Gyrification across psychotic disorders: A bipolar-schizophrenia network of intermediate phenotypes study.

BACKGROUND: The profiles of cortical gyrification across schizophrenia, bipolar I disorder, and schizoaffective disorder have been studied to a limited extent, report discordant findings, and are rarely compared in the same study. Here we assess gyrification in a large dataset of psychotic disorder probands, categorized according to the DSM-IV. Furthermore, we explore gyrification changes with age across healthy controls and probands. METHODS: Participants were recruited within the Bipolar-Schizophrenia Network of Intermediate Phenotypes study and received T1-MPRAGE and clinical assessment. Gyrification was measured using FreeSurfer 7.1.0. Pairwise t-tests were conducted in R, and age-related gyrification changes were analyzed in MATLAB. P values <0.05 after false discovery rate correction were considered significant. RESULTS: Significant hypogyria in schizophrenia, bipolar disorder, and schizoaffective disorder probands compared to controls was found, with a significant difference bilaterally in the frontal lobe between schizophrenia and bipolar disorder probands. Verbal memory was associated with gyrification in the right frontal and right cingulate cortex in schizophrenia. Age-fitted gyrification curves differed significantly among psychotic disorders and controls. CONCLUSIONS: Findings indicate hypogyria in DSM-IV psychotic disorders compared to controls and suggest differential patterns of gyrification across the different diagnoses. The study extends age related models of gyrification to psychotic disorder probands and supports that age-related differences in gyrification may differ across diagnoses. Fitted gyrification curves among probands categorized by DSM-IV significantly deviate from controls, with the model capturing early hypergyria and later hypogyria in schizophrenia compared to controls; this suggests unique disease and age-related changes in gyrification across psychotic disorders.

Linked patterns of symptoms and cognitive covariation with functional brain controllability in major depressive disorder.

BACKGROUND: Controllability analysis is an approach developed for evaluating the ability of a brain region to modulate function in other regions, which has been found to be altered in major depressive disorder (MDD). Both depressive symptoms and cognitive impairments are prominent features of MDD, but the case-control differences of controllability between MDD and controls can not fully interpret the contribution of both clinical symptoms and cognition to brain controllability and linked patterns among them in MDD. METHODS: Sparse canonical correlation analysis was used to investigate the associations between resting-state functional brain controllability at the network level and clinical symptoms and cognition in 99 first-episode medication-naïve patients with MDD. FINDINGS: Average controllability was significantly correlated with clinical features. The average controllability of the dorsal attention network (DAN) and visual network had the highest correlations with clinical variables. Among clinical variables, depressed mood, suicidal ideation and behaviour, impaired work and activities, and gastrointestinal symptoms were significantly negatively associated with average controllability, and reduced cognitive flexibility was associated with reduced average controllability. INTERPRETATION: These findings highlight the importance of brain regions in modulating activity across brain networks in MDD, given their associations with symptoms and cognitive impairments observed in our study. Disrupted control of brain reconfiguration of DAN and visual network during their state transitions may represent a core brain mechanism for the behavioural impairments observed in MDD. FUNDING: National Natural Science Foundation of China (82001795 and 82027808), National Key R&D Program (2022YFC2009900), and Sichuan Science and Technology Program (2024NSFSC0653).

Association between echocardiographic velocity time integral ratio of mitral valve and left ventricular outflow tract and clinical outcomes post transcatheter edge-to-edge mitral valve repair.

