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Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as a major concern despite decades of extensive research into novel treatment modalities. The considerable heterogeneity in TRD’s clinical manifestations and neurobiological bases has complicated efforts toward effective interventions. Recognizing the need for precise biomarkers to guide treatment choices in TRD, herein we introduce the SelecTool Project. This initiative focuses on developing (WorkPlane 1/WP1) and conducting preliminary validation (WorkPlane 2/WP2) of a computational tool (SelecTool) that integrates clinical data, neurophysiological (EEG) and peripheral (blood sample) biomarkers through a machine-learning framework designed to optimize TRD treatment protocols. The SelecTool project aims to enhance clinical decision-making by enabling the selection of personalized interventions. It leverages multi-modal data analysis to navigate treatment choices towards two validated therapeutic options for TRD: esketamine nasal spray (ESK-NS) and accelerated repetitive Transcranial Magnetic Stimulation (arTMS). In WP1, 100 subjects with TRD will be randomized to receive either ESK-NS or arTMS, with comprehensive evaluations encompassing neurophysiological (EEG), clinical (psychometric scales), and peripheral (blood samples) assessments both at baseline (T0) and one month post-treatment initiation (T1). WP2 will utilize the data collected in WP1 to train the SelecTool algorithm, followed by its application in a second, out-of-sample cohort of 20 TRD subjects, assigning treatments based on the tool’s recommendations. Ultimately, this research seeks to revolutionize the treatment of TRD by employing advanced machine learning strategies and thorough data analysis, aimed at unraveling the complex neurobiological landscape of depression. This effort is expected to provide pivotal insights that will promote the development of more effective and individually tailored treatment strategies, thus addressing a significant void in current TRD management and potentially reducing its profound societal and economic burdens.

IntroductionThere is accumulating evidence that many pathological conditions affecting human balance are consequence of postural control (PC) failure or overstimulation such as in motion sickness. Our research shows the potential of using the response to a complex postural control task to assess patients with early-stage Parkinson's Disease (PD).MethodsWe developed a unique measurement model, where the PC task is triggered by a moving platform in a virtual reality environment while simultaneously recording EEG, EMG and CoP signals. This novel paradigm of assessment is called BioVRSea. We studied the interplay between biosignals and their differences in healthy subjects and with early-stage PD.ResultsDespite the limited number of subjects (29 healthy and nine PD) the results of our work show significant differences in several biosignals features, demonstrating that the combined output of posturography, muscle activation and cortical response is capable of distinguishing healthy from pathological.DiscussionThe differences measured following the end of the platform movement are remarkable, as the induced sway is different between the two groups and triggers statistically relevant cortical activities in α and θ bands. This is a first important step to develop a multi-metric signature able to quantify PC and distinguish healthy from pathological response.

The use of Dating Applications (DAs) is widespread, and in some cases could be associated with psychosexological issues. Hence, we decided to investigate hypersexual behavior and depression symptoms among DA users and non-users. We recruited a snowball convenience sample of 1000 subjects through an online platform in 2020 for a cross-sectional study. One hundred and nineteen (11.9%) were classified as DA users and 881 as non-users. All subjects completed a sociodemographic questionnaire, the Hypersexual Behavior Inventory (HBI), to assess hypersexuality, and the Patient Health Questionnaire (PHQ-9) to evaluate depression symptoms. We primarily found higher levels of hypersexual behavior and depression symptoms in DA users compared to non-users. In particular, HBI Total (users = 42.27 ± 16.37 vs. non-users = 31.85 ± 12.06; p < 0.0001), HBI Coping (users = 17.92 ± 8.01 vs. non-users = 13.52 ± 6.03; p < 0.0001), HBI Control (users = 14.73 ± 6.68 vs. non-users = 10.71 ± 4.95; p < 0.0001), HBI Consequences (users = 9.62 ± 4.33 vs. non-users = 7.60 ± 3.37; p < 0.0001), PHQ-9 Depression (users = 12.82 ± 6.64 vs. nonusers = 10.05 ± 5.84; p < 0.0001). On the whole, we found that hypersexual behavior and depression symptoms strongly characterize DAs users; this evidence could represent an important associated factor in DA use for sexual purposes.

Abstract Background Different electrophysiological (EEG) indices have been investigated as possible biomarkers of schizophrenia. However, these indices have a very limited use in clinical practice, as their associations with clinical and functional outcomes remain unclear. This study aimed to investigate the associations of multiple EEG markers with clinical variables and functional outcomes in subjects with schizophrenia (SCZs). Methods Resting-state EEGs (frequency bands and microstates) and auditory event-related potentials (MMN-P3a and N100-P3b) were recorded in 113 SCZs and 57 healthy controls (HCs) at baseline. Illness- and functioning-related variables were assessed both at baseline and at 4-year follow-up in 61 SCZs. We generated a machine-learning classifier for each EEG parameter (frequency bands, microstates, N100-P300 task, and MMN-P3a task) to identify potential markers discriminating SCZs from HCs, and a global classifier. Associations of the classifiers’ decision scores with illness- and functioning-related variables at baseline and follow-up were then investigated. Results The global classifier discriminated SCZs from HCs with an accuracy of 75.4% and its decision scores significantly correlated with negative symptoms, depression, neurocognition, and real-life functioning at 4-year follow-up. Conclusions These results suggest that a combination of multiple EEG alterations is associated with poor functional outcomes and its clinical and cognitive determinants in SCZs. These findings need replication, possibly looking at different illness stages in order to implement EEG as a possible tool for the prediction of poor functional outcome.

Abstract Self-reports are conventionally used to measure political preferences, yet individuals may be unable or unwilling to report their political attitudes. Here, in 69 participants we compared implicit and explicit methods of political attitude assessment and focused our investigation on populist attitudes. Ahead of the 2019 European Parliament election, we recorded electroencephalography (EEG) from future voters while they completed a survey that measured levels of agreement on different political issues. An Implicit Association Test (IAT) was administered at the end of the recording session. Neural signals differed as a function of future vote for a populist or mainstream party and of whether survey items expressed populist or non-populist views. The combination of EEG responses and self-reported preferences predicted electoral choice better than traditional socio-demographic and ideological variables, while IAT scores were not a significant predictor. These findings suggest that measurements of brain activity can refine the assessment of socio-political attitudes, even when those attitudes are not based on traditional ideological divides.

