Social cognition in Turner’s Syndrome

doi:10.1016/j.jocn.2009.09.006

Journal of Clinical Neuroscience

Volume 17, Issue 3, March 2010, Pages 283-286

https://doi.org/10.1016/j.jocn.2009.09.006 Get rights and content

Abstract

Turner’s Syndrome (TS), or X-monosomy, is a common chromosomal disorder in women, and provides a valuable paradigm to investigate genotypic contributions to social cognition. We review evidence suggesting that some facets of social cognition, particularly emotion recognition and gaze perception, are impaired in women with TS, despite the absence of a global social-processing impairment. Further, these deficits co-exist with neuroanatomical abnormalities of the amygdala and other regions implicated in social processing. A parallel is drawn between the non-verbal profile of sociocognitive dysfunction in TS and autism spectrum disorders, possibly underpinned by genomic imprinting effects. TS provides a unique opportunity to identify genetic, and particularly sex chromosome, influences on social cognition and behaviour.

Introduction

Impaired social cognition is sometimes a prominent feature of neurological disorders affecting the frontal lobes and limbic system, such as frontotemporal dementia. Studies of the effects of brain lesions have contributed substantially to our understanding of the neurobiology of social cognition. The study of genetic disorders is an important extension of this paradigm, potentially providing insights into genotypic influences on social behaviour.

Turner’s Syndrome (TS) is one of the most common chromosomal disorders in women, affecting around 1 in every 2,500 live births. It occurs when one X-chromosome in a phenotypic female is missing, and it therefore produces, in the classic case, a karyotype of 45,X rather than the usual female karyotype of 46,XX. Physically, TS commonly results in ovarian failure with consequent oestrogen deficiency. Substantial inter-individual variability exists; however, the physical characteristics of TS usually include short stature, webbing of the neck, micrognathia, and low-set ears and hairline.¹ TS is also associated with a consistent neurocognitive profile.2, 3 The cognitive phenotype of TS includes relatively strong verbal IQ but deficits in visuospatial perception and memory, motor abilities, and attentional processes.⁴

Although social competence is not grossly impaired in TS, specific deficits in aspects of social processing have been identified. In contrast to some cognitive deficits associated with TS, which have been widely researched, the social and emotional difficulties these women face have received relatively little attention.

Section snippets

Psychosocial skills are commonly impaired in Turner’s Syndrome

TS is not characterised by increased risk of psychiatric illness relative to women attending gynaecological clinics or healthy controls. Nonetheless, TS is associated with increased risk of psychosocial difficulties and below-average social competence.3, 5, 6 Girls with TS tend to have fewer friends, to engage in fewer social activities, to have greater attentional and social difficulties, and to withdraw from social interactions more often than do controls.7, 8 Studies of adolescent girls with

Haploinsufficiency and genomic imprinting in TS

In normal women (46,XX), one of the two X-chromosomes is randomly inactivated, although some genes on that chromosome escape inactivation. Two copies of the latter genes are assumed to be required for normal female development. Haploinsufficiency of these genes in women with TS (45,X) is presumed to play a role in determining the TS phenotype.¹⁵ Females with mosaic TS (karyotypes other than the “pure” 45,X) typically demonstrate a more variable phenotype than 45,X women.16, 17, 18 A

Core emotion and face processing deficits may underlie the difficulties women with TS experience in social settings

Sociocognitive processes such as emotion recognition and gaze have been reported as aberrant in the TS population. Lawrence et al.’s study of 45,X_m women revealed statistically (but not clinically) significant impairment in face recognition, irrespective of depressed performance intelligence quotient (PIQ) score.²⁷ This finding supports earlier work identifying facial recognition and “fear” and “surprise” recognition deficits in adolescents and young women of mixed TS karyotype.²⁸ Lawrence et

The neuroanatomical substrate of emotion processing may be abnormal in Turner’s Syndrome

The amygdala has a crucial role in social cognition and, particularly, the processing of emotionally salient visual information.³⁷ Kluver and Bucy’s seminal studies of primates after bilateral temporal lobectomy showed strikingly inappropriate behaviour in social contexts and a greatly diminished fear response to the extent that the term “psychic blindness” was applied to the behaviour.³⁹ More recent primate and human studies, with lesions more confined to the amygdala, were able to dissociate

The amygdala: functional asymmetry and Turner’s Syndrome

Studies in people with unilateral amygdalar damage suggest that the left and right amygdalae differ in their function, with the right amygdala dominant in the autonomic response to emotionally salient stimuli, and the left amygdala dominant in the cognitive processes triggered by such stimuli.⁵² The proposal for a laterality effect in amygdalar function is strengthened by evidence from the TS literature. Amongst Skuse et al.’s healthy controls, better recognition of fearful facial expressions

A disorder umbrella for these deficits?

