* Understand the consolidated body of OCD comorbidity knowledge
* Identify current cerebral mechanisms of OCD
* Understand the unified theory of OCD

Abstract

Various theories exist concerning the philosophical, biopsychosocial, and anatomic aspects of obsessive-compulsive disorder (OCD). The heterogeneous symptomatology of OCD and the complex interaction between the brain as a physical structure and the mind demands a theory for OCD that recognizes the disorder as a unified emergent property. A unified theory of OCD is proposed, which incorporates the neurochemical, neuroanatomic, and psychiatric underpinnings of this disorder, explores the methods by which OCD pathologies impact the neuroanatomic circuits of the brain, and explains how, through its symptomatology, OCD is "communicated" by the mind to the outside world.
Introduction

Obsessive-compulsive disorder (OCD) is a syndrome comprising obsessions, compulsions, and doubting, all of which are historical, unchallenged clinical observations. The content of OCD symptoms assumes psychological expression of a person's approach to life. In this regard, obsessive and compulsive contents are manifested through symptoms, such as morbid or sexual obsessions, as well as washing or "double checking." Symptom and content quality provide directionality in life, as these properties represent some of the philosophical and biologic bases of life (eg, reproduction, death, and symbolism). Symptom and content quality are expressed not only by cerebral higher cortical functions, but also by the primitive brain (eg, the rhinencephalon, basal ganglia, and limbic system). The primitive brain, which is primarily located in the basal ganglia, regulates certain functions pertaining to motor compulsive activity, such as that observed in animal behavior (eg, grooming, hoarding, mutilation, or other primitive acts). A combination of both higher cortical and primitive functions results in the individual performance of rituals or ceremonies that remind us of the consecration of myths, which are a mixture of beliefs, symbols, and "magic thinking."

Considering the heterogeneous symptomatology of OCD and its content diversity, the concept of OCD and its nosologic construct require a revision. This paper introduces a clinical model of OCD known as the unified theory. This theory embraces three primary points: (1) the philosophical basis of OCD; (2) the biopsychosocial model; and (3) an organic framework. A complete understanding of OCD requires a discussion of neuroanatomy, histochemistry, cybernetic mechanisms, cerebral functions, symptomatology, and the ecosystem, with its component government, society, and family. For the sake of brevity, however, this article primarily focuses on the clinical and organic aspects of OCD, in addition to the philosophical and biopsychosocial components.
The Philosophical and Biopsychosocial Bases of OCD

The dynamic concept of OCD, a mosaic of factors pertaining to organic, clinical, and psychological pathologies, yields a paradigm that is difficult to prove, yet is certainly in need of verification. This paradigm is constructed assuming that OCD is a genetic upshot of the encephalon interacting with an anencephalic spirit or soul (a mind-body view). The involvement of the brain is succinctly highlighted by the statement that "encephalitis may be a useful clinical model for OCD,"1 while the involvement of the spirit is reflected in the statement that "the obsessive state is a way of life of the spirit, in which the subject's will is subjugated within a clearer consciousness."2 St. Ignatius Loyola called OCD the chronic interrogation of life. Paraphrasing him, compulsions are the chronic reenacting of life, while an obsession is the habitual phenomenon that represents the perpetuation of the self without causality and is manifested as a "being." This philosophical position or mind-body problem has created many arguments from persons attempting to resolve the existence or absence of the mind as a nonorganic entity.

Discussing OCD not as an epiphenomenon but as an original blend of the mental and the physical allows exploration into the mind-body problem and the mind-brain problem. To accept the mind-body problem as a dualistic posture where the mind and body coexist in parallel may a be simplistic view. A complete account of brain function in strictly neurophysiologic terms is admissible, if the idea of consciousness is rejected. Consciousness has been defined as "the perception of what passes in a man's own mind"3; in other words, consciousness acknowledges the awareness of our presence and of our mentation.

However, mentality, as a system property, cannot be located for its actions to any subsystem of the total information-flow pattern.4 This is in contrast to the position of Popper and Eccles,5 who later proposed the theory of interactionism to explain the body-brain problem. MacKay,6 although accepting interactionism, viewed this alternative as open to different interpretations when he stated that "the peculiar facts of our self-conscious experience should make us look for corresponding (self-modifying) features of the cerebral information-flow system, rather than any disturbances of its physical functioning."

