Autistic traits and cognitive profiles of treatment-resistant schizophrenia

Abstract

The complex pathophysiology of treatment-resistant schizophrenia (TRS) includes severe positive symptoms but also other symptom domains. The overlapping psychological profiles of schizophrenia and autistic spectrum disorder (ASD) are not established. We compared TRS patients (n = 30) with schizophrenia patients in remission (RemSZ, n = 28) and ASD patients (n = 28), focusing on both neurodevelopmental aspects and general and social cognitive impairments. The TRS group performed the worst on general neurocognition (measured by the MATRICS Consensus Cognitive Battery) and social cognition (measured by the theory of mind and emotional expression). The RemSZ group performed the best among the three groups. Regarding autistic traits, all measurements by the Autism-Spectrum Quotient/Autism Screening Questionnaire/Pervasive Developmental Disorder Assessment Rating Scale showed that (1) the ASD patients had the highest autistic traits (2) the TRS patients' scores were less severe than the ASD group's, but (3) the overall trends placed the TRS group between the ASD and the RemSZ group. These findings indicate that TRS patients and remitted patients could have distinctive neurodevelopmental and cognitive profiles. Further, the degrees of social cognitive dysfunction and autistic traits in TRS patients could be close to those of ASD patients, suggesting similarities between TRS and ASD.

Altered Neuroanatomical Signatures of Patients With Treatment-Resistant Schizophrenia Compared to Patients With Early-Stage Schizophrenia and Healthy Controls

“…In the comparison of TRS and ES-S subjects, only verbal memory was significantly worse in the TRS group, similar to another study ( 17 ). However, most previous studies reported overall cognitive dysfunction in TRS compared to NTRS ( 20 , 57 , 58 ). This may be due to the mild level of symptoms in our TRS group (mean PANSS total score, 61.96 ± 19.10), whereas other studies recruited TRS patients with mean PANSS total scores ranging from 71 to 91.…”

Autistic Symptoms in Schizophrenia: Impact on Internalized Stigma, Well-Being, Clinical and Functional Characteristics

“…These findings are of considerable clinical relevance: as individuals with prominent ASD features appear to be characterized by specific features, they could present substantial differences in the response to specific treatments. In fact, recent evidence suggests that ASD symptoms appear to be associated with poorer response to antipsychotic treatment in schizophrenia ( 24 , 25 ), a finding that could be indirectly related to the greater symptoms severity observed in “Autistic schizophrenia” participants. These patients, however, could represent valid candidates to targeted psychosocial interventions: for instance, cognitive remediation appears to produce greater cognitive and functional gains in participants that are more clinically compromised ( 74 , 75 ).…”

“…In fact, according to a recent network analysis, ASD features appear to be negatively and more closely related to social functioning than psychotic symptoms in people diagnosed with psychotic disorders or with familiar risk for psychosis ( 23 ). ASD features also appear to be associated with poorer response to antipsychotic treatment ( 24 , 25 ) and to a particular coping profile ( 26 ). A recent study, conducted on a large sample of people living with schizophrenia, found that participants with prominent ASD symptoms show poorer performance on most neurocognitive domains and in social cognition, as well as poorer functional capacity, real-world interpersonal relationships and participation in community-living activities, but better social acceptability ( 27 ).…”

Interacting Roles of COMT and GAD1 Genes in Patients with Treatment-Resistant Schizophrenia: a Genetic Association Study of Schizophrenia Patients and Healthy Controls

“…Recent studies of TRS patients indicated that the synthesis of dopamine or the dopamine volume in the synaptic clefts could differ in patients with TRS compared to other schizophrenia patients who achieve a good response to antipsychotic medications [Demjaha et al, 2012;Kim et al, 2017]. Several studies uniformly observed that more severe cognitive impairments in TRS patients [Joober et al, 2002;de Bartolomeis et al, 2013;Frydecka et al, 2016;Nakata et al, 2020 Buzsáki et al, 2004]. It was also reported that clozapine could enhance GABA signal transduction [Daskalalis et al, 2008;Liu et al, 2009;Kaster et al, 2015;Miyazawa et al, 2021].…”

“…It is estimated that the neural networks involving these negative domains could differ from the networks underlying positive symptoms: that is, glutamatergic and γ-aminobutyric acid (GABA) systems in the cortical area could be more directly involved in the origins of negative symptoms and cognitive dysfunctions [Schwartz et al, 2012;McCutcheon et al, 2020]. Several studies indicated that patients with TRS show more profound cognitive impairment compared to general (non-TRS) patients with schizophrenia [Joober et al, 2002;de Bartolomeis et al, 2013;Frydecka et al, 2016;Nakata et al, 2020]. Abnormalities in parvalbumin-positive GABA interneurons and lowered expressions of mRNA/protein of glutamic acid decarboxylase1 (GAD1) in the brains of individuals with schizophrenia have been consistently reported from multiple post-mortem studies, and these ndings are suggested to be related to the lower expression of γ-oscillation and cognitive dysfunctions in living patients with schizophrenia [Tallon-Baudry et al, 1998;Fries et al, 2001;Lewis et al, 2008;Buzsáki et al, 2004].…”