Healthy Comparison Subjects Research Articles

Increased levels of antibodies to synaptopodin and annexin 1 in patients with primary podocytopathies.

Circulating anti-podocyte antibodies have been proposed as potential factors contributing to increased permeability in primary podocytopathies, such as Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS). The aim of the study was to to assess the levels of antibodies targeting synaptopodin and annexin 1 in the blood serum of patients diagnosed with nephrotic syndrome, with the aim of evaluating their potential utility in diagnosing primary podocytopathies and predicting therapeutic response. The study included a total of 72 patients diagnosed with nephrotic syndrome, alongside 21 healthy subjects for comparison. Among the patients, 38 were diagnosed with FSGS, 12 with MCD, and 22 with MN. The levels of anti-synaptopodin and anti-annexin-1 antibodies were quantified using Enzyme-Linked Immunosorbent Assay. The levels of antibodies to annexin 1 and anti-synaptopodin in the blood were found to be higher in patients diagnosed with MCD and FSGS compared to those with MN and healthy individuals. The elevated levels of antibodies to annexin 1 and synaptopodin showed area under the curve values of 0.826 (95% CI 0.732-0.923) and 0.827 (95% CI 0.741-0.879), respectively. However, a model incorporating both antibodies demonstrated higher sensitivity (80.9%) and specificity (81.3%) with an AUC of 0.859 (95% CI 0.760-0.957). Notably, serum levels of annexin 1 and anti-synaptopodin antibodies did not predict the response to prednisolone and/or CNI therapy. Levels of antibodies targeting synaptopodin and annexin 1 were notably elevated in patients diagnosed with MCD and FSGS compared to those with MN and healthy controls. A panel comprising both antibodies demonstrated moderate to high sensitivity and specificity for diagnosis MCD or FSGS.

Differing Pattern of Mismatch Negativity Responses in Clinical and Nonclinical Voice Hearers Challenge Predictive Coding Accounts of Psychosis

BackgroundAmong people with schizophrenia (PSZ), reduced mismatch negativity (MMN) is conceptualized as evidence of disrupted prediction error signaling that underlies positive symptoms. However, this conceptualization has been challenged by observations that MMN and positive symptoms are often uncorrelated. In the current study, we tested the hypothesis that reduced MMN is associated with the presence of hallucinations and delusions specifically rather than the presence of a psychiatric illness. A second aim was to determine whether the strength of the association with positive symptoms increases for indices that reflect predictions at higher levels of abstraction. MethodsFifty-six PSZ, 34 nonclinical voice hearers, and 48 healthy comparison subjects (HCs) completed 2 MMN paradigms: one with a simple duration deviant type, and one with a higher-level, pattern-violation deviant type. We also measured the repetition positivity, which reflects the formation of auditory memory traces. ResultsWe observed that although PSZ exhibited the expected pattern of significantly reduced simple duration deviant type and reduced pattern-violation deviant type at the trend level compared with HCs, nonclinical voice hearers exhibited a pattern of simple duration deviant type and pattern-violation deviant type amplitude that was statistically similar to that of HCs (ps > .64). Similarly, PSZ exhibited a significantly reduced repetition positivity slope compared with HCs in the duration condition and a trend-level reduction compared with HCs in the pattern-violation condition. Nonclinical voice hearers did not differ from either group in repetition positivity slope in either condition. ConclusionsThese results indicate that the MMN as a prediction error signal does not reflect processes relevant for the manifestation of hallucinations and delusions.

Wearable accelerometers reveal objective assessment of walking symmetry and regularity in idiopathic scoliosis patients.

