Effects of frequent assessments on the severity of suicidal thoughts: an ecological momentary assessment study.

Objective: In recent years, there has been a significant increase in research using ecological momentary assessment (EMA) to explore suicidal thoughts and behaviors (STBs). Meanwhile, concerns have been raised regarding the potential impacts of frequent and intense STBs assessments on the study participants. Methods: From November 2021 to June 2023, a total of 83 adolescent and young adult outpatients (Mage = 21.0, SDage = 6.3, 71.1% female), who were diagnosed with mood disorders, were recruited from three psychiatric clinics in China. Smartphone-based EMA was used to measure suicidal thoughts three times per day at randomly selected times. We examined the change of suicidal thoughts in each measurement and within 1 day to evaluate potential adverse effects using Bayesian multilevel models. Results: The 3,105 effective surveys were nested in 83 participants (median follow-up days: 14 days). The results of two-level models indicated that suicidal thoughts decreased during the monitoring period. However, this effect varied among different individuals in the two-level model. Conclusion: Our findings did not support the notion that repeated assessment of suicidal thoughts is iatrogenic, but future research should continue to investigate the impact of frequent assessment on suicidal thoughts, taking into account individual differences and utilizing larger sample sizes.

Polysomnographic features of insomnia occurring in major depressive disorder, generalized anxiety disorder and bipolar mania: Comparison with primary insomnia and association with metabolic indicators.

BACKGROUND: Insomnia is very common in psychiatric disorders, but the polysomnographic (PSG) characteristics of insomnia in various psychiatric disorders are still not agreed upon. This study aimed to investigate the characteristics of PSG and its relationship with metabolic indicators in insomnia patients with affective disorders and primary insomnia (PI) patients. METHODS: A total of 38 patients with PI, 44 major depressive disorder patients with insomnia (DI), 49 generalized anxiety disorder patients with insomnia (GI), and 19 bipolar mania patients with insomnia (BI) were included. PSG was used to detect sleep problems in subjects, and biochemical indicators were also collected. RESULTS: The results of this study found that subjects with BI were lower on REM sleep latency (RL), awakenings number (AN), number of microarousals (NM), and apnea-hypopnea index (AHI) than those with DI and GI, and lower on RL and AN than those with PI. Subjects with PI had lower NM and AHI than those with DI and GI. Patients with DI had a higher RL than those with GI. All results passed Bonferroni correction (p < 0.00078). No differences in biochemical indices were found among the four groups of subjects. Also, AHI was found to be positively correlated with free triiodothyronine (FT3) and fasting blood glucose in subjects. CONCLUSION: This study suggests that various psychiatric disorders may have their characteristics in terms of PSG parameters, which prompted us to focus on the PSG characteristics of these disorders when assessing them, as well as to focus on their biochemical indicators.

Profile and mental health characterization of childhood overprotection/overcontrol experiences among Chinese university students: a nationwide survey.

Introduction: The childhood experiences of being overprotected and overcontrolled by family members have been suggested to be potentially traumatic. However, the possible associated factors of these experiences among young people are still not well studied. This study aimed to partly fill such gaps by a relatively large, nationwide survey of Chinese university students. Methods: A total of 5,823 university students across nine different provinces in China were included by the convenience sampling method in the data analyses. All participants completed the overprotection/overcontrol (OP/OC) subscale in a recently developed 33-item childhood trauma questionnaire (CTQ- 33). Data were also collected on all participants' socio-demographic profiles and characterization of mental health. Binary logistic regression was conducted to investigate the associated socio-demographic and psychological factors of OP/ OC. Results: The prevalence of childhood OP/OC was estimated as 15.63% (910/5,823) based on a cutoff OP/OC subscale score of ≥ 13. Binary logistic regression suggested that being male, being a single child, having depression, having psychotic-like experiences, lower family functioning, and lower psychological resilience were independently associated with childhood OP/OC experiences (all corrected-p < 0.05). The OP/OC was also positively associated with all the other trauma subtypes (abuses and neglects) in the CTQ-33, while there are both shared and unique associated factors between the OP/OC and other trauma subtypes. Post-hoc analyses suggested that OP/OC experiences were associated with depression in only females and associated with anxiety in only males. Discussion: Our results may provide initial evidence that childhood OP/OC experiences would have negative effects on young people's mental health which merits further investigations, especially in clinical populations.