Abstract The hypothalamus has been attributed an important role during the premonitory phase of a migraine attack. Less is known about the role played by the hypothalamus in the interictal period and its relationship with the putative neurocognitive networks previously identified in the pathophysiology of migraine. Our aim was to test whether the hypothalamic microstructure would be altered during the interictal period and whether this co-existed with aberrant connectivity at cortical level. We collected multimodal MRI data from 20 untreated patients with migraine without aura between attacks (MO) and 20 healthy controls (HC) and studied fractional anisotropy, mean (MD), radial (RD), and axial diffusivity of the hypothalamus ROI as a whole from diffusion tensor imaging (DTI). Moreover, we performed an exploratory analysis of the same DTI metrics separately for the anterior and posterior hypothalamic ROIs bilaterally. From resting-state functional MRI, we estimated the Higuchi’s fractal dimension (FD), an index of temporal complexity sensible to describe non-periodic patterns characterizing BOLD signature. Finally, we correlated neuroimaging findings with migraine clinical features. In comparison to HC, MO had significantly higher MD, AD, and RD values within the hypothalamus. These findings were confirmed also in the exploratory analysis on the sub-regions of the hypothalamus bilaterally, with the addition of lower FA values on the posterior ROIs. Patients showed higher FD values within the salience network (SN) and the cerebellum, and lower FD values within the primary visual (PV) network compared to HC. We found a positive correlation between cerebellar and SN FD values and severity of migraine. Our findings of hypothalamic abnormalities between migraine attacks may form part of the neuroanatomical substrate that predisposes the onset of the prodromal phase and, therefore, the initiation of an attack. The peculiar fractal dimensionality we found in PV, SN, and cerebellum may be interpreted as an expression of abnormal efficiency demand of brain networks devoted to the integration of sensory, emotional, and cognitive information related to the severity of migraine.

Psychosis can occur at high rates in individuals with autism spectrum disorder (ASD). However, the detection of prodromal psychotic symptoms, including attenuated psychosis syndrome (APS), conditions at high risk of converting to full psychosis, has not been extensively investigated in ASD. We longitudinally evaluate a sample of young ASD individuals (age, mean ± SD: 13 ± 2.9) with (n = 13) or without (n = 18) concomitant APS through a standardized assessment of autistic (Autism Diagnostic Observation Schedule–Second Edition; ADOS−2) and psychotic (Structured Interview for Psychosis-Risk Syndromes, SIPS) symptoms and cognitive and adaptive skills. Individuals with other neuropsychiatric disorders were excluded. We estimated the conversion rate to full psychosis (according to SIPS criteria) over time (39.6 ± 11.5 months) and explored the role of clinical variables at baseline in the transition to full psychosis. A conversion rate to full psychosis of 30.7% was found in ASD/APS. Conversion to full psychosis was not affected by the severity of the autistic and psychotic symptoms. At baseline, young individuals with ASD/APS who later converted to full psychosis showed lower cognitive performance (d = 2.05) and greater impairment of adaptive social functioning profile (d = 1.2) than those with ASD. The results of this preliminary report revealed that nearly a third of young individuals with ASD/APS convert to full psychosis over time. Conversion to full psychosis is affected by decreased cognitive and adaptive skills. Further investigations are needed to confirm the utility of APS detection and to better characterize the psychotic developmental trajectory in ASD, with consequent important implications on prognosis and therapeutic strategies.

Compared with the general population, people with severe mental disorders have significantly worse physical health and a higher mortality rate, which is partially due to the adoption of unhealthy lifestyle behaviors, such as heavy smoking, use of alcohol or illicit drugs, unbalanced diet, and physical inactivity. These unhealthy behaviors may also play a significant role in the personal and functional recovery of patients with severe mental disorders, although this relationship has been rarely investigated in methodologically robust studies. In this paper, we aim to: a) describe the levels of physical activity and recovery style in a sample of patients with severe mental disorders; b) identify the clinical, social, and illness-related factors that predict the likelihood of patients performing physical activity. The global sample consists of 401 patients, with a main psychiatric diagnosis of bipolar disorder (43.4%, N = 174), psychosis spectrum disorder (29.7%; N = 119), or major depression (26.9%; N = 118). 29.4% (N = 119) of patients reported performing physical activity regularly, most frequently walking (52.1%, N = 62), going to the gym (21.8%, N = 26), and running (10.9%, N = 13). Only 15 patients (3.7%) performed at least 75 min of vigorous physical activity per week. 46.8% of patients adopted sealing over as a recovery style and 37.9% used a mixed style toward integration. Recovery style is influenced by gender (p < 0.05) and age (p < 0.05). The probability to practice regular physical activity is higher in patients with metabolic syndrome (Odds Ratio - OR: 2.1; Confidence Interval - CI 95%: 1.2–3.5; p < 0.050), and significantly lower in those with higher levels of anxiety/depressive symptoms (OR: 0.877; CI 95%: 0.771–0.998; p < 0.01). Globally, patients with severe mental disorders report low levels of physical activities, which are associated with poor recovery styles. Psychoeducational interventions aimed at increasing patients' motivation to adopt healthy lifestyle behaviors and modifying recovery styles may improve the physical health of people with severe mental disorders thus reducing the mortality rates.

The 11th revision of the International Classification of Diseases has endorsed substantial changes in Post-Traumatic Stress Disorder (PTSD) and has introduced Complex PTSD (cPTSD). The objective of this study was to assess the symptom and network structure of PTSD and cPTSD using the International Trauma Questionnaire- Italian version (ITQ) and the prevalence of PTSD and cPTSD in a community sample of late adolescents enriched with exposure to a destructive earthquake. A 1,010 high school students participated to the study. Confirmatory Factor Analysis supports that a six first-order correlated factors was the best fitting model of ICD-11 PTSD/cPTSD. The network analysis supports a clear separation between core PTSD symptoms and disturbances in self-organization (DSO) symptoms, avoidance, and negative self-concept were the most central items. The prevalence of PTSD and cPTSD was 9.11 and 4.06%, respectively. Female participants reported higher rates of both PTSD and cPTSD. This is the first study to report on ICD-11 PTSD and cPTSD rates on an Italian adolescence community sample. Consistent with other community samples, we found higher rates of PTSD compared to cPTSD. The results confirmed the factorial validity of the ITQ. The network structure highlights the importance of negative self-concept in cPTSD and avoidance in PTSD.

Abstract Background Chronic migraine (CM) can be associated with aberrant long-range connectivity of MRI-derived resting-state networks (RSNs). Here, we investigated how the fractal dimension (FD) of blood oxygenation level dependent (BOLD) activity may be used to estimate the complexity of RSNs, reflecting flexibility and/or efficiency in information processing in CM patients respect to healthy controls (HC). Methods Resting-state MRI data were collected from 20 untreated CM without history of medication overuse and 20 HC. On both groups, we estimated the Higuchi’s FD. On the same subjects, fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from diffusion tensor imaging and correlated with the FD values. Results CM showed higher FD values within dorsal attention system (DAS) and the anterior part of default-mode network (DMN), and lower FD values within the posterior DMN compared to HC. Although FA and MD were within the range of normality, both correlated with the FD values of DAS. Conclusions FD of DAS and DMN may reflect disruption of cognitive control of pain in CM. Since the normal microstructure of the thalamus and its positive connectivity with the cortical networking found in our CM patients reminds similar results obtained assessing the same structures but with the methods of neurophysiology, in episodic migraine during an attack, this may be yet another evidence in supporting CM as a never-ending migraine attack.

