A machine learning approach on whole blood immunomarkers to identify an inflammation-associated psychosis onset subgroup.

Psychosis onset is a transdiagnostic event that leads to a range of psychiatric disorders, which are currently diagnosed through clinical observation. The integration of multimodal biological data could reveal different subtypes of psychosis onset to target for the personalization of care. In this study, we tested the existence of subgroups of patients affected by first-episode psychosis (FEP) with a possible immunopathogenic basis. To do this, we designed a data-driven unsupervised machine learning model to cluster a sample of 127 FEP patients and 117 healthy controls (HC), based on the peripheral blood expression levels of 12 psychosis-related immune gene transcripts. To validate the model, we applied a resampling strategy based on the half-splitting of the total sample with random allocation of the cases. Further, we performed a post-hoc univariate analysis to verify the clinical, cognitive, and structural brain correlates of the subgroups identified. The model identified and validated two distinct clusters: 1) a FEP cluster characterized by the high expression of inflammatory and immune-activating genes (IL1B, CCR7, IL12A and CXCR3); 2) a cluster consisting of an equal number of FEP and HC subjects, which did not show a relative over or under expression of any immune marker (balanced subgroup). None of the subgroups was related to specific symptoms dimensions or longitudinal diagnosis of affective vs non-affective psychosis. FEP patients included in the balanced immune subgroup showed a thinning of the left supramarginal and superiorfrontal cortex (FDR-adjusted p-values < 0.05). Our results demonstrated the existence of a FEP patients' subgroup identified by a multivariate pattern of immunomarkers involved in inflammatory activation. This evidence may pave the way to sample stratification in clinical studies aiming to develop diagnostic tools and therapies targeting specific immunopathogenic pathways of psychosis.

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.

Resting state networks activity in euthymic bipolar disorder.

OBJECTIVES: Bipolar disorder (BD) is a psychiatric condition causing shifts in mood, energy and activity levels severely altering the quality of life of the patients even in the euthymic phase. Although widely accepted, the neurobiological bases of the disorder in the euthymic phase remain elusive. This study aims at characterizing resting state functional activity of the BD euthymic phase in order to better understand the pathogenesis of the disease and build future neurobiological models. METHODS: Fifteen euthymic BD patients (10 females; mean age 40.2; standard deviation 13.5; range 20-61) and 27 healthy controls (HC) (21 females; mean age 37; standard deviation 10.6; range 22-60) underwent a 3T functional MRI scan at rest. Resting state activity was extracted through independent component analysis (ICA) run with automatic dimensionality estimation. RESULTS: ICA identified 22 resting state networks (RSNs). Within-network analysis revealed decreased connectivity in the visual, temporal, motor and cerebellar RSNs of BD patients vs HC. Between-network analysis showed increased connectivity between motor area and the default mode network (DMN) partially overlapping with the fronto-parietal network (FPN) in BD patients. CONCLUSION: Within-network analysis confirmed existing evidence of altered cerebellar, temporal, motor and visual networks in BD. Increased connectivity between the DMN and the motor area network suggests the presence of alterations of the fronto-parietal regions, precuneus and cingulate cortex in the euthymic condition. These findings indicate that specific connectivity alterations might persist even in the euthymic state suggesting the importance of examining both within and between-network connectivity to achieve a global understanding of the BD euthymic condition.

From research to clinical practice: a systematic review of the implementation of psychological interventions for chronic headache in adults.

BACKGROUND: Psychological interventions have been proved to be effective in chronic headache (CH) in adults. Nevertheless, no data exist about their actual implementation into standard clinical settings. We aimed at critically depicting the current application of psychological interventions for CH into standard care exploring barriers and facilitators to their implementation. Secondarily, main outcomes of the most recent psychological interventions for CH in adults have been summarized. METHODS: We conducted a systematic review through PubMed and PsycINFO in the time range 2008-2018. A quality analysis according to the QATSDD tool and a narrative synthesis were performed. We integrated results by: contacting the corresponding author of each paper; exploring the website of the clinical centers cited in the papers. RESULTS: Of the 938 identified studies, 28 papers were selected, whose quality largely varied with an average %QATSDD quality score of 64.88%. Interventions included CBT (42.85%), multi-disciplinary treatments (22.43%), relaxation training (17.86%), biofeedback (7.14%), or other interventions (10.72%). Treatments duration (1 day-9 months) and intensity varied, with a prevalence of individual-basis implementation. The majority of the studies focused on all primary headaches; 4 studies focused on medication-overuse headache. Most of the studies suggest interventions as effective, with the reduction in frequency of attacks as the most reported outcome (46.43%). Studies were distributed in different countries, with a prevalent and balanced distribution in USA and Europe. Ten researches (35.71%) were performed in academic contexts, 11 (39.28%) in clinical settings, 7 (25%) in pain/headache centres. Interventions providers were professionals with certified experience. Most of the studies were funded with private or public funding. Two contacted authors answered to our e-mail survey, with only one intervention implemented in the routine clinical practice. Only in three out of the 16 available websites a reference to the implementation into the clinical setting was reported. CONCLUSION: Analysis of contextual barriers/facilitators and cost-effectiveness should be included in future studies, and contents regarding dissemination/implementation of interventions should be incorporated in the professional training of clinical scientists. This can help in filling the gap between the existing published research and treatments actually offered to people with CH.

