Neurodevelopment regulators miR-137 and miR-34 family as biomarkers for early and adult onset schizophrenia
Early diagnosis of schizophrenia and detection of patients at high or ultrahigh risk of schizophrenia are current important issues in psychiatry. However, the conventional diagnostic criteria of schizophrenia, as proposed in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and International Classification of Diseases (ICD-10) show very low sensibility and a lack of reliability for early diagnosis of schizophrenia. Among the reasons that could explain these difficulties (especially in the context of early onset schizophrenia, EOS), some authors have suggested that DSM and ICD diagnostic criteria have simplified the clinical features of schizophrenia and consequently capture only a fragment of the clinical core of schizophrenia. More precisely, alterations of subjective experience, such as distortions of the perception of self are neglected, although alterations of the sense of self in schizophrenia have been reported in most seminal texts as well as in phenomenological descriptions of schizophrenia. Schizophrenia is nowadays considered as a disorder of the self. Self-consciousness disturbances in schizophrenia are various and can include different problems such as altered body self-consciousness, agency impairments, or social cognition disorders. According to several authors, self-consciousness disturbances are expressed in schizophrenia through notably difficulties of self-other differentiation. Identification of such disturbances might be clinically useful for identifying individuals with schizophrenia or at risk of schizophrenia.
Schizophrenia is a chronic psychiatric disorder with a prevalence of approximatively 0.3%-0.7% and typically adult onset schizophrenia (AOS, at age ≥18 years). The most common definition of EOS (prevalence of approximatively 0.03%) and very early onset schizophrenia (VEOS, prevalence of approximatively 0.002%) is, respectively, schizophrenia with onset before age 18 years and schizophrenia with onset before age 13 years. Research on EOS and VEOS remains limited due to their low prevalence and their lack of specificity in the DSM-5 or ICD-10 diagnostic classifications. A better understanding and detection of EOS and VEOS is nonetheless necessary, considering that early diagnosis and treatment of schizophrenia are associated with better prognosis.
Self-consciousness allows both self-recognition and self-other differentiation and is the basis of social interactions. Self-consciousness develops through a long process that starts in the first years of life and is reworked throughout an individual's life. Paul Schilder proposed the concept of body image to designate the way a person recognizes his or her body and face as being his or her own. The term body image may be considered restrictive because the concept of self is not only limited to visual perception. Ulric Neisser described two different perceptual aspects of self-development, first through body perceptions and interactions with external objects, and second through the relation to others, based on ideas already developed by Henri Wallon. Wallon has observed and studied how individuals, from an early age, interact with their environment through the body and use mirrors as a support of self-recognition. René Zazzo, inspired by Wallon, observed very young children and their reactions to their own images. He described, notably, the way in which recognition of others (acquired from 8 months) precedes by far self-recognition (acquired at approximately 2 years old) across different visual media (mirror, photo, film) with progressive awareness of the own body image concurrently with language development. This suggests that language development, in terms of its social communication dimension, requires self-other differentiation. More recently, these models and ideas were re-examined and enriched by several authors such as Damasio, Rochat, Decety, and Sommerville (Table 1). Other authors focused on the comprehension of the sensory component of self-consciousness and the key role of the body as the interface between self and the environment. They also described how body self-consciousness can vary depending on the sensory stimuli to which the body is exposed. The body becomes as much a component of self-consciousness (body self), as a receptacle of diverse sensory information that facilitates the development of self-consciousness over the lifespan.
Self-consciousness can be impaired in one or several of its components (identity, body, etc.). Self-recognition, and notably self-image recognition, can be disturbed in various disorders, including neurodegenerative disorders (such as dementia) and neurodevelopmental disorders (such as schizophrenia and Autism Spectrum Disorder). Studying impairments in self-consciousness and self-recognition may open important perspectives, especially for early diagnosis of schizophrenia and the development of adapted therapeutic strategies. However, a limit of such phenomenological inquiry remains the detection of these disturbances that relies on patients' verbal reports. These patients' reports should indeed be interpreted with caution, especially since body self is related to non-verbal aspects of consciousness. Thus a challenge consists in finding a way to quantify objectively such self-disturbances in schizophrenia with a non-verbal approach. As underlined by Tordjman and Mailhes, self-image development might be a good indicator of the evolution of the self-consciousness process, especially through self-image recognition in the mirror. The mirror was already used to observe pathological self-perception in mental disorders. Salem Shentoub was the first to report disturbances of self-image recognition in the mirror in intellectually disabled children. François Achille Delmas and Paul Abely both described at the onset of schizophrenia the "mirror sign," referring to the need of certain individuals with schizophrenia to observe themselves frequently and during a long time when facing a reflecting surface.
A new paradigm developed by Thirioux et al., based on the alter ego system designed and programmed by Moritz Wehrmann, allows specifically self-other differentiation and self-consciousness to be explored through self-other image recognition in the mirror. This paradigm can be used to study self-image recognition impairment in schizophrenia.
The objective of the present study was to examine self-other recognition in EOS and AOS individuals compared to typically developing controls (TDC) based on a new experimental paradigm using a mirror system and to examine effects of intermodal sensory perception on self-other differentiation.