Background: Residual mitral regurgitation (MR) is frequent after transcatheter edge-to-edge repair (TEER). There is controversy regarding the clinical impact of residual MR and its quantitative assessment by transthoracic echocardiography (TTE), which is often challenging with multiple eccentric jets and artifact from the clip. The utility of the velocity time integral (VTI) ratio between the mitral valve (MV) and left ventricular outflow tract (LVOT), (VTIMV/LVOT), a simple Doppler measurement that increases with MR, has not been assessed post TEER. Methods: Baseline characteristics, clinical outcomes, and TTE data from patients who underwent TEER between 2014 and 2021 across three academic centers were retrospectively analyzed. Post-procedure TTEs were evaluated for VTIMV/LVOT in the first three months after TEER. One-year outcomes including all-cause and cardiac mortality, major adverse cardiac events, and MV reintervention were compared between patients with high VTIMV/LVOT (≥2.5) and low (<2.5). Results: In total, 372 patients were included (mean age 78.7 ± 8.8 years, 68 % male, mean pre-TEER ejection fraction of 50.5 ± 14.7 %). Follow up TTEs were performed at a median of 37.5 (IQR 30-48) days post-procedure. Patients with high VTIMV/LVOT had significantly higher all-cause mortality (HR 2.10, p = 0.003), cardiac mortality (HR 3.03, p = 0.004) and heart failure admissions (HR 2.28, p < 0.001) at one-year post-procedure. There was no association between raised VTIMV/LVOT and subsequent MV reintervention. Conclusion: High VTIMV/LVOT has clinically significant prognostic value at one year post TEER. This tool could be used to select patients for consideration of repeat intervention.

Lipoprotein(a) and Long-term In-stent Restenosis after Percutaneous Coronary Intervention.

AIM: Lipoprotein(a) [Lp(a)] has demonstrated its association with atherosclerosis and myocardial infarction. However, its role in the development of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) is not clearly established. The aim of this study is to investigate the association between Lp(a) and ISR. METHODS: A retrospective study of adult patients who underwent successful PCI between January 2006 and December 2017 at the three Mayo Clinic sites and had a preprocedural Lp(a) measurement was conducted. Patients were divided into two groups according to the serum Lp(a) concentration (high Lp(a) ≥50 mg/dl and low Lp(a) <50 mg/dl). Univariable and multivariable analyses were performed to compare risk of ISR between patients with high Lp(a) versus those with low Lp(a). RESULTS: A total of 1209 patients were included, with mean age 65.9 ±11.7 years and 71.8% were male. Median follow-up after baseline PCI was 8.8 (IQR 7.4) years. Restenosis was observed in 162 (13.4%) patients. Median serum levels of Lp(a) were significantly higher in patients affected by ISR versus non-affected cases: 27 (IQR 73.8) vs. 20 (IQR 57.5) mg/dL, p=0.008. The rate of ISR was significantly higher among patients with high Lp(a) versus patients with low Lp(a) values (17.0% vs 11.6%, p=0.010). High Lp(a) values were independently associated with ISR events (HR 1.67, 95%CI 1.18 to 2.37, p=0.004), and this association was more prominent after the first year following the PCI. CONCLUSION: Lipoprotein(a) is an independent predictor for long-term in-stent restenosis and should be considered in the evaluation of patients undergoing PCI.

The role of Lp(a) in the development of in-stent restenosis is not clearly established. In this study including 1209 patients who underwent successful percutaneous coronary intervention and had a preprocedural Lp(a) measurement between 2006 and 2017, the rates of restenosis were significantly higher among patients with high Lp(a) versus patients with low Lp(a) values and high Lp(a) concentrations were independently associated with restenosis events. Lp(a) should be considered as a risk factor for long term in-stent restenosis in the evaluation of patients undergoing percutaneous coronary intervention and assessed as a potential therapeutic target for reducing residual cardiovascular risk in this population.

Frontal Cortex Hyperactivation and Gamma Desynchrony in Fragile X Syndrome: Correlates of Auditory Hypersensitivity.

Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity (hyperacusis) is a distressing symptom in FXS, its neural basis is not well understood. It is postulated that hyperacusis may stem from temporal lobe hyperexcitability or dysregulation in top-down modulation. Studying the neural mechanisms underlying sound sensitivity in FXS using scalp electroencephalography (EEG) is challenging because the temporal and frontal regions have overlapping neural projections that are difficult to differentiate. To overcome this challenge, we conducted EEG source analysis on a group of 36 individuals with FXS and 39 matched healthy controls. Our goal was to characterize the spatial and temporal properties of the response to an auditory chirp stimulus. Our results showed that males with FXS exhibit excessive activation in the frontal cortex in response to the stimulus onset, which may reflect changes in top-down modulation of auditory processing. Additionally, during the chirp stimulus, individuals with FXS demonstrated a reduction in typical gamma phase synchrony, along with an increase in asynchronous gamma power, across multiple regions, most strongly in temporal cortex. Consistent with these findings, we observed a decrease in the signal-to-noise ratio, estimated by the ratio of synchronous to asynchronous gamma activity, in individuals with FXS. Furthermore, this ratio was highly correlated with performance in an auditory attention task. Compared to controls, males with FXS demonstrated elevated bidirectional frontotemporal information flow at chirp onset. The evidence indicates that both temporal lobe hyperexcitability and disruptions in top-down regulation play a role in auditory sensitivity disturbances in FXS. These findings have the potential to guide the development of therapeutic targets and back-translation strategies.

