Family functioning as a moderator in the relation between perceived stress and psychotic-like experiences among adolescents during COVID-19

Background: The COVID-19 pandemic has increased psychological stress among adolescents, and the relation between perceived stress (PS) and psychotic-like experiences (PLEs) has been well-established. However, little is known about the role of family functioning (FF) in this relation, especially when adolescents experienced the extended lockdown period with family members. Methods: A total of 4807 adolescents completed this retrospective paper-and-pencil survey after school reopening between May 14th and June 6th, 2020 in Hunan Province, China. We measured PS with the Perceived stress scale (PSS-10), PLEs with the eight positive items from Community Assessment of Psychic Experiences (CAPE-8), and FF with the Family APGAR scale. We conducted subgroup analysis based on three FF levels (good, moderate, and poor) determined by previous studies. Finally, correlation and moderation analysis were performed to detect the effect of FF in the relation between PS and PLEs after adjusting for demographic variables. Results: Adolescents with poor FF had higher levels of PS and higher prevalence of PLEs compared to those with good FF (both p \u3c 0.001). FF was negatively associated with both PS (r = −0.34, p \u3c 0.001) and PLEs (r = −0.29, p \u3c 0.001). Higher FF significantly attenuated the effect of PS on PLEs after adjusting for sex and age (effect = −0.011, bootstrap 95% CI -0.018, −0.005). Conclusion: Our findings indicate that well-functioned family could protect against stress-induced PLEs among adolescents during this crisis. Thus family system could be an early interventional target for distressing psychotic-like experiences in youngsters

Inefficient DMN Suppression in Schizophrenia Patients with Impaired Cognitive Function but not Patients with Preserved Cognitive Function

Previous studies have observed reduced suppression of the default mode network (DMN) during cognitive tasks in schizophrenia, suggesting inefficient DMN suppression is critical for the cognitive deficits of schizophrenia. Cognitive function in schizophrenia patients, however, varies from relatively intact to severely impaired. This study, which compared the DMN suppression patterns between first-episode schizophrenia patients with (SZ-Imp) and without (SZ-Pre) impaired cognitive function, may provide further insight into the role of DMN dysfunction in cognitive deficits of schizophrenia. Independent component analysis (ICA) was applied to resting-state fMRI data to identify the DMN in each subject, and then general linear modeling based on the task-fMRI data was used to examine the different DMN activation patterns between groups. We observed that the SZ-Imp group, but not the SZ-Pre group, showed reduced suppression in the medial prefrontal cortex and posterior cingulated cortexPrevious studies have observed reduced suppression of the default mode network (DMN) when compared to the healthy controls (HC) group. Moreover, less DMN suppression was associated with poorer task performance in both HC and patient groups. Our findings provide the first direct evidence that disrupted DMN activity only exists in schizophrenia patients with impaired cognitive function, supporting the specific neuro-pathological role of inefficient DMN suppression in cognitive deficits of first-episode schizophrenia

The instability of functional connectivity in patients with schizophrenia and their siblings: A dynamic connectivity study

Background: The distributed connectivity among brain regions is in a constant state of flux, even when a subject is at rest. This instability (temporal variability), when optimal, may contribute to efficient cross-network communications. We investigate the role of this variability in the genetic diathesis and symptom expression of schizophrenia. Methods: Resting state functional MRI data acquired from 116 subjects (28 patients with schizophrenia, 28 siblings and 60 matched healthy controls). Using a sliding-window dynamic connectivity approach, we quantified the variability of whole-brain connectivity (dynamic functional connectivity or dFC) of each of the 90 brain regions obtained using a parcellation scheme that covered all contiguous brain regions of the cerebral cortex. Results: We noted a high degree of instability anchored on the precuneus in patients with schizophrenia compared to both healthy controls (t = 3.60, p = 0.0005) and unaffected siblings (t = 3.61, p = 0.001) indicating a role for dFC of precuneus in the clinical expression of schizophrenia. Compared to patients, siblings also showed an increase in medial orbitofrontal but reduced putaminal instability; these latter changes were not seen in patients when compared to controls, indicating a lack of specificity for diathesis or expression related effects. Conclusions: Instability in the intrinsic connectivity of precuneus, a functional core hub with a major role in task-free self-processing, is likely to be a core substrate of the clinical expression of schizophrenia

