Mixed depressive states are defined by the co-presence of depressive and manic symptoms. They represent extremely variable conditions from the point of view of clinical expressiveness and are difficult to recognize, ranging from clear schizophrenic-like psychoses and pseudodemented pictures to subsyndromal psychopathology. At the basis of the extreme variability of depressive pictures with mixed features are the different combinations that depressive and manic symptoms can assume. Furthermore, the intensity of depressive symptoms and manic symptoms, combined, can be variable, a factor that contributes to making the picture even more variable. Each form of mixed depressive state therefore presents its own specific symptomatic characteristics and specific difficulties in differential diagnosis and each form requires a different therapeutic strategy. In this work we have distinguished four possible specific subtypes of mixed depressive states, describing their specific clinical presentation and the therapeutic options most supported by the literature with the aim of contributing to a better recognition of mixed depressive states, to avoid incorrect diagnoses at patient and treatments that are useless if not worsening.
BACKGROUND: The present study aimed to examine clinical differences between subjects with early-onset (<21 years) and adult-onset (>30 years) bipolar I disorder, in particular, in relation to anxiety comorbidity. METHOD: Subjects were selected from a cohort of 161 consecutive patients with bipolar disorder type I as diagnosed by the Structured Clinical Interview for DSM Disorder (SCID-I). Clinical characteristics and axis I comorbidity were compared between those whose illness first emerged before the age of 21 years (n=58) and those whose first episode occurred after the age of 30 years (n=27). Psychopathology was assessed using the 18-item version of the Brief Psychiatric Rating Scale (BPRS). The frequency of delusions, hallucinations, and formal thought disorders was evaluated with the SCID-I. Overall, social and occupational functioning was assessed by the Global Assessment of Functioning (GAF). RESULTS: Most subjects with early-onset bipolar disorder were males, had panic disorder and substance abuse comorbidity, longer duration of illness, exhibited mood-incongruent delusions, and presented with a mixed episode at onset more frequently than the later adult-onset subjects. Mixed mania at the first episode of illness and lifetime panic disorder comorbidity predicted mixed polarity at the first hospitalization episode in the early-onset subjects. CONCLUSIONS: Overall, early age at onset seems to delineate a distinct bipolar I disorder subtype characterized by a greater likelihood of mixed episodes, lifetime panic disorder comorbidity, and schizophrenia-like delusions.
Alterations in sensory processing, a key component of autism spectrum disorder (ASD), have recently attracted increasing attention as they result in peculiar responses to sensory stimuli, possibly representing a risk factor for the development of somatic symptom disorder (SSD). Contextually, other features also associated with ASD, such as alexithymia, camouflaging and altered verbal, and non-verbal communication, have been suggested to represent risk factors for the occurrence and worsening of somatic symptomatology. The aim of this work was to review the available literature about the association between SSD and the autism spectrum. The results highlighted not only a higher prevalence of autistic features in patients suffering from SSD and a higher prevalence of reported somatic symptomatology in subjects with ASD but also how ASD subjects with co-occurrent somatic symptoms exhibit more severe autism-linked symptomatology. From the paper reviewed also emerged many shared features between the two conditions, such as alexithymia, altered sensitivity to sensory stimuli, cognitive inflexibility, intolerance of uncertainty, and an increased risk of experiencing stressful life events, which may provide an explanation for the correlation reported. Even though studies on the topic are still scant, the evidence reported suggests the importance of further assessing the correlation between the two disorders.
