IMPH Research in Mental Health

Cardiac Function As a Mechanism for Maladaptive Brain Aging 
Cultural Effects on Stress, Coping, and Symptom Expression 
Imaging Hippocampal Function in Psychosis 
Increasing Mental Health Research Infrastructure in Southeast Asia 
The MIND-USA Study 
Parent-Child Communication About Cancer 
The Pat Summitt Foundation of the East Tennessee Foundation 
Preventing Cognitive Decline in Older Adults with Dementia in Assisted-Living Facilities 
Stress, Parenting and Cognitive Function in Children with Sickle Cell Disease 
Telephone Counseling - Caregivers for Children with Cancer

Cardiac Function As a Mechanism for Maladaptive Brain Aging

As the population continues to age, the incidence of dementia is dramatically increasing, resulting in an urgent need to identify risk factors for abnormal brain aging and dementia. Alterations in cardiac function influence systemic blood flow, which impacts cerebral blood flow homeostasis as demonstrated by animal models. Such changes in cerebral blood flow homeostasis may pose a risk for accelerating age-related brain injury. Our preliminary research suggests that cardiac function is related to markers of maladaptive brain aging. It is not yet clear if cardiac function accelerates neuroimaging or cognitive markers of cerebrovascular or Alzheimer's disease among aging individuals with mild cognitive impairment (MCI). Individuals with MCI are at increased risk for cognitive progression and susceptible to more rapid abnormal brain aging when concomitant vascular disease is present. Our proposed study will examine relations between cardiac function and maladaptive brain aging and provide important information for developing novel strategies to delay the progression from MCI to dementia. Using a prospective observational matched design, we will cross-sectionally and longitudinally relate cardiac function to neuroimaging and cognitive markers of early Alzheimer's disease and cerebrovascular changes among aging adults with MCI and age-, sex-, and race-matched cognitively normal adults. Clinical or subclinical cardiac dysfunction may be due to complex systemic mechanisms that are preventable or treatable, such as enhanced inflammatory markers and insulin resistance, or genetic factors, such as apolipoprotein E. Therefore, we will consider systemic and genetic factors as potential mediating mechanisms in relations between cardiac function and brain aging. The proposed study leverages an existing Alzheimer's Association funded study directed by the principal investigator, the participant registry of our NIA-funded Boston University Alzheimer's Disease Center, a recent American Recovery & Reinvestment Act supplement grant focused on African American recruitment and retention, and the unique resources afforded by our local Clinical and Translational Science Institute housing the General Clinical Research Unit. Read more.

Funding Source: NIH/NIA
PI: Angela L. Jefferson

Cultural Effects on Stress, Coping, and Symptom Expression

Despite the fact that psychology and related fields generally have conceptualized themselves as science of universal human behavior, for the most part they have developed as Euro-American science of Euro-American behavior. Failure to consider more fully potential effects of cultural differences on human behavior and emotion has had a number of consequences, the foremost of which probably is that the field has reached conclusions about constructs being related as main effects when in fact they may be related via more complex interactive relations involving cultural processes. The overall purpose of the proposed project is to increase our understanding of how culture and cultural variation are related to human behavioral and emotional functioning, with a particular focus on what might be called the "stress - coping - symptom manifestation" system, with the ultimate goal of generating data that are useful for modifying or developing culturally informed psychosocial interventions. In the proposed project, cross-sectional questionnaire data will be obtained from 1000 Vietnamese and 1000 Vietnamese-American adolescents. Longitudinal interview data will be obtained from subsets of 500 of each of these groups, at three time points spaced three months apart. Data will focus on (a) stressful life events, (b) coping styles and strategies, (c) mental health symptoms, and (d) distal cultural as well as more proximal variables (e.g., collectivism vs. individualism; stigma associated with symptoms, respectively). Analyses will (a) determine the extent to which Vietnamese and Vietnamese-American adolescents differ cross-sectionally in regards to the life events they find stressful, the types of strategies that the adolescents use to cope with these stressful events, and the symptom manifestations (such as affective problems; somatization, conduct problems, etc.) that may occur when these coping attempts are not successful; (b) determine the extent to which cross-sectional group differences are related to cultural variables; (c) model longitudinal relations between life events, coping strategies, and symptom manifestations and determine the extent to which these relations are influenced by the cultural variables; (b) compare models the Vietnamese and Vietnamese-American adolescents to determine whether these relations differ across cultural groups and if they do, whether these differences are mediated by the cultural variables. Finally, results will be reviewed to identify potential factors relevant for developing culturally-informed interventions for Vietnamese- American, and ultimately Asian-American, adolescents. Read more.