Brain-Wide Functional Dysconnectivity in Schizophrenia: Parsing Diathesis, Resilience, and the Effects of Clinical Expression

Background: The functional dysconnectivity observed from functional magnetic resonance imaging (fMRI) studies in schizophrenia is also seen in unaffected siblings indicating its association with the genetic diathesis. We intended to apportion resting-state dysconnectivity into components that represent genetic diathesis, clinical expression or treatment effect, and resilience. Methods: fMRI data were acquired from 28 schizophrenia patients, 28 unaffected siblings, and 60 healthy controls. Based on Dosenbach’s atlas, we extracted time series of 160 regions of interest. After constructing functional network, we investigated between-group differences in strength and diversity of functional connectivity and topological properties of undirected graphs. Results: Using analysis of variance, we found 88 dysconnectivities. Post hoc t tests revealed that 62.5% were associated with genetic diathesis and 21.6% were associated with clinical expression. Topologically, we observed increased degree, clustering coefficient, and global efficiency in the sibling group compared to both patients and controls. Conclusion: A large portion of the resting-state functional dysconnectivity seen in patients represents a genetic diathesis effect. The most prominent network-level disruption is the dysconnectivity among nodes of the default mode and salience networks. Despite their predisposition, unaffected siblings show a pattern of resilience in the emergent connectomic topology. Our findings could potentially help refine imaging genetics approaches currently used in the pursuit of the pathophysiology of schizophrenia

Depression Uncouples Brain Hate Circuit

International audienceIt is increasingly recognized that we need a better understanding of how mental dis-orders such as depression alter the brain's functional connections to improve both early diagnosis and therapy. A new holistic approach has been used to investigate functional connectivity changes in the brains of patients suffering from major depres-sion using resting state fMRI data. A canonical template of connectivity in 90 differ-ent brain regions was constructed from healthy control subjects and this identified a six-community structure with each network corresponding to a different functional system. This template was compared to functional networks derived from fMRI scans of both first episode and longer-term, drug resistant, patients suffering from severe depression. The greatest change in both groups of depressed patients was uncoupling of the so-called "hate circuit" involving the superior frontal gyrus, insula and putamen. Other major changes occurred in circuits related to risk and action responses, reward and emotion, attention and memory processing. A voxel-based morphometry analysis was also carried out but this revealed no evidence in the depressed patients for altered grey or white matter densities in the regions showing altered functional connectivity. This is the first evidence for involvement of the "hate circuit" in depression and sug-gests a potential reappraisal of the key neural circuitry involved. We have hypothe-sized that this may reflect reduced cognitive control over negative feelings towards both self and others

Morphological Profiling of Schizophrenia: Cluster Analysis of MRI-Based Cortical Thickness Data

The diagnosis of schizophrenia is thought to embrace several distinct subgroups. The manifold entities in a single clinical patient group increase the variance of biological measures, deflate the group-level estimates of causal factors, and mask the presence of treatment effects. However, reliable neurobiological boundaries to differentiate these subgroups remain elusive. Since cortical thinning is a well-established feature in schizophrenia, we investigated if individuals (patients and healthy controls) with similar patterns of regional cortical thickness form naturally occurring morphological subtypes. K-means algorithm clustering was applied to regional cortical thickness values obtained from 256 structural MRI scans (179 patients with schizophrenia and 77 healthy controls [HCs]). GAP statistics revealed three clusters with distinct regional thickness patterns. The specific patterns of cortical thinning, clinical characteristics, and cognitive function of each clustered subgroup were assessed. The three clusters based on thickness patterns comprised of a morphologically impoverished subgroup (25% patients, 1% HCs), an intermediate subgroup (47% patients, 46% HCs), and an intact subgroup (28% patients, 53% HCs). The differences of clinical features among three clusters pertained to age-of-onset, N-back performance, duration exposure to treatment, total burden of positive symptoms, and severity of delusions. Particularly, the morphologically impoverished group had deficits in N-back performance and less severe positive symptom burden. The data-driven neuroimaging approach illustrates the occurrence of morphologically separable subgroups in schizophrenia, with distinct clinical characteristics. We infer that the anatomical heterogeneity of schizophrenia arises from both pathological deviance and physiological variance. We advocate using MRI-guided stratification for clinical trials as well as case-control investigations in schizophrenia