There is strong evidence for the existence of a high comorbidity between autism and psychosis with percentages reaching up to 34. 8% and several significant implications for treatment and prognosis of these patients. However, the identification of comorbid psychosis in patients with Autism Spectrum Disorder represents a complex challenge from a psychopathological point of view, in particular in patients with greater deficits in verbal communication. Intercepting the onset of a psychotic breakdown in autism may be very difficult, both disorders in fact occur along a phenotypic continuum of clinical severity and in many cases, psychotic symptoms are present in an attenuated form. In this paper, we reviewed the available scientific literature about comorbidity between psychosis and autism, focusing our attention on four specific dimensions: delusions, hallucinations, negative symptoms, and clinical course. The aim of this paper is to provide clinical tools to identify these psychotic phenomena in autistic patients, even when they occur in their attenuated form.

Abstract Background Symptoms of depression are transdiagnostic heterogenous features frequently assessed in psychiatric disorders, that impact the response to first-line treatment and are associated with higher suicide risk. This study assessed whether severe mental pain could characterize a specific phenotype of severely depressed high-risk psychiatric patients. We also aimed to analyze differences in treatments administered. Methods 2,297 adult patients (1,404 females and 893 males; mean age = 43.25 years, SD = 15.15) treated in several Italian psychiatric departments. Patients were assessed for psychiatric diagnoses, mental pain, symptoms of depression, hopelessness, and suicide risk. Results More than 23% of the patients reported high depression symptomatology and high mental pain (HI DEP/HI PAIN). Compared to patients with lower symptoms of depression, HI DEP/HI PAIN is more frequent among females admitted to an inpatient department and is associated with higher hopelessness and suicide risk. In addition, HI DEP/HI PAIN (compared to both patients with lower symptoms of depression and patients with higher symptoms of depression but lower mental pain) were more frequently diagnosed in patients with personality disorders and had different treatments. Conclusions Patients reporting severe symptoms of depression and high mental pain presented a mixture of particular dangerousness (high trait hopelessness and the presence of suicide ideation with more frequency and less controllability and previous suicide behaviors). The presence of severe mental pain may act synergically in expressing a clinical phenotype that is likewise treated with a more complex therapeutic regime than that administered to those experiencing symptoms of depression without mental pain.

Suicide ideation and behaviors are major health issues in the field of mental health. Several psychological and psychosocial factors have been taken into account as possible predictors of suicidality. Only recently affective temperaments have been considered as possible factors linked to suicide. This study aims to investigate the relationship between affective temperaments and suicidality, including the lifetime onset of suicide ideation, lifetime presence of suicide attempts and the total number of lifetime suicide attempts. This is a naturalistic multicentric observational study, involving outpatient units of seven University sites in Italy. Patients were administered with the short version of TEMPS-M and the Columbia Suicide Severity Rating Scale. A total of 653 participants were recruited, with a diagnosis of bipolar (55.7%), unipolar (35.8%) and cyclothymic disorder (8.4%). Regression models showed that the presence of lifetime suicide behaviors was increased in patients presenting trait related impulsivity (p < 0.0001), poor free-interval functioning (p < 0.05), higher number of affective episodes (p < 0.01), higher number of hospitalizations (p < 0.0001), cyclothymic and irritable affective temperaments (p < 0.05 and p < 0.05, respectively). Conversely, the presence of hyperthymic affective disposition reduced the likelihood of having suicidal behaviors (p < 0.01). Lifetime suicidal ideation was associated with trait-related impulsivity (p < 0.001), poor free-interval functioning (p < 0.05), higher number of affective episodes (p < 0.001) and of hospitalizations (p < 0.001). Depressive temperaments increased the likelihood of presenting suicidal ideation (p < 0.05), along with irritable temperaments (p < 0.01), contrary to hyperthymic affective (p < 0.05). Results of the present study confirm that affective disposition has a significant impact on the onset of suicidal ideation and behaviors, and that affective dispositions should be assessed in clinical settings to identify people at risk of suicide. Moreover, a wider clinical evaluation, including different clinical psychopathological dimensions, should be taken into consideration to develop effective preventive interventions.

Background: Negative symptoms represent a heterogeneous dimension with a strong impact on functioning of subjects with schizophrenia (SCZ). Five constructs are included in this dimension: anhedonia, asociality, avolition, blunted affect, and alogia. Factor analyses revealed that these symptoms cluster in two domains: experiential domain (avolition, asociality, and anhedonia) and the expressive deficit (alogia and blunted affect), that might be linked to different neurobiological alterations. Few studies investigated associations between N100, an electrophysiological index of early sensory processing, and negative symptoms, reporting controversial results. However, none of these studies investigated electrophysiological correlates of the two negative symptom domains.Objectives: The aim of our study was to evaluate, within the multicenter study of the Italian Network for Research on Psychoses, the relationships between N100 and negative symptom domains in SCZ.Methods: Auditory N100 was analyzed in 114 chronic stabilized SCZ and 63 healthy controls (HCs). Negative symptoms were assessed with the Brief Negative Symptom Scale (BNSS). Repeated measures ANOVA and correlation analyses were performed to evaluate differences between SCZ and HCs and association of N100 features with negative symptoms.Results: Our findings demonstrated a significant N100 amplitude reduction in SCZ compared with HCs. In SCZ, N100 amplitude for standard stimuli was associated with negative symptoms, in particular with the expressive deficit domain. Within the expressive deficit, blunted affect and alogia had the same pattern of correlation with N100.Conclusion: Our findings revealed an association between expressive deficit and N100, suggesting that these negative symptoms might be related to deficits in early auditory processing in SCZ.

Introduction: Medical comorbidities (MCs) represent a significant burden in terms of more frequent hospitalizations and overall lower life expectancy among people with severe mental disorders, such as schizophrenia and related psychotic disorders (SZ) and bipolar disorder (BD). The present article aims to compare the prevalence of MCs and to examine the associated characteristics as marital status, job occupation, level of education, and living arrangements, between BD and SZ patients.Methods: One-hundred-eight-one patients with MCs (85/47% had BD and 96/53% had SZ) were recruited retrospectively from the Acute Inpatients Psychiatry Unit of Policlinico Tor Vergata, Rome, between January-2017 and December-2020. MCs were: cardiovascular diseases (CVD), bacterial infections, mycoses, viral diseases, neoplasms, musculoskeletal, respiratory tract, urological and male genital, gynecological, neurological, gastrointestinal, metabolic syndrome, nutritional, and metabolic diseases.Results: BD had more MC than SZ (36.2 vs. 28.2%, respectively, p = 0.04). CVD and metabolic MC were more common among BD (51.8 vs.34.4%; 51.8 vs.35.3%; p = 0.018; p = 0.039; respectively), while viral diseases were more frequent in SZ (13.5 vs.3.5%, p = 0.035). Hypertension was common in both psychiatric illnesses (81.8% BD vs. 65.6% SZ, p = 0.18). Obesity was the most frequent metabolic disease in both BD and SZ (75% BD vs. 73.5% SZ, p = 0.91), followed by diabetes mellitus (52.3% BD vs. 55.9% SZ, p = 0.93), metabolic syndrome (54.5% BD vs. 47.1% SZ, p = 0.67) and dysthyroidism (47.7% BD vs. 25.7% SZ, p = 0.093). After performing a binary logistic regression analysis, only two MCs showed a statistically significant association: patients with SZ had an OR of 2.01 [CI 95% (1.00–4.01)] for CVD compared to BD; on the other hand, patients with BD had an OR of 16.57 [CI 95% (3.58–76.77)] for gynecological diseases compared to SZ patients.Conclusions: MCs are common among people with severe mental illness, especially CVD and metabolic diseases, highlighting the need for a more collaborative relationship between general medical providers and psychiatrists.

