Neural correlates of cognitive behavioral therapy-based interventions for bipolar disorder: A scoping review.

Cognitive Behavioral Therapy (CBT) is among the gold-standard psychotherapeutic interventions for the treatment of psychiatric disorders, including bipolar disorder (BD). While the clinical response of CBT in patients with BD has been widely investigated, its neural correlates remain poorly explored. Therefore, this scoping review aimed to discuss neuroimaging studies on CBT-based interventions in bipolar populations. Particular attention has been paid to similarities and differences between studies to inform future research. The literature search was conducted on PubMed, PsycINFO, and Web of Science databases in June 2023, identifying 307 de-duplicated records. Six studies fulfilled the inclusion criteria and were reviewed. All of them analyzed functional brain activity data. Four studies showed that the clinical response to CBT was associated with changes in the functional activity and/or connectivity of prefrontal and posterior cingulate cortices, temporal parietal junction, amygdala, precuneus, and insula. In two additional studies, a peculiar pattern of baseline activations in the prefrontal cortex, hippocampus, amygdala, and insula predicted post-treatment improvements in depressive symptoms, emotion dysregulation, and psychosocial functioning, although CBT-specific effects were not shown. These results suggest, at the very preliminary level, the potential of CBT-based interventions in modulating neural activity and connectivity of patients with BD, especially in regions ascribed to emotional processing. Nonetheless, the discrepancies between studies concerning aims, design, sample characteristics, and CBT and fMRI protocols do not allow conclusions to be drawn. Further research using multimodal imaging techniques, better-characterized BD samples, and standardized CBT-based interventions is needed.

Cannabis Dependence is Associated with Reduced Hippocampal Subregion Volumes Independently of Sex: Findings from an ENIGMA Addiction Working Group Multi-Country Study.

Background: Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of cannabis dependence as most neuroimaging studies have been conducted in largely male samples in which cannabis dependence, as opposed to use, is often not ascertained. Methods: We examined subregional hippocampus and amygdala volumetry in a sample of 206 people recruited from the ENIGMA Addiction Working Group. They included 59 people with cannabis dependence (17 females), 49 cannabis users without cannabis dependence (20 females), and 98 controls (33 females). Results: We found no group-by-sex effect on subregional volumetry. The left hippocampal cornu ammonis subfield 1 (CA1) volumes were lower in dependent cannabis users compared with non-dependent cannabis users (p<0.001, d=0.32) and with controls (p=0.022, d=0.18). Further, the left cornu ammonis subfield 3 (CA3) and left dentate gyrus volumes were lower in dependent versus non-dependent cannabis users but not versus controls (p=0.002, d=0.37, and p=0.002, d=0.31, respectively). All models controlled for age, intelligence quotient (IQ), alcohol and tobacco use, and intracranial volume. Amygdala volumetry was not affected by group or group-by-sex, but was smaller in females than males. Conclusions: Our findings suggest that the relationship between cannabis dependence and subregional volumetry was not moderated by sex. Specifically, dependent (rather than non-dependent) cannabis use may be associated with alterations in selected hippocampus subfields high in cannabinoid type 1 (CB1) receptors and implicated in addictive behavior. As these data are cross-sectional, it is plausible that differences predate cannabis dependence onset and contribute to the initiation of cannabis dependence. Longitudinal neuroimaging work is required to examine the time-course of the onset of subregional hippocampal alterations in cannabis dependence, and their progression as cannabis dependence exacerbates or recovers over time.

A critical overview of emotion processing assessment in non-affective and affective psychoses.

AIMS: Patients with affective and non-affective psychoses show impairments in both the identification and discrimination of facial affect, which can significantly reduce their quality of life. The aim of this commentary is to present the strengths and weaknesses of the available instruments for a more careful evaluation of different stages of emotion processing in clinical and experimental studies on patients with non-affective and affective psychoses. METHODS: We reviewed the existing literature to identify different tests used to assess the ability to recognise (e.g. Ekman 60-Faces Test, Facial Emotion Identification Test and Penn Emotion Recognition Test) and to discriminate emotions (e.g. Face Emotion Discrimination Test and Emotion Differentiation Task). RESULTS: The current literature revealed that few studies combine instruments to differentiate between different levels of emotion processing disorders. The lack of comprehensive instruments that integrate emotion recognition and discrimination assessments prevents a full understanding of patients' conditions. CONCLUSIONS: This commentary underlines the need for a detailed evaluation of emotion processing ability in patients with non-affective and affective psychoses, to characterise the disorder at early phases from the onset of the disease and to design rehabilitation treatments.