Much discussion has attempted to unify the neuroanatomical, endocrine, sociocognitive and neuropsychological abnormalities evident in girls and women with TS.2, 4, 26 Strong parallels have been drawn between the non-verbal impairments in TS and in autism, with the risk of autism increased 200 times in women with TS and X-monosomy common to both women with TS and healthy men.⁵³ There is also an argument for a protective role of the paternal X-chromosome in sociocognitive disorders. Males, by

Summary

Social and emotional difficulties exist in the TS population and at times prove clinically significant, above and beyond the well-described cognitive difficulties experienced in TS. The presence of specific deficits in elements of social cognition such as fearful facial emotion processing, gaze estimation, and the attribution of mental states in TS are reminiscent of autism, a disorder which shares genetic, neuroanatomical, and cognitive characteristics. That the maternally-derived X chromosome

References (57)

V.I. Rickert et al.
The effects of peer ridicule on depression and self-image among adolescent females with Turner syndrome
J Adolescent Health
(1996)
A.R. Zinn et al.
Turner syndrome and haploinsufficiency
Curr Opin Genet Dev
(1998)
D.G. Murphy et al.
X-chromosome effects on female brain: a magnetic resonance imaging study of Turner’s syndrome
Lancet
(1993)
D.G.M. Murphy et al.
The effects of sex steroids, and the X chromosome, on female brain function: a study of the neuropsychology of adult Turner syndrome
Neuropsychologia
(1994)
D.G.M. Murphy et al.
A PET study of Turner’s syndrome: effects of sex steroids and the X chromosome on brain
Biol Psychiat
(1997)
D.V.M. Bishop et al.
Distinctive patterns of memory function in subgroups of females with Turner syndrome: evidence for imprinted loci on the X-chromosome affecting neurodevelopment
Neuropsychologia
(2000)
S.R. Kesler et al.
Effects of X-monosomy and X-linked imprinting on superior temporal gyrus morphology in Turner syndrome
Biol Psychiatry
(2003)
D.Z. Loesch et al.
Effect of Turner’s syndrome and X-linked imprinting on cognitive status: analysis based on pedigree data
Brain Dev
(2005)
R. Adolphs et al.
Recognition of facial emotion in nine individuals with bilateral amygdala damage
Neuropsychologia
(1999)
K. Lawrence et al.
The development of mental state attributions in women with X-monosomy, and the role of monoamine oxidase B in the sociocognitive phenotype
Cognition
(2007)

R. Campbell et al.

The classification of ‘fear’ from faces is associated with face recognition skill in women

Neuropsychologia

(2002)

N.J. Emery

The eyes have it: the neuroethology, function and evolution of social gaze

Neurosci Biobehav Rev

(2000)

R. Adolphs et al.

Role of the amygdala in processing visual social stimuli

Prog Brain Res

(2006)

V.E. Stone et al.

Acquired theory of mind impairments in individuals with bilateral amygdala lesions

Neuropsychologia

(2003)

C.I. Hooker et al.

Brain networks for analyzing eye gaze

Brain Res Cognitive Brain Res

(2003)

T. Allison et al.

Social perception from visual cues: role of the STS region

Trends Cogn Sci

(2000)

W.J. Cutter et al.

Influence of X chromosome and hormones on human brain development: a magnetic resonance imaging and proton magnetic resonance spectroscopy study of Turner syndrome

Biol Psychiatry

(2006)

S.R. Kesler et al.

Amygdala and hippocampal volumes in Turner syndrome: a high-resolution MRI study of X-monosomy

Neuropsychologia

(2004)

W.E. Brown et al.

Brain development in Turner syndrome: a magnetic resonance imaging study

Psychiat Res Neuroimaging

(2002)

P.M. Lynn et al.