A considerable body of literature reports that individuals with psychotic disorders often suffer from sexual dysfunctions (SDs), with these representing a major unmet need. Long-term antipsychotic drug treatment may be the main cause for SDs in psychotic patients, through a plethora of different mechanisms, including prolactin dyscrasia, histamine-mediated sedation, and serotonin-induced sexual demotivation. However, a few pieces of evidence treat sexuality in patients at risk or the onset of psychosis. For this purpose, we systematically reviewed literature of the last 10 years in order to investigate sexuality in ultra-high risk (UHR) for psychosis and first-episode psychosis (FEP). We included in our review 34 articles fitting our research criteria on SDs in UHR and FEP. Evidence of SDs in the transition from UHR to FEP emerges through the selected studies. In FEP, sexuality is affected by the severity of the psychotic symptoms and, in some cases, by the iatrogenic effects of psychopharmacological treatment. Further experimental and clinical studies should systematically investigate the role of sexual functioning in the transition from UHR to FEP and, consequently, clarify whether or not SDs could be considered a possible marker for the onset of psychosis in at-risk populations. Moreover, psychiatrists and clinical psychologists should take into consideration the role of sexual life in young people with prodromal mental symptoms or at the onset of psychosis. Focusing on a thorough sexual evaluation might be a major challenge that could break down barriers of mental health promotion among young people with schizophrenia-spectrum disorders and therefore achieve better clinical outcomes.

Trait-related impulsiveness is highly prevalent in patients with mood disorders, being associated with negative outcomes. The predictive role of affective temperaments on trait-related impulsivity is still understudied. The aim of the present study is to investigate the relationship between impulsivity and affective temperaments in a sample of euthymic patients with mood disorders. This is a real-world multicentric observational study, carried out at the outpatient units of seven university sites in Italy. All patients filled in the short version of Munster Temperament Evaluation of the Memphis, Pisa, Paris and San Diego and the Barratt Impulsiveness Scale. The study sample included 653 participants, mainly female (58.2%), with a mean age of 46.9 (±14.1). Regression analyses showed that higher levels of trait-related impulsivity were associated to suicide attempts (p < 0.000), the presence of psychotic symptoms during acute phases (p < 0.05), a seasonal pattern (p < 0.05), a lower age at onset of the disorder (p < 0.05), cyclothymic (p < 0.01) and irritable temperaments (p < 0.01). The results of our study highlight the importance to screen patients with mood disorders for impulsivity and affective temperaments in order to identify patients who are more likely to present a worse outcome and to develop personalized and integrated early pharmacological and psychosocial treatment plans. Novelties of the present paper include the recruitment of patients in a stable phase, which reduced possible bias in patients’ self-reports, and the multicentric nature of the study, resulting in the recruitment of a large sample of patients with mood disorders, geographically distributed across Italy, thus improving the generalizability of study results.

Abstract Background A short ketogenic diet (KD) treatment can prevent migraine attacks and correct excessive cortical response. Here, we aim to prove if the KD-related changes of cortical excitability are primarily due to cerebral cortex activity or are modulated by the brainstem. Methods Through the stimulation of the right supraorbital division of the trigeminal nerve, we concurrently interictally recorded the nociceptive blink reflex (nBR) and the pain-related evoked potentials (PREP) in 18 migraineurs patients without aura before and after 1-month on KD, while in metabolic ketosis. nBR and PREP reflect distinct brain structures activation: the brainstem and the cerebral cortex respectively. We estimated nBR R2 component area-under-the-curve as well as PREP amplitude habituation as the slope pof the linear regression between the 1st and the 2nd block of 5 averaged responses. Results Following 1-month on KD, the mean number of attacks and headache duration reduced significantly. Moreover, KD significantly normalized the interictal PREP habituation (pre: + 1.8, post: − 9.1, p = 0.012), while nBR deficit of habituation did not change. Conclusions The positive clinical effects we observed in a population of migraineurs by a 1-month KD treatment coexists with a normalization at the cortical level, not in the brainstem, of the typical interictal deficit of habituation. These findings suggest that the cerebral cortex may be the primary site of KD-related modulation. Trial registration ClinicalTrials.gov NCT03775252 (retrospectively registered, December 09, 2018).

First-Person Shooter (FPS) game experience can be transferred to untrained cognitive functions such as attention, visual short-term memory, spatial cognition, and decision-making. However, previous studies have been using off-the-shelf FPS games based on predefined gaming settings, therefore it is not known whether such improvement of in game performance and transfer of abilities can be further improved by creating a in-game, adaptive in-game training protocol. To address this question, we compared the impact of a popular FPS-game (Counter-Strike:Global-Offensive–CS:GO) with an ad hoc version of the game based on a personalized, adaptive algorithm modifying the artificial intelligence of opponents as well as the overall game difficulty on the basis of individual gaming performance. Two groups of FPS-naïve healthy young participants were randomly assigned to playing one of the two game versions (11 and 10 participants, respectively) 2 h/day for 3 weeks in a controlled laboratory setting, including daily in-game performance monitoring and extensive cognitive evaluations administered before, immediately after, and 3 months after training. Participants exposed to the adaptive version of the game were found to progress significantly faster in terms of in-game performance, reaching gaming scenarios up to 2.5 times more difficult than the group exposed to standard CS:GO (p < 0.05). A significant increase in cognitive performance was also observed. Personalized FPS gaming can significantly speed-up the learning curve of action videogame-players, with possible future applications for expert-video-gamers and potential relevance for clinical-rehabilitative applications.

Despite that it is commonly accepted that migraine is a disorder of the nervous system with a prominent genetic basis, it is comorbid with a plethora of medical conditions. Several studies have found bidirectional comorbidity between migraine and different disorders including neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metaboloendocrine, and immunological conditions. Each of these has its own genetic load and shares some common characteristics with migraine. The bidirectional mechanisms that are likely to underlie this extensive comorbidity between migraine and other diseases are manifold. Comorbid pathologies can induce and promote thalamocortical network dysexcitability, multi-organ transient or persistent pro-inflammatory state, and disproportionate energetic needs in a variable combination, which in turn may be causative mechanisms of the activation of an ample defensive system with includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This strategy is designed to maintain brain homeostasis by regulating homeostatic needs, such as normal subcortico-cortical excitability, energy balance, osmoregulation, and emotional response. In this light, the treatment of migraine should always involves a multidisciplinary approach, aimed at identifying and, if necessary, eliminating possible risk and comorbidity factors.