Scoliosis is a multifaceted three-dimensional deformity that significantly affects patients' balance function and walking process. While existing research primarily focuses on spatial and temporal parameters of walking and trunk/pelvic kinematics asymmetry, there remains controversy regarding the symmetry and regularity of bilateral lower limb gait. This study aims to investigate the symmetry and regularity of bilateral lower limb gait and examine the balance control strategy of the head during walking in patients with idiopathic scoliosis. The study involved 17 patients with idiopathic scoliosis of Lenke 1 and Lenke 5 classifications, along with 17 healthy subjects for comparison. Three-dimensional accelerometers were attached to the head and L5 spinous process of each participant, and three-dimensional motion acceleration signals were collected during a 10-meter walking test. Analysis of the collected acceleration signals involved calculating five variables related to the symmetry and regularity of walking: root mean square (RMS) of the acceleration signal, harmonic ratio (HR), step regularity, stride regularity, and gait symmetry. Our analysis reveals that, during the walking process, the three-dimensional motion acceleration signals acquired from the lumbar region of patients diagnosed with idiopathic scoliosis exhibit noteworthy disparities in the RMS of the vertical axis (RMS-VT) and the HR of the vertical axis (HR-VT) when compared to the corresponding values in the healthy control (RMS-VT: 1.6±0.41 vs. 3±0.47, P<0.05; HR-VT: 3±0.72 vs. 3.9±0.71, P<0.05). Additionally, the motion acceleration signals of the head in three-dimensional space, including the RMS in the anterior-posterior and vertical axis, the HR-VT, and the values of step regularity in both anterior-posterior and vertical axis, as well as the values of stride regularity in all three axes, are all significantly lower than those in the healthy control group (P<0.05). The findings of the analysis suggest that the application of three-dimensional accelerometer sensors proves efficacious and convenient for scrutinizing the symmetry and regularity of walking in individuals with idiopathic scoliosis. Distinctive irregularities in gait symmetry and regularity manifest in patients with idiopathic scoliosis, particularly within the antero-posterior and vertical direction. Moreover, the dynamic balance control strategy of the head in three-dimensional space among patients with idiopathic scoliosis exhibits a relatively conservative nature when compared to healthy individuals.

Reduced amplitude and slowed latency of the acoustic startle response in adolescents and adults with 22q11.2 deletion syndrome

Background22q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS subjects' acoustic startle responses (ASRs), which putatively index psychosis risk. Latency of the ASR is a presumptive marker of neural processing speed and is prolonged (slower) in schizophrenia. ASR measures correlate with increased psychosis risk, depend on glutamate and dopamine receptor signaling, and could serve as translational biomarkers in interventions for groups at high psychosis risk. MethodsStartle magnitude, latency, and prepulse inhibition were assessed with a standard acoustic startle paradigm in 31 individuals with 22q11.2DS and 32 healthy comparison (HC) subjects. Surface electrodes placed on participants' orbicularis oculi recorded the electromyographic signal in ASR eyeblinks. Individuals without measurable startle blinks in the initial habituation block were classified as non-startlers. ResultsAcross the startle session, the ASR magnitude was significantly lower in 22q11DS subjects than HCs because a significantly higher proportion of 22q11DS subjects were non-startlers. Latency of the ASR to pulse-alone stimuli was significantly slower in 22q11DS than HC subjects. Due to the overall lower 22q11DS startle response frequency and magnitudes prepulse inhibition could not be analyzed. ConclusionsReduced magnitude and slow latency of 22q11DS subjects' responses suggest reduced central nervous system and neuronal responsiveness. These findings are consistent with significant cognitive impairments observed in 22q11DS subjects. Further research is needed to untangle the connections among basic neurotransmission dysfunction, psychophysiological responsiveness, and cognitive impairment.

Association of Lower Rostral Anterior Cingulate GABA+ and Dysregulated Cortisol Stress Response With Altered Functional Connectivity in Young Adults With Lifetime Depression: A Multimodal Imaging Investigation of Trait and State Effects.

Preclinical work suggests that excess glucocorticoids and reduced cortical γ-aminobutyric acid (GABA) may affect sex-dependent differences in brain regions implicated in stress regulation and depressive phenotypes. The authors sought to address a critical gap in knowledge, namely, how stress circuitry is functionally affected by glucocorticoids and GABA in current or remitted major depressive disorder (MDD). Multimodal imaging data were collected from 130 young adults (ages 18-25), of whom 44 had current MDD, 42 had remitted MDD, and 44 were healthy comparison subjects. GABA+ (γ-aminobutyric acid and macromolecules) was assessed using magnetic resonance spectroscopy, and task-related functional MRI data were collected under acute stress and analyzed using data-driven network modeling. Across modalities, trait-related abnormalities emerged. Relative to healthy comparison subjects, both clinical groups were characterized by lower rostral anterior cingulate cortex (rACC) GABA+ and frontoparietal network amplitude but higher amplitude in salience and stress-related networks. For the remitted MDD group, differences from the healthy comparison group emerged in the context of elevated cortisol levels, whereas the MDD group had lower cortisol levels than the healthy comparison group. In the comparison group, frontoparietal and stress-related network connectivity was positively associated with cortisol level (highlighting putative top-down regulation of stress), but the opposite relationship emerged in the MDD and remitted MDD groups. Finally, rACC GABA+ was associated with stress-induced changes in connectivity between overlapping default mode and salience networks. Lifetime MDD was characterized by reduced rACC GABA+ as well as dysregulated cortisol-related interactions between top-down control (frontoparietal) and threat (task-related) networks. These findings warrant further investigation of the role of GABA in the vulnerability to and treatment of MDD.

