How Mental Health and Suicidality Changed during the COVID-19 Pandemic: A Longitudinal Study in the General and Psychiatric Population Illustrating Risk and Protective Factors.

The COVID-19 pandemic has led to an increase in psychological distress in the general population, but contrasting results have been shown regarding its impact on psychological symptoms in clinical and non-clinical samples. Consequently, the aim of the present study was to compare in a longitudinal design (September-November 2020 and February-April 2021) the mental health outcomes of a clinical and a control sample and to determine the implications of various risk and protective factors in this regard. A total of 234 participants from the general population and 80 psychiatric patients took part in the present online study using the following measurements: the Brief Symptom Checklist (BSCL); Three-Item Loneliness Scale (TILS); Resilience Scale-13 (RS-13); and Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale-Non-Illness (FACIT-Sp Non-Illness). The results show an overall decrease in active suicidal ideation as well as "peace", a subscale of spiritual well-being, as well as increases in passive suicidal activation in the clinical sample, which did not change in the control sample. Psychological symptoms did not significantly change in either group. Significant group effects show an increase in resilience in the clinical sample. Resilience and peace turned out to be protective factors for negative mental health outcomes. However, loneliness, which interestingly increased only in the control sample, was shown to be an overall potential risk factor. Our results highlight the complex implications of the COVID-19 pandemic on the mental health outcomes of different groups in the population, demonstrating the necessity of further research, specifically regarding the risk of active and passive suicidal activation. Highlighted protective factors are discussed in regards to spirituality (i.e., peace), which is not strictly related to religion but rather personal spirituality related to the meaning of situations of one's life, as well as in terms of mental health interventions.

A shift in psychiatry through AI? Ethical challenges.

The digital transformation has made its way into many areas of society, including medicine. While AI-based systems are widespread in medical disciplines, their use in psychiatry is progressing more slowly. However, they promise to revolutionize psychiatric practice in terms of prevention options, diagnostics, or even therapy. Psychiatry is in the midst of this digital transformation, so the question is no longer "whether" to use technology, but "how" we can use it to achieve goals of progress or improvement. The aim of this article is to argue that this revolution brings not only new opportunities but also new ethical challenges for psychiatry, especially with regard to safety, responsibility, autonomy, or transparency. As an example, the relationship between doctor and patient in psychiatry will be addressed, in which digitization is also leading to ethically relevant changes. Ethical reflection on the use of AI systems offers the opportunity to accompany these changes carefully in order to take advantage of the benefits that this change brings. The focus should therefore always be on balancing what is technically possible with what is ethically necessary.

Falls at the interface between geriatric and psychiatric patients: a critical review from a psychopharmacological perspective.

Falls in the elderly represent one of the major clinical problems as they are serious events that often result in high residual disability and mortality rates. Knowledge on the subject derives mainly from geriatric and gerontopsychiatric research. However, gerontopsychiatric patients differ from geriatric patients not only for the psychiatric and neurological comorbidities, which are often not sufficiently taken into account in the scientific context, but also for the intake of psychotropic drugs, notoriously described as one of the main risk factors for falls. Such drugs are widely prescribed in this group of patients, often even off-label. Clinicians therefore should pay particular attention to falls, since various comorbidities and polypharmacy as a prescribing issue can have important consequences for clinical management. Falls have not been sufficiently investigated yet in a purely psychiatric context.

Activity-Based Prospective Memory in ADHD during Motor Sleep Inertia.

Prospective memory (PM) is essential in everyday life because it concerns the ability to remember to perform an intended action in the future. Individuals diagnosed with attention deficit hyperactivity disorder (ADHD) often show poor performance in PM. Because age can be confounding, we decided to test PM in ADHD patients (children and adults) and healthy controls (children and adults). We examined 22 children (four females; mean age = 8.77 ± 1.77) and 35 adults (14 females; mean age = 37.29 ± 12.23) with ADHD, in addition to 92 children (57 females; mean age = 10.13 ± 0.42) and 95 adults (57 females; mean age = 27.93 ± 14.35) as healthy controls. Each participant originally wore an actigraph around the non-dominant wrist and was requested to push the event-marker at get-up time. To assess the efficiency of PM performance, we calculated the time elapsing between the end of sleep in the morning and the pushing of the event-marker button. The results showed lower PM performance in ADHD participants, regardless of age. However, the differences between ADHD and control groups were more evident in the children group. Our data seem to confirm that PM efficiency is compromised in individuals diagnosed with ADHD regardless of age, and agree with the idea of considering the PM deficit as a neuropsychological marker of ADHD.

