Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.

Thalamic Connectivity System Across Psychiatric Disorders: Current Status and Clinical Implications.

The thalamic connectivity system, with the thalamus as the central node, enables transmission of the brain's neural computations via extensive connections to cortical, subcortical, and cerebellar regions. Emerging reports suggest deficits in this system across multiple psychiatric disorders, making it a unique network of high translational and transdiagnostic utility in mapping neural alterations that potentially contribute to symptoms and disturbances in psychiatric patients. However, despite considerable research effort, it is still debated how this system contributes to psychiatric disorders. This review characterizes current knowledge regarding thalamic connectivity system deficits in psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder, across multiple levels of the system. We identify the presence of common and distinct patterns of deficits in the thalamic connectivity system in major psychiatric disorders and assess their nature and characteristics. Specifically, this review assembles evidence for the hypotheses of 1) thalamic microstructure, particularly in the mediodorsal nucleus, as a state marker of psychosis; 2) thalamo-prefrontal connectivity as a trait marker of psychosis; and 3) thalamo-somatosensory/parietal connectivity as a possible marker of general psychiatric illness. Furthermore, possible mechanisms contributing to thalamocortical dysconnectivity are explored. We discuss current views on the contributions of cerebellar-thalamic connectivity to the thalamic connectivity system and propose future studies to examine its effects at multiple levels, from the molecular (e.g., glutamatergic) to the behavioral (e.g., cognition), to gain a deeper understanding of the mechanisms that underlie the disturbances observed in psychiatric disorders.

Aberrant cortico-striatal white matter connectivity and associated subregional microstructure of the striatum in obsessive-compulsive disorder.

The striatum and its cortical circuits play central roles in the pathophysiology of obsessive-compulsive disorder (OCD). The striatum is subdivided by cortical connections and functions; however, the anatomical aberrations in different cortico-striatal connections and coexisting microstructural anomalies in striatal subregions of OCD patients are poorly understood. Thus, we aimed to elucidate the aberrations in cortico-striatal white matter (WM) connectivity and the associated subregional microstructure of the striatum in patients with OCD. From diffusion tensor/kurtosis imaging of 107 unmedicated OCD patients and 110 matched healthy controls (HCs), we calculated the cortico-striatal WM connectivity and segmented the striatum using probabilistic tractography. For the segmented striatal subregions, we measured average diffusion kurtosis values, which represent microstructural complexity. Connectivity and mean kurtosis values in each cortical target and associated striatal subregions were compared between groups. We identified significantly reduced orbitofrontal WM connectivity with its associated striatal subregion in patients with OCD compared to that in HCs. However, OCD patients exhibited significantly increased caudal-motor and parietal connectivity with the associated striatal subregions. The mean kurtosis values of the striatal subregions connected to the caudal-motor and parietal cortex were significantly decreased in OCD patients. Our results highlighted contrasting patterns of striatal WM connections with the orbitofrontal and caudal-motor/parietal cortices, thus supporting the cortico-striatal circuitry imbalance model of OCD. We suggest that aberrations in WM connections and the microstructure of their downstream regions in the caudal-motor-/parietal-striatal circuits may underlie OCD pathophysiology and further provide potential neuromodulation targets for the treatment of OCD.

Unbalanced fronto-pallidal neurocircuit underlying set shifting in obsessive-compulsive disorder.

