Faculty Bibliography

PURPOSE: To examine perceived need for care for mental health problems as a possible contributor to ethnic disparities in receiving care among low-income depressed women. METHODS: The role of ethnicity, somatization, and stigma as they relate to perceived need for care is examined. Participants were 1577 low-income women who met criteria for depression. RESULTS: Compared with U.S.-born depressed white women, most depressed ethnic minority women were less likely to perceive a need for mental health care (black immigrants: OR 0.30, p < 0.001; U.S.-born blacks: OR 0.43, p < 0.001; immigrant Latinas: OR 0.52, p < 0.01). Stigma-related concerns decreased the likelihood of perceiving a need for mental health care (OR 0.80, p < 0.05). Having multiple somatic symptoms (OR 1.57, p < 0.001) increased the likelihood of endorsing perceived need. CONCLUSIONS: Findings suggest that there are ethnic differences in perceived need for mental healthcare that may partially account for the low rates of care for depression among low-income and minority women. The relations among stigma, somatization, and perceived need were strikingly similar across ethnic groups.

Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) alleviates both anxiety symptoms and associated physiologic disturbances in anxious patients. However, limited research considers the degree to which chronic SSRI treatment influences anxiety in healthy individuals. This study examined the effect of 2-week citalopram treatment on two threat responses: short- and long-duration-potentiated startle. Prior work suggests that these two responses provide neurally and functionally distinct models of fear and anxiety, respectively, in rodents. Healthy volunteers (n=53) received either placebo or citalopram (20 mg per day) for 2 weeks under double-blind conditions. They were each tested twice, before and after treatment. Participants were exposed to three conditions, including one in which predictable aversive shocks were signaled by a cue, a second in which unpredictable shocks were anticipated, and a third in which no shocks were administered. Aversive states were indexed by acoustic startle. Phasic fear-potentiated startle to the threat cue, as well as sustained startle potentiation to the experimental context in the predictable and unpredictable conditions, were investigated. Citalopram affected neither baseline startle nor short-duration fear-potentiated startle to discrete threat cues. However, citalopram reduced long-duration startle potentiation in the predictable conditions. These results are consistent with the hypothesis that short- and long-duration aversive states are mediated by distinct neural systems. They suggest that citalopram alleviates symptoms of anticipatory anxiety, not fear, by acting on mechanisms underlying long-duration aversive states.

Although the clarity of many memories fades with time, some memories may maintain their original precision. Here we used a context discrimination procedure to evaluate whether the hippocampus is important in maintaining precision as memories mature. Spared discrimination in hippocampal-lesioned mice indicated that precise, remote context memories may be supported by extra-hippocampal brain regions.

BACKGROUND: Associations between a functional polymorphism in the serotonin transporter gene and amygdala activation have been found in healthy, depressed, and anxious adults. This study explored these gene-brain associations in adolescents by examining predictive effects of serotonin transporter gene variants (S and L(G) allele carriers vs. L(A) allele homozygotes) and their interaction with diagnosis (healthy vs. patients) on amygdala responses to emotional faces. METHODS: Functional magnetic resonance data were collected from 33 healthy adolescents (mean age: 13.71, 55% female) and 31 medication-free adolescents with current anxiety or depressive disorders (or both; mean age: 13.58, 56% female) while viewing fearful, angry, happy, and neutral facial expressions under varying attention states. RESULTS: A significant three-way genotype-by-diagnosis-by-face-emotion interaction characterized right amygdala activity while subjects monitored internal fear levels. This interaction was decomposed to map differential gene-brain associations in healthy and affected adolescents. First, consistent with healthy adult data, healthy adolescents with at least one copy of the S or L(G) allele showed stronger amygdala responses to fearful faces than healthy adolescents without these alleles. Second, patients with two copies of the L(A) allele exhibited greater amygdala responses to fearful faces relative to patients with S or L(G) alleles. Third, although weaker, genotype differences on amygdala responses in patients extended to happy faces. All effects were restricted to the fear-monitoring attention state. CONCLUSIONS: S/L(G) alleles in healthy adolescents, as in healthy adults, predict enhanced amygdala activation to fearful faces. Contrary findings of increased activation in patients with L(A)L(A) relative to the S or L(G) alleles require further exploration.

