Corticostriatal-Limbic Gray Matter Morphology in Adolescents With Self-reported Exposure to Childhood Maltreatment

In the paper

“There was a trend towards an inverse association with left RPFC (BA10); the cluster size was beneath the study threshold at 44 voxels.”

In the paper

“In females, CTQ total scores were inversely correlated with volume in right RPFC (BA10), bilateral OFC (BA11/47), bilateral sgPFC (BA25/32), bilateral amygdala and hippocampus, right insula, bilateral temporal association cortex (BA20/21/38), bilateral fusiform gyrus (BA20)”

In the paper

“emotional neglect with bilateral DLPFC (BA46/9), bilateral RPFC (BA10), bilateral dorsal anterior cingulate cortex (BA24/32), right superior frontal gyrus (BA8), right OFC (BA47), bilateral sgPFC (BA25), bilateral striatum, bilateral amygdala and hippocampus”

In the paper

“Total CTQ scores showed a significant inverse correlation with GM volume in bilateral dorsolateral prefrontal cortex (DLPFC) [Brodmann's Area (BA) 46/9], bilateral rostral prefrontal cortex (RPFC) (BA10), left subgenual PFC (sgPFC) (BA25), bilateral striatum and right amygdala”

In the paper

“Physical abuse, physical neglect and emotional neglect were associated with rostral prefrontal reductions.”

In the paper

“Females and males did not differ significantly in age, CTQ total or CTQ subscale scores.”

In the paper

“These morphological changes are associated with behavioral changes, including increased impulsive, anxious and depressive behaviors.49,55–57”

What the sources say

• Not checked yetcites [49] Sciolino NR Bortolato M Eisenstein SA Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats Neuroscience 2010 168 371 386 20394803 PMC2882942
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In the paper

“Findings in females were in regions associated with emotional regulation, whereas in males with regions subserving impulse control.”

In the paper

“The RPFC is associated with behavioral control functions including directing attention, decision-making, response inhibition and emotional regulation.60–63”

What the sources say

• Not checked yetcites [60] Christoff K Prabhakaran V Dorfman J Rostrolateral prefrontal cortex involvement in relational integration during reasoning NeuroImage 2001 14 1136 1149 11697945
• Not checked yetcites [61] Burgess PW Gilbert SJ Dumontheil I Function and localization within rostral prefrontal cortex (area 10) Philos Trans R Soc Lond B Biol Sci 2007 362 887 899 17403644 PMC2430004
• Not checked yetcites [62] Miller EK Cohen JD An integrative theory of prefrontal cortex function Annu Rev Neurosci 2001 24 167 202 11283309
• Not checked yetcites [63] Wager TD Davidson ML Hughes BL Lindquist MA Ochsner KN Prefrontal-subcortical pathways mediating successful emotion regulation Neuron 2008 59 1037 1050 18817740 PMC2742320

In the paper

“DLPFC functions overlap RPFC functions, and include working memory, cognitive reappraisal of affective experience and behavioral planning.64–68”

What the sources say

• Not checked yetcites [64] Levy R Goldman-Rakic PS Segregation of working memory functions within the dorsolateral prefrontal cortex Exp Brain Res 2000 133 23 32 10933207
• Not checked yetcites [65] Goldin PR McRae K Ramel W Gross JJ The neural bases of emotion regulation: reappraisal and suppression of negative emotion Biol Psychiatry 2008 63 577 586 17888411 PMC2483789
• Not checked yetcites [66] Koechlin E Corrado G Pietrini P Grafman J Dissociating the role of the medial and lateral anterior prefrontal cortex in human planning Proc Natl Acad Sci U S A 2000 97 7651 7656 10852964 PMC16600
• Not checked yetcites [67] Mansouri FA Tanaka K Buckley MJ Conflict-induced behavioural adjustment: a clue to the executive functions of the prefrontal cortex Nat Rev Neurosci 2009 10 141 152 19153577
• Not checked yetcites [68] Ochsner KN Bunge SA Gross JJ Gabrieli JD Rethinking feelings: an FMRI study of the cognitive regulation of emotion J Cogn Neurosci 2002 14 1215 1229 12495527

In the paper

“Results of exploratory analyses, while preliminary, support prominent reductions in RPFC volume common across physical abuse, physical neglect and emotional neglect CM subtypes, as well as patterns of additional regional volume decreases in the CM subtypes.”

