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The objective of this study was to investigate associations between pharmacokinetic correlates and once-monthly paliperidone palmitate (PP1M)-related adverse drug reactions (ADRs). Plasma concentrations and dose-adjusted plasma concentrations (‘concentration-by-dose’ [C/D]) of paliperidone from a naturalistic therapeutic drug monitoring database of PP1M-treated patients were compared between patients with ADRs, classified according to the Udvalg for Kliniske Undersogelser side-effect rating scales categories, and patients without ADRs. Analyses included non-parametric tests and a logistic regression model with a significance level set at 0.05. In 172 patients, we found no differences in sex, age, smoking, body mass index, PP1M dose, paliperidone plasma concentrations, and C/D values (p > 0.05) between 44 patients with and 128 patients without PP1M-related ADRs. We did not detect differences when specifying for different types of ADRs (p > 0.05). Injection intervals were shorter in patients with vs patients without ADRs (p = 0.03). The logistic regression did not report effects for sex, plasma concentrations, or C/D values (p > 0.05). Post hoc analyses in male patients receiving PP1M every 28 weeks reported higher paliperidone concentrations and C/D values in patients with vs without ADRs (p = 0.049 and p = 0.022). Within the group of male patients, we found an odds ratio of 3.07 for PP1M-associated ADRs in patients with C/D values above 7.7 (ng/mL)/(mg/day). Our findings did not reveal distinct patterns of paliperidone concentrations in patients with PP1M-related ADRs. However, male patients receiving PP1M every 28 days with C/D values higher than 7.7 (ng/mL)/(mg/day) showed a higher risk for ADRs, implying that therapeutic drug monitoring may be useful in assessing the risk of PP1M-related ADRs.

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

(1) Background: In their efforts to contain the spread of COVID-19, most countries closed schools and kindergartens. To date, little is known about the strategies of working families reconciling work and parenting during repeated lockdown situations. (2) Methods: We performed a quantitative survey of working parents in Italy during a week of ‘hard lockdown’ in February/March 2021. (3) Results: 3725 voluntary adult participants from different households responded. Though officially not allowed, 53.4% of all participants sought help from people outside the nuclear family to bridge the situation, mostly the grandparents (79%, n = 1855). Overall, parental coping strategies included alternating working–childcare-turns with their partner (35%, n = 1316), working early in the morning or during nighttime (23%, n = 850), or leaving the children unattended (25%, n = 929). (4) Conclusions: The closure of schools/kindergartens forcefully shifts the responsibility for childcare onto the nuclear family, where new strategies arose, including health-damaging models of alternating work–childcare-shifts, ‘illegal’ involvement of third parties from outside the nuclear family, as well as neglect of age-related childcare. Our findings underline that working families need additional support strategies during repeated closure of childcare institutions to be able to reduce contact and minimize secondary damage.

The global handling of the COVID-19 pandemic illustrates that most governments are lacking intergenerational public health solutions. Discontinuity of health care services, mental and physical burden of isolation and school closures increase various pathologies and may provoke long-term health damage amongst the youngest. Unbalanced generational approaches within health policies have been evident before the pandemic and will continue to be a global challenge as both acute and chronic threats due to environmental hazards and social disparities are increasing. Beyond the current crisis and in dealing with any public health threat, intergenerational approaches focused on the welfare of children and adolescents and the long-term impact on their lives are imperative and must be a core part in the development and implementation of public health policies.

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.

Objective: To conduct a systematic review of studies assessing the relationship between exposure to pesticides and ADHD or Autism Spectrum Disorder (ASD). Methods: Based on a pre-registered protocol in PROPSERO (CRD42018107847), we searched PubMed, Ovid databases, and ISI Web of Knowledge with no date/language/document type restrictions, up to May 2019. The Newcastle Ottawa Scale was used to assess study quality. Results: Among the 29 retained studies, 13 focused on ADHD, 14 on ASD, and two on both disorders. Ten studies reported a significant association between exposure to pesticides and ADHD/ADHD symptoms and 12 studies found a significant association with ASD/ASD traits. The strengths of the association and the possible confounders controlled for varied substantially across studies. Conclusion: Whilst there is some evidence suggesting a possible link between pesticides and ADHD/ASD, heterogeneity across studies prevents firm conclusions. We provide methodological indications for future studies.

