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Psychiatric drugs have primacy for off-label prescribing. Among those, selective serotonin reuptake inhibitors (SSRIs) are highly versatile and, therefore, widely prescribed. Moreover, they are commonly considered as having a better safety profile compared to other antidepressants. Thus, when it comes to off-label prescribing, SSRIs rank among the top positions. In this review, we present the state of the art of off-label applications of selective serotonin reuptake inhibitors, ranging from migraine prophylaxis to SARS-CoV-2 antiviral properties. Research on SSRIs provided significant evidence in the treatment of premature ejaculation, both with the on-label dapoxetine 30 mg and the off-label paroxetine 20 mg. However, other than a serotoninergic syndrome, serious conditions like increased bleeding rates, hyponatremia, hepatoxicity, and post-SSRIs sexual dysfunctions, are consistently more prominent when using such compounds. These insidious side effects might be frequently underestimated during common clinical practice, especially by nonpsychiatrists. Thus, some points must be addressed when using SSRIs. Among these, a psychiatric evaluation before every administration that falls outside the regulatory agencies-approved guidelines has to be considered mandatory. For these reasons, we aim with the present article to identify the risks of inappropriate uses and to advocate the need to actively boost research encouraging future clinical trials on this topic.

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.

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.

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.

Key Points Question What are the mental health outcomes among Italian health care workers during the COVID-19 pandemic? Findings In this longitudinal cohort study of 2856 health care workers in Italy during the COVID-19 pandemic the prevalence of depression symptoms, anxiety symptoms, insomnia symptoms, and posttraumatic stress symptoms decreased among Italian health care workers 14 months after the beginning of the COVID-19 pandemic. Prolonged work with patients with COVID-19 was significantly associated with mental health outcomes, whereas quitting work as a frontline health care worker was significantly associated with decrease in mental health issues. Meaning These findings help to identify the potential risk factors for health care workers exposed to direct contact with patients with COVID-19 and could help inform better preventive policies regarding mental health in this particular population., Importance Health care workers (HCWs) exposed to COVID-19 have high rates of mental health issues. However, longitudinal data on the evolution of mental health outcomes in HCWs are lacking. Objective To evaluate the mental health outcomes among Italian HCWs 14 months after the beginning of the COVID-19 pandemic. Design, Setting, and Participants This longitudinal cohort study collected data from March 1 to April 30, 2020 (T1) and from April 1 to May 31, 2021 (T2), from 2856 Italian HCWs aged 18 years or older who responded to an online questionnaire. Participants were also recruited via snowballing, a technique in which someone who receives the invitation to participate forwards it to his or her contacts. Exposures Frontline vs second-line position, job type, hospitalization for COVID-19, and colleagues or family members affected by COVID-19. Main Outcomes and Measures Outcomes are depression symptoms, anxiety symptoms, insomnia symptoms, and posttraumatic stress symptoms (PTSSs). Four different trajectories are described for each condition: resilient, remittent, incident, and persistent. Results Of the 2856 HCWs, 997 (34.9%) responded to the follow-up assessment (mean [SD] age, 42.92 [10.66] years; 816 [82.0%] female). Depression symptoms (b = −2.88; 95% CI, −4.05 to −1.71), anxiety symptoms (b = −2.01; 95% CI, −3.13 to −0.88), and PTSSs (b = −0.77; 95% CI, −1.13 to −0.42) decreased over time; insomnia symptoms increased (b = 3.05; 95% CI, 1.63-4.47). Serving as a frontline HCW at T1 was associated with decreased symptoms of depression (b = −1.04; 95% CI, −2.01 to −0.07), and hospitalization for COVID-19 was associated with increased depression symptoms (b = 5.96; 95% CI, 2.01-9.91); younger age (b = −0.36; 95% CI, −0.70 to −0.03) and serving as a frontline HCW at T1 (b = −1.04; 95% CI, −1.98 to −0.11) were associated with decreased anxiety symptoms. Male sex was associated with increase in insomnia symptoms (b = 1.46; 95% CI, 0.39-2.53). Serving as a frontline HCW at T1 (b = −0.42; 95% CI, −0.71 to −0.13) and being a physician (b = −0.52; 95% CI, −0.81 to −0.24) were associated with a decrease in PTSSs, whereas younger age (b = 0.35; 95% CI, 0.09-0.61) and male sex (b = 0.12; 95% CI, 0.01-0.22) were associated with an increase in PTSSs. Depression trajectories were 629 resilient (65.5%), 181 remittent (18.8%), 58 incident (6.0%), and 92 persistent (9.6%). Anxiety trajectories were 701 resilient (73.3%), 149 remittent (15.6%), 45 incident (4.7%), and 61 persistent (6.4%). Insomnia trajectories were 858 resilient (88.9%), 77 remittent (8.0%), 20 incident (2.1%), and 10 persistent (1.0%). The PTSS trajectories were 363 resilient (38.5%), 267 remittent (28.3%), 86 incident (9.1%), and 226 persistent (24.0%). Conclusions and Relevance In this cohort study, relative to the beginning of the COVID-19 pandemic, mental health among HCWs has improved. Factors associated with change in mental health outcomes could help in the design of prevention strategies for HCWs., This cohort study assesses the prevalence and associated risk or protective factors of symptoms of depression, anxiety, insomnia, and posttraumatic stress among Italian health care workers in the 14 months after the COVID-19 pandemic began.