BACKGROUND:Panic disorder (PD) is hypothesized to be associated with altered function of the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). Previous proton magnetic resonance spectroscopy (MRS) studies found lower GABA concentrations in the occipital cortex of subjects with PD relative to healthy control subjects. The current study is the first MRS study to compare GABA concentrations between unmedicated PD subjects and control subjects in the prefrontal cortex (PFC). METHODS:Unmedicated subjects with PD (n = 17) and age- and sex-matched healthy control subjects (n = 17) were scanned on a 3 Tesla scanner using a transmit-receive head coil that provided a sufficiently homogenous radiofrequency field to obtain spectroscopic measurements in the dorsomedial/dorsal anterolateral and ventromedial areas of the PFC. RESULTS:The prefrontal cortical GABA concentrations did not differ significantly between PD subjects and control subjects. There also was no statistically significant difference in glutamate/glutamine (Glx), choline, or N-acetyl aspartate concentrations. CONCLUSIONS:The previously reported finding of reduced GABA concentrations in the occipital cortex of PD subjects does not appear to extend to the PFC.

Standard particle filtering technique have previously been applied to the problem of fiber tracking by Brun et al. [Brun, A., Bjornemo, M., Kikinis, R., Westin, C.F., 2002. White matter tractography using sequential importance sampling. In: Proceedings of the ISMRM Annual Meeting, p. 1131] and Bjornemo et al. [Bjornemo, M., Brun, A., Kikinis, R., Westin, C.F., 2002. Regularized stochastic white matter tractography using diffusion tensor MRI, In: Proc. MICCAI, pp. 435-442]. However, these previous attempts have not utilised the full power of the technique, and as a result the fiber paths were tracked in a goal directed way. In this paper, we provide an advanced technique by presenting a fast and novel probabilistic method for white matter fiber tracking in diffusion weighted MRI (DWI), which takes advantage of the weighting and resampling mechanism of particle filtering. We formulate fiber tracking using a non-linear state space model which captures both smoothness regularity of the fibers and the uncertainties in the local fiber orientations due to noise and partial volume effects. Global fiber tracking is then posed as a problem of particle filtering. To model the posterior distribution, we classify voxels of the white matter as either prolate or oblate tensors. We then construct the orientation distributions for prolate and oblate tensors separately. Finally, the importance density function for particle filtering is modeled using the von Mises-Fisher distribution on a unit sphere. Fast and efficient sampling is achieved using Ulrich-Wood's simulation algorithm. Given a seed point, the method is able to rapidly locate the globally optimal fiber and also provides a probability map for potential connections. The proposed method is validated and compared to alternative methods both on synthetic data and real-world brain MRI datasets.

This paper examines factors associated with adherence to antiretroviral medications (ARVs) in an HIV-infected population at high risk for non-adherence: individuals living with psychiatric and substance abuse disorders. Data were examined from baseline interviews of a multisite cohort intervention study of 1138 HIV-infected adults with both a psychiatric and substance abuse disorder (based on a structured psychiatric research interview using DSM-IV criteria). The baseline interview documented mental illness and substance use in the past year, mental illness and substance abuse severity, demographics, service utilization in the past three months, general health and HIV-related conditions, self-reported spirituality and self-reported ARV medication use. Among the participants, 62% were prescribed ARVs at baseline (n = 542) and 45% of those on ARVs reported skipping medications in the past three days. Reports of non-adherence were significantly associated with having a detectable viral load (p<.01). The factors associated with non-adherence were current drug and alcohol abuse, increased psychological distress, less attendance at medical appointments, non-adherence to psychiatric medications and lower self-reported spirituality. Increased psychological distress was significantly associated with non-adherence, independent of substance abuse (p<.05). The data suggest that both mental illness and substance use must be addressed in HIV-infected adults living with these co-morbid illnesses to improve adherence to ARVs

The way in which sex hormones influence cognitive and affective brain development is poorly understood. Despite increasing knowledge in the area of pediatric mood disorders, little is known about the influence of sex hormones on the regulation of emotion. Animal studies and preliminary human studies suggest a strong impact of testosterone on limbic structures such as the hippocampus and amygdala. We used functional magnetic resonance imaging (fMRI) to examine emotional processing in familial male-precocious puberty (FMPP), an extremely rare gonadotropin-independent form of precocious puberty characterized by early excess testosterone secretion. We compared this group (n = 7, mean age = 13 +/- 3.3 years) to healthy age and sex-matched controls (n = 14, mean age = 13 +/- 2.3 years). Participants were presented with emotional and neutral face stimuli and were required either to judge the hostility of the presented face, their subjective level of anxiety, or the width of the nose of the presented faces (nonemotional condition). In a fourth, passive viewing condition, no responses were required. Boys with FMPP responded faster to fearful faces during perception of threat compared to unaffected controls. Concurrently, fMRI data revealed significant differences in hippocampus activation in response to fearful faces relative to baseline whereas controls showed no differences. In contrast, no significant activation of the amygdala was found. These data are consistent with previous studies of the effects of sex hormones on brain function and support the role of testosterone on emotional development.