Neurobiology Confirms Psychopathology

Abstract

Background: Psychopathological concepts of the 19th and early 20th century postulated an antagonism between psychotic and obsessive-compulsive disorders, assuming obsessions and compulsions to have protective effects on psychotic disintegration. Although both disorders have been subject to intense multimodal research, their pathogeneses are yet to be fully understood. Methods: Here, we discuss recent neurobiological findings pointing towards opposite directions which are strongly reminiscent of the historical psychopathological antagonism. Results: Obsessive-compulsive syndromes (OCS) are efficiently treated with serotonergic substances, while on the other hand modern antipsychotic drugs exert antiserotonergic effects. Especially these atypical antipsychotic substances, however, were found to involve the risk of inducing second-onset OCS. Dopamine antagonists are potent antipsychotic substances, whereas the partial dopamine agonist aripiprazole has been associated with an antiobsessive potency. Within the glutamatergic system, reduced NMDA-dependent glutamatergic neurotransmission is discussed to be one major pathomechanism of psychotic disorders, whilst NMDA antagonists have proven to be effective in improving treatment-resistant OCS. While neurogenetic findings seem to separate the populations in heterogeneous samples, detailed neuroimaging studies suggest that both disorders affect similar neurocircuits in different manners. Conclusions: With regard to these findings, future research on schizo-obsessive syndromes will have to be multimodal, integrating psychopathology, neuropsychology, functional imaging, neurogenetics and psychopharmacology. Prospective trials involving these methods might be able to elucidate the dysbalances of neurotransmission and to locate the neuroanatomical and neuropsychological correlates. In particular, this might contribute to defining schizophrenic patients at risk for developing second-onset OCS and to evaluating new treatment strategies in patients suffering from both psychosis and OCS.

Clozapine-Induced Obsessive-Compulsive Symptoms in Schizophrenia: A Critical Review

“…Consequently they have a less favourable prognosis [8-11], in particular if recent concepts of response, remission and recovery [12,13] are applied. These well-documented facts correct former concepts, where comorbid OCS in schizophrenia were assumed to have protective effects regarding psychotic desintegration [14-18]. It is worth noting, that somatic obsessions and hoarding might indeed compensate psychotic anxiety and disorganization [11].…”

Schizo-Obsessive Disorder: A Brief Report of Neuroimaging Findings

“…The authors reported some controversial findings: (a) there are some functional and structural similarities between the neuroanatomical regions implicated in OCD and SCZ; (b) there is a partial overlap of findings between OCD and SCZ in the caudate nucleus and anterior cingulated gyrus; (c) no overlap has been found in thalamic structures, and (d) the evidence of a reduced volume of the caudate nucleus in SCZ seems to be corroborated by the precipitation of OCS by lesions to this structure in OCD patients. In a review published in 2008 by Zink et al [12], the findings were that OCS and psychotic disorders showed a variety of overlapping alterations in fMRI of frontocortical areas, such as a deficient frontocortical activation. More recently, Bleich-Cohen and colleagues published a number of articles dedicated to the characterization of schizo-obsessive patients using fMRI techniques.…”

“…Search terms included ‘schizo-obsessive' combined with ‘imaging' or ‘neuroimaging' or ‘computed axial tomography' or ‘CAT' or ‘computed tomography' or ‘CT' or ‘diffuse optical imaging' or ‘event-related optical signal' or ‘magnetic resonance imaging' or ‘MRI' or ‘functional magnetic resonance imaging' or ‘fMRI' or ‘magnetoencephalography' or ‘positron emission tomography' or ‘PET' or ‘single-photon emission computed tomography' or ‘SPECT'. As a result, a total of 9 studies were found, specifically 4 original research reports [2,8,9,10], 4 review articles [11,12,13,14] and 1 clinical case report [15]. One [9] of the above-mentioned original research articles was discarded as unrelated to the topic.…”

Reduced activity and connectivity of left amygdala in patients with schizophrenia treated with clozapine or olanzapine

“…In contrast, predominantly dopaminergic SGAs such as amisulpride [14] or the partial dopaminergic/serotonergic agonist aripiprazole [15] are two substances that rather seem to have a beneficial or at least neutral effect on OCS [16–20]. Hence, differences in receptor binding profiles of clozapine/olanzapine vs. amisulpride/aripiprazole might explain diverging effects on co-occurring OCS [21]. The assumption that SGAs aggravate OCS via an antiserotonergic mechanism also seems plausible, because treatment with selective serotonin reuptake inhibitors (SSRIs) has been proven effective in the treatment of OCD [22].…”