Biological Psychiatry : Oxytocin and Autism (Août 2013)

vendredi 2 août 2013

Le numéro d’août 2013 de Biological Psychiatry est consacré à l’ocytocine et l’autisme.

1. Weisman O, Feldman R. Oxytocin Effects on the Human Brain : Findings, Questions, and Future Directions. Biological Psychiatry ;2013 ;74(3):158-159.

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2. Young LJ. When Too Much of a Good Thing is Bad : Chronic Oxytocin, Development, and Social Impairments. Biological Psychiatry ;2013 ;74(3):160-161.

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3. Hutman T. From Attention to Interaction : The Emergence of Autism During Infancy. Biological Psychiatry ;2013 ;74(3):162-163.

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4. Domes G, Heinrichs M, Kumbier E, Grossmann A, Hauenstein K, Herpertz SC. Effects of Intranasal Oxytocin on the Neural Basis of Face Processing in Autism Spectrum Disorder. Biological Psychiatry ;2013 ;74(3):164-171.

Background Autism spectrum disorder (ASD) is associated with altered face processing and decreased activity in brain regions involved in face processing. The neuropeptide oxytocin has been shown to promote face processing and modulate brain activity in healthy adults. The present study examined the effects of oxytocin on the neural basis of face processing in adults with Asperger syndrome (AS). Methods A group of 14 individuals with AS and a group of 14 neurotypical control participants performed a face-matching and a house-matching task during functional magnetic resonance imaging. The effects of a single dose of 24 IU intranasally administered oxytocin were tested in a randomized, placebo-controlled, within-subject, cross-over design. Results Under placebo, the AS group showed decreased activity in the right amygdala, fusiform gyrus, and inferior occipital gyrus compared with the control group during face processing. After oxytocin treatment, right amygdala activity to facial stimuli increased in the AS group. Conclusions These findings indicate that oxytocin increases the saliency of social stimuli and in ASD and suggest that oxytocin might promote face processing and eye contact in individuals with ASD as prerequisites for neurotypical social interaction.

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5. Groppe SE, Gossen A, Rademacher L, Hahn A, Westphal L, Gründer G, Spreckelmeyer KN. Oxytocin Influences Processing of Socially Relevant Cues in the Ventral Tegmental Area of the Human Brain. Biological Psychiatry ;2013 ;74(3):172-179.

Background Evidence accumulates that the neuropeptide oxytocin plays an important role in mediating social interaction among humans and that a dysfunction in oxytocin-modulated brain mechanisms might lie at the core of disturbed social behavior in neuropsychiatric disease. Explanatory models suggest that oxytocin guides social approach and avoidance by modulating the perceived salience of socially meaningful cues. Animal data point toward the ventral tegmental area (VTA) as the brain site where this modulation takes place. Methods We used functional magnetic resonance imaging and a social incentive delay task to test the hypothesis that oxytocin modulates the neural processing of socially relevant cues in the VTA, hereby facilitating behavioral response. Twenty-eight nulliparous women (not taking any hormones) received intranasal oxytocin or placebo in a double-blind randomized clinical trial with a parallel-group design. Results Oxytocin significantly enhanced VTA activation in response to cues signaling social reward (friendly face) or social punishment (angry face). Oxytocin effects on behavioral performance were modulated by individual differences in sociability with enhanced performance in women scoring low but decreased performance in women scoring high on self-reported measures of agreeableness. Conclusions Our data provide evidence that the VTA is the human brain site where oxytocin attaches salience to socially relevant cues. This mechanism might play an important role in triggering motivation to react at the prospect of social reward or punishment.

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6. Bales KL, Perkeybile AM, Conley OG, Lee MH, Guoynes CD, Downing GM, Yun CR, Solomon M, Jacob S, Mendoza SP. Chronic Intranasal Oxytocin Causes Long-Term Impairments in Partner Preference Formation in Male Prairie Voles. Biological Psychiatry ;2013 ;74(3):180-188.

Background Oxytocin (OT) is a hormone shown to be involved in social bonding in animal models. Intranasal OT is currently in clinical trials for use in disorders such as autism and schizophrenia. We examined long-term effects of intranasal OT given developmentally in the prairie vole (Microtus ochrogaster), a socially monogamous rodent, often used as an animal model to screen drugs that have therapeutic potential for social disorders. Methods We treated voles with one of three dosages of intranasal OT, or saline, from day 21 (weaning) through day 42 (sexual maturity). We examined both social behavior immediately following administration, as well as long-term changes in social and anxiety behavior after treatment ceased. Group sizes varied from 8 to 15 voles (n = 89 voles total). Results Treatment with OT resulted in acute increases in social behavior in male voles with familiar partners, as seen in humans. However, long-term developmental treatment with low doses of intranasal OT resulted in a deficit in partner preference behavior (a reduction of contact with a familiar opposite-sex partner, used to index pair-bond formation) by male voles. Conclusions Long-term developmental treatment with OT may show results different to those predicted by short-term studies, as well as significant sex differences and dosage effects. Further animal study is crucial to determining safe and effective strategies for use of chronic intranasal OT, especially during development.