In 1973, Globus7 attempted to explicate the psychoneural identity thesis of Feigl,8 stating that consciousness is identical to neural events. Globus spoke of "private physical events," although he did not exclude consciousness from comprising physical events in general. This thesis cannot be well tested, since it is difficult for the brain to observe itself; therefore, a definite partiality arises. Globus' discussion calls to mind several concepts of the mind-brain problem that were posited for years without further challenge: (1) empirical findings, psychosomatic medicine, neuropsychology, etc; (2) the law of parsimony, which affirms a monist assumption rather than a dualist assumption; and (3) the unity of science, which allows psychological phenomena to be seen equally as physical phenomena. Along the same line of thought, two theories have been put forward to explain the body-mind problem. The first is the double aspect theory,9 which postulates that the mind is one aspect of a fundamental neutral reality (as with the two sides of a coin). The second is the double language theory,10 which argues that the apparent distinction between mind and matter is the reflection of a dualistic language.

Psychiatry has been reluctant to accept the mind-body problems as unavoidable dilemmas that require resolution to understand mental illness. Nevertheless, a reductionistic approach appears premature. Perhaps a partial or more effective compromise is to accept the general system theory and its emergents as viable answers to explain OCD brain pathology.

The above notions were challenged by Engel's biopsychosocial model,11 which is based on the writings of Weiss12 and von Bertalanffy13 regarding general system models. Weiss advanced a theory (also offered by Engel) proposing a hierarchically ordered continuum from the complex to the simple that is applicable to medical disorders. According to this biopsychosocial model, the brain is viewed as the sum of its subsystems ordered in different levels or strata, where at each level properties appear that are unique to that level.14 As a result of the interactions in the brain, the mind is seen as emergent. (Emergent is defined as a property possessed by a system but not by its components.) This approach prevents dichotomizing the physical versus the mental concept of OCD, rejecting the psychophysical dualism of Leibniz or Descartes (as did Goodman15 in his analysis, which concluded in an organic unity theory). This author ascribes to Engel's model with some modifications, by replacing the society-nation level of organization with an organization comprising the government, followed by society, and then by the family.16

With regard to OCD, an altered thought process is seen, with obsessionality and a corresponding irresistible urge to act. Both factors appear to operate as emergents with an underlying pathology. In accepting OCD as a neural event operated by a superior interpretive role that translates the anatomicochemical to a thought process, a possible emergent can be constructed. This author adopts Schwartz's17,18 description of an emergent as the properties and functioning of a system as a whole within the dynamic interactions of the components. According to Bunge,19 these components characterize the system. Bunge further posited that the emergent properties of the mind characterize the entire human system and give it a distinct quality, in which the mental is emergent relative to the physiologic complex of interacting processes. As stated above, Feigl20 preceded Bunge's theories by introducing the hypothesis of psychoneural identity, where consciousness is identical to neural events. This concept may be relevant to the revision of the OCD theory proposed in this article.

In conceptualizing OCD as a unified theory, this paper questions the psychological and physical meanings of OCD. Some relevant questions that need to be addressed are: Does OCD speak in a different vocabulary in its neural, molecular, or psychological aspects? In what way does OCD behave with respect to its neighboring clinical structures (some of which are known as nosologic or comorbid emergents)? Do these emergents comprise dormant nosologies or symptom clusters awakened by a pathologic proportionality that supersedes brain normalcy? Is the ego, which represents the consciousness, the expression of our individual human integral profile?

