Physiological foundations of obsessive-compulsive disorder

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The physiology of Obsessive Compulsive Disorder has been the subject of research since the 1970s. The leading hypotheses relate to changes in the prefrontal cortex , basal ganglia, and the limbic system . Obsessive-compulsive and obsessive-compulsive spectrum disorders as a result of an autoimmune disease are also discussed for a subgroup of patients.

Neuroanatomy / Neurophysiology

The results of numerous studies indicate that these three brain areas are particularly involved: the orbitofrontal cortex , the anterior cingulate gyrus and the head of the caudate nucleus . These brain areas are connected to the basal ganglia in a highly complex manner. Accordingly, recent theories suggest that obsessive-compulsive disorder is associated with an imbalance in the direct and indirect signaling pathways through the basal ganglia. Research on the treatment of severe therapy-resistant obsessive-compulsive disorder using deep brain stimulation showed that both the caudate nucleus and the accumbens and subthalamic nucleus appear to be involved in the functional process of an obsessive-compulsive disorder and thus represent possible target regions for stimulation. While the effect of the direct signal path is excitatory , the effect of the indirect signal path is inhibitory . The relatively increased activation could lead to a positive feedback loop, whereby thoughts of an obsessive character manifest themselves. It remains unclear why specific, thematically limited obsessions develop, how this thematic restriction comes about and why a state of generalized obsessions (equally strong on all topics) is unknown in the clinical picture.

Neurochemistry

Pharmacological studies have focused on the role of the serotonin (5-HT) neurotransmitter system . The effect of selective serotonin reuptake inhibitors (SSRIs) in obsessive-compulsive disorder seems to be stronger than that of psychotropic drugs, which act selectively on the metabolism of other messenger substances . These findings are supported by studies that show that the administration of 5-HT antagonists is suitable for exacerbating the symptoms of obsessive-compulsive disorder. However, more recent studies point in the direction of the involvement of other messenger substances, above all glutamine , dopamine and acetylcholine . The hypothesis of a change in the complex interaction of these messenger substances in obsessive-compulsive disorder also fits with the observation that the onset of action in the treatment of obsessive-compulsive disorder with selective serotonin reuptake inhibitors takes place more slowly than is the case, for example, with depression . This is interpreted by some researchers as an indication that the effect of the selective serotonin reuptake inhibitors is not only due to an effect on the serotonin metabolism, but as a consequence of a shift in the further brain metabolism through changes in the serotonin metabolism.

Neuroimmunology

After the discovery of the PANDA syndrome , there were indications that some of the obsessive-compulsive disorder could have an autoimmune basis, with the basal ganglia being defined as the crucial brain area. The Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) describes the hypothesis of a neurological-psychiatric disorder that sets in rapidly in childhood and is associated with compulsive behavioral stereotypes or tics. The generic term PANS includes non-infectious causes such as metabolic disorders as well as all possible infectious triggers, the latter under the group name “Pediatric Infection-Triggered Autoimmune Neuropsychiatric Disorders” (PITANDS). PANDA syndrome, an infection associated with neurological symptoms caused by β-hemolytic streptococci of group A , now forms the streptococcal subgroup of PITANDS. The results of the PANS / PITANDS / PANDAS research match findings that obsessive-compulsive behavioral stereotypes also occur in other neurological disorders that affect the basal ganglia. These include: Tourette's syndrome , Parkinson's , epilepsy , schizophrenia , Huntington's disease and minor chorea . A number of studies refer to the effectiveness of immunomodulatory therapeutic approaches using plasmapheresis or IV immunoglobulins . Long-term studies have shown a sustained and long-term improvement in the clinical picture through antibiotic prophylaxis and the prevention of streptococcal infections. In the 1990s it was also possible to prove that the B-lymphocyte antigen D8 / 17 is increased in patients with diseases from the compulsive spectrum. In addition, various autoimmunological parameters, e.g. B. pathological autoantibodies detected. One study found an increased incidence of anti-basal ganglia antibodies in patients with obsessive-compulsive disorder, comparable to Sydenham's chorea .

genetics

Genetic factors in the development of obsessive-compulsive disorder have been studied repeatedly. Evidence for a genetic connection emerges from the observation that parents and siblings of obsessive-compulsive patients are on average more likely to develop obsessive-compulsive disorder. The Hopkins family study found that the prevalence of OCD in first-degree relatives is 11.7%, while it is only 2.7% in more distant relatives. Study results also suggest a genetic connection, which showed an agreement of obsessive-compulsive symptoms in identical twins between 80% and 87%, whereas it was only between 47% and 50% for dizygoti twins. A study puts the hereditary share in classic obsessive-compulsive disorder at 45–65% (children) and 27–47% (adults), but also names the need for further research in this area. The current state of neurogenetic research therefore points to a genetic component in the sense of increased vulnerability . So far, specific gene segments could not be isolated. It also remains open to what extent the influence of shared environmental factors (e.g. in the family of origin) plays a role.

Individual evidence

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