Effects of early stress on brain structure and function: Implications for understanding the relationship between child maltreatment and depression

“While not reviewed comprehensively here, stress also significantly impacts developmental trajectories that are involved in various psychiatric disorders [2], including schizophrenia, depression, drug abuse, and a myriad of other psychiatric disorders [109].”

“For instance, childhood maltreatment is associated with subsequent neurobiological abnormalities characterized by reduced activity in the frontal cortex and an increased stress response (e.g., Kaufman & Charney, 2001).”

“…by numerous animal (e.g., Greenough & Black, 1992; Hebb, 1947; Nakamura, Kobayashi, Ohashi, & Ando, 1999; Wiesel & Hubel, 1963) and human studies (e.g., Bremner & Narayan, 1998; Dawson et al., 2000; Kaufman & Charney, 2001; Lenneberg, 1967; Maguire et al., 2000; Pally, 1997; Roeder et al., 1999).”

“Chronic alterations of HPA axis activity have been shown in rodents and non-human primates exposed to disruptions of parental care such as maternal separation [6,7] and maternal neglect [8], and in humans with childhood parental loss, and neglect or other forms of childhood maltreatment [2,9–17].”

“…and regulation being that prefrontally mediated fluid cognitive processes directly influence and, most important for present purposes, are influenced by emotional and autonomic responses to stimulation (Erickson et al. 2003; de Kloet et al. 1999; Groenewegen & Uylings 2000; Kaufman & Charney 2001).”

“…stressed, hyperactive HPA-axis (Deuschle et al, 1997; McEwen, 2002: McBruce and Wingfield, 2003; Rosmond et al, 1998) and has been observed in depressed adult (den Hartog et al, 2003; Sachar et al, 1970; Young et al, 2006) and adolescent (Kaufman and Charney, 2001; Forbes et al, 2006) outpatients.”

“Recent findings in adults (14, 15) suggest that extreme”

“Not surprisingly, infants and young children who experience early maltreatment show dysregulation at behavioral and biobehavioral levels (Dozier et al., 2006; Kaufman & Charney, 2001; Pears & Fisher, 2005; Sanchez, Ladd, & Plotsky, 2001).”

“…stressor exposure on the brain is predicated on a long tradition of research in the social (e.g., Heim & Nemeroff, 1999; Gunnar & Quevedo, 2007; Kaufman & Charney, 2001; Shonkoff, Boyce, & McEwen, 2009) and life sciences (e.g., Levine, 2001; Liu et al., 2000; Spinelli et al, 2009) suggesting…”

“…a primary implication is that prefrontally mediated executive cognitive processes directly influence and are influenced by emotional and autonomic responses to stimulation (de Kloet, Oitzl, & Joels, 1999; Erickson, Drevets, & Schulkin, 2003; Groenewegen & Uylings, 2000; Kaufman & Charney, 2001).”

“An increasing body of retrospective data also suggests a relationship between early nurturance, or the lack of nurturance based on the experience of trauma, and later stress reactivity and hippocampal volumes in a variety of human populations, including those with depression (24, 25).”

“Major depressive disorder (MDD) has a strong association with maltreatment, especially among female individuals (4,6,7).”

“A corpus of studies has firmly established that childhood maltreatment and adversity are associated with elevated depression levels (for reviews, see Downey, Feldman, Khuri, & Friedman, 1994; Kaplan, Pelcovitz, & Labruna, 1999; Kaufman & Charney, 2001; Pine & Cohen, 2002).”

“, 2002 ; Dawson , Ashman , & Carver , 2000 ; Greenough & Black , 1992 ; Kaufman & Charney , 2001 ; Rosenzwig & Bennett , 1996 ; Wiesel & Hubel , 1963 ) .”

“Among a number of nonhuman species, separations from caregivers have been associated with powerful, predictable effects on neuroendocrine functioning in the short- and long-term (e.g., Kaufman & Charney, 2001; Sanchez, Ladd, & Plotsky, 2001).”

“Regardless of transcultural differences, the neglect or maltreatment of children in early developmental periods increases the risk of anxiety, depression and psychoses in adulthood [9, 33, 48, 83], which are often resistant to treatment [14, 84].”

“2001) of early stress-related dysregulations of the hypothalamic-pituitary–adrenal axis (Kaufman and Charney 2001).”