Funding Source: NIH/NIMH
PI: Bahr Weiss

Imaging Hippocampal Function in Psychosis

We propose to study the evolution of hippocampal dysfunction in the early stage of psychosis (ESOP). Smaller hippocampal volume is one of the most robust structural brain abnormalities in patients with schizophrenia. In addition, there is now compelling evidence for an abnormality of hippocampal activity in schizophrenia. However, it is unclear when in the disease process hippocampal structure and function become abnormal and which regions of the hippocampus are affected. Clarifying these questions will improve our understanding of the disease mechanism and our ability to intervene in the disease process. We will recruit patients at an early stage of their emerging psychotic disorder to study hippocampal structure with high-field 7T magnetic resonance imaging and hippocampal activity with 3T magnetic resonance mapping of cerebral blood volume (CBV) and BOLD signal. We will measure performance on tests of relational memory, a form of hippocampus-dependent memory that is impaired in schizophrenia. We will follow patients for 2 years and measure the change of hippocampal volume in psychotic disorders. We predict that hippocampal activity is abnormal already at the onset of the illness and does not change significantly over the course of the illness. As a consequence of abnormal activity, memory function is already moderately impaired at illness onset. Over the course of the first 2 years of illness, the abnormally increased activity of the hippocampus leads to structural changes in the hippocampus. This structural change is associated with a further progression of memory deficits. To test our hypotheses, we will develop two types of high-resolution hippocampal maps. First, anatomical maps will distinguish the volume of four sectors and two regions throughout the entire anterior-posterior extent of the hippocampus. Using this high-resolution parcellation of the hippocampus, we will test the hypothesis that the anterior sector CA1 is primarily affected in psychotic disorder patients. Second, functional maps will assess CBV and BOLD signal in the four sectors and two regions of the hippocampus. With these maps we will test the hypothesis of decreased hippocampal inhibition in psychotic disorders. We will correlate the measures of hippocampal structure and activity with the performance on tests of relational memory, a form of hippocampus- dependent memory that is impaired in schizophrenia. The proposed longitudinal study design will allow us to study the timing of hippocampal dysfunction in psychotic disorders. The goal of this research project is the identification of hippocampal markers for the early diagnosis of psychotic disorders. Read more.

Funding Source: NIH/NIMH
PI: Stephan Heckers

Increasing Mental Health Research Infrastructure in Southeast Asia

This NCD-LIFESPAN project seeks to increase capacity in Southeast Asia, primarily in Vietnam and secondarily in Cambodia, in regards to (a) developing culturally-appropriate, research-based treatments for mental health problems; (b) conducting intervention trials of these treatments; (c) disseminating research results to favorably impact service provision. The NCD-LIFESPAN project builds on two successful ICOHRTA grants, the focus of which has been development of a child- and adolescent-focused, research-oriented PhD Clinical Sciences program at Vietnam National University (VNU). In 2009 our VNU Master's in Clinical Sciences enrolled its first cohort of 15 students, and a second cohort of 15 students in 2010. In addition to providing the curricular foundation for the PhD program, the master's program will be used as a dissemination platform and as a structure for dissemination research for the evidence-based treatment programs developed through the VNU Clinical Psychology program. The NCD-LIFESPAN Specific Aims are to (1) enhance the VNU Clinical Sciences program through: (1a) support for further development of VNU faculty in regards to research, clinical, instructional / mentoring, and administrative expertise; and (1b) development of a Subspecialty in Trauma and PTSD that was identified as of particular need in Vietnam, and Cambodia; and (2) broaden the geographical impact of our program within Vietnam, and Southeast Asia by: (2a) increasing the geographical diversity of our graduate students based within Vietnam, by providing scholarships to students who live a significant distance from the university; and (2b) collaborating with the Psychology Department at the Royal University of Phnom Penh (RUPP), Cambodia, to enhance their graduate program in Clinical Psychology and Trauma Treatment, by providing (2b1) training for RUPP faculty at VNU, (2b2) technical support around curriculum development, and (2b3) funding for small collaborative research projects. Vietnam National University would be LMIC site #1, and the Royal University of Phnom Penh would be LMIC site #2. Read more.