To begin to address these questions, a work scheme must be constructed that includes a physical concept vs a mental concept for OCD, and the dimensional meaning of the OCD concept; ie, its referent, its confirmatory evidence, and its place and relationship to neighboring structures. To elucidate the meaning of the OCD concept, it is essential to establish the presence of potential identity, extensional identity, and intentional identity. This task requires three operations: (1) for potential identity, its referent, its place, and its relationship to other concepts must be identified; (2) for extensional identity, a shared referent must be found; and (3) for intentional identity, the possibility of substitution between the two concepts must be recognized. First, we can ascribe to Goodman's organic unity theory,15 blending the mind-body construct as an indivisible entity. Second, we must accept the OCD referent as the mind-neural interaction of mental illness; its confirmatory evidence as the presence of OCD symptoms and signs; and its intentional identity as the association between the mind-neural concept and OCD symptoms and signs and other mental illnesses.

If OCD is considered a cerebral imbalance, a mental date of onset (ie, obsessions) and a physical date of onset (ie, compulsions) must be confirmed. To combine both dates of confirmation (mental and physical), a translation is required as proposed in Graham's linguistic parallelism,10 where one language can be translated into the other. This approach is in disagreement with the theories of Feigl20 and MacKay,21 which suggest that the mental and the physical represent not only different languages, but also different logical or categorical types and cannot be translated.

OCD speaks with an anatomic and chemical language externally translated using a cognitive and a behavioral style. Cognitive language communicates obsessions and some mental compulsions, while motor language communicates compulsions. Their vocabulary is constructed with symptoms (a phenomenologic awareness or message for the patient) and signs (an external awareness or message for both the patient and the examiner). As it is understood today, OCD has many symptoms but few signs. Therefore, a paucity of language exists between the observed (the patient) and the observer (the examiner), or one brain vs another brain, making events difficult to interpret. This cognitive language may include additional meanings corresponding to temperament, introversion, extroversion, other personality variables, or even the precursor of ego (ie, eutonic) function.

Subsequently, the criterion to observe the brain includes the incorporation of several subsystems to encompass the bodily system of OCD in its indivisible cannon. The subsystems are: (1) the anatomicofunctional structure of the brain; (2) the neurochemical pathway that collects, processes, stores, and delivers information; and (3) the emergent symptoms, as well as their sites of origin. This author agrees with Freedman22 with regard to the need to revise the conceptualization of mental illness, as "new knowledge about how cells and biological system acquire, code, and exchange information [constitutes] challenges all of medicine."22
The Structural Anatomy of OCD

The anatomy of OCD has been relatively determined following laboratory observations provided by electroencephalography, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and examination of brain blood-flow circulation and brain anatomic lesions with single-photon emission computed tomography (SPECT). Topographic brain mapping indicates a left hemispheric dysfunction, mostly localized to the temporal lobe23 and left posterior frontal to midtemporal region,24 as well as temporal25 and bitemporal abnormalities.26 Similar locations appear to be established in children and adolescents.27 Overall, the size of the samples analyzed has been small; therefore, some results are inconclusive, although a trend has been observed toward left hemispheric localization and nonspecific paroxysmal activity.

In addition, structural brain changes have been exhibited on MRI. The observable variables have included prolongation of the spin-lattice relaxation time and greater right-minus-left differences in frontal white matter, with a strong correlation between orbitofrontal cortex and symptom severity.28

Brain CT scans in OCD patients have measured ventricular brain ratios, caudate ratios, and frontal ratios to determine size. Reports appear to be consistent with equivocal morphologic changes.29,30 In addition, PET scanning has been of fundamental use in explaining aspects of OCD pathophysiology. This imaging technique has demonstrated significant increases in glucose metabolism in the left orbital gyrus and bilaterally in caudate nuclei.31 Moreover, two reviews of functional brain imaging studies, including medication and provocation trials, have indicated that the limbic-orbital-prefrontal cortex and the basal ganglia are involved in OCD anatomy.32,33 Two blood-flow studies in OCD using 133Xe SPECT have stimulated further research. Zohar et al34 reported a slight increase in regional cerebral blood flow (rCBF) in temporal regions, and a marked decrease in rCBF in several cortical regions following imaginal flooding. Rubin et al35 found an increase in OCD symptoms following challenge with the partial serotonin agonist meta-chlorophenyl-piperazine, accompanied by a greater increase in global rCBF.

