Neurobiology of Child Neglect/Abuse: Nemeroff Lecture Notes

I had the opportunity to attend the Warren Neuroscience Lecture presented by Dr. Charles Nemeroff in Tulsa, OK on June 2, 2015.

Dr. Nemeroff has been an international leader in research in mood and anxiety disorders. His recent focus has been on the effects of adverse childhood environments on risk for adult mood and anxiety disorders. 

Here are my notes that summarize some of the key points from his lecture.

Introduction:

• Stress is an important factor in understanding depression
• Early life stress is a risk factor for later adult depression
• Genes account for a significant portion of the variation in risk following stress exposure
• Brain systems that regulate emotions are disrupted during episodes of major depression

Psychiatry research slowed by complexity of brain, multiple cell types, complex heterogeneous disorders. But we are beginning to understand the key role genes play in a variety of key disorders. Genetic factors account for 65% of bipolar disorder variance, 50% of schizophrenia variance and around 35% of variance in major depression.

Early childhood abuse and neglect is common. Recent surveys estimate prevalence rates for each of the following:

• Physical abuse 15-28% of general population in U.S.
• Sexual abuse in 11-21% 
• Emotional abuse in 11-36%
• Parental divorce or separation in 25%

Early childhood abuse and neglect has multiple effects in neurobiology and later adult mood and anxiety disorder risk:

• Increased adult cerebral spinal marker of stress known as corticotrophin releasing factor (CRF)
• Increase serum ACTH and cortisol
• Increase inflammatory markers  such as interleukin-6
• Decreased cerebral spinal fluid oxytocin that may impair social function and bonding with children
• Reduced brain cortex thickness and hyperactivy amygdala response
• Increased adult PTSD and depression
• Increased adult rates of substance abuse
• Increased risk of suicidal behavior and completed suicide

There is a growing body of evidence that ten or more genes influence vulnerability to childhood abuse and neglect including genes regulating the HPA axis, serotonin function and a gene known as FKBP5. These genetic effects may interact with environmental stresses to reduce or amplify stress vulnerability. Stress may be viewed as a teratogen that influences genetic features through epigenetic and gene regulation effects.

For clinicians there are important treatment implications:

• Major depression in the context of moderate to severe childhood abuse is less responsive to medication or to psychotherapy intervention
• Childhood abuse and neglect in bipolar disorder is linked to early onset, greater severity and poor treatment response.

During the discussion following the lecture Dr. Nemeroff noted the importance of population-based efforts to reduce societal levels of exposure to child abuse and neglect including:

• Early education with teacher training to look for evidence of abuse/neglect
• Increased training for primary care physicians treating infants/children
• Increased training and funding for social services that evaluate and treat children referred for child abuse/neglect
• Increased detection and surveillance for sexual predators
• More research in the treatment of sexual disorders including pedophilia. There is almost no NIH funding in this area and little research interest and activity.

Below I have added citations featured in the presentation to allow readers with more interest to delve into some of the primary research studies.

Image is this post is "PBB Protein CRH image" from Wikipedia chapter on CRH. Image by ProteinBoxBot.  Licensed under Public Domain via Wikimedia Commons  

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Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, Miller AH, & Nemeroff CB (2000). Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA, 284 (5), 592-7 PMID: 10918705

Heim C, Mletzko T, Purselle D, Musselman DL, & Nemeroff CB (2008). The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma. Biological psychiatry, 63 (4), 398-405 PMID: 17825799

Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB, Tang Y, Gillespie CF, Heim CM, Nemeroff CB, Schwartz AC, Cubells JF, & Ressler KJ (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA, 299 (11), 1291-305 PMID: 18349090

Saveanu, R., & Nemeroff, C. (2012). Etiology of Depression: Genetic and Environmental Factors Psychiatric Clinics of North America, 35 (1), 51-71 DOI: 10.1016/j.psc.2011.12.001

Fatherhood and the Biology of Infant Care Behavior

Early positive parental-infant attachment provides a key developmental advantage.

The maternal-infant dyad has received the most research attention. However, fathers also can play an important role in infant development. An increasing number of studies focus on the biology of fatherhood and infant care behavior.

Ilanit Gordon along with colleagues in Israel and the United States examined the role of two central neuropeptides in paternal behavior during the first six months of infancy.

In their study, 43 fathers with a firstborn infant were studied when the infants were two and six months old. Fathers were rated on levels of emotional synchrony with their infant. Additionally, fathers were rated on levels of paternal involvement in exploratory play.

Paternal serum oxytocin and prolactin levels were obtained at both the two and six month time points. Oxytocin has been identified as a key neuropeptide in maternal-infant bonding, but it's role in fathers is unclear.

The authors found significant relationships between the two hormones and paternal-infant behavior. Paternal serum oxytocin levels correlated with emotional synchrony while serum prolactin levels correlated with coordinated exploratory play.

The authors note in their discussion that prolactin had previously been identified as important in animal studies of fathers but not in humans.

The mechanism of how these two hormones impact paternal behavior is unclear.

A recent study by Mascaro and colleagues suggest neuropeptides may influence specific brain regions known to be important in empathy (anterior insula and inferior frontal gyrus).

In their study, a series of fathers were studied for responsiveness to the cries of children between one and two years of age. Brain regional activation levels were compared across a paternal responsiveness to infant cries.

The key finding in this study was a nonlinear relationship between anterior insula activation and paternal responsiveness. Fathers with a moderate level of activation outperformed fathers with low or high levels of activation. 

These types of studies are important. They may hold promise for improving parental attachment to their children. Additionally, they may provide some insight into the biology of child abuse and neglect. These first studies are limited correlational design studies but they add evidence of the need for additional more complex and sophisticated research.

Readers with more interest in these two studies can get more information by clicking on the PMID links in the citations below.

Image of brain amygdala is a screen shot from the iPad app 3D Brain.

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Gordon I, Zagoory-Sharon O, Leckman JF, & Feldman R (2010). Prolactin, Oxytocin, and the development of paternal behavior across the first six months of fatherhood. Hormones and behavior, 58 (3), 513-8 PMID: 20399783

Mascaro JS, Hackett PD, Gouzoules H, Lori A, & Rilling JK (2014). Behavioral and genetic correlates of the neural response to infant crying among human fathers. Social cognitive and affective neuroscience, 9 (11), 1704-12 PMID: 24336349