Faculty Bibliography

BACKGROUND AND HYPOTHESIS:Microvascular and inflammatory mechanisms have been hypothesized to be involved in the pathophysiology of psychotic spectrum disorders (PSDs). However, data evaluating these hypotheses remain limited. STUDY DESIGN:We applied a three-compartment intravoxel incoherent motion free water imaging (IVIM-FWI) technique that estimates the perfusion fraction (PF), free water fraction (FW), and anisotropic diffusion of tissue (FAt) to examine microvascular and microstructural changes in gray and white matter in 55 young adults with a PSD compared to 37 healthy controls (HCs). STUDY RESULTS:We found significantly increased PF, FW, and FAt in gray matter regions, and significantly increased PF, FW, and decreased FAt in white matter regions in the PSD group versus HC. Furthermore, in patients, but not in the HC group, increased PF, FW, and FAt in gray matter and increased PF in white matter were significantly associated with poor performance on several cognitive tests assessing memory and processing speed. We additionally report significant associations between IVIM-FWI metrics and myo-inositol, choline, and N-acetylaspartic acid magnetic resonance spectroscopy imaging metabolites in the posterior cingulate cortex, which further supports the validity of PF, FW, and FAt as microvascular and microstructural biomarkers of PSD. Finally, we found significant relationships between IVIM-FWI metrics and the duration of psychosis in gray and white matter regions. CONCLUSIONS:The three-compartment IVIM-FWI model provides metrics that are associated with cognitive deficits and may reflect disease progression.

Iron deficits have been reported as a risk factor for psychotic spectrum disorders (PSD). However, examinations of brain iron in PSD remain limited. The current study employed quantitative MRI to examine iron content in several iron-rich subcortical structures in 49 young adult individuals with PSD (15 schizophrenia, 17 schizoaffective disorder, and 17 bipolar disorder with psychotic features) compared with 35 age-matched healthy controls (HC). A parametric approach based on a two-pool magnetization transfer model was applied to estimate longitudinal relaxation rate (R₁), which reflects both iron and myelin, and macromolecular proton fraction (MPF), which is specific to myelin. To describe iron content, a synthetic effective transverse relaxation rate (R₂*) was modeled using a linear fitting of R₁ and MPF. PSD patients compared to HC showed significantly reduced R₁ and synthetic R₂* across examined regions including the pallidum, ventral diencephalon, thalamus, and putamen areas. This finding was primarily driven by decreases in the subgroup with schizophrenia, followed by schizoaffective disorder. No significant group differences were noted for MPF between PSD and HC while for regional volume, significant reductions in patients were only observed in bilateral caudate, suggesting that R₁ and synthetic R₂* reductions in schizophrenia and schizoaffective patients likely reflect iron deficits that either occur independently or precede structural and myelin changes. Subcortical R₁ and synthetic R₂* were also found to be inversely related to positive symptoms within the PSD group and to schizotypal traits across the whole sample. These findings that decreased iron in subcortical regions are associated with PSD risk and symptomatology suggest that brain iron deficiencies may play a role in PSD pathology and warrant further study.

OBJECTIVE/UNASSIGNED:To develop an MMPI-2-RF reference group for persistently symptomatic patients with mTBI in order to aid interpretation and better evaluate atypical scale elevations. METHOD/UNASSIGNED:Using the Q Local MMPI-2-RF Comparison Group Generator (CGG), 200 valid MMPI-2-RF profiles were aggregated for mTBI outpatients with persisting symptoms 2-24 months post injury. RESULTS/UNASSIGNED:scores > 60 and standard deviations > 10 were observed for the F-r (Infrequent Responses), Fs (Infrequent Somatic Responses), FBS-r (Symptom Validity), RBS (Response Bias Scale), RC1 (Somatic Complaints), MLS (Malaise), HPC (Head Pain Complaints), NUC (Neurological Complaints), and COG (Cognitive Complaints) scales. All other scales were consistent with established norms for the general population. CONCLUSION/UNASSIGNED:This study is the first to establish an empirically derived MMPI reference group for individuals with persisting symptoms following mTBI. By comparing MMPI profiles of patients with mTBI against this reference group, clinicians may be better able to identify abnormal symptomatology. Evaluating profiles within this context may allow for more accurate case conceptualization and targeted treatment recommendations for those patients who demonstrate disproportionate symptomatology outside the range of the mTBI reference group.

OBJECTIVE:To explore the potential rehabilitative effect of art therapy and its underlying mechanisms in Parkinson's disease (PD). METHODS:Observational study of eighteen patients with PD, followed in a prospective, open-label, exploratory trial. Before and after twenty sessions of art therapy, PD patients were assessed with the UPDRS, Pegboard Test, Timed Up and Go Test (TUG), Beck Depression Inventory (BDI), Modified Fatigue Impact Scale and PROMIS-Self-Efficacy, Montreal Cognitive Assessment, Rey-Osterrieth Complex Figure Test (RCFT), Benton Visual Recognition Test (BVRT), Navon Test, Visual Search, and Stop Signal Task. Eye movements were recorded during the BVRT. Resting-state functional MRI (rs-fMRI) was also performed to assess functional connectivity (FC) changes within the dorsal attention (DAN), executive control (ECN), fronto-occipital (FOC), salience (SAL), primary and secondary visual (V1, V2) brain networks. We also tested fourteen age-matched healthy controls at baseline. RESULTS:At baseline, PD patients showed abnormal visual-cognitive functions and eye movements. Analyses of rs-fMRI showed increased functional connectivity within DAN and ECN in patients compared to controls. Following art therapy, performance improved on Navon test, eye tracking, and UPDRS scores. Rs-fMRI analysis revealed significantly increased FC levels in brain regions within V1 and V2 networks. INTERPRETATION/CONCLUSIONS:Art therapy improves overall visual-cognitive skills and visual exploration strategies as well as general motor function in patients with PD. The changes in brain connectivity highlight a functional reorganization of visual networks.

OBJECTIVE:Characterize relationships among substance misuse, depression, employment, and suicidal ideation (SI) following moderate to severe traumatic brain injury (TBI). DESIGN/METHODS:Prospective cohort study. SETTING/METHODS:Inpatient rehabilitation centers with telephone follow-up; level I/II trauma centers in the United States. PARTICIPANTS/METHODS:Individuals with moderate to severe TBI with data in both the National Trauma Data Bank and the Traumatic Brain Injury Model Systems National Database, aged 18 to 59 years, with SI data at year 1 or year 2 postinjury (N = 1377). MAIN OUTCOME MEASURE/METHODS:Primary outcome of SI, with secondary employment, substance misuse, and depression outcomes at years 1 and 2 postinjury. RESULTS:Cross-lagged structural equation modeling analysis showed that year 1 unemployment and substance misuse were associated with a higher prevalence of year 1 depression. Depression was associated with concurrent SI at years 1 and 2. Older adults and women had a greater likelihood of year 1 depression. More severe overall injury (injury severity score) was associated with a greater likelihood of year 1 SI, and year 1 SI was associated with a greater likelihood of year 2 SI. CONCLUSIONS:Substance misuse, unemployment, depression, and greater extracranial injury burden independently contributed to year 1 SI; in turn, year 1 SI and year 2 depression contributed to year 2 SI. Older age and female sex were associated with year 1 depression. Understanding and mitigating these risk factors are crucial for effectively managing post-TBI SI to prevent postinjury suicide.