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Cited by 266Hypothalamic control of reproductive hormonesSexual Differentiation and DisordersNeural and Behavioral Psychology Studies

Puberty influences medial temporal lobe and cortical gray matter maturation differently in boys than girls matched for sexual maturity

Open access
Bramen, J. E., Hranilovich, J. A., Dahl, R. E., Forbes, E. E., Chen, J., Toga, A. W., Dinov, I. D., Worthman, C. M. +1 more·2011·Cerebral Cortex
DOI 10.1093/cercor/bhq137PMC PMC3041011
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Abstract

Sex differences in age- and puberty-related maturation of human brain structure have been observed in typically developing age-matched boys and girls. Because girls mature 1-2 years earlier than boys, the present study aimed at assessing sex differences in brain structure by studying 80 adolescent boys and girls matched on sexual maturity, rather than age. We evaluated pubertal influences on medial temporal lobe (MTL), thalamic, caudate, and cortical gray matter volumes utilizing structural magnetic resonance imaging and 2 measures of pubertal status: physical sexual maturity and circulating testosterone. As predicted, significant interactions between sex and the effect of puberty were observed in regions with high sex steroid hormone receptor densities; sex differences in the right hippocampus, bilateral amygdala, and cortical gray matter were greater in more sexually mature adolescents. Within sex, we found larger volumes in MTL structures in more sexually mature boys, whereas smaller volumes were observed in more sexually mature girls. Our results demonstrate puberty-related maturation of the hippocampus, amygdala, and cortical gray matter that is not confounded by age, and is different for girls and boys, which may contribute to differences in social and cognitive development during adolescence, and lasting sexual dimorphisms in the adult brain.

AI snapshot

Written from the paper’s full text.

TL;DR

In 80 adolescents matched on sexual maturity rather than age, puberty-related gray matter maturation differed by sex: more sexually mature boys showed larger medial temporal lobe volumes, while more sexually mature girls showed smaller amygdala and cortical gray matter volumes. These sex-by-puberty interactions were significant for the right hippocampus, bilateral amygdala, and cortical gray matter, independent of age in several analyses.

Key findings

  • Significant sex-by-pubertal-status interactions were found for the right hippocampus (b = −0.540, P = 0.013) and bilateral amygdala (right: b = −0.572, P = 0.010; left: b = −0.470, P = 0.035) using Tanner stage, with sex differences larger in mid/late puberty than pre/early puberty.
  • Boys in mid/late puberty had larger left amygdala volumes than boys in pre/early puberty (z = 1.82, P = 0.034), with trends for right amygdala (z = 1.55, P = 0.060) and right hippocampus (z = 1.61, P = 0.053); however, these effects could not be dissociated from age.
  • Girls in mid/late puberty had smaller bilateral cortical gray matter volumes than girls in pre/early puberty (right: z = −2.60, P = 0.005; left: z = −2.88, P = 0.002), and advanced Tanner stage predicted declining bilateral amygdala (right: b = −0.363, P = 0.018; left: b = −0.090, P = 0.568) and cortical gray matter (right: b = −0.379, P = 0.013; left: b = −0.415, P = 0.006) independent of age.
  • In girls, circulating testosterone correlated inversely with right amygdala volume (r = −0.289, P = 0.046) and bilateral cortical gray matter (right: r = −0.355, P = 0.014; left: r = −0.380, P = 0.008); no significant sex-by-puberty interactions were detected for thalamus or caudate.

Methods

  • Cross-sectional study of 80 healthy adolescents (48 girls, 32 boys) with complete data; girls’ age range 10.75–13.48 years, boys’ 11.73–13.98 years. Pubertal status was measured by physical exam using Tanner stages and by circulating testosterone from finger-stick blood samples.
  • Structural MRI was acquired on a 3-T Siemens Allegra scanner; FreeSurfer was used for automated segmentation of amygdala, hippocampus, thalamus, caudate, and cortical gray matter, with manual editing of hippocampal and amygdala delineations.
  • Analyses included t-tests, simultaneous multiple regression for sex, age, whole-brain volume, and sex-by-puberty interactions, Wilcoxon–Mann–Whitney tests for Tanner-stage group differences, and Pearson correlations for testosterone; boys and girls were also analyzed separately.