Introduction: The global COVID-19 pandemic has affected the economy, daily life, and mental/physical health. The latter includes the use of electroencephalography (EEG) in clinical practice and research. We report a survey of the impact of COVID-19 on the use of clinical EEG in practice and research in several countries, and the recommendations of an international panel of experts for the safe application of EEG during and after this pandemic. Methods: Fifteen clinicians from 8 different countries and 25 researchers from 13 different countries reported the impact of COVID-19 on their EEG activities, the procedures implemented in response to the COVID-19 pandemic, and precautions planned or already implemented during the reopening of EEG activities. Results: Of the 15 clinical centers responding, 11 reported a total stoppage of all EEG activities, while 4 reduced the number of tests per day. In research settings, all 25 laboratories reported a complete stoppage of activity, with 7 laboratories reopening to some extent since initial closure. In both settings, recommended precautions for restarting or continuing EEG recording included strict hygienic rules, social distance, and assessment for infection symptoms among staff and patients/participants. Conclusions: The COVID-19 pandemic interfered with the use of EEG recordings in clinical practice and even more in clinical research. We suggest updated best practices to allow safe EEG recordings in both research and clinical settings. The continued use of EEG is important in those with psychiatric diseases, particularly in times of social alarm such as the COVID-19 pandemic., SCOPUS: ed.j, info:eu-repo/semantics/published

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.

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.

BackgroundOne in six adolescents suffers from mental health problems. Despite the presence of general information on Italian adolescents' mental health, researches conducted with standardized assessment tools are scarce in the literature. We evaluated the prevalence of self-reported behavioral and emotional problems in a group of Italian adolescents and examined their relation to socio-demographical variables.MethodsThis population-based sampling survey was conducted on high school students aged 14–18 from urban areas of Rome and Latina. Participants completed Youth Self-Report (YSR) and a socio-demographic schedule to collect information on age, gender, type of school attended, socio-economic status, urbanicity.ResultsFinal sample consisted of 1400 adolescents (38.61% male, mean age 16 years, s.d. 1.42). Prevalence of Internalizing Problems, Externalizing Problems and Total Problems was 29.55%, 18.34% and 24.13%. In our multivariable model, Internalizing Symptoms were not explained by sociodemographic variables while Externalizing Symptoms were explained by Male Gender [OR = 1.53 (1.14–2.06)], older age [OR = 2.06 (1.52–2.79)] and attending a Technical and Professional Institute [OR = 2.15 (1.53–3.02)], with an adjusted R2 = 4.32%. Total Problems were explained by School Type [Technical and Professional Institutes and Art and Humanities v. Grammar and Science School; OR respectively 1.93 (1.40–2.67) and 1.64 (1.08–2.47)], adjusted R2 = 1.94.ConclusionsThe study provides, for the first time, evidence of a great prevalence of self-reported behavioral and emotional problems in a large sample of Italian adolescents, highlighting the role of different socio-demographic variables as risk factors for externalizing behaviors. Our results emphasize the urgent need for implementing prevention programs on mental health in adolescence.

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 four 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. 18147 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.ResultsRespondents endorsing PTSS, depression, anxiety, insomnia, high perceived stress and adjustment disorder were 6604 (37%), 3084 (17.3%), 3700 (20.8%), 1301 (7.3%), 3895 (21.8%) and 4092 (22.9%), respectively. 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 three 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.

Background The 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. Methods A 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. Results Endorsement 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. Conclusion We 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.

A general personality and psychopathology evaluation is considered to be crucial part of the multidisciplinary assessment for weight-related problems. The Symptom Checklist-90-Revised (SCL-90-R) is commonly used to assess general psychopathology in both overweight and obese patients seeking weight-loss treatment. The main purpose of the present research was to investigate the psychometric properties of the brief form of the SCL-90-R (i.e., the SCL-K-9) in a clinical sample (N = 397) of patients seeking weight-loss treatment (i.e., bariatric surgery and a nutritional weight-loss program). The results of the confirmatory factor analysis supported a one-factor solution of the SCL-K-9, with all nine items loading significantly on the common latent factor (lambdas &ge, 0.587). The ordinal &alpha, (= 0.91), the inter-item mean indices of correlation (rii = 0.53), and the convergent validity were also satisfactory. A receiver operating characteristic curves procedure showed that both SCL-90-R and SCL-K-9 were able to classify patients with and without significant binge eating pathology according to the Binge Eating Scale (BES) total score. Overall, our results suggest that the SCL-K-9 has adequate psychometric properties and can be applied as a short screening tool to assess general psychopathology in overweight/obese individuals seeking weight-loss treatment and at follow-up interviews when time restraints preclude the use of the full-length form.

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.