Background As suicide is related to many factors in addition to psychiatric illness, broad and comprehensive risk-assessment for risk of suicide is required. This study aimed to differentiate nondiagnostic risk factors among suicides versus comparable psychiatric patients without suicidal behavior. Methods We carried out a pilot, case-control comparison of 131 cases of suicide in South Tyrol matched for age and sex with 131 psychiatric controls, using psychological autopsy methods to evaluate differences in clinically assessed demographic, social, and clinical factors, using bivariate conditional Odds Risk comparisons followed by conditional regression modeling controlled for ethnicity. Results Based on multivariable conditional regression modeling, suicides were significantly more likely to have experienced risk factors, ranking as: [a] family history of suicide or attempt ≥ [b] recent interpersonal stressors ≥ [c] childhood traumatic events ≥ [d] lack of recent clinician contacts ≥ [e] previous suicide attempt ≥ [f] non-Italian ethnicity, but did not differ in education, marital status, living situation, or employment, nor by psychiatric or substance-abuse diagnoses. Conclusions Both recent and early factors were associated with suicide, including lack of recent clinical care, non-Italian cultural subgroup-membership, familial suicidal behavior, and recent interpersonal distress.

The observation that people with schizophrenia misattribute the source of their own actions has led to the hypothesis that they suffer from altered sensorimotor processes underlying sense of agency. Furthermore, rubber hand studies suggest an abnormal experience of embodiment in schizophrenia. However, this latter finding is based on a procedure that elicits ownership sensations for a fake hand by visuo-tactile stimulation, leaving the agency subcomponent of embodiment relatively untouched. By using a visuo-motor version of the embodiment illusion able to actively elicit also sense of agency for an alien hand, we tested whether the putative sensorimotor deficits are also involved in altering embodiment sensations in schizophrenia. Subjective (questionnaire) and perceptual (forearm bisection performance) indexes of the embodiment illusion were collected. Differently from controls, both the explicit agency component and the implicit body metrics update were not modulated by the extent of visuo-motor congruency in participants with schizophrenia. We conclude that motor prediction and/or temporal binding window impairments may alter the feeling of embodiment and body representation in schizophrenia.

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.

Background: Mental disorders are associated with an increased prevalence of substance use disorders (SUDs). Despite this comorbidity being firmly established, alcohol and nicotine risky use and misuse are not routinely and systematically assessed in clinical practice. Objective: The aim of this study is to examine the prevalence of risky use of alcohol, alcohol use disorder (AUD), smoking, and nicotine use disorder in people with psychiatric diagnoses and their association with age, gender, and occupational functioning. Method: Participants were 210 patients from an inpatient psychiatric ward. Three self-reporting questionnaires were used: the Alcohol Use Disorders Identification Test (AUDIT), the Lübeck Alcoholism Screening Test (LAST), and the Fagerström Test for Nicotine Dependence (FTND). Results: Risky alcohol use or AUD was found in more than one third of patients and was more common in males than in females (p

Background:we aimed to compare socio-demographic and clinical differences between patients with versus without current RC in order to detect clinical factors that may favor early diagnosis and personalized treatment.Methods:A total of 1675 patients (males: n = 714 and females: n = 961; bipolar 1: n = 1042 and bipolar 2: n = 633) from different psychiatric clinics were grouped and compared according to the current presence of RC in terms of socio-demographic and clinical variables. Chi-squared tests for qualitative variables and Student’sttests for quantitative variables were executed for group comparison, and multivariable logistic regressions were performed, considering the current presence of RC as dependent variable, and socio-demographic/clinical factors as independent variables.Results:Female gender (male versus female: OR = 0.64, p = 0.04), unidentifiable prevalent polarity (versus depressive polarity: OR = 1.76, p = 0.02; versus manic polarity: OR: 2.86, p < 0.01) and hospitalization in the last year (no versus yes: OR = 0.63, p = 0.02) were found to be associated with RC in the final multivariable regression analysis.Conclusions:RC in BD seems to be more prevalent in female gender and associated with some unfavorable clinical features, such as an increased risk of hospitalization. These aspects should be taken into account in the management and monitoring of RC versus non-RC patients.