Evidence from comprehensive independent validation studies for smooth pursuit dysfunction as a sensorimotor biomarker for psychosis.

Smooth pursuit eye movements are considered a well-established and quantifiable biomarker of sensorimotor function in psychosis research. Identifying psychotic syndromes on an individual level based on neurobiological markers is limited by heterogeneity and requires comprehensive external validation to avoid overestimation of prediction models. Here, we studied quantifiable sensorimotor measures derived from smooth pursuit eye movements in a large sample of psychosis probands (N = 674) and healthy controls (N = 305) using multivariate pattern analysis. Balanced accuracies of 64% for the prediction of psychosis status are in line with recent results from other large heterogenous psychiatric samples. They are confirmed by external validation in independent large samples including probands with (1) psychosis (N = 727) versus healthy controls (N = 292), (2) psychotic (N = 49) and non-psychotic bipolar disorder (N = 36), and (3) non-psychotic affective disorders (N = 119) and psychosis (N = 51) yielding accuracies of 65%, 66% and 58%, respectively, albeit slightly different psychosis syndromes. Our findings make a significant contribution to the identification of biologically defined profiles of heterogeneous psychosis syndromes on an individual level underlining the impact of sensorimotor dysfunction in psychosis.

Body Satisfaction, Exercise Dependence, and White Matter Microstructure in Young Adults.

BACKGROUND: Self-body satisfaction is considered a psychological factor for exercise dependence (EXD). However, the potential neuropsychological mechanisms underlying this association remain unclear. PURPOSE: To investigate the role of white matter microstructure in the association between body satisfaction and EXD. STUDY TYPE: Prospective. POPULATION: One hundred eight regular exercisers (age 22.11 ± 2.62 years; 58 female). FIELD STRENGTH/SEQUENCE: 3.0 Tesla; diffusion-weighted echo planar imaging with 30 directions. ASSESSMENT: The Body Shape Satisfaction (BSS) and Exercise Dependence Scale (EDS); whole-brain tract-based spatial statistics (TBSS) and correlational tractography analyses; average fractional anisotropy (FA) and quantitative anisotropy (QA) values of obtained tracts. STATISTICAL TESTS: The whole-brain regression model, mediation analysis, and simple slope analysis. P values <0.05 were defined as statistically significant. RESULTS: The BSS and EDS scores were 37.33 ± 6.32 and 68.22 ± 13.88, respectively. TBSS showed negative correlations between EDS and FA values in the bilateral corticospinal tract (CST, r = -0.41), right cingulum (r = -0.41), and left superior thalamic radiation (STR, r = -0.50). Correlational tractography showed negative associations between EDS and QA values of the left inferior frontal occipital fasciculus (r = -0.35), STR (r = -0.42), CST (r = -0.31), and right cingulum (r = -0.28). The FA values, rather than QA values, mediated the BSS-EDS association (indirect effects = 0.30). The BSS was significantly associated with the EDS score at both low (ß = 1.02) and high (ß = 0.43) levels of FA value, while the association was significant only at the high level of QA value (ß = 1.26). DATA CONCLUSION: EXD was correlated with white matter in frontal-subcortical and sensorimotor networks, and these tracts mediated the body satisfaction-EXD association. White matter microstructure could be a promising neural signature for understanding the underlying neuropsychological mechanisms of EXD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

The prognostic value of artificial intelligence to predict cardiac amyloidosis in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

