Is Antipsychotic Drug Use During Pregnancy Associated with Increased Malformation Rates and Worsening of Maternal and Infant Outcomes? A Systematic Review.

There is much debate about continuing antipsychotic medication in patients who need it when they become pregnant because benefits must be weighed against potential teratogenic and malformation effects related to antipsychotics themselves. To address this, we conducted a systematic review on the PubMed, PsycINFO and CINHAL databases and the ClinicalTrials.gov register using the following strategy: (toxicity OR teratogenicity OR malformation* OR "birth defect*" OR "congenital abnormality" OR "congenital abnormalities" OR "brain changes" OR "behavioral abnormalities" OR "behavioral abnormalities") AND antipsychotic* AND (pregnancy OR pregnant OR lactation OR delivery OR prenatal OR perinatal OR post-natal OR puerperium) on September 27, 2023. We found 38 studies to be eligible. The oldest was published in 1976, while most articles were recent. Most studies concluded that the antipsychotics, especially the second-generation antipsychotics, were devoid of teratogenic potential, while few studies were inconclusive and recommended replication. Most authoritative articles were from the Boston area, where large databases were implemented to study the malformation potential of psychiatric drugs. Other reliable databases are from Northern European registers. Overall conclusions are that antipsychotics are no more related to malformations than the disorders themselves; most studies recommend that there are no reasons to discontinue antipsychotic medications in pregnancy.

New pharmacotherapies to tackle the unmet needs in bipolar disorder: a focus on acute suicidality.

INTRODUCTION: Suicidal behavior is relatively frequent in patients with bipolar disorder (BD) and constitutes their most frequent cause of death. Suicide rates remain high in patients with BD despite adherence to guidelines recommending lithium as first line, and/or antidepressants, antipsychotics, psychotherapy, psychosocial interventions, and electroconvulsive therapy. Hence the need to identify more effective and rapid anti-suicide interventions. AREAS COVERED: To tackle the unmet needs of pharmacotherapy, we investigated the PubMed database on 24-25 January 2024 using strategies like ('acute suicid*'[ti] OR 'suicide crisis syndrome' OR 'acute suicidal affective disturbance') AND (lithium[ti] OR clozapine[ti]), which obtained 3 results, and ('acute suicid*'[ti] OR 'suicide crisis syndrome' OR 'acute suicidal affective disturbance') AND (ketamine[ti] OR esketamine[ti] OR NMDA[ti] OR glutamat*[ti]), which yielded 14 results. We explored glutamatergic abnormalities in BD and suicide and found alterations in both. The noncompetitive NMDS antagonist ketamine and its S-enantiomer esketamine reportedly decrease acute suicidality. EXPERT OPINION: Intranasal esketamine or subcutaneous ketamine, single-bolus or intravenous, and possibly other glutamate receptor modulators may improve suicidal behavior in patients with unipolar and bipolar depression. This may be achieved through prompt remodulation of glutamate activity. The correct use of glutamatergic modulators could reduce acute suicidality and mortality in patients with BD.

Psychological factors and barriers to donating and receiving milk from human milk banks: A review.

Human milk banks (HMBs), established in the early 20th century, aimed to provide safe breast milk for infants with challenges obtaining it. The spread of infections since the 1980s resulted in strict regulations and screening in HMBs, to ensure the safety of donated milk. Several social and personal factors discourage mothers from practicing breastfeeding, making donated milk a viable alternative because of its protective and immunity-enhancing properties. However, psychological barriers can affect the decision to donate or receive donated milk. To identify psychological factors related to donating and receiving human milk from HMBs, we searched PubMed to identify studies reporting psychological factors in donating and receiving milk and excluding studies not reporting psychological factors. The search identified 28 articles meeting the inclusion criteria. Eligible studies from various countries spanned from 1995 to 2023 and focused on psychological factors influencing milk donation and receiving. Most studies were descriptive-qualitative. Factors facilitating or hindering milk donation and reception included perceptions, psychological aspects, and previous experiences. Positive factors for donors included the desire to help other mothers, support from health care professionals, and personal well-being. Negative factors included breast milk exclusivity and discomfort caused by health checks. For recipients, awareness of donated milk benefits was a positive factor, whereas fear regarding safety was negative. The altruistic motivation to help other mothers drove many women to donate. Proper awareness and support from health care professionals and families can help women understand the value of milk donation and support their personal and identity reintegration, especially in cases of the loss of a child.