Background ADHD (Attention-deficit/hyperactivity disorder) is a common neurodevelopmental disorder that manifests itself during childhood with various combinations of symptoms, including inattention, hyperactivity and impulsivity. Research has shown that psychiatric comorbidities play an important role in the development of suicidal behavior and, recently, there has been a growing interest in a possible association between ADHD and suicide during both childhood and adulthood. Furthermore, some authors have shown a relationship between pharmacological treatments and suicide in patients affected by ADHD. Aims We conducted a selective review of current literature to explore the factors which contribute to suicidal behavior and self-harm in those with ADHD. Methods We performed a PubMed/MEDLINE, Scopus, PsycLit, and PsycINFO search to identify all articles and book chapters on the topic up to 2017. Results Several studies have showed that ADHD may be correlated with an increased suicide ideation and attempts. Conclusions Although differences in studies design and samples made the results difficult to compare and interpret, many studies indicate an association between ADHD and suicidal behavior. It remains controversial whether there is a direct relationship or whether the association depends on the increased prevalence of pre-existing comorbid conditions and individual and family dysfunctional factors.

Major Depression Disorder (MDD) has a highly variable treatment response due to the large inter-individual variation in the pharmacokinetics and pharmacodynamics of drug treatments. In detail the correlation between plasma level and efficacy has been much debated. Among first-line drugs for MDD, one of the most used is escitalopram. In the present study we investigated the association between serum concentration of escitalopram (SCE) and antidepressant response (AR). 70 MDD patients treated with escitalopram monotherapy were recruited and followed for three months. Hamilton Depression Rating Scale - 21 (HAMD-21) was administrated at baseline, month 1, and month 3 to assess AR. SCE was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between SCE and AR. We found an association between SCE and AR both at month 1 (p

This study aims to describe the 24-hour activity rhythm in adults with attention-deficit/hyperactivity disorder (ADHD). A total of 18 ADHD patients and 37 healthy controls (HCs) wore an actigraph for 7 days. ADHD patients showed higher motor activity than HCs at 4:00, 6:00, 15:00 and 16:00 hour. Within the theoretical framework of the two-process model of sleep regulation, the observed data may be explained by lower homeostatic sleep pressure in ADHD. This could lead to an increase in motor activity in the second half of the night, when sleep need decreases more rapidly, and in the first half of the afternoon, when patients do not experience the typical post-lunch dip.

Background Methylenetetrahydrofolate reductase (MTHFR) genetic variations have been widely studied in major depressive disorder (MDD) and antidepressants outcome. An interaction with catechol-O-methyltransferase (COMT) has also been proved affecting depression. The aim of this study was to clarify the role of the most commonly studied single nucleotide polymorphisms (SNPs) of MTHFR gene in MDD and in treatment response mechanisms, along with the impact of the interaction with COMT. Methods A total of 613 MDD patients, of whom 389 were classified as having treatment resistant depression (TRD), and 463 controls were enrolled. The A1298C, C677T and COMT Val158Met were genotyped. Genetic data were integrated with a transcriptional level analysis in peripheral blood cells (PBCs) and fibroblasts. Results The A1298C CC homozygotes were more frequent in MDD patients compared to controls in women, increasing twice the genetic risk to develop depression. Moreover this genotype resulted in epistasis with COMT Met carriers in association with MDD. No significant effects were obtained concerning response to treatment. Transcriptional analyses highlighted a strong correlation between the mRNA levels of MTHFR in fibroblasts and COMT genotypes whereas no significant association with MDD was found. PBCs results revealed relevant influences of environmental factors. Limitation We did not measure folate and homocisteine levels. Conclusion This study showed the involvement of A1298C, Val158Met and their interaction in MDD. The transcriptional analyses supported the participation of COMT in the folate pathway, which partakes in the complex network of gene×gene and gene×environment interactions of MDD etiopathogenesis.

