OXTR Gene DNA Methylation Levels Are Associated with Discounting Behavior with Untrustworthy Proposers

Individual differences in temporal and probabilistic discounting are associated with a wide range of life outcomes in literature. Traditional approaches have focused on impulsiveness and cognitive control skills, on goal-oriented personality traits as well as on the psychological perception of time. More recently, literature started to consider the role of social and contextual factors in discounting behavior. Between others, higher generalized trust in human beings and specific trust in people who will deliver the future/probabilistic rewards have been related to a stronger willingness to wait and to assume risk. Moreover, the tendency to trust others has been associated with the oxytocin receptor gene regulation that can be modified by life experiences. In this perspective, we hypothesized that differences in the tendency to wait and to take risks for a more desirable reward according to the proposer’s trustworthiness could be related to a different level of DNA methylation at the oxytocin receptor gene. Findings confirmed that participants are less willing to wait and to risk when the proposer is considered highly untrustworthy and revealed how higher oxytocin receptor gene DNA methylation is associated with a stronger effect due to the presence of an untrustworthy proposer. Limits and future directions are outlined

Socio-demographic and clinical characterization of patients with obsessive-compulsive tic-related disorder (OCTD) : An Italian multicenter study

© Copyright by Pacini Editore SrlIn the DSM-5 a new "tic-related" specifier for obsessive compulsive disorder (OCD) has been introduced, highlighting the importance of an accurate characterization of patients suffering from obsessive-compulsive tic-related disorder ("OCTD"). In order to characterize OCTD from a socio-demographic and clinical perspective, the present multicenter study was carried out. The sample consists of 266 patients, divided in two groups with lifetime diagnoses of OCD and OCTD, respectively. OCTD vs OCD patients showed a significant male prevalence (68.5% vs 48.5%; p < .001), a higher rate of psychiatric comorbidities (69.4 vs 50%; p < .001) - mainly with neurodevelopmental disorders (24 vs 0%; p < .001), a lower education level and professional status (middle school diploma: 25 vs 7.6%; full-Time job 44.4 vs 58%; p < .001). Moreover, OCTD vs OCD patients showed significantly earlier age of OCD and psychiatric comorbidity onsets (16.1 ± 10.8 vs 22.1 ± 9.5 years; p < .001, and 18.3 ± 12.8 vs 25.6 ± 9.4: p < .001, respectively). Patients with OCTD patients were treated mainly with antipsychotic and with a low rate of benzodiazepine (74.2 vs 38.2% and 20.2 vs 31.3%, respectively; p < .001). Finally, OCTD vs OCD patients showed higher rates of partial treatment response (58.1 vs 38%; p < .001), lower rates of current remission (35.5 vs 54.8%; p < .001) and higher rates of suicidal ideation (63.2 vs 41.7%; p < .001) and attempts (28.9 vs 8.3%; p < .001). Patients with OCTD report several unfavorable socio-demographic and clinical characteristics compared to OCD patients without a history of tic. Additional studies on larger sample are needed to further characterize OCTD patients from clinical and therapeutic perspectives.Peer reviewedFinal Published versio

Tele-Psychiatry Assessment of Post-traumatic Stress Symptoms in 100 Patients With Bipolar Disorder During the COVID-19 Pandemic Social-Distancing Measures in Italy

The acute phase of the COrona VIrus Disease-19 (COVID-19) emergency determined relevant stressful burdens in psychiatric patients, particularly those with chronic mental disorders such as bipolar disorder (BD), not only for the threat of being infected but also for the strict lock-down and social-distancing measures adopted, the economic uncertainty, and the limited possibilities to access psychiatric services. In this regard, telepsychiatry services represented a new important instrument that clinicians could adopt to monitor and support their patients. The aim of the present study was to investigate acute post-traumatic stress symptoms (PTSS) reported by patients with BD followed in the framework of a telepsychiatry service, set up in the acute phase of the COVID-19 outbreak at the psychiatric clinic of the University of Pisa (Italy). A sample of 100 patients were consecutively enrolled and assessed by the IES-r, GAD-7, HAM-D, and YMRS. Patients reported a mean (±SD) IES-r total score of 18.15 ± 13.67. Further, 17% of the sample reported PTSS (IES-r &gt; 32), 17% depressive symptoms (HAM-D &gt; 17), and 26% anxiety symptoms (GAD-7 &gt; 10). Work and financial difficulties related to the COVID-19 pandemic and anxiety symptoms appeared to be positively associated with the development of acute PTSS. Acute manic symptoms appeared to be protective. The data of the present study suggest the relevance of monitoring patients with BD exposed to the burden related to the COVID-19 outbreak for prompt assessment and treatment of PTSS

Chronotype is differentially associated with lifetime mood and panic-agoraphobic spectrum symptoms in patients with bipolar disorder and healthy controls.

