Gender-Related Clinical Characteristics in Children and Adolescents with ADHD

Attention Deficit/Hyperactivity Disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder in school-age children, and it is usually associated with a significant impairment in global functioning. Traditionally, boys with ADHD are more likely to be referred for clinical assessments due to a higher prevalence of externalizing symptoms. However, as regards gender-related differential clinical characteristics between boys and girls with ADHD, further investigation is warranted in light of conflicting results found in currently available literature. In fact, a more precise clinical characterization could help increase appropriate diagnoses and treatment planning. In this context, we carried out a retrospective observational study on 715 children and adolescents diagnosed with ADHD from 2018 to 2020 at our center, in order to describe their gender-related clinical characteristics. Boys displayed higher average IQs, but they were comparable to girls in functional impairments and adaptive skills. Girls displayed higher scores on the Attention Problems subscale of the CBCL 6–18 and on several CPRS-R:L subscales, suggesting higher general ADHD symptom severity. Boys showed higher scores on CBCL 6–18 subscales, such as withdrawn/depressed, internalizing, and obsessive-compulsive problems. In conclusion, girls showed more severe ADHD features and lower IQ in clinically referred settings, while boys showed more internalizing problems and obsessive-compulsive symptoms.

Everyday Lives of Middle-Aged Persons with Multimorbidity: A Mixed Methods Systematic Review

The healthcare burden of patients with multimorbidity may negatively affect their family lives, leisure time and professional activities. This mixed methods systematic review synthesizes studies to assess how multimorbidity affects the everyday lives of middle-aged persons, and identifies skills and resources that may help them overcome that burden. Two independent reviewers screened title/abstracts/full texts in seven databases, extracted data and used the Mixed Methods Appraisal Tool (MMAT) to assess risk of bias (RoB). We synthesized findings from 44 studies (49,519 patients) narratively and, where possible, quantitatively. Over half the studies provided insufficient information to assess representativeness or response bias. Two studies assessed global functioning, 15 examined physical functioning, 18 psychosocial functioning and 28 work functioning. Nineteen studies explored skills and resources that help people cope with multimorbidity. Middle-aged persons with multimorbidity have greater impairment in global, physical and psychosocial functioning, as well as lower employment rates and work productivity, than those without. Certain skills and resources help them cope with their everyday lives. To provide holistic and dynamic health care plans that meet the needs of middle-aged persons, health professionals need greater understanding of the experience of coping with multimorbidity and the associated healthcare burden.

Reducing Anhedonia in Major Depressive Disorder with Future Event Specificity Training (FEST): A Randomized Controlled Trial

Objective: Improving future thinking may be one means to reduce anhedonia, particularly in Major Depressive Disorder (MDD) in which future thinking is impaired. The current study therefore examined whether enhancing future thinking is a viable method of reducing anhedonia in MDD. Methods: Participants (N=177; 80.8% women; M age=43.7, SD=11.8) with a current depressive episode including anhedonia and high symptom severity were randomized to a Future Event Specificity Training (FEST) program or wait-list control. Future thinking characteristics, anhedonia-related variables, and other clinical outcomes were assessed at baseline, one- and three-month follow-up. Results: The FEST group showed significantly improved future thinking characteristics compared to the control group, as expected. Relative to the control group, FEST was also associated with a reduced likelihood of anhedonia (35.1% vs 61.1%, p = .015), improvements on other anhedonia-related variables such as anticipatory (d = 0.63, p = .004) and anticipated pleasure (d = 0.77, p < .001), and desirable clinical outcomes such as less people meeting criteria for MDD (37.8% vs 64.8%, p = .011), lower symptom severity (d = 0.41, p = .048), higher behavioural activation (d = 0.71, p = .001) and improved global functioning (d = 0.52, p = .017). Changes in future thinking characteristics were found to mediate the effect of FEST on anhedonia.Conclusions: Future thinking can be enhanced in MDD, and this leads to a substantially reduced likelihood of anhedonia, other significant clinical effects and functional gains. Future research might examine FEST’s effects on other diagnostic groups with anhedonia and the utility of FEST as an adjunct to other treatments.