Intrinsic connectivity demonstrates a shared role of the posterior cingulate for cue reactivity in both gambling and cocaine use disorders

Cue reactivity is relevant across addictive disorders as a process relevant to maintenance, relapse, and craving. Understanding the neurobiological foundations of cue reactivity across substance and behavioral addictions has important implications for intervention development. The present study used intrinsic connectivity distribution methods to examine functional connectivity during a cue-exposure fMRI task involving gambling, cocaine and sad videos in 22 subjects with gambling disorder, 24 with cocaine use disorder, and 40 healthy comparison subjects. Intrinsic connectivity distribution implicated the posterior cingulate cortex (PCC) at a stringent whole-brain threshold. Post-hoc analyses investigating the nature of the findings indicated that individuals with gambling disorder and cocaine use disorder exhibited decreased connectivity in the posterior cingulate during gambling and cocaine cues, respectively, as compared to other cues and compared to other groups. Brain-related cue reactivity in substance and behavioral addictions involve PCC connectivity in a content-to-disorder specific fashion. The findings suggesting that PCC-related circuitry underlies cue reactivity across substance and behavioral addictions suggests a potential biomarker for targeting in intervention development.

Temperamental and Neurocognitive predictors in Korean basketball league draft selection

Introduction The Korean Basketball League(KBL) holds an annual draft to allow teams to select new players, mostly graduates from the elite college basketball teams even though some are from high school teams. In sports games, many factors might influence the success of an athlete. In addition to possessing excellent physical and technical factors, success in a sports game is also influenced by remarkable psychological factors. Several studies reported that elite sports players can control their anxiety during competition, which may lead to better performance. In particular, the temperament and characteristics of players have been regarded as crucial determinants of the player’s performance and goal. In this regard, numerous studies suggest that personality is considered to be an important predictor of long-term success in professional sportsObjectivesBased on previous reports and studies, we hypothesized that physical status, temperament and characteristics, and neurocognitive functions of basketball players could predict the result of KBL draft selection. Especially, temperament and characteristics were associated with the result of KBL selection. The basketball performances including average scores and average rebound were associated with emotional perception and mental rotation.MethodsWe recruited the number of 44 college elite basketball players(KBL selection, n=17; Non-KBL selection, n=27), and the number of 35 age-matched healthy comparison subjects who major in sports education in college. All participants were assessed with the Temperament and Character Inventory(TCI), Sports Anxiety Scales(SAS), Beck Depression Inventory(BDI), Perceived Stress Scale (PSS-10), Trail Making Test(TMT), and Computerized Neuro-cognitive Test(CNT) for Emotional Perception and Mental Rotation.ResultsCurrent results showed that physical status, temperament and characteristics, and Neurocognitive functions of college basketball players could predict the KBL draft selection. Among temperament and characteristics, novelty seeking and reward dependence were associated with KBL draft selection. The basketball performances including average scores and average rebound were associated with emotional perception and mental rotation.ConclusionsIn order to be a good basketball player for a long time, it was confirmed that temperamental factors and Neurocognitive factors were very closely related. Furthermore, it is also judged that these results can be used as basic data to predict potential professional basketball players.Disclosure of InterestNone Declared

Cortical white matter microstructural alterations underlying the impaired gamma-band auditory steady-state response in schizophrenia

