Faculty Bibliography

OBJECTIVE/UNASSIGNED:, defined as impulsive action in the context of high positive or negative emotion states. The current study leverages a machine learning approach to examine the association of SSD symptoms, urgency, and suicide risk. METHOD/UNASSIGNED:=10.95, 13.3% female) Model 1 included demographics, childhood trauma, SSD symptoms, global cognitive ability, and urgency. In addition, Model 2 added neuroimaging data. The use of LASSO logistic regression allows for the identification of the strongest predictors among a large number of predictors. RESULTS/UNASSIGNED:Model 1 suggested that greater hostility, guilt, and negative urgency predicted higher likelihood of belonging to the high-risk group, whereas greater difficulty with abstract thinking predicted lower likelihood of belonging to the high-risk group. Model 2 suggested that greater hostility predicted higher likelihood of high-risk, whereas greater anterior cingulate thickness and increased activity in six brain regions-right superior frontal gyrus, left superior medial frontal gyrus, left superior frontal gyrus, right middle frontal gyrus, and right middle cingulate gyrus-predicted a lower likelihood of high SIB. DISCUSSION/UNASSIGNED:Negative urgency and SSD symptoms can classify high-and low-risk groups accurately, and inclusion of brain data slightly increased predictive accuracy.

BACKGROUND:A subset of first-episode schizophrenia (FES) patients responds poorly to initial antipsychotic therapy. The hippocampus is an early-affected region in schizophrenia, yet neurobiological markers predicting treatment response remain unclear. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) allows non-invasive measurement of cerebral blood flow (CBF), but studies on hippocampal perfusion in acute FES, particularly in those receiving electroconvulsive therapy (ECT) with antipsychotics, are limited. METHODS:Fifty FES patients and 28 age- and sex-matched healthy controls underwent high-resolution ASL MRI to assess hippocampal CBF. Patients received either antipsychotics alone (n = 20) or in combination with ECT (n = 30). MRI Scans were acquired before and after six weeks of treatment. Analysis of covariance and linear mixed-effects models were used to assess group differences and longitudinal effects, adjusting for relevant covariates. RESULTS:At baseline, FES patients exhibited significantly lower hippocampal CBF compared to healthy controls, with no significant difference in hippocampal volume. Longitudinal analysis revealed a significant group × time interaction for hippocampal CBF. Post hoc analysis indicated a significant increase in CBF after treatment in the FES group, while hippocampal volume remained unchanged. CBF changes were not significantly correlated with symptom reduction. We further examined the group differences in longitudinal changes between the ECT + Drug group and the Drug group, however no significant results were found. CONCLUSION/CONCLUSIONS:Our findings suggest that functional, but not structural, hippocampal alterations are present in early schizophrenia and may be responsive to treatment. These preliminary results should be interpreted cautiously and validated in larger samples with extended follow-up and neurochemical assessments.

Myelin abnormalities in white matter have been implicated in the pathophysiology of psychotic spectrum disorders (PSD), which are characterized by brain dysconnectivity as a core feature. Among evidence from in vivo MRI studies, diffusion imaging findings have largely supported disrupted white matter integrity in PSD; however, they are not specific to myelin changes. Using a multimodal imaging approach, the current study aimed to further delineate myelin and microstructural changes in the white matter of a young PSD cohort. We utilized quantitative magnetization transfer (qMT) imaging combined with advanced diffusion imaging to estimate specific myelin-related biophysical properties in 51 young adult PSD patients compared with 38 age-matched healthy controls. The macromolecular proton fraction (MPF) obtained from qMT was used as a specific marker of myelin content. Additionally, MPF was employed along with diffusion metrics of axonal density (v_ic) and extra-cellular volume fraction to derive the g-ratio, a measure of relative myelin sheath thickness defined as the ratio of inner to outer axonal diameter. Compared to controls, we observed a widespread MPF reduction and localized g-ratio increase in patients, primarily those with a diagnosis of schizophrenia or depressive schizoaffective disorder. No between-group differences were noted in v_ic, suggesting similar axonal densities across groups. Correlation analysis revealed that lower MPF was significantly related to poorer working memory performance in PSD, while the HC group showed a positive association for working memory with both g-ratio and v_ic. The pattern of changes observed in our multimodal imaging markers suggests that PSD, depending on symptomatology, is characterized by specific alterations in white matter integrity and myelin-axonal geometry of major white matter tracts, which may impact working memory function. These findings provide a more detailed view of myelin-related white matter changes in early stages of PSD.

Deficits in cognitive control contribute to behavioral impairments across neuropsychiatric disorders. Cognitive control is captured as a construct in the Research Domain Construct (RDoC) matrix and incorporate subdomains of goal selection, response selection, and performance monitoring. Relevant tasks for these subdomains include the "AX" version of the continuous performance task (goal selection) and the Go/NoGo and Stop-Signal reaction time tasks (response selection). Underlying mechanisms for these domains have been investigated intensively using fMRI and event-related potential (ERP) approaches, which provide candidate biomarkers for translational research. In RDoC, impulsive behaviors are provisionally assigned to the cognitive control/response selection construct, but other factors may also contribute. Impulsivity has gained increased importance over recent years due to its link to aggression and suicidality, which is mediated especially through the constructs of urgency and frustrative nonreward. These constructs, in turn, may be captured through scales such as the Urgency, (Lack of) Premeditation, (Lack of) Perseverance, and Sensation Seeking (UPPS-P) impulsivity scale and the Point Subtraction Aggression Paradigm (PSAP), respectively. At present, no validated biomarkers exist for either urgency or aggressivity. Potential directions for the development of predictive biomarkers for both targets are discussed.

