Aberrant neurocognitive processing of fear in young girls with Turner syndrome

Abstract

Appraisal of fearful stimuli is an integral aspect of social cognition. Neural circuitry underlying this phenomenon has been well-described and encompasses a distributed network of affective and cognitive nodes. Interestingly, this ability to process fearful faces is impaired in Turner syndrome (TS), a genetic disorder of females in which all or part of an X chromosome is missing. However, neurofunctional correlates for this impairment have not been well-studied, particularly in young girls. Given that the core features of TS include X chromosome gene haploinsufficiency and secondary sex hormone deficiencies, investigation of fearful face processing may provide insights into the influence of X chromosome gene expression on this network. Therefore, we examined behavioral and neural responses during an explicit emotional face labeling task in 14 prepubertal girls with TS and 16 typically developing age-matched controls (6-13 years). We demonstrate that girls with TS have a specific impairment in the identification of fearful faces and show decreased activation in several cognitive control regions, including the anterior dorsal anterior cingulate cortex, dorsolateral prefrontal cortex and posterior cingulate gyrus. Our results indicate that aberrant functional activation in dorsal cognitive regions plays an integral role in appraisal of, and regulation of response to fear in TS.

Sex differences in amygdala shape: Insights from Turner syndrome

“…Thus, in this sample, we are able to examine the effects of absence of one complete X chromosome on amygdala structure before the administration of exogenous estrogen. The sample used in this study overlaps with previously published work [Hong et al, ; Lepage et al, ]. The local Institutional Review Board of the Stanford University School of Medicine approved this study and informed written consent was obtained from a legal guardian for all participants.…”

“…More specifically, girls with TS are thought to have impaired recognition of emotional facial expressions compared to TD females, with specific deficits in the recognition of fear [Lawrence et al, ; Mazzola et al, ]. Functional neuroimaging studies have additionally demonstrated altered activation in the amygdala [Skuse et al, ] and cognitive control regions [Hong et al, ] in girls with TS as they perform face emotion recognition tasks. Taken together, these findings, in context with prior work emphasizing the amygdala's role in fear [Dejean et al, 2015] and social perception [Rutishauser et al, 2015] provide persuasive evidence for a role of altered amygdala function in the behavioral phenotype associated with TS.…”

Sex differences and stress across the lifespan

“…In humans, observations of the brain and behavioral impact of sex chromosome abnormalities aid our understanding of the specific contributions of the X and Y chromosomes to sex differences. Brain studies comparing children in early puberty with Turner syndrome (XO) and Klinefelter syndrome (XXY) to age matched controls revealed a dose-dependency of the X chromosome to decreased parieto-occipital and increased temporo-insular gray matter volumes, suggesting an involvement of X-linked genes in structural brain development 47,48 . Another study reported smaller hippocampal volumes in XXY boys compared to age-matched controls 49 .…”

Assessing gonadal hormone contributions to affective psychopathologies across humans and animal models

“…For example, relative to matched-controls, women with TS have difficulty identifying negative emotional facial expressions that indicate fear or anger (Good et al, 2003;Hong et al, 2013). However, affective processing difficulties are not limited to the visual domain.…”

“…In humans, low androgens in males with Klinefelter Syndrome (KS), low estrogen in females with Turner Syndrome (TS), and low progesterone in females with Premenstrual Dysphoric Disorder (PMDD) increased manifestations of depression and anxiety (Bruining et al, 2009;Downey et al, 1989;Halbreich et al, 2003). Each of these disorders was reported to be associated with difficulties in labelling emotional facial expression (Good et al, 2003;Hong et al, 2013;Rubinow et al, 2007;Skuse et al, 2005;van Rijn et al, 2006) and assessing emotional prosody in speech (Ross et al, 1995;van Rijn et al, 2007). Likewise, excess androgen exposure in males with Male-Limited Precocious Puberty (FMPP) and females with Congenital…”