Wider and Stronger Inhibitory Ring of the Attentional Focus in Schizophrenia.

Anomalies of attentional selection have been repeatedly described in individuals with schizophrenia spectrum disorders. However, a precise analysis of their ability to inhibit irrelevant visual information during attentional selection is not documented. Recent behavioral as well as neurophysiological and computational evidence showed that attentional search among different competing stimuli elicits an area of suppression in the immediate surrounding of the attentional focus. In the present study, the strength and spatial extension of this surround suppression were tested in individuals with schizophrenia and neurotypical controls. Participants were asked to report the orientation of a visual "pop-out" target, which appeared in different positions within a peripheral array of non-target stimuli. In half of the trials, after the target appeared, a probe circle circumscribed a non-target stimulus at various target-to-probe distances; in this case, participants were asked to report the probe orientation instead. Results suggest that, as compared to neurotypical controls, individuals with schizophrenia showed stronger and spatially more extended filtering of visual information in the areas surrounding their attentional focus. This increased filtering of visual information outside the focus of attention might potentially hamper their ability to integrate different elements into coherent percepts and influence higher order behavioral, affective, and cognitive domains.

Venlafaxine and O-desmethylvenlafaxine serum levels are positively associated with antidepressant response in elder depressed out-patients.

BACKGROUND: Therapeutic Drug Monitoring (TDM) represents one of the most promising tools in clinical practice to optimise antidepressant treatment. Nevertheless, little is still known regarding the relationship between clinical efficacy and serum concentration of venlafaxine (VEN). The aim of our study was to investigate the association between serum concentration of venlafaxine + O-desmethylvenlafaxine (SCVO) and antidepressant response (AR). METHODS: 52 depressed outpatients treated with VEN were recruited and followed in a naturalistic setting for three months. Hamilton Depression Rating Scale-21 was administered at baseline, at month 1 and at month 3 to assess AR. SCVO was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between SCVO and AR. RESULTS: Our results showed an association between AR and SCVO that follows a bell-shaped quadratic function with a progressive increase of AR within the therapeutic reference range of SCVO (i.e. 100-400 ng/mL) and a subsequent decrease of AR at higher serum levels. DISCUSSION: This study strongly suggests that TDM could represent a more appropriate tool than the oral dosage to optimise the treatment with VEN. Specifically, highest efficacy might be achieved by titrating patients at SCVO levels around 400 ng/mL.

Antidepressant efficacy is correlated with plasma levels: mega-analysis and further evidence.

The debate around optimal target dose for first-line antidepressants (ADs) is still ongoing. Along this line, therapeutic drug monitoring (TDM) represents one of the most promising tools to improve clinical outcome. Nevertheless, a few data exist regarding the concentration-effect relationship of first-line ADs which limits TDM implementation in routine clinical practice. We conducted the first patient-level concentration-response mega-analysis including data acquired by us previously and explored the concentration dependency of first-line AD (206 subjects). Further, new data on mirtazapine are reported (18 subjects). Hamilton Depression Rating Scale-21 administered at baseline, at month 1 and month 3 was used as the measure of efficacy to assess antidepressant response (AR). When pooling all four first-line ADs together, normalized plasma levels and AR significantly fit a bell-shaped quadratic function with a progressive increase of AR up to around the upper normalized limit of the therapeutic reference range with a decrease of AR at higher serum levels. Our results complement the available evidence on the issue and the recent insights gained from dose-response studies. A concentration-dependent clinical efficacy, such as previously demonstrated for tricyclic compounds, also emerge for first-line ADs. Our study supports a role for TDM as a tool to optimize AD treatment to obtain maximum benefit.

Adult ADHD: a study on evaluation and treatment pathways in Italian Mental Health Services.

Attention Deficit and Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. The Italian situation regarding the clinical management of childhood ADHD shows some criticalities, despite the high prevalence rate: diagnostic assessments are often inaccurate, protocols for transition from childcare services are almost non-existent and the Italian National Registry for ADHD in childhood was drawn up only in 2007, hence the first specialized services were created later than the rest of Europe. On the basis of these issues, we investigated the Italian situation with regard to disorders in adulthood, comparing the different European operational models, assuming that these critical issues are reflected in the clinical management of the disorder in adulthood. In fact, unlike other European countries, there are no official guidelines governing the clinical management of the disorder in adulthood and evidence-based pharmacotherapies, available in most European countries, are off-label or not allowed in Italy. The aim of the study is to evaluate the current state of knowledge and working method in relation to adult ADHD in the Italian background and to identify the main evaluation and treatment pathways in Italian Mental Health Services. The study is also an attempt to clarify which services are operational on the Italian territory, with the aim of improving the quality of interventions for the clinical population. Three hundred thirty-eight services have been identified in all Italian Regions and Autonomous Provinces, including Mental Health Centres (CSM), Pathological Addition Services (SERD), Psychiatric Diagnosis and Treatment Services (SPDC). An ad-hoc survey with closed-ended questions was administered by telephone to each selected centre and the results were compared with the European literature.

