Faculty Bibliography

OBJECTIVE:The objective of this study was to assess the accuracy of the Substance Abuse and Mental Health Services Administration (SAMHSA) database for patients who use it to seek buprenorphine treatment. DESIGN AND MEASUREMENTS/METHODS:Buprenorphine providers within a 25-mile radius of the county with the highest drug-related death rates within the 10 states with the highest drug-related death rates were identified and called to determine whether the provider worked there, prescribed buprenorphine, accepted insurance, had appointments, or charged for visits. RESULTS:The number of providers listed in each county ranged from 1 to 166, with 5 counties having <10 providers. In 3 counties no appointments were obtained, and another 3 counties had ≤3 providers with availability. Of the 505 providers listed, 355 providers (70.3%) were reached, 310 (61.4%) of the 505 listings were correct numbers, and 195 (38.6%) of the 505 providers in the listings provided buprenorphine. Of the 173 clinics that provided buprenorphine and were asked about insurance, 131 (75.7%) accepted insurance. Of the 167 clinics that provided buprenorphine and were asked about Medicaid, 105 (62.9%) accepted it. Wait times for appointments ranged from 1 to 120 days, with an average of 16.8 days for those that had a waitlist. Among the 39 providers who reported out-of-pocket costs, the average cost was $231 (range: $90 to $600). One hundred forty of the 505 providers listed in the database had appointments available (27.7%). Three hundred sixty-five of the 505 providers did not have appointments available (72.3%) for various reasons, including the fact that 120 providers (32.9% of the 365 providers) could not be reached, and 137 of the numbers (37.5% of the 365 listed numbers) were wrong. Other reasons appointments could not be obtained included the fact that providers did not treat outpatients, were not accepting new patients, were out of office, or required a referral. CONCLUSION/CONCLUSIONS:Although the SAMHSA buprenorphine practitioner locator is used by patients and providers to locate treatment options, only a small portion of clinicians in the database ultimately offered initial appointments, implying that the database is only marginally useful for patients.

Few studies have examined the association between maternal and youth mental health among US Latinos, or its variation by nativity, country of origin, ethnic subgroup, and time in the mainland US. Using 2007-2014 Medical Expenditure Panel Survey data linking Latino youth (N = 15,686 aged 5-17 years) and their mothers, we estimated multivariate models of the relationship between probable maternal mental illness (a composite of measures) and youth mental health impairment (Columbia Impairment Scale). Children of mothers with probable mental illness were more than three times as likely to have impairment as children of mothers without mental illness (p < 0.01). In adjusted models, there was an 8.5-point (95% CI 5.1, 11.8) increased prevalence of child impairment associated with mother's probable mental illness among mainland US-born youth and mothers and a 6.0-point (95% CI 3.7, 8.3) increased prevalence among US-born youth of foreign/island-born mothers. There was no significant difference in the prevalence of youth impairment associated with maternal mental illness when both youth and mother were born outside of the mainland US. For the Puerto Rican subgroup, the association between maternal and youth mental health was greatest among island-born mothers and mainland US-born youth; for the Mexican subgroup, the link was strongest among US-born mothers and youth. While there were large point differences between those groups, the difference was not statistically significant. This study suggests a protective effect of island/foreign-born nativity on symptom association between Latino mothers and children. Considerations for future research and practice stemming from this finding are discussed.

New protein synthesis is known to be required for the consolidation of memories, yet existing methods of blocking translation lack spatiotemporal precision and cell-type specificity, preventing investigation of cell-specific contributions of protein synthesis. Here we developed a combined knock-in mouse and chemogenetic approach for cell-type-specific drug-inducible protein synthesis inhibition that enables rapid and reversible phosphorylation of eukaryotic initiation factor 2α, leading to inhibition of general translation by 50% in vivo. We use cell-type-specific drug-inducible protein synthesis inhibition to show that targeted protein synthesis inhibition pan-neuronally and in excitatory neurons in the lateral amygdala (LA) impaired long-term memory. This could be recovered with artificial chemogenetic activation of LA neurons, although at the cost of stimulus generalization. Conversely, genetically reducing phosphorylation of eukaryotic initiation factor 2α in excitatory neurons in the LA enhanced memory strength but reduced memory fidelity and behavioral flexibility. Our findings provide evidence for a cell-specific translation program during consolidation of threat memories.