Limitations

  • Stated: in boys, effects of sexual maturity on amygdala volume could not be dissociated from concomitant age effects; in girls, testosterone effects on right MTL volume did not remain significant when age was added.
  • Stated: the study was cross-sectional, and the authors note future longitudinal studies are needed to parse hormonal versus age-related influences; results were not corrected for multiple comparisons because a relatively small number of hypothesis-driven tests were conducted.
  • Stated/evident: FreeSurfer validity varies by region, with amygdala and hippocampus less valid than some other regions, though manual editing and reliability checks were performed; the restricted age range and sampling difference in pre/early versus mid/late puberty proportions between boys and girls may limit generalization.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/cercor/bhq137

Cites

75 of 75 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 38 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Age was not a significant predictor of regional or cortical gray matter volume for any region in the multiple regression analyses.

    “Age was not a significant predictor of regional or cortical gray matter volume for any region in the multiple regression analyses (see Table 5).”
    Quote in the paperSubstantial claim
  • Findingown data

    There was a significant interaction between sex and physical sexual maturity in predicting left amygdala volume (b = -0.470, P = 0.035).

    “and bilateral amygdala (right: b = -0.572,P = 0.010; left: b = -0.470,P = 0.035)”
    Quote in the paperSubstantial claim
  • Findingown data

    In female participants/adolescent girls, higher circulating TES levels are associated with smaller bilateral cortical gray matter volumes (right: r = -0.355, P = 0.014; left: r = -0.380, P = 0.008), including when compared with same-age girls with lower levels.

    “Consistent with both our hypotheses and our findings using measures of physical sexual maturity, female participants with higher circulating TES levels had smaller bilateral cortical gray matter volumes (right: r = -0.355,P = 0.014; left: r = -0.380,P = 0.008) than female participants with lower circulating TES levels.”
    • Also stated in: § Discussion · plain
      “Consistent with our findings using TS, adolescent girls with higher levels of TES had smaller bilateral cortical gray matter than adolescent girls of the same age with lower levels.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Circulating testosterone (TES) levels reflect brain-relevant pubertal hormone exposure.
  • Findingown data

    There was a significant interaction between sex and circulating TES in predicting right cortical gray matter volume (b = -0.479, P = 0.020).

    “We also found a significant interaction between sex and how well circulating TES predicted the volume of cortical gray matter bilaterally (right: b = -0.479,P = 0.020; left: b = -0.502,P = 0.015)”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Circulating testosterone level is a valid measure of pubertal status in both boys and girls.
  • Findingown data

    TES was not significantly associated with age in girls.

    “TES was not significantly associated with age in girls.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 29
  • Classified as probably not a substantial claim. 17
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    Significant sex by puberty interactions in the cerebral cortex were driven by volume reductions in girls at more advanced pubertal stages, but no effect of sexual maturity on cortical volumes in boys was seen.

    “Significant sex by puberty interactions in the cerebral cortex were driven by volume reductions in girls at more advanced pubertal stages, but no effect of sexual maturity on cortical volumes in boys was seen.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Tanner staging (TS) is a valid measure of pubertal status.
    • Rests on an assumption: Circulating testosterone (TES) levels reflect brain-relevant pubertal hormone exposure.

  • May combine two claims.

    Findingown data

    Advanced physical sexual maturity significantly predicted declining right amygdala volume (b = -0.363, P = 0.018), independent from and better than age.

    “Advanced physical sexual maturity significantly predicted declining volume bilaterally in the amygdala (right: b = -0.363,P = 0.018; left: b = -0.090,P = 0.568) and bilaterally in the cortex (right: b = -0.379,P = 0.013; left: b = -0.415,P = 0.006), independent from and better than age.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the same multiple regression, neither circulating TES nor age contributed significant unique variance to MTL volume.