The present overview was aimed at presenting the state of the art of the clinical use of Transcranial Magnetic Stimulation (TMS) protocols in the treatment of anxiety disorders. Available evidence shows that TMS therapeutic protocols over the prefrontal cortex, with excitatory stimulation at the left side and/or inhibitory stimulation of the right side, are effective and well tolerated to reduce anxiety symptoms in Panic Disorder and Generalized Anxiety Disorder. To date, the level of evidence is, however, relatively low regarding the clinical use of TMS therapeutic protocols in anxiety disorders. Future investigation, with an improvement both in methodological issues and in study design, will reveal the real usefulness of TMS therapeutic protocols in the treatment of anxiety disorders.

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.

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.

Health care workers (HCWs) involved in the coronavirus disease 2019 (COVID-19) pandemic are exposed to high levels of stressful or traumatic events and express substantial negative mental health outcomes,1 including stress-related symptoms and symptoms of depression, anxiety, and insomnia. In this cross-sectional study, we report on mental health outcomes among HCWs in Italy.

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., Highlights • Microstate C contribution and duration were increased in SCZ compared to HC. • Avolition-apathy was correlated with the contribution of microstate A. • Avolition-apathy might be associated with sensory processing deficit.

Here we aimed at determining the therapeutic effect of a very low-calorie diet in overweight episodic migraine patients during a weight-loss intervention in which subjects alternated randomly between a very low-calorie ketogenic diet (VLCKD) and a very low-calorie non-ketogenic diet (VLCnKD) each for one month. In a nutritional program, 35 overweight obese migraine sufferers were allocated blindly to 1-month successive VLCKD or VLCnKD in random order (VLCKD-VLCnKD or VLCnKD-VLCD). The primary outcome measure was the reduction of migraine days each month compared to a 1-month pre-diet baseline. Secondary outcome measures were 50% responder rate for migraine days, reduction of monthly migraine attacks, abortive drug intake and body mass index (BMI) change. Only data from the intention-to-treat cohort (n = 35) will be presented. Patients who dropped out (n = 6) were considered as treatment failures. Regarding the primary outcome, during the VLCKD patients experienced &minus, 3.73 (95% CI: &minus, 5.31, &minus, 2.15) migraine days respect to VLCnKD (p &lt, 0.0001). The 50% responder rate for migraine days was 74.28% (26/35 patients) during the VLCKD period, but only 8.57% (3/35 patients) during VLCnKD. Migraine attacks decreased by &minus, 3.02 (95% CI: &minus, 4.15, &minus, 1.88) during VLCKD respect to VLCnKD (p &lt, 0.00001). There were no differences in the change of acute anti-migraine drug consumption (p = 0.112) and BMI (p = 0.354) between the 2 diets. A VLCKD has a preventive effect in overweight episodic migraine patients that appears within 1 month, suggesting that ketogenesis may be a useful therapeutic strategy for migraines.

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).

Objective: No data are available about learning needs and career attitudes of Italian Psychiatry Residents (IPRs). Authors aimed to assess such needs through a survey to generate insight for implementing educational programs close to IPRs’ perceived learning needs. Methods: A 54-item questionnaire was developed in order to investigate career information, educational preference and learning needs of IPRs. A sample of 298 IPRs participated to the survey and was divided into four subgroups according to their location (North, Centre, South and Islands). The subgroups were compared through ANOVA for age and chi-square tests for qualitative variables (including gender and all sub-items of the survey), with Bonferroni post-hoc analysis. Results: IPRs were found to pursue, along with traditional and theoretical training, a quite practical approach, characterized by working groups, discussions on clinical cases and practical interactive sessions. The topics of major interest included: clinical psychiatry, psychopharmacology, psychiatric emergencies, communication and relationship skills (97%, 98.0%, 98.3% and 95.7% of the total sample, respectively). Indeed, a strong need for interaction with healthcare professionals emerged (97% of the total sample). North and Centre IPRs were more involved in Day Hospital activities than residents from South Italy and Islands (pp Conclusion: Reported findings should be taken into account as a starting point for planning and developing future targeted packages of educational proposals for IPRs and they should stand as a useful pilot study for further investigation in the field.

Inflammatory bowel diseases (IBD) are associated with comorbid depressive and anxiety disorders, but a significant proportion of IBD patients with psychiatric disorders (PsychD) remain undiagnosed and untreated. The aim of this study was to assess the frequency and type of undiagnosed PsychD in IBD patients. Two hundred and thirty-seven adult IBD (136 Crohn’s disease (CD) and 101 ulcerative colitis (UC)) outpatients were consecutively recruited at a single university hospital centre between January 2018 and June 2019. After a scheduled follow-up visit for IBD clinical evaluation, participants underwent a semi-structured interview with a trained psychiatrist. One hundred and fourteen (48%) IBD patients had at least one PsychD, and in 67 (59%) of them, a diagnosis was made for the first time during the study. The remaining 47 (41%) patients had received a previous psychiatric diagnosis, but in only six cases was it consistent with the diagnosis made during the study. PsychD were equally distributed in CD (72/136, 53%) and UC (42/101, 42%), and mostly represented by mood disorders (54/114, 47%) and anxiety (27/114, 24%) disorders. PsychD were not related to the disease severity, phenotype or localisation of IBD, even though having three or more concomitant PsychD was associated with more severe disease in CD. Our data indicate that undiagnosed PsychD are common in IBD and highlight the importance of considering psychiatric evaluation in the management of IBD patients.

