Obsessive-compulsive disorder - What's going on?

Pathogenesis of obsessive-compulsive disorder

Conditions resembling obsessive-compulsive disorder were first described over 300 years ago. At each stage in the development of ideas about obsessive-compulsive disorder, they have been modified by the intellectual and scientific climate of the era. In early theories, conditions resembling obsessive-compulsive disorder were explained by perverted religious experiences. English authors of the 18th and late 17th centuries attributed obsessive blasphemous images to the influence of Satan. Even today, some patients with obsessions of conscientiousness still believe themselves to be possessed by the devil and try to exorcise the evil spirit from themselves. French authors of the 19th century, discussing obsessions, emphasized the central role of doubt and indecision. In 1837, the French physician Esquirol used the term folie du doute (disease of doubt) to describe this group of symptoms. Later, French authors, including Pierre Janet in 1902, linked the development of obsessive states with loss of will and low mental energy.

For much of the 20th century, psychoanalytic theories of obsessive-compulsive disorder dominated. According to them, obsessions and compulsions are defense mechanisms that represent maladaptive attempts to cope with unresolved unconscious conflicts that originate in the early stages of psychosexual development. Psychoanalysis offers an elegant metaphor for mental activity, but it is not based on evidence from brain research. These theories have lost their appeal because they have not led to the development of effective and reproducible treatments. Psychoanalysts have focused on the symbolic meaning of obsessions and compulsions, but have not paid sufficient attention to the form of symptoms - repeated, unpleasant, meaningless, violent thoughts and actions. The content of symptoms, however, is more likely to indicate what is most important to a given patient or what frightens him or her, but it does not explain why a particular patient developed obsessive-compulsive disorder. On the other hand, the content of some symptoms, such as those associated with purging or hoarding, can be explained by the activation of stereotypical action programs (e.g. immature complex behavioral acts) implemented by those areas of the brain that are involved in OCD.

In contrast to psychoanalysis, learning theory models of obsessive-compulsive disorder have gained popularity due to the success of behavioral therapy. Behavioral therapy does not concern itself with the psychological interpretation of the meaning of symptoms. According to behavioral theories, obsessions and compulsions are reinforced first by the mechanism of classical and then operant conditioning. However, learning theory cannot explain all aspects of obsessive-compulsive disorder. For example, it cannot explain why some compulsions persist despite the fact that they cause anxiety rather than reduce it. Since compulsions are viewed as reactions to obsessions, learning theory cannot explain cases in which only compulsions are present. In addition, it cannot explain why obsessive-compulsive symptoms occur in organic brain lesions. Despite these conceptual limitations, the effectiveness of behavioral therapy based on exposure (presentation of feared stimuli) and response prevention is beyond doubt and has been confirmed in numerous studies.

Over the past 30 years, the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has remained the main target for research into the neurochemical mechanisms of obsessive-compulsive disorder. The role of serotonergic systems in the development of obsessive-compulsive disorder has been confirmed by drug trials and, above all, by the high efficacy of selective serotonin reuptake inhibitors (SSRIs). However, theories of pathogenesis that are built on the basis of the supposed mechanism of action of effective drugs may nevertheless be erroneous. It is reasonable to assume that SSRIs may 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 direct measurements of neurochemical parameters or by functional neuroimaging. Although these studies do suggest some dysfunction of the serotonergic system, they have failed to characterize it precisely and to identify the underlying defect. An example of such a study is the study of the behavioral and biochemical effects of the mixed serotonin receptor agonist/antagonist metachlorophenylpiperazine in OCD. The results of this study varied considerably not only across laboratories but also within laboratories. Unlike panic disorder, there is no evidence for dysfunction of the noradrenergic pathways in OCD.

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

1. studying the role of neurotransmitters other than serotonin;
2. elucidating the role of neural circuits in the brain;
3. identification of different subtypes of obsessive-compulsive disorder;
4. research into autoimmune mechanisms.

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

Accumulating evidence, including functional neuroimaging data, suggests that a neural circuit involving the basal ganglia and orbitofrontal cortex plays an important role in the pathogenesis of obsessive-compulsive disorder. Increased metabolic activity of the orbitofrontal cortex and anterior cingulate cortex is the most consistent finding in positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies of patients with OCD. Some researchers suggest that increased activity in these areas is a consequence of dysfunction of the caudate nucleus, which is closely associated with them. Scientists have suggested that abnormal activation of the orbitofrontal and cingulate cortex is explained by an imbalance between the direct and indirect pathways in the striatal-pallido-thalamo-cortical circuit. As a result, incoming information is mistakenly interpreted as signals of trouble, a feeling arises that “something is wrong”, and a need for certain corrective actions appears. In a patient with OCD, this process manifests itself in obsessive thoughts that disturb the patient and the activation of self-protective behavior, an example of which can be double-checking one’s actions or washing one’s hands.

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

In addition, heterogeneity explains why the results of studies on neurobiological changes in obsessive-compulsive disorder are so different. The most reasonable approach is to distinguish cases of obsessive-compulsive disorder associated with TS or chronic tics as a separate subtype. The role of dopaminergic dysfunction in TS will be discussed later. Based on experimental and clinical data, researchers have suggested that obsessive-compulsive symptoms in patients with TS are mediated or controlled by the interaction between the serotonergic and dopaminergic systems.

In recent years, it has been suggested that some cases of childhood-onset obsessive-compulsive disorder are caused by an autoimmune process triggered by infection, similar to that seen in Sydenham's chorea, a late manifestation of rheumatism. It should be noted that obsessive-compulsive symptoms are found in more than 70% of patients with Sydenham'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 neurons in the basal ganglia and other parts of the brain. Swedo coined the term PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus) to describe cases of obsessive-compulsive disorder with onset in childhood that, like Sydenham's chorea, developed acutely following a streptococcal infection and are characterized by the presence of neurological symptoms with a fluctuating course. This theory opens up a new direction that will undoubtedly be the subject of intensive research in the coming years.

In recent years, there has also been a trend to go beyond catecholaminergic neurotransmitter systems and investigate the role of other neurotransmitters in obsessive-compulsive disorder, including neuropeptides. Scientists (Leckman et al., 1994) suggested that obsessive-compulsive disorder in some patients may be based on altered neural functions associated with oxytocin. In one of their studies, oxytocin levels in the cerebrospinal fluid of patients with isolated obsessive-compulsive disorder were higher than in healthy controls and patients with tics (with or without concomitant obsessive-compulsive disorder). Additional research is needed on the possible role of neuropeptides in the pathogenesis and treatment of obsessive-compulsive disorder.