Faculty Bibliography

Recently, a great deal of interest has arisen in resting state fMRI as a measure of tonic brain function in clinical populations. Most studies have focused on the examination of temporal correlation between resting state fMRI low-frequency oscillations (LFOs). Studies on the amplitudes of these low-frequency oscillations are rarely reported. Here, we used amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF; the relative amplitude that resides in the low frequencies) to examine the amplitude of LFO in schizophrenia. Twenty-six healthy controls and 29 patients with schizophrenia or schizoaffective disorder participated. Our findings show that patients showed reduced low-frequency amplitude in proportion to the total frequency band investigated (i.e., fALFF) in the lingual gyrus, left cuneus, left insula/superior temporal gyrus, and right caudate and increased fALFF in the medial prefrontal cortex and the right parahippocampal gyrus. ALFF was reduced in patients in the lingual gyrus, cuneus, and precuneus and increased in the left parahippocampal gyrus. These results suggest LFO abnormalities in schizophrenia. The implication of these abnormalities for schizophrenic symptomatology is further discussed

Brain functional connectivity (FC) is often assessed from fMRI data using seed-based methods, such as those of detecting temporal correlation between a predefined region (seed) and all other regions in the brain; or using multivariate methods, such as independent component analysis (ICA). ICA is a useful data-driven tool, but reproducibility issues complicate group inferences based on FC maps derived with ICA. These reproducibility issues can be circumvented with hybrid methods that use information from ICA-derived spatial maps as seeds to produce seed-based FC maps. We report results from five experiments to demonstrate the potential advantages of hybrid ICA-seed-based FC methods, comparing results from regressing fMRI data against task-related a priori time courses, with 'back-reconstruction' from a group ICA, and with five hybrid ICA-seed-based FC methods: ROI-based with (1) single-voxel, (2) few-voxel, and (3) many-voxel seed; and dual-regression-based with (4) single ICA map and (5) multiple ICA map seed

OBJECTIVE: This study compared microstructural abnormalities in depressed elders and controls and studied the association of the serotonin transporter gene status to white matter abnormalities and to remission of depression. METHODS: The subjects were Caucasians with non-psychotic major depression and normal elders. Depressed subjects received escitalopram 10 mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed and voxel-based analysis of fractional anisotropy (FA) was conducted using age and mean diffusivity as covariates. RESULTS: Depressed elders (N=27) had lower FA than controls (N=27) in several frontolimbic areas. Depressed elderly S-allele carriers also had lower FA than L homozygotes in frontolimbic brain areas, including the dorsal and rostral anterior cingulate, posterior cingulate, dorsolateral prefrontal and medial prefrontal regions, thalamus, and in other regions. S-allele carriers had a lower remission rate than L homozygotes. LIMITATIONS: Small number of subjects, lack of random sampling, fixed antidepressant dose, short follow-up. CONCLUSIONS: Lower FA was observed in several frontolimbic and other regions in depressed elders compared to controls. Depressed S-allele carriers had both microstructural white matter abnormalities in frontolimbic networks and a low remission rate. It remains unclear whether the risk for chronicity of geriatric depression in S-allele carriers is mediated by frontolimbic compromise. However, these observations set the stage for studies aiming to identify the relationship of S allele to impairment in specific frontolimbic functions interfering with response of geriatric depression to antidepressants

BACKGROUND: Structural abnormalities of the anterior cingulate cortex (ACC) may interfere with the interaction of cortical and limbic networks involved in emotional regulation and contribute to chronic depressive syndromes in the elderly. This study examined the relationship of regional anterior cingulate cortical volumes with treatment remission of elderly depressed patients. We hypothesized that patients who failed to remit during a 12-week controlled treatment trial of escitalopram would exhibit smaller anterior cingulate gray matter volumes than patients who remitted. METHODS: The participants were 41 non-demented individuals with non-psychotic major depression. After a 2-week single-blind placebo period, subjects who still had a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for at least 2 consecutive weeks. The patient sample consisted of 22 depressed patients who achieved remission during the study and 19 depressed patients who remained symptomatic. High-resolution magnetization-prepared rapidly acquired gradient echo (MPRAGE) sequences were acquired on a 1.5 T scanner and regional ACC volumes were manually outlined (dorsal, rostral, anterior subgenual, and posterior subgenual). RESULTS: Repeated measure analyses revealed that patients who failed to remit following escitalopram treatment had smaller dorsal and rostral anterior cingulate gray matter volumes than patients who remitted, whereas subgenual cortical volumes did not differ between the groups. CONCLUSIONS: Structural abnormalities of the dorsal and rostral anterior cingulate may perpetuate late-life depression