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7. Elsabbagh M, Fernandes J, Jane Webb S, Dawson G, Charman T, Johnson MH. Disengagement of Visual Attention in Infancy is Associated with Emerging Autism in Toddlerhood. Biological Psychiatry ;2013 ;74(3):189-194.

Background Early emerging characteristics of visual orienting have been associated with a wide range of typical and atypical developmental outcomes. In the current study, we examined the development of visual disengagement in infants at risk for autism. Methods We measured the efficiency of disengaging from a central visual stimulus to orient to a peripheral one in a cohort of 104 infants with and without familial risk for autism by virtue of having an older sibling with autism. Results At 7 months of age, disengagement was not robustly associated with later diagnostic outcomes. However, by 14 months, longer latencies to disengage in the subset of the risk group later diagnosed with autism was observed relative to other infants at risk and the low-risk control group. Moreover, between 7 months and 14 months, infants who were later diagnosed with autism at 36 months showed no consistent increases in the speed and flexibility of visual orienting. However, the latter developmental effect also characterized those infants who exhibited some form of developmental concerns (but not meeting criteria for autism) at 36 months. Conclusions Infants who develop autism or other developmental concerns show atypicality in the development of visual attention skills from the first year of life.

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8. Chawarska K, Macari S, Shic F. Decreased Spontaneous Attention to Social Scenes in 6-Month-Old Infants Later Diagnosed with Autism Spectrum Disorders. Biological Psychiatry ;2013 ;74(3):195-203.

Background The ability to spontaneously attend to the social overtures and activities of others is essential for the development of social cognition and communication. This ability is critically impaired in toddlers with autism spectrum disorders (ASD) ; however, it is not clear if prodromal symptoms in this area are already present in the first year of life of those affected by the disorder. Methods To examine whether 6-month-old infants later diagnosed with ASD exhibit atypical spontaneous social monitoring skills, visual responses of 67 infants at high-risk and 50 at low-risk for ASD were studied using an eye-tracking task. Based on their clinical presentation in the third year, infants were divided into those with ASD, those exhibiting atypical development, and those developing typically. Results Compared with the control groups, 6-month-old infants later diagnosed with ASD attended less to the social scene, and when they did look at the scene, they spent less time monitoring the actress in general and her face in particular. Limited attention to the actress and her activities was not accompanied by enhanced attention to objects. Conclusions Prodromal symptoms of ASD at 6 months include a diminished ability to attend spontaneously to people and their activities. A limited attentional bias toward people early in development is likely to have a detrimental impact on the specialization of social brain networks and the emergence of social interaction patterns. Further investigation into its underlying mechanisms and role in psychopathology of ASD in the first year is warranted.

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9. Walker CK, Anderson KW, Milano KM, Ye S, Tancredi DJ, Pessah IN, Hertz-Picciotto I, Kliman HJ. Trophoblast Inclusions Are Significantly Increased in the Placentas of Children in Families at Risk for Autism. Biological Psychiatry ;2013 ;74(3):204-211.

Background Gestation is a critical window for neurodevelopmental vulnerability. This study examined whether the presence of trophoblast inclusions (TIs) in the placenta could serve as a predictor for children at elevated risk for autism spectrum disorder (ASD). Methods Placentas were obtained from 117 births in the MARBLES (Markers of Autism Risk in Babies—Learning Early Signs) cohort of families who have one or more previous biological children with ASD, placing their newborn at elevated risk for neurodevelopmental compromise. Control samples were obtained from 100 uncomplicated term pregnancies of multiparous women with one or more typically developing biological children. Frequency of TIs was compared across the two groups. Results Placentas from at-risk pregnancies had an eightfold increased odds of having two or more TIs compared with control samples (odds ratio : 8.0, 95% confidence interval : 3.6–18.0). The presence of≥2 TIs yielded a sensitivity of 41% and a specificity of 92% for predicting ASD risk status, whereas≥4 TIs yielded a sensitivity of 19%, a specificity of 99.9%, and a positive likelihood ratio of 242 and conservatively predicted an infant with a 74% probability of being at risk for ASD. Conclusions Our findings suggest that the placentas from women whose fetuses are at elevated risk for autism are markedly different from control placentas. These differences are manifested histologically as TIs. Their identification has the possibility of identifying newborns at risk for ASD who might benefit from targeted early interventions aimed at preventing or ameliorating behavioral symptoms and optimizing developmental outcomes.

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10. Lynch CJ, Uddin LQ, Supekar K, Khouzam A, Phillips J, Menon V. Default Mode Network in Childhood Autism : Posteromedial Cortex Heterogeneity and Relationship with Social Deficits. Biological Psychiatry ;2013 ;74(3):212-219.

