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A Double Dissociation Between Two Psychotic Phenotypes: Periodic Catatonia and Cataphasia

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A Double Dissociation Between Two Psychotic Phenotypes: Periodic Catatonia and Cataphasia Prog Neuropsychopharmaco Biol Psych 2018 Aug 30;86:363-369 doi: 10.1016/j.pnpbp.2018.03.008 A Double Dissociation Between Two Psychotic Phenotypes: Periodic Catatonia and Cataphasia Foucher Jack René*,1,2, Zhang Yi Fan1, Roser Mathilde1,2, Lamy Julien1, De Sousa Paulo Loureiro1, Weibel Sébastien3,4, Vidailhet Pierre3,4, Mainberger Olivier1,2, Berna Fabrice3,4 1. ICube – CNRS UMR 7357, Neurophysiology, FMTS, University of Strasbourg, France. 2. CEMNIS – Noninvasive Neuromodulation Center, University Hospital Strasbourg, France. 3. Physiopathologie et Psychopathologie Cognitive de la Schizophrénie – INSERM 1114, FMTS, University of Strasbourg, France. 4. Pôle de Psychiatrie, Santé Mentale et Addictologie, University Hospital Strasbourg, France. Abstract: Schizophrenia as a single liability model was confronted to the multiple psychotic phenotypes model proposed by the Wernicke-Kleist-Leonhard school, focusing on two: periodic catatonia (PC) and cataphasia (C). Both are stable and heritable psychotic phenotypes with no crossed liability and are coming with the buildup of specific residual symptoms: impairment of psychomotricity for PC and a specific disorganization of thought and language in C. Regional cerebral blood flow (rCBF) was used as a biomarker. We attempted to refute the single phenotype model by looking at relevant and specific rCBF anomalies for PC and C, that would exceed anomalies in common relative to controls (CTR), i.e. looking for a double dissociation. Twenty subjects with PC, 9 subjects with C and 27 matched controls had two MRI QUIPSS-II arterial spin labeling sequences converted in rCBF. One SPM analysis was performed for each rCBF measurement and the results were given as the conjunction of both analysis. There was a clear double dissociation of rCBF correlates between PC and C, both being meaningful relative to their residual symptomatology. In PC: rCBF was increased in the left motor and premotor areas. In C: rCBF was decreased bilaterally in the temporo-parietal junctions. Conversely, in both (schizophrenia): rCBF was increased in the left striatum which is known to be an anti-psychotics’ effect. These evidences refuted the single schizophrenia model and suggested better natural foundations for PC and C phenotypes. They plead for further research on them and further research on naturally founded psychotic phenotypes. Click here for a short introductory presentation (6 min) Key words: Schizophrenia; Endogenous Psychosis; Periodic Catatonia; Cataphasia; Regional Cerebral Blood Flow; Functional Brain Imaging. * Corresponding Author: Foucher, Jack René. CEMNIS (UF 4768) - Centre de neuromodulation Non Invasive de Strasbourg, Hôpitaux Universitaires de Strasbourg, 1 place de l'hôpital, BP 426, 67 091 Strasbourg cedex. Mail : [email protected] / [email protected]. Tel: +33 3 88 11 69 21. Clinical trial: ClinicalTrials.gov n° NCT02868879. 1 Periodic Catatonia vs Cataphasia - Foucher et al. analysis in a multiplex family study for predicting 1. Introduction heritability (11). We wanted to push the same The field of endogenous psychoses (1) is the one for question a little bit further in looking at brain which “cerebral diseases hypotheses” are the most correlates of these phenotypes. likely in psychiatry. But the failure to validate For the purpose of this study, both schizophrenia and schizophrenia as a model has generated a great schizo-affective disorders, as operationalized in the skepticism against the traditional naturalist DSM-5, were considered together as being part of paradigm of scientific medicine which supposes the the “single” schizophrenia model, which was existence of “natural morbid entities”, i.e. diseases confronted to the WKL “multiple” phenotypes (2). According to this framework, a disease is a model. Only two of the phenotypes that are regularly biological model of the "pathological dysfunction" taken for schizophrenia were used because of their able to account for a specific phenotype, i.e. clinical frequency: C and PC. Both have an estimated manifestations. The validation process of a disease prevalence between 0.1 and 0.2% of the West- model generally starts with the “correlation European population (12). Depending on the method” (3), looking for a robust and specific episode, both phenotypes generally fall within the association of the putative phenotype with a schizoaffective and schizophrenic disorders biomarker. We questioned the “single” according to ICD / DSM criteria although other schizophrenia model and confronted it to the diagnosis such as depressive, bipolar, or non- “multiple” psychotic phenotypes model proposed by otherwise specified