The association between adult ADHD and food addiction: A mediation analysis.

OBJECTIVES: The aim of this study was to investigate the association between food addiction severity (FA) and ADHD symptomatology. Furthermore, we investigated whether emotional distress, and the mentalization deficits could mediate this relationship. METHODS: Three hundred eighty-five Italian adults (307 women and 78 men) participated in the study and completed the Italian versions of the Modified Yale Food Addiction Scale version 2.0, the Adult ADHD Self-Report Scale, the Depression Anxiety Stress Scales 21 and the Mentalization Questionnaire. RESULTS: ADHD symptoms severity and general distress were significantly and independently associated with FA. Emotional distress partly mediated the relationship between FA and ADHD symptoms severity. In addition, mentalization deficits partly mediated this relationship only when evaluating the influence of FA on ADHD symptoms severity. LIMITATIONS: This is a cross-sectional study and causal interpretations of the relationships among the variables are speculative. CONCLUSIONS: It is important to assess emotional distress and mentalization deficits in individuals at risk of ADHD and FA because these conditions could increase the risk for the presence of disordered eating patterns.

Therapeutic Drug Monitoring of Long-Acting Injectable Antipsychotic Drugs.

BACKGROUND: The use of therapeutic drug monitoring (TDM) to guide treatment with long-acting injectable (LAI) antipsychotics, which are increasingly prescribed, remains a matter of debate. The aim of this review was to provide a practical framework for the integration of TDM when switching from an oral formulation to the LAI counterpart, and in maintenance treatment. METHODS: The authors critically reviewed 3 types of data: (1) positron emission tomography data evaluating dopamine (D2/D3) receptor occupancy related to antipsychotic concentrations in serum or plasma; D2/D3 receptors are embraced as target sites in the brain for antipsychotic efficacy and tolerability, (2) pharmacokinetic studies evaluating the switch from oral to LAI antipsychotics, and (3) pharmacokinetic data for LAI formulations. Based on these data, indications for TDM and therapeutic reference ranges were considered for LAI antipsychotics. RESULTS: Antipsychotic concentrations in blood exhibited interindividual variability not only under oral but also under LAI formulations because these concentrations are affected by demographic characteristics such as age and sex, genetic peculiarities, and clinical variables, including comedications and comorbidities. Reported data combined with positron emission tomography evidence indicated a trend toward lower concentrations under LAI administration than under oral medications. However, the available evidence is insufficient to recommend LAI-specific therapeutic reference ranges. CONCLUSIONS: Although TDM evidence for newer LAI formulations is limited, this review suggests the use of TDM when switching an antipsychotic from oral to its LAI formulation. The application of TDM practice is more accurate for dose selection than the use of dose equivalents as it accounts more precisely for individual characteristics.

Survey on centres and procedures for the diagnosis and treatment of adult ADHD in public services in Italy.

Attention deficit/hyperactivity disorder (ADHD) often persists into adulthood. Although its persistence and relative high prevalence, ADHD in adults is often underdiagnosed and undertreated in Italy, leading to poor clinical and functional outcomes, and higher costs of illness. The aims of the study were to identify the Italian mental health services for ADHD in adults, describe the diagnostic and treatment procedures they follow, and compare this offer with the recommendations of the German and English guidelines. The centres, that adopt a clinical and assessment protocol for adult ADHD diagnosis (carried out by specifically trained personnel) and prescribe pharmacological treatment for adult ADHD, were selected from the list of accredited services provided by the Appendix B.2 of the ISTISAN 16/37 Reports of the ISS. An ad-hoc survey including open-ended and close-ended questions was sent to each selected centre in February 2020. The overall picture resulting from the data analysis was compared with the recommendations of the German and English guidelines. The present survey shows that only a few centres are specialised in the diagnosis and treatment of ADHD in adults in Italy. Furthermore, there are no national guidelines for adult ADHD in Italy. The collected data also suggest that there is no a unified practice shared by the Centres both for the patient's transition from child and adolescent to adult mental health services and for the diagnostic-therapeutic process. It is therefore crucial to create specific protocols and develop national guidelines to better identify and diagnose ADHD in adults and provide targeted and more efficient multimodal treatments.