Measuring white matter microstructure in 1,457 cannabis users and 1,441 controls: A systematic review of diffusion-weighted MRI studies.

Introduction: Cannabis is the most widely used regulated substance by youth and adults. Cannabis use has been associated with psychosocial problems, which have been partly ascribed to neurobiological changes. Emerging evidence to date from diffusion-MRI studies shows that cannabis users compared to controls show poorer integrity of white matter fibre tracts, which structurally connect distinct brain regions to facilitate neural communication. However, the most recent evidence from diffusion-MRI studies thus far has yet to be integrated. Therefore, it is unclear if white matter differences in cannabis users are evident consistently in selected locations, in specific diffusion-MRI metrics, and whether these differences in metrics are associated with cannabis exposure levels. Methods: We systematically reviewed the results from diffusion-MRI imaging studies that compared white matter differences between cannabis users and controls. We also examined the associations between cannabis exposure and other behavioral variables due to changes in white matter. Our review was pre-registered in PROSPERO (ID: 258250; https://www.crd.york.ac.uk/prospero/). Results: We identified 30 diffusion-MRI studies including 1,457 cannabis users and 1,441 controls aged 16-to-45 years. All but 6 studies reported group differences in white matter integrity. The most consistent differences between cannabis users and controls were lower fractional anisotropy within the arcuate/superior longitudinal fasciculus (7 studies), and lower fractional anisotropy of the corpus callosum (6 studies) as well as higher mean diffusivity and trace (4 studies). Differences in fractional anisotropy were associated with cannabis use onset (4 studies), especially in the corpus callosum (3 studies). Discussion: The mechanisms underscoring white matter differences are unclear, and they may include effects of cannabis use onset during youth, neurotoxic effects or neuro adaptations from regular exposure to tetrahydrocannabinol (THC), which exerts its effects by binding to brain receptors, or a neurobiological vulnerability predating the onset of cannabis use. Future multimodal neuroimaging studies, including recently developed advanced diffusion-MRI metrics, can be used to track cannabis users over time and to define with precision when and which region of the brain the white matter changes commence in youth cannabis users, and whether cessation of use recovers white matter differences. Systematic review registration: www.crd.york.ac.uk/prospero/, identifier: 258250.

White matter modifications of corpus callosum in bipolar disorder: A DTI tractography review.

BACKGROUND: The recent widespread use of diffusion tensor imaging (DTI) tractography allowed researchers to investigate the diffusivity modifications and neuroanatomical changes of white matter (WM) fascicles in major psychiatric disorders, including bipolar disorder (BD). In BD, corpus callosum (CC) seems to have a crucial role in explaining the pathophysiology and cognitive impairment of this psychiatric disorder. This review aims to provide an overview on the latest results emerging from studies that investigated neuroanatomical changes of CC in BD using DTI tractography. METHODS: Bibliographic research was conducted on PubMed, Scopus and Web of Science datasets until March 2022. Ten studies fulfilled our inclusion criteria. RESULTS: From the reviewed DTI tractography studies a significant decrease of fractional anisotropy emerged in the genu, body and splenium of CC of BD patients compared to controls. This finding is coupled with reduction of fiber density and modification in fiber tract length. Finally, an increase of radial and mean diffusivity in forceps minor and in the entire CC was also reported. LIMITATIONS: Small sample size, heterogeneity in terms of methodological (diffusion gradient) and clinical (lifetime comorbidity, BD status, pharmacological treatments) characteristics. CONCLUSIONS: Overall, these findings suggest the presence of structural modifications in CC in BD patients, which may in turn explain the cognitive impairments often observed in this psychiatric disorder, especially in executive processing, motor control and visual memory. Finally, structural modifications may suggest an impairment in the amount of functional information and a morphological impact within those brain regions connected by CC.

Neuropsychological instruments for bipolar disorders: A systematic review on psychometric properties.