Funding Source: FIC 
PI: Bahr Weiss

The MIND-USA Study

The long-term objective of the proposed MIND-USA (Modifying the Impact of ICU-Induced Neurological Dysfunction-USA) Study is to define the role of antipsychotics in the management of delirium in vulnerable critically ill patients. We and others have shown that delirium is an independent predictor of more death, longer stay, higher cost, and long-term cognitive impairment often commensurate with moderate dementia. The rapidly expanding aging ICU population is especially vulnerable to develop delirium, with 7 of 10 medical and surgical ICU patients developing this organ dysfunction. Antipsychotics are the first-line pharmacological agents recommended to treat delirium, and over the past 30 years they gained widespread use in hospitalized patients globally prior to adequate testing of efficacy and safety for this indication. Haloperidol, the most commonly chosen antipsychotic, is used by over 80% of ICU doctors for delirium, while atypical antipsychotics are prescribed by 40%. Antipsychotics safety concerns include lethal cardiac arrhythmias, extrapyramidal symptoms, and the highly publicized increased mortality associated with their use in non-ICU geriatric populations. The overarching hypothesis is that administration of typical and atypical antipsychotics-haloperidol and ziprasidone, in this case-to critically ill patients with delirium will improve short- and long-term clinical outcomes. Aim 1 will determine whether haloperidol or ziprasidone will increase days alive without acute brain dysfunction (referred to as delirium/coma-free days or DCFDs) over a 14-day period compared with placebo and compared to one another. Aim 2 will determine whether haloperidol or ziprasidone will improve 30-day, 90-day, and 1-year survival compared with placebo and compared to one another. Aim 3 will determine whether haloperidol or ziprasidone will reduce ICU length of stay compared with placebo and compared to one another. Aim 4 will determine whether haloperidol or ziprasidone will reduce the incidence, severity, and/or duration of long-term neuropsychological dysfunction and improve quality of life at 90-day and 1-year follow-up compared with placebo and compared to one another. To address these Aims, we will conduct this multi-center, double blind, randomized, placebo-controlled investigation in 876 critically ill, delirious medical/surgical ICU patients who are (a) on mechanical ventilation or non-invasive positive pressure ventilation or (b) in shock on vasopressors. In each group (haloperidol, ziprasidone, and placebo), 292 patients will be enrolled and treated until delirium has resolved for 48 hours or to 14 days (whichever occurs first) and followed for 1 year. We will monitor many safety parameters such as cardiac dysrhythmias and extrapyramidal symptoms. This study will have adequate power to detect the effect of antipsychotics in 4 important subgroups including age >65 years, severity of illness (APACHE II > 25), severe sepsis at enrollment, and medical vs. surgical ICU patients, and a hypothesis generating analysis of patients with pre- existing cognitive impairment. Read more.

Funding Source: NIH/NIA 
PI: E. Wesley Ely

Parent-Child Communication About Cancer

This is a competing renewal application to conduct theoretically-driven research to determine the course and predictors of mental health, social, and physical health outcomes in a cohort of children with cancer and their parents. We have been following a sample of 258 children (ages 5 to 17-years at entry into the study) from near the time of their cancer diagnosis over the first year after their diagnosis with a very high retention rate. By the end of this grant period we will have collected 3 waves of data including observations, interviews and questionnaires and we now propose to collect 2 additional waves of data, including direct observations of parent-child interactions, up to 5 years after diagnosis. Child and their parents completed measures about sources of cancer-related stress, how they cope with cancer, standardized indicators of distress and mental health problems, and they participated in video recorded observations. We propose to extend this work to examine the transition off treatment and into survivorship. Our aims are: 1) To examine continuity and change in parent-child communication about cancer; 2) To identify early predictors of later mental and physical health outcomes for children with cancer and their parents; and 3) To examine reciprocal relationships between parent and child coping, mental and physical health. To meet these aims, we propose to collect 2 additional waves of interview, observational and multi-agent questionnaire data spaced 12 months apart. The project is designed to identify risk and protective factors and processes that can be used to establish a theory-driven model of coping and adaptation to childhood cancer and to identify targets for the future early preventive psychosocial interventions with children with cancer and their parents. Read more.

Funding Source: NIH/NCI 
PI: Bruce Compas

The Pat Summitt Foundation of the East Tennessee Foundation

This foundation grant was used to develop a guide for consumers in selecting a dementia care facility titled, "How to Evaluate the Quality of Residential Care for Persons with Dementia" (see attached web-friendly pdf version).  An overview of dementia care in both long-term care and residential care is provided as well as consumer tips and guidelines for what questions to ask and what to look for when visiting a facility.  The goal of this guide is to empower the consumer with the same knowledge and expertise that the authors of this guide have obtained based on years of both clinical and research experience in evaluating dementia care quality. Read more.

