Obsessive Compulsive Disorder: What's Happening?

Pathogenesis of obsessive-compulsive disorder

Conditions that resemble obsessive-compulsive disorder, were first described more than 300 years ago. At each stage of the development of ideas about obsessive-compulsive disorder, they underwent changes under the influence of the intellectual and scientific climate of the era. In early theories, states like obsessive-compulsive disorder were explained by perverted religious experiences. English authors of the XVIII - the end of the XVII century attributed obsessive blasphemous images to the influence of Satan. Even today, some patients with obsessions of conscientiousness "still consider themselves possessed by the devil and are trying to drive out evil forces. French authors of the nineteenth century, discussing the obsessions, emphasized the central role of doubt and indecisiveness. In 1837, the French doctor Esquirol used the term "folie du doute" ("disease of doubt") - to determine this group of symptoms. Later French authors, including Pierre Janet (Pierre Janet) in 1902, associated the development of obsessive states with a loss of will and a low mental energy.

For most of the XX century, psychoanalytic theories of obsessive-compulsive disorder dominated. According to them, obsessions and compulsions are some kind of protective mechanisms that are non-adaptive attempts to cope with the unresolved unconscious conflict that takes the beginning in the early stages of psychosexual development. Psychoanalysis offers a refined metaphor for mental activity, but it is not based on evidence obtained from brain research. These theories have lost appeal, since they did not lead to the development of effective and reproducible methods of treatment. Psychoanalysts focused on the symbolic meaning of obsession and compulsion, but did not pay enough attention to the form of symptoms-repetitive unpleasant for the patient senseless violent thoughts and actions. Meanwhile, the content of symptoms rather indicates what is most important for this patient or what scares him, but this does not explain why this patient developed obsessive-compulsive disorder. On the other hand, the content of some symptoms, for example, associated with cleansing or accumulation, can be explained by the activation of stereotyped action programs (for example, immature complex behavioral acts) realized by those areas of the brain that are involved in ROC.

In contrast to psychoanalysis, models of obsessive-compulsive disorder, developed on the basis of learning theory, have gained popularity due to the success of behavioral therapy. Behavioral therapy does not puzzle itself with the psychological interpretation of the meaning of symptoms. According to behavioral theories, obsessions and compulsions are first fixed according to the mechanism of the classical, and then the operative conditioned reflex. However, the theory of learning can not explain all aspects of obsessive-compulsive disorder. For example, with its help it is impossible to understand why some compulsions persist, despite the fact that they cause anxiety, but do not reduce it. Since compulsions are seen as a reaction to obsessions, the theory of learning can not explain the cases in which there are only compulsions. In addition, from the standpoint of this theory, it is impossible to understand why obsessive-compulsive symptomatology occurs with organic lesions of the brain. Despite these conceptual limitations, the effectiveness of the method of behavioral therapy based on exposure (the presentation of anxiety-provoking stimuli) and the prevention of reaction is unquestionable and confirmed in numerous studies.

Over the past 30 years, the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) remains the main target for studies of neurochemical mechanisms of obsessive-compulsive disorder. The role of serotonergic brain systems in the development of obsessive-compulsive disorder is confirmed by the results of drug testing and, above all, by the high efficacy of selective serotonin reuptake inhibitors (SSRIs). However, theories of pathogenesis, which are based on the presumed mechanism of action of effective drugs, can nevertheless be erroneous. It is reasonable to assume that SSRIs can more likely exert their therapeutic effect by enhancing the functioning of compensatory systems that remain intact, rather than by correcting the primary defect. Confirmation of the pathogenetic role of serotonin can be obtained by studying the direct measurement of neurochemical parameters or using functional neuroimaging. Although the results of such studies, indeed, indicate a certain dysfunction of the serotonergic system, they were not able to accurately characterize it and to reveal the primary defect. An example of such studies can be the study of the behavioral and biochemical effects of a mixed agonist / antagonist of serotonin metachlorophenylpiperazine receptors in OCD. The results of this study varied significantly not only in different laboratories, but also within a single laboratory. Unlike panic disorder, no evidence of dysfunction of noradrenergic tracts has been obtained with OCD.