Aims: Cardiac amyloidosis (CA) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Cardiac amyloidosis has poor outcomes, and its assessment in all TAVR patients is costly and challenging. Electrocardiogram (ECG) artificial intelligence (AI) algorithms that screen for CA may be useful to identify at-risk patients. Methods and results: In this retrospective analysis of our institutional National Cardiovascular Disease Registry (NCDR)-TAVR database, patients undergoing TAVR between January 2012 and December 2018 were included. Pre-TAVR CA probability was analysed by an ECG AI predictive model, with >50% risk defined as high probability for CA. Univariable and propensity score covariate adjustment analyses using Cox regression were performed to compare clinical outcomes between patients with high CA probability vs. those with low probability at 1-year follow-up after TAVR. Of 1426 patients who underwent TAVR (mean age 81.0 ± 8.5 years, 57.6% male), 349 (24.4%) had high CA probability on pre-procedure ECG. Only 17 (1.2%) had a clinical diagnosis of CA. After multivariable adjustment, high probability of CA by ECG AI algorithm was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.01-1.96, P = 0.046] and higher rates of major adverse cardiovascular events (transient ischaemic attack (TIA)/stroke, myocardial infarction, and heart failure hospitalizations] (HR 1.36, 95% CI 1.01-1.82, P = 0.041), driven primarily by heart failure hospitalizations (HR 1.58, 95% CI 1.13-2.20, P = 0.008) at 1-year follow-up. There were no significant differences in TIA/stroke or myocardial infarction. Conclusion: Artificial intelligence applied to pre-TAVR ECGs identifies a subgroup at higher risk of clinical events. These targeted patients may benefit from further diagnostic evaluation for CA.

Accelerated Theta Burst Transcranial Magnetic Stimulation for Refractory Depression in Autism Spectrum Disorder.

PURPOSE: Major depressive disorder (MDD) disproportionately affects those living with autism spectrum disorder (ASD) and is associated with significant impairment and treatment recidivism. METHODS: We studied the use of accelerated theta burst stimulation (ATBS) for the treatment of refractory MDD in ASD (3 treatments daily x 10 days). This prospective open-label 12-week trial included 10 subjects with a mean age of 21.5 years, randomized to receive unilateral or bilateral stimulation of the dorsolateral prefrontal cortex. RESULTS: One participant dropped out of the study due to intolerability. In both treatment arms, depressive symptoms, scored on the Hamilton Depression Rating Scale scores, diminished substantially. At 12 weeks post-treatment, full remission was sustained in 5 subjects and partial remission in 3 subjects. Treatment with ATBS, regardless of the site of stimulation, was associated with a significant, substantial, and sustained improvement in depressive symptomatology via the primary outcome measure, the Hamilton Depression Rating Scale. Additional secondary measures, including self-report depression scales, fluid cognition, and sleep quality, also showed significant improvement. No serious adverse events occurred during the study. Mild transient headaches were infrequently reported, which are expected side effects of ATBS. CONCLUSION: Overall, ATBS treatment was highly effective and well-tolerated in individuals with ASD and co-occurring MDD. The findings support the need for a larger, sham-controlled randomized controlled trial to further evaluate efficacy of ATBS in this population.

Differences in preoperative frailty assessment of surgical candidates by sex, age, and race.

Introduction: Surgical decision-making often relies on a surgeon's subjective assessment of a patient's frailty status to undergo surgery. Certain patient demographics can influence subjective judgment when compared to validated objective assessments. In this study, we explore the relationship between subjective and objective frailty assessments according to patient age, sex, and race. Methods: Patients were prospectively enrolled in urology, general surgery, and surgical oncology clinics. Using a visual analog scale (0-100), operating surgeons independently rated the patient's frailty status. Objective frailty was classified using the Fried Frailty Criteria ranging from 0 to 5. Multivariable proportional odds models were conducted to examine the potential association of factors with objective frailty, according to surgeon frailty rating. Subgroup analysis according to patient sex, race, and age was also performed. Results: Seven male surgeons assessed 203 patients preoperatively with a median age of 65. A majority of patients were male (61 %), white (67 %), and 60 % and 40 % underwent urologic and general surgery/surgical oncology procedures respectively. Increased subjective surgeon rating (OR 1.69; p < 0.001) was significantly associated with the presence of objective frailty. On subgroup analysis, a higher magnitude of such association was observed more in females (OR 1.86; p = 0.0007), non-white (OR 1.84; p = 0.0019), and older (>60, OR 1.75; p = 0.0001) patients, compared to male (OR 1.45; p = 0.0243), non-white (OR 1.48; p = 0.0109) and patients under 60 (OR 1.47; p = 0.0823). Conclusion: The surgeon's subjective assessment of frailty demonstrated tendencies to rate older, female, and non-white patients as frail; however, differences in patient sex, age, and race were not statistically significant.