Background: The COVID-19 pandemic, due to its disproportionated higher morbidity and mortality rates in the older age, has been considered to be a “geropandemic.” Several studies, however, have found that older age is associated with lower psychological distress in relation to the COVID-19 outbreak and related lockdown measures.Aim: To explore the role of Resilience as a mediator between stressful COVID-19 related life events and depressive and, anxiety symptoms and perceived stress, and to ascertain the role of age as a moderator of the mediator's effect.Methods: An on-line survey was spread through social networks during the first lockdown in Italy. Depressive and anxiety symptoms and perceived stress were measured using the Italian version of the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder Questionnaire-7 (GAD-7) and the Perceived Stress Scale (PSS). Resilience was measured using the Italian version of the Resilience Scale for Adults (RSA). Stressful COVID-19 related life events were explored using a checklist of events derived from the International Adjustment Disorder Questionnaire (IADQ). After a preliminary panel of linear regressions, mediation was tested using Structural Equation Modeling and inspecting the bootstrapped indirect effects. Afterwards, age was introduced as a mediator of the indirect effect in a moderated mediation analysis.Results: Twenty one thousand three hundred and thirty four subjects completed the questionnaire, 17,178 (80.52%) were female, 748 (3.5%) were >60 years old. In the whole sample, the presence of any stressful event was associated with depressive and anxiety symptoms and perceived stress. Resilience mediated the effects of stressful COVID-19-related events on depressive and anxiety symptoms and perceived stress. The moderated mediation analysis revealed that age moderated the mediation effect of Resilience between the presence of a stressful event and the selected outcomes.Conclusion: Taken together, our results show that age moderates the mediating effect of Resilience in the relationship between COVID-19-related stressful events and depressive and anxiety symptoms and perceived stress. Older adults' Resilience was less influenced by stressful events, and this could be one of the reasons accounting for the better mental health outcomes observed in the older age.

Abstract Background People with severe mental illnesses (SMI) have a mortality rate two times higher compared to the general population, with a decade of years of life lost. In this randomized controlled trial (RCT), we assessed in a sample of people with bipolar disorder, major depressive disorder, and schizophrenia spectrum disorder, the efficacy of an innovative psychosocial group intervention compared to a brief psychoeducational group intervention on patients’ body mass index (BMI), body weight, waist circumference, Framingham and HOMA-IR indexes. Methods This is a multicentric RCT with blinded outcome assessments carried out in six Italian university centers. After recruitment patients were randomized to receive a 6-month psychosocial intervention to improve patients’ physical health or a brief psychoeducational intervention. All recruited patients were assessed with standardized assessment instruments at baseline and after 6 months. Anthropometric parameters and blood samples have also been collected. Results Four-hundred and two patients with a diagnosis of bipolar disorder (43.3%), schizophrenia or other psychotic disorder (29.9%), or major depression (26.9%) were randomly allocated to the experimental (N = 206) or the control group (N = 195). After 6 months, patients from the experimental group reported a significant reduction in BMI (odds ratio [OR]: 1.93, 95% confidence intervals [CI]: 1.31–2.84; p

Background: The Wolframin His611Arg polymorphism can influence drug consumption in psychiatric patients with impulsive addictive behavior. This cross-sectional study aims to assess the prevalence of the Wolframin His611Arg polymorphism in MOH, a secondary headache belonging to the spectrum of addictive disorders, episodic migraine (EM), and healthy subjects (HS), and its influence on drug consumption.Methods: One-hundred and seventy-two EM, 107 MOH, and 83 HS were enrolled and genotyped for the Wolframin His611Arg polymorphism. Subjects were classified as homozygous for allele His (H/H subjects), homozygous for allele Arg (R/R subjects), and heterozygous (H/R subjects), regrouped as R/R and carriers of allele H (non-R/R), and matched for clinical data.Results: There were no differences in allelic distributions between the three groups (p = 0.19). Drug consumption and other clinical characteristics were not influenced by the Wolframin His611Arg polymorphism (p = 0.42; β = 0.04) in the EM group. Among the MOH population, R/R subjects consumed more analgesics (p < 0.0001; β = −0.38), particularly combination drugs (p = 0.0001; d = 2.32).Discussion: The Wolframin His611Arg polymorphism has a similar prevalence between the MOH, EM, and HS groups. The presence of the R/R genotype does not influence symptomatic drug consumption in EM, whereas it determines an increased use of symptomatic drugs in the MOH group, in particular combination drugs (i.e., drugs containing psychoactive compounds).Conclusions: Our findings are consistent with the hypothesis that the Wolframin His611Arg polymorphism plays its effect only in the MOH population, influencing the impulsivity control underlying addictive behavior.

Background: Recent evidence showed adverse mental health outcomes associated with the COVID-19 pandemic, including trauma-related symptoms. The Global Psychotrauma Screen (GPS) is a brief instrument designed to assess a broad range of trauma-related symptoms with no available validation in the Italian population. Aims: This study aimed to examine the factor structure of the Italian version of the GPS in a general population sample exposed to the COVID-19 pandemic and to evaluate trauma-related symptoms in the context of COVID-19 related risk factors associated with lockdown measures. Methods: We conducted a cross-sectional web-based observational study as part of a long-term monitoring programme of mental health outcomes in the general population. Eighteen thousand one hundred forty-seven participants completed a self-report online questionnaire to collect key demographic data and evaluate trauma-related symptoms using the GPS, PHQ-9, GAD-7, ISI, and PSS. Validation analyses included both exploratory and confirmatory factor analysis and correlation analyses. The relation with putative COVID-19 related risk factors was explored by multivariate regression analysis. Results: Exploratory factor analyses supported a two-factor model. Confirmatory factor analysis showed that the best fitting model was a three-factor solution, with core Post-traumatic Stress Symptoms (PTSS) (re-experiencing, avoidance, hyperarousal), Negative Affect (symptoms of depressed mood, anxiety, irritability), and Dissociative symptoms. GPS Risk factors and specific COVID-19 related stressful events were associated with GPS total and the three factor scores. Conclusions: Our data suggest that a wide range of trauma-spectrum symptoms were reported by a large Italian sample during the COVID-19 pandemic. The GPS symptoms clustered best in three factors: Negative Affect symptoms, Core PTSS, and Dissociative symptoms. In particular, high rates of core PTSS and negative affect symptoms were associated with the COVID-19 pandemic in Italy and should be routinely assessed in clinical practice.

IntroductionDuring the COVID-19 pandemic, healthcare workers in Italy have been exposed to an unprecedented pressure and traumatic events. However, no direct comparison with the general population is available so far. The aim of this study is to detail mental health outcomes in healthcare workers compared to the general population.Methods24050 respondents completed an on-line questionnaire during the contagion peak, 21342 general population, 1295 second-line healthcare workers, and 1411 front-line healthcare workers. Depressive, anxious, post-traumatic symptoms and insomnia were assessed. Specific COVID-19 related potential risk factors were also considered in healthcare workers.ResultsDepressive symptoms were more frequent in the general population (28.12%) and front-line healthcare workers (28.35%) compared to the second-line healthcare workers (19.98%) groups. Anxiety symptoms showed a prevalence of 21.25% in the general population, 18.05% for second-line healthcare workers, and 20.55% for front-line healthcare workers. Insomnia showed a prevalence of 7.82, 6.58, and 9.92% for the general population, second-line healthcare workers, and front-line healthcare workers, respectively. Compared to the general population, front-line healthcare workers had higher odds of endorsing total trauma-related symptoms. Both second-line healthcare workers and front-line healthcare workers had higher odds of endorsing core post-traumatic symptoms compared to the general population, while second-line healthcare workers had lower odds of endorsing negative affect and dissociative symptoms. Higher total traumatic symptom score was associated with being a front-line healthcare worker, having a colleague infected, hospitalized, or deceased, being a nurse, female gender, and younger age.ConclusionThis study suggests a significant psychological impact of the COVID-19 pandemic on the Italian general population and healthcare workers. Front-line healthcare workers represent a specific at-risk population for post-traumatic symptoms. These findings underline the importance of monitoring and intervention strategies.

