What Makes Us Who We Are?

As child and adolescent psychiatrists, it is our job to identify factors that influence the behaviors seen in front of us. Often the question is asked whether these factors are primarily due to nature or nurture: Is someone born a "bad kid," or are there environmental exposures that lead to less than ideal behaviors? Factors such as racism, poverty, bullying, social isolation, and even where we grow up could play a part in the behaviors seen. This is one of the most rewarding, but at times can be one of the most frustrating, parts of our job as child and adolescent psychiatrists. Hopefully we can explore the factors influencing behaviors seen by the children we work with, highlighting the good in them and the situations that have led to the concerns seen. At the same time, we can become frustrated knowing that some of these factors are difficult for us to change as an individual child and adolescent psychiatrist, such as racism, poverty, inequalities in education, or family support. Bearing witness to these societal issues and their impact on our patients hopefully sparks advocacy efforts toward larger system changes.

Rupture and Repair.

Rupture and repair are key ingredients to connection. When ruptures in relationships occur, which they will, it is important to revisit the situation to work on restoring safety, regulation, attunement, and understanding. Through engaging in this process and providing consistent secure base and safe haven supports, conflicts have the opportunity to heal. Developmentally, the practice of rupture and repair begins during infancy and early childhood, laying the foundation for secure attachment. What happens when ruptures repeatedly occur without repair? How does this impact self-esteem and the narratives children create about themselves as they grow? As you can imagine, repeated rupture without repair can lead to mistrust, cognitive distortions, resentment, and emotional stunting. As child and adolescent psychiatrists, we can help families understand that relationships, like people, can bend without breaking-and that a healthy serving of humble pie can be just what the doctor ordered.

The Cost of Avoidance.

As child psychiatrists, it is our job to ask questions, and many of us would say we are really good at it. We work with our patients to open up about their experiences, discussing fear, sadness, hope, and joy. By modeling this ability to open up in the office, we help guide children and adolescents through using other skills rather than avoidance. Although avoidance has its place at times, we help show our patients the connection between anxiety and avoidance. This necessity to embrace and challenge fears can be a difficult skill for our patients and also their families. Children bring forward questions that parents may want to avoid, fearing the answer might be more difficult for the child than the rejection of having the question avoided all together. As someone who works with children with chronic illnesses, this avoidance of the question can in fact increase the fear and anxiety of the child or adolescent. When talking to children, often they will express a greater fear than the reality of the situation because they determine that if their parent is avoiding the question, it must be really bad. This same struggle with avoidance can be true for us as child psychiatrists as well. The necessity to take on roles of leadership or run a team often presents itself, but excuses can come up to help us avoid these roles. We might say we are not properly trained, we did not go into medicine to do those responsibilities, or we are too busy. By avoiding these responsibilities, we are setting ourselves up for more frustration. As teams struggle, we have to follow the lead of others without the same clinical knowledge, which may result in additional errors. We must remember to practice what we preach and to identify the cost of avoidance.

Kaleidoscopes.

I remember the magic of looking through a kaleidoscope as a little girl. Brilliant, vibrant colors coming together to make symmetrical shapes that seemed as precise as they were chaotic. Each look through the lens offered something new and spectacular, different than the intricate images seen before. With a little shake and turning of a tube and the sound of colored beads, pebbles, or small pieces of glass swirling together, mirrors connect with the light in just a way to produce the beauty that we see. Who would have thought that such a small disruption leading to the destruction of a pattern could make room for the same materials to come together again to form something fantastic, though different? Each turn or shake of a kaleidoscope could represent life changes or new perspectives that require some level of deconstruction before evolving into magnificence. Or you can simply be a kid who likes pretty pictures and wild shapes, experiencing joy and the spirit of adventure with each look. Whatever your experience, interpretation, or developmental stage, kaleidoscopes allow us to appreciate wonder, creativity, and the power of play, all rolled into one mercurial lens.

The Developing Child.

As children age, there are set milestones that we follow clinically to help track fine motor, gross motor, social, and language development. Because we know what a 2-month-old vs 4-month-old vs 1-year-old child should be able to do, we are able to assess whether a given child is on track developmentally. In pediatrics, three developmental stages are assessed and, if, behind there is a clear next step, often to involve early intervention. In child psychiatry, work has been done to establish stages of development as well, seen through the work of Piaget, Erickson, and others. These stages help to define the thoughts and behaviors expected for different-aged children, and thus can help with putting together our diagnostic formulation. The difficulty is that these stages are much broader temporally then the early motor, social, and language developmental milestones. Students may also be participating in the same experiences, such as the same grade level, even though they are at different developmental levels based on their age when they started school, as there could be as much as a year difference between those in a given grade. This has led to concerns about being able to distinguish a child struggling with attention-deficit/hyperactivity disorder (ADHD) relative to a child who is younger than his peers, as teachers may compare a young child to their older peers when filling out assessment forms.1 These are the developmental questions that we often must ponder as child psychiatrists, inasmuch as mental health and behavioral development are complex and influenced by many factors. In this month's Book Forum, Rishab Chawla looks more into these questions in the review of Nasty, Brutish and Short by Scott Hershovitz, pointing out that there is an overlap between the skills of a child psychiatrist to assess the behavioral impact of these developmental questions and the philosophical questions that younger children start to ponder. The child's developmental understanding of right and wrong will better help us to assess the behaviors that present to us in the office. As Rishab points out in the review, we must ask more about these children whom we see regarding these philosophical questions to better understand some of the behaviors present. Looking more deeply into a student's understanding of these questions may better help us to distinguish developmentally appropriate or inappropriate behaviors.

