Psychiatry Research: Neuroimaging

Behavioural, structural and functional neuroimaging differences have been demonstrated between individuals with antisocial personality disorder with (ASPD+P) or without psychopathy (ASPD-P). However, the underlying mechanisms for such differences are poorly understood, hampering progress in the development of drug treatments for this population. Intranasal oxytocin (OT) has garnered significant attention due to its prosocial effects in healthy individuals. We sought to establish the impact of OT on resting-state brain function in individuals with ASPD, and to explore whether modulation differs between individuals with and without psychopathy. We used arterial spin labelling (ASL) to measure regional cerebral blood flow (rCBF) to investigate brain function at rest and modulation of key disease-targets by a single acute dose of OT (40 IU). We used a double-blind, placebo-controlled, crossover design in males with a history of violent offending with ASPD+P (N = 17) or ASPD-P (N = 14) and a group of healthy male non-offenders (N = 22). Both ASPD subtypes showed reduced rCBF in frontotemporal regions compared to non-offenders. However, those with ASPD+P demonstrated significantly greater rCBF increases in posterior default mode network regions compared to those with ASPD-P. OT administration selectively reduced rCBF in the left basal ganglia of the ASPD-P group, an effect not observed in the ASPD+P or non-offender groups. Our results provide further evidence of functional brain differences between ASPD+P and ASPD-P groups, and a differential modulating effect of oxytocin. The neurobiological distinctions between ASPD+P and ASPD-P groups are important considerations for future therapeutic developments.

Altered brain chemistry is thought to contribute to impairments in cognitive and perceptual functioning in people with psychotic psychopathology (PwPP). As heritable genetic factors shape the development of psychosis, these alterations in brain chemistry may extend to biological relatives of PwPP. Magnetic resonance spectroscopy (MRS) is a non-invasive method for quantifying the concentration of various neurochemicals in the human brain. A number of MRS studies in different brain regions have been performed in PwPP, and to a lesser extent in relatives, but results have been largely mixed. There are a number of methodological issues that may have influenced previous findings. We show here that when such issues are addressed, MRS reveals a pattern of neurometabolic dysfunction in PwPP. We acquired MRS data at 7 tesla with an ultra-short echo time (TE = 8 ms) sequence in both occipital and prefrontal cortices from 43 healthy controls, 42 first-degree biological relatives, and 64 PwPP. We saw reduced levels of N-acetyl-aspartate (NAA) in the occipital lobe in PwPP and their relatives (versus controls), and lower N-acetyl-aspartyl-glutamate (NAAG) in prefrontal cortex in PwPP versus controls. Surprisingly, we also saw markedly increased levels of glucose in both occipital and prefrontal cortices in PwPP. Hierarchical clustering analyses showed that higher glucose levels were linked to higher psychiatric symptom levels and impairments in visual task performance. Together, our findings point to a disruption in neural metabolism across multiple brain areas in PwPP that is associated with impaired cognitive and perceptual functioning.

IntroductionBipolar Disorder (BD) is characterized by marked disruptions in emotional regulation and cognitive control, often accompanied by structural abnormalities in the brains white matter. Diffusion tensor imaging (DTI) offers a window into white matter microstructure through metrics such as fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). This study aimed to examine white matter tract alterations in individuals with BD compared to healthy controls (HCs) and to explore potential associations between DTI metrics and clinical symptom severity. MethodsWe conducted a voxel-wise whole-brain DTI analysis in a sample of BD patients and age-matched HCs, focusing on FA, MD, RD, and AD values. Group comparisons were performed to identify significant differences in white matter integrity. In addition, we assessed correlations between DTI metrics and psychological assessment scores to investigate links between structural alterations and clinical features. ResultsCompared to HCs, BD patients exhibited significantly lower FA in several major white matter tracts, including the cingulum (olfactory tract), forceps minor of the corpus callosum, fornix, inferior fronto-occipital fasciculus, and superior longitudinal fasciculus. These reductions suggest disrupted microstructural coherence. In parallel, elevated MD, RD, and AD in overlapping regions point to possible myelin degeneration or axonal injury. However, associations between DTI metrics and psychological symptom scores were weak and did not reach statistical significance. Discussion/ConclusionThese findings reinforce the presence of widespread white matter abnormalities in BD, particularly in tracts relevant to emotional and cognitive processing. While structural disruptions were evident, their weak correlations with symptom severity highlight the complex relationship between brain microstructure and clinical expression in BD. Future studies are warranted to clarify the diagnostic and prognostic relevance of DTI-based biomarkers in mood disorders.