The present study investigates the differences in auditory mismatch negativity (MMN) parameters given in a sample of young subjects with autism spectrum disorder (ASD, n = 37) with or without co-occurrent attenuated psychosis syndrome (APS). Our results show that ASD individuals present an MMN decreased amplitude and prolonged latency, without being influenced by concurrent APS. Additionally, when correlating the MMN indexes to clinical features, in the ASD + APS group, we found a negative correlation between the severity of autistic symptoms and the MMN latency in both frequency (f-MMN r = −0.810; p < 0.0001) and duration (d-MMN r = −0.650; p = 0.006) deviants. Thus, our results may provide a more informative characterization of the ASD sub-phenotype when associated with APS, highlighting the need for further longitudinal investigations.

BackgroundThe psychological impact of the COronaVIrus Disease 2019 (COVID-19) outbreak and lockdown measures on the Italian population are unknown. The current study assesses rates of mental health outcomes in the Italian general population three to 4 weeks into lockdown measures and explores the impact of COVID-19 related potential risk factors.MethodsA web-based survey spread throughout the internet between March 27th and April 6th 2020. Eighteen thousand one hundred forty-seven individuals completed the questionnaire, 79.6% women. Selected outcomes were post-traumatic stress symptoms (PTSS), depression, anxiety, insomnia, perceived stress, and adjustment disorder symptoms (ADS). Seemingly unrelated logistic regression analysis was performed to identify COVID-19 related risk factors.ResultsEndorsement rates for PTSS were 6,604 (37%), 3,084 (17.3%) for depression, 3,700 (20.8%) for anxiety, 1,301 (7.3%) for insomnia, 3,895 (21.8%) for high perceived stress and 4,092 (22.9%) for adjustment disorder. Being woman and younger age were associated with all of the selected outcomes. Quarantine was associated with PTSS, anxiety and ADS. Any recent COVID-related stressful life event was associated with all the selected outcomes. Discontinued working activity due to the COVID-19 was associated with all the selected outcomes, except for ADS; working more than usual was associated with PTSS, Perceived stress and ADS. Having a loved one deceased by COVID-19 was associated with PTSS, depression, perceived stress, and insomnia.ConclusionWe found high rates of negative mental health outcomes in the Italian general population 3 weeks into the COVID-19 lockdown measures and different COVID-19 related risk factors. These findings warrant further monitoring on the Italian population’s mental health.

An earthquake hit the city of L’Aquila in central Italy in 2009, leaving the city completely destroyed and 309 casualties. Unexpectedly, lower rates of psychotic experiences in persons affected by the earthquake compared to non-affected persons were found 10 months after the earthquake. The very long-term impact of a natural disaster on the prevalence of psychotic experiences deserves more in-depth detailing. The Authors examined resilience and psychotic experiences in a university student sample of 494. No effect of direct exposure to the earthquake (odds ratio = 0.64, 95%CI [0.37, 1.11]), material damages (odds ratio = 0.86, 95%CI [0.60, 1.23]), psychological suffering (odds ratio = 1.06, 95% CI [0.83, 1.36]), or global impact severity (odds ratio = 0.92, 95%CI [0.76, 1.12]) on psychotic experiences was detected. Resilience levels did not differ between affected and non-affected persons. Resilience showed a strong protective effect on psychotic experiences (odds ratio=0.38, 95% CI [0.28, 0.51]. The protective effect of the RSA factor “Perception of Self” was significantly stronger in individuals affected by the earthquake compared to non-affected subjects. Being affected by an earthquake is not a risk factor for psychotic experiences in a university student sample, as no direct effect of the earthquake was detected after 10 years after the event. Resilience is confirmed as a strong protective factor for psychotic experiences irrespectively of large collective traumatic events. Extension of these results to a general population sample could provide interesting insights into recovery from natural disasters.

Several studies report on traumatic history in Obsessive Compulsive Disorder (OCD) and comorbidity between Posttraumatic Stress Disorder (PTSD) and OCD. First-line pharmacological treatments for both OCD and PTSD are primarily based on antidepressants, including Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Noradrenaline Reuptake Inhibitors (SNRI) such as Venlafaxine for PTSD. Second-Generation Antipsychotic (SGA) augmentation has shown good outcomes for nonresponsive OCD cases. However, evidence on the use of SGA in PTSD is more limited. In the present paper, we report on comorbid OCD-PTSD successfully treated with aripiprazole augmentation of sertraline. Shared psychopathological and pharmacological aspects of the disorders are discussed.

Background: The “Avolition-apathy” domain of the negative symptoms was found to include different symptoms by factor analytic studies on ratings derived by different scales. In particular, the relationship of anhedonia with this domain is controversial. Recently introduced negative symptom rating scales provide a better assessment of anhedonia, allowing the distinction of anticipatory and consummatory aspects, which might be related to different psychopathological dimensions. The study of associations with external validators, such as electrophysiological, brain imaging or cognitive indices, might shed further light on the status of anhedonia within the Avolition-apathy domain. Objectives: We used brain electrical microstates (MSs), which represent subsecond periods of quasi-stable scalp electrical field, associated with resting-state neural networks (and thus with global patterns of functional connectivity), to test whether the component symptoms of Avolition-apathy share the same correlates. Method: We analyzed multichannel resting EEGs in 142 individuals with schizophrenia (SCZ) and in 64 healthy controls (HC), recruited within the add-on EEG study of the Italian Network for Research on Psychoses. Relative time contribution, duration and occurrence of four MS classes (MS-A/-B/-C/−D) were calculated. Group differences on MS parameters (contribution and duration) and their associations with negative symptom domains (assessed using the Brief Negative Symptoms Scale) were investigated. Results: SCZ, in comparison to HC, showed increased contribution and duration of MS-C. The contribution of MS-A positively correlated with Avolition-apathy, but not with Expressive deficit. Within the Avolition-apathy domain, anticipatory anhedonia, avolition and asociality, but not consummatory anhedonia, showed the same correlations with MS-A contribution. Conclusion: Our findings support the existence of distinct electrophysiological correlates of Avolition-apathy with respect to Expressive deficit, and lend support to the hypothesis that only the anticipatory component of anhedonia shares the same pathophysiological underpinnings of the Avolition-apathy domain. Keywords: Schizophrenia, Avolition-apathy, Anhedonia, Resting-EEG, Brain electrical microstates

Neurocognitive deficits and negative symptoms (NS) have a pivotal role in subjects with schizophrenia (SCZ) due to their impact on patients’ functioning in everyday life and their influence on goal-directed behavior and decision-making. P3b is considered an optimal electrophysiological candidate biomarker of neurocognitive impairment for its association with the allocation of attentional resources to task-relevant stimuli, an important factor for efficient decision-making, as well as for motivation-related processes. Furthermore, associations between P3b deficits and NS have been reported. The current research aims to fill the lack of studies investigating, in the same subjects, the associations of P3b with multiple cognitive domains and the expressive and motivation-related domains of NS, evaluated with state-of-the-art instruments. One hundred and fourteen SCZ and 63 healthy controls (HCs) were included in the study. P3b amplitude was significantly reduced and P3b latency prolonged in SCZ as compared to HCs. In SCZ, a positive correlation was found between P3b latency and age and between P3b amplitude and the Attention-vigilance domain, while no significant correlations were found between P3b and the two NS domains. Our results indicate that the effortful allocation of attention to task-relevant stimuli, an important component of decision-making, is compromised in SCZ, independently of motivation deficits or other NS.