    “but neither circulating TES nor age contributed significant unique variance to MTL volume.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Circulating testosterone (TES) levels reflect brain-relevant pubertal hormone exposure.
    • Rests on an assumption: Age is an adequate covariate to dissociate pubertal from age-related effects.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims. The quote only partly states this claim.

    Findingown data

    Advanced physical sexual maturity was associated with left amygdala volume (b = -0.090, P = 0.568), independent from and better than age.

    “Advanced physical sexual maturity significantly predicted declining volume bilaterally in the amygdala (right: b = -0.363,P = 0.018; left: b = -0.090,P = 0.568) and bilaterally in the cortex (right: b = -0.379,P = 0.013; left: b = -0.415,P = 0.006), independent from and better than age.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were sex differences in age (P < 0.0001) and WBV (P < 0.0001) that did not change with advancing puberty.

    “There were sex differences in age (P < 0.0001) and WBV (P < 0.0001) that did not change with advancing puberty (i.e., the difference between boys and girls at early puberty was the same as differences between boys and girls in late puberty).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was a significant main effect of sex such that girls had smaller volumes than boys in all regions assessed (P < 0.001), with the exception of the caudate, which was not significantly different between the 2 sexes.

    “As predicted, there was a significant main effect of sex such that girls had smaller volumes than boys in all regions assessed (P < 0.001), with the exception of the caudate, which was not significantly different between the 2 sexes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Girls in mid/late puberty had a smaller right amygdala (z = 2.51, P = 0.006) than girls in pre/early puberty, though not significantly so, as these were results from a one-tailed test and in the unpredicted direction.

    “Specifically, girls in mid/late puberty had a smaller right amygdala (z = 2.51, P = 0.006) than girls in pre/ early puberty (see Fig. 4 and Table 4), though not significantly so, as these were results from a one-tailed test and in the unpredicted direction.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Circulating TES typically predicted regional volume qualitatively better than age; puberty had a larger estimated beta than age in most tests.

    “As with physical sexual maturity, circulating TES typically predicted regional volume qualitatively better than age; puberty had a larger estimated beta than age in most tests.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Circulating testosterone (TES) levels reflect brain-relevant pubertal hormone exposure.

  • May combine two claims.

    Findingown data

    In hippocampus, amygdala, and cortical gray matter, the effects of sex are not significant in pre/early puberty but are significant in mid/late pubertal children.

    “In these structures, we show that the effects of sex are not significant in pre/early puberty but are significant in mid/late pubertal children.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Tanner staging (TS) is a valid measure of pubertal status.
    • Rests on an assumption: Circulating testosterone (TES) levels reflect brain-relevant pubertal hormone exposure.

  • May combine two claims.

    Findingown data

    Significant interactions of sex with physical sexual maturity for the right hippocampus were driven by nonsignificant volume increases with increased sexual maturity in boys, and significant volume decreases with increased sexual maturity in girls, independent of age.

    “Significant interactions of sex with physical sexual maturity for the right hippocampus were driven by nonsignificant volume increases with increased sexual maturity in boys, and significant volume decreases with increased sexual maturity in girls, independent of age.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Tanner staging (TS) is a valid measure of pubertal status.
    • Rests on an assumption: Age is an adequate covariate to dissociate pubertal from age-related effects.

  • May combine two claims.

    Findingown data

    Advanced physical sexual maturity significantly predicted declining left cortical gray matter volume (b = -0.415, P = 0.006), independent from and better than age.

    “Advanced physical sexual maturity significantly predicted declining volume bilaterally in the amygdala (right: b = -0.363,P = 0.018; left: b = -0.090,P = 0.568) and bilaterally in the cortex (right: b = -0.379,P = 0.013; left: b = -0.415,P = 0.006), independent from and better than age.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In boys, sexual maturity measured using TS predicted volume increases in the MTL, significantly so in the left amygdala.