Objective. Although the association between chronotype and mood disorders has been con- sistently reported, conversely, attempts to measure the association between chronotype and anxiety symptoms have generated inconsistent results. We aimed at evaluating whether chron- otype (assessed through subjective and objective measures) is associated with lifetime mood and panic-agoraphobic spectrum symptoms in healthy controls (HCs) and in patients with bipolar disorder (BD). Methods. Overall, 173 subjects, patients with BD in euthymic phase (n = 76) and HC (n = 97), were evaluated through the reduced Morningness–Eveningness Questionnaire (rMEQ), acti- graphy monitoring and mood and panic-agoraphobic spectrum self-report (MOODS-SR and PAS-SR). The discrepancy between objective (actigraphic-based) versus subjective (rMEQ- based) circadian typology was estimated through the Circadian Classification Discrepancy Index (CCDI). Results. rMEQ-based evening chronotype (ET) was associated with higher scores in MOODS- SR depressive and rhythmicity and vegetative functions domains in HC and BD.Both ET and morning chronotypes (MT) were associated with higher PAS-SR scores in BD only. Actigraphic-based MT was associated with higher MOODS-SR depressive scores in HC. Likewise, the discrepancy between actigraphic-based and rMEQ-based circadian typology was associated with depressive symptoms in HC only. Conclusion. Self-reported ET was consistently associated with mood symptoms, while associ- ations with panic-agoraphobic symptoms only emerged in BD and involved both extreme chronotypes. The discrepancy between the preferred circadian typology (rMEQ-based) and the actual one (actigraphic-based) could contribute to depressive symptoms in HC. These results pave the way for interventional studies targeting circadian typology in an attempt to prevent or treat mental health disorders

Exploratory Study on the Associations between Lifetime Post-Traumatic Stress Spectrum, Sleep, and Circadian Rhythm Parameters in Patients with Bipolar Disorder

The present study aimed at exploring whether lifetime post-traumatic stress spectrum symptoms are associated with chronotype in patients with bipolar disorder (BD). Moreover, we explored whether the chronotype can moderate the potential associations between lifetime post-traumatic stress spectrum symptoms and rest–activity circadian and sleep-related parameters. A total of 74 BD patients were administered the Trauma and Loss Spectrum Self-Report (TALS-SR) lifetime version for lifetime post-traumatic stress spectrum symptoms, the Pittsburgh Sleep Quality Index (PSQI) for self-reported sleep quality, and the Reduced Morningness–Eveningness Questionnaire (rMEQ) to discriminate evening chronotypes (ETs), neither chronotype (NT), and morning chronotype (MT). Actigraphic monitoring was used to objectively evaluate sleep and circadian parameters. Patients classified as ET reported significantly higher scores in the re-experiencing domain, as well as poorer sleep quality, lower sleep efficiency, increased wake after sleep onset, and delayed mid-sleep point compared with both NT and MT (p-value ≤ 0.05). Moreover, ET presented significantly higher scores in the TALS-SR maladaptive coping domain than NT and lower relative amplitude than MT (p-value ≤ 0.05). Moreover, higher TALS-SR total symptomatic domains scores were significantly correlated with poor self-reported sleep quality. Regression analyses showed that the PSQI score maintained the association with the TALS total symptomatic domains scores after adjusting for potentially confounding factors (age and sex) and that no interaction effect was observed between the chronotype and the PSQI. Conclusions: This exploratory study suggests that patients with BD classified as ET showed significantly higher lifetime post-traumatic stress spectrum symptoms and more disrupted sleep and circadian rhythmicity with respect to other chronotypes. Moreover, poorer self-reported sleep quality was significantly associated with lifetime post-traumatic stress spectrum symptoms. Further studies are required to confirm our results and to evaluate whether targeting sleep disturbances and eveningness can mitigate post-traumatic stress symptoms in BD

