A novel comorbidity index in Italy based on diseases detected by the surveillance system PASSI and the Global Burden of Diseases disability weights.

BACKGROUND: Understanding comorbidity and its burden characteristics is essential for policymakers and healthcare providers to allocate resources accordingly. However, several definitions of comorbidity burden can be found in the literature. The main reason for these differences lies in the available information about the analyzed diseases (i.e., the target population studied), how to define the burden of diseases, and how to aggregate the occurrence of the detected health conditions. METHODS: In this manuscript, we focus on data from the Italian surveillance system PASSI, proposing an index of comorbidity burden based on the disability weights from the Global Burden of Disease (GBD) project. We then analyzed the co-presence of ten non-communicable diseases, weighting their burden thanks to the GBD disability weights extracted by a multi-step procedure. The first step selects a set of GBD weights for each disease detected in PASSI using text mining. The second step utilizes an additional variable from PASSI (i.e., the perceived health variable) to associate a single disability weight for each disease detected in PASSI. Finally, the disability weights are combined to form the comorbidity burden index using three approaches common in the literature. RESULTS: The comorbidity index (i.e., combined disability weights) proposed allows an exploration of the magnitude of the comorbidity burden in several Italian sub-populations characterized by different socioeconomic characteristics. Thanks to that, we noted that the level of comorbidity burden is greater in the sub-population characterized by low educational qualifications and economic difficulties than in the rich sub-population characterized by a high level of education. In addition, we found no substantial differences in terms of predictive values of comorbidity burden adopting different approaches in combining the disability weights (i.e., additive, maximum, and multiplicative approaches), making the Italian comorbidity index proposed quite robust and general.

Permutation-based true discovery proportions for functional magnetic resonance imaging cluster analysis.

We propose a permutation-based method for testing a large collection of hypotheses simultaneously. Our method provides lower bounds for the number of true discoveries in any selected subset of hypotheses. These bounds are simultaneously valid with high confidence. The methodology is particularly useful in functional Magnetic Resonance Imaging cluster analysis, where it provides a confidence statement on the percentage of truly activated voxels within clusters of voxels, avoiding the well-known spatial specificity paradox. We offer a user-friendly tool to estimate the percentage of true discoveries for each cluster while controlling the family-wise error rate for multiple testing and taking into account that the cluster was chosen in a data-driven way. The method adapts to the spatial correlation structure that characterizes functional Magnetic Resonance Imaging data, gaining power over parametric approaches.

Enhanced hyperalignment via spatial prior information.

Functional alignment between subjects is an important assumption of functional magnetic resonance imaging (fMRI) group-level analysis. However, it is often violated in practice, even after alignment to a standard anatomical template. Hyperalignment, based on sequential Procrustes orthogonal transformations, has been proposed as a method of aligning shared functional information into a common high-dimensional space and thereby improving inter-subject analysis. Though successful, current hyperalignment algorithms have a number of shortcomings, including difficulties interpreting the transformations, a lack of uniqueness of the procedure, and difficulties performing whole-brain analysis. To resolve these issues, we propose the ProMises (Procrustes von Mises-Fisher) model. We reformulate functional alignment as a statistical model and impose a prior distribution on the orthogonal parameters (the von Mises-Fisher distribution). This allows for the embedding of anatomical information into the estimation procedure by penalizing the contribution of spatially distant voxels when creating the shared functional high-dimensional space. Importantly, the transformations, aligned images, and related results are all unique. In addition, the proposed method allows for efficient whole-brain functional alignment. In simulations and application to data from four fMRI studies we find that ProMises improves inter-subject classification in terms of between-subject accuracy and interpretability compared to standard hyperalignment algorithms.

Procrustes Analysis for High-Dimensional Data.

The Procrustes-based perturbation model (Goodall in J R Stat Soc Ser B Methodol 53(2):285-321, 1991) allows minimization of the Frobenius distance between matrices by similarity transformation. However, it suffers from non-identifiability, critical interpretation of the transformed matrices, and inapplicability in high-dimensional data. We provide an extension of the perturbation model focused on the high-dimensional data framework, called the ProMises (Procrustes von Mises-Fisher) model. The ill-posed and interpretability problems are solved by imposing a proper prior distribution for the orthogonal matrix parameter (i.e., the von Mises-Fisher distribution) which is a conjugate prior, resulting in a fast estimation process. Furthermore, we present the Efficient ProMises model for the high-dimensional framework, useful in neuroimaging, where the problem has much more than three dimensions. We found a great improvement in functional magnetic resonance imaging connectivity analysis because the ProMises model permits incorporation of topological brain information in the alignment's estimation process.

Insula volumes in first-episode and chronic psychosis: A longitudinal MRI study.