Cross-sectional data suggest videogaming as promoting modifications in perceptual and cognitive skills of players, as well as inducing structural brain changes. However, whether such changes are both possible after a systematic gaming exposure, and last beyond the training period, is not known. Here, we originally quantified immediate and long-lasting cognitive and morphometric impact of a systematic gaming experience on a first-person shooter (FPS) game. Thirty-five healthy participants, assigned to a videogaming and a control group, underwent a cognitive assessment and structural magnetic resonance imaging at baseline (T0), immediately post-gaming (T1) and after 3 months (T2). Enhancements of cognitive performance were found on perceptual and attentional measures at both T1 and T2. Morphometric analysis revealed immediate structural changes involving bilateral medial and posterior thalamic nuclei, as well as bilateral superior temporal gyrus, right precentral gyrus, and left middle occipital gyrus. Notably, significant changes in pulvinar volume were still present at T2, while a voxel-wise regression analysis also linked baseline pulvinar volume and individual changes in gaming performance. Present findings extend over the notion that videogame playing might impact cognitive and brain functioning in a beneficial way, originally showing long-term brain structural changes even months after gaming practice. The involvement of posterior thalamic structures highlights a potential link between FPS games and thalamo-cortical networks related to attention mechanisms and multisensory integration processing.

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 EMDR in addition to antidepressant medication in treating recurrent depression. Design: A non-inferiority, single-blind, randomized clinical controlled trial comparing EMDR or CBT as adjunctive treatments to antidepressant medication. 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 antidepressant medication. Participants were followed up at six-months. Main outcome measure: Rate of depressive symptoms remission in both groups, as measured by a BDI-II score

Paraphilias are conditions characterized by atypical sexual interests, with hundreds of forms arising from any type of human experience, affecting individuals of all kinds of orientations and even different gender identities. Current psychiatric diagnostic classifications do not consider the presence of paraphilia as a pathological condition unless these atypical sexual thinking, desires, and conducts generate subjective distress, compromise individual’s sexual functioning, and increase the risk of the personal damage or the risk of damage to others. Against this background, this chapter presents the current clinical description and psychiatric diagnostic approach to paraphilic disorders, their epidemiology, and etiopathophysiological factors as well as treatment strategies of one of the most misunderstood groups of psychiatric disorders.

Aim: This study evaluated adherence to treatment, quality of life and subjective well-being in patients with psychosis treated with long-acting injectable risperidone. Subjects enrolled were part of a larger study where patients were observed in an adherence to treatment program of the University of Rome Tor Vergata. Materials and methods: A total of 27 nonadherent patients (21 men, six women; mean age: 36.1 years; range: 23–63 years) were enrolled. Maximum observational period was 30 months. Results: A total of 12 patients were under treatment for 30 months (44.44%) but only nine had a valid 30-month follow up, while the remaining three patients initially treated at our unit continued long-acting risperidone at their local centre. Reductions of monthly mean values of Scale for the Assessment of Positive Symptoms (SAPS) [repeated measures analysis of variance (rm-ANOVA): p < 0.0001] and Scale for Assessment of Negative Symptoms (SANS) ( p < 0.0001), increase of monthly mean values of Subjective Well-Being Under Neuroleptic Treatment Scale (SWN) ( p < 0.0001) and Schizophrenia Quality of Life Scale (S-QoL) ( p < 0.01) were observed. Significant differences with respect to SAPS baseline values from the sixth month, SANS baseline values from the seventh month, SWN baseline values from the eighth month, S-QoL baseline values from the eighteenth month were shown in post hoc tests. Reduction of SAPS mean values was associated with increase of SWN ( p < 0.0001) and S-QoL ( p < 0.0001) mean values as demonstrated by correlation analysis. The same inverse correlation was found between reduction of SANS mean values and increases of SWN ( p < 0.0001) and S-QoL ( p = 0.0001) mean values. Conclusions: Long-term treatment with long-acting risperidone may be associated with improvement to adherence to therapy and quality of life. Patients may show improvement in psychopathological symptoms, subjective well-being and quality of life.

Recent evidence shows how an extensive gaming experience might positively impact cognitive and perceptual functioning, leading to brain structural changes observed in cross-sectional studies. Importantly, changes seem to be game-specific, reflecting gameplay styles and therefore opening to the possibility of tailoring videogames according to rehabilitation and enhancement purposes. However, whether if such brain effects can be induced even with limited gaming experience, and whether if they can outlast the gaming period, is still unknown. Here we quantified both cognitive and grey matter thickness changes following 15 daily gaming sessions based on a modified version of a 3D first-person shooter (FPS) played in laboratory settings. Twenty-nine healthy participants were randomly assigned to a control or a gaming group and underwent a cognitive assessment, an in-game performance evaluation and structural magnetic resonance imaging before (T0), immediately after (T1) and three months after the end of the experiment (T2). At T1, a significant increase in thickness of the bilateral parahippocampal cortex (PHC), somatosensory cortex (S1), superior parietal lobule (SPL) and right insula were observed. Changes in S1 matched the hand representation bilaterally, while PHC changes corresponded to the parahippocampal place area (PPA). Surprisingly, changes in thickness were still present at T2 for S1, PHC, SPL and right insula as compared to T0. Finally, surface-based regression identified the lingual gyrus as the best predictor of changes in game performance at T1. Results stress the specific impact of core game elements, such as spatial navigation and visuomotor coordination on structural brain properties, with effects outlasting even a short intensive gaming period.