Cingulate abnormalities in bipolar disorder relate to gender and outcome: a region-based morphometry study [corrected].

Structural magnetic resonance imaging (MRI) studies reported gray matter (GM) loss in bipolar disorder (BD) in cingulate cortices, key regions subserving emotional regulation and cognitive functions in humans. The aim of this study was to further explore cingulate GM volumes in a sizeable group of BD patients with respect to healthy controls, particularly investigating the impact of gender and clinical variables. 39 BD patients (mean Age = 48.6 ± 9.7, 15 males and 24 females) and 39 demographically matched healthy subjects (mean Age = 47.9 ± 9.1, 15 males and 24 females) underwent a 1.5T MRI scan. GM volumes within the cingulate cortex were manually detected, including anterior and posterior regions. BD patients had decreased left anterior cingulate volumes compared with healthy controls (F = 6.7, p = 0.01). Additionally, a significant gender effect was observed, with male patients showing reduced left anterior cingulate cortex (ACC) volumes compared to healthy controls (F = 5.1, p = 0.03). Furthermore, a significant inverse correlation between right ACC volumes and number of hospitalizations were found in the whole group of BD patients (r = - 0.51, p = 0.04) and in male BD patients (r = - 0.88, p = 0.04). Finally, no statistically significant correlations were observed in female BD patients. Our findings further confirm the putative role of the ACC in the pathophysiology of BD. Interestingly, this study also suggested the presence of gender-specific GM volume reductions in ACC in BD, which may also be associated to poor outcome.

Correction to: Cingulate abnormalities in bipolar disorder relate to gender and outcome: a region-based morphometry study.

In the original publication of the article, the title was incorrect. The correct title should read as given below.

Pituitary gland shrinkage in bipolar disorder: The role of gender.

BACKGROUND: Hyperactivity of the Hypothalamic-Pituitary-Adrenal Axis (HPAA) has been consistently reported in mood disorders. However, only few studies investigated the Pituitary gland (PG) in Bipolar Disorder (BD) and the results are so far contrasting. Therefore, the aim of this study is to explore the integrity of the PG as well as the role of gender and the impact of clinical measurements on this structure in a sample of BD patients compared to healthy controls (HC). METHODS: 34 BD patients and 41 HC underwent a 1.5 T MRI scan. PG volumes were manually traced for all subjects. Psychiatric symptoms were assessed by means of the Brief Psychiatry Rating Scale, the Hamilton Depression Rating Scale and the Bech Rafaelsen Mania Rating Scale. RESULTS: We found decreased PG volumes in BD patients compared to HC (F = 24.9, p < 0.001). Interestingly, after dividing the sample by gender, a significant PG volume decrease was detected only in female BD patients compared to female HC (F = 9.1, p < 0.001), but not in male BD compared to male HC (F = -0.12, p = 0.074). No significant correlations were observed between PG volumes and clinical variables. CONCLUSIONS: Our findings suggest that BD patients have decreased PG volumes, probably due to the long-term hyperactivity of the HPAA and to the consequent strengthening of the negative feedback control towards the PG volume itself. This alteration was particularly evident in females, suggesting a role of gender in affecting PG volumes in BD. Finally, the absence of significant correlations between PG volumes and clinical variables further supports that PG disruption is a trait feature of BD, being independent of symptoms severity and duration of treatment.

Prosody abilities in a large sample of affective and non-affective first episode psychosis patients.