BACKGROUND: Cerebrovascular disease may increase vulnerability to geriatric depression, a syndrome often accompanied by frontal-subcortical lesions. High blood pressure is a risk factor for cerebrovascular disease and white matter changes. This study examined whether and in which brain regions blood pressure is associated with compromised white matter integrity in elderly depressed patients. METHODS: We studied the association between blood pressure and white matter integrity assessed by diffusion tensor imaging (fractional anisotropy, FA) in 41 older patients with major depression. Correlations between FA and blood pressure, after controlling for age, were examined with a voxelwise analysis. RESULTS: Significant associations between FA and blood pressure were detected throughout the anterior cingulate and in multiple frontostriatal and frontotemporal regions. LIMITATIONS: This study did not employ a healthy control group. Moreover, the relatively small sample size precluded a comparison of patients with and without hypertension. CONCLUSIONS: Compromised frontal-striatal white matter integrity may be the anatomical background through which blood pressure confers vulnerability to depression

Structural brain developmental anomalies, particularly those in frontotemporal white matter pathways, may have a genetic component and place people at increased risk for schizophrenia. The current study employed Diffusion Tensor Imaging (DTI) to measure fractional anisotropy (FA) as a quantitative indicator of white matter integrity. We examined twenty-two participants at high genetic risk for schizophrenia (HR), 23 people with schizophrenia (most of whom were family members of those at HR) and 37 non-psychiatric controls for comparison. In those at HR, reduced FA was observed in the cingulate and angular gyri bilaterally. In a few regions, FA was higher in HR participants than in comparison participants. These regional variations in FA might reflect differences in white matter development from comparison participants. Our data provide some evidence that abnormal white matter integrity may be detectable before the onset of a psychotic illness, although longitudinal studies are necessary to determine whether these individuals at genetic risk with abnormal FA will develop illness and whether these changes are associated with the genetic risk for the disorder

OBJECTIVE: Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, abnormalities in specific brain structures and their interconnections may confer vulnerability to the development of late-life depression. The objective of this study was to identify subtle white matter abnormalities in late-life depression. DESIGN: The authors used magnetization transfer ratio (MTR) imaging, a technique that is thought primarily to reflect myelin integrity, to examine the hypothesis that individuals with late-life depression would exhibit white matter abnormalities in frontostriatal and limbic regions. SETTING: The study was conducted in a university-based, geriatric psychiatry clinic. PARTICIPANTS: Fifty-five older patients with major depression and 24 elderly comparison subjects were assessed. MEASUREMENT: Voxel-based analysis of MTR data were conducted with a general linear model using age as a covariate. RESULTS: Relative to comparison subjects, patients demonstrated lower MTR in multiple left hemisphere frontostriatal and limbic regions, including white matter lateral to the lentiform nuclei, dorsolateral and dorsomedial prefrontal, dorsal anterior cingulate, subcallosal, periamygdalar, insular, and posterior cingulate regions. Depressed patients had lower MTR in additional left hemisphere locales including the thalamus, splenium of the corpus callosum, inferior parietal, precuneus, and middle occipital white matter regions. CONCLUSION: These findings suggest that geriatric depression may be characterized by reduced myelin integrity in specific aspects of frontostriatal and limbic networks, and complement diffusion tensor studies of geriatric depression that indicate decreased organization of white matter fibers in specific frontal and temporal regions

OBJECTIVE: White matter abnormalities may interfere with limbic cortical balance and lead to chronic depressive syndromes. The authors used diffusion tensor imaging to test the hypothesis that depressed elders who fail to achieve remission have microstructural white matter abnormalities in cortico-striato-limbic networks implicated in geriatric depression. METHOD: The subjects were nondemented individuals with nonpsychotic major depression. After a 2-week placebo period, those subjects who had a Hamilton Depression Rating Scale (HAM-D) score of 18 or greater received escitalopram, 10 mg daily, for 12 weeks. Remission was defined as a HAM-D score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed at a 1.5 Tesla scanner, and voxel-based analysis of fractional anisotropy was conducted using age as the covariate. RESULTS: Subjects who failed to achieve remission (N=23) had lower fractional anisotropy in multiple frontal limbic brain areas, including the rostral and dorsal anterior cingulate, dorsolateral prefrontal cortex, genu of the corpus callosum, white matter adjacent to the hippocampus, multiple posterior cingulate cortex regions, and insular white matter, relative to those who achieved remission (N=25). In addition, lower fractional anisotropy was detected in the neostriatum and midbrain as well as select temporal and parietal regions. CONCLUSIONS: Lower fractional anisotropy in distributed cerebral networks is associated with poor antidepressant response of geriatric depression and may represent a neuroanatomical substrate that predisposes to this disorder