BACKGROUND: Cognitive deficits are a core feature of bipolar disorder (BD) that persist during the euthymic phase and affect global functioning. However, nowadays, there is no consensus on the optimal tool to capture cognitive deficits in BD. Therefore, this review aims to examine the psychometric properties of tools commonly used to assess cognitive functioning in BD. METHODS: Literature search was conducted on PubMed and Web of Science databases on August 1, 2022 and on April 20, 2023, yielding 1758 de-duplicated records. Thirteen studies fulfilled the inclusion criteria and were included in the review. RESULTS: All tools examined showed acceptable-to-good psychometric properties suggesting that both brief cognitive screeners and comprehensive batteries may be appropriate for detecting or monitoring cognitive changes in BD. LIMITATIONS: Methodological differences between the included studies precluded a direct comparison of the results. Further research is needed to investigate the psychometric properties of cognitive tools that assess also affective and social cognition. CONCLUSIONS: The tools examined appear sensitive enough to distinguish between BD patients with versus without cognitive deficits, however, an optimal tool has not yet been identified. The applicability and clinical utility of the tools may depend on multiple factors such as available resources. That said, web-based instruments are expected to become the first-choice instrument for cognitive screening as they can be applied on a large scale and at an affordable cost. As for second-level assessment instruments, the BACA shows robust psychometric properties and tests both affective and non-affective cognition.

Feasibility and preliminary efficacy of brief tele-psychotherapy for COVID-19 patients and their first-degree relatives.

BACKGROUND: The SARS-CoV-2 pandemic compromised the mental health of COVID-19 patients and their family members. Due to social distancing and lockdown measures, a remote, tele-psychotherapy program for former or current COVID-19 patients and their relatives was implemented. OBJECTIVE: The primary goal of this project was to evaluate intervention feasibility. The secondary aim was to assess the impact of the intervention by means of pre-post psychological changes. METHODS: After a phone-based eligibility screening and remote neuropsychological testing, participants completed online self-reports assessing baseline COVID-related psychopathology. Next, participants attended eight tele-psychotherapy sessions. After treatment, the online self-reports were completed again. RESULTS: Of 104 enrolled participants, 88 completed the intervention (84.6 % completion rate). Significant pre-post improvements were observed for generalized anxiety (d = 0.38), depression (d = 0.37), insomnia (d = 0.43), post-traumatic psychopathology (d = 0.54), and general malaise (d = 0.31). Baseline cluster analysis revealed a subgroup of 41 subjects (47.6 %) with no psychopathology, and a second subgroup of 45 subject (52.3 %) with moderate severity. Thirty-three percent of the second group reached full symptom remission, while 66 % remained symptomatic after treatment. CONCLUSIONS: Remote brief tele-psychotherapy for COVID-19 patients and their first-degree relatives is feasible and preliminary efficacious at reducing COVID-related psychopathology in a subgroup of patients. Further research is needed to investigate distinct profiles of treatment response.

Brain ageing and neurodegeneration in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a psychiatric condition characterized by alternating episodes of mania and depression frequently associated with cognitive impairments. BD is associated with brain alterations in fronto-temporal and limbic networks. Recent conceptualizations view BD as a neurodegenerative disorder characterized by progressive deterioration of grey and white matter (GM, WM) volumes and accelerated brain ageing. Therefore, we conducted a review gathering neuroimaging evidence about neurodegenerative processes in BD. METHODS: A literature search was conducted on the PubMed, Scopus and Web of Science databases in September 2021. After title and abstract screening of the retrieved records, 19 studies that met our inclusion criteria were included in the review. RESULTS: The available evidence suggests the presence of a progressive reduction of GM volumes at the whole-brain level and in the amygdala, prefrontal regions and the anterior cingulate cortex. Conversely, WM lesions and alterations seem to emerge only in the early phases of the condition masking the effects of normal ageing. Lastly, machine learning models indicate that the gap between predicted and chronological brain age differs considerably between healthy controls and BD patients, as the latter are characterized by larger gaps. LIMITATIONS: The included studies had cross-sectional study design, small sample sizes and heterogeneous methodology, and lack of control for pharmacological treatment. CONCLUSIONS: BD seems to be associated with generalized age-related structural GM volumes reductions and functional brain alterations thus suggesting the presence of neurodegenerative processes. Future systematic reviews and meta-analyses should be conducted to quantify the magnitude of brain ageing-related effects in BD.

A critical overview of tools for assessing cognition in bipolar disorder.

Cognitive deficits are prevalent in bipolar disorder even during the euthymic phase, having a negative impact on global functioning and quality of life. As such, more and more mental health professionals agree that neuropsychological assessment should be considered an essential component of the clinical management of bipolar patients. However, no gold standard tool has been established so far. According to bipolar disorder experts targeting cognition, appropriate cognitive tools should be brief, easy to administer, cost-effective and validated in the target population. In this commentary, we critically appraised the strengths and limitations of the tools most commonly used to assess cognitive functioning in bipolar patients, both for screening and diagnostic purposes.