Hypoactive Visual Cortex, Prefrontal Cortex and Insula during Self-Face Recognition in Adults with First-Episode Major Depressive Disorder.

Self-face recognition is a vital aspect of self-referential processing, which is closely related to affective states. However, neuroimaging research on self-face recognition in adults with major depressive disorder is lacking. This study aims to investigate the alteration of brain activation during self-face recognition in adults with first-episode major depressive disorder (FEMDD) via functional magnetic resonance imaging (fMRI); FEMDD (n = 59) and healthy controls (HC, n = 36) who performed a self-face-recognition task during the fMRI scan. The differences in brain activation signal values between the two groups were analyzed, and Pearson correlation analysis was used to evaluate the relationship between the brain activation of significant group differences and the severity of depressive symptoms and negative self-evaluation; FEMDD showed significantly decreased brain activation in the bilateral occipital cortex, bilateral fusiform gyrus, right inferior frontal gyrus, and right insula during the task compared with HC. No significant correlation was detected between brain activation with significant group differences and the severity of depression and negative self-evaluation in FEMDD or HC. The results suggest the involvement of the malfunctioning visual cortex, prefrontal cortex, and insula in the pathophysiology of self-face recognition in FEMDD, which may provide a novel therapeutic target for adults with FEMDD.

The anatomical networks based on probabilistic structurally connectivity in bipolar disorder across mania, depression, and euthymic states.

BACKGROUNDS: There have pieces of evidence of the distinct aberrant functional network topology profile in bipolar disorder (BD) across mania, depression, and euthymic episodes. However, the underlying anatomical network topology pattern in BD across different episodes is unclear. METHODS: We calculated the whole-brain probabilistic structurally connectivity across 143 subjects (72 with BD [34 depression; 13 mania; 25 euthymic] and 53 healthy controls), and used graph theory to examine the trait- and state-related topology alterations of the structural connectome in BD. The correlation analysis was further conducted to explore the relationship between detected network measures and clinical symptoms. RESULTS: There no omnibus alteration of any global network metrics were observed across all diagnostic groups. In the regional network metrics level, bipolar depression showed increased clustering coefficient in the right lingual gyrus compared with all other groups, and the increased clustering coefficient in the right lingual gyrus positively correlated with depression, anxiety, and illness burden symptoms but negatively correlated with mania symptoms; manic and euthymic patients showed decreased clustering coefficient in the left inferior occipital gyrus compared with HCs. LIMITATIONS: The moderate sample size of all patient groups (especially for subjects with mania) might have contributed to the negative findings of the trait feature in this study. CONCLUSIONS: We demonstrated the altered regional connectivity pattern in the occipital lobe of the bipolar depression and mania episode, especially the lingual gyrus. The association of the clustering coefficient in the lingual gyrus with clinical symptoms helps monitor the state of BD.

Sex difference in the prevalence of psychotic-like experiences in adolescents: results from a pooled study of 21,248 Chinese participants.

Psychotic-like experiences (PLEs) are subclinical psychotic symptoms in the general population which are linked to increased risks for later psychiatric disorders. Male and female adolescents were reported to experience PLEs differently, but the results were mixed in previous studies. This study aimed to investigate possible sex differences in the prevalence of adolescent PLEs using a large pooled sample. A total of 21,248 Chinese adolescents aged 11 to 19 years were included, which were drawn from five separate cross-sectional surveys undertaken between 2015 to 2021 in China. PLEs were measured by the 8-item Community Assessment of Psychic Experiences. Using binary logistic regression analyses, no significant sex differences were found in the overall prevalence of PLEs after controlling for age and dataset effects. As for specific PLE subtypes, however, being female was associated with a higher prevalence of delusion of reference and a lower prevalence of visual hallucinations. Furthermore, post-hoc subgroup analyses showed that the sex differences in visual hallucinations persist across both early (<= 14 years old) and late (> 14 years old) adolescence, while differences in the delusion of reference were significant in only early adolescence. These findings may help us to further understand the biological basis of PLEs.

