The effects of childhood maltreatment on brain structure, function and connectivity

Journal name:
Nature Reviews Neuroscience
Year published:
Published online


Maltreatment-related childhood adversity is the leading preventable risk factor for mental illness and substance abuse. Although the association between maltreatment and psychopathology is compelling, there is a pressing need to understand how maltreatment increases the risk of psychiatric disorders. Emerging evidence suggests that maltreatment alters trajectories of brain development to affect sensory systems, network architecture and circuits involved in threat detection, emotional regulation and reward anticipation. This Review explores whether these alterations reflect toxic effects of early-life stress or potentially adaptive modifications, the relationship between psychopathology and brain changes, and the distinction between resilience, susceptibility and compensation.

At a glance


  1. Abuse type-specific effects on the developing brain.
    Figure 1: Abuse type-specific effects on the developing brain.

    Images depicting the potential effects of exposure to specific types of childhood maltreatment on grey-matter volume (GMV) or thickness and fibre-tract integrity. Exposure to parental verbal abuse was associated with increased GMV in the auditory cortex portion of the left superior temporal gyrus25 (part a) and decreased integrity of the left arcuate fasciculus (AF) interconnecting Wernicke's area and Broca's area26 (part b). Visually witnessing multiple episodes of domestic violence was associated with reduced GMV in right lingual gyrus, left occipital pole and bilateral secondary visual cortex (V2)27 (part c) and decreased integrity of the left inferior longitudinal fasciculus (ILF), which serves as a visual–limbic pathway28 (part d). Adults reporting exposure to multiple episodes of childhood forced-contact sexual abuse were found to have reduced GMV in right and left primary visual cortex (V1) and visual association cortices, as well as reduced thickness in right lingual, left fusiform and left middle occipital gyri29 (part e) and portions of the somatosensory cortex representing the clitoris and surrounding genital area30 (part f). Part a is adapted with permission from Ref. 25, Elsevier. Part b is adapted with permission from Ref. 26, Elsevier. Part c is adapted from Ref. 27. Part d is adapted with permission from Ref. 28, Elsevier. Part e is adapted with permission from Ref. 29, Elsevier. Part f is adapted from an image courtesy of C. Heim, Charité Universitätsmedizin Berlin, Germany, and J. Pruessner, McGill University, Canada.

  2. Circuitry underlying threat detection and response.
    Figure 2: Circuitry underlying threat detection and response.

    Simplified component diagram delineating brain regions found to be involved in detecting and responding to threatening sights and sounds. The figure is based primarily on work of LeDoux38, 39, with updates from translational studies2, 40, 41, 42, 43. Regions and pathways labelled in red have been reported to be altered in volume or integrity by childhood maltreatment. Visual information from the eyes is relayed to the superior colliculus (SC) and lateral geniculate nucleus (LG). From the SC, information can go to the LG or to the parabigeminal nucleus (PBG) and then to the amygdala. From the LG, information is projected to the visual cortex. Auditory information from the ears is relayed to the inferior colliculus (IC) or the medial geniculate nucleus (MG), with output from the IC projecting to the MG. From the MG, information can go to the auditory cortex or to the paraventricular thalamus (PVT) and then to the amygdala. Blue arrows delineate pathways through which information coding threatening sights or sounds can rapidly reach the amygdala without conscious awareness. Sensory cortical regions project to the amygdala, prefrontal cortex (PFC) and hippocampus. The PFC modulates the amygdala response, with the dorsal anterior cingulate cortex (dACC) amplifying this response (in the image, indicated by '+') and the ventromedial PFC (vmPFC) attenuating it (in the image, indicated by '−'). The dorsomedial PFC (dmPFC) helps to regulate the degree of dACC and vmPFC involvement. The hippocampus provides contextual information to the amygdala. The amygdala, in turn, projects to the paraventricular nucleus of the hypothalamus (PVN), which helps to regulate autonomic responses as well as pituitary adrenal and locus coeruleus (LC) responses. The PVN is also regulated by information from the hippocampus, via the subiculum and the bed nucleus of the stria terminalis (BNST). ACTH, adrenocorticotropic hormone; AF, arcuate fasciculus; ANS, autonomic nervous system; CRF, corticotropin-releasing factor; ILF, inferior longitudinal fasciculus; NA, noradrenaline; UF, uncinate fasciculus.

