Increased Rate of Amygdala Growth in Children Aged 2 to 4 Years With Autism Spectrum Disorders

Abstract

Context Precocious amygdala enlargement is commonly observed in young children with autism. However, the age at which abnormal amygdala enlargement begins and the relative growth trajectories of the amygdala and total brain remain unclear. Objective To determine whether the rate of amygdala growth is abnormal and disproportionate to total brain growth in very young children with autism spectrum disorders (ASDs). Design Longitudinal structural magnetic resonance imaging study. Setting Neuroimaging and diagnostic assessments were performed at an academic medical center. Participants were recruited from the community. Participants Baseline scans were acquired in 132 boys (85 with ASD and 47 control subjects with typical development [TD]; mean age, 37 months). Longitudinal magnetic resonance images were acquired in 70 participants (45 with ASD and 25 TD controls) 1 year later. Main Outcome Measure Amygdala volumes and total cerebral volumes (TCVs) were evaluated at both time points, and 1-year growth rates were calculated. Results The amygdala was larger in children with ASD at both time points, but the magnitude of enlargement was greater at time 2. The TCV was also enlarged in the children with ASD by the same magnitude at both time points. When we controlled for TCV, amygdala enlargement remained significant at both time points. The rate of amygdala growth during this 1-year interval was faster in children with ASD than in TD controls. The rate of TCV growth did not differ between groups. Post hoc exploratory analyses revealed 3 patterns of amygdala and TCV growth rates in the ASD group. Conclusions Disproportionate amygdala enlargement is present by 37 months of age in ASD. The amygdala continues to grow at an increased rate, but substantial heterogeneity exists in amygdala and TCV growth patterns. Future studies aimed at clinical characterization of different growth patterns could have implications for choice and outcomes of treatment and behavioral therapy.

Neuroimaging in autism spectrum disorder: brain structure and function across the lifespan

“…41 The amygdala is also signifi cantly enlarged in children with ASD compared with typically developing children. 42 However, enlargement of the basal ganglia has also been noted in individuals with obsessive-compulsive disorder without a comorbid diagnosis of ASD, 43 and increased total amygdala volume has been reported in children with general anxiety disorders. 44 Finally, frontal lobe abnormalities, which are a hallmark of ASD, have also been found in other neurodevelopmental disorders such as schizophrenia.…”

The Neuro-Environmental Loop of Plasticity: A Cross-Species Analysis of Parental Effects on Emotion Circuitry Development Following Typical and Adverse Caregiving

“…Although the most rapid postnatal volumetric growth occurs soon after birth (eg, over 100% increase in volume in 0-1 year followed by a 9% increase from years 1 to 2; Gilmore et al, 2012; also see Payne et al, 2010;Uematsu et al, 2012), the amygdala continues to increase in volume until 4 years of age in females and 18 years of age in males (Giedd et al, 1996;Mosconi et al, 2009;Nordahl et al, 2012;Schumann et al, 2004). Amygdala physiology also undergoes significant change early in life.…”

Correlatos estructurales de las alteraciones cognitivas en niños con TEA

“…Los resultados indicaron que los participantes con TEA tenían significativamente mayores volúmenes de SG que el grupo control en la corteza orbitofrontal inferior derecha y en el tálamo bilateral (núcleo dorsal medial izquierdo y núcleo dorsal lateral derecho). Además, en el estudio corroboraron los datos obtenidos en estudios previos de que la edad es un factor influyente en los patrones de crecimiento atípicos en el autismo (Nordahl et al, 2012;Scheel et al, 2011;Raznahan et al, 2010;Greimel et al, 2013;Zielinski et al, 2014;Langen et al, 2009;McAlonan et al, 2002).…”

“…Hay evidencia creciente en los estudios transversales que sugieren que en comparación con los controles, el volumen de la amígdala se incrementa en los niños pequeños con autismo (Kim et al, 2010a(Kim et al, , 2010bMosconi et al, 2009;Munson et al, 2006;Nordahl et al, 2012;Schumann et al, 2009;Sparks et al, 2002), no se modifica en jóvenes de mayor edad (Bigler et al, 2003;Haznedar et al, 2000, Palmen et al, 2006 y es menor en adultos (Aylward et al, 1999;Nacewicz et al, 2006, Pierce & Courchesne, 2001Rojas et al, 2004).…”

“…Estas regiones específicas corresponden a aquellas cuyo desarrollo se produce en personas neurotípicas en los primeros 4 años de vida, e incluyen zonas frontales mediales, zonas límbicas y zonas subcorticales. En concreto, estas zonas relevantes en el autismo son la corteza frontal medial (Carper et al, 2002;Carper & Courchesne, 2005;Herbert et al, 2004), el lóbulo temporal, áreas límbicas como el hipocampo Barnea-Goraly et al, 2014), la amígdala (Mosconi et al, 2009;Munson et al, 2006;Nordahl et al, 2012;Schumann et al, 2009;Sparks et al, 2002), y el córtex cingulado (Joseph, Ehrman, McNally & Keehn, 2008;Bush, Luu & Posner, 2000;Thakkar et al, 2008), y zonas subcorticales como el estriado (Sears et al, 1999;Hazlett et al, 2005;, y el tálamo (Say et al, 2014;Schuetze et al, 2016 Por tanto, la trayectoria de desarrollo cerebral observada en individuos con TEA indica un patrón de crecimiento acelerado durante la infancia, seguido de una ralentización en la adolescencia temprana para igualarse al final de la adolescencia y durante la edad adulta. Este proceso madurativo es diferente en el desarrollo cerebral humano típico, donde el volumen cerebral total presenta una trayectoria en forma de U invertida, con un crecimiento rápido en la infancia y con un punto máximo sobre 10-12 años para empezar a declinar sobre la adolescencia tardía (Lenroot et al, 2007) logrando el tamaño del volumen de adulto más tarde que el grupo con TEA.…”