Uncategorized

Schizophrenic Spectrum Disorders (Italian Edition)

Tuesday, August 20, 2019Tuesday, August 20, 2019 admin

In addition, the well-known difficulty to recognize social cues from the actions of others is tightly related to deficit in theory of mind that is a characteristic feature common to both SSD and ASD 5. In this context, it is critically important to underscore that the negative symptoms of SSD are often more disabling and more resistant to treatment than the so-called positive ones, e.

These negative symptoms include social avoidance and emotional flatness and might be regarded as closely linked to impairments in social communication and motivation. These so-called negative symptoms of SSD might be considered to fall within the same domain of social impairment as the social difficulties characteristic of ASD. Other pathognomonic features common to both conditions include impairments in facial recognition and emotion processing 7 , 8. Patients with both ASD and SSD have been shown to have significant difficulties in interpreting social cues associated with eye gaze and deficits on theory of mind tasks—one of the hallmarks of ASD.

Autism spectrum disorders and SSD share biological underpinnings that may emerge in early neural development and unfold during subsequent childhood development 9. It has to be mentioned that neurodevelopmental disorders are associated with known genetic abnormalities both in ASD and SSD phenotypes, as detailed in Table 1. These shared patterns suggest that the two spectra are likely to represent outcomes of common pathophysiological mechanisms. Glutamate and GABA are, respectively, the two main neurotransmitters involved in excitatory and inhibitory signaling in the brain.

Schizophrenia Spectrum Disorders

Such imbalances may arise from disturbances in neural circuit formation or, abnormalities in the genes which code for proteins involved in these processes and linkage and association studies have been implicated in ASD and SSD The synapse organizers neurexins and their binding neuroligins are implicated in the formation and maintenance of excitatory and inhibitory synapses.

In turn, an increased number of activated microglia cells in adults with ASD have been found Such an increase is likely to be implicated in seizures, macrocephaly, and core ASD symptoms The E—I ratio in neocortical structures is determined by pyramidal glutamatergic neurons and inhibitory GABAergic parvalbumin PV -positive interneurons that are modulated and fine-tuned by minicolumns groups of functionally autonomous neurons whose afferent and efferent connections influence the functioning of microcircuits which have been found to be abnormal in ASD 27 , There are a number of candidate mechanisms for glutamatergic hyperactivity-driven hyperexcitability.

Neuroligins NL1—4 and neurexins Nrxns 1—3 have been linked with ASD via point mutations and truncations, and chromosomal rearrangements have been identified in the region of interest 29 — Induced pluripotent stem cells iPSCs have been used to investigate putative abnormalities in neural substrate of individuals with ASD. Even if no known underlying genomic mutation could be identified in a new study herein presented, interestingly, transcriptome and gene network analyses revealed upregulation of genes involved in cell proliferation, neuronal differentiation, and synaptic formation.

Disrupted NMDAR function is implicated in altered neurodevelopment and may play a role in the progression of symptoms for SCZ especially for cognitive deficits 41 — NRG1and ErbB4 genes deserve attention, are expressed at excitatory synapses, and regulate spine structure and function. ErbB4 deletion is associated with neurodevelopmental abnormalities that are consistent with SSD 46 , The disrupted in SCZ 1 gene DISC1 is another important candidate gene implicated at different levels of neurodevelopment through a scaffolding protein and different mutations have been detected in SCZ emphasizing its role 48 , Hallucinations have been linked to inhibitory deficits such as impaired GABA transmission unfolding in a series of abnormalities such as impaired NDMA receptor plasticity, reductions in gamma frequency oscillations, sensory cortical hyperactivity, and cognitive inhibition deficits.

This elevated risk is not associated with any other neurogenetic syndrome.

Perspective ARTICLE

Social cognition is impaired in 22q Schizophrenia spectrum disorders and ASD have been described as polygenic disorders in which the onset and progression of disease are triggered by interactions among multiple susceptibility genes. Two lines of mutant mice with Shank3 mutations linked to ASD and SSD have been documented with shared and distinct synaptic and behavioral phenotypes. Mice with the ASD-linked InsG mutation manifest striatal synaptic transmission defects before weaning age and impaired juvenile social interaction, coinciding with the early onset of ASD symptoms. On the other hand, adult mice carrying the SCZ-linked RX mutation demonstrated synaptic defects in prefrontal cortex and social dominance behavior.

This is a paradigmatic example of different alleles of the same gene that have distinct phenotypes at molecular, synaptic, and circuit levels which may inform exploration of these divergences in human patients Dysregulation of the mTOR pathway in these conditions provides clues to the molecular pathophysiology of ASD as the synaptic and cellular alterations involved may converge to produce the core social impairment of these disorders In addition, mTOR inhibitor compounds have the potential to reverse many of the behavioral and neurophysiological abnormalities associated with ASD Dysfunction of diverse upstream activators and environmental stressors, that have been previously implicated in SCZ, can lead to either over-activation or inhibition of the signaling pathway.