The aim of this study was to characterize dysfunctional cerebral activation in patients with schizophrenia while they performed a response inhibition task. To achieve this, performance on the task and functional magnetic resonance imaging (fMRI) were compared between healthy control subjects (HC) and patients with schizophrenia (SZ). We focused on the default mode network (DMN), as there is strong evidence in the literature that lack of DMN suppression in schizophrenia is associated with cognitive impairment including poor response inhibition. fMRI was used to measure blood-oxygen-level-dependent activation in 84 subjects (44 SZ and 40 HC) while they performed a Go NoGo task. The subjects were also evaluated for psychiatric symptoms and immediate visual memory. SZ performed more poorly than HC on the task; they had a higher number of commission errors. On the fMRI, the patients consistently evidenced higher activation than the controls in several areas of the default mode network (DMN) including the precuneus, rostral anterior cingulate, parahippocampus and insula. The higher brain activation in the patients with schizophrenia indicates a failure to deactivate the DMN while they perform the response inhibition task. These findings point to the importance of DMN dysfunction as an underlying cause of impairment in response inhibition in schizophrenia. DMN disruptions play an essential role in the cognitive impairment present in schizophrenia.

INTRODUCTION/UNASSIGNED:Suicidal ideation and behavior (SIB) are serious problems in people with schizophrenia spectrum disorders (SSD). Nevertheless, relatively little is known about the circuitry underlying SIB in SSD. Recently, we showed that elevated emotional impulsivity (urgency) was associated with SIB in SSD. Here we examined brain activity in people with SSD and elevated SIB. METHODS/UNASSIGNED:We tested 16 people with SSD who had low SIB and 14 people with high SIB on a task in which emotion regulation in response to affective pictures was implicitly manipulated using spoken sentences. Thus, there were neutral pictures preceded by neutral statements (NeutNeut condition), as well as negative pictures preceded by either negative (NegNeg) or neutral (NeutNeg) statements. After each picture, participants rated how unpleasant each picture was for them. The latter two conditions were compared to the NeutNeut condition. We compared the emotion-regulated condition (NeutNeg) to the unregulated condition (NeutNeut). Statistics were threshold using threshold free cluster enhancement (TFCE). RESULTS/UNASSIGNED:People in the low SIB group showed higher activation in this contrast in medial frontal gyrus, right rostral anterior cingulate, bilateral superior frontal gyrus/DLPFC, and right middle cingulate gyrus, as well as right superior temporal gyrus. DISCUSSION/UNASSIGNED:This study provides clues to the neural basis of SIB in SSD as well as underlying mechanisms.

IMPORTANCE/UNASSIGNED:Individuals with schizophrenia are at higher risk for severe COVID-19 illness and severe breakthrough infection following vaccination. It is unclear whether immune response to vaccination differs in this population. OBJECTIVE/UNASSIGNED:To assess whether anti-SARS-CoV-2 spike antibody titers after vaccination differ in people with a diagnosis of schizophrenia or schizoaffective disorder (SZ) compared to controls without a psychiatric disorder. DESIGN/UNASSIGNED:This cohort study assessed antibody response following the first and second dose of mRNA vaccines at longitudinal timepoints, up to 7 weeks following the first dose of vaccine. SETTING/UNASSIGNED:A multi-center study including psychiatric healthcare settings in the United States and Europe. PARTICIPANTS/UNASSIGNED:205 adults with no history of COVID-19 infection, including 106 individuals with SZ and 99 controls without a psychiatric disorder, who received their first dose of SARS-CoV-2 mRNA vaccine between December 20, 2020 and May 27, 2021. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Mean SARS-CoV-2 anti-Spike IgG antibody levels within 7 weeks after the first dose of vaccination. RESULTS/UNASSIGNED: = 0.96). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of individuals with SZ and a control group without psychiatric disorders, SZ was associated with lower SARS-CoV-2 anti-spike antibody levels following 2 doses of SARS-CoV-2 mRNA vaccination. This highlights the need for further studies assessing vaccine immunogenicity in individuals with schizophrenia.

This study aimed to evaluate the dose-dependent brain temperature effects of transcranial photobiomodulation (t-PBM). Thirty adult subjects with major depressive disorder were randomized to three t-PBM sessions with different doses (low: 50 mW/cm², medium: 300 mW/cm², high: 850 mW/cm²) and a sham treatment. The low and medium doses were administered in continuous wave mode, while the high dose was administered in pulsed wave mode. A 3T MRI scanner was used to perform proton magnetic resonance spectroscopy (¹H-MRS). A voxel with a volume of 30 × 30 × 15 mm³ was placed on the left prefrontal region. Brain temperature (°C) was derived by analyzing ¹H-MRS spectrum chemical shift differences between the water (~ 4.7 ppm) and N-acetyl aspartate (NAA) (~ 2.01 ppm) peaks. After quality control of the data, the following group numbers were available for both pre- and post-temperature estimations: sham (n = 10), low (n = 11), medium (n = 10), and high (n = 8). We did not detect significant temperature differences for any t-PBM-active or sham groups post-irradiation (p-value range = 0.105 and 0.781). We also tested for potential differences in the pre-post variability of brain temperature in each group. As for t-PBM active groups, the lowest fluctuation (variance) was observed for the medium dose (σ² = 0.29), followed by the low dose (σ² = 0.47), and the highest fluctuation was for the high dose (σ² = 0.67). t-PBM sham condition showed the overall lowest fluctuation (σ² = 0.11). Our ¹H-MRS thermometry results showed no significant brain temperature elevations during t-PBM administration.