The 39, XO mouse as a model for the neurobiology of Turner syndrome and sex-biased neuropsychiatric disorders

Behav Brain Res

(2007)

M. Elsheikh et al.

Turner’s syndrome in adulthood

Endocr Rev

(2002)

E. McCauley et al.

The Turner syndrome: cognitive deficits, affective discrimination, and behaviour problems

Child Dev

(1987)

E. McCauley et al.

Psychosocial development in adolescents with Turner syndrome

J Dev Behav Pediatr

(2001)

J.L. Ross et al.

Neurodevelopmental and psychosocial aspects of Turner syndrome

Ment Retard Dev Disabil Res Rev

(2000)

K. Lesniak-Karpiak et al.

Behavioral assessment of social anxiety in females with Turner or fragile X syndrome

J Autism Dev Disord

(2003)

M.M.M. Mazzocco et al.

Language use in females with fragile X or Turner syndrome during brief initial social interactions

J Dev Behav Pediatr

(2006)

P.T. Siegel et al.

The psychological consequences of Turner syndrome and review of the National Cooperative Growth Study psychological substudy

Pediatrics

(1998)

K. Lagrou et al.

Age-related perception of stature, acceptance of therapy, and psychosocial functioning in human growth hormone-treated girls with Turner’s syndrome

J Clin Endocr Metab

(1998)

Cited by (32)