Neural underpinnings of Parkinsons Disease psychosis (PDP) remain unclear to this day with relatively few studies and reviews available. Using a systematic review approach, here we aimed to qualitatively synthesize evidence from studies investigating PD psychosis-specific alterations in brain structure, function or chemistry using different neuroimaging modalities. PubMed, Web of Science and Embase databases were searched for fMRI, rsfMRI, DTI, PET, and SPECT studies comparing PDP patients with PD patients without psychosis (PDnP). We report findings from 18 studies (291 PDP patients, mean age {+/-} SD = 68.65 {+/-} 3.76 years; 48.5% males; 433 PDnP patients, mean age {+/-} SD = 66.97 {+/-} 3.80 years; 52% males). Qualitative synthesis revealed widespread patterns of altered brain function across task-based and resting-state fMRI studies in PDP compared to PDnP patients. Similarly, white matter abnormalities were reported in parietal, temporal, and occipital regions. Hypometabolism and reduced dopamine transporter binding were also reported whole brain and in subcortical areas. This suggests extensive alterations affecting regions involved in high order visual processing and attentional networks.

Compulsive sexual behavior disorder (CSBD) and problematic pornography use (PPU) have garnered increasing attention as clinically significant conditions, potentially falling within the spectrum of behavioral addictions or impulse control disorders. However, neuroimaging findings to date have been inconsistent and scattered across studies, limiting our understanding of the neural mechanisms underlying these conditions. This protocol outlines a systematic review and coordinate-based meta-analysis (CBMA) designed to synthesize structural and functional neuroimaging results related to CSBD and PPU. By aggregating stereotactic coordinates from eligible studies, we aim to identify convergent patterns of brain alterations, particularly in regions implicated in reward processing, executive control, and salience attribution. The inclusion of both resting-state and task-based imaging data is expected to improve statistical power and facilitate a more integrative characterization of the neural correlates of CSBD and PPU. Findings from this review may help clarify the extent to which these conditions share neurobiological features with other addictive behaviors. This will advance theoretical models of dysregulated sexual behavior and inform future diagnostic and therapeutic strategies.

BackgroundWhile long-range white matter (WM) connectivity has been widely studied in schizophrenia-spectrum disorders (SSDs), recent evidence highlights the importance of local network disruptions. Superficial white matter (SWM), located between cortex and WM, comprises short association fibers supporting local connectivity. As SWM matures in the latter stages of development relative to deep WM structures, it may be particularly vulnerable to neurodevelopmental disruptions observed in SSDs. However, its complex fiber architecture and proximity to the cortex pose challenges for conventional diffusion tensor imaging. MethodsTo overcome these limitations, we applied an advanced diffusion MRI approach to assess fiber density (FD) in the SWM of 78 individuals with early psychosis (age 22.0{+/-}3.0, 45% female) and 78 controls (age 21.8{+/-}3.2, 45% female). ResultsEarly psychosis individuals showed widespread reductions in SWM FD, particularly in occipital, temporal, parietal, and insular regions, whereas no significant group differences were detected using fractional anisotropy from tensor imaging. FD reductions were associated with reduced cortical thickness (p<0.0005, r=0.32) and surface area (p=0.006, r=0.23), indicating coordinated cortex-WM alterations. SWM FD was associated with processing speed (p=0.0029) and working memory (p=0.048). Further, SWM mediated the relationship between cortical structure and processing speed in frontal and parietal regions. ConclusionsThese findings highlight SWM, supporting local network connectivity, as a tissue compartment showing widespread alterations in SSDs. By implementing an advanced diffusion MRI technique, we were able to assess changes that were specific to the complex WM at the cortical boundary, and to demonstrate functionally important alterations in this difficult-to-characterize tissue compartment.