Seeking Meaning in the Void.

One of the most important jobs in elementary school can be distilled down to 2 words: line leader. This is the mighty carrot to mobilize ordinarily sluggish children through their morning routine, as they look forward to standing proudly at the front of their classroom line. I have witnessed this phenomenon myself, as my first-grade son was chosen to be the glorious line leader of room 15. He moved with a sense of urgency in the morning to pack his backpack, fill his water bottle, and put on his shoes and socks, all with zero parental prompting. After I dropped him off, I secretly watched through the chain-link fence as he skipped over to his class with his head held high to claim his hard-earned position as the Tuesday line leader. The look of pride on his face was undeniable. This leadership position truly meant something to him, giving him a sense of purpose. As he marched his class to the same classroom door that they walk through every day, it was clear that the kid walking through the door had a little more shine than he had the day before.

The Power of Shared Experience.

The experiences of others can often be used as a motivator, caution tale, point of education, and much more. Parents describe their own experiences to help their children make the right choices, including avoiding some mistakes they might regret. We watch movies and read books about historical figures, actors, athletes, and other famous people to better understand how their experiences shaped the person they became. More recently the growth of influencer culture has led people to watch videos to make decisions based on what the person tells them of their own experience. The difficulty is that many of these experiences have been selectively crafted to fit what makes a good movie or to promote a product.

Peek-A-Boo, I See You!

Peek-A-Boo is a beloved game played around the world, crossing language and cultural barriers alike. In addition to reinforcing the magical principle of object permanence, Peek-A-Boo generates laughter and shared joy that is contagious. While engaging with a patient diagnosed with postpartum depression, I was delighted to witness the power of this game on full display. When her 10-month-old son grew fussy as she discussed her matrescence, the patient gave me a playful look before abruptly covering her eyes with both hands. She waited a moment, then quickly uncovered her eyes while squealing "Peek-A-Boo, I see you!" I can still hear his gasp of surprise followed by a hearty, deeply committed belly laugh that echoed in the room. Why is this game so universally loved? Is it because it promotes connection, can be used as a powerful learning tool, or perhaps because it reinforces the idea that things stick around even when you can't see them? Maybe it is all of these things swirling together at once, built on a deeper principle that feeling seen and accepted without condition feels pretty darn good. Either way, I walked away from that encounter reminded of the simple truth that laughter-especially from a spirited baby-can be the best medicine.

Representation Matters.

In the world of pediatrics, studies have shown that the majority of dermatology textbooks display pictures primarily of White skin.1 This lack of representation has led to pediatricians and dermatologists having less exposure to dermatologic conditions such as eczema in Black and Brown skin, even though studies show that it can be more prevalent in these populations.2 As such, trainees and others have advocated for and created more diverse picture libraries to better represent dermatologic presentations in various skin colors.3.

Adventures in Fortnite: Selections From Connect Corner.

JAACAP Connect, our developmental journal, began publishing in 2014 to support "the development of writing and editing skills among members of the American Academy of Child and Adolescent Psychiatry." JAACAP Connect "is dedicated to engaging trainees and practitioners in the process of continuous and applied career learning through readership, authorship, and publication experiences that emphasize translation of research findings into the day-to-day clinical practice of child and adolescent psychiatry." Over the past 8 years, dozens of new or early career authors have worked closely with JAACAP Connect editors to develop manuscripts into published articles.

The Search for Our Identity.

Identity has been a part of psychiatry from its roots. Sigmund Freud's description of the id, ego, and super ego reflects the various identities that lie within each of us. Carl Jung introduced the development of our identity through the stages of life. We have identity disorders in the DSM. In psychiatry, we diagnose patients, and that diagnosis can meaningfully impact identity formation. It plays a part in the way persons views themselves while also influencing how they are perceived by others. The discussion of identity development through our experiences and how we view our current identity plays an integral role in therapy. This month's Book Forum focuses on 3 books that look at identity through various lenses of experience, diagnosis, and treatment. Although they provide just a snapshot, it is clear from these reviews the significant impact that these books made on the reader.

