Heather L. Gray

Serotonin Transporter Polymorphism, Memory, and Hippocampal Volume in the Elderly: Association and Interaction with Cortisol

The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic–pituitary–adrenal (HPA) function on cognition in healthy, older adults, which may reflect developmental, functional or neurodegenerative effects of the serotonin transporter polymorphism. We investigated whether 5-HTT genotype interacts with cumulative life stress and HPA-axis measures of waking and diurnal cortisol slope to impact cognition in 154 non-depressed, older adults. Structural images of hippocampal volume were acquired on a subsample of 56 participants. The 5-HTT s allele was associated with both significantly lower delayed recall and higher waking cortisol levels. Presence of the s allele interacted with higher waking cortisol to negatively impact memory. We also observed a significant interaction of higher waking cortisol and the s allele on lower hippocampal volume. Smaller hippocampi and higher cortisol were associated with lower delayed recall only in s allele carriers. No impact or interactions of cumulative life stress with 5-HTT or cortisol were observed. This is the first investigation to identify an association of the 5-HTT s allele with poorer memory function in older adults. The interactive effects of the s allele and waking cortisol levels on reduced hippocampal volume and lower memory suggest that the negative effect of the serotonin polymorphism on memory is mediated by the HPA axis. Further, given the significant association of the s allele with higher waking cortisol in our investigation, future studies may be needed to evaluate the impact of the serotonin transporter polymorphism on any neuropsychiatric or behavioral outcome which is influenced by HPA axis function in older adults.

Ethnicity, Stress, and Cortisol Function in Hispanic and Non-Hispanic White Women: A Preliminary Study of Family Dementia Caregivers and Noncaregivers

OBJECTIVE This study examined differences in psychologic and physiological responses to caregiving stress in Hispanic and non-Hispanic white women dementia caregivers and noncaregivers. Dependent variables were perceived stress, depression, and salivary cortisol. METHOD Eighty-three women caregivers (20 Hispanic and 24 non-Hispanic white) and noncaregivers (19 Hispanic and 20 non-Hispanic white) completed the Perceived Stress Scale (PSS), Center for Epidemiological Studies-Depression Scale (CES-D), and collected three saliva samples daily for 3 consecutive days. A subsample of 17 Hispanic and 28 non-Hispanic white participants matched on age and education was used for the main analyses. RESULTS Caregivers had higher levels of 8 am, 5 pm, and 9 pm log cortisol as well as higher perceived stress than noncaregivers. Non-Hispanic whites had higher depression scores than noncaregivers, but there was no significant difference for Hispanics. Hispanics, regardless of caregiving status had flatter daytime cortisol slopes than the non-Hispanic whites. Multivariate regression analyses showed that both ethnicity and depressive symptoms independently predicted daytime cortisol slope. CONCLUSIONS Results support the relationship between chronic stress and hypothalamic-pituitary-adrenal axis dysregulation among women dementia caregivers and highlight the need to examine further the role of ethnicity and depressive symptoms in their physiological responses.

The Relationship Between Objectively Measured Sleep Disturbance and Dementia Family Caregiver Distress and Burden

The aim of this study was to determine whether distress and burden were associated with objective measures of sleep disturbance in dementia caregivers. Using wrist actigraphy, sleep was measured in 60 female, Caucasian dementia family caregivers (mean age, 64.8 years). Caregivers completed questionnaires about demographics, health, depression, duration of caregiving and care recipient nighttime behavior. Care recipients completed a mental status exam. We investigated whether these measures were associated with actigraphic sleep parameters. Greater depressive symptoms among caregivers were associated with poorer sleep efficiency. Older caregiver age and poorer self-rated health were associated with longer time in bed. Sleep disturbance, which is common among dementia caregivers, might be an important index of caregiver distress (ie, depression) but might not be associated with burden (based on the care recipients general cognitive impairment or nighttime awakenings.)

Exploring the relationship between physical health, depressive symptoms, and depression diagnoses in Hispanic dementia caregivers

Objectives: The present study examined the relationship between self-reported physical health, depressive symptoms, and the occurrence of depression diagnosis in Hispanic female dementia caregivers. Participants: Participants were 89 Hispanic female dementia caregivers. Design: This study used a cross-sectional design. Baseline depression and physical health data were collected from participants enrolled in the ‘Reducing Stress in Hispanic Anglo Dementia Caregivers’ study sponsored by the National Institute on Aging. Measurements: Physical health was assessed using the Medical Outcome Study Short Form-36 (SF-36), a one-item self-report health rating, body mass index, and the presence or history of self-reported physical illness. Depressive symptoms were assessed using the Center for Epidemiologic Studies–Depression Scale (CES-D). The occurrence of depression diagnosis was assessed using the Clinical Interview for DSM-IV Axis I Disorders (SCID). Analysis: Multiple linear and logistic regression analysis was used to examine the extent to which indices of physical health and depressive symptoms accounted for variance in participants’ depressive symptoms and depressive diagnoses. Results. Self-reported indices of health (e.g., SF-36) accounted for a significant portion of variance in both CES-D scores and SCID diagnoses. Caregivers who reported worsened health tended to report increased symptoms of depression on the CES-D and increased likelihood of an SCID diagnosis of a depressive disorder. Conclusion. Self-reported health indices are helpful in identifying Hispanic dementia caregivers at risk for clinical levels of depression.

Increasing the Ranks of Academic Researchers in Mental Health: A Multisite Approach to Postdoctoral Fellowship Training

This report highlights the use of multisite training for psychiatry and psychology postdoctoral fellows developing careers in academic clinical research in the field of mental health. The objective is to describe a model of training for young investigators to establish independent academic clinical research careers, including (1) program structure and eligibility, (2) program goals and development of a multisite curriculum, (3) use of technology for implementing the program across multiple sites, and (4) advantages and challenges of this multisite approach. In 2000, in collaboration with the Veterans Affairs (VA) Mental Illness Research, Education and Clinical Centers (MIRECCs), the VA Office of Academic Affiliations launched the Special Fellowship Program in Advanced Psychiatry and Psychology. Each of the 10 currently participating VA sites across the United States is affiliated with a MIRECC and an academic medical institution. In the first five years of this fellowship program, 83 fellows (34 psychiatrists and 49 psychologists) have participated. The success of this multisite approach is evidenced by the 58 fellows who have already graduated from the program: 70% have entered academic clinical research positions, and over 25 have obtained independent extramural grant support from the VA or the National Institutes of Health. Multisite training results in a greater transfer of knowledge and capitalizes on the nationwide availability of experts, creating unique networking and learning opportunities for trainees. The VAs multisite fellowship program plays a valuable role in preparing substantial numbers of psychiatry and psychology trainees for a range of academic clinical research and leadership positions in the field of mental health.