    “In boys, sexual maturity, measured using TS, predicted volume increases in the MTL, significantly so in the left amygdala.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Tanner staging (TS) is a valid measure of pubertal status.

  • May combine two claims.

    Findingown data

    TES level was positively correlated with age in boys, suggesting that older boys (P = 0.004) had higher TES levels than younger boys.

    “Similarly, TES level was positively correlated with age in boys, suggesting that older boys (P = 0.004) had higher TES levels than younger boys.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Advanced physical sexual maturity significantly predicted declining right cortical gray matter volume (b = -0.379, P = 0.013), independent from and better than age.

    “Advanced physical sexual maturity significantly predicted declining volume bilaterally in the amygdala (right: b = -0.363,P = 0.018; left: b = -0.090,P = 0.568) and bilaterally in the cortex (right: b = -0.379,P = 0.013; left: b = -0.415,P = 0.006), independent from and better than age.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the right hippocampus and bilateral amygdala, smaller volumes were observed in girls at later than earlier pubertal stages, with trends for boys to increase in volume with advancing pubertal status.

    “In these regions, smaller volumes were observed in girls at later than earlier pubertal stages, with trends for boys to increase in volume with advancing pubertal status (see Table 4).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In cortical gray matter regions, volume reductions were observed in girls at earlier than at later pubertal stages, whereas no differences were observed in the boys.

    “In these regions, volume reductions were observed in girls at earlier than at later pubertal stages, whereas no differences were observed in the boys.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Circulating testosterone level is a valid measure of pubertal status in both boys and girls.

  • May combine two claims.

    Findingown data

    In the bilateral thalamus, boys had larger volumes than girls in both pre/early and mid/late puberty; this effect was not different in pre/early than mid/late puberty.

    “In the bilateral thalamus, boys had larger volumes than girls in both pre/early and mid/late puberty; this effect was not different in pre/early than mid/late puberty.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    MTL volumes rise in boys and decline in girls when evaluated as a function of sexual maturity.

    “We show that MTL volumes rise in boys, and decline in girls, when evaluated as a function of sexual maturity.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Tanner staging (TS) is a valid measure of pubertal status.
    • Rests on an assumption: Circulating testosterone (TES) levels reflect brain-relevant pubertal hormone exposure.

  • May combine two claims.

    Findingown data

    TES was significantly correlated with age in boys, but not in girls.

    “TES was significantly correlated with age in boys, but not in girls.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Circulating testosterone (TES) levels reflect brain-relevant pubertal hormone exposure.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The criteria for Tanner stages are reliable.

    “While the literature states that the criteria for TS are reliable (Slora et al. 2009)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Slora et al. 2009

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The validity of regional delineations by FreeSurfer varies by region, with some regions, like the amygdala and hippocampus, being less valid than others.

    “As with manual methods, the validity of regional delineations by FreeSurfer varies by region, with some regions, like the amygdala and hippocampus, being less valid than others (Fischl et al. 2002).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fischl et al. 2002

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    A relatively small number of hypothesis-driven statistical tests were conducted to keep experiment-wise error low, and thus results presented were not corrected for multiple comparisons.

    “In these experiments, we conduct a relatively small number of hypothesis-driven statistical tests to keep experiment-wise error low, and thus, results presented were not corrected for multiple comparisons.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous structural MRI studies have shown that the volume of structures within the medial temporal lobe (MTL), specifically the amygdala and hippocampus, increases between childhood and adulthood.

    “Previous structural magnetic resonance imaging (sMRI) studies have shown that the volume of structures within the medial temporal lobe (MTL) (specifically, the amygdala and hippocampus) increases (Giedd et al. 1996;Sowell and Jernigan 1998;Yurgelun-Todd et al. 2003)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Giedd et al. 1996 source

      Not checked in the free run.