Among the different therapeutic alternatives for post-traumatic stress disorder (PTSD), Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) and Eye Movement Desensitization and Reprocessing (EMDR) Therapy have shown promising results in helping patients cope with PTSD symptoms. However, given the different theoretical and methodological substrate of TF-CBT and EMDR, a potentially different impact on the brain for the two interventions could be hypothesized, as well as an interaction between trauma-specific PTSD symptomatology and response to a given psychotherapy. In this study, we monitored psychological and spontaneous functional connectivity fMRI patterns in two groups of PTSD patients who suffered by the same traumatic event (i.e., natural disaster), before and after a cycle of psychotherapy sessions based on TF-CBT and EMDR. Thirty-seven (37) PTSD patients were enrolled from a larger sample of people exposed to a single, acute psychological stress (i.e., 2002 earthquake in San Giuliano di Puglia, Italy). Patients were randomly assigned to TF-CBT (n = 14) or EMDR (n = 17) psychotherapy. Clinical assessment was performed using the Clinician-Administered PTSD Scale (CAPS), the Davidson Trauma Scale (DTS) and the Work and Social Adjustment Scale (WSAS), both at baseline and after treatment. All patients underwent a fMRI data acquisition session before and after treatment, aimed at characterizing their functional connectivity (FC) profile at rest, as well as potential connectivity changes associated with the clinical impact of psychotherapy. Both EMDR and TF-CBT induced statistically significant changes in clinical scores, with no difference in the clinical impact of the two treatments. Specific changes in FC correlated with the improvement at the different clinical scores, and differently for EMDR and TF-CBT. However, a similarity in the connectivity changes associated with changes in CAPS in both groups was also observed. Specifically, changes at CAPS in the entire sample correlated with an (i) increase in connectivity between the bilateral superior medial frontal gyrus and right temporal pole, and a (ii) decrease in connectivity between left cuneus and left temporal pole. Results point to a similar, beneficial psychological impact of EMDR and TF-CBT for treatment of natural-disaster PTSD patients. Neuroimaging data suggest a similar neurophysiological substrate for clinical improvement following EMDR and TF-CBT, involving changes affecting bilateral temporal pole connectivity.

We present a case of celiac disease (CD) diagnosis in a 75-year-old woman with a long-term history of chronic delusional jealousy and a complex neurological involvement. The case describes a very unusual clinical picture, provides some clinical clues, and highlights the importance of being aware of CD extraintestinal manifestations in order to get a timely diagnosis.

Patients with severe mental disorders die on average 20 years prior to the general population. This mortality gap is mainly due to the higher prevalence of physical diseases and the adoption of unhealthy lifestyle behaviors.The LIFESTYLE trial aims to evaluate the efficacy of a new psychosocial group intervention (including psychoeducational, motivational, and problem-solving techniques) focused on healthy lifestyle behavior compared to a brief educational group intervention in a community sample of patients with severe mental disorders. The trial is a national-funded, multicentric, randomized controlled trial with blinded outcome assessments, which is carried out in six outpatient units of the Universities of Campania “Luigi Vanvitelli” in Naples, Bari, Genova, L'Aquila, Pisa, and Rome—Tor Vergata. All patients are assessed at the following time points: baseline (T0); 2 months post-randomization (T1); 4 months post-randomization (T2); 6 months post-randomization (T3); 12 months post-randomization (T4); and 24 months post-randomization (T5). T1 and T2 assessments include only anthropometric tests. The BMI, a reliable and feasible anthropometric parameter, has been selected as primary outcome. In particular, the mean value of BMI at 6 months from baseline (T3) will be evaluated through a Generalized Estimated Equation model. The work hypothesis is that the LIFESTYLE psychosocial group intervention will be more effective than the brief educational group intervention in reducing the BMI. We expect a mean difference between the two groups of at least one point (and standard deviation of two points) at BMI. Secondary outcomes are: the improvement in dietary patterns, in smoking habits, in sleeping habits, physical activity, personal and social functioning, severity of physical comorbidities, and adherence to medications. The expected sample size consists of 420 patients (70 patients for each of the six participating centers), and they are allocated with a 1:1 ratio randomization, stratified according to center, age, gender, and educational level. Heavy smoking, sedentary behavior, and unhealthy diet pattern are very frequent and are associated with a reduced life expectancy and higher levels of physical comorbidities in people with severe mental disorders. New interventions are needed and we hope that the LIFESTYLE protocol will help to fill this gap.Trial registration number: 2015C7374S.

Neuroimaging represents a powerful tool to investigate the neurobiological correlates of Eye Movements Desensitization and Reprocessing (EMDR). The impact of EMDR on cortical and sub-cortical brain regions has been proven by several investigations demonstrating a clear association between symptoms disappearance and changes in cortical structure and functionality. The aim of this study was to assess by electroencephalography (EEG) and for the first time by positron emission tomography (PET) the changes occurring after EMDR therapy in two cases of psychological trauma following brain concussion and comatose state due to traffic accident. A 28 and a 29 years old men underwent extensive neuropsychological examination, which investigated: (i) categorical and phonological verbal fluency; (ii) episodic verbal memory; (iii) executive functions; (iv) visuospatial abilities; (v) attention and working memory as well as clinical assessment by means of psychopathological tests (CAPS, IES, BDI, SCL90R, and DES). They were then treated by eight sessions of EMDR. During the first session EEG monitoring was continuously performed and 18F-FDG PET scans, depicting brain metabolism, were acquired at rest within a week (T0). After the last session, in which the two clients were considered to be symptoms-free, neuropsychological, clinical, and PET assessment were repeated (T1). PET data were semi-quantitatively compared to a group of 18 normal controls, as for EEG the preferential cortical activations were disclosed by thresholding the individual z-score to a p < 0.05. There was a significant improvement in clinical condition for both clients associated with a significant decrease in CAPS scores. IES and BDI were found to be pathological at T0 and improved at T1 in only one subject. Visuo-constructive abilities and abstract reasoning improved after EMDR in both subjects. As for EEG, the most striking changes occurred in fronto-temporal-parietal cortex in subject 1 while subject 2 showed only minor changes. PET showed more pronounced metabolism in orbito-frontal and prefrontal cortex at T1 as compared to T0 in both subjects. In conclusion both clients had a clear clinical improvement in PTSD symptoms associated with metabolic and electrophysiological changes in limbic and associative cortex, respectively, highlighting the value of EMDR also in such extreme pathological conditions.