Insomnia disorder may affect mental health, increasing suicidal risk. Targeting insomnia is crucial in the clinical practice. Sixty-six consecutive patients with insomnia disorder according with the DSM-5-TR criteria were treated with the dual orexin receptor antagonist, daridorexant 50 mg. Baseline (T0), 1 month (T1) and 3 month (T2) evaluations were performed. Insomnia severity (Insomnia Severity Index), mood, anxiety symptoms and suicidal risk (Beck Depression Inventory-II, Young Mania Rating Scale, Self-Reported Anxiety Scale, Suicidal Ideation Scale), dysfunctional insomnia-cognitive factors and pre-sleep arousal (Dysfunctional Beliefs About Sleep, Pre-Sleep Arousal Scale) were evaluated. The final sample included 66 patients (nâ = 36, 54% females, mean age 60 ± 13.6 years). Most of them, 64%, suffered from insomnia disorder comorbid with unipolar/bipolar depression, anxiety disorders and substance use disorders. Repeated ANOVA analyses showed that Insomnia Severity Index, Dysfunctional Beliefs About Sleep and Pre-Sleep Arousal Scale total score decreased across time (F = 68.818, p < 0.001; F = 47.561, p < 0.001; F = 28.142, p < 0.001, respectively). Similarly, Beck Depression Inventory-II, Self-Reported Anxiety Scale, Young Mania Rating Scale, and Suicidal Ideation Scale significantly decreased over time (p < 0.001). Predictors of insomnia remission (Insomnia Severity Index < 8) at T1 were improvement of Insomnia Severity Index at T1 (F = 60.205, p < 0.001), and improvement of Dysfunctional Beliefs About Sleep at T1 (F = 4.432, p = 0.041). Insomnia remission at T2 was best predicted by improvement of Dysfunctional Beliefs About Sleep at T2 (F = 3.993, p = 0.023). Multiple-regression models showed that clinical improvement of Beck Depression Inventory-II was best predicted by improvement in Dysfunctional Beliefs About Sleep at T1 and T2, manic symptoms by Insomnia Severity Index at T2, anxiety symptoms by Dysfunctional Beliefs About Sleep, Insomnia Severity Index and somatic Pre-Sleep Arousal Scale at T1 and T2. With the caution of a naturalistic design, early experience with daridorexant showed that by targeting insomnia it may be possible to improve not only insomnia symptoms but also comorbid symptoms.
Due to similar manifestations, some authors have proposed a potential correlation between autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD). This link has long been recognized and debated, with some authors arguing that these disorders frequently occur comorbid but distinct while others believe they are part of the same spectrum. The aim of our study was to explore the prevalence and correlates of autistic traits in 55 OCD patients and 55 matched controls and to assess possible autistic dimensions predictive of higher OCD symptoms. All participants were assessed with the Obsessive-Compulsive Spectrum-Short Version (OBS-SV) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). The OCD group scored significantly higher in both questionnaires. Total OBS-SV scores and domains were significantly correlated with all AdAS Spectrum domains and total score. The AdAS Spectrum total, Verbal Communication and Inflexibility and adherence to routine domain scores were significant positive predictors of higher OBS-SV scores. Lastly, when two clusters of subjects (high and low autism) were determined, Inflexibility and adherence to routine domain presented the greatest influence in forming the clusters. Our findings support the association between OCD and autistic traits in the adult population, supporting the hypothesis of a neurodevelopmental basis for these psychiatric conditions.
Depressive symptoms are a customary finding in hospitalized patients, particularly those who are undergoing long hospitalizations, underwent major surgical procedures or suffer from high levels of multimorbidity and frailty. The patients included in this case series shared high degrees of frailty-complexity and were evaluated within the ordinary consultation and liaison psychiatry service of the University Hospital in Pisa, Italy, from September 2021 to June 2023. Patients were administered at least one follow-up evaluation after a week and before discharge. To relate this case series to the extant literature, a comprehensive systematic review of vortioxetine safety and efficacy was performed. None of the six patients included developed serious safety issues, but one patient complained of mild-to-moderate nausea for some days after the vortioxetine introduction. Five out of six patients exhibited at least a slight clinical benefit as measured by the clinical global impression scale. Of the 858 entries screened via Scopus and Medline/PubMed, a total of 134 papers were included in our review. The present case series provides preliminary evidence for vortioxetine's safety in this healthcare domain. The literature reviewed in this paper seems to endorse a promising safety profile and a very peculiar efficacy niche for vortioxetine in consultation and liaison psychiatry.