As well, a putative depression of mTOR signaling with possible variation between and within brain regions affecting neuronal functioning in variable fashion has been proposed. Consistently, a preponderant decrease in glutamatergic activity with respect to GABAergic activity has been reported In this functional and still undefined background, abnormal synaptic function may be related to positive and negative symptoms of SSD Lastly, mTOR signaling undergoes variations as neurodevelopment unfold and environment plays a significant role especially through early life experiences that needs to be thoroughly considered There is epidemiological, clinical, neurobiological, and genetic evidence for a close relationship between ASD and SSD, and significant overlap in symptoms is frequently observed; however, there are also differences in clinical presentation, behavioral phenotype, and developmental trajectory.

The ways in which these shared mechanisms contribute to specific phenotypes such as ASD and SSD are still largely unknown. Shedding light on the shared functions of candidate genes for involvement in ASD and SSD is the key to translating genetic findings into descriptions of developmental and clinical subtypes. As to neuronal dysfunction hypothesized, abnormalities might be specific affecting only a subset of synapses in a selective group of neurons responsible of distinct symptoms but all that is still an hypothesis as evidence on the brain circuits potentially involved is lacking.

Research domain criteria RDoC project seems particularly indicated to this scope as it is directed to implement all the above level of understanding. One of the main purpose is to investigate mental illness through the dimensional approach to the fundamental components of behavior, through individual symptoms or symptom clusters, that cut across diagnoses, in this case specifically in ASD and SSD domains Aim and legacy of RDoC novel approach is to build a research perspective that reflects advances in genetics, neuroscience, and behavioral science to provide a foundation for precision diagnosis and treatment of complex mental disorders such as those herein examined.

These individuals do not fit under any of the current diagnostic labels listed under ASD and SSD and further research through an RDoC approach holds promise to describe the specific biobehavioral profiles and thus eventually establish the diagnostic category in which they should be included. RC and Mauro Pallagrosi equally participated in the substantial contribution to the conception or design of the work; drafted the work and revised it critically for important intellectual content; approved the final version to be published; and are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be constructed as a potential conflict of interest. Schizophrenia and autism-related disorders. Schizophr Bull 41 2: Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association Autism spectrum disorders and childhood-onset schizophrenia: Childhood onset schizophrenia and early onset schizophrenia spectrum disorders.

King BH, Lord C. Is schizophrenia on the autism spectrum? Brain Res Marwick K, Hall J.

Social cognition in schizophrenia: Social cognition and its neural correlates in schizophrenia and autism. CNS Spectrums , 9 5 , American Psychiatric Association A comparison of neuroimaging findings in childhood onset schizophrenia and autism spectrum disorder: Frontiers in Psychiatry , 20 4 , The life course of schizophrenic children. Biological Psychiatry , 2 2 , Theory of mind impairment in schizophrenia: Schizophrenia Research, , Twin studies of schizophrenia: American journal of medical genetics, 97 1 , Computer-aided neurocognitive remediation as an enhancing strategy for schizophrenia rehabilitation.

Psychiatry Research , 3 , Autistic disorders and schizophrenia: An anatomical likelihood estimation.

PLoS One , 5 8 , e The association between autism and schizophrenia spectrum disorders: A review of eight alternate models of co-occurrence. Neuroscience and biobehavioral reviews , 55 , The Kraepelinian dichotomy - going, going British Journal of Psychiatry. Revisiting the relationship between autism and schizophrenia: Annual review of clinical psychology , 9 , Commonalities in social and non-social cognitive impairments in adults with autism spectrum disorder and schizophrenia.

Schizophrenia Research , , Childhood and current autistic features in adolescents with schizotypal personality disorder. Modifiable risk factors for schizophrenia and autism--shared risk factors impacting on brain development. Neurobiology of Disease , 53 , Schizophrenia and autism-related disorders. Schizophrenia Bullettin , 41 2 , Autistic disturbances of affective contact. The Nervous Child , 2 , Is schizophrenia on the autism spectrum?

Brain Research , , Modified by de Lacy and King 9. Glutamate and GABA are, respectively, the two main neurotransmitters involved in excitatory and inhibitory signaling in the brain. Such imbalances may arise from disturbances in neural circuit formation or, abnormalities in the genes which code for proteins involved in these processes and linkage and association studies have been implicated in ASD and SSD The synapse organizers neurexins and their binding neuroligins are implicated in the formation and maintenance of excitatory and inhibitory synapses.