PurposePeople with psychotic psychopathology (PwPP) often experience subtle variations in visual perception, which can be quantified experimentally. In the contrast surround suppression illusion, a central pattern appears to have lower contrast in the presence of a surrounding pattern. PwPP typically show weaker contrast suppression from the surround than controls, but the mechanisms underlying this difference are still poorly understood. MethodsWe assessed perceptual and neural surround suppression in 38 controls, 44 first-degree biological relatives of PwPP, and 64 PwPP as part of the Psychosis Human Connectome Project. To better understand neural mechanisms contributing to diminished surround suppression we quantified contrast discrimination thresholds and examined 7 tesla fMRI responses in the lateral geniculate nucleus (LGN), primary visual cortex (V1), and lateral occipital complex (LOC). Additionally, we measured the concentration of {gamma}-aminobutyric acid (GABA; an inhibitory neurotransmitter) in occipital cortex using 7 T MR spectroscopy. ResultsResponses in LOC showed the expected effect of weaker surround suppression in PwPP and relatives versus controls. However, in V1 we found no differences in surround suppression strength between controls, relatives, and PwPP. Additionally, we saw no behavioral evidence for reduced surround suppression in PwPP. Suppression metrics were not significantly correlated with occipital GABA levels or symptom measures. Multi-voxel pattern analysis of V1 fMRI responses revealed a group difference in decoding Surround vs. No Surround, with a trend toward lower accuracy in PwPP vs. controls. ConclusionOur results suggest subtle differences in visual center-surround processing among people with schizophrenia. Possible explanations for the discrepancy with previous findings include differences in task design and the deployment of spatial attention across groups. Poorer decoding of center vs. surround may suggest neural representations of spatial context in V1 are less reliable in PwPP.

ObjectiveThe visual system is a significant site of pathology in psychosis spectrum disorders. However, there is limited research investigating human visual cortex (VC) subregions in this population. Using data from the Bipolar-Schizophrenia Network on Intermediate Phenotypes Consortium (BSNIP-1, BSNIP-2, PARDIP), this study examined structural measures in VC subregions in individuals with psychosis spectrum disorders. MethodsCortical surface area and thickness in five VC subregions (hOc1, hOc2, hOc3v, hOc4v, MT) were quantified using FreeSurfer v7.1.0 and compared between individuals with psychosis (n=1211) and healthy controls (n=734). Regional specificity was examined by controlling for total surface area or mean cortical thickness. ComBat was used to harmonize scanner effects. Associations between VC measures and symptom severity, cognition, and childhood trauma scores were assessed. ResultsIndividuals with psychosis demonstrated smaller surface area in hOc1, hOc2, and hOc3v, and lower cortical thickness in all five VC subregions compared to healthy controls. Thickness reductions in hOc1, hOc4v, and MT were regionally specific. hOc4v and MT were among the top three regions exhibiting the most robust cortical thickness deficits (d = -0.38 to -0.40) across all VC and Desikan-Killiany brain regions. Lower thickness in mid-level visual subregions were associated with greater positive symptoms, poorer cognition, and higher childhood trauma scores. ConclusionsThis study demonstrates that the visual cortex is among the most profoundly affected brain regions in psychotic disorders. Different patterns of area and thickness changes across early and mid-level visual subregions, along with their varying associations with clinical measures, suggest distinct developmental and disease-related influences.

Changes in basic associative learning processes have been identified in several psychiatric conditions. However, it remains unknown whether these findings result from ongoing psychopathology or represent an underlying transdiagnostic risk factor for multiple clinical states. In this study, 72 participants with subclinical psychopathology, 23 of whom met criteria for the clinical high-risk for psychosis transdiagnostic risk syndrome (CHR+), completed a fear conditioning and generalization paradigm while functional magnetic resonance imaging (fMRI) data were collected. During this procedure, participants were presented with face stimuli that were either paired (CS+) or not paired (CS-) with a mild electrical shock, as well as eight face "morphs" (between the CS+ and CS-) tailored to each participants perceptual discrimination ability. Following the scan session, participants rated the likelihood that each stimulus had been previously followed by a shock. Fear generalization-related neural responses and the memory ratings were then examined using both categorical and individual-level, psychometric modeling approaches. Expected patterns of fear generalization-related responses were observed in the anterior insula and superior frontal gyrus, and in the memory ratings. The psychometric modeling analysis revealed a significantly greater threshold in responses of the left anterior insula, representing a wider fear generalization curve, in the CHR+, compared to the control, group. Moreover, across the whole sample, symptoms of anxiety were associated with a wider fear generalization threshold. Thus, these findings suggest that specific features of one basic associative memory process, fear generalization, may be linked to CHR status and transdiagnostic risk for psychiatric illness.