BACKGROUND:Electroconvulsive therapy (ECT) has been shown to be effective in schizophrenia (SZ), particularly in drug-refractory cases or when rapid symptom relief is needed. However, its precise mechanisms of action remain largely unclear. To clarify the mechanisms underlying modified electroconvulsive therapy (mECT) for SZ, we conducted a longitudinal cohort study evaluating functional connectivity of the thalamus before and after mECT treatment using sub-regions of thalamus as regions of interest (ROIs). METHODS:Twenty-one SZ individuals taking only antipsychotics (DSZ group) for 4 weeks and 21 SZ patients receiving a regular course of mECT combining with antipsychotics (MSZ group) were observed in parallel. All patients underwent magnetic resonance imaging scans at baseline (t1) and follow-up (t2, ~4 weeks) time points. Data were compared to a matched healthy control group (HC group) consisting of 23 persons who were only scanned at baseline. Group differences in changes of thalamic functional connectivity between two SZ groups over time, as well as in functional connectivity among two SZ groups and HC group were assessed. RESULTS:Significant interaction of group by time was found in functional connectivity of the right thalamus to right putamen during the course of about 4-week treatment. Post-hoc analysis showed a significantly enhanced functional connectivity of the right thalamus to right putamen in the MSZ group contrasting to the DSZ group. In addition, a decreased and an increased functional connectivity of the thalamus to sensory cortex were observed within the MSZ and DSZ group after 4-week treatment trial, respectively. CONCLUSION/CONCLUSIONS:Our findings suggest that changes in functional connectivity of the thalamus may be associated with the brain mechanisms of mECT for schizophrenia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BACKGROUND:Major depressive disorder (MDD) is known to be characterized by altered brain functional connectivity (FC) patterns. However, whether and how the features of dynamic FC would change in patients with MDD are unclear. In this study, we aimed to characterize dynamic FC in MDD using a large multi-site sample and a novel dynamic network-based approach. METHODS:Resting-state functional magnetic resonance imaging (fMRI) data were acquired from a total of 460 MDD patients and 473 healthy controls, as a part of the REST-meta-MDD consortium. Resting-state dynamic functional brain networks were constructed for each subject by a sliding-window approach. Multiple spatio-temporal features of dynamic brain networks, including temporal variability, temporal clustering and temporal efficiency, were then compared between patients and healthy subjects at both global and local levels. RESULTS:). Corresponding local changes in MDD were mainly found in the default-mode, sensorimotor and subcortical areas. Measures of temporal variability and characteristic temporal path length were significantly correlated with depression severity in patients (corrected p < 0.05). Moreover, the observed between-group differences were robustly present in both first-episode, drug-naïve (FEDN) and non-FEDN patients. CONCLUSIONS:Our findings suggest that excessive temporal variations of brain FC, reflecting abnormal communications between large-scale bran networks over time, may underlie the neuropathology of MDD.

Vergence eye movements are the inward and outward rotation of the eyes responsible for binocular coordination. While studies have mapped and investigated the neural substrates of vergence, it is not well understood whether vergence eye movements evoke the blood oxygen level-dependent signal reliably in separate experimental visits. The test-retest reliability of stimulus-induced vergence eye movement tasks during a functional magnetic resonance imaging (fMRI) experiment is important for future randomized clinical trials (RCTs). In this study, we established region of interest (ROI) masks for the vergence neural circuit. Twenty-seven binocularly normal young adults participated in two functional imaging sessions measured on different days on the same 3T Siemens scanner. The fMRI experiments used a block design of sustained visual fixation and rest blocks interleaved between task blocks that stimulated eight or four vergence eye movements. The test-retest reliability of task-activation was assessed using the intraclass correlation coefficient (ICC), and that of spatial extent was assessed using the Dice coefficient. Functional activation during the vergence eye movement task of eight movements compared to rest was repeatable within the primary visual cortex (ICC = 0.8), parietal eye fields (ICC = 0.6), supplementary eye field (ICC = 0.5), frontal eye fields (ICC = 0.5), and oculomotor vermis (ICC = 0.6). The results demonstrate significant test-retest reliability in the ROIs of the vergence neural substrates for functional activation magnitude and spatial extent using the stimulus protocol of a task block stimulating eight vergence eye movements compared to sustained fixation. These ROIs can be used in future longitudinal RCTs to study patient populations with vergence dysfunctions.