    • cites Sowell and Jernigan 1998

      Not checked in the free run.

    • cites Yurgelun-Todd et al. 2003

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous structural MRI studies have shown that gray matter in the dorsal frontal and parietal lobes thins between childhood and adulthood.

    “and that gray matter in the dorsal frontal and parietal lobes thins between childhood and adulthood (Giedd et al. 1999;Sowell et al. 2003;Sowell, Thompson, Leonard, et al. 2004;Shaw et al. 2008).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Giedd et al. 1999 source

      Not checked in the free run.

    • cites Sowell et al. 2003 source

      Not checked in the free run.

    • cites Sowell, Thompson, Leonard, et al. 2004

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Puberty-related maturation of the hippocampus, amygdala, and cortical gray matter may contribute to differences in social and cognitive development during adolescence, and lasting sexual dimorphisms in the adult brain.

    “which may contribute to differences in social and cognitive development during adolescence, and lasting sexual dimorphisms in the adult brain.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: MRI-derived volume changes in the hippocampus, amygdala, and cortical gray matter reflect underlying maturational changes in these structures.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The volumes resulting from the two editing sessions were nearly perfectly correlated (95% CI for ICC: 0.993 < ICC < 0.998).

    “The 95% confidence interval estimated for ICC was as follows 0.993 < ICC < 0.998, showing that volumes resultant from the 2 sessions are nearly perfectly correlated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    FreeSurfer volume estimates are highly reliable, and comparison of manual and automated hippocampal and amygdala volume estimates revealed no discernible statistical difference.

    “However, being completely automated, FreeSurfer volume estimates are highly reliable, and comparison of manual and automated hippocampal and amygdala volume estimates revealed no discernible statistical difference (Fischl et al. 2002).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fischl et al. 2002

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Conditions of collinearity were met for all multiple regression analyses described above (correlations between any two simultaneous predictors < 0.800).

    “Conditions of collinearity were met for all multiple regression analyses described above using the following criteria: the correlations between any 2 simultaneous predictors must be less than 0.800 [CORR(x,y) < 0.800) (O'brien 2007).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites O'brien 2007

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The results demonstrate puberty-related maturation of the hippocampus, amygdala, and cortical gray matter that is not confounded by age.

    “Our results demonstrate puberty-related maturation of the hippocampus, amygdala, and cortical gray matter that is not confounded by age, and is different for girls and boys”
    Quote in the paperSubstantial claim
    • Rests on an assumption: MRI-derived volume changes in the hippocampus, amygdala, and cortical gray matter reflect underlying maturational changes in these structures.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    The finger-stick bloodspot method for measuring testosterone provides several advantages over salivary assays for gonadal steroids, and the correspondence of bloodspot-derived level and plasma level is high.

    “This method provides several advantages over salivary assays for gonadal steroids, and the correspondence of bloodspot-derived level and plasma level is high.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Worthman and Stallings 1997

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Boys and girls differ in the soma sizes of neurons with gonadal steroid hormone receptors within the amygdala.

    “Another potential cellular mechanism of the observed sex differences is that boys and girls differ in the soma sizes of neurons with gonadal steroid hormone receptors within the amygdala.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Romeo and Sisk 2001

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    The age range of male and female participants, which varies across studies, affects conclusions that can be drawn by comparing findings.

    “The age range of male and female participants, which varies across studies, undoubtedly affects conclusions that can be drawn by comparing findings.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In rats, more new cells are added to the amygdala in males than in females during puberty, and reducing endogenous levels of pubertal hormones via gonadectomy reduces the number of new cells created.

    “In rats, it has been found that more new cells are added to the amygdala in males than in females during puberty and that reducing endogenous levels of pubertal hormones via gonadectomy reduces the number of new cells created (Ahmed et al. 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ahmed et al. 2008

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The impact of rising pubertal hormones on brain structure may vary depending on the sex of the individual and the state of brain maturation at the time the hormones are introduced.

