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Jeremy D. Coplan, MD; Ronald C. Trost, PhD; Michael J. Owens, PhD; Thomas B. Cooper, MA; Jack M. Gorman, MD; Charles B. Nemeroff, MD, PhD; Leonard A. Rosenblum, PhD

Arch Gen Psychiatry. 1998;55:473-477.

Background  In an earlier study, infant primates were nursed by mothers randomly assigned to variable foraging demand (VFD) or nonvariable foraging conditions (non-VFD). A group of grown VFD-reared subjects demonstrated elevations of cisternal cerebrospinal fluid (CSF) corticotropin-releasing factor concentrations and decreased CSF cortisol levels vs non-VFD counterparts. To further characterize neurobiological sequelae of disturbed early rearing, CSF concentrations of serotonin, dopamine, and norepinephrine metabolites (5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenethyleneglycol [MHPG], respectively) and of somatostatin were determined.

Methods  Second CSF taps were obtained from the previously studied cohort of 30 subjects and from 28 age-matched ad libitum–reared control subjects. Relevant assays were performed.

Results  All neurochemicals assayed except MHPG were elevated in the VFD-reared compared with non-VFD subjects. In the VFD group, statistically significant positive correlations between corticotropin-releasing factor and each neurochemical was found, except for MHPG. In the non-VFD subjects, no significant correlations with corticotropin-releasing factor were observed. No effect of age was evident.

Conclusions  Reducing the predictability of maternal foraging demand during early rearing was associated with elevations of cisternal somatostatin and of serotonin and dopamine metabolite concentrations in grown offspring. The corticotropin-releasing factor elevations reported previously were positively correlated with all the elevated CSF parameters of the current study. The findings support the notion that adverse early rearing experiences in primates have longstanding and complex effects on a range of neurochemicals relevant to emotional regulation. Replication in prospective age-controlled studies is warranted.

From the Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY (Drs Coplan and Gorman and Mr Cooper); The Department of Psychiatry and Primate Behavior Laboratory, SUNY Health Sciences Center at Brooklyn, Brooklyn, NY (Drs Coplan, Trost, and Rosenblum); and the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Ga (Drs Owens and Nemeroff).

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