Maladaptive habitual behaviours of obsessive-compulsive disorder are characterized by cognitive inflexibility, which hypothetically arises from dysfunctions of a certain cortico-basal ganglia-thalamo-cortical circuit including the ventrolateral prefrontal region. Inside this neurocircuit, an imbalance between distinct striatal projections to basal ganglia output nuclei, either directly or indirectly via the external globus pallidus, is suggested to be relevant for impaired arbitration between facilitation and inhibition of cortically initiated activity. However, current evidence of individually altered cortico-striatal or thalamo-cortical connectivities is insufficient to understand how cortical dysconnections are linked to the imbalanced basal ganglia system in patients. In this study, we aimed to identify aberrant ventrolateral prefronto-basal ganglia-thalamic subnetworks representing direct-indirect imbalance and its association with cognitive inflexibility in patients. To increase network detection sensitivity, we constructed a cortico-basal ganglia-thalamo-cortical network model incorporating striatal, pallidal and thalamic subregions defined by unsupervised clustering in 105 medication-free patients with obsessive-compulsive disorder (age = 25.05 ± 6.55 years, male/female = 70/35) and 99 healthy controls (age = 23.93 ± 5.80 years, male/female = 64/35). By using the network-based statistic method, we analysed group differences in subnetworks formed by suprathreshold dysconnectivities. Using linear regression models, we tested subnetwork dysconnectivity effects on symptom severity and set-shifting performance assessed by well-validated clinical and cognitive tests. Compared with the healthy controls, patients were slower to track the Part B sequence of the Trail Making Test when the effects of psychomotor and visuospatial functions were adjusted (t = 3.89, P < 0.001) and made more extradimensional shift errors (t = 4.09, P < 0.001). In addition to reduced fronto-striatal and striato-external pallidal connectivities and hypoconnected striato-thalamic subnetwork [P = 0.001, family-wise error rate (FWER) corrected], patients had hyperconnected fronto-external pallidal (P = 0.012, FWER corrected) and intra-thalamic (P = 0.015, FWER corrected) subnetworks compared with the healthy controls. Among the patients, the fronto-pallidal subnetwork alteration, especially ventrolateral prefronto-external globus pallidal hyperconnectivity, was associated with relatively fewer extradimensional shifting errors (ß = -0.30, P = 0.001). Our findings suggest that the hyperconnected fronto-external pallidal subnetwork may have an opposite effect to the imbalance caused by the reduced indirect pathway (fronto-striato-external pallidal) connectivities in patients. This ventrolateral prefrontal hyperconnectivity may help the external globus pallidus disinhibit basal ganglia output nuclei, which results in behavioural inhibition, so as to compensate for the impaired set shifting. We suggest the ventrolateral prefrontal and external globus pallidus as neuromodulatory targets for inflexible habitual behaviours in obsessive-compulsive disorder.

Mapping thalamocortical functional connectivity with large-scale brain networks in patients with first-episode psychosis.

Abnormal thalamocortical networks involving specific thalamic nuclei have been implicated in schizophrenia pathophysiology. While comparable topography of anatomical and functional connectivity abnormalities has been reported in patients across illness stages, previous functional studies have been confined to anatomical pathways of thalamocortical networks. To address this issue, we incorporated large-scale brain network dynamics into examining thalamocortical functional connectivity. Forty patients with first-episode psychosis and forty healthy controls underwent T1-weighted and resting-state functional magnetic resonance imaging. Independent component analysis of voxelwise thalamic functional connectivity maps parcellated the cortex into thalamus-related networks, and thalamic subdivisions associated with these networks were delineated. Functional connectivity of (1) networks with the thalamus and (2) thalamic subdivision seeds were examined. In patients, functional connectivity of the salience network with the thalamus was decreased and localized to the ventrolateral (VL) and ventroposterior (VP) thalamus, while that of a network comprising the cerebellum, temporal and parietal regions was increased and localized to the mediodorsal (MD) thalamus. In patients, thalamic subdivision encompassing the VL and VP thalamus demonstrated hypoconnectivity and that encompassing the MD and pulvinar regions demonstrated hyperconnectivity. Our results extend the implications of disrupted thalamocortical networks involving specific thalamic nuclei to dysfunctional large-scale brain network dynamics in schizophrenia pathophysiology.

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis.

Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). Design, Setting, and Participants: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020. Main Outcomes and Measures: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group). Results: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001). Conclusions and Relevance: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.

White Matter Correlates of Theory of Mind in Patients With First-Episode Psychosis.