Connectomic signatures of working memory deficits in depression, mania, and euthymic states of bipolar disorder

Background: Working memory (WM) deficit is a feature persistently reported across mania, depression, and euthymic periods of bipolar disorder (BD). WM capacity relates to distributed brain regions that are systemically organized at the connectome level. It is not clear whether the same disruption of this network-level organization underlies the WM impairment seen in different phases of BD. Methods: We used graph theory to examine the topology of the functional connectome in different granularity in 143 subjects (72 with BD [32 depression; 15 mania; 25 euthymic] and 71 healthy controls) during a n-back task. Linear regression analysis was used to test associations of altered graph properties, clinical symptoms, and WM accuracy in patients. Results: Altered topological properties characterised by an increase in small-worldness of the whole-brain connectome, were specific for bipolar depressed, but not in manic and euthymic states. Depressed subjects showed a shift in the distribution of the number of connections per brain region (degree) within the connectome during WM task. Increased small-worldness related to worse WM accuracy in patients with more severe depression, anxiety and illness burden. Limitations: We used only 2-back load, limiting our ability to study the parametric effects of task demand. Conclusions: We demonstrate a putative state-dependent mechanistic link between connectome topology, hub re-distribution and impaired n-back performance in bipolar disorder. The aberrant task-dependent modulation of the connectome relates to worse WM performance especially when anxiety and depression are prominent in BD

Opposite effective connectivity in the posterior cingulate and medial prefrontal cortex between first-episode schizophrenic patients with suicide risk and healthy controls.

OBJECTIVE: The schizophrenic patients with high suicide risk are characterized by depression, better cognitive function, and prominent positive symptoms. However, the neurobiological basis of suicide attempts in schizophrenia is not clear. The suicide in schizophrenia is implicated in the defects in emotional process and decision-making, which are associated with prefrontal-cingulate circuit. In order to explore the possible neurobiological basis of suicide in schizophrenia, we investigated the correlation of prefrontal-cingulate circuit with suicide risk in schizophrenia via dynamic casual modelling. METHOD: Participants were 33 first-episode schizophrenic patients comprising of a high suicide risk group (N = 14) and a low suicide risk group (N = 19). A comparison group of healthy controls (N = 15) were matched for age, gender and education. N-back tasking functional magnetic resonance imaging data was collected. RESULTS: Compared with healthy controls group, the two patients groups showed decreased task-related suppression during 2-back task state versus baseline state in the left posterior cingulate and medial prefrontal cortex; the hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex existed in both schizophrenic patients groups, but hypo-connectivity in the opposite direction only existed in the schizophrenic patients group with high suicide risk. CONCLUSIONS: The hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex may suggest that the abnormal effective connectivity was associated with risk for schizophrenia. The hypo-connectivity in the opposite direction may represent a possible correlate of increased vulnerability to suicide attempt

Resilience and Cognitive Function in Patients With Schizophrenia and Bipolar Disorder, and Healthy Controls

Background: This study compared adaptive resilience among patients with schizophrenia, bipolar disorder, and healthy controls, and examined the relationship of resilience to cognitive function.Methods: A sample of 81 patients diagnosed with schizophrenia, 34 with bipolar disorder, and 52 healthy controls completed the Connor-Davidson Resilience Scale (CD-RISC) and cognitive tests of verbal comprehension, executive functioning, and working memory. Paired comparison of diagnostic groups on CD-RISC and cognitive tests was conducted. Linear regression was used to identify the independent association of clinical diagnoses and neurocognition with resilience deficits.Results: Both patient groups showed significantly lower CD-RISC scores and poorer cognitive function than healthy controls and the schizophrenia group scored lower than bipolar group on these measures as well. CD-RISC scores were positively correlated with all three cognitive measures in the entire sample but not within the diagnostic subgroups. Multiple regression analysis showed differences in CD-RISC between diagnostic groups were not mediated by differences in these three measures of neurocognition.Discussion: Schizophrenia and bipolar disorder are associated with impairments in both resilience and cognitive function but the impairment in resilience appears to be independent of deficits in cognitive function measured here and may reflect unmeasured dimensions of cognitive function, other impairments or environmental factors