delusions and hallucinations can be interpreted separately, as an attempt by the integrating function of the brain to make sense of the underlying dysfunction, often similarly observed in many physical conditions such as fever, brain trauma, toxic states or following heart surgery to name a few —all successfully treated by the same anti-psychotic medications. -The underlying, lopsided personality remains the same.


These presented materials suggest that studies of personality and temperamental   types in their above described form, are very important because, based on the presented evidence, the same clusters of gene loci associated with a specific mental disorder such as schizophrenia ought to be found congregated in individuals manifesting the same clusters of traits that confer vulnerability to mental disorders at a much higher rate compared to the general population, but not invariably expressing the disorder.1  The traditionally recognized cluster of five personality traits including neuroticism, antagonism versus agreeableness, extroversion versus introversion, and conscientiousness versus openness to new experience should all be renamed by using adjectives similar in meaning but, better reflecting their dual evolutionary origins. Then, by modifying existing personality and temperament tests,34,42 geneticists and clinicians alike will be better able to accurately identify vulnerable groups. This will enable researchers to discern patterns and relationships between genes, clusters of genes, and behavioral traits involved in the expression of temperamental phenotypes in individuals enabling creativity as well as a trade off to susceptibility to a mental disorder.  Importantly, this will also enable identification of circumstances and triggers that compromise the overall synchrony and coordinating faculty of brain functions for these populations that result for some in the periodic epiphenomena — which later, usually become permanent as in the case of schizophrenia and other mental diseases. In addition to the clinical evidence cited, this synthesis is  also based on  the author’s own longitudinal observations of over ten thousand pts ,spanning five decades .


I have no financial or personal relationships or affiliations that could influence (or bias) my decisions, work, or manuscript. I have no potential conflicts of interest, including specific financial interests relevant to the subject of my manuscript or The Aj of P. I especially would like to thank the  polymath John Rather, PhD  astrophysicist for helping me to edit this article for publication.


1. Bergen SE, Petryshen TL. Genome-wide association studies (GWAS) of schizophrenia: does bigger lead to better results? Curr Opin Psychiatry. 2012; 25(2):76–82.

2. Jia, P, Wang, L, Meltzer, HY, & Zhao Z. Common variants conferring risk of schizophrenia: a pathway analysis of GWAS data. Schizophrenic Res. 2010; 122(1):38-42.

3. Gershon ES, Alliey-Rodriguez N and Liu C. After GWAS: searching for genetic risk for schizophrenia and bipolar disorder. Am J of Psychiatry. 2011; 168(3):253-256.

4. Purcell SM, Wray NR et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009; 460 (7256):748-752.

5. Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. The Lancet. 2013; 381(9875):1371-1379.

6. Pediaditakis N. Origins and mechanisms in the development of major mental disorders: a clinical approach. J Behav and Brain Science. 2012;(2):269-275.

7. Pediaditakis N. Shared characteristics in the clinical expression and pharmacological responses of mental disorders and their possible collective significance. Med Hypotheses. 1998;50(4):347-352

8. Singh SM, McDonald P, Murphy B and O’Reilly R. Incidental neurodevelopmental episodes in the etiology of schizophrenia: an expanded model involving epigenetics and development. Clin Genet. 2004;65(6):435-440.

9. Solano JJR and González De Chávez M. Premorbid personality disorders in schizophrenia. Schizophr Res. 2000:137–144.

10. Solano JJR and González de Chávez M. Premorbid adjustment and previous personality in schizophrenic patients. Eur J Psychiatry. 2005;19 (4):243-254.

11. Wilson EO and Tarnita NA. The evolution of eusociality. Nature. 2010;(466):1057–1062.

12. Wilson EO. On Human Nature. Cambridge: Harvard University Press;2012.

13. Wilson EO. The Social Conquest of Earth, New York: Liveright Publishing Corp.;2013.

14. Jablensky A. Schizophrenia: its history, evolution, and future prospect. Dialogues Clin Neurosci. 2010; 12(3):271–287.

15. The Diagnostic and Statistical Manual of Mental Disorders (5th ed.); DSM–5; American Psychiatric Association [APA], 2013.

16. Pediaditakis N. Addressing a Conundrum: Why, According to the Genome-Wide Association Study and Psychiatric Genome Consortium are Clusters of Gene Loci Variants Associated with Schizophrenia Found Scattered in Non-Schizophrenia Populations? A Consilience International J of Molecular Genetics. 2015; 6(1): 21-29.

17. Fenton WS. Co-morbid conditions in schizophrenia. Current Opinion in Psychiatry. 2001;14(1):17-23.

18. Manschreck TC, Maher BA, Waller NG, Ames D, Latham CA. Deficient motor synchrony in schizophrenic disorders: clinical correlates. Biol Psych. 1985;20(9):990–1002.