Incidental findings on brain MRI in patients with first-episode and chronic psychosis.

Brain incidental findings (IFs) are unexpected brain abnormalities detected by a structural magnetic resonance (MRI) examination. We conducted a study to assess whether brain IFs are associated with first-episode psychosis (FEP) and chronic psychosis (affective vs. non-affective) compared to healthy controls (HC). Chi-squared analyses were run to compare the frequency of several IFs across groups. Logistic regression analyses were run to explore the association between group and IFs, accounting for sex, age, MRI field strength. We observed a higher frequency of most IFs in both FEP and chronic psychosis groups compared to HC, however most of the chi-squared tests did not reach significance. Patients with FEP and chronic psychosis were 3-4 times more likely to show deep white matter hyperintensities (WMH) than HC. Patients with FEP and affective chronic psychosis were 3-4 times more likely to show ventricular asymmetries than HC. All chronic patients were more likely to show periventricular WMH, liquoral spaces enlargements and ventricular system enlargements respectively. Our results suggest that deep WMH and ventricular asymmetries are associated with both the early and the chronic stages of psychosis, thus representing potential vulnerability factors already present before the onset of the symptoms, possibly due to neurodevelopmental insults.

The Italian version of the Brief Assessment of Cognition in Affective Disorders: performance of patients with bipolar disorder and healthy controls.

OBJECTIVES: Cognitive deficits in Bipolar Disorder (BD) are significant enough to have an impact on daily functioning. Therefore, appropriate tools must be used to improve our understanding of the nature and severity of cognitive deficits in BD. In this study, we aimed to compare the cognitive profiles of patients with BD and healthy controls (HC) applying the Italian version of the Brief Assessment of Cognition in Affective Disorders (BAC-A). METHODS: This cross-sectional study included 127 patients with BD and 134 HC. The participants' cognitive profiles were evaluated using the Italian version of the BAC-A, which assesses verbal memory, working memory, motor speed, verbal fluency, attention & processing speed, executive functions, and two new measures of affective processing. The BAC-A raw scores were corrected using the normative data for the Italian population. In addition, we explored whether intelligence quotient (IQ) and specific clinical variables would predict the BAC-A affective, non-affective, and total composite scores of patients with BD and HC. RESULTS: HC performed better than patients with BD in all BAC-A subtests (all p < .001), except for subtests of the Affective Interference Test. (p ≥ .05). The effect sizes varied in magnitude and ranged between d = 0.02 and d = 1.27. In patients with BD, lower BAC-A composite scores were predicted by a higher number of hospitalizations. There was a significant association between IQ and BAC-A composite scores in both bipolar patients and HC. CONCLUSIONS: The Italian BAC-A is sensitive to the cognitive impairments of patients with BD in both affective and non-affective cognitive domains.

The Influence of 5-HTTLPR, BDNF Rs6265 and COMT Rs4680 Polymorphisms on Impulsivity in Bipolar Disorder: The Role of Gender.

Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted ß for Total BIS score: 5.35, p < 0.001). No significant interaction effect was evident between disease status (HC vs. BD) and SNP status for any polymorphism. Considering the whole sample, BDNF Met/Met homozygosis was associated with lower BIS scores across all three factors (adjusted ß for Total BIS score: −10.2, p < 0.001). A significant 5-HTTLPR x gender interaction was found for the SS genotype, associated with higher BIS scores in females only (adjusted ß for Total BIS score: 12.0, p = 0.001). Finally, COMT polymorphism status was not significantly associated with BIS scores. In conclusion, BD diagnosis did not influence the effect on impulsivity scores for any of the three SNPs considered. Only one SNP­the BDNF rs6265 Met/Met homozygosis­was independently associated with lower impulsivity scores. The 5-HTTLPR SS genotype was associated with higher impulsivity scores in females only. Further studies adopting genome-wide screening in larger samples are needed to define the genetic basis of impulsivity in BD.

Sex and dependence related neuroanatomical differences in regular cannabis users: findings from the ENIGMA Addiction Working Group.