“…causes of death, but these findings may also be interpreted in the light of neurobiological studies showing that there are early windows of vulnerability duringwhich the developing brain ismore sensitive to adversity and stress (Kaufman & Charney, 2001; Lupien, Mcewen, Gunnar, & Heim, 2009).”

“…affects structural and functional connectivity of the prefrontal cortex and other regions regulating reward (Govindan et al., 2010; Kaufman & Charney, 2001; Sanchez et al., 1998; Teicher et al., 2002), it is possible that exposure to chronic stress compromises dopamine modulation of…”

“These results seem to contradict other studies demonstrating that exposure to stress early in life increases the risk for depression at least in some individuals (Heim and Nemeroff 2001; Kaufman and Charney 2001; Caspi et al. 2003; Teicher et al. 2006).”

“Associated changes in circulating concentrations of cortisol or pro-inflammatory cytokines may subsequently influence signaling pathways, including dopamine, which directly modulate VS function (Kaufman and Charney, 2001; Brenhouse et al., 2013).”

“This is increasingly supported by a growing literature on the role of child abuse on the neural mechanisms of stress responsiveness.([4,5]) Our findings are consistent with recent studies pointing to the importance of specific aspects of child abuse in understanding the long-term effect of childhood maltreatment.”

“…such as the dysregulation of stress systems and long-term neurological alterations related to betrayal trauma (Cicchetti, 2002; De Bellis, 2001; Kaufman & Charney, 2001) may contribute to greater stress reactivity, difficulties in noticing, interpreting, and processing physical and emotional…”

“Common long-term effects of maltreatment include school failure and absenteeism, less anticipation of attending college, social and thought problems, physical and sexual revictimization, violence perpetration, and various psychopathologies such as depression, substance abuse, personality disorder, and posttraumatic st…”

“The reader is referred to Bremner further consideration. and Vermetten (2001), Heim and Nemeroff (2001) The contribution of early life events in shaping an and Kaufman and Charney (2001) for more detailed individual’s perception of themselves, their world reviews.”

“It has been well established that early stress, such as that of child maltreatment, increases rates of major depressive disorder in children and adults (for review, see [ 22 ]).”

“…of different brain regions. suggesting sensitive periods of brain (Andersen, 2003; Andersen and Teicher, 2008, 2009; Andersen et aI., 2008) and neuroendocrine systems development (Weiss et al.. 1999; Paus et al.. 2008; Kaufman and Charney, 2001; Heim et al.. 1997; Wingenfeld et aI.. 2010).”

“in brain structure and function [12, 13].”

“4) [23–59] 39.”

“…as maternal care giving behaviors, maternal deprivation, and maternal separation, affect gene expression, as well as brain structure and function (Kaufman & Charney, 2001; Meaney et al., 1996; Sanchez et al., 2001), it is highly probable that child maltreatment affects the expression of genes…”

“These results may provide novel molecular targets influencing the long-lasting effects of early-life experience on learning and memory functions (35).”

“BPD lags behind that of many other clinical disorders (see e.g., Kaufman and Charney 2001 ).”

“Most empirical evidence concentrates on the altered activity of the hypothalamic-pituitary-adrenal axis that is associated with early adversities such as recollections of childhood emotional, physical, and sexual abuse (18–22), which is among the most consistently demonstrated neurobiologic adversities in depressive s…”

“Different types of maltreatment including physical, sexual, and emotional abuse or neglect in the early period of life (i.e., early live stress, ELS) are associated with mood disorders (Afifi et al.”

“Prior research has documented differences in psychosocial outcomes for maltreated and nonmaltreated children, including criminal behavior (e.g., Widom, 1989a) and depressive symptomatology (e.g., Kaufman & Charney, 2001).”

“Detailed discussions of these findings, beyond the scope of this review, can be found in recent publications (Bremner 2002; Kaufman and Charney 2001).”

“, 2006), or adolescent outpatients (Kaufman and Charney, 2001; Forbes et al., 2006).”

“It is important to also acknowledge at this point that the depth of the interaction between traumatisation and other factors such as familial/genetic factors, environment, and pharmacological intervention on long-term neurobiological changes as yet is not well understood (Bremne and Vermetten 2001; Kaufman and Charney…”

“Alhough advances in functional neuroimaging and molecuar biology have provided increased insight into the mechnisms by which early experiences of deprivation contribte to psychiatric pathology (Heim and Nemeroff, 2001; aufman and Charney, 2001; Hariri et al., 2002), we still ave only a rudimentary understanding of the…”

“Dysregulation of the HPA axis has also been implicated in impaired stress regulation in maltreated populations, where feedback loops regulating glucocorticoid hormones are disrupted by consistently unpredictable or adverse attachment interactions (29), resulting in the individual becoming highly sensitive to stress (3…”

“…and prospective studies have shown that exposure to parental abuse or neglect early in life increases risk for developing psychopathologies such as anxiety disorders, depression and psychosis (Mullen et al., 1996; Kaufman and Charney, 2001; Bebbington et al., 2004; Gilbert et al., 2009).”