Mediating role of impaired wisdom in the relation between childhood trauma and psychotic-like experiences in Chinese college students: a nationwide cross-sectional study.

BACKGROUND: The association between childhood trauma (CT) and psychotic-like experiences (PLEs) is well-established. Many previous studies have recognized wisdom as a protective factor for mental health, but its role in the relation between CT and PLEs remains unknown. We aimed to investigate the mediating effect of wisdom in the above association among Chinese college students. METHODS: We conducted a nationwide survey covering 9 colleges across China and recruited a total of 5873 students using online questionnaires between September 14 and October 18, 2021. Convenience sampling was adopted. We employed the San Diego Wisdom Scale (SD-WISE), the Childhood Trauma Questionnaire (CTQ-28), and the 15-item Positive Subscale of the Community Assessment of Psychic Experiences (CAPE-15) to measure the wisdom, CT and PLEs, respectively. Descriptive, correlation, and mediation analysis were utilized. RESULTS: The positive correlation between CT and PLEs was well-replicated among college students (Pearson's r = 0.30, p < 0.001). Wisdom was negatively associated with CT (Pearson's r = - 0.46, p < 0.001) and frequency of PLEs (Pearson's r = - 0.25, p < 0.001). Total wisdom scores partially mediated the relationship between cumulative childhood trauma, neglect, abuse and PLEs, separately. The mediated model respectively explained 21.9%, 42.54% and 18.27% of the effect of CT on PLEs. Our model further suggested that childhood trauma could be related to PLEs through decreasing the following wisdom components: decisiveness, emotional regulation and prosocial behavior. CONCLUSION: For the first time, our results suggested that impaired wisdom played a role in the translation from childhood adversity to subclinical psychotic symptoms, implicating wisdom as a possible target for early intervention for psychosis among young individuals. Longitudinal work is warranted to verify the clinical implications.

Aberrant brain dynamics in major depressive disorder with suicidal ideation.

BACKGROUND: Suicidal ideation (SI) is a common symptom of major depressive disorder (MDD). Accumulating studies demonstrated that MDD with SI was associated with static alterations in brain activity and functional connectivity. However, given that brain is a highly dynamic system, the changes of brain dynamic patterns in MDD with SI remain unknown. METHODS: We included 60 MDD patients with SI (MDD-SI), 58 MDD patients without SI (MDD-NSI), and 58 healthy controls (HCs) who underwent resting-state functional magnetic resonance imaging. The sliding-window approach was used to calculate the dynamic fractional amplitude of low-frequency fluctuation (dfALFF) and dynamic degree centrality (dDC) to characterize the temporal dynamic regional activity and distant functional connectivity. We compared dfALFF and dDC across groups and further conducted correlations between abnormal dynamic metrics and the severity of suicidality. RESULTS: In terms of the dynamic regional activity, MDD-SI showed decreased dfALFF in the left lingual gyrus and right middle occipital gyrus compared with MDD-NSI; in terms of the dynamic distant connectivity, MDD-SI showed decreased dDC in the right middle frontal gyrus compared with MDD-NSI. The decreased dDC in the right middle frontal gyrus was correlated with increased severity of suicidality. LIMITATIONS: The relatively small sample size. CONCLUSIONS: We demonstrate the specific brain dynamic patterns of MDD-SI in regional activity and distant functional connectivity compared to MDD-NSI. Especially the decreased temporal variability of the distant connectivity in the middle frontal gyrus was associated with SI. These altered dynamic patterns may represent a potential neurobiological diathesis of SI in MDD.

Aberrant integrity of the cortico-limbic-striatal circuit in major depressive disorder with suicidal ideation.

