The cortical thickness of tricenarian cocaine users assembles features of an octogenarian brain.

It has been suggested that substance use disorders could lead to accelerated biological aging, but only a few neuroimaging studies have investigated this hypothesis so far. In this cross-sectional study, structural neuroimaging was performed to measure cortical thickness (CT) in tricenarian adults with cocaine use disorder (CUD, n1 = 30) and their age-paired controls (YC, n1 = 30), and compare it with octogenarian elder controls (EC, n1 = 20). We found that CT in the right fusiform gyrus was similar between CUD and EC, thinner than the expected values of YC. We also found that regarding CT of the right inferior temporal gyrus, right inferior parietal cortex, and left superior parietal cortex, the CUD group exhibited parameters that fell in between EC and YC groups. Finally, CT of the right pars triangularis bordering with orbitofrontal gyrus, right superior temporal gyrus, and right precentral gyrus were reduced in CUD when contrasted with YC, but those areas were unrelated to CT of EC. Despite the 50-year age gap between our age groups, CT of tricenarian cocaine users assembles features of an octogenarian brain, reinforcing the accelerated aging hypothesis in CUD.

Exploring the potential link between ΔFosB and N-acetylcysteine in craving/relapse dynamics: can N-acetylcysteine stand out as a possible treatment candidate?

From a neuroscientific point of view, one of the unique archetypes of substance use disorders is its road to relapse, in which the reward system plays a crucial role. Studies on the neurobiology of substance use disorders have highlighted the central role of a protein belonging to the Fos family of transcription factors, ΔFosB. Relying on the roles ΔFosB plays in the pathophysiology of substance use disorders, we endeavour to present some evidence demonstrating that N-acetylcysteine, a low-cost and well-tolerated over-the-counter medicine, may influence the downstream pathway of ΔFosB, thereby serving as a treatment strategy to mitigate the risk of relapse in cases of substance use.

Cocaine-use disorder and childhood maltreatment are associated with the activation of neutrophils and increased inflammation.

BACKGROUND: Cocaine-use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of neutrophil extracellular traps (NETs) and related intracellular signalling. We also investigated the role of early life stress in inflammatory profiles. METHODS: Blood samples, clinical data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HCs). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular reactive oxygen species (ROS) generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry. RESULTS: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1ß, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared to HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signalling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation. CONCLUSION: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.

A single dose of cocaine raises SV2A density in hippocampus of adolescent rats.

OBJECTIVE: Cocaine is a highly addictive psychostimulant that affects synaptic activity with structural and functional adaptations of neurons. The transmembrane synaptic vesicle glycoprotein 2A (SV2A) of pre-synaptic vesicles is commonly used to measure synaptic density, as a novel approach to the detection of synaptic changes. We do not know if a single dose of cocaine suffices to affect pre-synaptic SV2A density, especially during adolescence when synapses undergo intense maturation. Here, we explored potential changes of pre-synaptic SV2A density in target brain areas associated with the cocaine-induced boost of dopaminergic neurotransmission, specifically testing if the effects would last after the return of dopamine levels to baseline. METHODS: We administered cocaine (20 mg/kg i.p.) or saline to rats in early adolescence, tested their activity levels and removed the brains 1 hour and 7 days after injection. To evaluate immediate and lasting effects, we did autoradiography with [3H]UCB-J, a specific tracer for SV2A, in medial prefrontal cortex, striatum, nucleus accumbens, amygdala, and dorsal and ventral areas of hippocampus. We also measured the striatal binding of [3H]GBR-12935 to test cocaine's occupancy of the dopamine transporter at both times of study. RESULTS: We found a significant increase of [3H]UCB-J binding in the dorsal and ventral sections of hippocampus 7 days after the cocaine administration compared to saline-injected rats, but no differences 1 hour after the injection. The [3H]GBR-12935 binding remained unchanged at both times. CONCLUSION: Cocaine provoked lasting changes of hippocampal synaptic SV2A density after a single exposure during adolescence.

Effects of substance use disorder on oxidative and antioxidative stress markers: A systematic review and meta-analysis.

