Mitigating the health effects of systemic racism: Evaluation of the Race-Based Stress and Trauma Empowerment intervention.

BACKGROUND: Disparities in physical and mental health among Black, Indigenous, and People of Color (BIPOC) are well-documented and mirrored in the Veteran population. Chronic stress due to racism and discrimination is one possible mechanism driving these negative health outcomes. The Race-Based Stress and Trauma Empowerment (RBSTE) group is a novel, manualized, health promotion intervention designed to address the direct and indirect impacts of racism among Veterans of Color. This paper describes the protocol of the first pilot randomized controlled trial (RCT) of RBSTE. This study will examine the feasibility, acceptability, and appropriateness of RBSTE compared to an active control (an adaptation of Present-Centered Therapy; PCT) in a Veterans Affairs (VA) healthcare setting. A secondary aim is to identify and optimize strategies for holistic evaluation. METHODS: Veterans of Color (N = 48) endorsing perceived discrimination and stress will be randomized to RBSTE or PCT; both groups will be delivered in 8 weekly, 90-min virtual group sessions. Outcomes will include measures of psychological distress, discrimination and ethnoracial identity, holistic wellness, and allostatic load. Measures will be administered at baseline and post-intervention. CONCLUSION: This study will inform future interventions targeting identity-based stressors and represents an important step in advancing equity for BIPOC in medicine and research. CLINICAL TRIAL REGISTRATION NUMBER: NCT05422638.

HIV Transgenic Rats Demonstrate Impaired Sensorimotor Gating But Are Insensitive to Cannabinoid (Δ9-Tetrahydrocannabinol)-Induced Deficits.

BACKGROUND: HIV-associated neurocognitive disorder (HAND) is commonly observed in persons living with HIV (PWH) and is characterized by cognitive deficits implicating disruptions of fronto-striatal neurocircuitry. Such circuitry is also susceptible to alteration by cannabis and other drugs of abuse. PWH use cannabis at much higher rates than the general population, thus prioritizing the characterization of any interactions between HIV and cannabinoids on cognitively relevant systems. Prepulse inhibition (PPI) of the startle response, the process by which the motor response to a startling stimulus is attenuated by perception of a preceding non-startling stimulus, is an operational assay of fronto-striatal circuit integrity that is translatable across species. PPI is reduced in PWH. The HIV transgenic (HIVtg) rat model of HIV infection mimics numerous aspects of HAND, although to date the PPI deficit observed in PWH has yet to be fully recreated in animals. METHODS: PPI was measured in male and female HIVtg rats and wild-type controls following acute, nonconcurrent treatment with the primary constituents of cannabis: Δ 9-tetrahydrocannabinol (THC; 1 and 3 mg/kg, s.c.) and cannabidiol (1, 10, and 30 mg/kg, i.p.). RESULTS: HIVtg rats exhibited a significant PPI deficit relative to wild-type controls. THC reduced PPI in controls but not HIVtg rats. Cannabidiol exerted only minor, genotype-independent effects on PPI. CONCLUSIONS: HIVtg rats exhibit a relative insensitivity to the deleterious effects of THC on the fronto-striatal function reflected by PPI, which may partially explain the higher rates of cannabis use among PWH.

Prepulse inhibition in HIV-1 gp120 transgenic mice after withdrawal from chronic methamphetamine.

HIV infection is frequently comorbid with methamphetamine (METH) dependence. Both factors are associated with impairment in inhibitory function that continues even after abstinence from the drug. Deficits in prepulse inhibition (PPI), a measure of sensorimotor gating, are induced by acute stimulant administration, but the combined effect of HIV and chronic METH exposure on PPI is not well characterized. We quantified baseline acoustic startle and PPI in mice expressing the HIV-1 gp120 envelope protein (gp120tg) and in wild-type (WT) littermates; thereafter, we administered a chronic regimen of METH or vehicle and tested startle and PPI after 7 days of drug withdrawal. We hypothesized that METH-treated gp120tg mice would exhibit PPI deficits compared with vehicle-treated WT or gp120tg animals. Before METH administration, drug-naive female gp120tg mice exhibited decreased PPI compared with female WT mice, whereas male gp120tg mice exhibited increased startle compared with other groups. After drug withdrawal, no consistent genotype effect was observed, but METH-treated mice exhibited increased PPI compared with vehicle, in contrast to previous reports of acute METH-induced PPI deficits. In summary, PPI impairment in HIV could depend on factors such as sex, whereas changes in PPI following METH withdrawal may depend on the quantity and duration of drug exposure.