BACKGROUND: Suicidal ideation is a common symptom of major depressive disorder (MDD) that reflects a cognitive alteration in the background of intense emotional dysregulation. Amygdala is a critical emotion processing center that facilitates moving from emotional appraisal to action. However, whether MDD patients with suicidal ideation show dysconnectivity of the amygdala within a large-scale neurocognitive circuitry remains unknown. METHODS: Participants were 22 MDD patients without suicidal ideation (MDD-NSI), 59 MDD patients with suicidal ideation (MDD-SI), and 60 healthy controls (HCs). We compared the amygdala-based resting-state functional connectivity of four amygdala subregions across the three groups. We selected brain regions with significant between-group differences in amygdalar conectivity as the regions of interest (ROI) and performed ROI-to-ROI and graph-theoretical analyses to explore dysconnectivity patterns at various granularity levels. RESULTS: Brain regions showing omnibus differences across the three groups were distributed across a cortico-limbic-striatal circuitry. MDD-SI had unique dysconnectivity of the lateral amygdala with caudate, middle temporal gyrus, and postcentral gyrus compared with the other two groups. MDD-SI and MDD-NSI had shared dysconnectivity of the medial amygdala with medial superior frontal gyrus and middle temporal gyrus. Within the derived cortico-limbic-striatal circuitry, MDD-SI exhibited lower global connectivity, reduced sigma (small-worldness), but increased lambda (path-length) than HCs. Reduced sigma correlated with increased severity of suicidal ideation. We achieved high classification accuracy (84.09%, with AUC 0.82) in distinguishing MDD-SI from MDD-NSI. CONCLUSIONS: Aberrant integrity of the cortico-limbic-striatal circuit centered on the amygdala provides a promising neural substrate for suicidal ideation that requires further investigation in MDD.

Imbalance Between Prefronto-Thalamic and Sensorimotor-Thalamic Circuitries Associated with Working Memory Deficit in Schizophrenia.

BACKGROUND: Thalamocortical circuit imbalance characterized by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity has been consistently documented at rest in schizophrenia (SCZ). However, this thalamocortical imbalance has not been studied during task engagement to date, limiting our understanding of its role in cognitive dysfunction in schizophrenia. METHODS: Both n-back working memory (WM) task-fMRI and resting-state fMRI data were collected from 172 patients with SCZ and 103 healthy control subjects (HC). A replication sample with 49 SCZ and 48 HC was independently obtained. Sixteen thalamic subdivisions were employed as seeds for the analysis. RESULTS: During both task-performance and rest, SCZ showed thalamic hyperconnectivity with sensorimotor cortices, but hypoconnectivity with prefrontal-cerebellar regions relative to controls. Higher sensorimotor-thalamic connectivity and lower prefronto-thalamic connectivity both relate to poorer WM performance (lower task accuracy and longer response time) and difficulties in discriminating target from nontarget (lower d' score) in n-back task. The prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity were anti-correlated both in SCZ and HCs; this anti-correlation was more pronounced with less cognitive demand (rest>0-back>2-back). These findings replicated well in the second sample. Finally, the hypo- and hyper-connectivity patterns during resting-state positively correlated with the hypo- and hyper-connectivity during 2-back task-state in SCZ respectively. CONCLUSIONS: The thalamocortical imbalance reflected by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity is present both at rest and during task engagement in SCZ and relates to working memory performance. The frontal reduction, sensorimotor enhancement pattern of thalamocortical imbalance is a state-invariant feature of SCZ that affects a core cognitive function.

Changes of psychotic-like experiences and their association with anxiety/depression among young adolescents before COVID-19 and after the lockdown in China.