The presence of brain lesions at several sites, including cerebrovascular accidents, tumors, cysts, and other sites of structural damage in patients with OCD, have failed to demonstrate a clear anatomicoclinical correlation between lesion sites and symptoms.36 Neurosurgical studies, however, have indirectly corroborated the transmission of OCD symptoms utilizing anatomic pathways.37 These findings have indicated a basal ganglia-limbic-striatal-thalamocortical circuit as a major target of OCD pathology. The small number of patients involved in these studies and the complexity of the methodology, however, make these findings inconclusive.
Neuroanatomic and Neurochemical Pathways in OCD

OCD is an experiential manifestation of human behavior enveloping thought, movement, affect, volition, and somatosensory activity. This manifestation expresses itself utilizing circuits that operate in the brainan organ consisting of tens of billions of neurons at the age of 20 years, each of them connected to another 10,000 to 25,000 neurons.38 These neurons appear to work in a columnar fashion and to exhibit three properties: (1) they are strengthened by use; (2) they can establish new connections; and (3) they may be debilitated by use. The concept of neural plasticity, a quality that allows histologic repair, has been brilliantly proposed by Ramon y Cajal,39 Tanzi,40 and Sherrington.41 This concept may even allow physicians to entertain the idea of partial "restitutio ad integrum" (complete healing if damaged), considering that the process of brain aging modifies its circuitry, functionality, and OCD mechanics. It is possible to accept the concept that streams of information are combined, forming new representations that can later be retrieved.42 Therefore, synaptic plasticity may challenge the old notion that the pathologies of cerebral chronicity (including OCD) are irreversible.

Five main neuroanatomic circuits appear to be related to OCD: (1) orbitofrontal, (2) prefrontal dorsolateral, (3) oculomotor, (4) classical motor, and (5) limbic. The first, second, and fifth of these are complex loops whose functions are mnemic, cognitive, and emotional. In addition, this group of circuits may also include the striatum, an area associated primarily with movement, cognition, memory, and affect.43 Therefore, OCD taxonomy comprises and connects: (1) classical corticostriatal systems, (2) segregated cortico-basal ganglia-thalamocortical circuits, and (3) the neostriatal mosaic. These areas control somatosensory, emotional, motor, and some endocrine mechanisms. In addition, basal ganglia circuitry is connected to the anterior cingulum,44 a gyrus involved in the neurosurgical treatment of OCD.

To date, the following associations between brain anatomy and function have been established: (1) the frontal lobes with higher intellectual functions; (2) the limbic system with the autonomic nervous system and with endocrine linkages to emotional modulation; (3) the basal ganglia with motor compulsions and hoarding; and (4) the amygdala with self-mutilation. Gastó45 has conducted an excellent review on brain anatomy and its function.

Neurochemically, the hypothesis was originally put forth that a deficit in serotonin is involved in the chemistry of OCD.46 This hypothesis, which has been partially validated,47 has been modified by the acceptance of the involvement of other neurotransmitters (eg, noradrenaline and acetylcholine). These neurotransmitters are the information carriers of the brain, and "ride" the OCD anatomic circuit pathways.

Further research must be performed on correlating anatomic functions or lesions, and neurotransmitter sites and modus operandi, with clinical findings. In this regard, MacKay48 speculated that conscious neural activity may lack a specific anatomic location so much as the information traffics at a specific level of the cerebral information flow system. Moreover, it has been assumed that the localized functional anatomy of OCD may operate from other neuronal clusters located far away from the site of recorded action. Because of this fact, it may be difficult to isolate the correct anatomicochemical and functional locus or loci for OCD. Based on the information available to date, it can be concluded that the understanding of OCD cerebral anatomicochemical organization and metabolic physiology is still in its seminal state.
Symptomatology of OCD

Obsessive-compulsive disorder is a multivaried and open-ended condition with a nuclear, peripheral, and preformed symptomatology. The nuclear symptomatology comprises obsessions, compulsions, doubting, hypervigilance, and the need for control. The peripheral symptomatology includes secondary symptoms such as anxiety, depression, dysperceptions, and motor dysfunctions. The preformed symptomatology comprises units of unspecific clinical observations existing in a dormant state, such as those suggested for psychiatric predicaments in general49 or as emergents associated with comorbid pathology.1