Deficits in theory of mind (ToM) are considered as a distinctive feature of schizophrenia. Functional magnetic resonance imaging (fMRI) studies have suggested that aberrant activity among the regions comprising the mentalizing network is related to observed ToM deficits. However, the white matter structures underlying the ToM functional network in schizophrenia remain unclear. To investigate the relationship between white matter integrity and ToM impairment, 35 patients with first-episode psychosis (FEP) and 29 matched healthy controls (HCs) underwent diffusion tensor imaging (DTI). Using tract-based spatial statistics (TBSS), fractional anisotropy (FA) values of the two regions of interest (ROI)-the cingulum and superior longitudinal fasciculus (SLF)-were acquired, and correlational analysis with ToM task scores was performed. Among the patients with FEP, ToM strange story scores were positively correlated with the FA values of the left cingulum and left SLF. There was no significant correlation between FA and ToM task scores in HCs. These results suggest that the left cingulum and SLF constitute a possible neural basis for ToM deficits in schizophrenia. Our study is the first to demonstrate the white matter connectivity underlying the mentalizing network, as well as its relation to ToM ability in patients with FEP.

Distinct neural networks associated with obsession and delusion: a connectome-wide association study.

BACKGROUND: Obsession and delusion are theoretically distinct from each other in terms of reality testing. Despite such phenomenological distinction, no extant studies have examined the identification of common and distinct neural correlates of obsession and delusion by employing biologically grounded methods. Here, we investigated dimensional effects of obsession and delusion spanning across the traditional diagnostic boundaries reflected upon the resting-state functional connectivity (RSFC) using connectome-wide association studies (CWAS). METHODS: Our study sample comprised of 96 patients with obsessive-compulsive disorder, 75 patients with schizophrenia, and 65 healthy controls. A connectome-wide analysis was conducted to examine the relationship between obsession and delusion severity and RFSC using multivariate distance-based matrix regression. RESULTS: Obsession was associated with the supplementary motor area, precentral gyrus, and superior parietal lobule, while delusion was associated with the precuneus. Follow-up seed-based RSFC and modularity analyses revealed that obsession was related to aberrant inter-network connectivity strength. Additional inter-network analyses demonstrated the association between obsession severity and inter-network connectivity between the frontoparietal control network and the dorsal attention network. CONCLUSIONS: Our CWAS study based on the Research Domain Criteria (RDoC) provides novel evidence for the circuit-level functional dysconnectivity associated with obsession and delusion severity across diagnostic boundaries. Further refinement and accumulation of biomarkers from studies embedded within the RDoC framework would provide useful information in treating individuals who have some obsession or delusion symptoms but cannot be identified by the category of clinical symptoms alone.

Intact thalamic microstructure in asymptomatic relatives of schizophrenia patients with high genetic loading.

BACKGROUND: Disrupted thalamic connectivity system, which encompasses the deficits in the thalamus and thalamocortical connectivity, is regarded to contribute to the pathophysiology of schizophrenia. Recent reports suggest the possible genetic contribution to the disrupted thalamo-prefrontal connectivity, however, research on elucidating thalamic connectivity system components, specifically the thalamic nuclei, associated with the genetic predisposition to schizophrenia has been limited. Here, we investigated the genetic aspects of thalamic nuclei-specific microstructural integrities in schizophrenia. METHODS: A total of 34 asymptomatic relatives of schizophrenia patients with high genetic loading and 33 healthy control subjects underwent diffusion tensor imaging, diffusion kurtosis imaging, and T1-weighted magnetic resonance imaging. The thalamus was segmented via a connectivity-based segmentation method using the region-of-interest masks. The microstructural integrity of each thalamic nucleus, measured by averages of the diffusion kurtosis values, was then compared between the groups. RESULTS: The volumetric and mean kurtosis values of the thalamic nuclei were intact in asymptomatic relatives of schizophrenia patients with high genetic loading. CONCLUSIONS: Our results revealed that, in the thalamic connectivity system, the genetics may hold different weights of effects on different components, and that more is given on the thalamo-prefrontal connectivity than on the thalamus. Further, the current results may add further evidence to the current literature that thalamic nuclei microstructural abnormalities present in psychosis may have state marker characteristics.

Relationship between resting-state theta phase-gamma amplitude coupling and neurocognitive functioning in patients with first-episode psychosis.

