Faculty Bibliography

INTRODUCTION/BACKGROUND:We examined data from a large, high acuity, pediatric psychiatric emergency department (ED) to assess both the immediate and longer-term impact of the pandemic on ED visits for suicidal thoughts and behaviors (STBs) among youth. METHODS:Youth ages 5-17 years presenting at a pediatric psychiatric ED in New York, NY from March 2019-November 2021 were included in this study. Visits were categorized as pre-pandemic, pandemic year 1, or pandemic year 2. We examined changes in demographic and clinical characteristics among patients presenting across the three time periods, as well as multivariable associations between these characteristics and STBs. RESULTS:Over 32 months, 2728 patients presented at 4161 visits. The prevalence of a discharge diagnosis of STBs increased from 21.2% pre-pandemic to 26.3% (p < 0.001) during pandemic year 1, and further increased to 30.1% (p = 0.049) during pandemic year 2. Youth were 21% more likely to receive a discharge diagnosis of STBs in pandemic year 1 (RR 1.21, 95% CI 1.07, 1.36) and 35% more likely in pandemic year 2 (RR 1.35, 95% CI 1.19, 1.52) compared to pre-pandemic baseline. CONCLUSIONS:In a large, high-acuity ED, STBs continued to increase 20 months after the initial COVID-19 lockdown. These findings highlight the persistent detrimental impact of the pandemic on youth mental health.

Parkinson's disease (PD) is well known for motor deficits such as bradykinesia. However, patients often experience additional deficits in working memory, behavioral selection, decision-making and other executive functions. Like other features of PD, the incidence and severity of these cognitive symptoms differ in males and females. However, preclinical models have not been used to systematically investigate the roles that sex or sex hormones may play in these complex signs. To address this, we used a Barnes maze spatial memory paradigm to compare the effects of a bilateral nigrostriatal dopamine lesion model of early PD on cognitive behaviors in adult male and female rats and in adult male rats that were gonadectomized or gonadectomized and supplemented with testosterone or estradiol. We found that dopamine lesions produced deficits in working memory and other executive operations, albeit only in male rats where circulating androgen levels were physiological. In males where androgen levels were depleted, lesions produced no additional Barnes maze deficits and attenuated those previously linked to androgen deprivation. We also found that while most measures of Barnes maze performance were unaffected by dopamine lesions in the females, lesions did induce dramatic shifts from their preferred use of thigmotactic navigation to the use of spatially guided place strategies similar to those normally preferred by males. These and other sex- and sex hormone-specific differences in the effects of nigrostriatal dopamine lesions on executive function highlight the potential of gonadal steroids as protective and/or therapeutic for the cognitive symptoms of PD. However, their complexity also indicates the need for a more thorough understanding of androgen and estrogen effects in guiding the development of hormone therapies that might effectively address these non-motor signs.

Re-exposure to drug-associated cues causes significant drug craving in recovering addicts, which may precipitate relapse. In animal models of craving, drug-seeking responses for contingent delivery of drug-associated cues sensitizes or "incubates" across drug withdrawal. To date there is limited evidence supporting an incubation effect for behaviors mediated by non-contingent presentation of drug-associated cues. Here we used a model of cue-induced conditioned activity to determine if the conditioned locomotor response to a non-contingent presentation of a drug-associated cue sensitizes across drug withdrawal. In addition, because cue-induced drug-seeking responses are mediated by the rostral basolateral amygdala (BLA), we investigated whether this structure is critical for the expression of cue-induced conditioned activity. A conditioned association between cocaine (15mg/kg) and a compound discrete cue (flashing bicycle light+a metronome) was established over 12 conditioning sessions in male Sprague-Dawley rats. In experiment 1, cue-induced conditioned activity was assessed on 3 occasions: 3, 14 and 28days following the final drug-cue conditioning session. Cocaine-conditioned rats demonstrated reliable cue-induced conditioned activity across all 3 test sessions, however there was no evidence of an incubation effect. To determine whether repeated testing prevented the observation of an incubation effect, rats in experiment 2 were tested either 3days or 28days following conditioning; again no incubation effect was observed. In experiment 3, either saline or the GABAA receptor agonist muscimol was infused prior to testing. Intra-BLA infusions of muscimol prevented the expression of cue-induced conditioned activity. These data support the role of the rBLA in mediating conditioned responses to drug-associated cues. The failure to observe an incubation effect for cue-induced conditioned activity may point to a fundamental difference in the manner by which contingent and non-contingent presentations of drug-associated cues influence behavior.

Several reports indicate either increased or decreased pain sensitivity associated with psychiatric disorders. Chronic pain is highly prevalent in many of these conditions. We reviewed the literature regarding experimental pain sensitivity in patients with major depression, bipolar disorder, posttraumatic stress disorder (PTSD), generalized anxiety disorder, panic disorder, obsessive-compulsive disorder and schizophrenia. Electronic searches were performed to identify studies comparing experimental pain in patients with these conditions and controls. Across 31 depression studies, reduced pain threshold was noted except for ischemic stimuli, where increased pain tolerance and elevated sensitivity to ischemic pain was observed. A more pervasive pattern of low pain sensitivity was found across 20 schizophrenia studies. The majority of PTSD studies (n = 20) showed no significant differences compared with controls. The limited number of bipolar disorder (n = 4) and anxiety (n = 9) studies precluded identification of clear trends. Wide data variability was observed. Awareness of psychiatric patients' pain perception abnormalities is needed for active screening and addressing physical comorbidities, in order to enhance quality of life, life expectancy and mental health.