Disproportionately High Aortic Valve Calcium Scores in Atrial Fibrillation: Implications for Transcatheter Aortic Valve Replacement.

AIMS: Doppler mean gradient (MG) can underestimate aortic stenosis (AS) severity in patients with atrial fibrillation (AF) compared to patients in sinus rhythm (SR), potentially delaying intervention in AF. This study compared outcomes in patients with AF and SR following transcatheter aortic valve replacement (TAVR) and investigated delay in TAVR based on computed tomography aortic valve calcium score (AVCS). METHODS AND RESULTS: Patients who underwent TAVR from 2013 to 2017 for native valve severe AS were identified from an institutional database. Baseline characteristics and overall survival were compared between those in SR and AF. There were 820 patients (mean age 81 years; 41.6% female) included. AF was present in 356 patients. Patients in AF were older (82.2 vs. 80.5, p = 0.003), had lower MG compared to SR patients (42.0 vs. 44.9, p = 0.002) with similar indexed aortic valve area (0.4 vs. 0.4, p = 0.17). Median AVCS was higher in AF (males: AF 2850.0 vs. SR 2561.0, p = 0.044; females: AF 1942.0 vs. SR 1610.5, p = 0.025). Projected AVCS assuming same age of diagnosis was similar between AF and SR. Median survival post-TAVR was worse in AF compared to SR (3.2 vs 5.4 years, log rank p < 0.001). AF, lower MG, higher RVSP, dialysis, diabetes, and significant TR were associated with higher mortality (p < 0.05 for all). CONCLUSION: Older age and higher AVCS in patients with AF compared to SR suggests that AS was both underestimated and more advanced at TAVR referral.

Trends and Disparities in Valvular Heart Disease Mortality in the United States From 1999 to 2020.

BACKGROUND: Percutaneous heart valve procedures have been increasingly performed over the past decade, yet real-world mortality data on valvular heart disease (VHD) in the United States remain limited. METHODS AND RESULTS: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database among patients ≥15 years old from 1999 to 2020. VHD and its subtypes were listed as the underlying cause of death. We calculated age-adjusted mortality rate (AAMR) per 100 000 individuals and determined overall trends by estimating the average annual percent change using the Joinpoint regression program. Subgroup analyses were performed based on demographic and geographic factors. In the 22-year study, there were 446 096 VHD deaths, accounting for 0.80% of all-cause mortality (56 014 102 people) and 2.38% of the total cardiovascular mortality (18 759 451 people). Aortic stenosis recorded the highest mortality of VHD-related death in both male (109 529, 61.74%) and female (166 930, 62.13%) populations. The AAMR of VHD has declined from 8.4 (95% CI, 8.2-8.5) to 6.6 (95% CI, 6.5-6.7) per 100 000 population. Similar decreasing AAMR trends were also seen for the VHD subtypes. Men recorded higher AAMR for aortic stenosis and aortic regurgitation, whereas women had higher AAMR for mitral stenosis and mitral regurgitation. Mitral regurgitation had the highest change in average annual percent change in AAMR. CONCLUSIONS: The mortality rate of VHD among the US population has declined over the past 2 decades. This highlights the likely efficacy of increasing surveillance and advancement in the management of VHD, resulting in improved outcomes.

A subtype of schizophrenia patients with altered methylation level of genes related to immune cell activity.