BACKGROUND: Although cognitive dysfunction is a core element of schizophrenia, the neurobiological underpinnings of the pathophysiology are not yet sufficiently understood. Because the resting state is crucial for cognitive functioning and electroencephalography (EEG) can reflect instantaneous neural activity, we investigated theta phase-gamma amplitude coupling (TGC) of resting-state EEG and its relationship with cognitive function in patients with first-episode psychosis (FEP) to reveal the neural correlates of cognitive dysfunction. METHODS: A total of 59 FEP patients and 50 healthy controls (HCs) underwent resting-state, eyes-closed EEG recordings and performed the Trail Making Test Part A (TMT-A) and Part B (TMT-B) and California Verbal Learning Test (CVLT). TGC from the source signal of the resting-state EEG in default mode network (DMN)-related brain regions was compared between groups. Correlation analyses were performed between TGC and cognitive function test performance in FEP patients. RESULTS: Mean resting-state TGC was larger for the FEP patients than for the HCs. Patients with FEP showed increased TGC in the left posterior cingulate cortex, which was correlated with better performance on the TMT-A and TMT-B and on immediate and delayed recall in the CVLT. CONCLUSIONS: These results suggest that patients with FEP show compensatory hyperactivation of resting-state TGC in DMN-related brain regions, which may be related to the reallocation of cognitive resources to prepare for successful cognitive execution. This study not only highlights the neural underpinnings of cognitive dysfunction in FEP patients but also provides useful background to support the development of treatments for cognitive dysfunction in schizophrenia.

Predicting Symptomatic and Functional Improvements over 1 Year in Patients with First-Episode Psychosis Using Resting-State Electroencephalography.

OBJECTIVE: Although early intervention from the beginning of a psychotic episode is essential for a better prognosis, biomarkers predictive of symptomatic and functional improvement in early psychotic disorders are lacking. This study aimed to investigate whether the spectral power of resting-state electroencephalography (EEG) can be used as a predictive marker of the 1-year prognosis in patients with first-episode psychosis (FEP). METHODS: Twenty-four patients with FEP and matched healthy control (HC) subjects were examined with resting-state EEG at baseline. The symptomatic severity and functional status of FEP patients were assessed at baseline and reassessed after 1 year of usual treatment. Repeated measures analysis of variance was conducted to compare EEG spectral powers across the groups. Multiple regression analysis revealed EEG spectral powers predictive of symptomatic and functional improvement in FEP patients at the 1-year follow-up. RESULTS: Delta band power in the frontal and posterior regions was significantly higher in patients with FEP than in HCs. Higher delta band power in the posterior region predicted later improvement of positive symptoms and general functional status. Lower delta band power in the frontal region predicted improvement of negative symptoms and general functioning after 1 year. CONCLUSION: These results suggest that increased delta absolute power is observed from the beginning of psychotic disorders. Furthermore, decreased delta power in the frontal region and increased delta power in the posterior region might be used as a predictive marker of a better prognosis of FEP, which would aid early intervention in clinical practice.

Dysfunctional attentional bias and inhibitory control during anti-saccade task in patients with internet gaming disorder: An eye tracking study.

BACKGROUND: Although internet gaming disorder (IGD) is considered an addictive disorder, evidence of the neurobiological underpinnings of IGD as an addictive disorder is currently lacking. We investigated whether attentional bias toward game-related stimuli was altered in IGD patients using an eye-tracking method during an anti-saccade task. METHODS: Twenty-three IGD patients and 27 healthy control (HC) subjects participated in the anti-saccade task with game-related, neutral, and scrambled images during eye tracking. Participants rated subjective scores of valence, arousal, and craving for each image stimulus after finishing eye tracking. Mixed design analysis of variance was performed to compare the differences between eye movement latency and error rate in the pro-saccade and anti-saccade conditions according to image type across the IGD and HC groups. RESULTS: In the anti-saccade task, the IGD group exhibited higher error rates in the case of game-related images than in neutral or scrambled images. However, ratings on valence, arousal, and craving did not vary among image types. The error rates of the HCs did not vary across image types, but higher arousal/craving and lower valence were reported with respect to the game-related images. CONCLUSIONS: Increased error rate during anti-saccade tasks with game-related stimuli in IGD may be due to disabilities in goal-directed behavior or inhibitory control, as observed in other addictive disorders. These findings suggest that attentional bias toward game-related stimuli can be a sensitive biological marker of IGD as an addictive disorder.

