TABLE 2.

Long-term biological consequences of childhood sexual abuse (CSA) exposure.

Article	Adult/Child	Age	Blood/Saliva/Buccal/Hair	Sample size	Biological function affected	Main results
Heim et al., 2000	A	18–45 years	Blood	49	HPA	↑	Women with a history of childhood sexual/physical abuse exhibited increased pituitary adrenal and autonomic responses to stress compared to controls.
Schalinski et al., 2015	A	16–56 years	Saliva-Hair	43	HPA	↕	CSA group displayed lower levels of saliva cortisol, measured after exposure to idiographic adverse experiences (phasic), and higher hair cortisol levels compared to control (tonic).
Hulme et al., 2015	A	29–66 years	Saliva	17	HPA	↑	CSA is associated with long-lasting changes in diurnal patterns of cortisol secretion in bariatric surgery patients. Thus, altered HPA axis regulation may be risk factor to adult obesity in CSA victims.
Bublitz and Stroud, 2012	A	18–40 years	Saliva	135	HPA	↑	Women with CSA histories displayed significantly higher pre-pregnancy BMI, greater anxiety symptoms, increasing cortisol awakening response, and did not display the protective shift to responsiveness, over pregnancy.
Bertone-Johnson et al., 2012	A	25–42 years	Blood	702	Immune system	↑	CRP and IL-6 levels are higher in CSA survivors compared to the non-abused group, the association between sexual abuse and inflammation markers is slightly stronger when the abuse occurs in adolescence rather than childhood.
McCall et al., 2018	A	40–60 years	–	100	Immune system	↓	The rates of CSA in people living with HIV positivity are estimated at 30 to 53%, together with high rates of illicit drug use, and sex trade experiences.
LeGrand et al., 2015 (review)	A	–	–	–	Immune system	↓	Trauma is associated with lower rates of HIV disclosure and increases in risk behaviors, poorer mental health, substance abuse, and immunologic outcomes.
D’Elia et al., 2018 (review)	A	–	–	–	Immune system	↕	Articles based on children samples reported blurred results, while in adult samples the effects seem to be clearer with most studies reporting increased inflammatory activity, i.e., higher levels of IL-6, TNF-α, and C-reactive protein.
Grosse et al., 2016	A	18–65 years	Blood	394	Immune system	↑	In Major Depressive Disorder patients a linear relationship was shown between CSA and pro-inflammatory cytokine levels, while more recent stressful life events were not related to these inflammatory markers.
Cai et al., 2015	A	>18 years	Blood-Saliva	1,1647	Epigenetic and chromatin	NO	Increase in mtDNA and reduction in telomeric DNA were found contingent on the presence of Major Depression. No changes were reported in subjects who reported stressful life events, including CSA, but had never been depressed.
Mason et al., 2015	A	25–42 years	Blood	1135	Epigenetic and chromatin	NO	The relationship between physical abuse and telomere length seemed stronger than that for sexual abuse, but the effects were not statistically significant and there was no evidence of a dose-response relationship.
Vincent et al., 2017	A	20–84 years	Blood	180	Epigenetic and chromatin	NO	Only physical neglect in childhood activates telomere-shortening mechanisms (e.g., excessive cortisol, inflammatory activation), with the impact being greatest amongst older individuals, where the mechanism has had a longer time to evoke its detrimental effects.
Sosnowski et al., 2019	A	35–70 years	Blood	99	Epigenetic and chromatin	NO	There were no effects of exposure to abuse or abuse severity on mean telomere length. However, as social support increased, mean telomere length increased, but only for those women exposed to less severe forms of sexual abuse.
Warner et al., 2020	A	>18 years	Blood	3232	Epigenetic and chromatin	↓	Sexual abuse in childhood or adolescence was associated with a marker of accelerated biological aging, decreased telomere length. Sexual abuse was more strongly and consistently associated with telomere length than physical abuse.
Perroud et al., 2011	A	20–45 years	Blood	215	Epigenetic and chromatin	↑	Childhood sexual abuse was associated with increased NR3C1 promoter methylation. The severity of childhood abuses and neglect positively correlated with NR3C1 promoter methylation.
Beach et al., 2011	A	32–48 years	Blood	155	Epigenetic and chromatin	↑	CSA was associated with degree of methylation of the CpG island upstream of the SLC6A4, which mediated the impact of CSA on antisocial personality disorder symptoms, also potentiating the effect of 5HTT risk alleles.
York et al., 2013	A	39–57 years	Blood	51	Epigenetic and chromatin	↑	Female twins exposed to CSA exhibited a 1.63-fold average increase in the frequency of Micronuclei compared to non-exposed cotwins. The biological age of the CSA exposed twins was inferred to be 9.9 years older, suggesting cumulative effect.
The transgenerational inheritance of CSA
Bosquet Enlow et al., 2018	A + C	Mother > 18 years; infants	Blood	151	Epigenetic and Chromatin	↓	Severity of CSA was associated with shorter cord blood relative telomere length (rTL), and greater maternal familial emotional support in childhood was associated with longer cord blood rTL among male infants.
Esteves et al., 2020	A + C	Mother > 18 years; child 4, 12, and 18 months	Buccal	155	Epigenetic and Chromatin	↓	Mothers’ high scores in the ACE questionnaire predicted shorter telomere length and emerging behavioral problems, especially externalizing ones in the next generation

HPA, hypothalamic-pituitary-adrenal axis; BMI, body mass index; HIV, human immunodeficiency virus; IL-6, Interleukin 6; TNF-α, tumor necrosis factor- α; mtDNA, mitochondrial DNA; NR3C1, nuclear receptor subfamily 3 group C member 1; 5HTT, solute carrier family 6 member 4.