Turner Syndrome: transition from childhood to adolescence
2018, Metabolism: Clinical and Experimental
Transition from pediatric to adult care for young women with Turner Syndrome (TS) is characterized by high drop-out rates and inadequate follow-up, leading to increased morbidity and mortality. The complexity of the health issues young women with TS face or new problems that may arise warrants a well-structured and efficiently coordinated gradual transition plan, which is adapted to the individual needs of the emerging young adult and is based on interdisciplinary communication between physicians. In order to achieve a high level of care, it is important for the patient to be sincerely informed about her condition but also supported throughout this critical period of rising responsibility and autonomy by an experienced, multidisciplinary team. In this review, we present the basic concepts that should characterize transition and the major health issues that should be thoroughly addressed, including growth, Hormone Replacement Treatment and fertility options, cardiovascular disease, bone health, gastrointestinal disorders, autoimmunity, orthopaedic and ENT issues, as well as the overall psychological well-being of the young adult with TS.
Face perception in women with Turner syndrome and its underlying factors
2016, Neuropsychologia
Citation Excerpt :
Some structural imaging studies show greater amygdalar volumes in TS (Good et al., 2003; Kesler et al., 2004a but see Cutter, Daly, Robertson, et al., 2006). Areas connected to the amygdala such as the right hippocampus, orbitofrontal cortex and superior temporal sulcus show reduced volume in TS (Burnett et al., 2010; Hong et al., 2011). In addition, fMRI studies that have probed the role of the amygdala in TS emotional processing have found aberrant patterns of amygdalar activation in response to fearful stimuli.
Turner syndrome (TS) is a chromosomal condition that affects development in females. It is characterized by short stature, ovarian failure and other congenital malformations, due to a partial or complete absence of the sex chromosome. Women with TS frequently suffer from various physical and hormonal dysfunctions, along with impairments in visual-spatial processing and social cognition difficulties. Previous research has also shown difficulties in face and emotion perception. In the current study we examined two questions: First, whether women with TS, that are impaired in face perception, also suffer from deficits in face-specific processes. The second question was whether these face impairments in TS are related to visual-spatial perceptual dysfunctions exhibited by TS individuals, or to impaired social cognition skills. Twenty-six women with TS and 26 control participants were tested on various cognitive and psychological tests to assess visual-spatial perception, face and facial expression perception, and social cognition skills. Results show that women with TS were less accurate in face perception and facial expression processing, yet they exhibited normal face-specific processes (configural and holistic processing). They also showed difficulties in spatial perception and social cognition capacities. Additional analyses revealed that their face perception impairments were related to their deficits in visual-spatial processing. Thus, our results do not support the claim that the impairments in face processing observed in TS are related to difficulties in social cognition. Rather, our data point to the possibility that face perception difficulties in TS stem from visual-spatial impairments and may not be specific to faces.
Turner syndrome: From birth to adulthood
2015, Endocrinologia y Nutricion
El síndrome de Turner es definido por un conjunto de rasgos fenotípicos característicos resultantes de la alteración completa o parcial del cromosoma X.
Estudio descriptivo retrospectivo en el que se analiza el diagnóstico, la evolución y la situación actual de pacientes controladas en los últimos 40 años de síndrome de Turner en un hospital terciario (Bizkaia) mediante revisión de historias clínicas y encuestas telefónicas.
Estudiamos 45 mujeres, con edad media actual de 22,95 años (rango 2-38) y edad media de diagnóstico de 4,71 años. El 63% presentaron mosaicismo en su cariotipo. El motivo de consulta más frecuente fue talla baja (54%), objetivándose un incremento de diagnóstico prenatal en los casos más recientes. Han recibido tratamiento con hormona de crecimiento el 72%, y el 26% además recibieron oxandrolona. En el 69% de las pacientes la talla final alcanzada fue baja. Han presentado fallo gonadal el 66%, recibiendo la mayoría tratamiento hormonal sustitutivo. Tres pacientes han tenido descendencia con óvulo de donante. El seguimiento de las 31 pacientes adultas es llevado a cabo fundamentalmente por endocrinología (37,5%) y/o ginecología (34,4%). En el ámbito psicosocial han precisado ayuda durante la escolarización el 22%, alcanzando el 80% estudios de nivel medio-alto. Dos pacientes han fallecido, una por disección de aneurisma aórtico y la otra paciente, con múltiples patologías, por insuficiencia respiratoria.
La talla baja es el motivo más frecuente de consulta en pacientes con síndrome de Turner. En la mayoría de los casos el cariotipo es mosaico. Las manifestaciones clínicas más frecuentes son talla baja y fallo gonadal. El 80% consiguen realizar estudios de nivel medio-alto. En la edad adulta el seguimiento es irregular y en ocasiones escaso, siendo claramente mejorable.
Turner syndrome is characterized by a great variability of clinical manifestations caused by a total or partial loss of X-chromosome.
A retrospective, descriptive study of the diagnosis, course, and current status of patients with Turner syndrome followed up at our section over the past 40 years, based on review of medical records supplemented with a telephone survey.
Forty-five female patients with a current mean age of 22.95 years (range 2-38) and a mean age at diagnosis of 4.71 were included. Sixty-three percent of them showed a mosaic karyotype. Short stature was the most common reason for consultation (54%), with increased prenatal diagnosis in most recent cases. Seventy-two percent have been treated with growth hormone, together with oxandrolone in 26%. Final stature was short in 69% of patients. Gonadal failure was found in 66%; most of whom received replacement therapy. Three patients achieved pregnancy by oocyte donation. The 31 adult patients are mainly monitored by the endocrinology (37.5%) and/or gynecology (34.4%) departments. As regards psychosocial aspects, 22% required support during school, and 80% completed middle to high level education. Two patients died, one due to dissecting aortic aneurysm and the other one, who had multiple pathological conditions, from respiratory failure.
Short stature is the main cause of diagnosis in patients with Turner syndrome; most cases show genetic mosaicism. The most common clinical manifestations include short stature and gonadal failure. Eighty percent of patients complete middle or high education. In adulthood, follow-up is irregular, sometimes scarce, and clearly improvable.
Mouse model systems to study sex chromosome genes and behavior: Relevance to humans
2014, Frontiers in Neuroendocrinology
Citation Excerpt :
Turner syndrome is associated with cognitive deficits, including problems with visuospatial perception and memory, emotionality, and attention (Skuse, 2005; Skuse et al., 2005). Girls with Turner syndrome also have reduced social competence and facial recognition (Hong et al., 2011; Lawrence et al., 2003), and may be at higher risk for autism (Burnett et al., 2010; Marco and Skuse, 2006). Using a tracking task that required increasing amounts of attention, Beaton and colleagues (Beaton et al., 2010) examined BOLD patterns in normal and Turner syndrome girls.
Sex chromosome genes directly influence sex differences in behavior. The discovery of the Sry gene on the Y chromosome (Gubbay et al., 1990, Koopman et al., 1990) substantiated the sex chromosome mechanistic link to sex differences. Moreover, the pronounced connection between X chromosome gene mutations and mental illness produces a strong sex bias in these diseases. Yet, the dominant explanation for sex differences continues to be the gonadal hormones. Here we review progress made on behavioral differences in mouse models that uncouple sex chromosome complement from gonadal sex. We conclude that many social and cognitive behaviors are modified by sex chromosome complement, and discuss the implications for human research. Future directions need to include identification of the genes involved and interactions with these genes and gonadal hormones.
Cortical thickness correlates of socioemotional difficulties in adults with Turner syndrome
2014, Psychoneuroendocrinology
Turner syndrome (TS) is a non-inherited genetic disorder associated with a specific cognitive phenotype and socioemotional impairments. The present study aimed at characterizing the neuroanatomical basis of socioemotional dysfunctions in TS using the Emotional Quotient inventory (EQ-I) and cortical morphology analysis in 17 individuals with TS (45,X) and 17-age and verbal IQ matched healthy females. Individuals with TS reported significantly greater socioemotional impairment than controls. Cortical thickness analysis showed that participants with TS had an overall thicker cortex than controls, with extensive alterations in the temporal, frontal, parietal and insular regions bilaterally. Using the total EQ-I score as regressor in the cortical thickness analysis revealed a number of brain regions where the relationship between cortical thickness and EQ-I score differed between groups; these areas included brain regions critically involved in socioemotional processes, such as bilateral insula, the anterior cingulate and the orbitofrontal cortex. These results show that socioemotional dysfunctions seen in women with TS are associated with significant alterations in brain morphology.
A review on sex differences in processing emotional signals
2012, Neuropsychologia
Citation Excerpt :
Both demonstrate decrements in face and affect recognition (Skuse et al., 1997). The deficits in TS co-exist with neuro-anatomical abnormalities of the amygdala and other regions implicated in social processing (for a review, see Burnett, Reutens, & Wood, 2010). Sex differences in brain structure are well-documented, although not necessarily consistent.
Interest in sex-related differences in psychological functioning has again come to the foreground with new findings about their possible functional basis in the brain. Sex differences may be one way how evolution has capitalized on the capacity of homologous brain regions to process social information between men and women differently. This paper focuses specifically on the effects of emotional valence, sex of the observed and sex of the observer on regional brain activations. We also discuss the effects of and interactions between environment, hormones, genes and structural differences of the brain in the context of differential brain activity patterns between men and women following exposure to seen expressions of emotion and in this context we outline a number of methodological considerations for future research. Importantly, results show that although women are better at recognizing emotions and express themselves more easily, men show greater responses to threatening cues (dominant, violent or aggressive) and this may reflect different behavioral response tendencies between men and women as well as evolutionary effects. We conclude that sex differences must not be ignored in affective research and more specifically in affective neuroscience.