Recently, it has been suggested that central and peripheral toxicities identified in persons with substance use disorder (SUD) could be partially associated with an imbalance in reactive oxygen species and antioxidant defenses. We conducted a systematic review and meta-analysis to investigate whether SUD is associated with oxidative stress and to identify biomarkers possibly more affected by this condition. We have included studies that analysed oxidant and antioxidant markers in individuals with SUD caused by stimulants, alcohol, nicotine, opioids, and others (cannabis, inhalants, and polysubstance use). Our analysis showed that persons with SUD show higher oxidant markers and lower antioxidant markers than healthy controls. SUD was associated specifically with higher levels of oxidant markers malondialdehyde, thiobarbituric acid reactive substances and lipid peroxidation. Conversely, the antioxidant superoxide dismutase and the total antioxidant capacity/status were lowered in the SUD group. A meta-regression analysis revealed that persons with alcohol use disorder had higher oxidative stress estimates than those with stimulant use disorder. Moreover, individuals evaluated during abstinence showed smaller antioxidant effect sizes than non-abstinent ones. Our findings suggest a clear oxidative imbalance in persons with SUD, which could lead to cell damage and result in multiple associated comorbidities, particularly accelerated aging.

Sex differences in brain regional homogeneity during acute abstinence in cocaine use disorder.

There are significant sex differences in the clinical characteristics of cocaine use disorder (CUD). As this is a brain disorder that involves changes in functional connectivity, we investigated the existence of sex differences among people with CUD and controls. We used a data-driven method comparing males (n = 20, CK-M) and females with CUD (n = 20, CK-F) and healthy controls (20 males, HC-M and 20 females, HC-F). The participants undertook a resting-state functional magnetic resonance imaging exam. Regional homogeneity (ReHo) was performed to identify group and sex differences. Persons with CUD of both sexes presented lower ReHo parameters than controls, especially within the parietal lobule. Males with CUD showed higher ReHo than females in three right-side brain areas: postcentral gyrus, putamen and fusiform gyrus. It was found that abstinence symptoms severity was associated with lower ReHo values in the right postcentral gyrus and the right fusiform gyrus. Participants with CUD exhibited altered ReHo parameters compared to controls, similar to what is found in ageing-related disorders. Our data also indicate that cocaine has sex-specific effects on brain functioning when analysing ReHo.

Cingulate cortical thickness in cocaine use disorder: mediation effect between early life stress and cocaine consumption.

OBJECTIVE: The cingulate gyrus is implicated in the neurobiology of addiction, such as chronic cocaine consumption. Early life stress (ELS) is an important moderator of cocaine use disorder (CUD). Therefore, we investigated the effect of CUD on cingulate cortical thickness and tested whether a history of ELS could influence the effects of CUD. METHODS: Participants aged 18-50 years (78 with CUD due to crack cocaine consumption and 53 healthy controls) underwent magnetic resonance imaging and the cingulate thickness (rostral anterior, caudal anterior, posterior, and isthmus regions) was analysed. The clinical assessment comprised the Childhood Trauma Questionnaire (CTQ) and the Addiction Severity Index. Group comparisons adjusting by sex, age, and education were performed. Mediation models were generated where lifetime cocaine use, CTQ score, and cortical thickness corresponded to the independent variable, intermediary variable, and outcome, respectively. RESULTS: Group comparisons revealed significant differences in six out of eight cingulate cortices, showing lower thickness in the CUD group. Furthermore, years of regular cocaine use was the variable most associated with cingulate thickness. Negative correlations were found between CTQ scores and the isthmus cingulate (right hemisphere), as well as with the rostral anterior cingulate (left hemisphere). In the mediation analysis, we observed a significant negative direct effect of lifetime cocaine use on the isthmus cingulate and an indirect effect of cocaine use mediated by CTQ score. CONCLUSION: Our findings suggest that a history of ELS could aggravate the negative effects of chronic cocaine use on the cingulate gyrus, particularly in the right isthmus cingulate cortex.

Hair cortisol levels and mental health problems in children and adolescents exposed to victimization.