The gamma-band auditory steady-state response (ASSR), primarily generated from the auditory cortex, has received substantial attention as a potential brain marker indicating the pathophysiology of schizophrenia. Previous studies have shown reduced gamma-band ASSR in patients with schizophrenia and demonstrated correlations with impaired neurocognition and psychosocial functioning. Recent studies in clinical and healthy populations have suggested that the neural substrates of reduced gamma-band ASSR may be distributed throughout the cortices surrounding the auditory cortex, especially in the right hemisphere. This study aimed to investigate associations between the gamma-band ASSR and white matter alterations in the bundles broadly connecting the right frontal, parietal and occipital cortices to clarify the networks underlying reduced gamma-band ASSR in patients with schizophrenia. We measured the 40 Hz ASSR using electroencephalography and diffusion tensor imaging in 42 patients with schizophrenia and 22 healthy comparison subjects. The results showed that the gamma-band ASSR was positively correlated with fractional anisotropy (an index of white matter integrity) in the regions connecting the right frontal, parietal and occipital cortices in healthy subjects (β = 0.41, corrected p = 0.075, uncorrected p = 0.038) but not in patients with schizophrenia (β = 0.17, corrected p = 0.46, uncorrected p = 0.23). These findings support our hypothesis that the generation of gamma-band ASSR is supported by white matter bundles that broadly connect the cortices and that these relationships may be disrupted in schizophrenia. Our study may help characterize and interpret reduced gamma-band ASSR as a useful brain marker of schizophrenia.

Transdiagnostic psychopathology in the light of robust single-trial event-related potentials.

Recent evidence indicates that event-related potentials (ERPs) as measured on the electroencephalogram (EEG) are more closely related to transdiagnostic, dimensional measures of psychopathology (TDP) than to diagnostic categories. A comprehensive examination of correlations between well-studied ERPs and measures of TDP is called for. In this study, we recruited 50 patients with emotional disorders undergoing 14 weeks of transdiagnostic group psychotherapy as well as 37 healthy comparison subjects (HC) matched in age and sex. HCs were assessed once and patients three times throughout treatment (N = 172 data sets) with a battery of well-studied ERPs and psychopathology measures consistent with the TDP framework The Hierarchical Taxonomy of Psychopathology (HiTOP). ERPs were quantified using robust single-trial analysis (RSTA) methods and TDP correlations with linear regression models as implemented in the EEGLAB toolbox LIMO EEG. We found correlations at several levels of the HiTOP hierarchy. Among these, a reduced P3b was associated with the general p-factor. A reduced error-related negativity correlated strongly with worse symptomatology across the Internalizing spectrum. Increases in the correct-related negativity correlated with symptoms loading unto the Distress subfactor in the HiTOP. The Flanker N2 was related to specific symptoms of Intrusive Cognitions and Traumatic Re-experiencing and the mismatch negativity to maladaptive personality traits at the lowest levels of the HiTOP hierarchy. Our study highlights the advantages of RSTA methods and of using validated TDP constructs within a consistent framework. Future studies could utilize machine learning methods to predict TDP from a set of ERP features at the subject level.

Association of Cytokine IL-17, IL-4, IL-6, and IL-12 Gene Polymorphisms in Rheumatoid Arthritis Patients in a Tertiary Care Hospital in Bangladesh.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that involves cytokines in its pathogenesis. This study is aimed at investigating if gene polymorphisms in cytokines like IL-17, IL-4, IL-6, and IL-12 affect RA susceptibility and severity in the Bangladeshi population. This was a cross-sectional comparative study that included 40 diagnosed RA patients according to the American College of Rheumatology (ACR) criteria 2010, who were free from other rheumatological diseases, and 40 healthy subjects for comparison. The study used PCR-RFLP to determine the IL-17, IL-4, IL-6, and IL-12 cytokine gene polymorphisms. Patients had a mean age of 37.22 ± 6.70 years. Among the patients, 31 were female and 9 were male. The mean disease duration was 18.11 ± 7.39 months. The study found that rheumatoid arthritis patients with the IL-17F (7488 A/G) polymorphism with GG genotype (P = 0.006, OR = 8.56, 95% CI = 1.77 - 41.33) and IL-12B (1188 A/C) polymorphism with AC (P = 0.012, OR = 3.69, 95% CI = 1.43 - 9.53) and CC (P = 0.013, OR = 7.58, 95% CI = 1.56 - 36.88) genotypes were significantly associated with disease risk. Furthermore, patients with the IL-17F (7488) GG genotype and IL-12B (1188) AC and CC genotypes had higher rheumatoid arthritis disease severity and activity parameters. The study found no significant association between polymorphisms involving IL-4 (590 C/T) and IL-6 (174 G/C) genes and rheumatoid arthritis disease risk in the Bangladeshi population. Gene polymorphisms in cytokines IL-17F (7488 A/G) and IL-12B (1188 A/C) can predict disease susceptibility and severity in Bangladeshi rheumatoid arthritis patients.

