Sex Differences in Brain Maturation during Childhood and Adolescence

“…al., 1996; Lange et al., 1997; Kennedy et al., 1998, 2003; Paus et al., 1999; Sowell et al., 1999, 2002, 2003, 2004a,b; Courchesne et al., 2000; Bartzokis et al., 2001; Blanton et al., 2001, 2004; De Bellis et al., 2001; Durston et al., 2001; Mazziotta et al., 2001a,b; Gogtay et al., 2002, 2004).”

“[47] De Bellis MD, Keshavan MS, Beers SR, Hall J, Frustaci K, Masalehdan A, Noll J, Boring AM.”

“In a cross-sectional sample of 118 healthy children and adolescents growth rates were faster in males than females for total gray and white matter volumes and the area of the corpus callosum (De Bellis et al., 2001).”

“Also, hormonal changes during puberty may trigger changes in emotion-related neural circuitry differently for boys and girls, further contributing to gender differences in emotion expression (e.g., De Bellis et al., 2001).”

“The fact that white matter develops until late in childhood has been shown in previous studies (Schmithorst et al., 2002; De Bellis et al., 2001; Mukherjee et al., 2001; Giedd, Blumenthal, Jeffries, Castellanos, et al., 1999; Klingberg et al., 1999; Paus et al., 1999; Sowell et al., 1999; Caviness…”

“…sizes in males emerging during the first 4 or 5 years of life (Dekaban 1978), findings that have been confirmed in numerous developmental imaging studies (Caviness and others 1996; Giedd and others 1997, 1999; Courchesne and others 2000; De Bellis and others 2001; Sowell, Trauner, and others 2002).”

“At the cellular level, synaptic pruning and myelination even takes place until after puberty and adolescence (De Bellis et al., 2001; Levitt, 2003).”

“…have documented both steeper slopes of white matter growth curves in males compared with females and males having an overall more protracted period of development, suggesting brain dimorphism not only in overall growth but also in growth trajectories (De Bellis et al. 2001; Lenroot et al. 2007).”

“Some sex differences have been related to structural neuroimaging (e.g., De Bellis et al., 2001; Goldstein et al., 2001; Gur et al., 1999; Lenroot et al., 2007) and functional imaging measures (e.g., Gur et al., 2000; Gur et al., 1982, Gur et al., 1995; Lenroot & Giedd, 2010), including volumetric…”

“Cross-sectional neuroimaging studies of older children indicate that cortical gray matter volumes decrease after 4 –5 years of age to puberty (Pfefferbaum et al., 1994; Reiss et al., 1996; Courchesne et al., 2000; De Bellis et al., 2001).”

“Initial cross-sectional studies indicate that male youth have larger white matter volumes with steeper increases in white matter growth and a more protracted maturation time course than females (De Bellis et al., 2001; Filipek et al., 1994; Lenroot et al., 2007).”

“The adolescent brain undergoes dramatic maturational changes, which may partly be influenced by underlying pubertal hormone changes (De Bellis et al. 2001; Giedd 2004).”

“…and subcortical grey matter volumes typically peak 1–2 years earlier in females than males (Lenroot and Giedd 2006), male children and adolescents show more prominent grey matter reductions and white matter volume increases with age than do females (Blanton et al. 2004; De Bellis et al. 2001).”

“…in brain anatomy have been increasingly documented with methods for morphometric analysis of magnetic resonance imaging (MRI) data (Gur et al., 1991, 1999; Raz et al., 1997; Coffey et al., 1998; Courchesne et al., 2000; Nopolus et al., 2000; De Bellis et al., 2001; Goldstein et al., 2001).”

“The fact that white matter develops until late in childhood has been shown in previous studies (Caviness et al., 1996; De Bellis et al., 2001; Giedd et al., 1999; Klingberg et al., 1999; Mukherjee et al., 2001; Paus et al., 1999; Pfefferbaum et al., 1994; Reiss et al., 1996; Schmithorst et al.,…”

“These have been found to influence brain tissue volumes and cortical thickness measures in previous studies [Courchesne et al., 2000; De Bellis et al., 2001; Good et al., 2001b; Sowell et al., 2003, 2004].”

“For example, during adolescence, boys show a steeper slope of increase in global white matter volume with age than girls, resulting in larger white matter volumes in boys compared with girls (Giedd et al. 1999; De Bellis et al. 2001; Lenroot et al. 2007).”

“The growth of WM during childhood and adolescence follows a strikingly different trajectory in girls and boys; it increases with age slightly in girls and steeply in boys (De Bellis et al., 2001; Lenroot et al., 2007).”

“In the NIH longitudinal sample [23] and in an independent cohort of 188 children and adolescents [57], WM in males grew more rapidly, resulting in increasingly larger volumes relative to females with age.”

