Clozapine and neutrophil response in patients of African descent: A six-month, multinational, prospective, open-label clinical trial.

INTRODUCTION: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific "ACKR1-null" ("Duffy null") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent. METHODS: We completed a multisite, 6-month, prospective, open-label clinical trial of clozapine treatment in people of African descent with schizophrenia spectrum disorders for whom clozapine was clinically indicated, with or without the ACKR1-null genotype. We examined clozapine safety and weekly ANC during clozapine treatment and evaluated ANC variability by ACKR1-null genotype, sex, study site, and clozapine dosing using repeated measures analysis of covariance. Genotype was assayed using TaqMan® technology. RESULTS: We enrolled 274 participants, of whom 227 (82.8 %) completed 6 months of clozapine treatment. There was one case of severe neutropenia (<500 cells/mm3) (0.36 %) over 1467.6 person-months of clozapine exposure. This participant recovered without sequelae after discontinuation of clozapine. Of the 249 participants with known genotypes, 199 (79.9 %) had the ACKR1-null genotype. Neutropenia (<1500 cells/mm3) occurred significantly more often in the ACKR1-null group (33 % [65/199]) than in those with the T allele (6 % (3/50); p < 0.001). Fourteen (5 %) patients discontinued due to adverse events. Rates of infection and fever were low and sialorrhea was the commonest side effect (N = 187, 68 %). CONCLUSION: To our knowledge, this is the largest prospective clozapine trial in people of African descent. Severe neutropenia was rare, despite the high prevalence (80 %) of the ACKR1-null genotype. Our findings suggest that clozapine can be used safely in Black patients including those with BEN.

Overlapping Risky Decision-Making and Olfactory Processing Ability in HIV-Infected Individuals.

OBJECTIVE: Given neuroimaging evidences of overlap in the circuitries for decision-making and olfactory processing, we examined the hypothesis that impairment in psychophysical tasks of olfaction would independently predict poor performances on Iowa Gambling Task (IGT), a laboratory task that closely mimics real-life decision-making, in a US cohort of HIV-infected (HIV+) individuals. METHOD: IGT and psychophysical tasks of olfaction were administered to a Washington DC-based cohort of largely African American HIV+ subjects (N=100), and to a small number of demographically-matched non-HIV healthy controls (N=43) from a different study. Constructs of olfactory ability and decision-making were examined through confirmatory factor analysis (CFA). Structural equation models (SEMs) were used to evaluate the validity of the path relationship between these two constructs. RESULT: The 100 HIV+ participants (56% female; 96% African Americans; median age = 48 years) had median CD4 count of 576 cells/µl and median HIV RNA viral load <48 copies per milliliter. Majority of HIV+ participants performed randomly throughout the course of IGT tasks, and failed to demonstrate a learning curve. Confirmatory factor analysis provided support for a unidimensional factor underlying poor performances on IGT. Nomological validity for correlations between olfactory ability and IGT performance was confirmed through SEM. Finally, factor scores of olfactory ability and IGT performance strongly predicted 6 months history of drug use, while olfaction additionally predicted hallucinogen use. CONCLUSION: This study suggests that combination of simple, office-based tasks of olfaction and decision-making may identify those HIV+ individuals who are more prone to risky decision-making. This finding may have significant clinical, public health value if joint impairments in olfaction and IGT task correlates with more decreased activity in brain regions relevant to decision-making.

A Pilot Study of Reduced Olfactory Bulb Volume as a Marker of PTSD in Childhood Trauma-Exposed Adult HIV-Infected Patients.

Evidence suggests that olfactory bulb (OB), a key structure in odor processing, may also be involved in mechanisms of traumatic stress. In animals, chronic stress reduces OB plasticity, and olfactory bulbectomy results in stress-enhanced startle reflex and autonomic dysregulation. However, OB morphometry has not been adequately studied in the development of stress disorders following childhood trauma in humans. The researchers conducted a pilot study evaluating the relationships between OB volume, childhood trauma, and lifetime posttraumatic stress disorder (PTSD) in a sample of 16 HIV-positive individuals, 13 of whom were exposed to childhood trauma of 9 developed PTSD. Participants were recruited from a larger cohort of inner city-dwelling HIV-positive populations in Washington, DC. Mean OB volumes were significantly reduced when PTSD and non-PTSD groups were compared, p = .019, as well as when trauma-exposed PTSD-positive and trauma-exposed PTSD-negative groups were compared, p = .008. No significant difference was observed when trauma-exposed and nonexposed participants were compared. The association between PTSD and right OB volume remained strong p = 0.002 after adjusting for group differences in sex, age, depression, hippocampal volume, and total intracranial volume. Because this study is limited by small sample size, further elucidation of relationships between OB, trauma, and PTSD should be investigated in larger cross-sectional and prospective studies and in diverse cohorts.