Examination of symptoms and their contents has led to the formulation of a series of clinical events that are customarily grouped as part of the OCD classification. Accepting the integrational models of Engel and Yaryura-Tobias,50 a classification demands scientific intensity and accuracy, but may require the analysis of sociopolitical ramifications. In 1983, Luys51 advanced the most important OCD classification, dividing obsessionality into three groups: intellectual, emotional, and psychomotor. From this clinical conception stems a variety of subsets that constitute today's OCD foundation of allied conditions, comorbidity, and the unified theory. Allied conditions (eg, Parkinson's disease, Sydenham's chorea), and comorbidities have been widely discussed.52,53 The unified theory of OCD is discussed below as the theoretical aggregate of the preceding sections.
The Unified Theory of OCD

OCD is a direct or indirect referent to several neuropsychiatric illnesses. These associations suggest the possibility that a theory can be postulated to encompass all these clinical entities (eg, body dysmorphia, Tourette's syndrome) under a single unified theory of OCD.

The unified theory accepts a priori the Aristotelian idea of a continuum, which states that a moving object never reaches the end of the line because it first must reach the end of a series of infinities. Aristotle also examined how two objects position with each other, suggesting three requirements for their positioning: sequence, contiguity, and continuity. In areas of contact, these objects perhaps fuse into each other to merge together. These emergents may be transient or lasting and heterogenous or homogenous, and they may not constitute a final fusion.

OCD appears as a continuum, an idea that is partially analogous to Griesinger's theory of mental illness.54 The OCD continuum is based on the creation of energy that, accepting the line of thought of Heraclitus and Plato, flows unidirectionally, and can be located in time and space within the cerebral boundaries. In other words, the OCD trajectory determines the distance to cover in time and space. Therefore, it may be argued that the brain has continuity in selected circuitries, while rejecting the notion of a cerebral hiatus, as Leibniz did.

The unified theory is explained as a theme painted on a Spanish fan that, when unfolded, shows the whole painting (ie, the aggregated nosology). Accordingly, in OCD one condition leads to another, extending from one subsystem to another and manifesting new pathologies. It is possible to speak of a noxa impacting the brain tissue like two subatomic particles that collide and cause a ripple effect. This ripple effect overlaps on cerebral areas possessing different functions, and causes new flows of energy. Certainly, this flow is pathologic and produces chaos, which in turn may cause creative or novel structures described as bifurcations.55 This author proposes that these bifurcations originate OCD symptoms and signs, originate reverberation, aggregation, or segregation. Along this pathologic highway are detours or bifurcations that create symptoms and signs that permit a continuum or, in other instances, comorbidity. This physical state also causes the qualities observed in OCD symptoms and signs.

Finally, it can be said that OCD, with its large spectrum, follows a gradual course of evolution that, if untreated, becomes chronic. When the disorder moves beyond the boundaries of neural plasticity, it becomes irreversible. Irreversibility becomes a functional dimension of OCD evolution if the condition remains untreated, or if treatment is applied at the final stages of its course. Conversely, if treatment is applied at the earliest stages of onset, improvement, and sometimes complete resolution, may be expected.
References