OBJECTIVE: Prosody comprehension deficits have been reported in major psychoses. It is still not clear whether these deficits occur at early psychosis stages. The aims of our study were to investigate a) linguistic and emotional prosody comprehension abilities in First Episode Psychosis (FEP) patients compared to healthy controls (HC); b) performance differences between non-affective (FEP-NA) and affective (FEP-A) patients, and c) association between symptoms severity and prosodic features. METHODS: A total of 208 FEP (156 FEP-NA and 52 FEP-A) patients and 77 HC were enrolled and assessed with the Italian version of the "Protocole Montréal d'Evaluation de la Communication" to evaluate linguistic and emotional prosody comprehension. Clinical variables were assessed with a comprehensive set of standardized measures. RESULTS: FEP patients displayed significant linguistic and emotional prosody deficits compared to HC, with FEP-NA showing greater impairment than FEP-A. Also, significant correlations between symptom severity and prosodic features in FEP patients were found. CONCLUSIONS: Our results suggest that prosodic impairments occur at the onset of psychosis being more prominent in FEP-NA and in those with severe psychopathology. These findings further support the hypothesis that aprosodia is a core feature of psychosis.

A diffusion weighted imaging study of basal ganglia in schizophrenia.

OBJECTIVES: Several magnetic resonance imaging (MRI) studies provided evidence of selective brain abnormalities in schizophrenia, both in cortical and subcortical structures. Basal ganglia are of particular interest, given not only the high concentration of dopaminergic neurons and receptors, but also for their crucial role in cognitive functions, commonly impaired in schizophrenia. To date, very few studies explored basal ganglia using diffusion imaging, which is sensitive to microstructural organization in brain tissues. The aim of our study is to explore basal ganglia structures with diffusion imaging in a sizeable sample of patients affected by schizophrenia and healthy controls. METHODS: We enrolled 52 subjects affected by schizophrenia according to DMS-IV-R criteria and 46 healthy controls. Diffusion weighted images were obtained using a 1.5 Tesla scanner and apparent diffusion coefficient (ADC) values were determined in axial and coronal sections at the level of basal ganglia. RESULTS: Patients affected by schizophrenia showed a significantly higher ADC compared to healthy controls in the left anterior lenticular nucleus (F = 3.9, p = .05). A significant positive correlation between right anterior lenticular nucleus and psychotropic dosages was found (r = 0.4, p = .01). CONCLUSIONS: Our study provides evidence of lenticular nucleus microstructure alterations in schizophrenia, potentially sustaining cognitive and motor deficits in schizophrenia. Key points The basal ganglia structures was explored with diffusion imaging in a sizeable sample of patients affected by schizophrenia and healthy controls. Patients affected by schizophrenia showed a significantly higher ADC compared to healthy controls in the left anterior lenticular nucleus. Our study provides evidence of lenticular nucleus microstructure alterations in schizophrenia, potentially sustaining cognitive and motor deficits in schizophrenia.

Classification of first-episode psychosis in a large cohort of patients using support vector machine and multiple kernel learning techniques.

First episode psychosis (FEP) patients are of particular interest for neuroimaging investigations because of the absence of confounding effects due to medications and chronicity. Nonetheless, imaging data are prone to heterogeneity because for example of age, gender or parameter setting differences. With this work, we wanted to take into account possible nuisance effects of age and gender differences across dataset, not correcting the data as a pre-processing step, but including the effect of nuisance covariates in the classification phase. To this aim, we developed a method which, based on multiple kernel learning (MKL), exploits the effect of these confounding variables with a subject-depending kernel weighting procedure. We applied this method to a dataset of cortical thickness obtained from structural magnetic resonance images (MRI) of 127 FEP patients and 127 healthy controls, who underwent either a 3Tesla (T) or a 1.5T MRI acquisition. We obtained good accuracies, notably better than those obtained with standard SVM or MKL methods, up to more than 80% for frontal and temporal areas. To our best knowledge, this is the largest classification study in FEP population, showing that fronto-temporal cortical thickness can be used as a potential marker to classify patients with psychosis.

Potential Gender-Related Aging Processes Occur Earlier and Faster in the Vermis of Patients with Bipolar Disorder: An MRI Study.