Background: Treatment of recurrent depressive disorders is currently only moderately successful. Increasing evidence suggests a significant relationship between adverse childhood experiences and recurrent depressive disorders, suggesting that trauma-based interventions could be useful for these patients.Objectives: To investigate the efficacy of Eye Movement Desensitization and Reprocessing therapy (EMDR) in addition to antidepressant medication (ADM) in treating recurrent depression.Design: A non-inferiority, single-blind, randomized clinical controlled trial comparing EMDR or CBT as adjunctive treatments to ADM. Randomization was carried out by a central computer system. Allocation was carried out by a study coordinator in each center.Setting: Two psychiatric services, one in Italy and one in Spain.Participants: Eighty-two patients were randomized with a 1:1 ratio to the EMDR group (n = 40) or CBT group (n = 42). Sixty-six patients, 31 in the EMDR group and 35 in the CBT group, were included in the completers analysis. Intervention: 15 ± 3 individual sessions of EMDR or CBT, both in addition to ADM. Participants were followed up at 6-months.Main outcome measure: Rate of depressive symptoms remission in both groups, as measured by a BDI-II score

IntroductionDrug-resistant cluster headache (CH) is still an open clinical challenge. Recently, our group observed the clinical efficacy of a ketogenic diet (KD), usually adopted to treat drug-resistant epilepsies, on migraine.AimHere, we aim to detect the effect of KD in a group of drug-resistant chronic CH (CCH) patients.Materials and methodsEighteen drug-resistant CCH patients underwent a 12-week KD (Modified Atkins Diet, MAD), and the clinical response was evaluated in terms of response (≥50% attack reduction).ResultsOf the 18 CCH patients, 15 were considered responders to the diet (11 experienced a full resolution of headache, and 4 had a headache reduction of at least 50% in terms of mean monthly number of attacks during the diet). The mean monthly number of attacks for each patient at the baseline was 108.71 (SD = 81.71); at the end of the third month of diet, it was reduced to 31.44 (SD = 84.61).ConclusionWe observed for the first time that a 3-month ketogenesis ameliorates clinical features of CCH.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT03244735.

Insomnia might occur as result of increased cognitive and physiological arousal caused by acute or long acting stressors and associated cognitive rumination. This might lead to alterations in brain connectivity patterns as those captured by functional connectivity fMRI analysis, leading to potential insight about primary insomnia (PI) pathophysiology as well as the impact of long-term exposure to sleep deprivation. We investigated changes of voxel-wise connectivity patterns in a sample of 17 drug-naïve PI patients and 17 age-gender matched healthy controls, as well as the relationship between brain connectivity and age of onset, illness duration, and severity. Results showed a significant increase in resting-state functional connectivity of the bilateral visual cortex in PI patients, associated with decreased connectivity between the visual cortex and bilateral temporal pole. Regression with clinical scores originally unveiled a pattern of increased local connectivity as measured by intrinsic connectivity contrast (ICC), specifically resembling the default mode network (DMN). Additionally, age of onset was found to be correlated with the connectivity of supplementary motor area (SMA), and the strength of DMN←→SMA connectivity was significantly correlated with both age of onset (R2 = 41%) and disease duration (R2 = 21%). Chronic sleep deprivation, but most importantly early insomnia onset, seems to have a significant disruptive effect over the physiological negative correlation between DMN and SMA, a well-known fMRI marker of attention performance in humans. This suggests the need for more in-depth investigations on the prevention and treatment of connectivity changes and associated cognitive and psychological deficits in PI patients.

BACKGROUND: Eye Movement Desensitization and Reprocessing (EMDR) is a recognized first-line treatment for psychological trauma. However its neurobiological bases have yet to be fully disclosed. METHODS: Electroencephalography (EEG) was used to fully monitor neuronal activation throughout EMDR sessions including the autobiographical script. Ten patients with major psychological trauma were investigated during their first EMDR session (T0) and during the last one performed after processing the index trauma (T1). Neuropsychological tests were administered at the same time. Comparisons were performed between EEGs of patients at T0 and T1 and between EEGs of patients and 10 controls who underwent the same EMDR procedure at T0. Connectivity analyses were carried out by lagged phase synchronization. RESULTS: During bilateral ocular stimulation (BS) of EMDR sessions EEG showed a significantly higher activity on the orbito-frontal, prefrontal and anterior cingulate cortex in patients at T0 shifting towards left temporo-occipital regions at T1. A similar trend was found for autobiographical script with a higher firing in fronto-temporal limbic regions at T0 moving to right temporo-occipital cortex at T1. The comparisons between patients and controls confirmed the maximal activation in the limbic cortex of patients occurring before trauma processing. Connectivity analysis showed decreased pair-wise interactions between prefrontal and cingulate cortex during BS in patients as compared to controls and between fusiform gyrus and visual cortex during script listening in patients at T1 as compared to T0. These changes correlated significantly with those occurring in neuropsychological tests. CONCLUSIONS: The ground-breaking methodology enabled our study to image for the first time the specific activations associated with the therapeutic actions typical of EMDR protocol. The findings suggest that traumatic events are processed at cognitive level following successful EMDR therapy, thus supporting the evidence of distinct neurobiological patterns of brain activations during BS associated with a significant relief from negative emotional experiences.

Previous research has reported that a functional polymorphism in the monoamine oxidase A (MAOA) gene promoter can moderate the association between early life adversity and increased risk for violence and antisocial behavior. In this study of a combined population of psychiatric outpatients and healthy volunteers (N = 235), we tested the hypothesis that MAOA genotype moderates the association between early traumatic life events (ETLE) experienced during the first 15 years of life and the display of physical aggression during adulthood, as assessed by the Aggression Questionnaire. An ANOVA model including gender, exposure to early trauma, and MAOA genotype as between-subjects factors showed significant MAOAxETLE (F(1,227) = 8.20, P = 0.005) and genderxMAOAxETLE (F(1,227) = 7.04, P = 0.009) interaction effects. Physical aggression scores were higher in men who had experienced early traumatic life events and who carried the low MAOA activity allele (MAOA-L). We repeated the analysis in the subgroup of healthy volunteers (N = 145) to exclude that the observed GxE interactions were due to the inclusion of psychiatric patients in our sample and were not generalizable to the population at large. The results for the subgroup of healthy volunteers were identical to those for the entire sample. The cumulative variance in the physical aggression score explained by the ANOVA effects involving the MAOA polymorphism was 6.6% in the entire sample and 12.1% in the sub-sample of healthy volunteers. Our results support the hypothesis that, when combined with exposure to early traumatic life events, low MAOA activity is a significant risk factor for aggressive behavior during adulthood and suggest that the use of dimensional measures focusing on behavioral aspects of aggression may increase the likelihood of detecting significant gene-by-environment interactions in studies of MAOA-related aggression.