Psychotic Misdiagnosis of Racially Minoritized Patients: A Case-Based Ethics, Equity, and Educational Exploration.

ABSTRACT: The overdiagnosis and misdiagnosis of racially minoritized groups as having a primary psychotic disorder is one of psychiatry's longest-standing inequities born of real-time clinician racial bias. Evidence suggests that providers assign a diagnosis of schizophrenia and/or schizoaffective disorder according to race more than any other demographic variable, and this inequity persists even in the absence of differences in clinician symptom ratings. This case report describes the journey of one young Black woman through her racialized misdiagnosis of schizophrenia and the process by which interdisciplinary, health equity-minded providers across the spectrum of medical education and practice joined together to provide a culturally informed, systematic rediagnosis of major depressive disorder and post-traumatic stress disorder. Expert discussion is provided by three Black academic psychiatrists with expertise in social justice and health equity. We provide an evidence-based exploration of mechanisms of clinician racial bias and detail how the psychosis misdiagnosis of racially minoritized groups fails medical ethics and perpetuates iatrogenic harm to patients who truly need help with primary mood, trauma, and substance use disorders.

Multimodal and Site-Specific Plasticity of Amygdala Parvalbumin Interneurons after Fear Learning.

Stimulus processing in fear conditioning is constrained by parvalbumin interneurons (PV-INs) through inhibition of principal excitatory neurons. However, the contributions of PV-IN microcircuits to input gating and long-term plasticity in the fear system remain unknown. Here we interrogate synaptic connections between afferent pathways, PV-INs, and principal excitatory neurons in the basolateral amygdala. We find that subnuclei of this region are populated two functionally distinct PV-IN networks. PV-INs in the lateral (LA), but not the basal (BA), amygdala possess complex dendritic arborizations, receive potent excitatory drive, and mediate feedforward inhibition onto principal neurons. After fear conditioning, PV-INs exhibit nucleus- and target-selective plasticity, resulting in persistent reduction of their excitatory input and inhibitory output in LA but not BA. These data reveal previously overlooked specializations of amygdala PV-INs and indicate specific circuit mechanisms for inhibitory plasticity during the encoding of associative fear memories.

Mice lacking TrkB in parvalbumin-positive cells exhibit sexually dimorphic behavioral phenotypes.

Activity-dependent brain-derived neurotrophic factor (BDNF) signaling through receptor tyrosine kinase B (TrkB) is required for cued fear memory consolidation and extinction. Although BDNF is primarily secreted from glutamatergic neurons, TrkB is expressed by other genetically defined cells whose contributions to the behavioral effects of BDNF remain poorly understood. Parvalbumin (PV)-positive interneurons, which are highly enriched in TrkB, are emerging as key regulators of fear memory expression. We therefore hypothesized that activity-dependent BDNF signaling in PV-interneurons may modulate emotional learning. To test this hypothesis, we utilized the LoxP/Cre system for conditional deletion of TrkB in PV-positive cells to examine the impact of cell-autonomous BDNF signaling on Pavlovian fear conditioning and extinction. However, behavioral abnormalities indicative of vestibular dysfunction precluded the use of homozygous conditional knockouts in tests of higher cognitive functioning. While vestibular dysfunction was apparent in both sexes, female conditional knockouts exhibited an exacerbated phenotype, including extreme motor hyperactivity and circling behavior, compared to their male littermates. Heterozygous conditional knockouts were spared of vestibular dysfunction. While fear memory consolidation was unaffected in heterozygotes of both sexes, males exhibited impaired extinction consolidation compared to their littermate controls. Our findings complement evidence from human and rodent studies suggesting that BDNF signaling promotes consolidation of extinction and point to PV-positive neurons as a discrete population that mediates these effects in a sex-specific manner.