Neural dynamics in co-morbid schizophrenia and OCD: A computational approach

The co-morbidity of obsessive-compulsive disorder (OCD) and schizophrenia is higher than what would be expected by chance and the common underlying neuropathophysiology is not well understood. Repetitive stereotypes and routines can be caused by perseverative thoughts and motor sequences in both of these disorders. We extended a previously published computational model to investigate cortico-striatal network dynamics. Given the considerable overlap in symptom phenomenology and the high degree of co-morbidity between OCD and schizophrenia, we examined the dynamical consequences of functional connectivity variations in the overlapping network. This was achieved by focusing on the emergence of network oscillatory activity and examining parameter sensitivity. Opposing activity levels are present in orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) in schizophrenia and OCD. We found that with over-compensation of the primary pathology, emergence of the other disorder can occur. The oscillatory behavior is delicately modulated by connections between the OFC/ACC to the ventral and dorsal striatum and by the coupling between the ACC and dorsolateral prefrontal cortex (DLPFC). Modulation on cortical self-inhibition (e.g. serotonin reuptake inhibitor treatment) together with dopaminergic input to the striatum (e.g. anti-dopaminergic medication) has non-trivial complex effects on the network oscillatory behavior, with an optimal modulatory window. Additionally, there are several disruption mechanisms and compensatory processes in the cortico-striato-thalamic network which may contribute to the underlying neuropathophysiology and clinical heterogeneity in schizo-obsessive spectrum disorders. Our mechanistic model predicts that dynamic over-compensation of the primarily occuring neuropathophysiology can lead to the secondary co-morbid disease.