BACKGROUND: In the last decades, there has been increasing interest in investigating the role of the vermis in bipolar disorder (BD), especially because of its involvement in cognitive processes. The main aims of this study were to explore the integrity of the vermis and elucidate the role of demographic and clinical variables on vermis volumes in BD patients, stratified according to gender. METHODS: T1-weighted images were obtained for 38 BD patients and 38 healthy controls using a 1.5-T MRI scanner. Images were analyzed with a PC workstation with BRAINS2 software on a Linux system. Anatomical regions were traced manually from a blinded operator, with respect to subject identity and other clinical variables. RESULTS: The direct comparison between the 2 groups showed no significant gray matter differences in vermis volumes. Interestingly, vermis volumes were significantly inversely associated with chronological age and age of BD onset, particularly in male subjects. CONCLUSIONS: Our study provides evidence of the impact of aging on the vermis in BD, potentially related to earlier and faster gender-related neurodegenerative phenomena occurring during the progression of the disease.

Temperament and Character Inventory in Bipolar Disorder versus Healthy Controls and Modulatory Effects of 3 Key Functional Gene Variants.

BACKGROUND: Bipolar disorder (BD) has been associated with temperamental and personality traits, although the relationship is still to be fully elucidated. Several studies investigated the genetic basis of temperament and character, identifying catechol-O-methyltransferase (COMT), brain derived neurotrophic factor (BDNF), and serotonin transporter (5-HTT) gene variants as strong candidates. METHODS: In the GECO-BIP study, 125 BD patients and 173 HC were recruited. Subjects underwent to a detailed assessment and the temperament and character inventory 125 items (TCI) was administrated. Three functional genetic variants within key candidate genes (COMT rs4680, BDNF rs6265, and the serotonin-transporter-linked polymorphic region (5-HTTLPR)) were genotyped. Univariate and multivariate analyses were performed. RESULTS: Compared to HC, BD patients showed higher scores in novelty seeking (NS; p = 0.001), harm avoidance (HA; p < 0.001), and self transcendence (St; p < 0.001), and lower scores in self directness (p < 0.001) and cooperativeness (p < 0.001) TCI dimensions. Concerning the genetic analyses, COMT rs4680 was associated with NS in the total sample (p = 0.007) and in the male subsample (p = 0.022). When performing the analysis in the HC and BD samples, the association was confirmed only in HC (p = 0.012), and in the HC male subgroup in particular (p = 0.004). BDNF rs6265 was associated with St in the BD group (p = 0.017). CONCLUSION: COMT rs4680 may modulate NS in males in the general population. This effect was not detected in BD patients, probably because BD alters the neurobiological basis of some TCI dimensions. BDNF rs6265 seems to modulate St TCI dimension only in BD patients, possibly modulating the previously reported association between rs6265 and BD treatment response. Further studies are needed to confirm our findings.

Sexual dimorphism of the planum temporale in schizophrenia: A MRI study.

OBJECTIVE: Anatomical alterations in the superior temporal gyrus have been consistently reported in patients with schizophrenia, and they have mostly been linked to positive symptoms, including hallucinations and thought disorders. The superior temporal gyrus is considered one of the most asymmetric and lateralized structure of the human brain, and the process of lateralization seems to vary according to gender in the normal population. However, although it has been consistently suggested that patients with schizophrenia did not show normal brain lateralization in several regions, only few studies investigated it in the superior temporal gyrus and its sub-regions considering the effects of gender. In this context, the aim of this study was to evaluate sexual dimorphism in superior temporal gyrus volumes in a sample of patients with schizophrenia compared to age- and gender-matched healthy controls. METHODS: A total of 72 right/left-handed males (40 schizophrenia patients and 32 healthy controls) and 45 right/left-handed females (18 schizophrenia patients and 27 healthy controls) underwent clinical evaluation and a 1.5T magnetic resonance imaging scan. Gray and white matter volumes of regions of interest within the superior temporal gyrus were manually detected, including the Heschl's gyrus and the planum temporale. RESULTS: Female patients with schizophrenia presented a reduction in left planum temporale gray matter volumes ( F = 4.58, p = 0.03) and a lack of the normal planum temporale asymmetry index ( t = 0.27; p = 0.79) compared to female controls ( t = 5.47; p = 0.001). No differences were found between males for any volumes or laterality indices. Finally, in female patients with schizophrenia, Heschl's gyrus gray and white matter volumes negatively correlated with positive symptoms ( r = -0.56, p = 0.01). CONCLUSION: Our results showed that sexual dimorphism plays a key role on planum temporale in schizophrenia, underlining the importance of gender as a modulator of brain morphology and lateralization of schizophrenia.