Primary emotional systems, childhood trauma, and suicidal ideation in youths with bipolar disorders.

BACKGROUND: Bipolar disorders (BD) in youths are strongly associated with suicidal ideation. Childhood trauma is a prominent environmental stressor associated with both BD diagnosis and suicide. Primary emotional systems are altered in adult BD and may contribute to suicide risk in youths. OBJECTIVE: The aim of this study was to investigate primary emotional systems distribution patterns and childhood trauma in youths' BD with and without suicidal ideation (BD-IS, BD-NIS). PARTICIPANTS AND SETTING: We assessed 289 participants, 103 youths with DSM-5 BD and 186 healthy controls (HCs). METHODS: Primary emotional systems were obtained with Panksepp's Affective Neuroscience Personality Scale (ANPS), and history of childhood trauma using the Childhood Trauma Questionnaire (CTQ). Suicidal ideation was assessed through the Columbia Suicide Scale for the Rating of Suicide Severity (C-SSRS). The associations with suicidal ideation were tested using two different multivariate models. RESULTS: Over 48 % of participants reported lifetime suicidal ideation and differed on clinical variables from BD-NIS. According to the first model (Wilk's Lambda = 0.72, p < 0.0001), BD-IS scored higher on Panksepp's ANGER and lower on PLAY and CARE than BD-NIS. Both BD-SI and BD-NSI scored higher on ANGER and SEEK and lower on PLAY and CARE than HCs. BD-IS reported more emotional abuse than BD-NIS. They also reported more emotional, sexual, and physical abuse, and emotional neglect than HCs. Only ANGER (OR = 1.13, 95 % CI = 1.01-1.26, Wald = 5.72) and CTQ-Emotional abuse (OR = 1.26, 95 % C.I. = 1.04-1.52, Wald = 5.72) independently predicted suicidal ideation. CONCLUSIONS: Findings support the importance of assessing primary emotional systems and childhood trauma, in particular emotional abuse, in youths with BD at risk for suicide.

Outpatient care for adolescents' and young adults' mental health: promoting self- and others' understanding through a metacognitive interpersonal therapy-informed psychological intervention.

Introduction: Psychological distress may result in impairment and difficulty understanding oneself and others. Thus, addressing metacognitive issues in psychotherapy may improve psychopathology in adolescents and young adults (AYAs). We aimed to compare metacognitive interpersonal therapy (MIT)-informed psychotherapy with other treatment-as-usual (TAU) therapies. Methods: We administered the Global Assessment of Functioning (GAF) scale, the Clinical Global Impressions-Severity (CGI-S) scale, and the Brief Psychiatric Rating Scale (BPRS) at baseline (BL) and at treatment termination (the endpoint was at 6 months and any last results obtained before that term were carried forward in analyzes). Patients received concomitant psychiatric and psychological treatment. Results: Sixty AYAs were involved in the study. There was a significant reduction in symptomatology after the intervention. Twelve patients (17%) dropped out; treatment adherence was 83%. In the MIT group, 2 patients dropped out (11%), and in the TAU group, 9 patients dropped out (19%). All scales showed a significant reduction in symptoms between baseline (BL) and the 6-month endpoint: GAF (χ2 = 6.61, p < 0.001), BPRS (χ2 = 6.77, p < 0.001), and CGI (χ2 = 7.20, p < 0.001). There was a greater efficacy for the MIT group in terms of symptom reduction on the BPRS (t = 2.31; p < 0.05). Conclusion: The study confirmed the efficacy of early and integrated care in adolescence and suggested greater symptom reduction for a psychotherapeutic intervention focused on stimulating mentalization skills. The study indicates the usefulness of this type of approach in the treatment of adolescent psychopathology. Due to the small sample size, the results need replication.

A systematic review on gender dysphoria in adolescents and young adults: focus on suicidal and self-harming ideation and behaviours.