The current literature globally highlights the efficacy of Clozapine in several psychiatric disorders all over the world, with an FDA indication for reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder. A growing field of research is also stressing a possible broader beneficial effect of Clozapine in promoting neuroprotection and neurotrophism. However, this drug is linked to several life-threatening side effects, such as agranulocytosis, myocarditis and seizures, that limit its use in daily clinical practice. For this work, a search was performed on PubMed using the terms "Clozapine indications", "Clozapine adverse effects", "Clozapine regenerative effects", and "Clozapine neuroplasticity" with the aim of reviewing the scientific literature on Clozapine's treatment indications, adverse effects and potential regenerative role. The results confirmed the efficacy of clozapine in clinical practice, although limited by its adverse effects. It appears crucial to raise awareness among clinicians about the potential benefits of using Clozapine, as well educating medical personnel about its risks and the early identification of possible adverse effects and their management.
Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free-text responses to a 29-item questionnaire on relevant aspects of TR-AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR-AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR-AD vs. "difficult-to-treat" anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method-based consensus on operational criteria for TR-AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence-based stepped-care treatment algorithms for patients with anxiety disorders.
BACKGROUND AND AIMS OF THE STUDY: Type 1 diabetes (T1D) impacts lung function and exercise capacity in adults, but limited information is available in children. We hypothesize that T1D causes alterations in pulmonary function and cardiorespiratory fitness, i.e., exercise capacity, at early stages of the disease, due to the presence of inflammation and vascular damage. Therefore, we aim to investigate pulmonary function before and after exercise in children with T1D as compared to age matched healthy controls. METHOD: Twenty-four children with T1D and twenty healthy controls underwent body plethysmography, diffusion lung capacity for carbon monoxide and fractional exhaled nitric oxide at rest and after cardio-pulmonary exercise test. RESULTS: In children with T1D, baseline total lung capacity and diffusion lung capacity for carbon monoxide were reduced as compared to healthy controls. Children with T1D also showed a reduced exercise capacity associated with poor aerobic fitness. Accordingly, diffusion lung capacity for carbon monoxide tended to increase with exercise in healthy controls, while no change was observed in children with T1D. Fractional exhaled nitric oxide was significantly higher at baseline and tended to increase with exercise in children with T1D, while no changes were observed in healthy controls. CONCLUSIONS: Altered diffusion lung capacity for carbon monoxide, increased fractional exhaled nitric oxide and a poor aerobic fitness to exercise suggests the presence of early pulmonary abnormalities in children with T1D.
Diabetes Mellitus, Type 1 , Adult , Child , Humans , Diabetes Mellitus, Type 1/complications , Carbon Monoxide , Lung , Exercise Test , Inflammation , Nitric Oxide
Orexin is a neurotransmitter produced by a small group of hypothalamic neurons. Besides its well-known role in the regulation of the sleep-wake cycle, the orexin system was shown to be relevant in several physiological functions including cognition, mood and emotion modulation, and energy homeostasis. Indeed, the implication of orexin neurotransmission in neurological and psychiatric diseases has been hypothesized via a direct effect exerted by the projections of orexin neurons to several brain areas, and via an indirect effect through orexin-mediated modulation of sleep and wake. Along with the growing evidence concerning the use of dual orexin receptor antagonists (DORAs) in the treatment of insomnia, studies assessing their efficacy in insomnia comorbid with psychiatric and neurological diseases have been set in order to investigate the potential impact of DORAs on both sleep-related symptoms and disease-specific manifestations. This narrative review aimed at summarizing the current evidence on the use of DORAs in neurological and psychiatric conditions comorbid with insomnia, also discussing the possible implication of modulating the orexin system for improving the burden of symptoms and the pathological mechanisms of these disorders. Target searches were performed on PubMed/MEDLINE and Scopus databases and ongoing studies registered on Clinicaltrials.gov were reviewed. Despite some contradictory findings, preclinical studies seemingly support the possible beneficial role of orexin antagonism in the management of the most common neurological and psychiatric diseases with sleep-related comorbidities. However, clinical research is still limited and further studies are needed for corroborating these promising preliminary results.
Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/drug therapy , Orexins/pharmacology , Orexin Receptor Antagonists/therapeutic use , Orexin Receptor Antagonists/pharmacology , Orexin Receptors/physiology , Sleep
Social anxiety disorder (SAD) has been frequently reported by subjects with Autism Spectrum Disorder (ASD). However, interestingly, the overlap between social anxiety and autistic traits may sometimes impede ASD diagnosis in subjects without intellectual or language impairment. The aim of the present work was to evaluate the presence and correlates of social phobic features among subjects with ASD, with a specific focus on evaluating which social anxiety symptoms may be statistically predictive of an ASD diagnosis. With this purpose, 48 subjects with ASD and 48 gender- and age- matched healthy controls (HCs) were recruited and assessed with the SHY-SV and the AdAS Spectrum questionnaires. Results highlighted higher scores in all SHY-SV Spectrum domains and total scores for the ASD group. Moreover, AdAS Spectrum scores were significantly correlated with all SHY-SV domain and total scores. A logistic regression analysis highlighted the SHY-SV Interpersonal sensitivity and Substance Abuse domains scores as significant positive predictors of an ASD diagnosis. These results confirm the link between ASD and SAD. Because of this association, particular attention should be paid to subjects with high interpersonal sensitivity traits and substance abuse problems.
Burning mouth syndrome is a chronic painful condition characterized by a subjective intraoral pain and burning sensations in the absence of an identifiable medical, dental, or psychiatric cause. Although the underlying etiology is currently unclear, an idiopathic (or primary) form and a secondary form to other conditions are formally recognized. However, as several authors have suggested, it might be of clinical utility to consider the existence of a third clinical entity, namely Drug-Induced Burning mouth syndrome, for its therapeutic implications. The latter has been reported with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antiretrovirals, anticoagulants, chemotherapy, and drugs commonly used in the treatment of neuropsychiatric disorders such as antidepressants, benzodiazepines, and antipsychotics. Regarding anticonvulsants a literature search found a previous case of Topiramate-Induced Burning mouth syndrome but no previous report of valproate-induced Burning mouth syndrome. Our case is, to date, the first case in the literature of Burning mouth syndrome onset following the administration of valproate to a patient suffering from fibromyalgia and bipolar spectrum disorder. Symptoms resolved completely when the drug was stopped, and the association between symptoms and drug was replicated after drug re-administration.
Drug-induced parkinsonism has been commonly studied and discussed regarding antipsychotic agents, but lithium-induced parkinsonism should also be considered when patients present with parkinsonian symptoms and chronic lithium use. There are several reports of parkinsonism arising during lithium administration and regressing following its reduction or discontinuation. Our case is, to date, the first case in the literature in which vocal cord paralysis occurred as the first symptom of lithium-induced parkinsonism, contributing to confuse doctors and patients and to delay diagnosis and treatment. In our clinical case prompt withdrawal of lithium and its reintroduction at lower doses led to complete resolution of this disabling clinical presentation. This report emphasizes the importance of careful monitoring of lithium levels, especially in elderly subjects, and the need to consider lithium-induced parkinsonism even when unusual motor symptoms appear in chronic lithium users.
AIM: This study aimed to investigate whether separation anxiety (SA) constitutes a dimension related to age at onset of panic disorder (PD), in homogeneous subgroups of outpatients with PD, based on their age of onset and symptom severity. METHODS: A sample of 232 outpatients with PD was assessed with the Panic Disorder Severity Scale (PDSS) and the Sheehan Disability Scale (SDS) for functional impairments. Separation anxiety was evaluated using structured interviews and questionnaires. We applied a K-Means Cluster Analysis based on the standardized "PD age of onset" and "the PDSS total score" to identify distinct but homogeneous groups. RESULTS: We identified three groups of patients: group 1 ("PD early onset/severe", N = 97, 42%, onset 23.2 ± 6.7 years), group 2 ("PD early onset/not severe", N = 76, 33%, onset 23.4 ± 6.0 years) and group 3 ("PD adult onset/not severe", N = 59, 25%, onset 42.8 ± 7.0 years). Patients with early onset/severe PD had significantly higher scores on all SA measures than PD late-onset/not severe. Regression analyses showed that SA scores, but not PDSS scores, were predictive of impairment in SDS work/school, social life, and family functioning domains. CONCLUSIONS: Our data indicate a significant relationship between SA and PD with an earlier age of onset and an impact on individual functioning. This may have important implications for implementing preventive interventions targeting early risk factors for the subsequent onset of PD.