  3. Maltreatment-associated changes in functional connectivity.
    Figure 3: Maltreatment-associated changes in functional connectivity.

    Summary of alterations in resting-state functional connectivity reported in individuals with histories of childhood maltreatment58, 60, 91, 121, 171. Alterations are expressed in relationship to the degree and direction of connectivity in unexposed controls. Decreased correlation indicates that there were positive correlations in blood-oxygen-level-dependent (BOLD) signal fluctuations between regions in controls and that the degree of correlation was reduced to a less positive or negative degree in maltreated individuals. Decreased anti-correlation indicates that there was an inverse correlation in BOLD signal between regions in controls and that this was reduced to a less negative or positive degree in maltreated subjects. Increased correlation and increased anti-correlation indicate that the correlation between regions was in the same direction in maltreated subjects as in controls but was present to a greater — more positive or more negative — degree, respectively. Multiple arrows between regions indicate discrepant findings, which probably stem from methodological differences between studies in the way that global signals related to blood flow or movements were handled. Reports of both decreased correlation and decreased anti-correlation suggest that the regions are less coupled in maltreated individuals. Decreased correlation and increased anti-correlation suggest that the coupling is shifting from a positive relationship to a negative (reciprocal) relationship in maltreated subjects. These studies provide evidence for reduced coupling of the amygdala with medial–orbital prefrontal cortex (PFC), anterior cingulate cortex, posterior cingulate cortex (PCC) or precuneus, hippocampus and insula, as well as a shift in the direction of coupling of the amygdala with lateral PFC and putamen, plus increased connectivity of the amygdala with locus coeruleus (LC) and cerebellum. These studies also indicate that maltreatment is associated with reduced coupling of the hippocampus with the medial–orbital PFC and anterior cingulate cortex, but increased positive or negative coupling of the hippocampus with the PCC or precuneus, cerebellum and lateral PFC. Overall, these findings are indicative of reduced top-down regulation of the amygdala by prefrontal regions, reduced contextual input to the amygdala from hippocampus, and increased connectivity of the amygdala with LC and cerebellum that may result in a more rapid noradrenergic and postural response following amygdala activation.

  4. Maltreatment-sensitivity periods for different brain areas.
    Figure 4: Maltreatment-sensitivity periods for different brain areas.

    Developmental differences in sensitivity to effects of specific forms of childhood maltreatment on grey-matter measures or fibre-tract integrity (fractional anisotropy (FA)) show that different regions and pathways are maximally susceptible to maltreatment at different ages. a | Ages of exposure to sexual abuse in females are inversely correlated to reductions in hippocampal volume50. b | Predictive importance of visually witnessing domestic violence at specific ages and FA in the inferior longitudinal fasciculus, as assessed using predictive analytics and machine learning28. c | Predictive importance of maltreatment (composite score) at specific ages on reduction of the grey-matter volume of the right amygdala67. d | Predictive importance of visually witnessing domestic violence at specific ages on thinning of the secondary visual cortex (V2)27. e | Ages at exposure to sexual abuse in females show inverse correlation with grey-matter volume of the prefrontal cortex (PFC)50.

  5. The dopaminergic reward system.
    Figure 5: The dopaminergic reward system.

    Anatomical location of key structures that make up the reward system and mesocorticolimbic (red) and nigrostriatal (black) ascending dopaminergic pathways. Dopamine-neuron cell bodies for these ascending pathways are located primarily in the ventral tegmental area and substantia nigra. Dopaminergic neurons in the substantia nigra project to dorsal portions of the striatum (caudate and putamen), whereas dopaminergic neurons in the ventral tegmental area project to ventral portions of the striatum (particularly the nucleus accumbens and more ventral aspects of the caudate and putamen), as well as limbic regions (that is, the amygdala) and cortical regions (particularly the orbitofrontal cortex and anterior cingulate cortex). Childhood maltreatment has been reported to be associated with alterations in blood flow to the caudate, putamen, portions of prefrontal cortex, substantia nigra and nucleus accumbens48, 172, as well as reductions in size of the striatum37, 49, 75, alterations in developmental trajectory of the nucleus accumbens173, and reduced volume, thickness or connectivity of the anterior cingulate cortex30, 45, 75, 89, 90, 91 and orbitofrontal cortex53, 89, 92. Maltreatment is also consistently associated with an attenuated striatal response to anticipation or receipt of reward in functional MRI tasks82, 83, 84, 85, 86, 87. Green-shaded regions represent cell body regions or primary target regions of the ascending dopamine system.

