Dorsal Raphe Serotonin Neurons Mediate CO2-Induced Arousal from Sleep.

Arousal from sleep in response to CO2 is a critical protective phenomenon. Dysregulation of CO2-induced arousal contributes to morbidity and mortality from prevalent diseases, such as obstructive sleep apnea and sudden infant death syndrome. Despite the critical nature of this protective reflex, the precise mechanism for CO2-induced arousal is unknown. Because CO2 is a major regulator of breathing, prevailing theories suggest that activation of respiratory chemo- and mechano-sensors is required for CO2-induced arousal. However, populations of neurons that are not involved in the regulation of breathing are also chemosensitive. Among these are serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) that comprise a component of the ascending arousal system. We hypothesized that direct stimulation of these neurons with CO2 could cause arousal from sleep independently of enhancing breathing. Dialysis of CO2-rich acidified solution into DRN, but not medullary raphe responsible for modulating breathing, caused arousal from sleep. Arousal was lost in mice with a genetic absence of 5-HT neurons, and with acute pharmacological or optogenetic inactivation of DRN 5-HT neurons. Here we demonstrate that CO2 can cause arousal from sleep directly, without requiring enhancement of breathing, and that chemosensitive 5-HT neurons in the DRN critically mediate this arousal. Better understanding mechanisms underlying this protective reflex may lead to interventions to reduce disease-associated morbidity and mortality.SIGNIFICANCE STATEMENT Although CO2-induced arousal is critical to a number of diseases, the specific mechanism is not well understood. We previously demonstrated that serotonin (5-HT) neurons are important for CO2-induced arousal, as mice without 5-HT neurons do not arouse to CO2 Many have interpreted this to mean that medullary 5-HT neurons that regulate breathing are important in this arousal mechanism. Here we found that direct application of CO2-rich aCSF to the dorsal raphe nucleus, but not the medullary raphe, causes arousal from sleep, and that this arousal was lost with genetic ablation or acute inhibition of 5-HT neurons. We propose that 5-HT neurons in the dorsal raphe nucleus can be activated directly by CO2 to cause arousal independently of respiratory activation.

"Dysregulated not deficit": A qualitative study on symptomatology of ADHD in young adults.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a common condition that often persists into adulthood, although data suggest that the current diagnostic criteria may not represent how the condition presents in adults. We aimed to use qualitative methods to better understand ADHD symptomatology in young adults, especially regarding attentional and emotional dysregulation. METHODS: Nine focus groups involving young adults (aged 18-35 years; N = 43; 84% female; 86% US and Canada) with diagnoses of ADHD were conducted. Participants were asked about their perceptions of the current diagnostic criteria and how their symptoms have presented and changed over time. Data were analyzed using an interpretive phenomenological analysis framework. RESULTS: Most participants reported that the diagnostic criteria did not accurately capture their experiences with ADHD. They reported struggling with attention dysregulation, including hyperfocusing, and emotional dysregulation, including rejection-sensitive dysphoria. Many participants believed that their changing environments and behavioral adaptations influenced how their symptoms presented into adulthood. CONCLUSION: Current diagnostic criteria for ADHD may not capture the range of symptoms present in young adults. More research is needed to characterize attentional and emotional dysregulation in this population.

The lived experiences of adults with attention-deficit/hyperactivity disorder: A rapid review of qualitative evidence.

Attention-deficit/hyperactivity disorder (ADHD) is a common condition that frequently persists into adulthood, although research and diagnostic criteria are focused on how the condition presents in children. We aimed to review qualitative research on lived experiences of adults with ADHD to characterize potential ADHD symptomatology in adulthood and provide perspectives on how needs might be better met. We searched three databases for qualitative studies on ADHD. Studies (n = 35) in English that included data on the lived experiences of adults with ADHD were included. These studies covered experiences of receiving a diagnosis as an adult, symptomatology of adult ADHD, skills used to adapt to these symptoms, relationships between ADHD and substance use, patients' self-perceptions, and participants' experiences interacting with society. Many of the ADHD symptoms reported in these studies had overlap with other psychiatric conditions and may contribute to misdiagnosis and delays in diagnosis. Understanding symptomatology of ADHD in adults may inform future diagnostic criteria and guide interventions to improve quality of life.

"A good mother": Impact of motherhood identity on women's substance use and engagement in treatment across the lifespan.

BACKGROUND: Women are underrepresented in substance use disorder (SUD) treatment. Interpersonal and structural factors affect women's access to SUD treatment, but limited research evaluates how motherhood is a potential barrier and facilitator to engagement in SUD treatment. We focus on women from young to middle adulthood, and capture women's identities as mothers, caretakers, and grandmothers, outside of pregnancy and the postpartum period. METHODS: Study staff conducted twenty qualitative interviews with women in SUD treatment to assess experiences with SUD treatment, in which motherhood emerged as a key theme. Twelve women then participated in four focus groups centered on motherhood. The study audio-recorded and transcribed interviews, and two independent authors analyzed interviews, followed by group consensus. RESULTS: Most women identified their children and responsibilities as mothers and caretakers as important motivators to accessing SUD treatment. Motherhood was also a barrier to treatment, in that women feared losing child custody by disclosing substance use and few residential programs accommodate women with children. Multiple women expressed guilt about their substance use, sensing that it contributed to perceived abandonment or separation from their children. Reunification was important to SUD recovery. CONCLUSION: Women with SUD who are mothers experience specific barriers to treatment engagement and recovery. Women need SUD treatment programs that address these interpersonal and structural factors across the lifespan.