    “The results presented here, and those of prior studies (Neufang et al. 2008), further support the notion that the impact of rising pubertal hormones on brain structure may vary depending on the sex of the individual and the state of brain maturation at the time the hormones are introduced.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Neufang et al. 2008

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The offsets between maturation of cortical and limbic structures, or right and left hemispheres, may differ by gender, even in puberty-matched populations.

    “Also, as we state above, the offsets between maturation of cortical and limbic structures, or right and left hemispheres, may differ by gender, even in puberty-matched populations.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Right frontal cortical thinning occurs prior to left frontal cortical thinning in children 5-11 years of age.

    “Previous studies have shown that right frontal cortical thinning occurs prior to left frontal cortical thinning in children 5--11 years of age (Sowell et al. 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sowell et al. 2001 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Both may be due to pubertal hormones causing an increase in MTL size when adolescents are young and a decrease in size when adolescents are older.

    “Both may be due to pubertal hormones causing an increase in MTL size when adolescents are young and a decrease in size when adolescents are older.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Thinner cortex in frontal and parietal cortices has been linked to more mature brain activation patterns in children and adolescents.

    “Thinner cortex in frontal and parietal cortices has been linked to more mature brain activation patterns in children and adolescents (Lu et al. 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lu et al. 2007

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Rates of depression in females increase sharply during adolescence, with evidence that pubertal hormones are stronger predictors than age.

    “For example, rates of depression in females increase sharply during adolescence, with evidence that pubertal hormones are stronger predictors than age (Angold et al. 1999).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Angold et al. 1999

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The incidence of depression and anxiety symptoms is much higher in girls than in boys starting in late childhood.

    “Indeed, the incidence of depression and anxiety symptoms are much higher in girls than in boys starting in late childhood (Bailey et al. 2007;Van Oort et al. 2009)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Bailey et al. 2007

      Not checked in the free run.

    • cites Van Oort et al. 2009

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This sexual dimorphism in soma sizes has been observed in the amygdala of rodents and depends on TES levels.

    “This sexual dimorphism has been observed in the amygdala of rodents and has also been found to depend on TES levels (Romeo and Sisk 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Romeo and Sisk 2001

      Not checked in the free run.

41 of 41

  • The paper relies on this without support.

    MRI-derived volume changes in the hippocampus, amygdala, and cortical gray matter reflect underlying maturational changes in these structures.

    “The cellular etiology of human brain maturational change is not well understood given the paucity of postmortem material in the childhood to adolescent age range.”
    “Our results demonstrate puberty-related maturation of the hippocampus, amygdala, and cortical gray matter that is not confounded by age, and is different for girls and boys”

  • The paper relies on this without support.

    Circulating testosterone level is a valid measure of pubertal status in both boys and girls.

    “We focus on TES in our report of hormonal effects on brain maturation because TES was collected in both boys and girls.”

  • The paper relies on this without support.

    Tanner staging (TS) is a valid measure of pubertal status.

    “Experiment 1: pubertal status determined by TS”

  • The paper relies on this without support.

    Circulating testosterone (TES) levels reflect brain-relevant pubertal hormone exposure.

    “Experiment 2: pubertal status determined by TES”

  • The paper relies on this without support.

    Cross-sectional differences in brain volume across pubertal stages reflect developmental changes (maturation) rather than cohort effects.

    “Future longitudinal studies will be ideal in parsing hormonal or other age-related influences on changes in the trajectories of gray matter volumes.”

  • The paper relies on this without support.

    Age is an adequate covariate to dissociate pubertal from age-related effects.

    “All these effects were significant even when age was used as an additional predictor”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • When controlling for age, both pubertal hormones and stage of puberty correlate with changes in gray matter across adolescent development in disparate regions of cortex, including frontal cortex.