Prepulse inhibition in HIV-associated neurocognitive disorders.

Sensorimotor inhibition, or the ability to filter out excessive or irrelevant information, theoretically supports a variety of higher-level cognitive functions. Impaired inhibition may be associated with increased impulsive and risky behavior in everyday life. Individuals infected with HIV frequently show impairment on tests of neurocognitive function, but sensorimotor inhibition in this population has not been studied and may be a contributor to the profile of HIV-associated neurocognitive disorders (HAND). Thirty-seven HIV-infected individuals (15 with HAND) and 48 non-infected comparison subjects were assessed for prepulse inhibition (PPI), an eyeblink startle paradigm measuring sensorimotor gating. Although HIV status alone was not associated with PPI deficits, HIV-positive participants meeting criteria for HAND showed impaired PPI compared to cognitively intact HIV-positive subjects. In HIV-positive subjects, PPI was correlated with working memory but was not associated with antiretroviral therapy or illness factors. In conclusion, sensorimotor disinhibition in HIV accompanies deficits in higher-order cognitive functions, although the causal direction of this relationship requires investigation. Subsequent research on the role of sensorimotor gating on decision-making and risk behaviors in HIV may be indicated.

Prepulse inhibition of startle in adults with ADHD.

Prepulse inhibition of startle (PPI) is a measure of sensorimotor gating, a pre-conscious regulator of attention. PPI is impaired in adults with schizophrenia and several other neuropsychiatric disorders associated with attentional abnormalities. The core feature of ADHD involves deficits in attention and, like schizophrenia, ADHD is associated with dysregulation of cortical-striatal circuits and dopamine transmission. Therefore, PPI may be disrupted in ADHD. While ADHD persists into adulthood in approximately half the children with ADHD, there has not been any published report of PPI in ADHD adults. In this study, PPI was measured in a sample of ADHD adults and compared to a sample of healthy comparison (HC) subjects. Twenty unmedicated adults with ADHD (11 inattentive subtype, 9 combined subtype) and 17 HC subjects were administered an eyeblink startle PPI paradigm. The PPI of ADHD adults was not significantly different from that of HC subjects in any of the PPI conditions. There was no significant effect of ADHD subtype nor of gender. The lack of PPI deficits in ADHD adults has important implications and suggests that, despite the presence of PPI dysregulation in a large number of disparate neuropsychiatric disorders, it is not a general feature of all neuropsychiatric disorders with attention abnormalities. Furthermore, the attentional deficiency in ADHD may have a neurobiological substrate somewhat distinct from schizophrenia and other neuropsychiatric disorders that are associated with PPI deficits. This distinction may be related to a relative sparing of pre-conscious attentional functions in ADHD compared to other disorders with PPI impairment.

A randomized controlled trial of cognitive-behavior therapy for tinnitus.

This study is a randomized, waitlist-controlled trial testing the effect of a brief, "manualized" cognitive-behavioral group therapy on distress associated with tinnitus, quality of well-being, psychological distress including depression, and internal focus. Cognitive-behavioral therapy (CBT) included training in activity planning, relaxation training and, primarily, cognitive restructuring. Sixty-five participants were recruited, and 41 completed treatment. Participants were randomly assigned to receive 8 weeks of manualized group CBT either immediately or after an 8-week waiting period. Participants completed outcome measures at the time of their random assignment and at 8, 16, and 52 weeks later. Repeated-measure analysis of covariance revealed significant group-by-time interactions on measures of tinnitus distress and depression, indicating that CBT led to greater improvement in those symptoms. The current results suggest that CBT, applied in a group format using a manual, can reduce the negative emotional distress, including depression, associated with tinnitus.

Sensorimotor gating deficits in adults with autism.