Novel Pharmacological Targets of Post-Traumatic Stress Disorders

Post-traumatic stress disorder (PTSD) is a psychopathological condition with a heteroge- neous clinical picture that is complex and challenging to treat. Its multifaceted pathophysiology still remains an unresolved question and certainly contributes to this issue. The pharmacological treatment of PTSD is mainly empirical and centered on the serotonergic system. Since the therapeutic response to prescribed drugs targeting single symptoms is generally inconsistent, there is an urgent need for novel pathogenetic hypotheses, including different mediators and pathways. This paper was conceived as a narrative review with the aim of debating the current pharmacological treatment of PTSD and further highlighting prospective targets for future drugs. The authors accessed some of the main databases of scientific literature available and selected all the papers that fulfilled the purpose of the present work. The results showed that most of the current pharmacological treatments for PTSD are symptom-based and show only partial benefits; this largely reflects the limited knowledge of its neurobiology. Growing, albeit limited, data suggests that the hypothalamic-pituitary-adrenal axis, opioids, glutamate, cannabinoids, oxytocin, neuropeptide Y, and microRNA may play a role in the development of PTSD and could be targeted for novel treatments. Indeed, recent research indicates that examining different pathways might result in the development of novel and more efficient drugs

Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis

Background: Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results: Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions: This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies

Prevalence study of mental disorders in an Italian region. Preliminary report

Background Mental disorders are a major public health problem. However, over the last few years, there have been few studies aimed at evaluating their diffusion. Therefore, this study aimed at evaluating: the prevalence of the most frequent psychiatric disorders in the general population residing in Tuscany using a clinical scale administered by trainee in psychiatry. Methods The study was carried out on a representative sample of the general population aged &gt; 18 years, randomly extracted from the register of patients in the Tuscany region, adopting a proportional sampling method stratified by gender, age group and Local Health Units (LHU). Each person was contacted by letter followed by a phone call from an operator who makes an appointment with the trainee in psychiatry. The diagnostic interview conducted was the Mini-International Neuropsychiatric Interview (MINI). Point and lifetime prevalence by gender and age group were calculated. Differences and associations were considered statistically significant if their p-values were less than 0.05. Results Of the 408 people involved, 390 people were enrolled (of which 52.6% female). The 28.5% of the sample had been affected by a psychiatric disorder during their lifetime. In their lifetime, the most represented psychiatric disorders were major depressive episode (20.4%), major depressive disorder (17.0%) and panic disorder (10.3%), more frequent in the female than the male group. Current conditions were predominantly major depressive episode (3.1%) and agoraphobia (2.8%). A 5.9% rate of current suicidal ideation was also found. Conclusions In the general population, 28.5% of people reported a psychiatric disorder during their lifetime. This prevalence is considerably higher than that reported in a previous study carried out in central Italy

Clinical correlates of loss of insight in bipolar depression

IntroductionAffective state may influence insight, especially regarding mania. Nevertheless, studies have so far suggested that depression seems not to significantly impair insight. To the best of our knowledge, this study pioneers the evaluation of how insight variations in bipolar depression correlate with clinical variables.MethodA group of 165 bipolar patients, 52 of whom had depressive episodes according to DSM-5 criteria, were followed during a year. All patients underwent clinical assessment, and insight was evaluated through the Insight Scale for Affective Disorders (ISAD). Repeated-measures ANOVA was calculated comparing scores on the four ISAD factors (insight into symptoms, the condition itself, self-esteem and social relationships) in order to investigate differences in insight according to different objects. Correlational analysis explored which clinical symptoms were linked to reduced insight.ResultsWorse total insight correlated with suicide attempt/ideation and fewer subsyndromal manic symptoms such as mood elevation, increased energy and sexual interest. Worse self-esteem insight was associated with not only suicide ideation/attempt but also with activity reduction and psychomotor retardation. Worse symptom insight also correlated with psychomotor retardation. Better insight into having an affective disorder was associated with more intense hypochondria symptoms. Finally, worse insight into having an illness was associated with psychotic episodes.ConclusionOur study found that symptoms other than psychosis – suicide ideation, psychomotor retardation and reduction of activity and work – correlate with insight impairment in bipolar depression