Panic Disorder , Adult , Humans , Panic Disorder/epidemiology , Panic Disorder/diagnosis , Anxiety, Separation/complications , Anxiety, Separation/epidemiology , Anxiety, Separation/diagnosis , Age of Onset , Surveys and Questionnaires
AIMS: Candidates for bariatric surgery are routinely screened for psychiatric disorders because abnormal eating behaviors are considered common among these patients. This study aimed to evaluate the frequency and persistence, in terms of one month-to-lifetime prevalence ratio, of binge eating disorder (BED) and the potential association with impulsivity features and bipolar spectrum comorbidity in a sample of obese patients undergoing a psychiatric evaluation for bariatric intervention. METHODS: Overall, 80 candidates to bariatric surgery were assessed consecutively over 12 months within the framework of a collaboration between the University of Pisa Psychiatry and Internal Medicine Departments. Patients were evaluated through structured clinical interviews and self-report questionnaires. RESULTS: The lifetime and last-month frequencies of BED according to DSM-5 criteria were 46.3% and 17.5%, respectively, with a prevalence ratio of 37.8%. Rates of formal bipolar disorder diagnoses were extremely low in patients with or without BED. However, patients with BED showed more severe dyscontrol, attentional impulsivity and bipolar spectrum features than patients with no BED. CONCLUSIONS: The relationship of BED, impulsivity, and mood disorders in bariatric patients is more complex than usually reported in the literature. In particular, the presence of bipolar spectrum features should be systematically investigated in these patients because of their essential clinical and therapeutical implications.
Bariatric Surgery , Binge-Eating Disorder , Bipolar Disorder , Obesity, Morbid , Humans , Binge-Eating Disorder/complications , Binge-Eating Disorder/epidemiology , Bipolar Disorder/complications , Bipolar Disorder/epidemiology , Obesity, Morbid/complications , Obesity, Morbid/epidemiology , Obesity, Morbid/surgery , Obesity/complications , Obesity/epidemiology , Obesity/surgery , Bariatric Surgery/psychology , Comorbidity , Impulsive Behavior
Acute respiratory failure (ARF) is a common life-threatening medical condition, with multiple underlying etiologies. In these cases, many factors related to systemic inflammation, prolonged use of steroids, and lung mechanical abnormalities (such as hyperinflation or increased elastic recoil due to pulmonary oedema or fibrosis) may act as synergic mechanisms leading to diaphragm dysfunction. The assessment of diaphragm function with ultrasound has been increasingly investigated in the emergency department and during hospital stay as a valuable tool for providing additional anatomical and functional information in many acute respiratory diseases. The diaphragmatic ultrasound is a noninvasive and repeatable bedside tool, has no contraindications, and allows the physician to rapidly assess the presence of diaphragmatic dysfunction; this evaluation may help in estimating the need for mechanical ventilation (and the risk of weaning failure), as well as the risk of longer hospital stay and higher mortality rate. This study presents an overview of the recent evidence regarding the evaluation of diaphragmatic function with bedside ultrasound and its clinical applications, including a discussion of real-life clinical cases.