Introduction Drug-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. Aim Here, we aim to detect the effect of KD in a group of drug-resistant chronic CH (CCH) patients. Materials and methods Eighteen 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). Results Of 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). Conclusion We observed for the first time that a 3-month ketogenesis ameliorates clinical features of CCH. Clinical Trial Registration www.ClinicalTrials.gov, identifier NCT03244735.

The study aimed at investigating the role of the hippocampal subfields in cognitive insight and the clinical and neuropsychological underpinnings of the related two sub-dimensions, Self-Reflectiveness (SR), i.e., openness to external feedback, and Self-Certainty (SC), i.e., unrealistic overconfidence in one's opinions. In order to do this, 45 patients with a diagnosis of schizophrenia and 45 age- and gender-matched healthy control subjects (HC) were administered the Beck Cognitive Insight Scale (BCIS), along with neuropsychological, clinical and psychopathological assessment, and underwent an MRI investigation. Hippocampal segmentation was carried out. Regression analyses were performed for BCIS indexes, volumetric parameters of hippocampal subfields and clinical and neuropsychological variables. Results highlighted that in the schizophrenia group, higher levels of SC were related to reduced volume of the left presubiculum, and worse episodic memory. No significant relationship emerged for the SR index. There was no significant relationship between any of the BCIS indexes and volumetric data of the hippocampal subfields in the HC group. Our data support the hypothesis that unrealistic self-overconfidence in schizophrenia is related to the hippocampal presubiculum atrophy, which is involved in episodic memory and cognitive control and is supposed to be underpinned by difficulty in integrating new memories and thus in generating new hypotheses about the self.

The relationships of personal resources with symptom severity and psychosocial functioning have never been tested systematically in a large sample of people with schizophrenia. We applied structural equation models to a sample of 921 patients with schizophrenia collected in a nationwide Italian study, with the aim to identify, among a large set of personal resources, those that may have an association with symptom severity or psychosocial functioning. Several relevant demographic and clinical variables were considered concurrently. Poor service engagement and poor recovery style, as well as older age and younger age at onset, were related to greater symptom severity and poorer social functioning. Higher resilience and higher education were related to better social functioning only. Poor problem-focused coping and internalized stigma, as well as male gender and depression, were related to symptom severity only. The explored variables showed distinctive and partially independent associations with symptom severity and psychosocial functioning. A deeper understanding of these relationships may inform treatment decisions.

An under-recognised U-shaped model states that unconscious and conscious perceptual effects are functionally exclusive and that unconscious perceptual effects manifest themselves only at the objective detection threshold, when conscious perception is completely absent. We tested the U-shaped line model with a between-subjects paradigm. Angry, happy, neutral faces, or blank slides were flashed for 5.5 ms and 19.5 ms before Chinese ideographs in a darkened room. A group of volunteers ( n = 84) were asked to rate how much they liked each ideograph and performed an identification task. According to the median identification score two subgroups were composed; one with 50% or 50% high-identification group (supraliminal perception). The two intermediate points (19.5 ms of the low-identification group and 5.5 ms of the high-identification group) did not correspond to significant priming effects. These results confirm that a complete absence of conscious perception is the condition for the deployment of unconscious perceptual effects.

Background Here, we aim to identify cortical electrofunctional correlates of responsiveness to short-lasting preventiveintervention with ketogenic diet (KD) in migraine. Methods Eighteen interictal migraineurs underwent visual (VEPs) and median nerve somatosensory (SSEPs) evokedpotentials before and after 1 month of KD during ketogenesis. We measured VEPs N1-P1 and SSEPs N20-P25 amplitudes respectively in six and in two sequential blocks of 100 sweeps as well as habituation as theslope of the linear regression between block 1 to 6 for VEPs or between 1 to 2 for SSEPs. Results After 1-month of KD, a significant reduction in the mean attack frequency and duration was observed (all P

Objective: We used MRI to search for changes in thalamo-cortical networks and thalamic microstructure during spontaneous migraine attacks by studying at the same time structure with diffusion tensor imaging and resting state function in interconnected brain networks with independent component analysis. Methods: Thirteen patients with untreated migraine without aura (MI) underwent 3T MRI scans during an attack and were compared to a group of 19 healthy controls (HC). We collected resting state data in 2 selected networks identified using group independent component (IC) analysis. Fractional anisotropy (FA) values of bilateral thalami were calculated in the same participants and correlated with resting state IC z scores. Results: Functional connectivity between the executive and the dorso-ventral attention networks was reduced in MI compared to HC. In HC, but not in MI, the higher the IC24 z score, encompassing interconnected areas of the dorso-ventral attention system, the lower the bilateral thalamic FA values. In patients, the higher the executive control network z scores, the lower the number of monthly migraine days. Conclusions: These results provide evidence for abnormal connectivity between the thalamus and attentional cerebral networks at rest during migraine attacks. This abnormality could subtend the known ictal impairment of cognitive performance and suggests that the latter might worsen with increasing attack frequency.

