Similarities and differences of functional connectivity in drug-naïve, first-episode adolescent and young adult with major depressive disorder and schizophrenia

Major depressive disorder (MDD) and schizophrenia (SZ) are considered two distinct psychiatric disorders. Yet, they have considerable overlap in symptomatology and clinical features, particularly in the initial phases of illness. The amygdala and prefrontal cortex (PFC) appear to have critical roles in these disorders; however, abnormalities appear to manifest differently. In our study forty-nine drug-naïve, first-episode MDD, 45 drug-naïve, first-episode SZ, and 50 healthy control (HC) participants from 13 to 30 years old underwent resting-state functional magnetic resonance imaging. Functional connectivity (FC) between the amygdala and PFC was compared among the three groups. Significant differences in FC were observed between the amygdala and ventral PFC (VPFC), dorsolateral PFC (DLPFC), and dorsal anterior cingulated cortex (dACC) among the three groups. Further analyses demonstrated that MDD showed decreased amygdala-VPFC FC and SZ had reductions in amygdala-dACC FC. Both the diagnostic groups had significantly decreased amygdala-DLPFC FC. These indicate abnormalities in amygdala-PFC FC and further support the importance of the interaction between the amygdala and PFC in adolescents and young adults with these disorders. Additionally, the alterations in amygdala-PFC FC may underlie the initial similarities observed between MDD and SZ and suggest potential markers of differentiation between the disorders at first onset

Identifying and validating subtypes within major psychiatric disorders based on frontal-posterior functional imbalance via deep learning

Converging evidence increasingly implicates shared etiologic and pathophysiological characteristics among major psychiatric disorders (MPDs), such as schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Examining the neurobiology of the psychotic-affective spectrum may greatly advance biological determination of psychiatric diagnosis, which is critical for the development of more effective treatments. In this study, ensemble clustering was developed to identify subtypes within a trans-diagnostic sample of MPDs. Whole brain amplitude of low-frequency fluctuations (ALFF) was used to extract the low-dimensional features for clustering in a total of 944 participants: 581 psychiatric patients (193 with SZ, 171 with BD, and 217 with MDD) and 363 healthy controls (HC). We identified two subtypes with differentiating patterns of functional imbalance between frontal and posterior brain regions, as compared to HC: (1) Archetypal MPDs (60% of MPDs) had increased frontal and decreased posterior ALFF, and decreased cortical thickness and white matter integrity in multiple brain regions that were associated with increased polygenic risk scores and enriched risk gene expression in brain tissues; (2) Atypical MPDs (40% of MPDs) had decreased frontal and increased posterior ALFF with no associated alterations in validity measures. Medicated Archetypal MPDs had lower symptom severity than their unmedicated counterparts; whereas medicated and unmedicated Atypical MPDs had no differences in symptom scores. Our findings suggest that frontal versus posterior functional imbalance as measured by ALFF is a novel putative trans-diagnostic biomarker differentiating subtypes of MPDs that could have implications for precision medicine

Structural and functional abnormities of amygdala and prefrontal cortex in major depressive disorder with suicide attempts

Finding neural features of suicide attempts (SA) in major depressive disorder (MDD) may be helpful in preventing suicidal behavior. The ventral and medial prefrontal cortex (PFC), as well as the amygdala form a circuit implicated in emotion regulation and the pathogenesis of MDD. The aim of this study was to identify whether patients with MDD who had a history of SA show structural and functional connectivity abnormalities in the amygdala and PFC relative to MDD patients without a history of SA. We measured gray matter volume in the amygdala and PFC and amygdala-PFC functional connectivity using structural and functional magnetic resonance imaging (MRI) in 158 participants [38 MDD patients with a history of SA, 60 MDD patients without a history of SA, and 60 healthy control (HC)]. MDD patients with a history of SA had decreased gray matter volume in the right and left amygdala (F = 30.270, P = 0.000), ventral/medial/dorsal PFC (F = 15.349, P = 0.000), and diminished functional connectivity between the bilateral amygdala and ventral and medial PFC regions (F = 22.467, P = 0.000), compared with individuals who had MDD without a history of SA, and the HC group. These findings provide evidence that the amygdala and PFC may be closely related to the pathogenesis of suicidal behavior in MDD and implicate the amygdala-ventral/medial PFC circuit as a potential target for suicide intervention