1. Yaryura-Tobias JA, Neziroglu FA. Obsessive-Compulsive Disorders: Pathogenesis-Diagnosis-Treatment. New York, NY: Marcel Dekker; 1983.
2. Green A. Obsession et Psychoneur. Obsess. Encyclopedie Medico Chirurgicale. Paris, France: Psychiatrie; 1965.
3. Locke J. Consciousness. In: Micropedia Encyclopedia Brittanica. Chicago, IL: University of Chicago; 1980:92.
4. MacKay DM. Mindlike behaviour in artefacts. Br J Phil Sci. 1951;11:105-121.
5. Popper KR, Eccles JC. The Self and Its Brainan Argument for Interactionism. Berlin, Germany: Springer International; 1977.
6. MacKay DM. The interdependence of mind and brain. Neuroscience. 1980;5:1389-1391.
7. Globus GG. Consciousness and brain. Arch Gen Psychiatry. 1973;29:153-160.
8. Feigl H. The "Mental" and the "Physical." Minneapolis, Minn: Minnesota Press; 1967.
9. Gerard R. The scope of science. Sci Month. 1947;50:496-512.
10. Graham DT. Health, disease, and the mind-body problem: linguistic parallelism. Psychosom Med. 1967;29:52-71.
11. Engel GL. The clinical application of the biopsychosocial model. Am J Psychiatry. 1980;137:535-544.
12. Weiss P. Animal behavior as system reaction: orientation toward light and gravity in the resting postures of butterflies. In: General Systems: Yearbook of the Society for General Systems Research. Vanessa 1925. 1959;4:1-44.
13. von Bertalanffy L. Chance or law. In: Koestler A, Symthies JR, eds. Beyond Reductionism. New York, NY: Macmillan Publishing Co; 1969.
14. Dismukes K. What mind-body problem? Behav Brain Sci. 1978;3:351-352.
15. Goodman A. Organic unity theory: the mind-body problem revisited. Am J Psychiatry. 1991;148:553-563.
16. Yaryura-Tobias JA. The Integral Being: A New Path to Personal Growth and Meaningful Living. New York, NY: Henry Holt and Company; 1987.
17. Schwartz GE. A systems analysis of psychobiology and behavior therapy. Psychother Psychosom. 1981;36:159-184.
18. Schwartz GE. Testing the biopsychological model: the ultimate challenge facing behavioral medicine? J Consult Clin Psychol. 1982;50:1040-1053.
19. Bunge M. Emergence and the mind. Neuroscience. 1977;2:501-509.
20. Feigl H. The mind-body problem in the development of logical empiricism. In: Inquiries and Provocations. Dordrecht, Holland: Reidel; 1981.
21. MacKay DM. Ourselves and our brains: duality without dualism. Psychoneuroendocrinology. 1982;7:285-294.
22. Freedman DX. The search: body, mind, and human purpose. Am J Psychiatry. 1992;149:858-866.
23. Okasha A, Raafat M. Neurophysiological substrate of obsessive compulsive disorder: an evidence from topographic EEG. Egypt J Psychiatry. 1990;13:97-106.
24. Perros P, Young ES, Ritson JJ, Price GW. Power spectral EEG analysis and EEG variability in obsessive-compulsive disorder. Brain Topogr. 1992;4:187-192.
25. Jenike MA, Brotman AW. The EEG in obessive-compulsive disorder. J Clin Psychiatry. 1984;45:122-124.
26. Aslanov AS. Correlation between cortical potentials in patients with obsessive neuroses. In: Rusinov VS, ed. Electrophysiology of the Central Nervous System. Haigh B, trans. New York, NY: Plenum; 1970:39-47.
27. Knolker U. EEG frequency analyses in children and adolescents with obsessive-compulsive neuroses. Z Kinder Jugenpsychiatr. 1988;16:180-185.
28. Garber JH, Ananth JV, Chiu LC, Griswold VJ, Oldendorf WH. Nuclear magnetic resonance study of obsessive-compulsive disorder. Am J Psychiatry. 1989;146:1001-1005.
29. Aylward EH, Schwartz J, Machlin S, Pearlson G. Bicaudate ratio as a measure of caudate volume on MR images. Am J Neuroradiol. 1991;12:1217-1222.
30. Kellner CH, Jolley RR, Holgate RC, et al. Brain MRI in obsessive-compulsive disorder. Psychiatry Res. 1991;36:45-49.
31. Baxter LR, Phelps ME, Mazziotta JC, et al. Local cerebral glucose metabolic rates in obsessive-compulsive disorder: a comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry. 1987;44:211-218.