OBJECTIVE: Lockdown policies during COVID-19 pandemic have potential adverse psychological impacts on youth. However, little is known about their influence on the changes of psychotic-like experiences (PLEs) among adolescents, nor about the possible association between changes in PLEs and changes in anxiety/depression symptoms. We investigated these two questions through a longitudinal comparative study. METHODS: In total, 1825 adolescents were surveyed before COVID-19 and after the lockdown in China (T0, October 20th, 2019 and T1, May 18th, 2020). PLEs, anxiety, and depression were measured with paranoia, anxiety and depression subscales of the Mental Health Inventory of Middle school students (MMHI-60). Within-subjects Wilcoxon test, Spearman correlation test, and Kruskal-Wallis test were adopted. RESULTS: Significant increase in adolescent PLEs scores was observed after the lockdown (Wilcoxon's w = 9.302, p < 0.001). We also found positive correlation between changes of PLEs and changes of anxiety/depression (Spearman's rho = 0.59/0.53, both p < 0.001). Furthermore, four PLEs trajectories were identified based on the report of PLEs at two timepoints: 60.4% with no PLEs, 9.3% remitted PLEs, 16.7% new PLEs, and 13.6% persistent PLEs. Significant difference was found in changes of anxiety/depression among four groups (p < 0.001); notably, the group with new-onset PLEs had the greatest exacerbation in anxiety/depression symptoms (both p Bonferroni <0.001). CONCLUSIONS: This work is the first to identify increases in adolescent PLEs across the COVID-19 pandemic and suggested a close longitudinal association between PLEs and anxiety/depression. Our findings have implications for adolescent mental health crisis interventions during the pandemic.

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 < 0.001). FF was negatively associated with both PS (r = -0.34, p < 0.001) and PLEs (r = -0.29, p < 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.

The Role of Military Training in Improving Psychological Resilience and Reducing Depression Among College Freshmen.

Background: Military training plays an important protective role in enhancing mental health. However, the effects of military training on psychological resilience and depression among college freshmen in China remain unclear. The present study aimed to evaluate changes in psychological resilience and depression through military training among college freshmen, and to investigate associated psychosocial factors including childhood trauma that may influence its effects on psychological resilience. Methods: A prospective and self-comparison study design was employed. College freshmen who received 3 weeks of military training were recruited. Socio-demographic variables were collected and childhood trauma exposure was estimated by the Childhood Trauma Questionnaire (CTQ). The Connor-Davidson Resilience Scale (CD-RISC) and Patient Health Questionnaire (PHQ-9) were used to assess psychological resilience and depression before and after the military-style training. Results: The military training significantly increased the total and subscale scores of CD-RISC (p < 0.001), and decreased the PHQ-9 score (p < 0.001). The proportion of students with clinical depression reduced from 10.5% at baseline to 7.2% after the training (p < 0.001). Improvement of CD-RISC scores was positively affected by male gender and urban area, while negatively affected by older age, and higher baseline scores of PHQ-9 and CTQ. A significant correlation was found between changes in scores of CD-RISC and PHQ-9 through the training (r = -0.238, p < 0.001). Conclusions: Military training may have a positive effect on increasing psychological resilience and reducing depressive symptoms among college freshmen, especially in male students and those from an urban area, while older age, childhood trauma, higher depression levels, and resilience at baseline may weaken, or even mask its positive effect. Follow-up research should be considered for the long-term effects of military-style training.

Abnormal Large-Scale Network Activation Present in Bipolar Mania and Bipolar Depression Under Resting State.

Introduction: Previous studies have primarily focused on the neuropathological mechanisms of the emotional circuit present in bipolar mania and bipolar depression. Recent studies applying resting-state functional magnetic resonance imaging (fMRI) have raise the possibility of examining brain-wide networks abnormality between the two oppositional emotion states, thus this study aimed to characterize the different functional architecture represented in mania and depression by employing group-independent component analysis (gICA). Materials and Methods: Forty-one bipolar depressive patients, 20 bipolar manic patients, and 40 healthy controls (HCs) were recruited and received resting-state fMRI scans. Group-independent component analysis was applied to the brain network functional connectivity analysis. Then, we calculated the correlation between the value of between-group differences and clinical variables. Results: Group-independent component analysis identified 15 components in all subjects, and ANOVA showed that functional connectivity (FC) differed significantly in the default mode network, central executive network, and frontoparietal network across the three groups. Further post-hoc t-tests showed a gradient descent of activity-depression > HC > mania-in all three networks, with the differences between depression and HCs, as well as between depression and mania, surviving after family wise error (FWE) correction. Moreover, central executive network and frontoparietal network activities were positively correlated with Hamilton depression rating scale (HAMD) scores and negatively correlated with Young manic rating scale (YMRS) scores. Conclusions: Three brain networks heighten activity in depression, but not mania; and the discrepancy regions mainly located in prefrontal, which may imply that the differences in cognition and emotion between the two states is associated with top-down regulation in task-independent networks.