Robust single-trial event-related potentials differentiate between distress and fear disorders.

Recent evidence indicates that measures of brain functioning as indexed by event-related potentials (ERPs) on the electroencephalogram align more closely to transdiagnostic measures of psychopathology than to categorical taxonomies. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a transdiagnostic, dimensional framework aiming to solve issues of comorbidity, symptom heterogeneity, and arbitrary diagnostic boundaries. Based on shared features, the emotional disorders are allocated into subfactors Distress and Fear. Evidence indicates that disorders that are close in the HiTOP hierarchy share etiology, symptom profiles, and treatment outcomes. However, further studies testing the biological underpinnings of the HiTOP are called for. In this study, we assessed differences between Distress and Fear in a range of well-studied ERP components. In total, 50 patients with emotional disorders were divided into two groups (Distress, N = 25; Fear, N = 25) according to HiTOP criteria and compared against 37 healthy comparison (HC) subjects. Addressing issues in traditional ERP preprocessing and analysis methods, we applied robust single-trial analysis as implemented in the EEGLAB toolbox LIMO EEG. Several ERP components were found to differ between the groups. Surprisingly, we found no difference between Fear and HC for any of the ERPs. This suggests that some well-established results from the literature, e.g., increased error-related negativity in OCD, are not a shared neurobiological correlate of the Fear subfactor. Conversely, for Distress, we found reductions compared to Fear and HC in several ERP components across paradigms. Future studies could utilize HiTOP-validated psychopathology measures to more precisely define subfactor groups.

Impairment of daily occupations in multiple sclerosis: analysis of neuroimaging, general and social cognition, and reserve

BackgroundMultiple Sclerosis (MS) can impact performance of daily occupations in both relapsing-remitting (RRMS) and secondary-progressive (SPMS) clinical courses. Work force participation decreases with advancing physical disability but the influence of non-motor factors, neuroimaging, and reserve have been scarcely investigated. We aimed to evaluate MRI, clinical, and cognitive (social and general) factors associated with impairment in different daily occupations and address whether cognitive and brain reserve have a positive impact on the ability to maintain these activities. MethodsWe prospectively enrolled persons with MS (PwMS) who underwent clinical examination (Expanded Disability Status Scale – EDSS; Timed 25-Foot Walk Test - T25FW; and the Nine Hole Peg Test - 9HPT), general neuropsychological assessment (Brief Repeatable Battery of Neuropsychological Tests – BRBN, including the Symbol Digit Modalities Test - SDMT), social cognition evaluation (Reading the Mind in the Eyes Test), cognitive reserve questionnaire, and MRI (FreeSurfer). We also enrolled healthy subjects for comparison as a control group. Daily occupations (employment, money management, and driving abilities) were assessed in all individuals with questionnaires. ResultsWe included 62 PwMS (32 RRMS and 30 SPMS; mean age 42.8 years; median educational time 12.75 years) and 67 controls (mean age 39.7; median educational time 12.0 years) which were similar regarding demographics, education, and socioeconomic status (p > 0.1). Most PwMS (67.7%) had work-restrictions. They also reported fewer money management and driving abilities than controls (p < 0.001). Work-restriction was associated with physical disability (p = 0.006), SDMT and BRBN performance (p = 0.035 and p = 0.031, respectively), and T2-lesion volume (p = 0.022), with large effect sizes (d > 0.75). After hierarchical linear regression, money management was associated with hand dexterity, general and social cognition, and cognitive reserve (p < 0.03). Variables associated with driving abilities included fatigue, verbal fluency, striatum volume, and brain reserve (p < 0.05). ConclusionsPwMS have more frequent work-restrictions and impairment in money management and driving abilities compared to controls. Cognitive function, physical disability, and MS-lesion burden are strongly associated with work-restriction. Social cognition can also influence financial capacity. Cognitive and brain reserve can help retain some of these daily occupations.