Structural and functional abnormities of amygdala and prefrontal cortex in major depressive disorder with suicide attempts

Finding neural features of suicide attempts (SA) in major depressive disorder (MDD) may be helpful in preventing suicidal behavior. The ventral and medial prefrontal cortex (PFC), as well as the amygdala form a circuit implicated in emotion regulation and the pathogenesis of MDD. The aim of this study was to identify whether patients with MDD who had a history of SA show structural and functional connectivity abnormalities in the amygdala and PFC relative to MDD patients without a history of SA. We measured gray matter volume in the amygdala and PFC and amygdala-PFC functional connectivity using structural and functional magnetic resonance imaging (MRI) in 158 participants [38 MDD patients with a history of SA, 60 MDD patients without a history of SA, and 60 healthy control (HC)]. MDD patients with a history of SA had decreased gray matter volume in the right and left amygdala (F = 30.270, P = 0.000), ventral/medial/dorsal PFC (F = 15.349, P = 0.000), and diminished functional connectivity between the bilateral amygdala and ventral and medial PFC regions (F = 22.467, P = 0.000), compared with individuals who had MDD without a history of SA, and the HC group. These findings provide evidence that the amygdala and PFC may be closely related to the pathogenesis of suicidal behavior in MDD and implicate the amygdala-ventral/medial PFC circuit as a potential target for suicide intervention

A real-world observation of antipsychotic effects on brain volumes and intrinsic brain activity in schizophrenia

Background: The confounding effects of antipsychotics that led to the inconsistencies of neuroimaging findings have long been the barriers to understanding the pathophysiology of schizophrenia (SZ). Although it is widely accepted that antipsychotics can alleviate psychotic symptoms during the early most acute phase, the longer-term effects of antipsychotics on the brain have been unclear. This study aims to look at the susceptibility of different imaging measures to longer-term medicated status through real-world observation. Methods: We compared gray matter volume (GMV) with amplitude of low-frequency fluctuations (ALFFs) in 89 medicated-schizophrenia (med-SZ), 81 unmedicated-schizophrenia (unmed-SZ), and 235 healthy controls (HC), and the differences were explored for relationships between imaging modalities and clinical variables. We also analyzed age-related effects on GMV and ALFF values in the two patient groups (med-SZ and unmed-SZ). Results: Med-SZ demonstrated less GMV in the prefrontal cortex, temporal lobe, cingulate gyri, and left insula than unmed-SZ and HC ( Conclusion: GMV loss appeared to be pronounced to longer-term antipsychotics, whereby imbalanced alterations in regional low-frequency fluctuations persisted unaffected by antipsychotic treatment. Our findings may help to understand the disease course of SZ and potentially identify a reliable neuroimaging feature for diagnosis

The Relationship Between Cognitive Dysfunction and Symptom Dimensions Across Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Background: Cognitive dysfunction is considered a core feature among schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Despite abundant literature comparing cognitive dysfunction among these disorders, the relationship between cognitive dysfunction and symptom dimensions remains unclear. The study aims are a) to identify the factor structure of the BPRS-18 and b) to examine the relationship between symptom domains and cognitive function across SZ, BD, and MDD.Methods: A total of 716 participants [262 with SZ, 104 with BD, 101 with MDD, and 249 healthy controls (HC)] were included in the study. One hundred eighty participants (59 with SZ, 23 with BD, 24 with MDD, and 74 HC) completed the MATRICS Consensus Cognitive Battery (MCCB), and 507 participants (85 with SZ, 89 with BD, 90 with MDD, and 243 HC) completed the Wisconsin Card Sorting Test (WCST). All patients completed the Brief Psychiatric Rating Scale (BPRS).Results: We identified five BPRS exploratory factor analysis (EFA) factors (“affective symptoms,” “psychosis,” “negative/disorganized symptoms,” “activation,” and “noncooperation”) and found cognitive dysfunction in all of the participant groups with psychiatric disorders. Negative/disorganized symptoms were the most strongly associated with cognitive dysfunctions across SZ, BD, and MDD.Conclusions: Our findings suggest that cognitive dysfunction severity relates to the negative/disorganized symptom domain across SZ, BD, and MDD, and negative/disorganized symptoms may be an important target for effective cognitive remediation in SZ, BD, and MDD