Gerard Martínez-Vilavella

Prader–Willi syndrome (PWS) is a rare neurogenetic disorder associated with neuropsychiatric, metabolic, endocrine, and physical abnormalities. Although previous neuroimaging studies have identified regional gray matter alterations, cortical thickness (CT) abnormalities and their distribution across large-scale functional brain networks remain poorly characterized in adults with PWS. We investigated cortical morphology in 23 adults with PWS and 22 age- and sex-matched healthy controls who underwent structural MRI. Cortical reconstruction and surface-based morphometric analyses were performed using FreeSurfer. Between-group differences in CT were assessed using age, sex, and intracranial volume as covariates. Associations between CT and clinical, cognitive, anthropometric, and endocrine measures were examined using Spearman correlations. Significant cortical regions were further mapped onto an a priori functional network atlas. Adults with PWS showed reduced CT in a left-hemispheric cluster involving the inferior precentral gyrus, insula, inferior temporal cortex, and orbitofrontal cortex. This cluster overlapped predominantly with the somatomotor, auditory, cingulo-opercular, language, and frontoparietal networks. Within the PWS group, lower CT was associated with higher body mass index and poorer global functioning. CT was positively associated with IGF-1 levels and was greater in participants with a history of growth hormone therapy during childhood. These findings indicate cortical thinning across regions belonging to multiple functional networks involved in sensorimotor, attentional, language, and executive processes, extending previous volumetric findings. The associations with body mass index, functional measures, and the GH/IGF-1 axis suggest that cortical morphology may reflect an interplay between genetic vulnerability and potentially modifiable metabolic and endocrine factors, raising the possibility of a neuroprotective role for GH/IGF-1 signaling.

Background Pain in knee osteoarthritis (KOA) often shows a limited correlation with radiographic severity, complicating treatment decision-making and highlighting the need to understand central mechanisms of pain. Functional magnetic resonance imaging (fMRI) allows investigation of brain regions such as the amygdala and nucleus accumbens, which are increasingly recognized as key modulators of pain chronification and may influence therapeutic choices, including the decision to undergo total knee replacement (TKR). This study is part of the HOLOA Project (Clinical and virtual examination of patients for holistic and objective description of the osteoarthritis progression mechanisms). Methods We conducted a cross-sectional observational study nested within the HOLOA cohort. Thirty-one patients with KOA (20 managed conservatively [CM], 11 undergoing TKR) aged 60–70 years with Kellgren-Lawrence (KL) grades 2–3 were included. Participants underwent two fMRI paradigms with pressure stimulation (Knee Interline and Tibial Surface tests). Clinical assessment included WOMAC, Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HAD), and Numeric Rating Scale (NRS). Group comparisons and correlation analyses were performed to explore associations between clinical variables and brain activation. Results Demographics were comparable between groups, although TKR patients had higher BMI (Body mass index) and more frequent KL grade 3. TKR patients scored higher on WOMAC (mean difference 19.3, p = 0.009) and PCS (mean difference 9.1, p = 0.022), reflecting greater functional impairment and catastrophizing. Across the whole cohort, painful stimulation evoked robust activation of classical pain-processing regions, but no significant amygdala or nucleus accumbens activation. However, nucleus accumbens activity correlated positively with PCS scores (p ≤ 0.004). In group comparisons, TKR patients exhibited significant bilateral amygdala activation during Tibial Surface stimulation, absent in the CM group, and reported higher post-test NRS scores (mean difference 2.0, p = 0.027). Conclusion Our findings suggest that heightened limbic activation and catastrophizing contribute to the decision to undergo TKR in KOA patients, independent of radiographic severity. The amygdala and nucleus accumbens appear central in linking affective–motivational processes with treatment choice. Our findings suggest that heightened limbic activation and catastrophizing are associated with the decision to undergo TKR in KOA patients, independent of radiographic severity.

Background: Fibromyalgia (FM) is a chronic condition characterized by widespread pain, fatigue, cognitive difficulties, and psychological symptoms. Patients often present distinct personality traits and psychopathological patterns associated with symptom severity. Objective: To examine psychopathological profiles in FM patients based on functional, physical–somatic, and emotional impairment domains, as well as on cumulative disease severity. Materials and Methods: A cross-sectional study was conducted with 70 women clinically diagnosed with FM at a specialized Fibromyalgia Unit. Psychological functioning was assessed using the Personality Assessment Inventory, and disease impact was measured with the Fibromyalgia Impact Questionnaire. Hierarchical cluster analyses were used to classify participants into mild and severe clusters across FIQ domains, and psychological profiles were compared. Results: Patients with severe functional impairment had more affective dysregulation (76.43 vs. 70.20, p < 0.01) and somatic complaints (85.57 vs. 79.76, p < 0.05) than those with mild impairment. The severe–physical cluster showed greater mood instability, somatization, and suicidal ideation (60.94 vs. 53.61, p < 0.05). The severe–emotional cluster had higher rates of major depression (85.71% vs. 64.28%) and persistent depressive disorder (76.19% vs. 70.61%, p < 0.05). Severe showed more emotional instability and somatization, distinguishing it from mild. Greater cumulative severity intensified depressive and somatic disorders. Discussion: Findings support FM’s biopsychosocial profile, where emotional distress may relate to psychological and physical symptoms, reinforcing the need for personalized, multidisciplinary care and comprehensive assessment.

