Influence of Auditory Integrative Training on Casein Kinase 2 and Its Impact on Behavioral and Social Interaction in Children with Autism Spectrum Disorder

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This study evaluated Casein Kinase-2 (CK2) concentration in plasma, which can be related to autism, before and after auditory integrative training and found that childhood autism rating scale (CARS) and other related scores were improved whereas CK2 concentration did not decrease. The results of this clinical study may be slightly valuable for basic researchers. Following are the concerns before the publish of this article:
1) Fig. 1-4
The error bars should be added.
2) Line 24-5
> There was an improvement in the measures of autism severity as an effect of AIT which induced the down-regulation of CK2 in plasma.
The significant decrease was observed immediately and 3 months after AIT. The description should be stated more precisely. Why was there no significance after 1 month?
3) Table 6, Fig 5
What is the aim of this analysis?

Author Response

A point-by-point answer to reviewers’ comments with the revised manuscript.  Responses to the reviewer’s comments are marked in red and changes are highlighted in yellow in the revised manuscript.

Reviewer 1:

This study evaluated Casein Kinase-2 (CK2) concentration in plasma, which can be related to autism, before and after auditory integrative training and found that childhood autism rating scale (CARS) and other related scores were improved whereas CK2 concentration did not decrease. The results of this clinical study may be slightly valuable for basic researchers. Following are the concerns before the publish of this article:

1) Fig. 1-4
- The error bars should be added.

-The error bars were added up to your request

2) Line 24-5
> There was an improvement in the measures of autism severity as an effect of AIT which induced the down-regulation of CK2 in plasma.
The significant decrease was observed immediately and 3 months after AIT. The description should be stated more precisely. Why was there no significance after 1 month?

Thanks for your valuable comment. The statement was corrected to describe the effect of AIT precisely in relation to CARS, SRS, and SSP.
3) Table 6, Fig 5
What is the aim of this analysis?

Explanation for the importance of the Receiver Operating Characteristic (ROC) analysis in the evaluation of the prognostic and predictive value of CK2 after AIT treatment in relation to CARS, SRS, and SP as three measures of ASD severity were inserted under the statistical analysis subheading (Wish the aim of Table 6 and Fig. 5 is clear now). You can find highlighted in yellow within the text.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

In the manuscript entitled ‘Influence of Auditory Integrative Training on Casein Kinase 2 2 and Its Impact on Behavioral and Social Interaction in Children 3 with Autism Spectrum Disorder’, authors investigated the impact of auditory integration therapy (AIT) on plasma casein kinase-2 (CK2) levels in children with ASD. CK2 is a protein kinase and plays a crucial role in neuronal and glial homeostasis and inflammatory signaling across synapses. The research enrolled 25 ASD children aged 5-12 years with AIT treatment and autism severity measures with plasma CK2 levels were assessed before and after AIT. Results showed a significant decline in autistic behavior and improvement in autism severity measures after AIT, which was associated with the downregulation of plasma CK2 levels. Authors proposed a link between decreased CK2 and etiological mechanisms in ASD. The project was well-designed, and the manuscript was concisely and clearly written. I think the conclusions were supported by the designed experiments and provides valuable information for ASD measurement and treatment. Besides some minor issues for authors to answer/revise, the whole manuscript could be suitable for publication. Comments are below:

 

1.     In Material and Method part, how did authors measure CK2 plasma level? Could authors specify in detail?

2.     What the possible mechanisms of the positive effects of auditory integrative training on CK2? Are there any pharmacological approaches to reduce CK2 levels in autism children besides the AIT therapy?

3.     How do authors explain the correlation between reduced CK2 levels and improved behaviors in autism children, such as social behaviors?

Author Response

Reviewer 2:

 

 

In the manuscript entitled ‘Influence of Auditory Integrative Training on Casein Kinase 2 2 and Its Impact on Behavioral and Social Interaction in Children 3 with Autism Spectrum Disorder’, authors investigated the impact of auditory integration therapy (AIT) on plasma casein kinase-2 (CK2) levels in children with ASD. CK2 is a protein kinase and plays a crucial role in neuronal and glial homeostasis and inflammatory signaling across synapses. The research enrolled 25 ASD children aged 5-12 years with AIT treatment and autism severity measures with plasma CK2 levels were assessed before and after AIT. Results showed a significant decline in autistic behavior and improvement in autism severity measures after AIT, which was associated with the downregulation of plasma CK2 levels. Authors proposed a link between decreased CK2 and etiological mechanisms in ASD. The project was well-designed, and the manuscript was concisely and clearly written. I think the conclusions were supported by the designed experiments and provides valuable information for ASD measurement and treatment. Besides some minor issues for authors to answer/revise, the whole manuscript could be suitable for publication.

 

Comments are below:

 

1. In Material and Method part, how did authors measure CK2 plasma level? Could authors specify in detail?

– Done, and methodology was described

2. What the possible mechanisms of the positive effects of auditory integrative training on CK2? Are there any pharmacological approaches to reduce CK2 levels in autism children besides the AIT therapy?

• Yes Inhibition of CK2 is well known approach in treating many neurological and Psychiatric disorders and pharmacological inhibitors are available. This was mentioned up to your comment and you can find highlighted in yellow within the text. Two new references were cited (Highlighted in yellow).

 

3. How do authors explain the correlation between reduced CK2 levels and improved behaviors in autism children, such as social behaviors?

 

- It is already discussed in relation to neuroinflammation and glutamate excitotoxicity (Kindly see lines 271-284 & 285-300)

 

Author Response File: Author Response.pdf