Methylphenidate challenge test in adults with attention deficit/hyperactivity disorder (ADHD): Clinical effects and their predictors.

OBJECTIVE: Adult and children attention deficit/hyperactivity disorder (ADHD) share similar symptoms and responses to drugs such as methylphenidate (MPH). Yet, in Europe, these drugs remain unlicensed for adults. We aimed to assess the effects of an acute MPH challenge on the four dimensions concentration, impulsivity, tension, and general well-being in ADHD adults, and identify predictors of improvement. METHODS: Therapeutic Drug Monitoring was performed to measure MPH plasma levels. A Visual Analogue Scale was administered to patients before and after the acute MPH challenge to measure self-reported changes in the four dimensions. RESULTS: After the acute MPH challenge, our 71 patients showed significant improvement in concentration and tension. The MPH challenge dose correlated with lower patients' age, greater side effects, increased concentration (p = .008) and decreased tension (p = .001). At multiple linear regression MPH plasma levels and absence of postdose side effects predicted concentration improvement, MPH plasma levels predicted tension improvement. MPH plasma levels were significantly higher in patients who reported an improvement in concentration, tension, and impulsivity compared to nonimprovers (p's from .001 to .004). CONCLUSIONS: These findings point to the efficacy of MPH challenge in improving concentration and tension in adult ADHD, thus emphasizing the need for a broader treatment access for these patients.

Sleep and Prospective Memory: A Retrospective Study in Different Clinical Populations.

Prospective memory (PM) is essential in everyday life because it concerns the ability to remember to perform an intended action in the future. This ability could be influenced by poor sleep quality, the role of which, however, is still being debated. To examine the role of sleep quality in PM in depth, we decided to perform a retrospective naturalistic study examining different clinical populations with a primary sleep disorder or comorbid low sleep quality. If sleep is important for PM function, we could expect poor sleep to affect PM performance tasks both directly and indirectly. We examined a total of 3600 nights, recorded using actigraphy in participants belonging to the following groups: primary insomnia (731 nights); narcolepsy type 1 (1069 nights); attention deficit hyperactivity disorder (152 nights in children and 239 in adults); severe obesity (232 nights); essential hypertension (226 nights); menopause (143 nights); healthy controls (808 nights). In a naturalistic activity-based PM task, each participant originally wore an actigraph around the non-dominant wrist and was requested to push the event-marker button at two specific times of day: bedtime (activity 1) and get-up time (activity 2). Each clinical group showed significantly lower sleep quality in comparison to the control group. However, only narcolepsy type 1 patients presented a significantly impaired PM performance at get-up time, remembering to push the event-marker button around half the time compared not only to healthy controls but also to the other clinical groups. Overall, the present results seem to point to sleep quality having no effect on the efficiency of a naturalistic activity-based PM task. Moreover, the data indicated that narcolepsy type 1 patients may show a disease-specific cognitive deficit of PM.

The Characteristics of Mood Polarity, Temperament, and Suicide Risk in Adult ADHD.

The present study was designed to shed light on a topic rarely explored and to suggest possible ways to detect risk factors for the presence of suicidal ideation and behaviors in a sample of adult patients with Attention-Deficit Hyperactivity Disorder (ADHD). This study also explored the association between ADHD, affective temperaments, the presence of hypomania symptoms, and suicide risk. We hypothesized that (compared to healthy controls) (1) patients with adult ADHD would report more negative affective temperaments and more hypomania symptoms and (2) that they would have a higher suicide risk. The participants included 63 consecutive adult inpatients (18 women, 45 men) with ADHD and 69 healthy controls (42 women, 22 men). All participants were administered the Wender Utah Rating Scale (WURS), the Hypomania Check-List-32 (HCL-32), the Mood Disorder Questionnaire (MDQ), the Temperament Evaluation for Memphis, Pisa, Paris, and San Diego (TEMPS-A), and the Columbia-Suicide Severity Rating Scale (C-SSRS). Forty-six percent of the ADHD patients had an Axis 1 comorbid disorder. ADHD patients (compared to controls) more often reported suicidal ideation (46.0% vs. 5.9%, one-way Fisher exact test p < 0.001; phi = 0.46). ADHD patients and the controls also significantly differed in all the scales administered (with Cohen's d between 0.92-4.70), except for the TEMPS-A Hyperthymia scale. A regression model indicated that ADHD was independently associated with higher scores of a negative temperaments/hypomania factor (Odd Ratio = 14.60) but not with suicidal ideation. A high incidence of suicidal ideation, comorbid psychiatric disorders, and negative affective temperaments was reported in adult ADHD patients, and clinicians should routinely assess risk factors for suicide among these patients.