In the paper

“The PFC is one of the brain regions most vulnerable to stress in animal models, showing stress-related decreases in dendritic length, branching and spine densities.3, 48,50.59”

What the sources say

• Not checked yetcites 3, 48,50.59

In the paper

“acute effects of stress on corticostriatal-limbic morphology demonstrated in the basic models include epigenetic effects on the hypothalamic-pituitary-adrenal (HPA) axis, dysregulated functioning of neurotransmitter and intracellular signaling pathways, as well as reductions in neurotrophic factors and neurogenesis.3,50–54”

What the sources say

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• Not checked yetcites [54] Gould E Tanapat P McEwen BS Flugge G Fuchs E Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress Proc Natl Acad Sci U S A 1998 95 3168 3171 9501234 PMC19713

In the paper

“Timing and duration of CM exposure may influence GM differences.110”

What the sources say

• Not checked yetcites [110] Tottenham N Sheridan MA A review of adversity, the amygdala and the hippocampus: a consideration of developmental timing Frontiers in Human Neuroscience 2010 3 1 18 PMC2813726 20161700

In the paper

“Adolescence is a particularly vulnerable time for the development of mood, anxiety and addictive disorders and CM has been linked to increased vulnerability to these disorders.25,69,117–119”

What the sources say

• Not checked yetcites [25] Spinhoven P Elzinga BM Hovens JG The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders J Affect Disord 2010 In Press 20304501
• Not checked yetcites [69] Ferry AT Ongur D An X Price JL Prefrontal cortical projections to the striatum in macaque monkeys: evidence for an organization related to prefrontal networks J Comp Neurol 2000 425 447 470 10972944
• Not checked yetcites [117] Parker G Hadzi-Pavlovic D Greenwald S Weissman M Low parental care as a risk factor to lifetime depression in a community sample J Affect Disorders 1995 33 173 180 7790669
• Not checked yetcites [118] Galler JR Bryce CP Waber D Early childhood malnutrition predicts depressive symptoms at ages 11–17 J Child Psychol Psychiatry 2010 51 789 798 20331492 PMC2906663
• Not checked yetcites [119] Colvert E Rutter M Beckett C Emotional difficulties in early adolescence following severe early deprivation: findings from the English and Romanian adoptees study Dev Psycopathol 2008 20 547 567 18423094

In the paper

“it has been theorized that an individual's perception of the neglect and/or maltreatment may be especially relevant in the psychological and neuropsychological development of the child.116”

What the sources say

• Not checked yetcites [116] Browne C Winkelman C The effect of childhood trauma on later psychological adjustment J Interpers Violence 2007 22 684 697 17515430

In the paper

“self-reports have been shown previously to be reliable and may be sensitive to CM that may not reach clinical awareness.41,42,114,115”

What the sources say

• Not checked yetcites [41] Bernstein DP Stein JA Newcomb MD Development and validation of a brief screening version of the Childhood Trauma Questionnaire Child Abuse Negl 2003 27 169 190 12615092
• Not checked yetcites [42] Scher CD Stein MB Asmundson GJ McCreary DR Forde DR The childhood trauma questionnaire in a community sample: psychometric properties and normative data J Trauma Stress 2001 14 843 857 11776429
• Not checked yetcites [114] Fink LA Bernstein D Handelsman L Foote J Lovejoy M Initial reliability and validity of the childhood trauma interview: a new multidimensional measure of childhood interpersonal trauma Am J Psychiatry 1995 152 1329 1335 7653689
• Not checked yetcites [115] Bernstein DP Fink L Handelsman L Initial reliability and validity of a new retrospective measure of child abuse and neglect Am J Psychiatry 1994 151 1132 1136 8037246

In the paper

“emotional neglect was the most frequently reported subtype; findings seen only within this subgroup may have resulted from greater power to detect differences.”