BACKGROUND: Alterations in insular grey matter (GM) volume has been consistently reported for affective and non-affective psychoses both in chronic and first-episode patients, ultimately suggesting that the insula might represent a good region to study in order to assess the longitudinal course of psychotic disorders. Therefore, in this longitudinal Magnetic Resonance Imaging (MRI) study, we aimed at further investigating the key role of insular volumes in psychosis. MATERIAL AND METHODS: 68 First-Episode Psychosis (FEP) patients, 68 patients with Schizophrenia (SCZ), 47 Bipolar Disorder (BD) patients, and 94 Healthy Controls (HC) were enrolled and underwent a 1.5 T MRI evaluation. A subsample of 99 subjects (10 HC, 23 BD, 29 SCZ, 37 FEP) was rescanned after 2,53 ± 1,68 years. The insular cortex was manually traced and then divided into an anterior and posterior portion. Group and correlation analyses were then performed both at baseline and at follow-up. RESULTS: At baseline, greater anterior and lower posterior insular GM volumes were observed in chronic patients. At follow-up, we found that FEP patients had a significant GM volume increase from baseline to follow-up, especially in the posterior insula whereas chronic patients showed a relative stability. Finally, significant negative correlations between illness severity and pharmacological treatment and insular GM volumes were observed in the whole group of psychotic patients. CONCLUSIONS: The longitudinal assessment of both chronic and first-episode patients allowed us to detect a complex pattern of GM abnormalities in selective sub-portions of insular volumes, ultimately suggesting that this structure could represent a key biological marker of psychotic disorders.

The Effect of DHA Supplementation on Cognition in Patients with Bipolar Disorder: An Exploratory Randomized Control Trial.

Bipolar disorder (BD) is a severe mental disorder with a wide range of cognitive deficits, both in the euthymic and acute phase of the disease. Interestingly, in recent years, there has been a growing interest in investigating the impact of ω-3 polyunsaturated fatty acids on cognition in BD. In this context, the aim of this study is to evaluate the effect of docosahexaenoic acid (C22:6 ω-3, DHA) supplementation on cognitive performances in euthymic BD patients. This is an exploratory, single-centre, double-blind randomized controlled trial evaluating 12 weeks DHA supplementation (1250 mg daily) vs. a placebo (corn oil) in 31 euthymic BD patients compared to 15 healthy controls (HCs) on cognitive functions, assessed by the Brief Assessment of Cognition in Affective Disorder (BAC-A). Plasma levels of DHA were measured. After 12 weeks of treatment, no significant group differences were observed in all neuropsychological tests between the four groups, except for the emotion inhibition test, where HCs with DHA had higher scores compared to either BD with DHA (z = 3.9, p = 0.003) or BD with placebo (t = 3.7, p = 0.005). Although our results showed that DHA could be effective for ameliorating cognition in healthy subjects, future studies are still needed to clarify the impact of DHA on cognition in BD.

Altered syntactic abilities in first episode patients: An inner phenomenon characterizing psychosis.

BACKGROUND: Research has consistently shown that language abilities represent a core dimension of psychosis; however, to date, very little is known about syntactic comprehension performance in the early stages of psychosis. This study aims to compare the linguistic abilities involved in syntactic comprehension in a large group of First Episode Psychosis (FEP) patients and healthy controls (HCs). METHODS: A multiple choice test of comprehension of syntax was administered to 218 FEP patients (166 non-affective FEP patients [FEP-NA] and 52 affective FEP patients [FEP-A]) and 106 HCs. All participants were asked to match a sentence they listen with one out of four vignettes on a pc screen. Only one vignette represents the stimulus target, while the others are grammatical or non-grammatical (visual) distractors. Both grammatical and non-grammatical errors and performance in different syntactic constructions were considered. RESULTS: FEP committed greater number of errors in the majority of TCGB language domains compared to HCs. Moreover, FEP-NA patients committed significantly more non-grammatical (z = -3.2, p = 0.007), locative (z = -4.7, p < 0.001), passive-negative (z = -3.2, p = 0.02), and relative (z = -4.6, p < 0.001) errors compared to HCs as well as more passive-affirmative errors compared to both HCs (z = -4.3, p < 0.001) and FEP-A (z = 3.1, p = 0.04). Finally, we also found that both FEP-NA and FEP-A committed more grammatical (FEP-NA: z = -9.2, p < 0.001 and FEP-A: z = -4.4, p < 0.001), total (FEP-NA: z = -8.2, p < 0.001 and FEP-A: z = 3.9, p =  0.002), and active-negative (FEP-NA: z = -5.8, p < 0.001 and FEP-A: z = -3.5, p = 0.01) errors compared to HCs. CONCLUSIONS: This study shows that the access to syntactic structures is already impaired in FEP patients, especially in those with FEP-NA, ultimately suggesting that language impairments represent a core and inner feature of psychosis even at early stages.

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.