PI: Sandra Simmons, PhD, John Schnelle, PhD, and Anna Rahman, PhD

Preventing Cognitive Decline in Older Adults with Dementia in Assisted-Living Facilities

The purpose of this study is to evaluate two structured cognitive stimulation – activity programs in a local assisted-living facility on residents’ cognitive and psychosocial status.  Research staff will administer a battery of neuropsychological assessments in conjunction with other behavioral measures to determine the impact of each program on resident functioning and quality of life. Read more.

Funding Source: West End Home Foundation
PI: Sandra F. Simmons, PhD

Stress, Parenting and Cognitive Function in Children with Sickle Cell Disease

Children with sickle cell disease (SCD) experience significant problems in neurocognitive development, including deficits in overall intellectual functioning and in specific areas such as attention and executive function. A number of disease-related factors have been shown to be predictive of the extent of neurocognitive problems including sickle cell genotype, history of overt stroke/cerebral infarct, history of silent infarct/micro infarcts, chronic hypoxia due to anemia, acute hypoxia, nutritional deficits, increased peak cerebral blood flow velocity, and sleep disordered breathing/sleep apnea. However, social-environmental risk factors that may contribute additional risk for neurocognitive problems in children with SCD have received relatively little attention. The lone exceptions are two studies that have shown that low family socioeconomic status (SES) is related to poorer neurocognitive function in children with SCD. A growing body of research on children growing up in poverty has shown that environmental stress is a significant risk factor for cognitive impairment in children growing up poor and that disrupted/non-responsive parenting is a central mediator of the effects of poverty and stress on children's cognitive function and development. However, no studies to date have examined the potential role of parenting as a contributing factor in neurocognitive impairment in children with SCD. The goal of the proposed research is to test the feasibility, acceptability and initial proof of concept of social-environmental predictrs of cognitive function in children with SCD. We will (a) recruit a wide age range of children with SCD and their parents; (b) recruit a sibling control sample; (c) recruit a sample of healthy contro children from families without chronic illness; (d) administer cognitive tests to children with SCD their parents, and their siblings, as well as healthy control children and their parents; and (e) conduct direct observations of interactions of parents with children with SCD and interactions of parents with sibling controls and healthy controls and their parents. Read more.

Funding Source: NIH/NICHD
PI: Bruce Compas

Telephone Counseling - Caregivers for Children with Cancer

The rate of survival for childhood cancer continues to improve and now approaches 80%. Coincident with this survival are adverse long-term health-related outcomes for survivors and their family members. Throughout the cancer care continuum, from time of diagnosis through long-term survivorship, children and their families are confronted with multiple and pervasive stressors, including uncertainty about the chance of survival, treatment- related adverse health effects, disruption in daily activities and disruption of the parental role function. This may result in clinically significant global distress, depression, posttraumatic stress (PTS) and reduced self-efficacy. Therefore, providing psychosocial services to parents of children with cancer is necessary. Yet, feasible and theory-based psychosocial intervention studies are extremely limited, particularly at the completion of the child's cancer treatment, a time known to be anxiety-provoking and often characterized by feelings of abandonment and uncertainty about the future. Barriers to participation in face-to-face interventions at the treating institution include the considerable distance that many families live from the institution, difficulty leaving children, households or jobs and potential for sensory and interpersonal experiences at the treating institution to trigger symptoms of anxiety and PTS. In response to these concerns, we are proposing to extend the reach of essential psychosocial counseling services to primary caregivers of children with cancer by designing and implementing a small-scale feasibility pilot of an innovative and highly translatable telephone-based psychosocial intervention. This intervention will be implemented during the transition from primary active oncology treatment to follow-up care, reflecting a neglected area of research. Specifically, we propose to design and then test the feasibility of a two-group randomized trial of a psychosocial telephone counseling program for primary caregivers of children who have completed cancer therapy in the previous year, consisting of an attention control condition (educational materials and outcalls with no counseling) and an experimental condition (telephone counseling plus the educational materials). We will evaluate the proposed telephone counseling intervention for feasibility, satisfaction and perceived helpfulness. The primary endpoints will include psychosocial distress and benefit finding. Furthermore, we will assess and explore the plausible intervention mechanisms and pathways that may explain and elucidate intervention efficacy (mediator variables). The main theory-based mediator variables that will be tested include secondary appraisal (coping self-efficacy) and coping effort. Lastly, based on the preliminary data obtained from this study, we will seek funding to design and implement a larger randomized clinical efficacy trial, whose ultimate goal will be to develop a highly effective and exportable telephone counseling intervention for primary caregivers of children with cancer that could be become an integral component of care given to pediatric oncology patients. Read more.

Funding Source: NIH/NCI 
PI: Debra Friedman