Functional connectivity of the raphe nucleus as a predictor of the response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder.

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological agents for treating obsessive-compulsive disorder (OCD). However, because nearly half of patients show insufficient SSRI responses, serotonergic dysfunction in heterogeneous OCD patients should be investigated for precision medicine. We aimed to determine whether functional connectivity (FC) of the raphe nucleus (RN), the major source of most serotonergic neurons, was altered in OCD patients and could predict the SSRI response. A total of 102 medication-free OCD patients and 101 matched healthy control (HC) subjects participated in resting-state functional magnetic resonance imaging. Among them, 54 OCD patients were treated with SSRIs for 16 weeks, resulting in 26 responders and 28 nonresponders. Seed-based whole brain FC with the RN as a seed region was compared between the OCD and HC groups, as well as between SSRI responders and nonresponders. FC cluster values showing significant group differences were used to investigate factors correlated with symptomatic severity before treatment and predictive of SSRI response. Compared to HCs, OCD patients exhibited significantly larger FC between the RN and temporal cortices including the middle temporal gyrus (MTG), paracingulate gyrus, amygdala, hippocampus, putamen, thalamus, and brain stem. Greater RN-left MTG FC was positively correlated with OC symptom severity at baseline. In addition, larger FC of the RN-left MTG was also found in SSRI nonresponders compared to responders, which was a significant predictor of SSRI response after 16 weeks. The FC of RN may reflect the neurobiological underpinning of OCD and could aid future precision medicine as a differential brain-based biomarker.

Adjunctive use of anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials.

OBJECTIVE: Recent evidence suggests that adjuvant anti-inflammatory agents could improve the symptoms of patients with schizophrenia. However, the effects of the adjuvant anti-inflammatory agents on cognitive function, general functioning and side effects have not yet been systematically investigated. The present meta-analysis aimed to explore the effects of anti-inflammatory agents in patients with schizophrenia comprehensively. METHOD: We performed a literature search in online databases, including PubMed, EMBASE and the Cochrane Database of Systematic Reviews. Randomized, placebo-controlled double-blind studies that investigated clinical outcomes including psychopathology, neurocognition, general functioning and extrapyramidal side effects were included. The examined anti-inflammatory agents included aspirin, celecoxib, omega-3 fatty acids, estrogen, selective estrogen receptor modulator, pregnenolone, N-acetylcysteine, minocycline, davunetide and erythropoietin. RESULTS: Sixty-two double-blind randomized clinical trials studying 2914 patients with schizophrenia met the inclusion criteria for quantitative analysis. Significant overall effects were found for anti-inflammatory agents for reducing total, positive and negative symptom scores in the Positive and Negative Syndrome Scale. Cognitive improvements were significant with minocycline and pregnenolone augmentation therapy. General functioning was significantly enhanced by overall anti-inflammatory agents. There were no significant differences in side effects compared with placebo. Baseline total Positive and Negative Syndrome Scale score and illness duration were identified as moderating factors in the effects of anti-inflammatory augmentation on psychiatric symptom improvements. CONCLUSION: The comparative evaluation of efficacy and safety supported the use of anti-inflammatory adjuvant therapy over the use of antipsychotics alone. However, future studies could focus on patients with homogeneous clinical profile to figure out more detailed effects of anti-inflammatory therapy.

Predicting prognosis in patients with first-episode psychosis using auditory P300: A 1-year follow-up study.