BACKGROUND: Epigenetic changes are plausible molecular sources of clinical heterogeneity in schizophrenia. A subgroup of schizophrenia patients with elevated inflammatory or immune-dysregulation has been reported by previous studies. However, little is known about epigenetic changes in genes related to immune activation in never-treated first-episode patients with schizophrenia (FES) and its consistency with that in treated long-term ill (LTS) patients. METHODS: In this study, epigenome-wide profiling with a DNA methylation array was applied using blood samples of both FES and LTS patients, as well as their corresponding healthy controls. Non-negative matrix factorization (NMF) and k -means clustering were performed to parse heterogeneity of schizophrenia, and the consistency of subtyping results from two cohorts. was tested. RESULTS: This study identified a subtype of patients in FES participants (47.5%) that exhibited widespread methylation level alterations of genes enriched in immune cell activity and a significantly higher proportion of neutrophils. This clustering of FES patients was validated in LTS patients, with high correspondence in epigenetic and clinical features across two cohorts. CONCLUSIONS: In summary, this study demonstrated a subtype of schizophrenia patients across both FES and LTS cohorts, defined by widespread alterations in methylation profile of genes related to immune function and distinguishing clinical features. This finding illustrates the promise of novel treatment strategies targeting immune dysregulation for a subpopulation of schizophrenia patients.

Divergent effects of sex on hippocampal subfield alterations in drug-naive patients with major depressive disorder.

BACKGROUND: The hippocampus is a crucial brain structure in etiological models of major depressive disorder (MDD). It remains unclear whether sex differences in the incidence and symptoms of MDD are related to differential illness-associated brain alterations, including alterations in the hippocampus. This study investigated divergent the effects of sex on hippocampal subfield alterations in drug-naive patients with MDD. METHODS: High-resolution structural MR images were obtained from 144 drug-naive individuals with MDD early in their illness course and 135 age- and sex-matched healthy controls (HCs). Hippocampal subfields were segmented using FreeSurfer software and analyzed in terms of both histological subfields (CA1-4, dentate gyrus, etc.) and more integrative larger functional subregions (head, body and tail). RESULTS: We observed a significant overall reduction in hippocampal volume in MDD patients, with deficits more prominent deficits in the posterior hippocampus. Differences in anatomic alterations between male and female patients were observed in the CA1-head, presubiculum-body and fimbria in the left hemisphere. Exploratory analyses revealed different patterns of clinical and memory function correlations with histological subfields and functional subregions between male and female patients primarily in the hippocampal head and body. LIMITATIONS: This cross-sectional study cannot clarify the causality of hippocampal alterations or their association with illness risk or onset. CONCLUSIONS: These findings represent the first reported sex-specific alterations in hippocampal histological subfields in patients with MDD early in the illness course prior to treatment. Sex-specific hippocampal alterations may contribute to diverse sex differences in the clinical presentation of MDD.

Common and distinct cortical thickness alterations in youth with autism spectrum disorder and attention-deficit/hyperactivity disorder.

BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders with overlapping behavioral features and genetic etiology. While brain cortical thickness (CTh) alterations have been reported in ASD and ADHD separately, the degree to which ASD and ADHD are associated with common and distinct patterns of CTh changes is unclear. METHODS: We searched PubMed, Web of Science, Embase, and Science Direct from inception to 8 December 2023 and included studies of cortical thickness comparing youth (age less than 18) with ASD or ADHD with typically developing controls (TDC). We conducted a comparative meta-analysis of vertex-based studies to identify common and distinct CTh alterations in ASD and ADHD. RESULTS: Twelve ASD datasets involving 458 individuals with ASD and 10 ADHD datasets involving 383 individuals with ADHD were included in the analysis. Compared to TDC, ASD showed increased CTh in bilateral superior frontal gyrus, left middle temporal gyrus, and right superior parietal lobule (SPL) and decreased CTh in right temporoparietal junction (TPJ). ADHD showed decreased CTh in bilateral precentral gyri, right postcentral gyrus, and right TPJ relative to TDC. Conjunction analysis showed both disorders shared reduced TPJ CTh located in default mode network (DMN). Comparative analyses indicated ASD had greater CTh in right SPL and TPJ located in dorsal attention network and thinner CTh in right TPJ located in ventral attention network than ADHD. CONCLUSIONS: These results suggest shared thinner TPJ located in DMN is an overlapping neurobiological feature of ASD and ADHD. This alteration together with SPL alterations might be related to altered biological motion processing in ASD, while abnormalities in sensorimotor systems may contribute to behavioral control problems in ADHD. The disorder-specific thinner TPJ located in disparate attention networks provides novel insight into distinct symptoms of attentional deficits associated with the two neurodevelopmental disorders. TRIAL REGISTRATION: PROSPERO CRD42022370620. Registered on November 9, 2022.