32. Baxter LR, Saxena S, Brody AL, et al. Brain mediation of obsessive-compulsive disorder symptoms: evidence from functional brain imaging studies in the human and nonhuman primate. Seminars in Clinical Neuropsychiatry. 1996;1:32-47.
33. Brody AL, Saxena S. Brain imaging in obsessive-compulsive disorder: evidence for the involvement of frontal-subcortical circuitry in mediation of symptomatology. CNS Spectrums. 1996;1:27-42.
34. Zohar J, Insel T, Berman K, et al. Anxiety and cerebral blood flow during behavioral challenge: dissociation of central from peripheral and subjective measures. Arch Gen Psychiatry. 1989;46:505-510.
35. Rubin RT, Villanueva-Meyer J, Ananth J, Trajmar PG, Mena I. Regional xenon 133 cerebral blood flow and cerebral technetium 99m HMPAO uptake in unmedicated patients with obsessive-compulsive disorder and matched normal control subjects. Determination by high-resolution single-photon emission computed tomography. Arch Gen Psychiatry. 1992;49:695-702.
36. Yaryura-Tobias JH, Neziroglu FA. Organicity in obsessive compulsive disorder. Biol Psychiatry. 1991;29:337.
37. Irle E, Exner C, Thielen K, et al. Obsessive-compulsive disorder and ventromedial frontal lesions: clinical and neuropsychological findings. Am J Psychiatry. 1998;155:255-263.
38. Creasey H, Rapoport SI. The aging human brain. Ann Neurol. 1985;17:2-10.
39. Ramón Y, Cajal S. Histology of the nervous system of man and vertebrates. In: History of Neuroscience No. 6. Swanson N, trans. New York, NY: Oxford University Press; 1995;1.
40. Bunge M. El Problema Mente-Crebro: Un Enfoque Psicobiologico. Madrid, Spain: Editoriel Tecnos; 1985.
41. Sherrington C. The Integrative Action of the Nervous System. New York, NY: Scribner's Sons; 1906.
42. Jeffery, KJ, Reid IC. Modifiable neuronal connections: an overview for psychiatrists. Am J Psychiatry. 1997;154:156-164.
43. Nauta WJH, Domesick UB. Afferent and efferent relationships of the basal ganglia. In: Ciba Foundation Symposium 107. Functions of the Basal Ganglia. London, England: Pitman; 1984:2-23.
44. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986;9:357-381.
45. Gastó C. Modelos neuroanatómicos y cibernéticos. In: Ruiloba JV, Berrios GE, eds. Estados Obsesivos. Barcelona, Spain: Masson; 1995:223-260.
46. Yaryura-Tobias JH, Bebirian RJ, Neziroglu F, Bhagaban HN. Obsessive-compulsive disorders as a serotonergic defect. Research Communications in Psychology, Psychiatry, and Behavior. 1977;2:279-286.
47. Yaryura-Tobias JA, Neziroglu FA. Obsessive-Compulsive Disorder Spectrum. Washington, DC: American Psychiatric Press; 1997.
48. MacKay DM. Selves and brains. Neuroscience. 1978;3:599-606.
49. Hoche AE. Die bedeutung der symptomkomplexe in der psychiatric. Z Ges Neurol Psychiat. 1912;12:540-541.
50. Wallace ER. Psychiatry and its nosology: a historical philosophical overview. In: Sadler JZ, Wiggins OP, Schwartz MA, eds. Philosophical Perspectives on Psychiatric Diagnostic Classification. Baltimore, Md: Johns Hopkins University Press; 1994:16-86
51. Luys M. Des obsession pathologique dans leurs rapports avec 1'activité automatique des éléments nerveux. Encephale. 1983;3:20-61.
52. Hollander E, Benzaquen SD. Is there a distinct OCD spectrum? CNS Spectrums. 1996;1:17-26.
53. Aristóteles. Aristoteles' acht Bucher physik. In: Frantl K, ed. Aristoteles Werke. Aalen, Scientia; 1978.
54. Griesinger W. Mental Pathology and Therapeutics (1867). Robertson LC, Rutherford J, trans. New York, NY: Hafner Publishing; 1965.
55. Sabelli HC, Carlson-Sabelli L. Biological priority and psychological supremecy: a new integrative paradigm derived from process theory. Am J Psychiatry. 1989;142:1541-1551. home

* Dr. Yaryura-Tobias is the medical director of the Institute of Bio-Behavioral Therapy and Research in Great Neck, NY, and associate professor of psychiatry at New York University in New York City.