Background The default mode network (DMN), a brain system anchored in the posteromedial cortex, has been identified as underconnected in adults with autism spectrum disorder (ASD). However, to date there have been no attempts to characterize this network and its involvement in mediating social deficits in children with ASD. Furthermore, the functionally heterogeneous profile of the posteromedial cortex raises questions regarding how altered connectivity manifests in specific functional modules within this brain region in children with ASD. Methods Resting-state functional magnetic resonance imaging and an anatomically informed approach were used to investigate the functional connectivity of the DMN in 20 children with ASD and 19 age-, gender-, and IQ-matched typically developing (TD) children. Multivariate regression analyses were used to test whether altered patterns of connectivity are predictive of social impairment severity. Results Compared with TD children, children with ASD demonstrated hyperconnectivity of the posterior cingulate and retrosplenial cortices with predominately medial and anterolateral temporal cortex. In contrast, the precuneus in ASD children demonstrated hypoconnectivity with visual cortex, basal ganglia, and locally within the posteromedial cortex. Aberrant posterior cingulate cortex hyperconnectivity was linked with severity of social impairments in ASD, whereas precuneus hypoconnectivity was unrelated to social deficits. Consistent with previous work in healthy adults, a functionally heterogeneous profile of connectivity within the posteromedial cortex in both TD and ASD children was observed. Conclusions This work links hyperconnectivity of DMN-related circuits to the core social deficits in young children with ASD and highlights fundamental aspects of posteromedial cortex heterogeneity.

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11. Parma V, Bulgheroni M, Tirindelli R, Castiello U. Body Odors Promote Automatic Imitation in Autism. Biological Psychiatry ;2013 ;74(3):220-226.

Background Autism spectrum disorders comprise a range of neurodevelopmental pathologies characterized, among other symptoms, by impaired social interactions. Individuals with this diagnosis are reported to often identify people by repetitively sniffing pieces of clothing or the body odor of family members. Since body odors are known to initiate and mediate many different social behaviors, smelling the body odor of a family member might constitute a sensory-based action promoting social contact. In light of this, we hypothesized that the body odor of a family member would facilitate the appearance of automatic imitation, an essential social skill known to be impaired in autism. Methods We recruited 20 autistic and 20 typically developing children. Body odors were collected from the children’s mothers’ axillae. A child observed a model (their mother or a stranger mother) execute (or not) a reach-to-grasp action toward an object. Subsequently, she performed the same action. The object was imbued with the child’s mother’s odor, a stranger mother’s odor, or no odor. The actions were videotaped, and movement time was calculated post hoc via a digitalization technique. Results Automatic imitation effects—expressed in terms of total movement time reduction—appear in autistic children only when exposed to objects paired with their own mother’s odor. Conclusions The maternal odor, which conveys a social message otherwise neglected, helps autistic children to covertly imitate the actions of others. Our results represent a starting point holding theoretical and practical relevance for the development of new strategies to enhance communication and social behavior among autistic individuals.

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12. ter Huurne N, Onnink M, Kan C, Franke B, Buitelaar J, Jensen O. Behavioral Consequences of Aberrant Alpha Lateralization in Attention-Deficit/Hyperactivity Disorder. Biological Psychiatry ;2013 ;74(3):227-233.

Background Attention-deficit/hyperactivity disorder (ADHD) is characterized by problems in directing and sustaining attention. Recent findings suggest that alpha oscillations (8–12 Hz) are crucially involved in gating information between brain regions when allocating attention. The current study investigates whether aberrant modulation of alpha oscillations contributes to attention problems in ADHD patients. Methods Magnetoencephalographic signals were recorded in adults with ADHD (n = 17) and healthy control subjects (n = 18) while they performed a visuospatial attention task. Cues directed attention to the left or right visual hemifield with an 80% validity with respect to the upcoming target. Results Unlike the control group, subjects with ADHD showed a higher accuracy for invalidly cued right targets compared with invalidly cued left targets (p = .04). This coincided with an inability of the ADHD subjects to sustain the posterior hemispheric alpha lateralization in the period before the target for the left cue condition (p = .011). Furthermore, the control group showed a strong correlation between the degree of alpha lateralization and the magnitude of the cueing effect assessed in terms of accuracy (rs = .71, p = .001) and reaction times (rs =−.81, p<.001). These correlations were absent in the ADHD group. Conclusions Our results demonstrate that subjects with ADHD have a failure in sustaining hemispheric alpha lateralization when cued to the left, resulting in an attentional bias to the right visual hemifield. These findings suggest that aberrant modulations of alpha oscillations reflect attention problems in ADHD and might be related to the neurophysiological substrate of the disorder.

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13. Meherwan Mehta U, Agarwal SM, Kalmady SV, Shivakumar V, Kumar CN, Venkatasubramanian G, Thirthalli J, Gangadhar BN, Pascual-Leone A, Keshavan MS. Enhancing Putative Mirror Neuron Activity with Magnetic Stimulation : A Single-Case Functional Neuroimaging Study. Biological Psychiatry ;2013 ;74(3):e1-e2.

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14. Amiet C, Gourfinkel-An I, Laurent C, Carayol J, Génin B, Leguern E, Tordjman S, Cohen D. Epilepsy in Simplex Autism Pedigrees is Much Lower Than the Rate in Multiplex Autism Pedigrees. Biological Psychiatry ;2013 ;74(3):e3-e4.

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