OBJECTIVE: To clarify the role of auditory P300 in predicting prognosis in patients with first-episode psychosis (FEP) during a 1-year follow-up. METHODS: Auditory P300 of 24 patients with FEP and 24 matched healthy control (HC) participants were measured at baseline. The clinical status of the FEP patients was assessed at baseline and reassessed after 1 year. P300 amplitudes and latencies among the groups were analyzed using repeated measures analysis of variance. Multiple regression analysis was conducted to assess the predictive value of P300 in patients with FEP during the 1-year follow-up. RESULTS: Auditory P300 amplitudes were significantly smaller in FEP patients than HCs. Higher baseline P300 amplitudes at CPz significantly predicted better improvements in the Positive and Negative Syndrome Scale total, positive, and general scores, as well as in the Global Assessment of Functioning and Brief Psychiatric Rating Scale. CONCLUSIONS: P300 may predict improvements in symptoms, functional status, and overall psychiatric status in patients with FEP. SIGNIFICANCE: We first show that P300 amplitude at baseline predicts symptomatic and functional improvements after 1 year of treatment in patients with FEP. This finding may aid in effective interventions from the beginning of a psychotic episode to improve subsequent outcomes in clinical practice.

Microstructural Changes in Higher-Order Nuclei of the Thalamus in Patients With First-Episode Psychosis.

BACKGROUND: Disruption in the thalamus, such as volume, shape, and cortical connectivity, is regarded as an important pathophysiological mechanism in schizophrenia. However, there is little evidence of nuclei-specific structural alterations in the thalamus during early-stage psychosis, mainly because of the methodological limitations of conventional structural imaging in identifying the thalamic nuclei. METHODS: A total of 37 patients with first-episode psychosis and 36 matched healthy control subjects underwent diffusion tensor imaging, diffusion kurtosis imaging, and T1-weighted magnetic resonance imaging. Connectivity-based segmentation of the thalamus was performed using diffusion tensor imaging, and averages of the diffusion kurtosis values, which represent microstructural complexity, were estimated using diffusion kurtosis imaging and were compared in each thalamic nucleus between the groups. RESULTS: The mean kurtosis values in the thalamic regions with strong connections to the orbitofrontal cortex (F1,70 = 8.40, p < .01) and the lateral temporal cortex (F1,70 = 8.46, p < .01) were significantly reduced in patients with first-episode psychosis compared with those of the healthy control subjects. The mean kurtosis values in the thalamic region with strong connection to the orbitofrontal cortex showed a significant correlation with spatial working memory accuracy in patients with first-episode psychosis (r = .36, p < .05), whereas no significant correlation between these variables was observed in the healthy control subjects. CONCLUSIONS: The observed pattern of reduced microstructural complexity in the nuclei not only highlights the involvement of the thalamus but also emphasizes the role of the higher-order nuclei in the pathophysiology beginning in the early stage of schizophrenia.

Reduced cortical thickness in subjects at clinical high risk for psychosis and clinical attributes.

OBJECTIVES: Although neuroanatomical abnormalities in subjects at clinical high risk for psychosis have been considered a putative biomarker of psychosis, relevance of cortical thickness alterations remains contested due to discrepant findings. Inconsistencies persist in Asian clinical high risk studies, despite their advantageous settings well-controlled for confounds. Attributes of cortical thickness alterations in clinical high risk subjects warrant further examination. METHODS: We examined cortical thickness at the whole-brain level in 74 clinical high risk subjects and 34 demographically matched healthy controls recruited from Seoul Youth Clinic, South Korea. Clinical symptoms were assessed using the Scale of Prodromal Symptoms, and their associations with cortical thickness were explored using partial correlation analysis. RESULTS: Compared to healthy control, clinical high risk exhibited significant cortical thinning in bilateral prefrontal cortex and inferior parietal lobule clusters. Reduced thickness in the left prefrontal cortex cluster was associated with more severe Scale of Prodromal Symptoms general symptoms scores and the right inferior parietal lobule cluster with Scale of Prodromal Symptoms disorganization symptoms. CONCLUSIONS: Thickness deficits found in the present clinical high risk sample demonstrated a degree of consistency with those reported in the previous Seoul Youth Clinic study. While inconsistencies reported between the present and previous Seoul Youth Clinic samples may reflect markedly decreased rate of converters, consistencies may be relevant to clinical attributes beyond transition, such as the prevalence of comorbidities. Particular recruitment strategies employed for sample selections should also be considered for findings in Asian clinical high risk samples. Our results suggest potential utility of cortical thickness alterations in clinical high risk subjects beyond the frame of transition.