19. Rothenberg A. Creativity and madness: New findings and old stereotypes. Baltimore: Johns Hopkins University Press, 1990.

20. Waddell C. Creativity and mental illness: is there a link? Can J Psychiatry. 1998;43(2):166-172.

21. Fox, Robin, L. Alexander the Great. London, England: Penguin Books Ltd, 2004.

22. Isaacson, W. Steve Jobs. N.Y, N.Y. Simon & Schuster, 2013.

23. Woolf, J. The Mystery of Lewis Carroll: Discovering the Whimsical, Thoughtful, and Sometimes Lonely Man Who Created “Alice in Wonderland.” Macmillan, 2010.

24. Hodges A. Alan Turing: The Enigma. NY: Simon and Schuster, 1983.

25. Davis, Robert, C. Renaissance People : Lives That Shaped the Modern Age. J. Paul Getty Trust, 11th Ed. 2011.

26. Krauss L. The Quantum Man. NY: W. W. Norton & Company, Inc.; 2011.

27. Issacson W. Einstein: His Life and Universe. Simon and Schuster, 2007.

28. Bora E, Gökçen S, Kayahan B, and Veznedaroglu B. Deficits of social-cognitive and social-perceptual aspects of theory of mind in remitted patients with schizophrenia: effect of residual symptoms. J of Nerv Ment Dis. 2008;196(2):95-99.

29. Pediaditakis N. The association between major mental disorders and geniuses. Psych Times. Sep 2014.

30. Haro, Josep Maria, et al. Remission and relapse in the outpatient care of schizophrenia: three-year results from the Schizophrenia Outpatient Health Outcomes study. J of Clinical Psychopharmacology. 2006; 26(6): 571-578.

31. Jahangir, A., et al. Long-term progression and outcomes with aging in patients with lone atrial fibrillation, a 30-year follow-up study. Circulation. 2007; 115(24): 3050-3056.

32. Obsessive-compulsive disorder (OCD), 2015. Mayo Clinic Staff.

33. Pediaditakis N. Borderline phenomena revisited:a synthesis. Psych Times. Feb 2002:37-41.

34. Laceulle, Odilia M., Ormel, Johan, Vollebergh,Wilma A., Van Aken, Marcel, A.G., Nederhof, Esther. A test of the vulnerability model: temperament and temperament change as predictors of future mental disorders– the TRAILS study.J of Child Psychology and Psychiatry. 2014; 55 (3): 227–236.

35. Andreasen NC, Nopoulos P, O’Leary DS, Miller DD, Wassink T, Flaum M. Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms. Biol Psychiatry. 1999;46(7):908-920.

36. Insel, Thomas, et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Amer J of Psychiatry. 2010; 167(7): 748-751.

37. Ekstrøm M, Lykke ME, Sørensen HJ, Mednick SA. Premorbid personality in schizophrenia spectrum: a prospective study. Nord J Psychiatry. 2006;60(5):417-22.

38. Kho KH. Treatment of rapid cycling bipolar disorder in the acute and maintenance phase with ECT. J ECT. 2002;18(3):159-161.

39. Grassi G, Pallanti S, Cantisani A and Pellegrini M. Obsessive–compulsive disorder comorbidity: clinical assessment and therapeutic implications. Front Psychiatry. 2011;(2):70.

40. Lewinsohn, PM. Lifetime comorbidity among anxiety disorders and between anxiety disorders and other mental disorders in adolescents. J Anxiety Disord. 1997;11(4): 377-394.

41. Parker GB. Co-morbidities in bipolar disorder: models and management. Med J Aust. 2010;193 (4):18.
42. Jorgenson, E.  Development of the open extended jungian type scales 1.2.Creative Commons Attribution-NonCommercial-Share Alike. 4.0 International License. 2014.

43. Uhlhaas PJ, Singer W. Neural synchrony in brain review disorders: relevance for cognitive dysfunctions and pathophysiology. Neuron. 2006; 52(1):155–168.

44. Pediaditakis N. Considering the major mental disorders as clinical expressions of periodic pathological oscillations of the overall operating mode of brain function. Med Hypotheses. 2006; 67(2):395-400.

45. Pediaditakis N. Deterministic Nonlinear Chaos in Brain Function and Borderline Psychopathological Phenomena. Med Hypotheses. 1992; 39: 67-72.


Nicholas Pediaditakis, MD, DLFAPA

Affiliate Professor, East Carolina University, Brody School of Medicine

Department of Psychiatry and Behavioral Medicine, Greenville, NC

Word Count Text: 1673

Contact Address: 5100 Lead Mine Rd., Raleigh, NC 27612



Email: niko15@bellsout



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