INTRODUCTION: Gender dysphoria (GD) is characterized by the incongruence between one's experienced and expressed gender and assigned-sex-at-birth; it is associated with clinically significant distress. In recent years, the number of young patients diagnosed with GD has increased considerably. Recent studies reported that GD adolescents present behavioural and emotional problems and internalizing problems. Furthermore, this population shows a prevalence of psychiatric symptoms, like depression and anxiety. Several studies showed high rates of suicidal and non-suicidal self-injurious thoughts and behaviour in GD adolescents. To increase understanding of overall mental health status and potential risks of young people with GD, this systematic review focused on risk of suicide and self-harm gestures. METHODS: We followed the PRISMA 2020 statement, collecting empirical studies from four electronic databases, i.e., PubMed, Scopus, PsycINFO, and Web of Science. RESULTS: Twenty-one studies on GD and gender nonconforming identity, suicidality, and self-harm in adolescents and young adults met inclusion criteria. Results showed that GD adolescents have more suicidal ideation, life-threatening behaviour, self-injurious thoughts or self-harm than their cisgender peers. Assessment methods were heterogeneous. CONCLUSION: A standardised assessment is needed. Understanding the mental health status of transgender young people could help develop and provide effective clinical pathways and interventions.

Are the Post-COVID-19 Posttraumatic Stress Disorder (PTSD) Symptoms Justified by the Effects of COVID-19 on Brain Structure? A Systematic Review.

COVID-19 affects brain function, as deduced by the "brain fog" that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a patient in the post-COVID-19 period. Approximately one-third of patients, even when they have recovered from the acute somatic disease, continue to show posttraumatic stress disorder (PTSD) symptoms. We hypothesized that the persistent changes induced by COVID-19 on brain structure would overlap with those associated with PTSD. We performed a thorough PubMed search on 25 April 2023 using the following strategy: ((posttraumatic OR PTSD) AND COVID-19 AND (neuroimaging OR voxel OR VBM OR freesurfer OR structural OR ROI OR whole-brain OR hippocamp* OR amygd* OR "deep gray matter" OR "cortical thickness" OR caudate OR striatum OR accumbens OR putamen OR "regions of interest" OR subcortical)) OR (COVID-19 AND brain AND (voxel[ti] OR VBM[ti] OR magnetic[ti] OR resonance[ti] OR imaging[ti] OR neuroimaging[ti] OR neuroimage[ti] OR positron[ti] OR photon*[ti] OR PET[ti] OR SPET[ti] OR SPECT[ti] OR spectroscop*[ti] OR MRS[ti])), which produced 486 records and two additional records from other sources, of which 36 were found to be eligible. Alterations were identified and described and plotted against the ordinary PTSD imaging findings. Common elements were hypometabolism in the insula and caudate nucleus, reduced hippocampal volumes, and subarachnoid hemorrhages, while white matter hyperintensities were widespread in both PTSD and post-COVID-19 brain infection. The comparison partly supported our initial hypothesis. These data may contribute to further investigation of the effects of long COVID on brain structure and function.

Resilience and Attachment in Patients with Major Depressive Disorder and Bipolar Disorder.

BACKGROUND: Resilience represents one of the fundamental elements of attachment and has often been investigated in mood disorders. This study aims to investigate possible correlations between attachment and resilience in patients with major depressive disorder (MDD) and bipolar disorder (BD). METHODS: 106 patients (51 MDD, 55 BD) and 60 healthy controls (HCs) were administered the 21-item Hamilton Depression Rating Scale (HAM-D-21), the Hamilton Anxiety Rating Scale (HAM-A), the Young Mania Rating Scale (YMRS), the Snaith-Hamilton Pleasure Scale (SHAPS), the Barratt Impulsiveness Scale-11 (BIS-11), the Toronto Alexithymia Scale (TAS), the Connor-Davidson Resilience Scale (CD-RISC), and Experiences in Close Relationship (ECR). RESULTS: MDD and BD patients did not significantly differ from each other according to the HAM-D-21, HAM-A, YMRS, SHAPS, and TAS, while they scored higher than HCs on all these scales. Patients in the clinical group scored significantly lower on CD-RISC resilience than HCs (p < 0.01). A lower proportion of secure attachment was found among patients with MDD (27.4%) and BD (18.2%) compared to HCs (90%). In both clinical groups, fearful attachment prevailed (39.2% patients with MDD; 60% BD). CONCLUSIONS: Our results highlight the central role played by early life experiences and attachment in participants with mood disorders. Our study confirms the data from previous research showing a significant positive correlation between the quality of attachment and the development of resilience capacity, and supports the hypothesis that attachment constitutes a fundamental aspect of resilience capacity.