  6. Network changes associated with childhood maltreatment.
    Figure 6: Network changes associated with childhood maltreatment.

    Maltreatment during childhood has been found to be associated with changes in structural connectivity at the network level. Here, the entire cerebral cortex of young adults with (n = 142) or without (n = 123) histories of childhood maltreatment was divided into 112 regional nodes. Within each group, between-subject correlations in the cortical thicknesses of each nodal pairing were used to infer connectivity, as brain regions that co-vary reliably in size between subjects are either structurally or functionally interconnected90. Network architecture and the centrality of each node were then determined by applying graph theory to the 112 × 112-node maltreated and non-maltreated cross-correlation matrices. Three key differences in structural nodal centrality between maltreated and non-maltreated groups are shown here. Green circles indicate nodal centres (the regions of interest) in each case for the left anterior cingulate cortex (left), the right anterior insula (middle) and the right precuneus (right). Red circles indicate primary nodes, which are regions with direct connections to the nodal centre. Blue circles delineate secondary nodes, which have direct connections with the primary nodes but do not have direct connections with the nodal centre. Childhood maltreatment was associated with a marked decrease in the centrality of the left anterior cingulate, as indicated by a substantial decrease in primary and secondary connections. Conversely, maltreatment was associated with a significant increase in the centrality of the right anterior insula and the right precuneus, as indicated by the greater number of primary and secondary nodal connections in these regions in the maltreated group. Adapted with permission from Ref. 90, Elsevier.


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  1. Department of Psychiatry, Harvard Medical School, 401 Park Drive, Boston, Massachusetts 02215, USA.

    • Martin H. Teicher,
    • Jacqueline A. Samson,
    • Carl M. Anderson &
    • Kyoko Ohashi
  2. Developmental Biopsychiatry Research Program, McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02478, USA.

    • Martin H. Teicher,
    • Jacqueline A. Samson,
    • Carl M. Anderson &
    • Kyoko Ohashi

Competing interests statement

The authors declare no competing interests.

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  • Martin H. Teicher

    Martin H. Teicher is Director of the Developmental Biopsychiatry Research Program at McLean Hospital and an associate professor of psychiatry at Harvard Medical School, Boston, Massachusetts, USA. He has spent nearly 40 years studying the influence of early experience on the brain, behavioural development and psychopathology in humans and animal models.

  • Jacqueline A. Samson

    Jacqueline A. Samson is a clinical psychologist at McLean Hospital and an assistant professor of psychology in the Department of Psychiatry at Harvard Medical School, Boston, Massachusetts, USA. Her chief research interests involve understanding the biopsychosocial underpinnings of depressive illnesses, particularly the contributions of developmental trauma to psychopathology.

  • Carl M. Anderson

    Carl M. Anderson was an assistant professor at Harvard Medical School and an assistant psychobiologist at McLean Hospital, Boston, Massachusetts, USA, and has just accepted a position as Research Director at CooperRiis, a healing community in Mill Spring, North Carolina, USA. His interests include brain morphometry, the cerebellar vermis, neurofeedback and complementary medicine, and he is actively seeking to integrate these within psychiatry.

  • Kyoko Ohashi

    Kyoko Ohashi is an instructor of psychiatry at Harvard Medical School and an assistant neuroscientist at McLean Hospital, Boston, Massachusetts, USA. She received her doctorate from University of Tokyo, Japan, and currently focuses on the influence of childhood adversity on brain connectivity and network architecture, and the relationship between alterations in network architecture and psychopathology.

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