“…alterations take place during this period, such as maturational processes in the medial prefrontal cortex (mPFC) and limbic regions, which are characterized by both progressive and regressive changes, e.g. myelination and synaptic pruning (Spear 2000; De Bellis et al. 2001; Powell 2006).”

“Many parameters of brain function and structure vary between men and women (eg Gur et al, 1995; Murphy et al, 1996; De Courten-Myers, 1999; De Bellis et al, 2001; Goldstein et al, 2001; Preece and Cairns, 2003; De Vries, 2004), and most psychiatric disorders show sex differences in one or more…”

“Brain structure and function undergo rapid and dynamic changes over the childhood and adolescent periods, and sex differences have been found in the development of a number of brain regions (De Bellis et al., 2001; Giedd et al., 1997).”

“…MRI studies have demonstrated sex differences and lateral asymmetries in the global/regional brain gray matter volume/white matter volume/cortical thickness (De Bellis et al. 2001; Durston et al. 2001; Allen et al. 2003; Luders et al. 2005, 2006; for extensive review see Lenroot and Giedd 2006).”

“These outcomes agree with reports of greater age-related changes in posterior regions than in anterior regions in subjects aged 4 –18 years (Giedd et al., 1996, 1997, 1999; Rajapakse et al., 1996), 7–22 years (Chung et al., 2001), and 6 –15 years (Thompson et al., 2000).”

“No rescaling of brain images, images measured in native space ( De Bellis et al. 2001 ) F 57 12 768 420 1.83 10.3% 16.2%”

“Clinical studies with magnetic resonance imaging have shown robust decreases in grey matter density occurring in several areas of brain growth during the transitions between childhood, adolescence and adulthood (De Bellis et al., 2001; Sowell et al., 2001).”

“…alterations take place during puberty, such as maturational processes in the cortical and limbic regions (e.g., amygdala, nucleus accumbens) as characterized by both progressive and regressive changes, e.g., myelination and synaptic pruning (De Bellis et al. 2001; Powell 2006; Spear 2000).”

“While there are significant changes in grey and white matter during adolescence, which clearly can have major effects on cognitive functions (De Bellis et al., 2001), we doubt that the folding pattern of the cortex would alter with these changes, although this has yet to be addressed directly.”

“…size, a significant sex–age interaction has been demonstrated, with boys displaying greater rates of increase with age of normalized white matter volume, and greater rates of decrease with age of normalized gray matter volume, relative to girls between the ages of 7–17 [De Bellis et al., 2001].”

“…et al., 2005; Hua et al., 2009), while white matter connecting gray matter areas increases steadily from birth to adulthood (Paus et al., 1999; De Bellis et al., 2001; Schmithorst et al., 2002; Suzuki et al., 2003; Nagy et al., 2004; Barnea-Goraly et al., 2005; Schmithorst et al., 2008; Olson…”

“Sex differences in brain structure are well documented (48, 49) and are increasingly tied to developmental effects related to puberty (13, 46, 50–53).”

“…functional neurodevelopmental processes, including differentiation and specialisation of cortical regions/networks, synaptic and axonal pruning, and alterations in excitatory and inhibitory (E/I) circuits (De Bellis et al., 2001; Feinberg & Campbell, 2010; Lujan et al., 2005; Uhlhaas et al., 2010).”

“…changes in anisotropy that reflect maturation of the right SLF and PLIC showed smaller effect sizes in females and may coincide with previous findings of increased volumetric growth of white matter in male than female adolescents (De Bellis et al., 2001; Lenroot et al., 2007; Perrin et al., 2009).”

“…were recruited so as to minimize the influences of age and possible interactions of age with gender, which have been demonstrated to influence tissue measures in previous studies (Courchesne et al., 2000; De Bellis et al., 2001; Jernigan et al., 2001; Good et al., 2001b; Sowell et al., 2003 ).”

“During adolescence, white matter rowth follows a remarkably different trajectory in girls and oys; it increases with age slightly in girls and steeply in oys (De Bellis et al., 2001; Lenroot et al., 2007; Perrin et l., 2009).”

“This is consistent with sex differences in brain development and rates of maturation that have previously been observed by magnetic resonance imaging in slightly older children (6–17 years of age) [41] and represent a possible regulatory mechanism requiring additional investigation.”

“Some sex differences have been related to structural neuroimaging (e.g., De Bellis et al., 2001; Goldstein et al., 2001; Gur et al., 1999; Lenroot, et al., 2007) and functional imaging measures (e.g., Gur et al., 1982; 1995; 2000; Lenroot & Giedd, 2010), including volumetric differences in…”

“On the other hand, agerelated increases in the volume of white matter are linear, with a much steeper age-related increase in males compared with females (Giedd et al. 1999; De Bellis et al., 2001).”