COVID-19 pandemic in the intensive care unit: Psychological implications and interventions, a systematic review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic produced changes in intensive care units (ICUs) in patient care and health organizations. The pandemic event increased patients' risk of developing psychological symptoms during and after hospitalisation. These consequences also affected those family members who could not access the hospital. In addition, the initial lack of knowledge about the virus and its management, the climate of fear and uncertainty, the increased workload and the risk of becoming infected and being contagious, had a strong impact on healthcare staff and organizations. This highlighted the importance of interventions aimed at providing psychological support to ICUs, involving patients, their relatives, and the staff; this might involve the reorganisation of the daily routine and rearrangement of ICU staff duties. AIM: To conduct a systematic review of psychological issues in ICUs during the COVID-19 pandemic involving patients, their relatives, and ICU staff. METHODS: We investigated the PubMed and the ClinicalTrials.gov databases and found 65 eligible articles, upon which we commented. RESULTS: Our results point to increased perceived stress and psychological distress in staff, patients and their relatives and increased worry for being infected with severe acute respiratory syndrome coronavirus-2 in patients and relatives. Furthermore, promising results were obtained for some psychological programmes aiming at improving psychological measures in all ICU categories. CONCLUSION: As the pandemic limited direct inter-individual interactions, the role of interventions using digital tools and virtual reality is becoming increasingly important. All considered, our results indicate an essential role for psychologists in ICUs.

The Nrf2 Pathway in Depressive Disorders: A Systematic Review of Animal and Human Studies.

There is increasing interest in the involvement of antioxidative systems in protecting from depression. Among these, Nrf2 occupies a central place. We aimed to review the role of Nrf2 in depression. For this reason, we conducted a PubMed search using as search strategy (psychiatr*[ti] OR schizo*[ti] OR psychot*[ti] OR psychos*[ti] OR depress*[ti] OR MDD[ti] OR BD[ti] OR bipolar[ti] OR Anxiety[ti] OR antidepress*[ti] OR panic[ti] OR obsess*[ti] OR compulsio*[ti] OR "mood disord*"[ti] OR phobi*[ti] OR agoraphob*[ti] OR anorex*[ti] OR anorect*[ti] OR bulimi*[ti] OR "eating disorder*"[ti] OR neurodevelopm*[ti] OR retardation[ti] OR autism[ti] OR autistic[ti] OR ASM[ti] OR adhd[ti] OR "attention-deficit"[ti]) AND nrf2, which on the 9th of March produced 208 results of which 89 were eligible for our purposes. Eligible articles were studies reporting data of Nrf2 manipulations or content by any treatment in human patients or animals with any animal model of depression. Most studies were on mice only (N = 58), 20 on rats only, and three on both rats and mice. There were two studies on cell lines (in vitro) and one each on nematodes and fish. Only four studies were conducted in humans, one of which was post mortem. Most studies were conducted on male animals; however, human studies were carried out on both men and women. The results indicate that Nrf2 is lower in depression and that antidepressant methods (drugs or other methods) increase it. Antioxidant systems and plasticity-promoting molecules, such as those in the Nrf2-HO-1, BDNF-TrkB, and cyclic AMP-CREB pathways, could protect from depression, while glycogen synthase kinase-3ß and nuclear factor κB oppose these actions, thus increasing depressive-like behaviours. Since Nrf2 is also endowed with tumorigenic and atherogenic potential, the balance between benefits and harms must be taken into account in designing novel drugs aiming at increasing the intracellular content of Nrf2.

Depressive Symptoms during Pregnancy: Prevalence and Correlates with Affective Temperaments and Psychosocial Factors.

Pregnancy is a unique experience in women's life, requiring a great ability of adaptation and self-reorganization; vulnerable women may be at increased risk of developing depressive symptoms. This study aimed to examine the incidence of depressive symptomatology during pregnancy and to evaluate the role of affective temperament traits and psychosocial risk factors in predicting them. We recruited 193 pregnant women, collected data regarding sociodemographic, family and personal clinical variables, social support and stressful life events and administered the Mood Disorder Questionnaire (MDQ), the Patient Health Questionnaire-9 (PHQ-9), and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). In our sample, prevalence of depressive symptomatology was 41.45% and prevalence of depression was 9.85% (6.75% mild and 3.10% moderate depression). We have chosen a cutoff >4 on PHQ-9 to identify mild depressive symptoms which may predict subsequent depression. Statistically significant differences between the two groups were found in the following factors: gestational age, occupation, partner, medical conditions, psychiatric disorders, family psychiatric history, stressful life events, and TEMPS-A mean scores. In our sample mean scores on all affective temperaments but the hyperthymic, were significantly lower in the control group. Only depressive and hyperthymic temperaments were found to be, respectively, risk and protective factors for depressive symptomatology. The current study confirms the high prevalence and complex aetiology of depressive symptomatology during pregnancy and suggests that affective temperament assessment seems to be a useful adjunctive instrument to predict depressive symptomatology during pregnancy and postpartum.