In the paper

“Pubertal hormones have organizing effects on the development of this system, and its development has been shown to be sexually dimorphic.31,32,102”

What the sources say

• Not checked yetcites [31] Lenroot RK Gogtay N Greenstein DK Sexual dimorphism of brain developmental trajectories during childhood and adolescence NeuroImage 2007 36 1065 1073 17513132 PMC2040300
• Not checked yetcites [32] McEwen BS Permanence of brain sex differences and structural plasticity of the adult brain Proc Natl Acad Sci U S A 1999 96 7128 7130 10377379 PMC33584
• Not checked yetcites [102] McCormick CM Mathews IZ HPA function in adolescence: role of sex hormones in its regulation and the enduring consequences of exposure to stressors Pharmacol Biochem Behav 2007 86 220 233 16901532

In the paper

“CTQ ratings are limited by the use of retrospective self-reports and do not assess ages at which maltreatment occurred, making exploration of possible differential effects of the timing of maltreatment on brain development difficult.”

In the paper

“Findings in these sensory association regions are consistent with parietal alterations found in adults reporting CM exposure and borderline personality disorder86 and parietal and occipital alterations in PTSD,87 suggesting CM may alter perceptual integration through adulthood via GM changes.”

What the sources say

• Not checked yetcites [86] Irle E Lange C Sachsse U Reduced size and abnormal asymmetry of parietal cortex in women with borderline personality disorder Biol Psychiatry 2005 57 173 182 15652877
• Not checked yetcites [87] Bremner JD Vermetten E Vythilingam M Neural correlates of the classic color and emotional stroop in women with abuse-related posttraumatic stress disorder Biol Psychiatry 2004 55 612 620 15013830

In the paper

“Animal models suggest that estrogen may mediate stress sensitivity in PFC103 and hippocampus.104”

What the sources say

• Not checked yetcites [103] Shansky RM Glavis-Bloom C Lerman D Estrogen mediates sex differences in stress-induced prefrontal cortex dysfunction Mol Psychiatry 2004 9 531 538 14569273
• Not checked yetcites [104] Dalla C Whetstone AS Hodes GE Shors TJ Stressful experience has opposite effects on dendritic spines in the hippocampus of cycling versus masculinized females Neurosci Lett 2009 449 52 56 18952150 PMC3289544

In the paper

“These findings suggest that early emotional neglect may alter the development of this emotional regulation system, conferring increased risk for the development of mood disorders.”

In the paper

“these regions are key components in the neural circuitry that underlies impulse control.69,70”

What the sources say

• Not checked yetcites [69] Ferry AT Ongur D An X Price JL Prefrontal cortical projections to the striatum in macaque monkeys: evidence for an organization related to prefrontal networks J Comp Neurol 2000 425 447 470 10972944
• Not checked yetcites [70] Sinha R Chronic stress, drug use, and vulnerability to addiction Ann N Y Acad Sci 2008 1141 105 130 18991954 PMC2732004

In the paper

“Development of this circuitry is also sexually dimorphic;31,105 estrogen has been demonstrated to have a neuroprotective effect in the striatum, suggesting reduced vulnerability in this region in females.106”

What the sources say

• Not checked yetcites [31] Lenroot RK Gogtay N Greenstein DK Sexual dimorphism of brain developmental trajectories during childhood and adolescence NeuroImage 2007 36 1065 1073 17513132 PMC2040300
• Not checked yetcites [105] Filipek PA Richelme C Kennedy DN Caviness VS Jr The young adult human brain: an MRI-based morphometric analysis Cereb Cortex 1994 4 344 360 7950308
• Not checked yetcites [106] Dluzen DE Neuroprotective effects of estrogen upon the nigrostriatal dopaminergic system J Neurocytol 2000 29 387 399 11424955

In the paper

“As the regional distribution of the volume decreases with CM are similar to those found in psychiatric and behavioral difficulties, we interpreted the volume decreases to represent vulnerability factors.”

In the paper

“Subjects were without history of neurological illness, head trauma with loss of consciousness or major medical disorder.”

In the paper

“Results were considered significant at p<0.005 (uncorrected) and clusters >50voxels.”

In the paper

“Subjects were recruited from a sample of children identified at birth to be at high risk for CM and followed longitudinally (by LCM). Participants were also recruited from the greater New Haven Connecticut community, allowing for a sample of adolescents reporting a spectrum of CM severity.”

In the paper

“Written informed consent was obtained from parents/guardians, and assent from minors, in accordance with the institutional review board of the Yale School of Medicine.”