Distress associated with physical illness is a well-known risk factor for adverse illness course in general hospitals. Understanding the factors contributing to it should be a priority and among them dysfunctional illness perception and poor sleep quality may contribute to it. As poor sleep quality is recognised as a major risk factor for health problems, we aimed to study its association with illness perception and levels of distress during hospitalisation. This cross-sectional study included a consecutive series of 409 individuals who were hospitalised in medical and surgical units of different hospitals located throughout the Italian national territory and required an assessment for psychopathological conditions. Sleep quality was assessed with the Pittsburgh (Sleep Quality Index), emotional and physical distress with the Edmonton Symptom Assessment System (ESAS), and illness perception with the Brief Illness Perception Questionnaire (BIPQ). Differences between groups, correlations and mediations analyses were computed. Patients with poor sleep quality were more frequently females, with psychiatric comorbidity, with higher scores in the ESAS and BIPQ. Poor sleep quality was related to dysfunctional illness perception, and to both emotional and physical distress. In particular, by affecting cognitive components of illness perception, poor sleep quality may, directly and indirectly, predict high levels of distress during hospitalisation. Poor sleep quality may affect >70% of hospitalised patients and may favour dysfunctional illness perception and emotional/physical distress.Assessing and treating sleep problems in hospitalised patients should be included in the routine of hospitalised patients.
Psychological Distress , Sleep Initiation and Maintenance Disorders , Female , Humans , Sleep Quality , Cross-Sectional Studies , Quality of Life/psychology , Perception , Surveys and Questionnaires
Introduction: The prevalence of Autism Spectrum Disorder (ASD) is four times higher in males than females; however, females are significantly more likely to go undiagnosed due to the existence of a "female autistic phenotype", a manifestation unique to females that conflicts with conventional, masculine conceptualizations of ASD. Furthermore, subthreshold autistic traits, which exert a significantly negative impact on quality of life and represent a vulnerability factor for the development of other psychopathological conditions, may remain even more under-recognized. Subsequently, many women with ASD may never receive a diagnosis or any resulting care, with serious consequences for their health. Aims: We aimed to describe two brief cases in order to confirm the diagnostic difficulties that ASD female undergo during their clinical evaluation and the possible alternative phenotype that they can manifest. Methods: We reported the cases of two young women on the autism spectrum that came to clinical attention only after the development of severe symptomatology attributed to other mental disorders, overlooking the presence of underlying autism spectrum features and a brief résumé of the literature on this topic. Results: These cases confirm the need for a timely and proper identification of females on the autism spectrum in order to prevent complications and improve the outcome. Conclusions: Research on gender differences could lead to a reexamination of the sex ratio in the prevalence of ASD and provide a better understanding of several psychiatric conditions that are frequently diagnosed in women, supporting the neurodevelopmental approach to psychopathology.
Introduction: Due to their similar behavioral presentation, it can sometimes be challenging to distinguish between a social anxiety disorder (SAD) and the social avoidance that is frequently described in autism spectrum disorder (ASD). Moreover, a growing body of evidences is reporting that a significant proportion of subjects with ASD also meet the requirements for SAD and, vice versa, subjects with SAD tend to exhibit a higher prevalence of autistic traits. Aim: In this framework, the current study aims to evaluate prevalence and correlates of autistic traits in a sample of adult subjects diagnosed with SAD and healthy controls (HC), also evaluating which autism spectrum dimensions may statistically predict higher SAD symptoms. Methods: 56 subjects with a clinical diagnosis of SAD and 56 gender and age matched HC were recruited from the Psychiatric Clinic of the University of Pisa. Subjects were assessed with the SCID-5, the Social Anxiety Spectrum - Short Version (SHY- SV) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). Results: SAD group scored significantly higher in all AdAS Spectrum and SHY-SV domains and total score compared to the HC group with no significant gender difference. SHY-SV total and domain scores, were strongly and positively and strongly correlated with all AdAS Spectrum domains and total score. AdAS Spectrum total score and Childhood/Adolescence, Non-Verbal Communication, Empathy and Restricted interests and Rumination domain scores score were significant predictors of higher SHY-SV score. Conclusion: Our results confirm the link between SAD and autistic traits also in adult population, describing not only high levels of autistic traits in SAD adults, but also significant correlations between many core features of the two disorders and a predictive role of autistic traits on higher SAD symptoms.