Background: An underestimated feature of schizophrenia is the impaired processing of the metaphoric speech, mainly due to a reduced activation of the right hemisphere. Objective/hypothesis: We investigated whether anodal tDCS over the right posterior superior temporal sulcus may improve the processing of metaphoric speech of schizophrenia patients (SCZ). Methods: Ten SCZ subjects were randomly allocated to receive a single session of active tDCS or sham stimulation. Metaphoric speech processing was investigated through a discrimination task between literal or metaphoric expressions. Results: tDCS improved significantly the reaction time but not the accuracy of the answers at the discrimination task compared to sham stimulation. Conclusion: These preliminary results should be verified in larger studies with more sessions of tDCS.

Several contributions have reported an altered expression of pseudoneglect in psychiatric disorders, highlighting the existence of an anomalous brain lateralization in affected subjects. Surprisingly, no studies have yet investigated pseudoneglect in first-degree relatives (FdR) of psychiatric patients. We investigated performance on “paper and pencil” line bisection (LB) tasks in 68 schizophrenic patients (SCZ), 42 unaffected FdR, 41 unipolar depressive patients (UP), and 103 healthy subjects (HS). A subgroup of 20 SCZ and 16 HS underwent computerized LB and mental number line bisection (MNL) tasks requiring judgment of prebisected lines and numerical intervals. Moreover, we evaluated, in a subgroup of 15 SCZ, performance on LB and MNL before and after parietal transcranial direct current stimulation (tDCS). In comparison to HS and UP, SCZ showed a systematic rightward bias on LB, partially corrected by selective right posterior parietal tDCS. Interestingly, even FdR showed a lack of pseudoneglect on LB, expressing a mean error lying in the middle between those of HS and SCZ. On the other hand, our results showed no significant difference between the performance of SCZ and HS on MNL. Both groups showed a comparable leftward bias that could not be significantly altered after left or right parietal tDCS. These findings confirm the existence of reduced lateralization in SCZ, suggesting specific impaired functioning of the right parietal lobule. Notably, we report a lack of pseudoneglect not only in SCZ but also in FdR, raising the hypothesis that an inverted laterality pattern may be considered a concrete marker of schizotypal traits.

Several studies have shown that physical and/or sexual abuse during childhood may lead to the development of obesity later in life. Despite these consistent findings, the mechanism for the increased risk of obesity following developmental trauma is unknown. It has been suggested that psychological dysfunction, including the presence of disordered eating behavior, may account for the added risk of adult obesity. To test this hypothesis, we analyzed the prevalence and severity of different types of early traumatic life events, assessed the presence of co-existing psychiatric disorders and measured adult attachment style in a sample of 200 subjects including non-obese healthy volunteers and obese participants undergoing a psychiatric assessment to determine suitability for bariatric surgery. Participants who scored higher on a scale measuring the severity of traumatic events experienced during the first 15 years of their lives were more likely to be obese at the time of testing. The exclusion of the participants who experienced physical and/or sexual abuse did not change the results of statistical analysis. Severity of early trauma remained a significant predictor of adult obesity when the influence of psychiatric diagnosis and anxious attachment was taken into account. These findings suggest that: (1) not only sexual or physical abuse but also less severe forms of early-life stress are linked to the development of obesity later in life; and (2) psychological dysfunction is not the only mechanism mediating the elevated risk of obesity in persons exposed to early-life trauma.

Medication overuse headache (MOH) can be considered a clinical condition at the boundaries between drug addiction and chronic pain disorder. The common 196G > A single-nucleotide polymorphism of BDNF gene, resulting in a valine 66 to methionine (Val66Met), is related with behaviour disorders and substance abuse. With the aim of identifying a worsening factor in MOH, rather than the detection of a specific risk factor for the development of the disease, we investigated whether the presence of a functional BDNF polymorphism might determine clinical differences within a group of 90 MOH patients, particularly in monthly drug consumption, that is the hallmark of disease. Directly comparing MOH patients homozygous for G allele (G/G) with carriers of A allele (non-G/G), we have observed 47 G/G genotypes and 60 non-G/G genotypes. Non-G/G had a higher consumption of monthly drug number (Cohen’s d = 0.76) than G/G patients. At multiple regression analysis, the Val66Met BDNF polymorphism emerged as a significant independent predictor of analgesic drug consumption (Beta = 0.33, Cohen’s f2 = 0.134). These findings showed an influence of examined BDNF polymorphism in the MOH clinical features, supporting the idea that MOH is a substance abuse disorder.