Effect of recombinant human nerve growth factor treatment on corneal nerve regeneration in patients with neurotrophic keratopathy.

Neurotrophic Keratopathy (NK) is a neurodegenerative corneal disease that results in diminished corneal sensation. Previous studies have found that Cenegermin 0.002%, a recombinant human nerve growth factor (rhNGF), improves corneal epithelial healing in stage 2 and 3 NK patients. However, rhNGF effect on corneal sensation and nerve regeneration has not been well established. Thus, this study aims to analyze the effect of rhNGF on corneal nerve regeneration using in vivo confocal microscopy (IVCM) and on corneal sensitivity in NK patients. This is a retrospective, longitudinal, case-control study that included patients with NK, treated with rhNGF for at least 4 weeks, with pre- and post-treatment IVCM images available for analysis. Chart reviews were conducted documenting prior medical and surgical history, clinical signs and symptoms, and corneal sensation using Cochet-Bonnet esthesiometry. Corneal nerve parameters were assessed by IVCM. Sex- and age-matched reference controls were selected from a database of healthy subjects for comparison. The study included 25 patients, with 22 (88%) stage 1, two (8%) stage 2, and 1 (4%) stage 3 NK patients, with a median age of 64 years (range: 30-93 years). Total, main, and branch nerve densities [median (range) in mm/mm2] were lower in the NK group pre-treatment [2.3 (0.0-21.1); 1.7 (0.0-13.0); 0.5 (0.0-10.2); respectively] vs. controls [22.3 (14.9-29.0); 10.1 (3.2-15.4); and 12.1 (6.2-18.4), (p < 0.0001 for all), respectively]. Post-treatment nerve densities increased compared to pre-treatment to 5.3 (0.0-19.4, p = 0.0083) for total, 3.5 (0.0-13.2, p = 0.0059) for main, and 2.0 (0.0-10.4, p = 0.0251) for branch nerves, but remained lower than controls (p < 0.0001 for all). Corneal sensation increased from 2.3 ± 1.1 cm pre-treatment to 4.1 ± 1.4 cm post-treatment (p = 0.001). Median best corrected visual acuity significantly increased following rhNGF treatment from 0.4 (0.0-1.6) to 0.12 (-0.1 to 1.6) (p = 0.007). Patients with NK treated with at least 4 weeks of rhNGF, showed a significant increase in corneal nerve densities after treatment. A significant increase in corneal sensation, as well as best corrected visual acuity, was observed following treatment.

Diagnostic group differences and exploratory sex differences in intrinsic connectivity during fMRI Stroop in individuals with and without cocaine use disorder

BackgroundSex-/gender-related differences in cognitive control and how they relate to addictions may inform novel treatment options. Cognitive control, including Stroop performance, has been linked to addictions and treatment outcomes. The extent to which women and men with cocaine use disorder (CUD) show brain and behavioral differences relating to Stroop performance has not been previously studied. We examined sex-related differences in Stroop-related brain connectivity in female and male CUD and healthy-comparison (HC) subjects. Methods40 individuals with CUD (20 female) and 40 HC (20 female) subjects matched on age, race, and ethnicity completed an fMRI Stroop task. Intrinsic connectivity distribution (ICD) and mean-adjusted ICD analyses were conducted to identify differences related to sex and diagnostic group. Stroop task performance was also considered. ResultsBehavioral results confirmed a Stroop effect. A main effect of diagnostic group indicated that the CUD versus HC group showed lower connectivity in the prefrontal cortex, frontal gyrus, cingulate gyrus, precuneus, cerebellum, and somatosensory, visual, and auditory areas. An exploratory main effect of sex suggested that males may show relatively lower connectivity than females in the cerebellum and brainstem, although connectivity was largely similar across sexes. ConclusionsIntrinsic connectivity during cognitive control varied by diagnostic group and possibly by sex. The findings suggest that interventions targeting cognitive control in CUD should consider sex.

MIDLINE BRAIN STRUCTURES IN ADULT NIEMANN-PICK TYPE C DISEASE: A CROSS-SECTIONAL STUDY.