Psychosis is frequently associated with the occurrence of visual hallucinations (VH), but their etiology remains largely unknown. While patients with psychosis show deficits on various behavioral visual and attentional tasks, previous studies have not specifically related these deficits to the presence of VH. This suggests that tasks used in these studies do not target the visual-cognitive neural mechanisms that mediate VH, which in turn limits the development of effective therapies. We therefore designed a study to target these mechanisms directly. In this case control study we asked patients with psychosis who had previously experienced VH to indicate when they recognized objects that were gradually emerging from dynamic visual noise, while scanning their brains using functional Magnetic Resonance Imaging. In a previous study, this recognition task was used to identify the neural basis of VH in patients with Parkinsons Disease. Based on this earlier work, we decided to test the following hypothesis: when compared to psychosis patients not experiencing VH and age-matched healthy controls, psychosis patients with VH show reduced occipital activity and frontal activity around the moment of recognition (known as pop-out). For all groups, neuroimaging revealed increased activity in all examined visual areas around pop-out. However, psychosis patients with VH showed reduced occipital responsiveness, especially in the inferior part of the bilateral lateral occipital complex, a region known to play a key role in object recognition. We did not observe altered frontal or prefrontal activity before pop-out in this group. A possible explanation is that the relatively sustained activation of the visual memory-related angular gyri around pop-out may have compensated for the impaired early visual processing in psychosis patients with VH. We discuss our results in terms of current theories of visual hallucinations, such as predictive coding and contextual modulation. Our study is the first to show that visual processing deficits contribute to the occurrence of VH in psychosis. These findings could be used to develop tests to identify the visual-cognitive mechanisms that mediate VH in this group.

ObjectivesHyperorality is one of the core features of behavioral variant frontotemporal dementia (bvFTD), however, the cognitive, psychiatric, and neuroanatomic correlates of hyperorality across disease stages remain unclear. This study works to fill this knowledge gap by exploring these associations in the early and advanced stages of bvFTD. MethodsParticipants with sporadic and genetic bvFTD were enrolled in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium (ALLFTD). The primary analyses used baseline data to compare cognitive and psychiatric symptoms in those with and without hyperorality stratified by disease severity. Linear multivariable regressions adjusting for age and total intracranial volume were used to examine baseline associations between regional gray matter volumes and hyperorality status. Five anatomic regions of interest were pre-selected for analysis based on previously identified neuroanatomic correlates of hyperorality in bvFTD. ResultsHyperorality was present in 50% of early-stage bvFTD participants (n = 136) and was associated with higher rates of ritualistic/compulsive behavior. Hyperorality was present in 63% of advanced-stage participants (n = 208) and was associated higher rates of apathy, and ritualistic/compulsive behavior. Regional gray matter volumes were similar in those with and without hyperorality in early-stage participants. In the advanced-stage participants, hyperorality was associated with lower gray matter volumes in the right dorsal and ventral striatum. ConclusionsHyperorality emerges early in bvFTD and is accompanied by deficits in social cognition and complex-ritualistic behavior prior to clinically significant gray matter volume loss. These findings suggest that early identification and treatment of hyperorality could improve neuropsychiatric trajectories in bvFTD.