“…and anxiety [Etkin and Wager 2007], especially in individuals who have been maltreated in childhood [Hanson et al., 2015a,b; van Harmelen et al., 2010; Teicher et al., 2014; Dannlowski et al., 2012; Kaufman and Charney, 2001; Kelly et al., 2013; DeBrito et al., 2013; Teicher and Samson, 2013].”

“…Health Disorders Dysregulation of the HPA system has been implicated in the etiology of a number of mental health disorders, including posttraumatic stress disorder (PTSD), depressive disorders, and disruptive behavior disorders (De Bellis 2001; Kaufman and Charney 2001; Repetti et al. 2002).”

“…diurnal profile (with elevated afternoon/evening cortisol and awakening levels that may be somewhat lower; Shirtcliff and Essex, 2008) or with elevated evening (peri-sleeponset) cortisol levels (e.g., Dahl et al., 1991; Goodyer et al., 2001; Kaufman and Charney, 2001; Forbes et al., 2006).”

“All rights reserve doi:10.1016/j.psyneuen.2010.02.002 ciation with depression and some anxiety disorders (Holsboer, 2000; Kaufman and Charney, 2001; Hasler et al., 2004; Risbrough and Stein, 2006).”

“, 2011); likewise, childhood trauma and chronic developmental stress are associated with hippocampal atrophy and adult-onset depression (Kaufman and Charney, 2001).”

“Similarly, environmental contributions, such as stressful life events [Heim et al., 1997; Kaufman and Charney, 2001; Sandberg et al., 2001] or parental behavior may also influence the emotional development of children.”

“…more frequent hospitalizations, increased prevalence of obesity, greater drug abuse, increased risk for poor physical health (Batten, Aslan, Maciejewski, & Mazure, 2004; Flaherty et al., 2006; Hussey, Chang, & Kotch, 2006) and poor mental health as well (Bremner, 1999; Kaufman & Charney, 2001).”

“CRH, along with increased levels of arginine vasopressin, stimulate the release of adrenocorticotropin hormone (ACTH) from the pituitary gland into general circulation (Herman & Cullinan, 1997).”

“For example, magnetic resonance imaging studies in adult humans report reduced hippocampal volume in stress-related pathologies, such as anxiety and affective disorders (Kaufman and Charney 2001).”

“…differences in cortical volumes of specific regions of interest in humans, monkeys and rodents and this is the most parsimonious explanation for the results reported here (Chugani et al., 2001; De Bellis et al., 1999; Kaufman & Charney, 2001; Teicher, Andersen, Polcari, Anderson, & Navalta, 2002).”

“Given that chronic elevations in cortisol can pose risks for typical brain development, behavioral outcomes, and physical health (Kaufman & Charney, 2001; Kiecolt-Glaser et al., 2003; Sapolsky, 1996), examining the long-term effects of the anomalous cortisol increase across the childcare day is…”

“Elevated rates of depression and depressive symptomatology have been found in children, adolescents, and adults with histories of child abuse (Kaufman & Charney, 2001; Toth, Manly, & Cicchetti, 1992).”

“, the amygdala and hippocampus, that may modulate responses to stress (32,33).”

“…changes in neurotransmitter systems and structural and functional alterations in brain regions associated with early stress can be modified by familial or genetic factors, the quality of the subsequent caregiving environment, and pharmacological interventions (Kaufman & Charney, 2001).”

“These include factors such as childhood maltreatment, which has been shown to be related to the development of later internalizing and externalizing problems (Kaufman and Charney 2001; McCord 1983; Smith et al. 2006; Tarren-Sweeney and Hazell 2006; Toth et al. 1992).”

“Neglect during childhood is known to have detrimental effects on overall neurodevelopment and brain structure (Kaufman & Charney 2001, Hedges & Woon 2011, Cisler et al. 2013) and is strongly associated with psychiatric disorders such as depression, post-traumatic disorder and schizophrenia (Morgan…”