Youths who experience multiple forms of victimization are at a heightened risk for psychopathology across the lifespan. The hypothalamic-pituitary-adrenal (HPA) axis is a key target for the investigation of neurobiological changes induced by chronic stress and violence exposure. The measurement of hair cortisol concentration allows the investigation of long-term HPA activity and its association with victimization. The present study investigated the impact of exposure to polyvictimization in Latin-American children and adolescents on hair cortisol levels. We investigated association among cortisol, mental health problems and victimization. The study included 83 youths (mean age 10.84 years-old) from southern Brazil. We assessed self-reported victimization scores (Juvenile Victimization Questionnaire - JVQ-R2), mental health problems (Child Behavior Checklist - CBCL/6-18), and hair cortisol concentrations for the previous 30 days. The results showed an association between exposure to multiple forms of victimization and higher concentrations of hair cortisol; the results also showed that cortisol levels and mental health problems were associated with the severity of polyvictimization. These findings suggest that preadolescent victimization is associated with hyperactivation of HPA axis and with increased risk of mental health issues.

Maternal separation induces long-term oxidative stress alterations and increases anxiety-like behavior of male Balb/cJ mice.

Early life stress (ELS) exposure is a well-known risk factor for the development of psychiatric conditions, including anxiety disorder. Preclinical studies show that maternal separation (MS), a classical model of ELS, causes hypothalamic-pituitary-adrenal (HPA) axis alterations, a key contributor to the stress response modulation. Given that HPA axis activation has been shown to induce oxidative stress, it is possible to hypothesize that oxidative stress mediates the relationship between chronic ELS exposure and the development of several disorders. Here, we investigate the effects of MS in the oxidative status [plasma and brain reduced glutathione, catalase and thiobarbituric acid reactive substances (TBARS)], metabolism (glucose, triglycerides and cholesterol) and anxiety-like behaviors in adult Balb/cJ mice. In short, we found that MS increased anxiety-like behaviors in the open field, light/dark test but not in the elevated-plus maze. Animals also presented increased circulating cholesterol, increased TBARS in the plasma and decreased catalase in the hippocampus. Our findings suggest that MS induces long-term alterations in oxidative stress and increased anxiety-like behaviors.

Are serum brain-derived neurotrophic factor concentrations related to brain structure and psychopathology in late childhood and early adolescence?

OBJECTIVE: Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence. METHODS: Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder. RESULTS: Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers. CONCLUSIONS: No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.

Subjective and physiological stress measurement in a multiple sclerosis sample and the relation with executive functions performance.

In multiple sclerosis (MS), hypothalamic-pituitary-adrenal (HPA) axis functioning may be dysregulated due to the high cortisol levels involved in the disease activity. HPA axis dysregulation can affect cognitive performance, including executive functions. This study aimed to evaluate hair cortisol concentration and perceived stress as well as verify the association with the performance of executive function in both individuals diagnosed with MS and control individuals. Hair cortisol concentration and perceived stress were evaluated and their association with the performance of healthy individuals (n = 33) and those with MS (n = 64), most of them with remitting-relapsing multiple sclerosis (RRMS) assessed using the Expanded Disability Status Scale (EDSS). Instruments that were employed to measure perceived stress and health aspects included the Behavioral Assessment Dysexecutive Syndrome, Wisconsin Card Sorting Test, Stroop Test, and Perceived Stress Scale. No significant statistical difference was found in the comparison of means among the groups; however, an association was found when using statistical correlation tests between cortisol and cognitive performance in the clinical group (r = 0.31, p = 0.10). Further, an absence of correlations with perceived stress measure was noted. It was possible to observe interaction between group factors and low level of cortisol and problem-solving/cognitive flexibility in the MS group. The results indicated that stress measures used in the present study seem to influence the performance of inhibitory control and problem-solving/cognitive flexibility, the latter with low levels of cortisol in individuals with MS. We suggest studies that examine different measures of physiological stress and characteristics of the disease such as more time of stress.