Aerobic exercise in severe mental illness: requirements from the perspective of sports medicine

Major depression, bipolar disorder, and schizophrenia are severe mental illnesses. Despite receiving psychopharmacological and psychosocial treatments, about half of patients develop a chronic course with residual cognitive and negative symptoms and have a high risk for cardiovascular disease and reduced life expectancy. Therefore, add-on innovative treatment approaches are needed to improve outcome. Aerobic exercise interventions have been shown to improve global functioning, cognition, and negative and depressive symptoms in these patients. The basic mechanism of these exercise-related changes has been reported to be improved brain plasticity, e.g., increased volume of disease-related brain regions such as the hippocampus. The optimal type, duration, and frequency of exercise have not yet been determined and need to be addressed in supervised physical exercise studies. Because of the low physical activity levels, lack of drive related to negative and depressive symptoms, and high prevalence of cardiovascular comorbidities in patients with severe mental illness, besides aiming to improve symptoms of mental illness, exercise interventions should also aim to increase cardiorespiratory fitness, which they should comprehensively assess by direct measurements of maximal oxygen uptake. Based on the recommendations for developing cardiorespiratory fitness by the American College of Sports Medicine, 150 min moderate-intensity training per week or vigorous-intensity exercise training for 75 min per week are appropriate. Most studies have had relatively short intervention periods, so future studies should focus on long-term adherence to exercise by implementing motivational strategies supported by telemedicine and by identifying and targeting typical barriers to exercise in this patient population.

Boosting the ToM network: Specific psychotherapy increases neural correlates of affective theory of mind in euthymic bipolar disorder

Objectives: Impairments in social cognitive processes are discussed as a vulnerability factor for bipolar disorder (BD). Previous studies demonstrated aberrant neural activation in brain areas related to theory of mind (ToM) and impaired affective ToM (aToM) task performance in BD. However, it is yet unknown whether successful psychotherapy of BD influences neuroimaging markers of aToM.Methods: In the present study conducted within the multicentric randomized controlled trial of the BipoLife consortium, euthymic BD patients underwent two group interventions: a specific, cognitive-behavioral intervention (SEKT, n = 31) encompassing psychoeducation and the training of self-management, impulse regulation, and ToM and social skills versus a supportive, unstructured, emotion-focused intervention (FEST, n = 28). To compare the effect of SEKT and FEST on neural correlates of aToM, patients performed an aToM task during functional magnetic resonance imaging before and after interventions. Because ToM skills were trained in SEKT, we expected an increased ToM network activation in SEKT relative to FEST post intervention. Results: Both treatments were effective in stabilizing patients’ euthymic state in terms of affective symptoms, life satisfaction and global functioning. Confirming our expectations, patients who had completed SEKT showed an increased neural activation within four regions of the ToM brain network, the bilateral temporoparietal junction (TPJ), the posterior cingulate cortex (PCC), and the precuneus, whereas FEST patients did not. Conclusions: The stabilizing effect of SEKT on clinical outcomes went along with a boost in neural activation of the ToM network, while FEST possibly exerted its positive effect by other, yet unexplored routes.

Case Report: Cariprazine Efficacy in Young Patients Diagnosed With Schizophrenia With Predominantly Negative Symptoms

Negative symptoms of schizophrenia are among the most invalidating clinical manifestations of this disorder, and they are correlated with poorer prognosis, lower quality of life, and fewer chances for successful social reintegration and professional rehabilitation. Although atypical antipsychotics have been associated with higher efficacy on negative symptoms than typical agents, not all of them are equally effective. Cariprazine is a new D3 and D2 receptor partial agonist, and its high D3 affinity may be useful for decreasing several adverse events (e.g., extrapyramidal symptoms or hyperprolactinemia), and also for increasing this drug's efficacy over negative symptoms. This case series presents three young adults with predominantly negative symptoms during treatment with an atypical antipsychotic, administered in stable dose within the therapeutic range, and for at least 4 weeks prior to the cariprazine switch. These patients (two male and one female, mean age 35.7 years) were diagnosed with schizophrenia, according to the DSM-5 criteria. They were evaluated using Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), and Global Assessment of Functioning (GAF). Their mean initial values were 80.3 on PANSS, 4.3 on CGI-S, and 48 on GAF. All these patients were already on a treatment with stable doses of atypical antipsychotics (olanzapine 10 mg/day, n = 1, risperidone 6 mg/day, n = 1, and quetiapine 600 mg/day, n = 1). Cross-titration to cariprazine was initiated, from 1.5 mg qd up to 6 mg qd, during a mean period of 2.7 weeks. After 12 weeks of cariprazine 6 mg/day, the positive scale of PANSS was relatively stable compared to baseline, while the negative mean score decreased by 22%. Also, the mean CGI-S improvement was 15.4% and the GAF mean score increased by 17%. The overall tolerability was good, without severe adverse events being reported. Conclusions: Cariprazine is well tolerated and efficient for patients diagnosed with schizophrenia who have significant negative symptoms that impair daily functioning. After 12 weeks cariprazine succeeded in improving negative symptoms, global functioning, and clinical global impression.