Background: Fibromyalgia (FM) is a complex condition marked by increased pain sensitivity and central sensitization. Studies often explore the link between FM and depressive anxiety disorders, but few focus on dysthymia or persistent depressive disorder (PDD), which can be more disabling than major depression (MD). Objective: To identify clinical scales and subscales of the Personality Assessment Inventory (PAI) that effectively describe and differentiate the psychological profile of PDD, with or without comorbid MD, in FM patients with PDD previously dimensionally classified by the Millon Clinical Multiaxial Inventory III (MCMI-III). Method: An observational, cross-sectional study was conducted with 66 women (mean age 49.18, SD = 8.09) from Hospital del Mar. The PAI, the MCMI-III, and the Fibromyalgia Impact Questionnaire (FIQ) were used to assess the sample. Results: The PAI showed strong discriminative ability in detecting PDD, characterized by high scores in cognitive and emotional depression and low scores in identity alteration, dominance, and grandeur. High scores in cognitive, emotional, and physiological depression, identity alteration, cognitive anxiety, and suicidal ideation, along with low scores in dominance and grandeur, were needed to detect MD with PDD. Discriminant analysis could differentiate 69.6–73.9% of the PDD group and 84.6% of the PDD+MD group. Group comparisons showed that 72.2% of patients with an affective disorder by PAI were correctly classified in the MCMI-III affective disorder group, and 70% without affective disorder were correctly classified. Conclusions: The PAI effectively identifies PDD in FM patients and detects concurrent MD episodes, aiding in better prognostic and therapeutic guidance.

Background. Fibromyalgia (FM) is a complex condition marked by increased pain sensitivity and central sensitization. Studies often explore the link between FM and depressive-anxiety disorders, but few focus on dysthymia or persistent depressive disorder (PDD), which can be more disabling than major depression (MD). Objective. To identify clinical scales and subscales of the Personality Assessment Inventory (PAI) that effectively describe and differentiate the psychological profile of PDD, with or without comorbid MD, in FM patients with PDD previously dimensionally classified by the Millon Clinical Multiaxial Inventory III (MCMI-III). Method. An observational, cross-sectional study was conducted with 66 women (mean age 49.18, SD=8.09) from Hospital del Mar. The PAI, the MCMI-III, and Fibromyalgia Impact Questionnaire (FIQ) were used to assess the sample. Results. The PAI showed strong discriminative ability in detecting PDD, characterized by high scores in cognitive and emotional depression, and low scores in identity alteration, dominance, and grandeur. High scores in cognitive, emotional, and physiological depression, identity alteration, cognitive anxiety, and suicidal ideation, along with low scores in dominance and grandeur, were needed to detect MD with PDD. Discriminant analysis could differentiate 69.6-73.9% of the PDD group and 84.6% of the PDD+MD group. Group comparisons showed that 72.2% of patients with an affective disorder by PAI were correctly classified in the MCMI-III affective disorder group, and 70% without affective disorder were correctly classified. Conclusions. The PAI effectively identifies PDD in FM patients and detects concurrent MD episodes, aiding in better prognostic and therapeutic guidance.

Background: Observations from different fields of research coincide in indicating that a defective gamma-aminobutyric acid (GABA) interneuron system may be among the primary factors accounting for the varied clinical expression of schizophrenia. GABA interneuron deficiency is locally expressed in the form of neural activity desynchronization. We mapped the functional anatomy of local synchrony in the cerebral cortex in schizophrenia using functional connectivity MRI. Methods: Data from 86 patients with schizophrenia and 137 control subjects were obtained from publicly available repositories. Resting-state functional connectivity maps based on Iso-Distant Average Correlation measures across three distances were estimated detailing the local functional structure of the cerebral cortex. Results: Patients with schizophrenia showed weaker local functional connectivity (i.e., lower MRI signal synchrony) in (i) prefrontal lobe areas, (ii) somatosensory, auditory, visual, and motor cortices, (iii) paralimbic system at the anterior insula and anterior cingulate cortex, and (iv) hippocampus. The distribution of the defect in cortical area synchrony largely coincided with the synchronization effect of the GABA agonist alprazolam previously observed using identical functional connectivity measures. There was also a notable resemblance between the anatomy of our findings and cortical areas showing higher density of parvalbumin (prefrontal lobe and sensory cortices) and somatostatin (anterior insula and anterior cingulate cortex) GABA interneurons in humans. Conclusions: Our results thus provide detail of the functional anatomy of synchrony changes in the cerebral cortex in schizophrenia and suggest which elements of the interneuron system are affected. Such information could ultimately be relevant in the search for specific treatments.

Background: Personality traits are relevant for pain perception in persistent pain disorders, although they have not been studied in depth in sensitized and nonsensitized patients with knee osteoarthritis (OA). Objective: To explain and compare the personality profile of patients with OA, with and without central sensitization (CS), and fibromyalgia (FM). Setting: Participants were selected at the Rheumatology Department in two major hospitals in Spain. Participants: Case-control study where the sample consists of 15 patients with OA and CS (OA-CS), 31 OA without CS (OA-noCS), 47 FM, and 22 controls. We used a rigorous and systematic process that ensured the sample strictly fulfilled all the inclusion/exclusion criteria, so the sample is very well delimited. Primary outcome measures: Personality was assessed by the Temperament and Character Inventory of Cloninger. Results: The percentile in harm-avoidance dimension for the FM group is higher compared to OA groups and controls. The most frequent temperamental profiles in patients are cautious, methodical, and explosive. Patients with FM are more likely to report larger scores in harm-avoidance, with an increase in logistic regression adjusted odds ratio (OR_adj) between 4.2% and 70.2%. Conclusions: Harm-avoidance seems to be the most important dimension in personality patients with chronic pain, as previously found. We found no differences between OA groups and between sensitized groups, but there are differences between FM and OA-noCS, so harm-avoidance might be the key to describe personality in patients with CS rather than the presence of prolonged pain, as found in the literature before.