A new stage in the study of the pathogenesis of obsessive-compulsive disorder is associated with the development of the following areas:

1. the study of the role of other neurotransmitters, in addition to serotonin;
2. clarifying the role of neural circles in the brain;
3. identification of various subtypes of obsessive-compulsive disorder;
4. study of autoimmune mechanisms.

Some modern theories of the pathogenesis of obsessive-compulsive disorder include many of these elements.

Evidence is accumulating, including data from functional neuroimaging, which indicate an important role in the pathogenesis of obsessive-compulsive disorder of the neuronal circle, including the basal ganglia and the orbitofrontal cortex. The increase in the metabolic activity of the orbitofrontal cortex and anterior cingulate cortex is the most consistent finding in the study of patients with OCD using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Some researchers suggest that the increased activity of these zones is a consequence of dysfunction of the caudate nucleus closely associated with them. Scientists have suggested that the pathological activation of the orbitofrontal and cingulate cortex is explained by an imbalance between the direct and indirect pathways in the striato-pallido-thalamo-cortical circle. As a result, incoming information is misinterpreted as signals of trouble, there is a feeling that "something is going wrong", there is a need for certain corrective actions. In a patient with OCD, this process manifests itself obsessively disturbing the patient's thoughts and activating self-protective behavior, an example of which can be a recheck of their actions or washing their hands.

It is generally accepted that obsessive-compulsive disorder is an etiologically heterogeneous state. Direct evidence is provided by practice. In the literature, there are numerous reports on the development of obsessive-compulsive symptoms in Enconomium encephalitis, craniocerebral trauma, carbon monoxide poisoning, stroke, rheumatic chorea (Sydenham's chorea), Huntington's disease and other bilateral injuries of the basal ganglia. The wide variability manifested in the response to treatment, flow, the spectrum of concomitant disorders, also indicates the heterogeneity of obsessive-compulsive disorder.

In addition, heterogeneity explains why the results of the study of neurobiological changes in obsessive-compulsive disorder are so different. The most justified isolation as a separate subtype of cases of obsessive-compulsive disorder associated with CT or chronic tics. Later, the question of the role of dysfunction of dopaminergic systems in CT will be discussed. Based on experimental and clinical data, the researchers suggested that obsessive-compulsive symptomatology in patients with CT is mediated or controlled by the interaction between serotonergic and dopaminergic systems.

In recent years, it has been suggested that some cases of obsessive-compulsive disorder with onset in childhood are caused by an autoimmune process triggered by an infection and similar to what occurs with Sydenham chorea, one of the late manifestations of rheumatism. It should be borne in mind that obsessive-compulsive symptoms are detected in more than 70% of patients with Sidenham's chorea. The development of Sydenham's chorea is associated with the formation of antibodies to group A beta-hemolytic streptococcus, which cross-react with the neurons of the basal ganglia and other parts of the brain. Swedo introduced the term PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus) to describe cases of obsessive-compulsive disorder with onset in childhood, which, like Sydenham's chorea, developed sharply following streptococcal infection and are characterized by the presence of neurological symptoms with a fluctuating course. This theory opens a new direction, which, undoubtedly, will be the subject of intensive research in the coming years.

In recent years, there has also been a tendency to go beyond the catecholaminergic neurotransmitter systems and to explore the role of other neurotransmitters in obsessive-compulsive disorder, including neuropeptides. Scientists (Leckman et al., 1994) suggested that the basis of obsessive-compulsive disorder in some patients may be a change in the neuronal functions associated with oxytocin. In one of their studies, the level of oxytocin in the cerebrospinal fluid in patients with isolated obsessive-compulsive disorder was higher than in healthy and patients with tics (with or without accompanying obsessive-compulsive disorder). Further research is needed on the possible role of neuropeptides in pathogenesis and the treatment of obsessive-compulsive disorder.