Males and females show different patterns of cannabis use and related psychosocial outcomes. However, the neuroanatomical substrates underlying such differences are poorly understood. The aim of this study was to map sex differences in the neurobiology (as indexed by brain volumes) of dependent and recreational cannabis use. We compared the volume of a priori regions of interest (i.e., amygdala, hippocampus, nucleus accumbens, insula, orbitofrontal cortex (OFC), anterior cingulate cortex and cerebellum) between 129 regular cannabis users (of whom 70 were recreational users and 59 cannabis dependent) and 114 controls recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age, IQ, and alcohol and tobacco use. Dependent cannabis users, particularly females, had (marginally significant) smaller volumes of the lateral OFC and cerebellar white matter than recreational users and controls. In dependent (but not recreational) cannabis users, there was a significant association between female sex and smaller volumes of the cerebellar white matter and OFC. Volume of the OFC was also predicted by monthly standard drinks. No significant effects emerged the other brain regions of interest. Our findings warrant future multimodal studies that examine if sex and cannabis dependence are specific key drivers of neurobiological alterations in cannabis users. This, in turn, could help to identify neural pathways specifically involved in vulnerable cannabis users (e.g., females with cannabis dependence) and inform individually tailored neurobiological targets for treatment.

The association of childhood trauma, lifetime stressful events and general psychopathological symptoms in euthymic bipolar patients and healthy subjects.

BACKGROUND: Psychopathological symptoms during euthymia in Bipolar Disorder (BD) affect quality of life and predispose to the occurrence of new acute episodes, however only few studies investigated potential risk-factors. This study aims to explore the association between childhood trauma (CT), lifetime stressful events (SLEs) and psychopathological symptoms in BD patients during euthymia and controls (HC). METHODS: A total of 261 participants (93 euthymic patients with BD, 168 HC) were enrolled. Generalized linear models and multiple logistic models were used to assess the association among the Symptom Check List-90-R (SCL-90-R), the Infancy Trauma Interview, the Paykel Life Events Scale. RESULTS: The rate of participants reporting CT was higher in BD (n=47; 53%) than HC (n=43; 30%) (p=0.001). The experience of neglect was strongly related to BD (OR 6.5; p=0.003). CT was associated to higher scores on the SCL-90-R subscales (all the subscales except Phobia). No effects of the interaction between CT and diagnosis were found on SCL-90-R. Finally, there was a main effect of CT on lifetime SLEs (p<.001), that was not associated with diagnosis (p=0.833), nor with the interaction between CT and diagnosis (p=0.624). LIMITATIONS: The cross-sectional design does not allow causal inferences; the exclusion of subjects reporting medical or psychiatric comorbidity limits generalizability. CONCLUSIONS: CT was associated both to psychopathological symptoms during euthymia and the lifetime SLEs, thus it may represent a vulnerability factor influencing the course of BD. Overall, these data contribute to overcome the limited evidences documenting the influence of environmental factors on euthymic phase in BD.

Gender-related neuroanatomical differences in alcohol dependence: findings from the ENIGMA Addiction Working Group.

Gender-related differences in the susceptibility, progression and clinical outcomes of alcohol dependence are well-known. However, the neurobiological substrates underlying such differences remain unclear. Therefore, this study aimed to investigate gender differences in the neuroanatomy (i.e. regional brain volumes) of alcohol dependence. We examined the volume of a priori regions of interest (i.e., orbitofrontal cortex, hippocampus, amygdala, nucleus accumbens, caudate, putamen, pallidum, thalamus, corpus callosum, cerebellum) and global brain measures (i.e., total grey matter (GM), total white matter (WM) and cerebrospinal fluid). Volumes were compared between 660 people with alcohol dependence (228 women) and 326 controls (99 women) recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age and education years. Compared to controls, individuals with alcohol dependence on average had (3-9%) smaller volumes of the hippocampus (bilateral), putamen (left), pallidum (left), thalamus (right), corpus callosum, total GM and WM, and cerebellar GM (bilateral), the latter more prominently in women (right). Alcohol-dependent men showed smaller amygdala volume than control men, but this effect was unclear among women. In people with alcohol dependence, more monthly standard drinks predicted smaller amygdala and larger cerebellum GM volumes. The neuroanatomical differences associated with alcohol dependence emerged as gross and widespread, while those associated with a specific gender may be confined to selected brain regions. These findings warrant future neuroscience research to account for gender differences in alcohol dependence to further understand the neurobiological effects of alcohol dependence.

Neuroimaging studies exploring the neural basis of social isolation.