bipolar or psychotic disorders the Wernicke-Kleist-Leonhard (WKL) school focusing might be determined for an episode (13). Both on two of them: periodic catatonia (PC) and typically have a bipolar relapsing-progressive course. cataphasia (C). This means that both excited and inhibited phases As the other ICD / DSM diagnoses, schizophrenia and can be observed and that their respective specific schizo-affective disorders were constructed by residual symptoms will progressively increase consensus, a procedure that only favors minimal especially after each relapse. Both phenotypes are common views. Following Carl Hempel, Rober among the most hereditable WKL “psychotic” Spitzer only focused on the strengthening of their phenotypes, with affected first degree relatives’ reliability (4), not questioning their natural percentage, ranging between 15-26% depending on foundations as proposed by Eli Robin and Samuel the study (12,14,15). PC has a major susceptibility Guze (5). Definitions of natural phenotypes are locus on chromosome 15q15 (MIM 605419)(15). generally constructed by an optimization process Importantly, C and PC appear to be independent consisting in a back and forth between observation phenotypes as there is no crossed inheritance and description, which could not go on if the (12,14). The core residual symptoms of the definition remained fixed (6). To our knowledge, only cataphasic phenotype consist in a disordered logic or the Wernicke-Kleist-Leonhard (WKL) school incoherence and a specific language disorder, sustained this optimization effort over three affecting both syntax and semantic (7). This is generations, guided by three specifications of the especially present during the episode, variably principle of parsimony (1) (see S1). This ended up associated with unspecific affective or psychotic with the distinction of 35 major phenotypes which features, but it is also more and more apparent span from affective to psychotic disorders, with 22 of between the episodes while the phenotype them being able to fulfill the DSM-5’s schizophrenia progresses. Conversely, the core residual symptoms diagnosis (7). All have a good reliability (8), but also of PC consist in a quantitative and qualitative excellent predictive validity (9) and differential disorder of psychomotricity (7). validity on age of onset, inheritance, fetal event and This study intends to confront the single treatment response (1). schizophrenia model to the PC and C independence Previous attempt to select among the best model, using a comprehensive biological marker, the categorical model used heritability as an external whole brain regional cerebral blood flow (rCBF). We validator. The WKL framework outperformed the anticipated two main issues. 1) PC and C show the DSM-III in a twin study (10) and more recently the same rCBF changes in the same brain regions relative DSM-IV, ICD-10 and an exploratory latent class to controls (CTR), without any phenotype-specific changes. This would validate schizophrenia as a 2 Periodic Catatonia vs Cataphasia - Foucher et al. single liability model, especially if the changes had symptoms using the Calgary Depression Scale some relevance for psychosis proneness. 2) PC and C (CDSS)(23) and according to the eight dimensions of have specific anomalies, and these anomalies are the Clinician-Rated Dimension of Psychosis Symptom relevant with their core symptoms. This would Severity (CRDPSS)(17). Specific catatonic symptoms refute, in the Popperian sense, the single were evaluated using the Bush and Francis Catatonia schizophrenia model and provide some validation to Rating Scale (BFCRS)(24) whereas specific cataphasic PC and C as independent phenotypes. Specificity was symptoms were evaluated using the French version operationalized as a double dissociation between PC of the psychic experimental test operationalized for and C (16), which means that PC had to differ from Cataphasia (TePEO-C)(25), an operationalized CTR in the same regions than it differed from C and version of the test used by the WKL school for vice versa. thought and language disorders. Antipsychotics doses were converted to olanzapine equivalent 2. Material and methods (OLZ)(26), and benzodiazepines doses were 2.1. Participants converted to diazepam equivalent (DZP)(27). Thirty-one patients were recruited by WKL-trained 2.2. Imaging Protocol psychiatrists (MR, OM, SW, FB, JF) from the non- The scanner was a 3 Tesla VERIO with a 32-channel invasive neuromodulation center and the university head receiver antenna (Siemens, Erlangen, psychiatric ward of Strasbourg, by convenience Germany). All scanning session took place in the sampling method. They had to be right-handed, aged morning, and participants were instructed to have a between 18 and 65 years, in outpatient setting, good night before, not taking more than one cup of stabilized for more than
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