Validating brain activity measures as reliable indicators of individual diagnostic group and genetically mediated sub-group membership Fragile X Syndrome.

Recent failures translating preclinical behavioral treatment effects to positive clinical trial results in humans with Fragile X Syndrome (FXS) support refocusing attention on biological pathways and associated measures, such as electroencephalography (EEG), with strong translational potential and small molecule target engagement. This study utilized guided machine learning to test promising translational EEG measures (resting power and auditory chirp oscillatory variables) in a large heterogeneous sample of individuals with FXS to identify best performing EEG variables for reliably separating individuals with FXS, and genetically-mediated subgroups within FXS, from typically developing controls. Best performing variables included resting relative frontal theta power, all combined whole-head resting power bands, posterior peak alpha frequency (PAF), combined PAF across all measured regions, combined theta, alpha, and gamma power during the chirp, and all combined chirp oscillatory variables. Sub-group analyses best discriminated non-mosaic FXS males via whole-head resting relative power (AUC = .9250), even with data reduced to a 20-channel clinical montage. FXS females were nearly perfectly discriminated by combined theta, alpha, and gamma power during the chirp (AUC = .9522). Results support use of resting and auditory oscillatory tasks to reliably identify neural deficit in FXS, and to identify specific translational targets for genetically-mediated sub-groups, supporting potential points for stratification.

Enlarged pituitary gland volume: a possible state rather than trait marker of psychotic disorders.

BACKGROUND: Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders. METHODS: The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration. RESULTS: Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006). CONCLUSIONS: Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis.

Pons-to-Cerebellum Hypoconnectivity Along the Psychosis Spectrum and Associations With Sensory Prediction and Hallucinations in Schizophrenia.

BACKGROUND: Sensory prediction allows the brain to anticipate and parse incoming self-generated sensory information from externally generated signals. Sensory prediction breakdowns may contribute to perceptual and agency abnormalities in psychosis (hallucinations, delusions). The pons, a central node in a cortico-ponto-cerebellar-thalamo-cortical circuit, is thought to support sensory prediction. Examination of pons connectivity in schizophrenia and its role in sensory prediction abnormalities is lacking. METHODS: We examined these relationships using resting-state functional magnetic resonance imaging and the electroencephalography-based auditory N1 event-related potential in 143 participants with psychotic spectrum disorders (PSPs) (with schizophrenia, schizoaffective disorder, or bipolar disorder); 63 first-degree relatives of individuals with psychosis; 45 people at clinical high risk for psychosis; and 124 unaffected comparison participants. This unique sample allowed examination across the psychosis spectrum and illness trajectory. Seeding from the pons, we extracted average connectivity values from thalamic and cerebellar clusters showing differences between PSPs and unaffected comparison participants. We predicted N1 amplitude attenuation during a vocalization task from pons connectivity and group membership. We correlated participant-level connectivity in PSPs and people at clinical high risk for psychosis with hallucination and delusion severity. RESULTS: Compared to unaffected comparison participants, PSPs showed pons hypoconnectivity to 2 cerebellar clusters, and first-degree relatives of individuals with psychosis showed hypoconnectivity to 1 of these clusters. Pons-to-cerebellum connectivity was positively correlated with N1 attenuation; only PSPs with heightened pons-to-postcentral gyrus connectivity showed this pattern, suggesting a possible compensatory mechanism. Pons-to-cerebellum hypoconnectivity was correlated with greater hallucination severity specifically among PSPs with schizophrenia. CONCLUSIONS: Deficient pons-to-cerebellum connectivity linked sensory prediction network breakdowns with perceptual abnormalities in schizophrenia. Findings highlight shared features and clinical heterogeneity across the psychosis spectrum.