Verbal fluency tasks are often used in neuropsychological research and may have predictive and diagnostic utility in psychiatry and neurology. However, researchers using verbal fluency have uncritically assumed that there are no category-or phoneme-specific effects on verbal fluency performance. We recruited 16 healthy young adult subjects and administered two semantic (animals, trees) and phonemic (K, M) fluency tasks. Because of the small sample size, results should be regarded as preliminary and exploratory. On the animal compared to the tree task, subjects produced significantly more legal words, had a significantly lower intrusion rate, significantly shorter first-response latencies and final silence periods, as well as significantly shorter between-cluster response latencies. These differences may be explained by differences in the category sizes, integrity of the categories borders, and efficiency of the functional connectivity between subcategories. On the K compared to the M task, subjects produced significantly more legal words and had significantly shorter between-cluster response times. Counterintuitively, a corpus analysis revealed there are more words starting with [&lt;]m[&gt;] compared to [&lt;]k[&gt;] in the experimental language. Our results potentially have important implications for research utilizing verbal fluency, including decreased reproducibility, questionable reliability of diagnostic and predictive tools based on verbal fluency, decreased knowledge accumulation, and increased number of publications with potentially misleading clinical interpretations.

ObjectiveThe pathophysiology of psychosis remains unclear. Preclinical, postmortem, and imaging evidence implicates iron and neuromelanin, but the consistency and magnitude of effects are uncertain. We aimed to characterise brain iron and neuromelanin alterations in psychosis through a systematic review and meta-analysis of iron-sensitive MRI and neuromelanin-sensitive MRI (NM-MRI) studies. MethodsWe searched EMBASE, PubMed, and PsycINFO from inception to October 31, 2025, for case-control studies using iron-sensitive MRI or NM-MRI in patients with psychosis. We used random-effects models to calculate effect sizes (Hedges g) and meta-regressions to examine clinical confounders. The primary outcomes included effect sizes for NM-MRI and iron-sensitive MRI measures--transverse relaxation rate (R2), effective relaxation rate (R2*), and quantitative susceptibility mapping (QSM). ResultsTwenty-seven reports, including 879 individuals with psychosis and 813 controls, were analysed. Meta-analyses were conducted across the caudate nucleus, putamen, globus pallidus, thalamus, and substantia nigra. In psychosis, R2* was significantly lower across all examined regions (g= -0.27 to -0.40), QSM values were lower in the substantia nigra (g= - 0.61; 95% CI, -0.84 to -0.38), and R2 was lower in the caudate nucleus (g= -0.30; 95% CI, - 0.56 to -0.04). NM-MRI values in the substantia nigra were significantly higher (g= 0.39; 95% CI, 0.23 to 0.55), though this effect strongly correlated with chlorpromazine daily equivalent dose ({beta}= 0.001; 95% CI, 0.0003 to 0.0018), suggesting medication-related effects. ConclusionsPsychosis is associated with lower subcortical iron-sensitive MRI values. This was most marked in the substantia nigra, where NM-MRI values--which index neuromelanin-bound iron in dopamine neurones--were significantly higher. This suggests that while subcortical iron is overall lower in psychosis, neuromelanin-bound iron is increased within dopamine neurones. Investigating the mechanisms underlying iron alterations may provide new treatment targets.

Growing concerns about the addictive nature of internet and computer games led to the endorsement of Internet Gaming Disorder (IGD) as an emerging disorder by the American Psychological Association (APA) in 2013 and the recognition of Gaming Disorder (GD) as a new diagnosis by the World Health Organization (WHO) in 2019. While the definition of clear diagnostic criteria for IGD is beneficial for clinicians and those in need of treatment, it may also stigmatize normal behavior. Furthermore, the neurobiological mechanisms underlying IGD symptoms, and whether they resemble those of other addictive disorders remains highly debated. To this end the present study employed a dimensional imaging approach to determine associations between IGD symptom-load according to the APA and WHO diagnostic frameworks and brain structure in a comparably large sample of healthy subjects. It was found that higher symptom-load on psychometric tests assessing the APA and WHO diagnostic frameworks convergently associated with lower volumes of the striatum. The present results suggest for the first time a neurobiological foundation of the proposed diagnostic criteria for IGD according to both diagnostic classification systems, further indicating that the transition from non-disordered to disordered gaming is accompanied by progressive neuroplastic changes in the striatum, thus resembling progressive changes in other addictive disorders.