Hair cortisol concentration, cognitive, behavioral, and motor impairment in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease that is characterized by the demyelinated inflammatory processes that occur within the central nervous system. Hypothalamus-pituitary-adrenal axis (HPA axis) dysfunctions have been associated with the triggering or increase in MS symptoms. We thus aimed at evaluating motor and behavioral functions, planning skills, processing speed, and their relationship with stress through measuring hair cortisol concentration from patients with MS. The sample was composed of 40 volunteers that were clinically diagnosed with MS, along with 33 healthy adults. Evaluations included: Clinical Evaluation Form, Mini-Mental State Exam, Hamilton Depression Rating Scale, Multiple Sclerosis Functional Composite Measure, Expanded Disability Status Scale, Berg Balance Scale, Perceived Stress Scale, Zoo Map task, and a hair sample to analyze cortisol levels in the last 30 days. MS patients showed highly elevated hair cortisol levels in comparison to the control group (p = 0.048). All groups presented some degree of depressive and anxiety symptoms, aside from considerable perceived stress levels. The MS group presented deficits in gait, balance, manual skills and processing speed, and this was particularly so in individuals with moderate impairments when compared to control group (p < 0.001). Individuals with MS spent less time planning on ZooMap1 (p = 0.024) and made more mistakes (p < 0.001). No correlation was found between hair cortisol and the symptoms we assessed. However, depressive symptoms and anxiety were related to perceived stress, and higher hair cortisol suggests a change in levels in the HPA axis in MS. Nevertheless, future studies will be necessary to further understand how basal hair cortisol is related to MS symptoms.

Effects of DRD2 splicing-regulatory polymorphism and DRD4 48 bp VNTR on crack cocaine addiction.

There is evidence that dopamine receptors D2 (DRD2) and D4 (DRD4) polymorphisms may influence substance use disorders (SUD) susceptibility both individually and through their influence in the formation of DRD2-DRD4 heteromers. The dopaminergic role on the vulnerability to addiction appears to be influenced by sex. A cross-sectional study with 307 crack cocaine addicts and 770 controls was conducted. The influence of DRD2 rs2283265 and DRD4 48 bp VNTR in exon 3 variants, as well as their interaction on crack cocaine addiction susceptibility and severity were evaluated in women and men separately. An association between the DRD2 T allele and crack cocaine addiction was found in women. In this same group, interaction analysis demonstrated that the presence of DRD2-T allele and concomitant absence of DRD4-7R allele were associated with risk for crack cocaine addiction. No influence of DRD2 and DRD4 variants was observed in men regarding addiction severity. This study reinforces the role of dopaminergic genes in externalizing behaviors, especially the influence of DRD2-DRD4 interaction on SUD. This is the fourth sample that independently associated the DRD2-DRD4 interaction with SUD itself or related disorders. In addition, our findings point out to a potential difference of dopaminergic neurotransmission across sex influencing addiction susceptibility.

Association between cognitive performance and SYT1-rs2251214 among women with cocaine use disorder.

The SNP rs2251214 of the SYT1 gene was recently associated with externalizing phenotypes, including ADHD and cocaine use disorder (CUD). Here, we investigated whether SYT1-rs2251214 could also be implicated with cognitive performance variations among women with CUD. Results showed that G homozygous (n = 146) have lower cognitive performance in the Stroop, Trail Making and Matrix Reasoning tests compared with A-allele carriers (n = 64), suggesting that rs2251214 may influence the severity of cognitive impairments in CUD.

Violence and Latin-American preadolescents: A study of social brain function and cortisol levels.

The present study investigated exposure to violence and its association with brain function and hair cortisol concentrations in Latin-American preadolescents. Self-reported victimization scores (JVQ-R2), brain imaging (fMRI) indices for a social cognition task (the 'eyes test'), and hair cortisol concentrations were investigated, for the first time, in this population. The eyes test is based on two conditions: attributing mental state or sex to pictures of pairs of eyes (Baron-Cohen, Wheelwright, Hill, Raste, & Plumb, 2001). The results showed an association among higher victimization scores and (a) less activation of posterior temporoparietal right-hemisphere areas, in the mental state condition only (including right temporal sulcus and fusiform gyrus); (b) higher functional connectivity indices for the Amygdala and Right Fusiform Gyrus (RFFG) pair of brain regions, also in the mental state condition only; (c) higher hair cortisol concentrations. The results suggest more exposure to violence is associated with significant differences in brain function and connectivity. A putative mechanism of less activation in posterior right-hemisphere regions and of synchronized Amygdala: RFFG time series was identified in the mental state condition only. The results also suggest measurable effects of exposure to violence in hair cortisol concentrations, which contribute to the reliability of self-reported scores by young adolescents. The findings are discussed in light of the effects of exposure to violence on brain function and on social-cognitive development in the adolescent brain. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=qHcXq7Y9PBk.