A range of neuropathological changes occur in the brains of individuals with adult Niemann-Pick type C disease (NPC), a recessive disorder of cholesterol trafficking that results in in accumulation of cholesterol and gangliosides in lysosomes, particularly in neurons. One of the most significant regions of grey matter loss occurs in the thalami, which abut the midline. What is not known is whether these are neurodevelopmental in origin well prior to symptomatic onset. We aimed to examine other markers of midline developmental anomalies in adults with NPC. We examined the size of adhesio interthalamica (AI) and cavum septum pellucidum (CSP) (if present) in 9 individuals diagnosed with NPC and 9 healthy comparison subjects, matched for age and gender, using a 3T magnetic resonance volumetric sequence and measured the length of the AI and CSP in mm. We found that 5/9 NPC patients and 0/9 controls had a missing AI. AI length was significantly shorter in the patient group. No subject in other group had a large CSP, and CSP length did not differ. Duration of illness showed a trend to a negative correlation with AI length in patients. Our findings suggest that adult NPC patients show some markers of early neurodevelopmental disturbance, matching findings seen in psychotic disorders. The differences in AI, but not CSP, suggest neurodevelopmental change may occur early in gestation rather than post-partum. The relationship with duration of illness suggests that there may be atrophy over time in these structures, consistent with prior analyses of grey matter regions in NPC.

Elevated serum leptin is associated with attenuated reward anticipation in major depressive disorder independent of peripheral C-reactive protein levels

Major depressive disorder (MDD) is associated with immunologic and metabolic alterations linked to central processing dysfunctions, including attenuated reward processing. This study investigated the associations between inflammation, metabolic hormones (leptin, insulin, adiponectin), and reward-related brain processing in MDD patients with high (MDD-High) and low (MDD-Low) C-reactive protein (CRP) levels compared to healthy comparison subjects (HC). Participants completed a blood draw and a monetary incentive delay task during functional magnetic resonance imaging. Although groups did not differ in insulin or adiponectin concentrations, both MDD-High (Wilcoxon p = 0.004, d = 0.65) and MDD-Low (Wilcoxon p = 0.046, d = 0.53) showed higher leptin concentrations than HC but did not differ from each other. Across MDD participants, higher leptin levels were associated with lower brain activation during reward anticipation in the left insula (r = − 0.30, p = 0.004) and left dorsolateral putamen (r = -− 0.24, p = 0.025). In contrast, within HC, higher leptin concentrations were associated with higher activation during reward anticipation in the same regions (insula: r = 0.40, p = 0.007; putamen: r = 0.37, p = 0.014). Depression may be characterized by elevated pro-inflammatory signaling via leptin concentrations through alternate inflammatory pathways distinct to CRP.

Deep psychophysiological phenotyping of adolescents and adults with 22q11.2 deletion syndrome: a multilevel approach to defining core disease processes

Background22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal interstitial-deletion disorder, occurring in approximately 1 in 2000 to 6000 live births. Affected individuals exhibit variable clinical phenotypes that can include velopharyngeal anomalies, heart defects, T-cell-related immune deficits, dysmorphic facial features, neurodevelopmental disorders, including autism, early cognitive decline, schizophrenia, and other psychiatric disorders. Developing comprehensive treatments for 22q11.2DS requires an understanding of both the psychophysiological and neural mechanisms driving clinical outcomes. Our project probes the core psychophysiological abnormalities of 22q11.2DS in parallel with molecular studies of stem cell-derived neurons to unravel the basic mechanisms and pathophysiology of 22q11.2-related psychiatric disorders, with a primary focus on psychotic disorders. Our study is guided by the central hypothesis that abnormal neural processing associates with psychophysiological processing and underlies clinical diagnosis and symptomatology. Here, we present the scientific background and justification for our study, sharing details of our study design and human data collection protocol.MethodsOur study is recruiting individuals with 22q11.2DS and healthy comparison subjects between the ages of 16 and 60 years. We are employing an extensive psychophysiological assessment battery (e.g., EEG, evoked potential measures, and acoustic startle) to assess fundamental sensory detection, attention, and reactivity. To complement these unbiased measures of cognitive processing, we will develop stem-cell derived neurons and examine neuronal phenotypes relevant to neurotransmission. Clinical characterization of our 22q11.2DS and control participants relies on diagnostic and research domain criteria assessments, including standard Axis-I diagnostic and neurocognitive measures, following from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and the North American Prodrome Longitudinal Study (NAPLS) batteries. We are also collecting measures of autism spectrum (ASD) and attention deficit/hyperactivity disorder (ADHD)-related symptoms.DiscussionStudying 22q11.2DS in adolescence and adulthood via deep phenotyping across multiple clinical and biological domains may significantly increase our knowledge of its core disease processes. Our manuscript describes our ongoing study’s protocol in detail. These paradigms could be adapted by clinical researchers studying 22q11.2DS, other CNV/single gene disorders, or idiopathic psychiatric syndromes, as well as by basic researchers who plan to incorporate biobehavioral outcome measures into their studies of 22q11.2DS.

