Thomas Spencer’s research while affiliated with Massachusetts General Hospital and other places

Objective To provide an overview of Joe Biederman’s contributions to child and adolescent psychiatry. Method Nine colleagues described his contributions to: psychopharmacology, comorbidity and genetics, pediatric bipolar disorder, autism spectrum disorders, Tourette’s and tic disorders, clinical and neuro biomarkers for pediatric mood disorders, executive functioning, and adult ADHD. Results Joe Biederman left us with many concrete indicators of his contributions to child and adolescent psychiatry. He set up the world’s first pediatric psychopharmacology clinic and clinical research program in child adolescent psychiatry. As a young faculty member he began a research program that led to many awards and eventual promotion to full professor at Harvard Medical School. He was for many years the most highly cited researcher in ADHD. He achieved this while maintaining a full clinical load and was widely respected for his clinical acumen. Conclusion The world is a better place because Joe Biederman was here.

Objective We offer an overview of ADHD research using mouse models of nicotine exposure. Method Nicotine exposure of C57BL/6 or Swiss Webster mice occurred during prenatal period only or during the prenatal and the pre-weaning periods. Behavioral, neuroanatomical and neurotransmitter assays were used to investigate neurobiological mechanisms of ADHD and discover candidate ADHD medications. Results Our studies show that norbinaltorphimine, a selective kappa opioid receptor antagonist is a candidate novel non-stimulant ADHD treatment and that a combination of methylphenidate and naltrexone has abuse deterrent potential with therapeutic benefits for ADHD. Other studies showed transgenerational transmission of ADHD-associated behavioral traits and demonstrated that interactions between untreated ADHD and repeated mild traumatic brain injury produced behavioral traits not associated with either condition alone. Conclusion Preclinical models contribute to novel insights into ADHD neurobiology and are valuable tools for drug discovery and translation to benefit humans with ADHD.

In this issue of the Journal, the important story of height and weight issues related to stimulant medication in attention-deficit/hyperactivity disorder (ADHD) is yet again addressed, in the largest study to date.1 Controversy related to potential growth decrements in youth with ADHD receiving stimulants has been around for decades. In fact, in a quick PubMed search of the literature, we identified more than 100 studies, 15 reviews, and meta-analyses in this area. In a general score card, about three-fourths of studies seem to support some degree of decrement, but clinical significance has yet to be determined. What is not being debated anymore is the short- and longer-term effectiveness of stimulants for ADHD with reductions in mood disorders, suicide, substance use/disorders, criminality, motor vehicle accidents, injuries, concussions, and academic failure documented in the Swedish and other register studies.2 Many of these improvements are linked with a decrease in major morbidity and even mortality. Hence, we need to put the issue of potential stimulant-related growth velocity changes in the context of the very real adverse outcomes associated with non-treatment of ADHD.

Military service can add stress to military-connected family members, and this stress has been linked to their overall well-being. This study examined the acceptability and explored the effectiveness of a mind-body stress management program for military-connected families and whether it was more effective delivered in person or online. Participants ( n = 55; 96% female; M age = 39.98±10.11) completed assessments of mood, functioning, mindfulness, and coping at pre- and post-program, as well as post-program qualitative feedback surveys. All participants reported that they felt comfortable during the program, and most (>90%) reported that it was helpful and would recommend it for others. Participants experienced significant improvement in stress, depressive symptoms, and self-efficacy (Cohen's d > 0.60). No significant differences in the outcomes for the in-person versus the online program were found. This program, whether delivered online or in person, seems to improve stress, self-efficacy, and depressive symptoms in military-connected families. [ Psychiatr Ann . 2022;52(5):179–185.]

Objective: While the comparative efficacy of prolonged exposure (PE) and cognitive processing therapy (CPT) has been examined in outpatient settings, there is a dearth of literature on the relative effectiveness of these interventions when adapted for an intensive treatment format. In an expanded secondary analysis of a previous study, we sought to examine the comparative effectiveness of PE and CPT delivered in the naturalistic setting of an intensive treatment format including maintenance of outcomes through a 6-month follow-up period. Method: A sample of 296 veterans with posttraumatic stress disorder (PTSD) received either PE (n = 186) or CPT (n = 90), alongside other trauma-informed interventions, in a 2-week intensive clinical program. Treatment selection was determined collaboratively between patient and therapist. Our primary outcome was self-reported PTSD symptom severity (i.e., PTSD Checklist for DSM-5, PCL-5); secondarily, we examined self-reported depression (i.e., Patient Health Questionnaire) symptom severity outcomes. Results: A mixed-model regression controlling for age and gender revealed a significant effect of time from baseline to endpoint (p < .001), 3-month (p < .001), and 6-month follow-up (p < .001) on PCL-5 scores but no significant effect of treatment or effect of treatment by time interaction (all ps > .05; model: Wald's χ² = 232.38, p < .001). Results were similar for depression outcomes. Attrition at posttreatment was not significantly different between groups: 7.2% for CPT and 6.5% PE (z score = 0.22). Conclusions: Both PE and CPT are associated with comparable improvements when delivered as part of a 2-week intensive outpatient program. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Perinatal nicotine exposure (PNE) produces frontal cortical hypo-dopaminergic state and attention and working memory deficits consistent with neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). Methylphenidate alleviates ADHD symptoms by increasing extracellular dopamine and noradrenaline. Kappa opioid receptor (KOR) antagonism may be another mechanism to achieve the same results because KOR activation inhibits frontal cortical dopamine release. We administered the selective KOR antagonist norbinaltorphimine (norBNI) (20 mg/kg; intraperitoneal) or methylphenidate (0.75 mg/kg; intraperitoneal) to PNE mouse model and examined frontal cortical monoamine release, attention, and working memory. Both compounds increased dopamine and noradrenaline release but neither influenced serotonin release. Both compounds improved object-based attention and working memory in the PNE group, with norBNI's effects evident at 2.5 h and 5.5 h but absent at 24 h. Methylphenidate's effects were evident at 0.5 h but not at 2.5 h. norBNI's effects temporally coincided with frontal cortical c-Jun N-terminal kinase phosphorylation. norBNI did not alter tissue dopamine content in the nucleus accumbens, offering preliminary support for lack of reinforcement.