Editorial: Frontiers in Brain-Based Therapeutic Interventions and Biomarker Research in Child and Adolescent Psychiatry

The Editorial on the Research Topic 
 
Frontiers in Brain-Based Therapeutic Interventions and Biomarker Research in Child and Adolescent Psychiatry 
 
Childhood psychiatric disorders present challenges given the heterogeneity of presentations, instability of phenotypes, and nascent understanding of neurodevelopment. Recent efforts, such as the National Institute of Mental Health Research Domain Criteria, aim to hone precision medicine approaches for psychiatric disorders (1). Elucidating the ontogeny of psychiatric illnesses and underlying neurobiology is a mandate for advancing modern clinical practice. Recent advances in neuroimaging, preclinical studies, genomics, and non-invasive brain stimulation may soon provide improved monitoring of development in health and disease. These tools also hold great promise for developing biological markers of illness that may be targeted through treatment innovation. This research topic surveys recent developmentally informed clinical neuroscience efforts focused on conditions that affect children and adolescents. Broadly, this includes studies focusing on neurodevelopmental disorders, eating disorders, mood disorders, and treatment innovations.


Frontiers in Brain-Based Therapeutic Interventions and Biomarker Research in Child and Adolescent Psychiatry
Childhood psychiatric disorders present challenges given the heterogeneity of presentations, instability of phenotypes, and nascent understanding of neurodevelopment. Recent efforts, such as the National Institute of Mental Health Research Domain Criteria, aim to hone precision medicine approaches for psychiatric disorders (1). Elucidating the ontogeny of psychiatric illnesses and underlying neurobiology is a mandate for advancing modern clinical practice. Recent advances in neuroimaging, preclinical studies, genomics, and non-invasive brain stimulation may soon provide improved monitoring of development in health and disease. These tools also hold great promise for developing biological markers of illness that may be targeted through treatment innovation. This research topic surveys recent developmentally informed clinical neuroscience efforts focused on conditions that affect children and adolescents. Broadly, this includes studies focusing on neurodevelopmental disorders, eating disorders, mood disorders, and treatment innovations.

NEUrodEVEloPMENtal diSordErS
Recent changes in descriptive diagnostic criteria, such as DSM-5 (2), aim to bridge basic science findings with clinical practice (3). Goldani et al. examine existing literature focused on putative biomarkers of autism spectrum disorder (ASD). Markers of mitochondrial function, oxidative stress, genetic clustering, and inflammation are promising approaches. However, at present, there is insufficient evidence to embed these markers into clinical practice (Goldani et al.). In other efforts to better understand neurobiology in ASD and related neurodevelopmental disorders, Baribeau and Anagnostou review neuroimaging correlates of ASD and schizophrenia. Volumetric changes, cortical thickness differences, and white matter changes in childhood onset schizophrenia (COS) appear to attenuate with age. Impaired local connectivity may also be coupled with amplified long-range connectivity in this condition. Neuroimaging findings in ASD collectively suggest an initial period of brain verdancy followed by dysmorphogenesis in adolescence. Furthermore in ASD, patterns of local hyper-connectivity are coupled with impaired long-range neural communication (Baribeau and Anagnostou). Nagamitsu et al. present recent dimensional work with brain single-photon emission computed tomography (SPECT) in participants with attention deficit hyperactivity disorder (ADHD). Children with ADHD, and higher scores on the child behavior checklist-dysregulation profile had significantly increased 123 I-iomazenil biding in the posterior cingulate cortex. These data suggest that GABAergic inhibitory neurons are involved in the pathophysiology of ADHD (Nagamitsu et al.).

aFFECtiVE diSordErS
Recent controversies surrounding the phenotyping of childhood mood disorders underscore the necessity of ongoing work focused on the neurobiological characterization of affective disorders during neurodevelopment (4)

EatiNG diSordErS
Eating disorders are severely impairing psychiatric illnesses, with high mortality rates, and profound neurobiologic underpinnings (5). Herein, McAdams and Krawczyk describe findings from a study of patients with anorexia, patients with bulimia, and healthy controls. Participants were exposed to social attribution, social identity, and physical identity fMRI tasks. Consistently throughout each region of interest, average activation levels for bulimic participants were greater than the group of patients with anorexia, but less than healthy participants. The authors concluded that patients with eating disorders could have a similar biological substrate in terms of social functioning, yet a distinctive functional characterization is a plausible pursuit for future work (McAdams and Krawczyk). Nagamitsu et al. also present intriguing work focused on developing SPECT biomarkers to guide the treatment of children with anorexia nervosa. In children with anorexia nervosa, decreased 123 I-iomazenil binding in the anterior cingulate and left parietal cortices was associated with a suboptimal response to treatment. Successful weight restoration was associated with increased relative binding of 123 I-iomazenil in the posterior cingulate and occipital cortices (Nagamitsu et al.).

trEatMENt iNNoVatioN iN CHildrEN aNd YoUtH
Transcranial magnetic stimulation (TMS) is a powerful therapeutic and neurophysiological probe. Neurocognitive outcomes are key both in terms of safety and for intervention development, as they may serve as optimal clinical outcome measures in youth (6, 7 In conclusion, the synthesis of neuroscience with child and adolescent psychiatry is yielding important discoveries and new directions for treatment innovation. However, we have yet to make the discoveries necessary to bring neuroscience research into the clinical realm through specific biomarker discovery that could pave the way for precision medicine where biomarkers are profiled in the clinic and individualized treatments are selected to optimize neurodevelopmental trajectories, mitigate the long-term effects of psychiatric illness, and maximize functioning for individuals. Novel research tools, innovative study designs that go beyond the case-control model, longitudinal research that identifies developmental trajectories within heterogeneous conditions, and largescale studies with the power to detect small effects are likely the next frontier in research focused on advancing our understanding of neurobiological underpinnings and developing biologically informed treatments for children and youth with mental illness.

aUtHor CoNtriBUtioNS
All authors listed have made substantial, direct, and intellectual contribution to the work and approved it for publication.