There is abundant evidence that the cerebral white matter and in particular the corpus callosum show several structural abnormalities in both schizophrenia (SCZ) and bipolar disease (BD). However, which cognitive functions are impaired as a result of these anomalies is still unclear. Previous behavioural tests of interhemispheric crosstalk have shown a differential impairment in SCZ with interhemispheric transmission time, as tested with the Poffenberger paradigm, essentially normal but with an abnormally enhanced interhemispheric summation effect, as tested with the redundant signal effect. The present study was inspired by this discrepancy and by the more general question of a possible overlap between the pathophysiology of SCZ and BD. We tested both SCZ and BD patients in the Poffenberger paradigm and redundant signal effect and found a similar dissociation, namely a normal interhemispheric transfer time and an abnormal redundant signal effect. The only difference between the two groups was a selective slowing of speed of response of the dominant right hand in the SCZ group suggesting an impairment of left hemisphere functions. These results cast further light on the question of common and differential impairments of basic psychological functions in the two diseases.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate- and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint effort.

Background Charge-free heroin use disorder treatment in Italy follows two main approaches, i.e., harm reduction treatment (HRT) strategy in community low-threshold facilities for drug addiction and opioid agonist treatment (OAT) in high-threshold facilities for opioid addiction, focusing on pharmacological maintenance according to the Dole and Nyswander strategy. We aimed to compare the impact of HRT and OAT on patient outcome, as assessed through negativity for drugs on about 1-year urinalyses. Methods We examined retrospectively the urinalyses of HRT and OAT patients for which at least four randomly sampled urinalyses per month were available for about 1 year, during which patients were undergoing methadone or buprenorphine maintenance; urinalyses focused on heroin, cocaine, cannabinoids, and their metabolites. Results Included were 189 HRT and 58 OAT patients. The latter were observed for a significantly longer period. There was a higher proportion of heroin- and cocaine-clean urinalyses in OAT patients, with cocaine-clean urinalyses discriminating best between the two groups. OAT patients were older, with longer dependence duration, more severe addiction history, and received lower methadone doses. Buprenorphine maintenance was more often associated with heroin-clean urinalyses. The higher the methadone doses, the lower were the percentage of heroin-clean urinalyses in HRT patients (negative correlation). Conclusions The OAT approach was related to higher recovery and polyabuse abstinence rates compared to the HRT approach, despite greater severity of substance use, psychiatric and physical comorbidities. Our results are consistent with the possibility to use lower maintenance opiate doses (after induction and stabilization in methadone treatment according to Dole and Nyswander methodology) in treating heroin addiction. This seemed to be impossible adopting the currently accepted HRT model.

Background In recent years, the identification of peripheral biomarkers that are associated with psychiatric diseases, such as Major Depressive Disorder (MDD), has become relevant because these biomarkers may improve the efficiency of the differential diagnosis process and indicate targets for new antidepressant drugs. Two recent candidate genes, ErbB3 and Fgfr1, are growth factors whose mRNA levels have been found to be altered in the leukocytes of patients that are affected by bipolar disorder in a depressive state. On this basis, the aim of the study was to determine if ErbB3 and Fgfr1 mRNA levels could be a biomarkers of MDD. Methods We measured by Real Time PCR ErbB3 and Fgfr1 mRNA expression levels in leukocytes of MDD patients compared with controls. Successively, to assess whether ErbB3 mRNA levels were influenced by previous antidepressant treatment we stratified our patients sample in two cohorts, comparing drug-naive versus drug-free patients. Moreover, we evaluated the levels of the transcript in MDD patients after 12 weeks of antidepressant treatment, and in prefrontal cortex of rats stressed and treated with an antidepressant drug of the same class. Results These results showed that ErbB3 but not Fgfr1 mRNA levels were reduced in leukocytes of MDD patients compared to healthy subjects. Furthermore, ErbB3 levels were not affected by antidepressant treatment in either human or animal models Conclusions Our data suggest that ErbB3 might be considered as a biomarker for MDD and that its deficit may underlie the pathopsysiology of the disease and is not a consequence of treatment. Moreover the study supports the usefulness of leukocytes as a peripheral system for identifying biomarkers in psychiatric diseases.