Cocaine use disorder in females is associated with altered social decision-making: a study with the prisoner's dilemma and the ultimatum game.

BACKGROUND: Chronic cocaine use is associated with cognitive deficits, including poor performance on neuropsychological tasks of memory, executive functions, theory of mind and decision-making. However, the relationship between cocaine use disorder and social decision-making remains unclear. This is particularly relevant given the fact that many cocaine abusers present impairments in social functioning. In this sense, game theory paradigms have been helping to comprehend the behavior of psychiatric patients when they directly engage in social situations, which may better approximate many of their real-life choices. METHODS: The present study investigated social decision-making in individuals with or without cocaine use disorder, examining their behavior in the Prisoner's Dilemma and in the Ultimatum Game. Thus, 129 females diagnosed with cocaine use disorder and 55 females with no history of substance abuse were recruited and performed both social decision-making tasks. Additional assessments included information about demographics, patterns of substance consumption and executive function performance. RESULTS: Females with cocaine use disorder opted more often to not defect in the Prisoner's Dilemma, while in the Ultimatum Game they frequently chose to accept the first and unfair offer as responders. These effects were more pronounced within females with long-term history of cocaine use. Associations between cocaine use disorder and altered social decision-making were independent from demographic and executive function variables. CONCLUSIONS: The influence of cocaine use disorder on social decision-making was detected in both game paradigms, resulting in more cooperative behavior in the Prisoner's Dilemma and higher acceptance rate of unfair offers in the Ultimatum Game. Further studies should focus on investigating these associations to shed light on the putative biopsychosocial factors underlying the observed effects.

Maternal behavior of the mouse dam toward pups: implications for maternal separation model of early life stress.

Maternal care is essential for an adequate pup development, as well as for the health of the dam. Exposure to stress in early stages of life can disrupt this dam-pup relationship promoting altered neurobiological and behavioral phenotypes. However, there is a lack of consensus regarding the effects of daily maternal separation (MS) on the pattern of maternal behavior. The aim of this study is to compare the patterns of maternal behavior between mice exposed to MS and controls. BALB/c mice were subjected to MS for a period of 180 min/day from postnatal day 2-7 (n = 17) or designated to be standard animal facility reared (AFR) controls (n = 19). Maternal behaviors were computed as frequency of nursing, licking pups and contact with pups, and nonmaternal behaviors were computed as frequency of actions without interaction with pups and eating/drinking. A total of 18 daily observations of maternal behavior were conducted during these six days, and considering the proportion of maternal and nonmaternal behaviors, an index was calculated. There was no difference when comparing the global index of maternal behavior between the AFR and MS animals by the end of the observed period. However, the pattern of maternal behavior between groups was significantly different. While MS dams presented low frequency of maternal behavior within the first couple days of the stress protocol, but increasing over time, AFR dams showed higher maternal behavior at the beginning, reducing over time. Together, our results indicate that MS alters the maternal behavior of the dams toward pups throughout the first week of the stress protocol and provoked some anxiety-related traits in the dams. The inversion of maternal behavior pattern could possibly be an attempt to compensate the low levels of maternal care observed in the first days of MS.

Self-reported inhibition predicts history of suicide attempts in bipolar disorder and major depression.