Sensory gating, neurocognition, social cognition and real-life functioning: a 2-year follow-up of early psychosis

Background Diminished sensory gating (SG) is a robust finding in psychotic disorders, but studies of early psychosis (EP) are rare. It is unknown whether SG deficit leads to poor neurocognitive, social, and/or real-world functioning. This study aimed to explore the longitudinal relationships between SG and these variables. Methods Seventy-nine EP patients and 88 healthy controls (HCs) were recruited at baseline. Thirty-three and 20 EP patients completed 12-month and 24-month follow-up, respectively. SG was measured using the auditory dual-click (S1 & S2) paradigm and quantified as P50 ratio (S2/S1) and difference (S1-S2). Cognition, real-life functioning, and symptoms were assessed using the MATRICS Consensus Cognitive Battery, Global Functioning: Social (GFS) and Role (GFR), Multnomah Community Ability Scale (MCAS), Awareness of Social Inference Test (TASIT), and the Positive and Negative Syndrome Scale (PANSS). Analysis of variance (ANOVA), chi-square, mixed model, correlation and regression analyses were used for group comparisons and relationships among variables controlling for potential confounding variables. Results In EP patients, P50 ratio (p < 0.05) and difference (p < 0.001) at 24-month showed significant differences compared with that at baseline. At baseline, P50 indices (ratio, S1-S2 difference, S1) were independently associated with GFR in HCs (all p < 0.05); in EP patients, S2 amplitude was independently associated with GFS (p = 0.037). At 12-month and 24-month, P50 indices (ratio, S1, S2) was independently associated with MCAS (all p < 0.05). S1-S2 difference was a trending predictor of future function (GFS or MCAS). Conclusions SG showed progressive reduction in EP patients. P50 indices were related to real-life functioning.

Basic self-disturbance trajectories in clinical high risk for psychosis: a one-year follow-up study

Basic self-disturbance (BSD) has been proposed as a driver of symptom development in schizophrenia spectrum disorders (SSDs). In a one-year follow-up of 32 patients (15–30 years) at putative risk for psychosis, we investigated trajectories of BSD levels from baseline to follow-up, and associations between clinical characteristics at baseline and follow-up, including follow-up levels of BSD (assessed with the EASE). Clinical high risk (CHR) for psychosis status and symptom severity were assessed with the SIPS/SOPS scales and also according to the cognitive basic symptoms high-risk criteria (COGDIS). DSM-IV diagnoses, functioning and other clinical characteristics were assessed with standard clinical instruments. Higher severity of negative symptoms and meeting COGDIS criteria at baseline were associated with higher BSD levels at follow-up. All measured at follow-up, higher BSD levels correlated with higher severity of positive, negative, disorganization and general symptoms, and with a lower level of global functioning. We found higher BSD levels at follow-up in subjects with schizotypal personality disorder (SPD) at baseline (n = 5) and in SSDs at follow-up (n = 12, including nine with SPD). Mean BSD levels decreased significantly from baseline to follow-up, but individual trajectories varied considerably. Increased BSD levels were associated with higher baseline BSD levels, non-remission of positive symptoms and functional decline. Overall, the current study indicates that subgroups in the CHR population with a higher risk of non-remission or deterioration may be identified by supplementing CHR criteria with assessment of BSD and negative symptoms.

Inherited and Acquired Rhythm Disturbances in Sick Sinus Syndrome, Brugada Syndrome, and Atrial Fibrillation: Lessons from Preclinical Modeling

Rhythm disturbances are life-threatening cardiovascular diseases, accounting for many deaths annually worldwide. Abnormal electrical activity might arise in a structurally normal heart in response to specific triggers or as a consequence of cardiac tissue alterations, in both cases with catastrophic consequences on heart global functioning. Preclinical modeling by recapitulating human pathophysiology of rhythm disturbances is fundamental to increase the comprehension of these diseases and propose effective strategies for their prevention, diagnosis, and clinical management. In silico, in vivo, and in vitro models found variable application to dissect many congenital and acquired rhythm disturbances. In the copious list of rhythm disturbances, diseases of the conduction system, as sick sinus syndrome, Brugada syndrome, and atrial fibrillation, have found extensive preclinical modeling. In addition, the electrical remodeling as a result of other cardiovascular diseases has also been investigated in models of hypertrophic cardiomyopathy, cardiac fibrosis, as well as arrhythmias induced by other non-cardiac pathologies, stress, and drug cardiotoxicity. This review aims to offer a critical overview on the effective ability of in silico bioinformatic tools, in vivo animal studies, in vitro models to provide insights on human heart rhythm pathophysiology in case of sick sinus syndrome, Brugada syndrome, and atrial fibrillation and advance their safe and successful translation into the cardiology arena.