Book Forum: An Introduction to the JAACAP Editorial Team.

Children's books are often our first window into the magic of the written word. As child and adolescent psychiatrists, these books not only lay a foundation for our own introduction into reading, but also are a tool used to connect with the youth and families we serve. We felt there was no better way to continue to introduce some of the new members of JAACAP's Editorial Board than through reading reviews of their favorite children's books. Featured are book reviews from the JAACAP Editor-in-Chief, Associate Editor, and new Deputy Editors. Next month we will highlight children's book reviews from members of JAACAPOpen's inaugural Editorial Board.

Development of a Meso Scale Discovery ligand-binding assay for measurement of free (drug-unbound) target in nonhuman primate serum.

Aim: To quantify the free form of a protein as a target-engagement biomarker in nonhuman primate serum, a Meso Scale Discovery ligand-binding assay was developed and qualified. Results: The initial assay produced an unexpected artifact when used to measure the free target in study samples dosed with drug. By using incurred study samples dosed with high drug levels to test assay performance, we developed an alternative assay that does not suffer from drug interference. Conclusion: Our work demonstrated that an assay designed to measure free target may not necessarily deliver reliable quantitation. In our case, incurred study samples dosed with drug proved to be useful in developing an alternative free assay that does not suffer from drug interference.

Orofacial Clefts May Be a Window Into Identifying Common Psychopathology Development.

The research supporting a connection between physical and psychiatric illness continues to grow and advance. For example, there is continued work to identify whether this is due to connected brain pathology or to psychosocial stressors that inherently come with having another illness. Congenital illnesses may represent a window into our better understanding this connection, as the defect during embryogenesis that leads to the illness is sometimes known. Oral facial clefts (OCF) represent a congenital malformation that is well suited to study this question, as it is a common congenital condition and there are studies showing the increased prevalence of psychiatric comorbidities for those with OFC.1 Of all patients with OFC, 70% are nonsyndromic, meaning they do not have an associated genetic syndrome leading to the development of the OFC.2 There are three different types of OFC-cleft lip, cleft lip and palate, and cleft palate only-but it has been shown that all three seem to be associated with an increased risk for psychiatric illness. The timing of when OFC is believed to develop reflects a period when cells are differentiating from the neural tube, and thus a critical period in brain development.3 Some risk factors for developing OFC, such as alcohol use, antiepileptics, and smoking, may also affect brain development and are also associated with risk for the development of psychiatric disorders. What previous studies of OFC and psychiatric comorbidities have not been able to do is to control for other potential causes of OFC, especially familial risks.

Amino-terminal isoforms of the human glycine transporter GlyT1 exhibit similar pharmacology.

Alternative promoter usage and mRNA precursor splicing produce three amino-terminal isoforms of the human glycine transporter type 1 (GlyT1). To enable discovery of pharmacological tools that might distinguish them, each of these isoforms was stably expressed in CHO-K1 cells and clonal isolates were generated by limiting dilution. Glycine uptake assays were validated for two lines for each isoform, one low and one high expressor. The data show a modest trend for lower potency against higher expressing lines. IC(50) values for reference GlyT1 inhibitors ALX-5407 (Allelix), (S)-13h (Merck), and SSR504734 (Sanofi-Synthelabo) were similar across isoforms. The greatest variation was observed for ALX-5407, and its IC(50) values across isoforms were still within one log unit of each other. Antipsychotics previously shown to be weak inhibitors of GlyT1 likewise had similar potency against all three isoforms. The cell lines validated here are tools for discovering inhibitors that might distinguish among GlyT1 isoforms.

Glycine transporter (GlyT1) inhibitors with reduced residence time increase prepulse inhibition without inducing hyperlocomotion in DBA/2 mice.

Inhibition of the glycine transporter type 1 (GlyT1) leading to potentiation of the glycine site (GlyB) on the N-methyl-d-aspartate (NMDA) receptor has been proposed as a novel therapeutic approach for schizophrenia. However, sarcosine-based GlyT1 inhibitors produce undesirable side effects including compulsive walking and respiratory distress. The influence of specific biochemical properties of GlyT1 inhibitors, such as mode of inhibition and residence time, on adverse effects is unknown. Two GlyT1 inhibitors that contain a sarcosine moiety, sarcosine and ALX-5407, and two compounds that do not contain a sarcosine moiety, Roche-7 and Merck (S)-13h, were evaluated for their potency, mode of inhibition, and target residence times in vitro, and modulation of prepulse inhibition (PPI) and locomotor activity in vivo. (S)-13h and sarcosine were competitive inhibitors while ALX-5407 and Roche-7 demonstrated mixed noncompetitive inhibition. Potency of GlyT1 inhibition (ALX-5407>(S)-13h>Roche-7≫sarcosine) did not correlate with residence time on GlyT1 (sarcosine=Roche-7≪(S)-13h