Whole-brain structural and functional neuroimaging of individuals who attempted suicide and people who did not: A systematic review and exploratory coordinate-based meta-analysis

Suicide is the cause of death of approximately 800,000 people a year. Despite the relevance of this behaviour, risk assessment tools rely on clinician experience and subjective ratings. Given that previous suicide attempts are the single strongest predictors of future attempts, we designed a systematic review and coordinate-based meta-analysis to demonstrate whether neuroimaging features can help distinguish individuals who attempted suicide from subjects who did not. Out of 5,659 publications from PubMed, Scopus, and Web of Science, we summarised 102 experiments and meta-analysed 23 of them. A cluster in the right superior temporal gyrus, a region implicated in emotional processing, might be functionally hyperactive in individuals who attempted suicide. No statistically significant differences in brain morphometry were evidenced. Furthermore, we used JuSpace to show that this cluster is enriched in 5-HT1A heteroreceptors in the general population. This exploratory meta-analysis provides a putative neural substrate linked to previous suicide attempts. Heterogeneity in the analytical techniques and weak or absent power analysis of the studies included in this review currently limit the applicability of the findings, the replication of which should be prioritised

Dynamic functional connectivity in schizophrenia and bipolar disorder: A review of the evidence and associations with psychopathological features

Alterations of functional network connectivity have been implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). Recent studies also suggest that the temporal dynamics of functional connec-tivity (dFC) can be altered in these disorders. Here, we summarized the existing literature on dFC in SCZ and BD, and their association with psychopathological and cognitive features. We systematically searched PubMed, Web of Science, and Scopus for studies investigating dFC in SCZ and BD and identified 77 studies. Our findings support a general model of dysconnectivity of dFC in SCZ, whereas a heterogeneous picture arose in BD. Although dFC alterations are more severe and widespread in SCZ compared to BD, dysfunctions of a triple network system underlying goal-directed behavior and sensory-motor networks were present in both disorders. Furthermore, in SCZ, positive and negative symptoms were associated with abnormal dFC.Implications for understanding the pathophysiology of disorders, the role of neurotransmitters, and treatments on dFC are discussed. The lack of standards for dFC metrics, replication studies, and the use of small samples represent major limitations for the field

Increased gyrification in schizophrenia and non affective first episode of psychosis

Prefrontal cortex gyrification has been suggested to be altered in patients with schizophrenia and first episode psychosis. Therefore, it may represent a possible trait marker for these illnesses and an indirect evidence of a disrupted underlying connectivity. The aim of this study was to add further evidence to the existing literature on the role of prefrontal gyrification in psychosis by carrying out a study on a sizeable sample of chronic patients with schizophrenia and non-affective first-episode psychosis (FEP-NA) patients. Methods: Seventy-two patients with schizophrenia, 51 FEP-NA patients (12 who later develop schizophrenia) and 95 healthy controls (HC) underwent magnetic resonance imaging (MRI). Cortical folding was quantified using the automated gyrification index (GI). GI values were compared among groups and related to clinical variables. Results: Both FEP-NA and patients with schizophrenia showed a higher mean prefrontal GI compared to HC (all p. <. 0.05). Interestingly, no differences have been observed between the two patients groups as well as between FEP-NA patients who did and did not develop schizophrenia. Conclusions: Our results suggest the presence of a shared aberrant prefrontal GI in subjects with both schizophrenia and first-episode psychosis. These findings support the hypothesis that altered GI represents a neurodevelopmental trait marker for psychosis, which may be involved in the associated neurocognitive deficits

The Risk for Schizophrenia-Bipolar Spectrum: Does the Apple Fall Close to the Tree? A Narrative Review

: Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric disorders that share clinical features and several risk genes. Important information about their genetic underpinnings arises from intermediate phenotypes (IPs), quantifiable biological traits that are more prevalent in unaffected relatives (RELs) of patients compared to the general population and co-segregate with the disorders. Within IPs, neuropsychological functions and neuroimaging measures have the potential to provide useful insight into the pathophysiology of SCZ and BD. In this context, the present narrative review provides a comprehensive overview of the available evidence on deficits in neuropsychological functions and neuroimaging alterations in unaffected relatives of SCZ (SCZ-RELs) and BD (BD-RELs). Overall, deficits in cognitive functions including intelligence, memory, attention, executive functions, and social cognition could be considered IPs for SCZ. Although the picture for cognitive alterations in BD-RELs is less defined, BD-RELs seem to present worse performances compared to controls in executive functioning, including adaptable thinking, planning, self-monitoring, self-control, and working memory. Among neuroimaging markers, SCZ-RELs appear to be characterized by structural and functional alterations in the cortico-striatal-thalamic network, while BD risk seems to be associated with abnormalities in the prefrontal, temporal, thalamic, and limbic regions. In conclusion, SCZ-RELs and BD-RELs present a pattern of cognitive and neuroimaging alterations that lie between patients and healthy individuals. Similar abnormalities in SCZ-RELs and BD-RELs may be the phenotypic expression of the shared genetic mechanisms underlying both disorders, while the specificities in neuropsychological and neuroimaging profiles may be associated with the differential symptom expression in the two disorders

The effect of polygenic risk scores for major depressive disorder, bipolar disorder and schizophrenia on morphological brain measures: A systematic review of the evidence

Background: Major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SCZ) share clinical features and genetic bases. Magnetic Resonance Imaging (MRI) studies assessing the effect of polygenic risk score (PRS) for psychiatric disorders on brain structure show heterogeneous results. Therefore, we provided an overview of the existing evidence on the association between PRS for MDD, BD and SCZ and MRI abnormalities in clinical and healthy populations. Methods: A search on PubMed, Web of Science and Scopus was performed to identify the studies exploring the effect of PRS for MDD, BD and SCZ on MRI measures. A total of 25 studies were included (N = 13 on healthy individuals and N = 12 on clinical populations). Results: Both in affected and unaffected individuals, PRS for BD and SCZ showed either positive or negative correlations with cortical thickness (CT), mostly involving fronto-temporal areas, whereas PRS for MDD was associated with cortical alterations in prefrontal regions in healthy subjects. Limitations: The heterogeneity in the methods limits the conclusions of this review. Conclusions: Overall the evidence on the effect of PRS for MDD, BD and SCZ on brain is considerably heterogeneous and far to be conclusive. However, from the results emerged that PRS for MDD, BD and SCZ were associated with widespread cortical abnormalities in all the populations explored, suggesting that genetic risk for MDD, BD and SCZ might affect neurodevelopmental processes, resulting in cortical alterations that transcend diagnostic boundaries and seem to be independent from the clinical status

Neuroimaging alterations associated with medication use in early-onset bipolar disorder: An updated review

Background: Pediatric bipolar disorder (PBD) is a severe disorder characterized by mood fluctuations starting at a young age. Several neuroimaging studies revealed a specific biological signature of PBD involving alterations in the amygdala and prefrontal regions. Considering the growing concerns regarding the effects of PBD treatments on developing brains, this review aims to provide an overview of the studies investigating the effect of mood stabilizers, antipsychotics, and anticonvulsants on neuroimaging findings in PBD.Methods: We searched PubMed, Scopus, and Web of Science to identify all structural magnetic resonance imaging (sMRI), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI) studies exploring the effects of medications on neuroimaging findings in PBD. A total of 18 studies met our inclusion criteria (fMRI n = 11, sMRI n = 6, DTI n = 1).Results: Although the findings varied highly across the studies, some investigations consistently indicated that medications primarily affect the prefrontal cortex and the amygdala. Moreover, despite some exceptions, the reported medication effects predominantly lean towards structural and functional normalization. Limitations: The reviewed studies differ in methods, medications, and fMRI paradigms. Furthermore, most studies used observational approaches with small sample sizes, minimizing the statistical power.Conclusions: Evidence suggests the potential of antipsychotics and mood stabilizers to modulate the neuroimaging findings in PBD patients, mostly normalizing brain structure and function in key mood-regulating regions