Natural Oscillatory Frequency Slowing in the Premotor Cortex of Early-Course Schizophrenia Patients: A TMS-EEG Study.

Despite the heavy burden of schizophrenia, research on biomarkers associated with its early course is still ongoing. Single-pulse Transcranial Magnetic Stimulation coupled with electroencephalography (TMS-EEG) has revealed that the main oscillatory frequency (or "natural frequency") is reduced in several frontal brain areas, including the premotor cortex, of chronic patients with schizophrenia. However, no study has explored the natural frequency at the beginning of illness. Here, we used TMS-EEG to probe the intrinsic oscillatory properties of the left premotor cortex in early-course schizophrenia patients (<2 years from onset) and age/gender-matched healthy comparison subjects (HCs). State-of-the-art real-time monitoring of EEG responses to TMS and noise-masking procedures were employed to ensure data quality. We found that the natural frequency of the premotor cortex was significantly reduced in early-course schizophrenia compared to HCs. No correlation was found between the natural frequency and age, clinical symptom severity, or dose of antipsychotic medications at the time of TMS-EEG. This finding extends to early-course schizophrenia previous evidence in chronic patients and supports the hypothesis of a deficit in frontal cortical synchronization as a core mechanism underlying this disorder. Future work should further explore the putative role of frontal natural frequencies as early pathophysiological biomarkers for schizophrenia.

Accelerated long-term forgetting of recall and recognition memory in people with epilepsy

PurposePersons with epilepsy (PWE) report memory deficits as one of the most distressing aspects of their disorder. Recently, a long-term memory deficit known as Accelerated Long-Term Forgetting (ALF) has been described in PWE. ALF is characterized by the initial retention of learned information, followed by an accelerated rate of memory decay. However, the rate of ALF varies widely across literature and it is unclear how it impacts different memory retrieval types. The current study aimed to capture the time course of ALF on both free recall and recognition memory using a movie-based task in PWE. MethodsA sample of 30 PWE and 30 healthy comparison (HC) subjects watched a nature documentary and were tested on their recall and recognition of the film’s content immediately after viewing and at delays of 24 hours, 48 hours, and 72 hours. Participants also rated the confidence they had in their recognition memory trial responses. ResultsFor recall, PWE exhibit ALF at 72 hours (β = −19.840, SE = 3.743, z(226) = −5.301, p < 0.001). For recognition, PWE had decreased performance compared to controls at the 24-hour (β = −10.165, SE = 4.174, z(224) = −3.166, p = 0.004), 48-hour (β = −8.113, SE = 3.701, z(224) = −2.195, p = 0.044), and 72-hour (β = −10.794, SE = 3.017, z(224) = −3.295, p = 0.003) delays. The PWE group showed positive correlations (tau = 0.165, p < 0.001) between confidence ratings and accuracy, with higher confidence reflecting successful recognition. PWE were 49% less likely to answer either retrieval type correctly at 72 hours (OR 0.51, 95% CI [0.35, 0.74], p < 0.001). Left hemispheric seizure onset decreased the odds of successful retrieval by 88% (OR 0.12, 95% CI [0.01, 0.42], p = 0.019). ConclusionsThese findings provide evidence of ALF in PWE, with a differential impact on recall and recognition memory. This further supports the call to include ALF assessments in standard memory evaluations in PWE. Additionally, identifying the neural correlates of ALF in the future will be important in developing targeted therapies to alleviate the burden of memory impairment for PWE.

Applying Functional Imaging to Clinical Practice: Are We Making Progress Toward Its Promise?

Applying Functional Imaging to Clinical Practice: Are We Making Progress Toward Its Promise?