O028. Thalamo-cortical network changes during the migraine cycle: insights from MRI-based microstructural and functional resting-state network correlation analysis Gianluca Coppola, Antonio Di Renzo, Emanuele Tinelli, Chiara Lepre, Elisa Iacovelli, Cherubino Di Lorenzo, Giorgio Di Lorenzo, Vincenzo Parisi, Mariano Serrao, Flavia Pauri, Giancarlo Fiermonte, Claudio Colonnese, Jean Schoenen, Francesco Pierelli

OBJECTIVE Major depressive disorder (MDD) is associated with low-grade inflammation, and it is considered a risk factor for coronary artery disease (CAD). CD40 ligand (CD40L) plays an important role in inflammation, platelet activation, and clotting system activation. We investigated soluble CD40L (sCD40L) expression in MDD and assessed whether it may represent a molecular mechanism that links inflammation and a prothrombotic state and whether this condition may be modified by selective serotonin reuptake inhibitor (SSRI) therapy. METHOD Levels of sCD40L, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble P-selectin (sP-selectin), activated factor VII (FVIIa), and prothrombin fragment 1+2 (F1+2) were measured in 46 drug-naive, first-episode MDD patients without conventional CAD risk factors and in 46 matched healthy controls. Participants were screened between March 2002 and November 2005. Twenty of the 46 MDD patients were then randomly assigned to either sertraline 100 mg/day (N = 10) or citalopram 20 mg/day (N = 10); the aforementioned variables were measured at baseline and after 6 weeks of treatment. RESULTS Compared with control subjects, MDD patients had higher baseline levels of sCD40L, IL-1beta, IL-6, TNF-alpha, sP-selectin, FVIIa, and F1+2. In the clinical group, sCD40L levels, HAM-D total scores, and proinflammatory markers were strongly intercorrelated. In contrast, there were no significant correlations in the control group. Mood improvement achieved with SSRI therapy was associated with significant reduction in sCD40L, proinflammatory markers, and prothrombotic markers expression. (All p values < .0001.) CONCLUSIONS This pilot study shows that CD40/ CD40L pathway up-regulation in MDD patients relates increased levels of sCD40L to a prothrombotic state and, preliminarily, indicates that SSRI therapy may significantly reduce sCD40L and CD40L levels associated with proinflammatory and prothrombotic states.

It has been suggested that an insecure style of attachment may be one of the factors implicated in the etiology of body dissatisfaction, which, in turn, is a risk factor for eating disorders. The present study analyzed the association among early separation anxiety, insecure attachment, and body dissatisfaction in a clinical sample of 96 women with anorexia nervosa (n = 31) or bulimia nervosa (n = 65).Body dissatisfaction was measured using the Body Shape Questionnaire (BSQ), early separation anxiety was measured using the Separation Anxiety Symptom Inventory (SASI), and adult attachment style was measured using the Attachment Style Questionnaire (ASQ).In both anorectic and bulimic women, BSQ scores were strongly correlated with SASI and ASQ scores. In a hierarchical regression model controlling for the confounding effects of body mass index and depressive symptoms, early separation anxiety and preoccupied attachment emerged as significant predictors of high levels of body dissatisfaction.Based on the cross-sectional findings of this study, insecure attachment appears to be a consistent correlate of negative body image evaluations in women with either anorexia nervosa or bulimia nervosa. If future prospective studies will confirm that an insecure style of attachment plays a role in promoting the development of body dissatisfaction, prevention and treatment of disordered eating pathology might be enhanced by focusing greater attention on attachment relationships.

Objectives.—To define predictors of migraine-related disability in patients with episodic and chronic migraine referred to a specialty migraine clinic, focusing on depressive symptoms and insecure attachment style that, because of their association with responses to pain and physical illness, might be predictive of greater migraine-related disability. Background.—The Migraine Disability Assessment questionnaire (MIDAS) has proved to be a reliable and easy-to-use instrument to assess migraine-related disability. As clinicians are increasingly using MIDAS in their diagnostic and treatment decisions for patient care, an understanding of the factors influencing migraine-related disability is essential for a rationale use of such an instrument. Methods.—Two-hundred patients suffering from episodic migraine without aura (EM), and chronic migraine (CM) with and without medication overuse, and referred to a specialty headache clinic were evaluated using the MIDAS, the Beck Depression Inventory (BDI), and the Attachment Style Questionnaire (ASQ). Diagnosis of episodic and chronic migraine was operationally defined according to the International Headache Society (IHS) and Silberstein–Lipton criteria. Results.—Multiple regression analysis showed that, in the total sample, disability was higher in those patients with CM, more severe depressive symptoms, an insecure style of attachment (as reflected by a lower score on the ASQ confidence scale), and experiencing more severe headache pain intensity. In the subgroup of patients with episodic migraine, an insecure style of attachment emerged as the most significant predictor of disability (other significant predictors were female sex and number of headache days per month). In contrast, in the subgroup of patients with CM, the only significant predictor of the total MIDAS score was a greater severity of depressive symptoms. Conclusions.—Our findings demonstrate the relevance of attachment style, an enduring psychological trait not evaluated in previous studies, in influencing the disability level in patients with migraine and confirm the role of comorbid depressive symptoms in modulating the impact of migraine on every day functioning.