“Using nonquantitative methods, numerous imaging studies of preterm children have shown that recognizable cerebral insults such as parenchymal brain injury and observable abnormalities of myelination are correlated with suboptimal developmental and cognitive outcome.(30,31) Recently, Nosarti et al performed quantitativ…”

“Various neuronal maturation and rearrangement processes occur during this period, such as myelination, synaptic pruning and dendritic plasticity ( De Bellis et al. 2001 ).”

“Increase in white matter during childhood has been demonstrated to be smaller in girls than in boys [60], which could make girls more vulnerable to neurotoxic effects of chemotherapy.”

“…interact with sex to affect white matter volume in multiple tracts in the human brain, including those connecting higher association cortices (Asato et al., 2010; Chavarria et al., 2014; De Bellis et al., 2001; Herting et al., 2012; Peper et al., 2008; Perrin et al., 2008; Perrin et al., 2009).”

“There is at present not enough data to demonstrate which underlying inXuences model these diVerences: genetic, environmental, hormonal, or combined inXuences would seem to be the most likely candidates (Cameron 2001; De Bellis et al. 2001; Thompson et al. 2001).”

“Significant interactions of age-by-sex, sex-by-IQ, or age-by-sex-by-IQ have been identified in previous studies of children on functional connectivity [97,105,106], anatomical connectivity [107], brain perfusion [23], and brain structure [50,108,109,110,111,112].”

“In addition, Giedd et al. (1996) highlighted that there are gender specific differences in brain development and it has been proposed that these differences may be related to hormone production (De Bellis et al., 2001).”

“Due to the substantial influence on brain morphology, age (in months at date of MR exam), gender, and handedness were considered covariates of no interest (nuisance variables) in order to allow factoring out their effects (Amunts et al., 1996; Courchesne et al., 2000; DeBellis et al., 2001; Good et al., 2001; Lange et…”

“volume in adolescence is steeper in males than in females [52] due to delayed brain maturation in males relative to females.”

“…age-related effects on GM and WM, are consistent across laboratories, corroborating our reports highlighted above (e.g., Giedd et al., 1999; De Bellis et al., 2001; Sowell et al., 2003; Paus, 2005; Lenroot et al., 2007; Hsu et al., 2008; Blakemore et al., 2010; Clayden et al., 2012; Hertig et…”

“The mechanism for sex-specific risk is not fully understood but may result from differences in cerebral myelination (21,22).”

“This fine-tuning within and between brain regions strengthens a number of particular pathways, which increases brain efficiency, critical to the development of cognitive abilities.(39,40) School age will be marked by the highest rate of development of specific areas of the brain, particularly the posterior sensorimoto…”

“Some magnetic resonance imaging studies have also found that, for at least some memory-related brain structures, ageing effects might be more apparent in men than women (De Bellis et al., 2001; Sowell et al., 2007; Sullivan, Rosenbloom, Serventi, & Pfefferbaum, 2004).”

“…Sullivan and Pfefferbaum, 2006), sex (Hsu et al., 2008; Szeszko et al., 2003), brain development (Ashtari et al., 2007; Courchesne et al., 2000; De Bellis et al., 2001; Giorgio et al., 2008; Schneiderman et al., 2007), behavioral variables (Deutsch et al., 2005) or reaction times (Madden et al.,…”

“Increase in white matter during childhood has been demonstrated to be smaller in girls than in boys [55], which could leave them more vulnerable.”

“Males have consistently been described in the literature as having greater increase in total WM during childhood and young adulthood than females (Caviness et al., 1996; De Bellis et al., 2001; Giedd et al., 1999; Gur et al., 1999; Perrin et al., 2009).”

“Although reports on regional sex differences between boys and girls are somewhat equivocal (e.g., compare De Bellis et al., 2001; Giedd et al., 1997; Sowell et al., 2007), several studies reported emerging regional differences limited to subcortical structures and WM (Giedd et al., 1997; Neufang et…”

“Gender differences show that males exhibit steeper developmental slopes in grey matter reduction and white matter increase than females (De Bellis et al., 2001; Giedd et al., 1999, 2006), partly explained by earlier maturation peaks in females in frontal, striatal, temporal and parietal NeuroImage…”

“By accounting for age and gender effects that have been previously reported in developmental MRI studies (De Bellis et al., 2001; Reiss et al., 1996; Sowell et al., 2002), we found significant relationships between general cognitive ability (IQ) and the volume of subcortical brain structures…”

“The focus of this work on boys at risk will be on the androgen testosterone, which causes male and female brains to develop differently in prenatal periods, infancy, childhood, adolescence, and adulthood (De Bellis et al., 2001; Hutchinson, 1997).”

“…matter and corpus callosum volume from 6–17 years of age; however, girls show these developmental changes gradually over this age range, while boys show a dramatic increase over a shorter time period, with greater volumetric changes than the girls between ages 10–14 years (De Bellis et al., 2001).”