    “When controlling for age, both pubertal hormones and stage of puberty correlate with changes in gray matter across adolescent development in disparate regions of cortex (De Bellis et al., 2001), including in the frontal cortex (Bramen et al., 2011; Gogtay et al., 2004; Herting et al., 2014; Herting et al., 2015; Koolschijn et al., 2014; Neufang et al., 2009; Peper et al., 2009a; Raznahan et al., 2”

    From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Bramen et al., 2011

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Consistentz = 1.82reported p = .034 · recomputed p = .069

    “(z = 1.82,p = .034”

    The paper states a one-tailed test

  • Consistentz = 1.55reported p = .06 · recomputed p = .121

    “(z = 1.55,p = .060”

    The paper states a one-tailed test

  • Consistentz = 1.61reported p = .053 · recomputed p = .107

    “(z = 1.61,p = .053”

    The paper states a one-tailed test

  • Consistentz = -2.6reported p = .005 · recomputed p = .009

    “(z = -2.60,p = .005”

    The paper states a one-tailed test

  • Consistentz = -2.88reported p = .002 · recomputed p = .004

    “z = -2.88,p = .002”

    The paper states a one-tailed test

  • Consistentz = 2.51reported p = .006 · recomputed p = .012

    “(z = 2.51, p = .006”

    The paper states a one-tailed test

6 of 6

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Bilateral amygdala effect is claimed although the left-sided result is nonsignificant

    Major

    The text calls the age-adjusted association significant bilaterally, but reports P = 0.568 for the left amygdala. Only the right-sided P value is below 0.05.

  • Right hippocampal decrease in girls is called significant despite its reported P value

    Major

    The discussion says the decrease with sexual maturity in girls was significant independently of age. Table 5 reports P = 0.087 for sexual maturity predicting right hippocampal volume in girls after accounting for age, above the paper's 0.05 threshold.

  • Direction of cortical volume change in girls is reversed

    Minor

    One results paragraph says girls had cortical volume reductions at earlier rather than later pubertal stages. The later description says girls in earlier stages had larger cortical volumes than those in later stages.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 6

  1. 2009, 30, 1
  2. 2006, 138, 997
  3. 2006, STAT COMPUT GRAPHICS, 17, 11
  4. 2009, FRONT NEUROINFORMAT, 3, 22
  5. 2002, 33, 341
  6. 2009, 34, 332

Cited by

Sorted by citations

Related

Authors
Bramen, J. E., Hranilovich, J. A., Dahl, R. E., Forbes, E. E., Chen, J., Toga, A. W., Dinov, I. D., Worthman, C. M., & Sowell, E. R.
Affiliations
  • University of California, Los Angeles (US)
  • University of Pittsburgh (US)
  • Emory University (US)
ORCID
Venue
Cerebral Cortex
Publisher
Oxford University Press (OUP)
Published
2010-08-16
Volume
21
Issue
3
Pages
636-646
ISSN
  • 1047-3211 (ISSN-L)
  • 1460-2199
DOI
10.1093/cercor/bhq137
PMC
PMC3041011
OpenAlex
W2169286936
Semantic Scholar
38f422c22d6af3848629975eef9f94899a178353
Cited by
266
References
75
Citations by year
2026: 6 · 2025: 8 · 2024: 8 · 2023: 20 · 2022: 7 · 2021: 17 · 2020: 24 · 2019: 13 · 2018: 17 · 2017: 14 · 2016: 24 · 2015: 25 · 2014: 18 · 2013: 27 · 2012: 28
FWCI
24.66
Type
journal article
Language
en
Open access
Locations
  • Cerebral Cortex (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Drug Abuse (R01DA018910, R01 DA 017831)
  • National Center for Research Resources (P41RR013642, U54RR021813)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD053893)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
puberty, brain maturation, sex differences, medial temporal lobe, hippocampus, amygdala, cortical gray matter, sexual maturity, testosterone, thalamus, caudate nucleus, adolescent brain development, sexual dimorphism
MeSH terms
Adolescent, Cerebral Cortex, Child, Female, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Puberty, Sex Characteristics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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