Objective: To investigate the dynamics of communication within the primary somatosensory neuronal network. Methods: Multichannel EEG responses evoked by median nerve stimulation were recorded from six healthy participants. We investigated the directional connectivity of the evoked responses by assessing the Partial Directed Coherence (PDC) among five neuronal nodes (brainstem, thalamus and three in the primary sensorimotor cortex), which had been identified by using the Functional Source Separation (FSS) algorithm. We analyzed directional connectivity separately in the low (1-200. Hz, LF) and high (450-750. Hz, HF) frequency ranges. Results: LF forward connectivity showed peaks at 16, 20, 30 and 50. ms post-stimulus. An estimate of the strength of connectivity was modulated by feedback involving cortical and subcortical nodes. In HF, forward connectivity showed peaks at 20, 30 and 50. ms, with no apparent feedback-related strength changes. Conclusions: In this first non-invasive study in humans, we documented directional connectivity across subcortical and cortical somatosensory pathway, discriminating transmission properties within LF and HF ranges. Significance: The combined use of FSS and PDC in a simple protocol such as median nerve stimulation sheds light on how high and low frequency components of the somatosensory evoked response are functionally interrelated in sustaining somatosensory perception in healthy individuals. Thus, these components may potentially be explored as biomarkers of pathological conditions. © 2012 International Federation of Clinical Neurophysiology.

Introduction: Recent studies have found a lack of normal pseudoneglect in schizophrenia patients and in their first degree relatives. Similarly, several contributions have reported that measures of schizotypy in the healthy population may be related to signs of right-sided lateralization, but most of these studies differ greatly in methodology (sample size, choice of schizotypy scales, and laterality tasks) and, consequently, the results cannot be compared and so definitive conclusion cannot be drawn. In this study, our purpose is to investigate whether some tasks of spatial attention may be related to different dimensions of schizotypy not only in a larger sample of healthy subjects (HS), but testing the same people with several supposedly related measures several times. Materials and Methods: In the first part of the study (Part I), the performance on “paper and pencil” line bisection (LB) tasks in 205 HS was investigated. Each task was repeated three times. In the second part of the study (Part II), a subgroup of 80 subjects performed a computerized version of the LB test and of the mental number line bisection (MNL) test. In both parts of the study, every subject completed the 74-item version of the Schizotypal Personality Questionnaire (SPQ) and the Edinburgh Handedness Inventory (EHI). Results: In both parts of the study, high scores on the subscale “magical thinking” of SPQ have resulted in being closely linked to a decreased pseudoneglect as assessed by the LB task. On the contrary, right handedness is related to an increased leftward bias at the same task. No association was found between MNL and the other variables. Discussion: The main finding of this study is that a decreased spatial leftward bias at the LB task correlates with positive schizotypy in the healthy population. This finding supports the hypothesis that a deviation from leftward hemispatial visual preference may be related to the degree of psychosis-like schizotypal signs in non-clinical population and should be investigated as a possible marker of psychosis.

We investigated 50 young patients with a diagnosis of Rolandic Epilepsy (RE) for the presence of abnormalities in autonomic tone compared with 50 young patients with idiopathic generalized epilepsy with absences and 50 typically developing children of comparable age. We analyzed time domain (N-N interval, pNN50) and frequency domain (High Frequency (HF), Low Frequency (LF) and LF/HF ratio) indices from ten-minute resting EKG activity. Patients with RE showed significantly higher HF and lower LF power and lower LF/HF ratio than controls, independent of the epilepsy group, and did not show significant differences in any other autonomic index with respect to the two control groups. In RE, we found a negative relationship between both seizure load and frequency of sleep interictal EEG abnormalities with parasympathetic drive levels. These changes might be the expression of adaptive mechanisms to prevent the excessive sympathetic drive seen in patients with refractory epilepsies.

Electroencephalography (EEG), due to its peculiar time and spatial resolution, was used for the first time to fully monitor neuronal activation during the whole eye movement desensitization and reprocessing (EMDR) session, including the autobiographical script. The present case report describes the dominant cortical activations (Z-score >1.5) during the first EMDR session and in the last session after the client processed the index trauma. During the first EMDR session, prefrontal limbic cortex was essentially activated during script listening and during lateral eye movements in the desensitization phase of EMDR. In the last EMDR session, the prevalent electrical activity was recorded in temporal, parietal, and occipital cortical regions, with a clear leftward lateralization. These findings suggest a cognitive processing of the traumatic event following successful EMDR therapy and support evidence of distinct neurobiological patterns of brain activations during lateral eye movements in the desensitization phase of EMDR.

Medication overuse headache (MOH) is a secondary form of chronic headache (occur­ ing > 15 days/month), usually developed in migraine patients after regular symptomatic drug overuse (1,2). Prevalence is about 1.5-3% of gen­ eral population, whereas in headache clinics it

Background One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. Methods/Design The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. Discussion The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia. Trial Registration Clincaltrials.gov Identifier: NCT00395915

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.

Adiponectin is the most abundant adipose-derived plasma protein. Recently adiponectin levels have been linked to most variables of metabolic syndrome and conventional risk factors for cardiovascular disease. However, its relation with major depression is yet unclear. We evaluated plasma adiponectin levels in 32 first-episode drug-naive major depression (DSM-IV-TR) patients without conventional risk factors for cardiovascular disease and 32 matched healthy subjects. Major depression patients displayed lower adiponectin plasma levels compared to controls (P