This elevated risk is not associated with any other neurogenetic syndrome. Social cognition is impaired in 22q Schizophrenia spectrum disorders and ASD have been described as polygenic disorders in which the onset and progression of disease are triggered by interactions among multiple susceptibility genes. Two lines of mutant mice with Shank3 mutations linked to ASD and SSD have been documented with shared and distinct synaptic and behavioral phenotypes.

Mice with the ASD-linked InsG mutation manifest striatal synaptic transmission defects before weaning age and impaired juvenile social interaction, coinciding with the early onset of ASD symptoms. On the other hand, adult mice carrying the SCZ-linked RX mutation demonstrated synaptic defects in prefrontal cortex and social dominance behavior. This is a paradigmatic example of different alleles of the same gene that have distinct phenotypes at molecular, synaptic, and circuit levels which may inform exploration of these divergences in human patients Dysregulation of the mTOR pathway in these conditions provides clues to the molecular pathophysiology of ASD as the synaptic and cellular alterations involved may converge to produce the core social impairment of these disorders In addition, mTOR inhibitor compounds have the potential to reverse many of the behavioral and neurophysiological abnormalities associated with ASD Dysfunction of diverse upstream activators and environmental stressors, that have been previously implicated in SCZ, can lead to either over-activation or inhibition of the signaling pathway.

Autism Spectrum Disorder and Schizophrenia: Do They Overlap? | OMICS International

As to neuronal dysfunction hypothesized, abnormalities might be specific affecting only a subset of synapses in a selective group of neurons responsible of distinct symptoms but all that is still an hypothesis as evidence on the brain circuits potentially involved is lacking. Research domain criteria RDoC project seems particularly indicated to this scope as it is directed to implement all the above level of understanding.

One of the main purpose is to investigate mental illness through the dimensional approach to the fundamental components of behavior, through individual symptoms or symptom clusters, that cut across diagnoses, in this case specifically in ASD and SSD domains Aim and legacy of RDoC novel approach is to build a research perspective that reflects advances in genetics, neuroscience, and behavioral science to provide a foundation for precision diagnosis and treatment of complex mental disorders such as those herein examined.

The details obtained by the use of RDoC matrix likely will help to shed light on ASD and SSD relationships as well as on the longitudinal monitoring of emerging convergent and divergent symptoms of the two spectra It should also be noted that there is a subset of individuals with complex neurodevelopmental disorders whose symptoms span multiple functional domains including cognition and social communication. These individuals do not fit under any of the current diagnostic labels listed under ASD and SSD and further research through an RDoC approach holds promise to describe the specific biobehavioral profiles and thus eventually establish the diagnostic category in which they should be included.

RC and Mauro Pallagrosi equally participated in the substantial contribution to the conception or design of the work; drafted the work and revised it critically for important intellectual content; approved the final version to be published; and are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be constructed as a potential conflict of interest.

National Center for Biotechnology Information , U. Journal List Front Psychiatry v. Published online May 1. Author information Article notes Copyright and License information Disclaimer. Rutten, Maastricht University, Netherlands. This article was submitted to Child and Adolescent Psychiatry, a section of the journal Frontiers in Psychiatry. Received Aug 5; Accepted Apr The use, distribution or reproduction in other forums is permitted, provided the original author s or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.

Login using

No use, distribution or reproduction is permitted which does not comply with these terms. This article has been cited by other articles in PMC.

.
The Man Painter (The Painter Series Book 2);
Autism Spectrum Disorder (ASD) and Schizophrenia Spectrum Disorder (SSD): Current Understanding.

Abstract Autism spectrum disorders ASD and schizophrenia spectrum disorders SSD share clinical and genetic components that have long been recognized. Current Understanding The clinical interplay and overlap between SSD and ASD have long been recognized as the two classes of disorder that share phenotypic and clinical features and a number of individuals diagnosed with ASD subsequently develop SSD symptoms 1. Open in a separate window. Region and type Candidate genes Phenotypes 1q Divergent Phenotype in ASD and SSD Schizophrenia spectrum disorders and ASD have been described as polygenic disorders in which the onset and progression of disease are triggered by interactions among multiple susceptibility genes.

Final Remarks and Future Directions There is epidemiological, clinical, neurobiological, and genetic evidence for a close relationship between ASD and SSD, and significant overlap in symptoms is frequently observed; however, there are also differences in clinical presentation, behavioral phenotype, and developmental trajectory. Author Contributions RC and Mauro Pallagrosi equally participated in the substantial contribution to the conception or design of the work; drafted the work and revised it critically for important intellectual content; approved the final version to be published; and are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be constructed as a potential conflict of interest. Funding This was a self-funded manuscript. Schizophrenia and autism-related disorders. Schizophr Bull 41 2: Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association;