BACKGROUND: Studies have reliably identified an association between suicide attempts and executive functions such as decision making (DM) and inhibitory control (IC) in patients with mood disorders. As such, the present study aimed to investigate the association between inhibition, DM, impulsivity and the history of suicide attempts in individuals with bipolar (BD) or major depressive disorder (MDD), identifying which assessment instruments may be most strongly associated with suicide in clinical samples. METHODS: The sample included 80 control subjects and two groups of patients with BD and MDD, matched by age and education (26 with a history of suicide attempts [MD+], and 26 with no such history [MD-]). Participants completed behavioral and self-report measures of DM and IC, which were compared between groups using ANCOVA, followed by logistic regression for patients with mood disorders only, and the presence or absence of a history of suicide as the outcome. RESULTS: Cognitive performance did not differ between groups. The MD+ group showed significantly higher motor and attentional impulsivity on the BIS-11 than the MD- and control groups. A regression analysis containing these scores showed that motor impulsivity was the only significant predictor of a history of suicide (OR = 1.14; 95%CI 1.00-1.30). CONCLUSIONS: Self-reported motor impulsivity was a significant predictor of suicide. These findings underscore the importance of self-report measures in neuropsychological assessment, and their contributions to the management and prognosis of patients with mood disorders. Lastly, they point to the role of impulsivity as a target for interventions and public policy on suicide prevention.

Maternal separation induces hippocampal changes in cadherin-1 (CDH-1) mRNA and recognition memory impairment in adolescent mice.

In rodents, disruption of mother-infant attachment induced by maternal separation (MS) is associated with recognition memory impairment and long-term neurobiological consequences. Particularly stress-induced modifications have been associated to disruption of cadherin (CDH) adhesion function, which plays an important role in remodeling of neuronal connection and synaptic plasticity. This study investigated the sex-dependent effect of MS on recognition memory and mRNA levels of classical type I and type II CDH and the related ß -catenin (ß -Cat) in the hippocampus and prefrontal cortex of late adolescent mice. We provided evidence that the BALB/c mice exposed to MS present deficit in recognition memory, especially females. Postnatal MS induced higher hippocampal CDH-2 and CDH-8 mRNA levels, as well as an upregulation of CDH-1 in the prefrontal cortex in both males and females. MS-reared female mice presented lower CDH-1 mRNA levels in the hippocampus. In addition, hippocampal CDH-1 mRNA levels were positively correlated with recognition memory performance in females. MS-reared male mice exhibited higher ß -Cat mRNA levels in the hippocampus. Considering sex-specific effects on CDH mRNA levels, it has been demonstrated mRNA changes in CDH-1, ß -Cat, and CDH-6 in the hippocampus, as well as CDH-1, CDH-8 and CDH-11 in the prefrontal cortex. Overall, these findings suggest a complex interplay among MS, CDH mRNA expression, and sex differences in the PFC and hippocampus of adolescent mice.

Intimate partner violence is associated with increased maternal hair cortisol in mother-child dyads.

BACKGROUND: The chronic consequences of intimate partner violence (IPV) on HPA activation are a topic of debate. The current study investigated hair cortisol concentrations in female victims of IPV and their children. METHODS: A total of 52 mother-child dyads were divided into two groups depending on exposure to IPV: IPV group (n=27 dyads) and control group (n=25 dyads). Hair cortisol concentration was measured in 1-cm-long hair strands, representing 30days of exposure before assessment. PTSD and depression symptoms were assessed in the mother and child. RESULTS: Women reporting IPV presented with higher hair cortisol levels, depression and PTSD symptoms severity in comparison to control women. Children who witnessed IPV reported more severe PTSD symptoms, but depressive symptoms and hair cortisol were not statistically different than those in control children. Correlation analyses revealed a positive association between the number of injury events and the level of hair cortisol in children. No associations between the hair cortisol levels in mothers and those in their children were found. CONCLUSION: Higher hair cortisol levels detected in women exposed to IPV reflected long-lasting changes in HPA axis functioning associated with chronic stress exposure. Children whose parents recurrently engage in violent conflicts with intimate partners may often feel threatened and consequently reporting more PTSD-related symptoms. Given that experiencing and witnessing violence during childhood and adolescence are predictive of intimate partner violence in adulthood, the need of early interventions is crucial.