Objectives: To identify the relationship between the core Diagnostic and Statistical Manual of Mental Disorders (5th ed.) ADHD symptoms and executive function deficits (EFDs), to evaluate ADHD characteristics of those with executive dysfunction (ED), and to examine the predictive utility of the Adult ADHD Investigator Symptom Rating Scale (AISRS) in identifying those with adult ADHD and ED. Method: Two samples (referred and primary care practice) were pooled together for present analysis. Results: Final analysis included 297 respondents, 171 with adult ADHD. Spearman correlation coefficients and binary logistic regressions demonstrated that ADHD inattentive (IA) and hyperactive-impulsive (H-I) symptoms were moderately to strongly correlated with and highly predictive of EFDs. Receiver operating characteristic curve analysis showed that an AISRS DSM 18-item score of ⩾ 28 was most predictive of clinical ED. Conclusion: ADHD symptoms were strongly correlated with and predictive of EFDs, clinicians should screen adults with ADHD for EFDs and ADHD treatment providers should track EFD improvement in addition to DSM-5 ADHD symptoms.

Early childhood deprivation is associated with higher rates of neurodevelopmental and mental disorders in adulthood. The impact of childhood deprivation on the adult brain and the extent to which structural changes underpin these effects are currently unknown. To investigate these questions, we utilized MRI data collected from young adults who were exposed to severe deprivation in early childhood in the Romanian orphanages of the Ceaușescu era and then, subsequently adopted by UK families; 67 Romanian adoptees (with between 3 and 41 mo of deprivation) were compared with 21 nondeprived UK adoptees. Romanian adoptees had substantially smaller total brain volumes (TBVs) than nondeprived adoptees (8.6% reduction), and TBV was strongly negatively associated with deprivation duration. This effect persisted after covarying for potential environmental and genetic confounds. In whole-brain analyses, deprived adoptees showed lower right inferior frontal surface area and volume but greater right inferior temporal lobe thickness, surface area, and volume than the nondeprived adoptees. Right medial prefrontal volume and surface area were positively associated with deprivation duration. No deprivation-related effects were observed in limbic regions. Global reductions in TBV statistically mediated the observed relationship between institutionalization and both lower intelligence quotient (IQ) and higher levels of attention deficit/hyperactivity disorder symptoms. The deprivation-related increase in right inferior temporal volume seemed to be compensatory, as it was associated with lower levels of attention deficit/hyperactivity disorder symptoms. We provide compelling evidence that time-limited severe deprivation in the first years of life is related to alterations in adult brain structure, despite extended enrichment in adoptive homes in the intervening years.

Background. Neuroimaging studies of spinal cord injury (SCI) have mostly examined the functional organization of the cortex, with only limited focus on the subcortical substrates of the injury. However, thalamus is an important modulator and sensory relay that requires investigation at a subnuclei level to gain insight into the neuroplasticity following SCI. Objective. To use resting-state functional magnetic resonance imaging to examine the functional connectivity (FC) of thalamic subnuclei in complete SCI patients. Methods. A seed-based connectivity analysis was applied for 3 thalamic subnuclei: pulvinar, mediodorsal, and ventrolateral nucleus in each hemisphere. A nonparametric 2-sample t test with permutations was applied for each of the 6 thalamic seeds to compute FC differences between 22 healthy controls and 19 complete SCI patients with paraplegia. Results. Connectivity analysis showed a decrease in the FC of the bilateral mediodorsal nucleus with right superior temporal gyrus and anterior cingulate cortex in the SCI group. Similarly, the left ventrolateral nucleus exhibited decreased FC with left superior temporal gyrus in SCI group. In contrast, left pulvinar nucleus demonstrated an increase in FC with left inferior frontal gyrus and left inferior parietal lobule in SCI group. Our findings also indicate a negative relationship between postinjury durations and thalamic FC to regions of sensorimotor and visual cortices, where longer postinjury durations (~12 months) is associated with higher negative connectivity between these regions. Conclusion. This study provides evidence for reorganization in the thalamocortical connections known to be involved in multisensory integration and affective processing, with possible implications in the generation of sensory abnormalities after SCI.