INTRODUCTIONFrontotemporal dementia involves progressive atrophy in deep gray matter nuclei, including the thalamus and basal ganglia (such as the caudate, putamen, nucleus accumbens, and globus pallidus), which are critical for cognition and behavior. This study examined cross-sectional and longitudinal atrophy using a state-of-the-art multi-atlas segmentation method sTHOMAS. METHODST1-weighted MRI scans from 274 participants at baseline and 237 at follow-up obtained from the Frontotemporal Lobar Degeneration Neuroimaging Initiative database were analyzed using sTHOMAS. Group differences were assessed using ANCOVA, adjusting for age, gender and intracranial volume as covariates. RESULTSAtrophy was significant in the mediodorsal, pulvinar, anterior ventral nuclei, nucleus accumbens, and claustrum, with bvFTD most affected cross-sectionally. Longitudinally, the nucleus accumbens, mediodorsal, and pulvinar nuclei declined further. Atrophy correlated with naming (mediodorsal), working memory (ventrolateral posterior), and executive dysfunction (nucleus accumbens) neuropsychological tests. DISCUSSIONThese findings highlight progressive, nucleus-specific atrophy in FTD and emphasize the importance of cross-sectional as well as longitudinal imaging and sex-specific analyses in understanding disease progression.

BackgroundGeneralized anxiety disorder (GAD) is characterized by chronic worry and emotional dysregulation, yet its underlying white matter (WM) architecture remains inconsistent in previous neuroimaging studies. This study aimed to delineate microstructural WM alterations in GAD using ultra-high field (7T) diffusion tensor imaging (DTI) and advanced correlational tractography, evaluating their associations with symptom severity and diagnostic-aided value. MethodsEighty-eight participants (27 GAD, 61 healthy controls, HCs) underwent 7T DTI scanning with 1.5-mm isotropic resolution. Whole-brain correlational tractography was applied to identify tracts exhibiting significant group-related differences in diffusion indices while controlling for demographic covariates. Associations with Hamilton Anxiety Rating Scale (HAM-A) and Penn State Worry Questionnaire (PSWQ) scores were examined, and machine learning-based models were used to assess the diagnostic-aided utility of identified WM features. ResultsTwo tract bundles showed significant fractional anisotropy (FA) alterations in GAD: decreased FA in the right prefrontal pathway (PFDR = 0.039) and increased FA in the right cingulum (PFDR < 0.001). The anterior portions of both tracts exhibited stronger effects of GAD. FA in the right cingulum positively correlated with HAM-A and PSWQ scores, indicating that greater microstructural coherence was associated with higher anxiety and worry severity (both PFDRs < 0.001). Inclusion of WM features could improve classification performance beyond neuropsychological measures alone. ConclusionsUltra-high field 7T tractometry revealed a differential pattern of WM abnormalities in GAD, suggesting weakened prefrontal control and hyper-integrated cingulate connectivity as structural correlates of emotional dysregulation. These findings indicate the potential of 7T DTI markers for advancing mechanistic and diagnostic understanding of GAD.

BackgroundThere is growing evidence for inflammatory mechanisms in schizophrenia spectrum disorders (SSD) that have been associated with blood-brain barrier (BBB) disruption. Previous studies investigating the BBB in SSD focused on cerebrospinal fluid (CSF) markers, that cannot adequately assess BBB integrity. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) represents a sensitive method for investigating subtle barrier breakdown in vivo. So far, only one pilot study has investigated BBB breakdown in SSD with DCE-MRI, in a relatively small cohort. We hypothesized higher leakage in SSD compared to HC, indicative of a clinical sub-phenotype of SSD. MethodsForty-one people with SSD and 40 age- and sex-matched healthy controls (HC) were included in the final analyses of the cross-sectional study. DCE-MRI, clinical characterization, cognitive assessments, blood and CSF analyses were conducted. The volume transfer constant Ktrans was calculated with pharmacokinetic modelling (Patlak method), to estimate the rate of contrast agent transfer between blood and the brains extravascular space. Ktrans maps were compared between the groups to detect group differences in BBB leakage. Within the SSD cohort, the association between leakage and clinical characteristics was investigated with linear regression analyses. ResultsGroup comparisons of Ktrans maps showed higher leakage in SSD compared to HC on a whole brain level. The effect was more pronounced in first episode compared to multiple episode psychosis. No association was detected between leakage and measures of cognition, psychopathology, peripheral inflammation and albumin CSF/serum ratio. DiscussionThis is the largest study to date investigating the BBB in SSD with DCE-MRI in a multimodal approach, allowing direct exploration of the BBB, compared to a HC group. The integrity of the BBB is crucial for maintaining the brains microenvironment, and its disruption could be associated with potential immune system abnormalities. The results of this study provide the first in vivo evidence of higher BBB leakage on a whole brain level compared to HC. The disruption of the BBB in SSD, as detected through DCE-MRI, may provide insights into the diseases mechanisms and potential for targeted treatments. Further research in this area may clarify specific biological disease mechanisms and identify new therapeutic targets.