According to the social brain hypothesis, the human brain includes a network designed for the processing of social information. This network includes several brain regions that elaborate social cues, interactions and contexts, i.e. prefrontal paracingulate and parietal cortices, amygdala, temporal lobes and the posterior superior temporal sulcus. While current literature suggests the importance of this network from both a psychological and evolutionary perspective, little is known about its neurobiological bases. Specifically, only a paucity of studies explored the neural underpinnings of constructs that are ascribed to the social brain network functioning, i.e. objective social isolation and perceived loneliness. As such, this review aimed to overview neuroimaging studies that investigated social isolation in healthy subjects. Social isolation correlated with both structural and functional alterations within the social brain network and in other regions that seem to support mentalising and social processes (i.e. hippocampus, insula, ventral striatum and cerebellum). However, results are mixed possibly due to the heterogeneity of methods and study design. Future neuroimaging studies with longitudinal designs are needed to measure the effect of social isolation in experimental v. control groups and to explore its relationship with perceived loneliness, ultimately helping to clarify the neural correlates of the social brain.

Sex differences in the neuroanatomy of alcohol dependence: hippocampus and amygdala subregions in a sample of 966 people from the ENIGMA Addiction Working Group.

Males and females with alcohol dependence have distinct mental health and cognitive problems. Animal models of addiction postulate that the underlying neurobiological mechanisms are partially distinct, but there is little evidence of sex differences in humans with alcohol dependence as most neuroimaging studies have been conducted in males. We examined hippocampal and amygdala subregions in a large sample of 966 people from the ENIGMA Addiction Working Group. This comprised 643 people with alcohol dependence (225 females), and a comparison group of 323 people without alcohol dependence (98 females). Males with alcohol dependence had smaller volumes of the total amygdala and its basolateral nucleus than male controls, that exacerbated with alcohol dose. Alcohol dependence was also associated with smaller volumes of the hippocampus and its CA1 and subiculum subfield volumes in both males and females. In summary, hippocampal and amygdalar subregions may be sensitive to both shared and distinct mechanisms in alcohol-dependent males and females.

Classification of Psychoses Based on Immunological Features: A Machine Learning Study in a Large Cohort of First-Episode and Chronic Patients.

For several years, the role of immune system in the pathophysiology of psychosis has been well-recognized, showing differences from the onset to chronic phases. Our study aims to implement a biomarker-based classification model suitable for the clinical management of psychotic patients. A machine learning algorithm was used to classify a cohort of 362 subjects, including 160 first-episode psychosis patients (FEP), 70 patients affected by chronic psychiatric disorders (schizophrenia, bipolar disorder, and major depressive disorder) with psychosis (CRO) and 132 health controls (HC), based on mRNA transcript levels of 56 immune genes. Models distinguished between FEP, CRO, and HC and between the subgroup of drug-free FEP and HC with a mean accuracy of 80.8% and 90.4%, respectively. Interestingly, by using the feature importance method, we identified some immune gene transcripts that contribute most to the classification accuracy, possibly giving new insights on the immunopathogenesis of psychosis. Therefore, our results suggest that our classification model has a high translational potential, which may pave the way for a personalized management of psychosis.

Structural neuroimaging of somatoform disorders: A systematic review.

Although there has been an increment in neuroimaging research in somatoform disorders (SD), to date little is known about the neural correlates of these diseases. Therefore, in this systematic, review we aimed at summarizing the existing evidence of structural brain alterations in SD as per DSM-IV and DSM-5 criteria. Three electronic databases (Scopus, PubMed and Web of Science) were searched. Only case-control studies using structural neuroimaging were included. Forty-five out of 369 articles fulfilled inclusion criteria and were reviewed. Compared to controls, subjects with SD showed morphological alterations encompassing motor, limbic and somatosensory circuits. Although far from being conclusive, the results suggested that SD are characterized by selective alterations of large-scale brain networks implicated in cognitive control, emotion regulation and processing, stress and somatic-visceral perception. This review highlights the need for further multimodal neuroimaging studies with longitudinal designs, in larger and better-characterized samples, to elucidate the temporal and causal relationship between neuroanatomical changes and SD, which is paramount for informing tailored treatments.

Default mode network activity in bipolar disorder.

Since its discovery in 1997, the default mode network (DMN) and its components have been extensively studied in both healthy individuals and psychiatric patients. Several studies have investigated possible DMN alterations in specific mental conditions such as bipolar disorder (BD). In this review, we describe current evidence from resting-state functional magnetic resonance imaging studies with the aim to understand possible changes in the functioning of the DMN in BD. Overall, several types of analyses including seed-based and independent component have been conducted on heterogeneous groups of patients highlighting different results. Despite the differences, findings seem to indicate that BD is associated with alterations in both frontal and posterior DMN structures, mainly in the prefrontal, posterior cingulate and inferior parietal cortices. We conclude this review by suggesting possible future research directions.