Altered Eye-Movement Patterns During Text Reading in Obsessive-Compulsive Disorder and Internet Gaming Disorder.

Obsessive-compulsive disorder (OCD) and internet gaming disorder (IGD), which are similar in that both involve repetitive behaviors and related with cognitive dysfunctions, frequently begin in early adolescence, which is a critical period for learning. Although the deterioration in cognitive functioning caused by these conditions may have adverse effects on information processing, such as text reading, there has been no comprehensive research on the objective indicators of altered reading patterns in these patients. Therefore, we evaluated eye-movement patterns during text reading in patients with OCD or IGD. In total, 20 patients with OCD, 28 patients with IGD and 24 healthy controls (HCs) participated in the reading task using an eye tracker. We compared the fixation durations (FDs), saccade amplitudes and eye-movement regressions of the three groups during reading. We explored relationships between the parameters reflecting altered reading patterns and those reflecting the severity of clinical symptoms. The average FDs and forward saccade amplitudes did not differ significantly among the groups. There were more eye-movement regressions in patients with OCD than in patients with IGD and HCs. No correlation was found between altered eye-movement patterns during reading and the severity of clinical symptoms in any of the patient groups. The significantly increased number of regressions (NRs) in the OCD group during reading may reflect these patients' difficulties with inferential information processing, whereas the reading pattern in the IGD group is relatively intact. These findings suggest that patients with OCD and patients with IGD have different eye-movement patterns during reading reflecting distinct cognitive impairments in the two patient groups.

A Systematic Review and Meta-Analysis of Applicability of Web-Based Interventions for Individuals with Depression and Quality of Life Impairment.

OBJECTIVE: The purpose of this meta-analysis was to determine the applicability of web-based treatment programs for individuals with depression and quality of life impairments. METHODS: We conducted database and manual searches using imprecise search-term strategy and inclusion criteria. Research published from 2005 to December 2015 was included in this study. Upon review, a total of 12 published papers on web-based intervention for individuals with depression were assessed eligible for this meta-analysis. Effect sizes were estimated for depression and quality of life. RESULTS: The mean effect size of web-based treatment on depressive symptoms was 0.72. However, unlike the result showing medium to large effect size, the analysis on the quality of life did not yield adequate effects of web-based interventions. CONCLUSION: Our results suggest robust benefits of employing web-based treatments for depressive symptoms. However, the adequacy of these relatively new intervention tools for individuals who suffer severe impairments of quality of life was found insufficient. The current study demonstrates the need to further develop web-based intervention techniques to improve overall functioning, as well as the clinical symptoms of patients with mental disorders.

Thalamo-cortical system involving higher-order nuclei in patients with first-episode psychosis.

Based on the piling reports of disruptions in the thalamus of patients with schizophrenia, the alteration in the thalamo-cortical system has been regarded as the core pathophysiology. As the thalamus is composed of distinctive nuclei with different cytoarchitecture and cortical connections, nuclei specific investigations have been actively conducted in post-mortem studies. In addition, the importance of early changes has been highlighted, which in turn has led to investigations of the thalamo-cortical system using non-invasive neuroimaging methods. From this perspective, the early structural changes in the thalamo-cortical system, such as the thalamo-cortical connection and nuclei specific microstructural changes (which are coherent with findings from post-mortem methods) will be briefly discussed. The main findings, which are the reduced thalamo-prefrontal connection and reduced microstructural complexity in the higher-order nuclei detected in first-episode psychosis patients, suggest the occurrence of early alterations within and between the communication hub of the brain and cortex. These findings suggest not only directions for further studies for unveiling the thalamo-cortical system related pathophysiology, but also the possibility of using the reduced microstructural complexity in the higher order nucleus as a biomarker for schizophrenia. [BMB Reports 2018; 51(9): 427-428].