EDITOR’S NOTE
New Insights Highlighting Neurodevelopmental
Issues That Predispose to Childhood and
Adolescent Psychopathology
Ned H. Kalin, M.D.
Most psychiatric illnesses have their onset early in life, and
many of them are hypothesized to be disorders of neuro-
development. Because of the importance of development to
psychiatry, this issue of the Journal is focused on new findings
relevant to factors that are involved in the childhood and
adolescent expression of psychopathology. As behavioral
neuroscience moves forward, numerous findings from pre-
clinical and clinical studies have emerged that emphasize the
genetic and environmental factors that converge to result in
illness vulnerability. In this issue, we learn about new findings
relevant to the genetics of childhood-onset illnesses such as
Tourette’s syndrome and attention deficit hyperactivity
disorder (ADHD). We also learn about factors related to the
within-family, nongenetic transmission of substance abuse,
as well as early-life predictors of adolescent self-harm as it
relates to violent crime.
This issue begins with an overview by Drs. Heidi Meyer
and Francis Lee that puts into perspective how findings
from developmental neuroscience have informed our un-
derstanding of the early-life factors that confer risk for the
development of psychiatric disorders. Dr. Lee is a leading
clinician-scientist focusing on basic mechanisms linking
neurodevelopment to psychopathology, and Dr. Meyer is a
postdoctoral trainee in his laboratory. Their overview pro-
vides a framework for the importance of understanding the
effects of environmental events during childhood and ado-
lescence on the developmental trajectories of neural circuits
that underlie cognition, motivation, and emotion regulation.
Drs. Meyer and Lee also discuss two articles in this issue that
are relevant to altered development of neural circuits that
underlie emotion regulation and cognition. The article by
Jalbrzikowski et al., studying youths with psychotic spectrum
disorders, presents data suggesting that these individuals
have alterations in the normative adolescent developmental
trajectory of amygdala functional connectivity. The article by
Tromp et al. addresses early-life mechanisms that may un-
derlie alterations in prefrontal-subcortical connectivity as-
sociated with anxiety disorders by demonstrating diminished
microstructural integrity in the uncinate fasciculus in pre-
adolescent boys with anxiety disorders.
Two other articles in this issue directly address the genetic
underpinnings of childhood-onset psychiatric illnesses: 1)
Am J Psychiatry 176:3, March 2019
Tourette’s syndrome and other tic disorders and 2) volu-
metric brain alterations that are associated with ADHD.
In the article by Yu et al. and the Psychiatric Genomics
Consortium Tourette Syndrome Workgroup, findings are
presented from a genome-wide association meta-analysis
representing the largest sample studied to date. The find-
ings point to some shared genetics between tic disorders and
Tourette’s syndrome and suggest that across these disorders,
symptom severity is associated with a computed polygenic
risk score. Interestingly, the dorsolateral prefrontal cortex, a
region of the brain known to be involved with executive
function, was found to preferentially express the identified
risk genes. In relation to ADHD, research demonstrates re-
ductions in total and subcortical regional brain volume that
are associated with the illness. In this issue, the article by
Klein et al. provides in-
sights into this brain al- Because of the importance
teration by demonstrating of development to
a genetic correlation be- psychiatry, this issue of the
tween reductions in total Journal is focused on new
brain volume with ADHD
findings relevant to factors
risk. This suggests that
that are involved in the
these two features share
similar genetic under- childhood and adolescent
pinnings. This work also expression of
identifies specific genes psychopathology.
that may be important to
the shared genetics between brain volume and ADHD risk,
suggesting leads for further studies focused on mechanisms
underlying ADHD-related decreases in brain volume.
Moving away from genes to psychosocial influences,
Kendler et al. demonstrate that nongenetic contagion factors
are important in the development and “transmission” of drug
abuse. This study capitalizes on a large Swedish cohort by
focusing analyses on the timing of the development of drug
abuse among related family members. This design allows for
the control of genetic influences. The findings demonstrate
that the likelihood of drug abuse transmission is greater from
parent to child (adolescent to early adulthood years), from
older sibling to younger sibling, and greater in closer com-
pared with more distant relatives. Taken together, and be-
yond genetic risk, these findings highlight the potential
ajp.psychiatryonline.org 171
EDITOR’S NOTE
importance of within-family patterns of substance abuse
and the social learning that may take place in relation to its
intrafamilial transmission.
Substance dependence, childhood victimization, and
higher rates of psychotic symptoms are factors that we learn,
from the paper by Richmond-Rakerd et al., are associated
with adolescents who engage in “dual-harm” behavior. These
individuals not only engage in self-harm behavior but also
have committed violent crimes. Notably, the findings from
this work demonstrate that self-harm is associated with
a marked increase in the likelihood of committing violent
crimes, and the findings importantly underscore the need for
early interventions focused on mitigating the influences of
the risk factors identified in this study.
Taken together, the articles in this issue of the Journal
underscore the importance of studying early development at
multiple levels to better understand mechanisms that pre-
dispose to the emergence of psychopathology. While perhaps
not a surprise to clinicians, these articles demonstrate the
172 ajp.psychiatryonline.org
value of understanding the complicated developmental in-
teractions among such factors as early stressors, genetic
predispositions, and family behavior. As our science teaches
us more about these early-life risk factors, the hope is that
a better understanding of the environmental, familial, and
genetic determinants of specific psychopathologies will en-
hance our abilities to transform vulnerability into resilience.
AUTHOR AND ARTICLE INFORMATION
Department of Psychiatry, University of Wisconsin School of Medicine and
Public Health, Madison.
Send correspondence to Dr. Kalin (nkalin@wisc.edu).
Dr. Kalin has received research support from NIH and NIMH; has served as
a consultant for APA, CME Outfitters, the Pritzker Neuropsychiatric Dis-
orders Research Consortium, the Skyland Trail Advisory Board, and TC
MSO; owns stock in Seattle Genetics; and received honoraria from
Elsevier as co-editor of the journal Psychoneuroendocrinology.
Accepted January 28, 2019.
Am J Psychiatry 2019; 176:171–172; doi: 10.1176/appi.ajp.2019.19010092
Am J Psychiatry 176:3, March 2019