Brain anatomy of symptom stratification in schizophrenia: a voxel-based morphometry study.

BACKGROUND: Although some Magnetic Resonance Imaging (MRI) studies have investigated the relationship between clinical severity and neuroanatomical alterations in patients with schizophrenia (SCZ), the biological signature associated with illness severity in schizophrenia is still uncertain. Therefore, this study aims to investigate structural brain abnormalities in SCZ, with particular regards to the identification of potential deficits associated with the severity of illness. METHODS: In total, 1.5T MRI data were acquired for 61 subjects with SCZ and 59 matched healthy controls (HC). The patient group was divided in two sub-groups based on clinical severity, one composed of 34 mild-to-moderately ill patients, and the other of 27 severely ill patients, and compared with matched HC. RESULTS: The whole group of patients with SCZ had significantly reduced grey matter (GM) volumes in the left inferior and middle temporal gyrus compared to HC (p < 0.05, pFWE corrected). Furthermore, compared to HC, patients with mild-to-moderate illness showed decreased GM volumes in the inferior and middle temporal gyrus, whereas those with severe illness had reduced GM volumes in the middle temporal gyrus and cerebellum bilaterally (all p < 0.001 uncorrected). No differences were observed between the two sub-groups of patients. CONCLUSION: The results showed significant GM volume reductions in temporal regions in patients with SCZ compared to matched HC, confirming the role of these regions in the pathophysiology of SCZ. Furthermore, specific cerebellar grey matter volume reductions were identified in patients with severe illness, which may contribute to stratifying patients with SCZ according to their clinical phenotype expression, ultimately helping in guiding targeted therapeutic/rehabilitation interventions.

Classification of first-episode psychosis: a multi-modal multi-feature approach integrating structural and diffusion imaging.

Currently, most of the classification studies of psychosis focused on chronic patients and employed single machine learning approaches. To overcome these limitations, we here compare, to our best knowledge for the first time, different classification methods of first-episode psychosis (FEP) using multi-modal imaging data exploited on several cortical and subcortical structures and white matter fiber bundles. 23 FEP patients and 23 age-, gender-, and race-matched healthy participants were included in the study. An innovative multivariate approach based on multiple kernel learning (MKL) methods was implemented on structural MRI and diffusion tensor imaging. MKL provides the best classification performances in comparison with the more widely used support vector machine, enabling the definition of a reliable automatic decisional system based on the integration of multi-modal imaging information. Our results show a discrimination accuracy greater than 90 % between healthy subjects and patients with FEP. Regions with an accuracy greater than 70 % on different imaging sources and measures were middle and superior frontal gyrus, parahippocampal gyrus, uncinate fascicles, and cingulum. This study shows that multivariate machine learning approaches integrating multi-modal and multisource imaging data can classify FEP patients with high accuracy. Interestingly, specific grey matter structures and white matter bundles reach high classification reliability when using different imaging modalities and indices, potentially outlining a prefronto-limbic network impaired in FEP with particular regard to the right hemisphere.

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.

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.

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.

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.

e-Health Interventions Targeting Pain-Related Psychological Variables in Fibromyalgia: A Systematic Review.

There is growing evidence to support the potential benefit of e-Health interventions targeting psychosocial outcomes and/or pain-related psychological variables for chronic pain conditions, including fibromyalgia syndrome (FMS). This systematic review aims at providing an in-depth description of the available e-Health psychological and/or multicomponent interventions for patients with FMS. Searches were made in PubMed, Cochrane, Web of Science, and PsycINFO up to 15 May 2023, finally including twenty-six articles. The quality of the included articles was medium-high (average quality assessment score of 77.1%). 50% of studies were randomized controlled trials (RCTs) (n = 13), and the majority of them focused exclusively on adult patients with FMS (n = 23) who were predominantly female. Four categories of e-Health modalities were identified: web-based (n = 19), mobile application (m-Health) (n = 3), virtual reality (VR) (n = 2), and video consulting (n = 2). Interventions were mainly based on the cognitive behavioral therapy (CBT) approach (n = 14) and mostly involved contact with a healthcare professional through different digital tools. Overall, a growing number of psychological and multicomponent interventions have been created and delivered using digital tools in the context of FMS, showing their potentiality for improving psychosocial outcomes and pain-related psychological variables. However, some digital tools resulted as underrepresented, and the literature on this topic appears highly heterogeneous precluding robust conclusions.