BACKGROUND: Prepulse inhibition (PPI) is an operational measure of sensorimotor gating and is impaired in a family of neuropsychiatric disorders characterized by abnormalities of inhibitory function. Adults with autistic disorder (AD) exhibit clinical features of inhibitory deficits, such as restrictive and repetitive behaviors, that may be explained by deficits in sensorimotor gating. METHODS: Acoustic startle reactivity, habituation, and PPI (30-, 60-, 120-msec interstimulus intervals) were assessed in 14 adult men diagnosed with AD and 16 typically developing normal comparison (NC) participants. All participants were administered measures of intelligence and frontal-executive functioning. RESULTS: Adults with AD exhibited significantly less PPI in the 60-msec condition than NC participants, which was correlated with increased ratings of restricted and repetitive behaviors. The groups did not differ on measures of startle amplitude or overall habituation. There was, however, a significant group-by-block habituation effect. Furthermore, PPI was not related to intelligence but was moderately associated with performance on a measure of frontal-executive functioning. CONCLUSIONS: Adults with AD have sensorimotor gating deficits similar to other neurodevelopmental disorders, implicating a failure of normal inhibitory regulation of sensory, motor, and attentional mechanisms. Thus, PPI deficits may be indirectly linked to one of the hallmark features of AD.

The relationship between sensorimotor gating and clinical improvement in acutely ill schizophrenia patients.

It has been suggested that sensorimotor gating deficits as indexed by prepulse inhibition (PPI) of the acoustic startle reflex represent an endophenotypic marker of psychotic conditions such as schizophrenia (SCZ). This hypothesis has been questioned as several studies have found that PPI levels change with improvement in symptoms and are responsive to medications. We tested PPI in a sample of acutely decompensated schizophrenia patients who were re-tested after 2 weeks of hospital treatment. PPI was assessed at three interstimulus intervals (30, 60, and 120 ms) in 23 SCID-diagnosed SCZ patients shortly after admission to an inpatient psychiatric hospital. Eight of these patients were initially tested in a medication-free state, and all were re-tested approximately 2 weeks later after initiation or increase/change of antipsychotic medications. Symptom ratings were collected at both sessions. 20 nonpatient comparison subjects (NCS) were also tested at a 2-week interval. While SCZ patients showed lower PPI at the first session than NCS, after 2 weeks of treatment their PPI increased to levels not different than those of NCS. In contrast, the PPI of NCS remained consistent over a 2-week period. For the SCZ patients, increase in PPI was correlated with a decrease in symptom scores. Our results suggest that PPI can be improved by short-term treatment, and that improvement in sensorimotor gating is associated with treatment-related improvement of symptoms of schizophrenia.

Information processing deficits in acutely psychotic schizophrenia patients medicated and unmedicated at the time of admission.

OBJECTIVE: In patients with schizophrenia, information processing deficits, such as those reported in studies that measured prepulse inhibition of the human startle response and habituation of startle magnitude, may be improved with atypical antipsychotic treatment. However, it remains unclear whether antipsychotic medication is directly responsible for the improvement or whether differences in prepulse inhibition reflect other factors, such as acuity status. The present study investigated the effects of antipsychotics on prepulse inhibition and startle habituation in acutely hospitalized patients with schizophrenia. METHOD: Forty-one acutely psychotic schizophrenia patients (21 who were unmedicated at the time of admission and 20 who had been receiving antipsychotic treatment) were tested within 72 hours of hospital admission. Thirteen healthy subjects were also studied for comparative purposes. Primary dependent measures were startle responsivity, reactivity, prepulse inhibition, and startle habituation. RESULTS: Schizophrenia patients, whether medicated or unmedicated at admission, showed prepulse inhibition deficits compared with healthy subjects and did not statistically differ from each other in startle magnitude, prepulse inhibition, or habituation. There was a higher number of startle "nonresponders" among those who had been receiving medication versus those unmedicated at the time of admission. CONCLUSIONS: The present findings suggest that antipsychotic effects on prepulse inhibition may not be evident at a time when schizophrenia patients are acutely symptomatic. These results suggest that the neurobiological substrate underlying prepulse inhibition deficits may be dysregulated during acute psychotic states while the patients are in early phases of medication treatment.