Culturally Sensitive Approaches to Identification and Treatment of Depression among HIV Infected African American Adults: A Qualitative Study of Primary Care Providers' Perspectives.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent among HIV-infected (HIV+) individuals, and is associated with non-adherence to antiretroviral therapy (ART), and accelerated disease progression. MDD is underdiagnosed and undertreated among low-income African Americans, who are disproportionately impacted by the HIV epidemic. To improve detection and treatment of depression among African Americans living with HIV/AIDS, it is important to understand culturally and contextually relevant aspects of MDD and attitudes about mental health treatment. METHODS: A focus group session was conducted with seven providers and staff at a primary care center that serves a largely African-American community heavily impacted by the HIV epidemic in Washington, DC. Data were analyzed using an inductive approach to distill prominent themes, perspectives, and experiences among participating providers. RESULTS: Five themes emerged to characterize the lived experiences of HIV+ African-American patients: (a) Changes in perceptions of HIV over time; (b) HIV is comorbid with mental illness, particularly depression and substance abuse; (c) Stigma is associated with both HIV and depression; (d) Existing mental health services vary and are insufficient and (e) Suggestions for optimal treatment for comorbid HIV and depression. LIMITATION: This study reflects the views of providers from one clinic in this community. CONCLUSION: Substantial economic disadvantage, pervasive childhood adversity, limited education and limited resources jointly put members of this community at risk for acquisition of HIV and for development of depression and addictions. These contextual factors provide an important reminder that any patient-level depression identification or intervention in this community will have to be mindful of such circumstances.

Recovery in a family context: experiences of mothers with serious mental illnesses.

OBJECTIVE: Adults with mental illness are as likely as those without mental illness to be parents. Yet parenting and family life have received considerably less attention than employment, housing, and community integration in psychiatric rehabilitation and mental health services research. This ethnographic pilot study aimed to understand the lived experiences of urban low-income African American mothers diagnosed with serious mental illnesses. METHOD: Ethnographic observations and informal interviews were conducted over 12 months with three mothers diagnosed with serious mental illnesses and their children. Data were analyzed using a case study approach to distill prominent themes, perspectives, and experiences within and across participating families. RESULTS: Five themes emerged to characterize the lived experiences of African American mothers with serious mental illnesses: (a) mental illness and mental health services are not a prominent focus in everyday life; (b) families live in a context of ubiquitous violence, loss, and everyday stress; (c) family life is the main focus for mothers as they strive for a better life; (d) mothers have limited social support; and (e) religion is a source of meaning and a resource for the everyday work of recovery. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings from this exploratory pilot study suggest that rehabilitative efforts tailored for this population should not focus on, or reside in, professional mental health services. Meaningful rehabilitative strategies for families might include supported employment, social support, youth mentoring, faith-based supports, and community-based antiviolence efforts. Peer-based approaches may be a promising way to provide supports within this population.

"Right here is an oasis": how "recovery communities" contribute to recovery for people with serious mental illnesses.

OBJECTIVE: "Creating Communities" is a study that examines the influence of stable housing on recovery within intentional communities of people living with severe mental illnesses in Washington, DC. We label these configurations "recovery communities" (RCs). The authors aim to identify features of the contextual environment of RCs that contribute to recovery from the perspective of RC residents. METHOD: Focus groups were conducted with RC residents at 4-month intervals to inquire into day-to-day life in the communities. Focus group transcripts were reviewed and thematic analysis was conducted to identify prominent and emergent themes relating to the RC and recovery. RESULTS: Thematic analysis yielded three contextual domains through which study participants articulate the RC contributing to their recovery: (a) service environment, (b) physical environment, and (c) social environment. RCs are embedded in a complementary service system; the physical environment provides a refuge from homelessness, drug activity, and violence; and the social environment offers a place to "belong" amid peer-support for mental health and sobriety. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings suggest the need for recovery-oriented services to be holistic and prepared to address multiple, complex needs that include, but go beyond, clinical efforts to reduce psychiatric symptomatology, substance use, and the impact of trauma. People with serious mental illnesses living in RCs express the need for support that ranges from the very concrete to the less tangible, fundamental need for connection and belonging. As a rehabilitative strategy, RCs offer support for the mitigation of psychiatric challenges as well as a refuge from poverty and homelessness.

Sleep disturbances in the aftermath of trauma and posttraumatic stress disorder.

Sleep disturbances, including nightmares and insomnia, are prominent following trauma and with posttraumatic stress disorder (PTSD) and likely contribute to the pathogenesis of the disorder. Findings from laboratory studies of PTSD have been inconsistent in terms of documenting objective impaired sleep maintenance but have been somewhat more consistent in indicating alterations of rapid eye movement (REM) sleep. Studies of the early aftermath of trauma can reduce the complexity associated with chronicity and comorbidity, and may have implications for early diagnosis and prevention. Multiple studies indicate that dream content is affected by recent threatening experiences. The development of PTSD is associated with a more replicative type of nightmare content. Sleep is reported to be generally disrupted following trauma especially among those developing PTSD. The limited number of studies that provide objective recorded indices during the early aftermath of trauma also provide a mixed picture regarding overall sleep maintenance. Recent data suggest that a more specific disruption of REM sleep may be associated with the development of PTSD and that this disruption is associated with an increased signal of sympathetic nervous system activation during REM sleep. Disrupted REM sleep and increased sympathetic/noradrenergic activity may have implications for understanding recent promising interventions for PTSD sleep disturbance that can be applied to early intervention.