Bipolar Mood State Reflected in Functional Connectivity of the Hate Circuit: A Resting-State Functional Magnetic Resonance Imaging Study.

BACKGROUND: Previous studies suggested bipolar disorder caused an aberrant alteration in the insular, putamen, and left superior frontal gyrus, which are the main components of the hate circuit. However, the relationship between the hate circuit and the pathophysiologic substrate underlying different phases of bipolar disorder remain unclear. In this study, we aimed to identify group differences of resting-state functional connectivity within the hate circuit in healthy controls (HCs) and bipolar patients in different mood states. METHODS: Resting-state functional magnetic resonance imaging of the brain were acquired from 54 HCs and 81 patients with bipolar disorder including 20 with bipolar mania (BM), 35 with bipolar depression (BD), and 26 with bipolar euthymia (BE). We selected bilateral insula (L.INS and R.INS), bilateral putamen (L.PUT and R.PUT), and left superior frontal gyrus (L.SFGd) as seed regions, and conducted the seed-based functional connectivity analysis to identify group differences of connectivity strength within the hate circuit. Spearman correlations were performed to evaluate the relationship between the hate circuit and manic/depressive symptoms. RESULTS: Significant group differences of connectivity strength within the hate circuit were found in links of the R.INS-L.SFGd, R.PUT-L.SFGd, and L.INS- R.PUT after false discovery rate was corrected. The BM group showed an opposite hate circuit pattern to BD, BE, and HCs. The BD group showed decreased hate circuit connectivity in the L.INS-R.PUT compared with the BE group. No significant difference was detected among BD, BE, and HCs. Furthermore, functional connectivity of the R.INS-L.SFGd and R.PUT-L.SFGd were positively correlated with manic symptoms, while the L.INS- R.PUT was negatively correlated with depressive symptoms. CONCLUSIONS: Our preliminary findings suggest that altered functional connectivity of the hate circuit in different mood phases may be related to state markers and underpin the neuropathological basis of bipolar disorder.

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.

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.

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.

Abnormal Connectivity Within Anterior Cortical Midline Structures in Bipolar Disorder: Evidence From Integrated MRI and Functional MRI.

Background: Aberrant functional and structural connectivity across multiple brain networks have been reported in bipolar disorder (BD). However, most previous studies consider the functional and structural alterations in isolation regardless of their possible integrative relationship. The present study aimed to identify the brain connectivity alterations in BD by capturing the latent nexus in multimodal neuroimaging data. Methods: Structural and resting-state images were acquired from 83 patients with BD and 94 healthy controls (HCs). Combined with univariate methods conducted to detect the dysconnectivity in BD, we also employed a semi-multimodal fusion framework fully utilizing the interrelationship between the two modalities to distinguish patients from HCs. Moreover, one-way analysis of variance was adopted to explore whether the detected dysconnectivity has differences across stages of patients with BD. Results: The semi-multimodal fusion framework distinguished patients from HCs with 81.47% accuracy, 85.42% specificity, and 74.75% sensitivity. The connection between the anterior cingulate cortex (ACC) and superior medial prefrontal cortex (sMPFC) contributed the most to BD diagnosis. Consistently, the univariate method also identified that this ACC-sMPFC functional connection significantly decreased in BD patients compared to HCs, and the significant order of the dysconnectivity is: depressive episode < HCs and remission episode < HCs. Conclusions: Our findings, by adopting univariate and multivariate analysis methods, shed light on the decoupling within the anterior midline brain in the pathophysiology of BD, and this decoupling may serve as a trait marker for this disease.

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.