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ReviewSocial cognition in Turner’s Syndrome

Abstract

Introduction

Section snippets

Psychosocial skills are commonly impaired in Turner’s Syndrome

Haploinsufficiency and genomic imprinting in TS

Core emotion and face processing deficits may underlie the difficulties women with TS experience in social settings

The neuroanatomical substrate of emotion processing may be abnormal in Turner’s Syndrome

The amygdala: functional asymmetry and Turner’s Syndrome

A disorder umbrella for these deficits?

Summary

J Adolescent Health

Curr Opin Genet Dev

Lancet

Neuropsychologia

Biol Psychiat

Neuropsychologia

Biol Psychiatry

Brain Dev

Neuropsychologia

Cognition

Neuropsychologia

Neurosci Biobehav Rev

Prog Brain Res

Neuropsychologia

Brain Res Cognitive Brain Res

Trends Cogn Sci

Biol Psychiatry

Neuropsychologia

Psychiat Res Neuroimaging

Behav Brain Res

Turner’s syndrome in adulthood

Endocr Rev

The Turner syndrome: cognitive deficits, affective discrimination, and behaviour problems

Child Dev

Psychosocial development in adolescents with Turner syndrome

J Dev Behav Pediatr

Neurodevelopmental and psychosocial aspects of Turner syndrome

Ment Retard Dev Disabil Res Rev

Behavioral assessment of social anxiety in females with Turner or fragile X syndrome

J Autism Dev Disord

Language use in females with fragile X or Turner syndrome during brief initial social interactions

J Dev Behav Pediatr

The psychological consequences of Turner syndrome and review of the National Cooperative Growth Study psychological substudy

Pediatrics

Age-related perception of stature, acceptance of therapy, and psychosocial functioning in human growth hormone-treated girls with Turner’s syndrome

J Clin Endocr Metab

Review
Social cognition in Turner’s Syndrome