Plasma Risperidone-related Measures in Children and Adolescents with Oppositional Defiant/Conduct Disorders.

OBJECTIVE: Therapeutic drug monitoring helps clinicians in choosing the right drug and adjust its dose in specific patients. To this end, we aimed to assess time patterns of risperidone and its metabolite, 9-hydroxyrisperidone, in children and adolescents with oppositional defiant and/or conduct disorder. METHODS: We measured plasma concentrations of risperidone and 9-hydroxyrisperidone, their sum (active moiety, AM) and ratio, as well as plasma concentrations corrected for daily dose (C/D), from 140 children/adolescents with the above-mentioned disorders. We used Student's t test to compare females versus males, patients under versus over 16-year-old, patients with lower versus higher than the median body weight, and patients with lower versus higher than the median body mass index (BMI). Two mixed-effects logistic regression models were fitted for risperidone/9- hydroxyrisperidone ratio and AM, respectively, by considering risperidone daily dose and patients' demographic characteristics. RESULTS: Females had higher 9-hydroxyrisperidone and AM plasma concentrations than males (p = 0.004 and p = 0.034). Younger patients had lower risperidone plasma concentration and risperidone/9-hydroxyrisperidone ratio (p = 0.02 and p = 0.021), but higher C/D 9-hydroxyrisperidone and AM than older patients (p = 0.013 and p = 0.043). Lower-weight patients had lower plasma risperidone and risperidone/9-hydroxyrisperidone ratio (p = 0.014 and p = 0.019), but higher C/D 9-hydroxyrisperidone concentration than heavier patients (p = 0.03). All these results could be accounted for by daily dose. Patients with lower and higher BMI did not differ significantly. Regression analyses showed that only risperidone daily dose predicted risperidone/9-hydroxyrisperidone ratio, whereas risperidone daily dose, sex, and age predicted AM. CONCLUSION: Clinicians prescribing risperidone need to consider sex, age, and weight, but not BMI when adjusting daily doses.

Influence of Spiritual Dimensions on Suicide Risk: The Role of Regional Differences.

The field of suicide prevention has been enriched by research on the association between spirituality and suicide. Many authors have suggested focusing on the various dimensions of religiosity in order to better understand the association between religion and suicidal risk, but it is unclear whether the relationship between spirituality and suicidality differs between countries with different cultures, life values, and sociohistorical experiences. To explore this, the aim of this multicenter study was to investigate the possible relationship between suicide and spirituality in Italy and Austria. In the two countries, two different groups of subjects participated: psychiatric patients and university students. The patients were evaluated with the Mini International Neuropsychiatric Interview. In addition, the following measures were used: a sociodemographic questionnaire, the Columbia-Suicide Severity Rating Scale-B, the Symptom-Checklist-90-Standard, and the Multidimensional Inventory for Religious/Spiritual Well-Being. Our results confirmed the multifactorial nature of the relation between suicide risk and the various religious/spiritual dimensions, including religious/spiritual well-being and hope immanent. However, regional differences moderated this relationship in both the clinical and nonclinical samples.

Suicide and Personality Traits: A Multicenter Study of Austrian and Italian Psychiatric Patients and Students.

OBJECTIVE: The aim of this multicenter study was to investigate the differences in personality traits, particularly Neuroticism, in three clinical samples and three student samples in Austria and Italy and their impact on suicide. METHODS: In total, 1,043 people (410 psychiatric inpatients and 633 university students) were tested in three regions of Europe: central Italy, northeast Italy, and eastern Austria. Psychiatric diagnoses were evaluated using the Mini-International Neuropsychiatric Interview, and the following instruments were used: Sociodemographic Questionnaire, Columbia-Suicide Severity Rating Scale-B, Symptom-Checklist-90-Standard, and Big Five Inventory. RESULTS: The study found that the intensity of Suicidal Ideation was associated with the personality traits of Neuroticism, Anxiety, and Extraversion but also with Depression. CONCLUSIONS: In conclusion, without the presence of Depression symptoms, neuroticism was a protective factor against Suicidal Ideation, whereas neuroticism when comorbid with Depression symptoms increased suicide risk in psychiatric patients. In all three regions, the clinical samples had higher scores for Neuroticism and for Depression symptoms than the student sample and consequently higher scores for Suicide. Furthermore, we demonstrated an interaction between gender and culture on personality traits, supporting the hypothesis that the distribution of self-reported personality traits is organized geographically.