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      The influence of 5-HTTLPR transporter genotype on amygdala-subgenual anterior cingulate cortex connectivity in autism spectrum disorder

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          Abstract

          Social deficits in autism spectrum disorder (ASD) are linked to amygdala functioning and functional connection between the amygdala and subgenual anterior cingulate cortex (sACC) is involved in the modulation of amygdala activity. Impairments in behavioral symptoms and amygdala activation and connectivity with the sACC seem to vary by serotonin transporter-linked polymorphic region (5-HTTLPR) variant genotype in diverse populations. The current preliminary investigation examines whether amygdala-sACC connectivity differs by 5-HTTLPR genotype and relates to social functioning in ASD. A sample of 108 children and adolescents (44 ASD) completed an fMRI face-processing task. Youth with ASD and low expressing 5-HTTLPR genotypes showed significantly greater connectivity than youth with ASD and higher expressing genotypes as well as typically developing (TD) individuals with both low and higher expressing genotypes, in the comparison of happy vs. baseline faces and happy vs. neutral faces. Moreover, individuals with ASD and higher expressing genotypes exhibit a negative relationship between amygdala-sACC connectivity and social dysfunction. Altered amygdala-sACC coupling based on 5-HTTLPR genotype may help explain some of the heterogeneity in neural and social function observed in ASD. This is the first ASD study to combine genetic polymorphism analyses and functional connectivity in the context of a social task.

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          Emotional processing in anterior cingulate and medial prefrontal cortex.

          Amit Etkin, Tobias Egner, Raffael Kalisch (2011)
          Negative emotional stimuli activate a broad network of brain regions, including the medial prefrontal (mPFC) and anterior cingulate (ACC) cortices. An early influential view dichotomized these regions into dorsal-caudal cognitive and ventral-rostral affective subdivisions. In this review, we examine a wealth of recent research on negative emotions in animals and humans, using the example of fear or anxiety, and conclude that, contrary to the traditional dichotomy, both subdivisions make key contributions to emotional processing. Specifically, dorsal-caudal regions of the ACC and mPFC are involved in appraisal and expression of negative emotion, whereas ventral-rostral portions of the ACC and mPFC have a regulatory role with respect to limbic regions involved in generating emotional responses. Moreover, this new framework is broadly consistent with emerging data on other negative and positive emotions. Published by Elsevier Ltd.
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            A self-report measure of pubertal status: Reliability, validity, and initial norms.

            A Petersen, L. Crockett, M. Richards … (1988)
            Puberty is a central process in the complex set of changes that constitutes the transition from childhood to adolescence. Research on the role of pubertal change in this transition has been impeded by the difficulty of assessing puberty in ways acceptable to young adolescents and others involved. Addressing this problem, this paper describes and presents norms for a selfreport measure of pubertal status. The measure was used twice annually over a period of three years in a longitudinal study of 335 young adolescent boys and girls. Data on a longitudinal subsample of 253 subjects are reported. The scale shows good reliability, as indicated by coefficient alpha. In addition, several sources of data suggest that these reports are valid. The availability of such a measure is important for studies, such as those based in schools, in which more direct measures of puberty may not be possible.
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              Neurons in medial prefrontal cortex signal memory for fear extinction.

              Mohammed R Milad, Gregory J Quirk (2002)
              Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction, indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.
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                Author and article information

                Contributors
                Francisco Velasquez
                Journal
                Journal ID (nlm-ta): Dev Cogn Neurosci
                Journal ID (iso-abbrev): Dev Cogn Neurosci
                Title: Developmental Cognitive Neuroscience
                Publisher: Elsevier
                ISSN (Print): 1878-9293
                ISSN (Electronic): 1878-9307
                Publication date PMC-release: 23 December 2016
                Publication date Collection: April 2017
                Publication date (Electronic): 23 December 2016
                Volume: 24
                Pages: 12-20
                Affiliations
                [a ]Department of Psychology, University of Michigan, United States
                [b ]Department of Human Genetics, University of Michigan, United States
                [c ]Center for Autism and the Developing Brain, Weill Cornell Medicine, United States
                [d ]Department of Psychology, Neuroscience Program, Department of Psychiatry, Center for Growth and Human Development, University of Michigan, United States
                Author notes
                [* ]Corresponding author at: Box 357115, University of Washington, Seattle, WA, 98195, United States. velasqfr@ 123456umich.edu
                [1]

                Present address: Department of Radiology, University of Washington, United States.

                [2]

                Present address: Department of Psychology, San Diego State University and San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, United States.

                Article
                Publisher ID: S1878-9293(16)30049-4
                DOI: 10.1016/j.dcn.2016.12.002
                PMC ID: 5858904
                PubMed ID: 28088648
                SO-VID: 0ed52152-338e-4ba1-826a-fb9c50454234
                Copyright © © 2016 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 6 April 2016
                Date revision received : 15 December 2016
                Date accepted : 16 December 2016
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Neurosciences
                Keywords: autism spectrum disorder,serotonin,amygdala,subgenual anterior cingulate cortex,5-httlpr,connectivity,face-processing,heterogeneity
                Data availability:
                ScienceOpen disciplines: Neurosciences
                Keywords: autism spectrum disorder, serotonin, amygdala, subgenual anterior cingulate cortex, 5-httlpr, connectivity, face-processing, heterogeneity

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