BackgroundSchizophrenia is associated with abnormalities in neurodevelopmental processes. Furthermore, dysfunctional neural circuits involved in reward processing may be linked to the development of symptoms in schizophrenia and are predictive of long-term functional outcome. It is however unknown whether neural signatures of reward processing are detectable in children with an increased risk of psychosis and/or predictive of their prodromal psychosis score. MethodsUsing data from the ABCD study 4.1, we defined a healthy control (N=50) and a risk for psychosis (N=50) group with a Prodromal Psychosis Syndrome (PPS) score>3 at baseline (9- 10 years) and 2nd-year-follow-up (11-12 years). While undergoing functional MR-imaging, all children completed the Monetary Incentive Delay task. Using the preprocessed ABCD-data, we explore whether behaviour and brain activations for reward and loss anticipation in areas underlying reward processing differed between groups and time-points. Furthermore, we investigated whether those brain activations that showed differences between the groups were predictive of later PPS scores. ResultsWhile behavioural results did not differ, we found that at-risk children demonstrated lower activation during reward anticipation in the caudate for both timepoints, and the nucleus accumbens, the putamen, the dorsolateral and the ventral medial prefrontal cortex for the 2nd-year-follow-up compared to controls. Regression analysis revealed that right caudate deactivation for both timepoints was predictive of later PPS scores. ConclusionThis study reveals that neural alterations during reward anticipation are detectable in children at-risk of psychosis. These dysfunctions in neural activation patterns may serve as a potential predictive biomarker for psychosis.

BackgroundSchizophrenia is associated with aberrant gamma band power, hypothesized to reflect imbalance in the excitation-inhibition (E/I) ratio and undermine neural signal efficiency. Relationships between resting-state gamma, E/I balance, and regional hemodynamics from the fMRI BOLD signal are unknown. MethodsWe recorded simultaneous EEG-fMRI at rest, with eyes open, in people with schizophrenia (n= 57) and people without a psychiatric diagnosis (n= 46) and identified gamma and aperiodic EEG parameters associated with E/I balance. Measures from all EEG channels were entered into a whole-brain, parametric modulation analysis followed by statistical correction for multiple comparisons. Sensory gating was assessed using the Sensory Gating Inventory, and psychotic symptoms were assessed using the Positive and Negative Syndrome Scale. ResultsAcross groups, gamma power modestly predicts a steeper aperiodic slope (greater inhibition), without group differences in either gamma power or aperiodic slope. In schizophrenia, gamma-BOLD coupling was reduced in bilateral auditory regions of the superior temporal gyri and inversely correlated with sensory gating deficits and symptom severity. Analysis of the spectral features of scanner sounds revealed distinct peaks in the gamma range, reflecting a rapidly repeating scanner pulse sound present throughout the resting state recording. ConclusionRegional hemodynamic support for putative inhibitory and excitatory contributions to resting EEG are aberrant in SZ. Deficient gamma coupling to auditory BOLD may reflect impaired gating of fMRI-scanner sound.

BackgroundEmerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls (CTR) using diffusion tensor imaging (DTI). MethodsOur sample included 321 adolescents with EOP (mean age: 16.3 {+/-} 1.4 years, 46.4% females) and 265 adolescent CTR (mean age: 16.0 {+/-} 1.7 years, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. ResultsWe found widespread lower FA in EOP compared to CTR, with the largest effect sizes in the superior longitudinal fasciculus (Cohens d = 0.37), posterior corona radiata (d = 0.32), and superior fronto{square}occipital fasciculus (d = 0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. ConclusionUsing the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male patients with early-onset schizophrenia and patients with a shorter duration of illness.