COVID-19 and New-Onset Psychosis: A Comprehensive Review.

Psychosis is a multifactorial condition that typically involves delusions, hallucinations, and disorganized thought, speech or behavior. The observation of an association between infectious epidemics and acute psychosis dates back to the last century. Recently, concerns have been expressed regarding COVID-19 and the risk for the development of new-onset psychosis. This article reviewed the current evidence of a possible link between SARS-CoV-2 and risk of psychosis as an acute or post-infectious manifestation of COVID-19. We here discuss potential neurobiological and environmental factors as well as a number of challenges in ascribing a causal pathogenic relationship between SARS-CoV-2 infection and new-onset psychosis.

Use of Lithium in Pediatric Bipolar Disorders and Externalizing Childhood- related Disorders: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Lithium is the standard treatment for bipolar disorders (BD) in adults. There is a dearth of data on its use in the pediatric age. This review aimed to investigate the use of lithium in pediatric bipolar disorder (BD) and other externalizing childhood-related disorders. METHODS: We applied the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria (PRISMA) to identify randomized controlled trials evaluating the use of lithium in pediatric (BD), conduct disorder (CD), attention deficit hyperactivity disorder, oppositional defiant disorder, and disruptive mood dysregulation disorder. The primary outcome of our study was to evaluate the efficacy of lithium compared to a placebo or other pharmacological agents. The secondary outcomes were acceptability and tolerability. RESULTS: Twelve studies were eligible, 8 on BD and 4 on CD. Overall, 857 patients were treated with lithium. No studies for externalizing disorder diagnoses were identified. Regarding BD patients (n = 673), efficacy results suggested that lithium was superior to placebo in manic/mixed episodes but inferior to antipsychotics. Lithium efficacy ranged from 32% to 82.4%. Results on maintenance need to be expanded. Comorbidity rates with other externalizing disorders were extremely high, up to 98.6%. Results in CD patients (n= 184) suggested the efficacy of lithium, especially for aggressive behaviors. No severe adverse events directly related to lithium were reported in BD and CD; common side effects were similar to adults. CONCLUSION: This systematic review supports the use of lithium in BD and CD as an efficacious and generally well-tolerated treatment in the pediatric age. However, evidence is limited due to the paucity of available data.

Depressive Symptoms in Expecting Fathers: Is Paternal Perinatal Depression a Valid Concept? A Systematic Review of Evidence.

BACKGROUND: Since the identification of Couvade syndrome in the late 1950s, little attention has been dedicated to the issue of depression in expecting fathers. OBJECTIVE: To quantify the extent of depression in expecting fathers and find out if they match their pregnant partners' depression. METHODS: We conducted a PubMed and ClinicalTrials.gov search using paternal depression and all its variants as terms. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement to include eligible studies. RESULTS: We identified a grand total of 1443 articles, of which 204 were eligible. The total number of fathers/expecting fathers involved was 849,913. Longitudinal studies represented more than half of the included studies; more than three-quarters of the studies used the Edinburgh Postnatal Depression Scale (EPDS). The average occurrence of paternal depression was around 5%, which confers the entity some clinical dignity. Depression tends to occur more in expecting women and new mothers than in expecting partners or new fathers, while the co-occurrence in the same couple is quite low. LIMITATIONS: The methodological heterogeneity of the included studies prevents us from meta-analyzing the obtained data. The validity of the instruments used is another issue. CONCLUSIONS: Paternal depression is distinct from maternal depression and occurs at lower rates (about half). The very existence of a paternal depression clinical entity is beyond any doubt. Future research should address methodological heterogeneity.

Craving variations in patients with substance use disorder and gambling during COVID-19 lockdown: The Italian experience.

BACKGROUND: Following the development of the coronavirus disease-2019 (COVID-19) pandemic in Italy, a strict lockdown was imposed from March 9 to May 5, 2020. The risks of self-medication through alcohol or psychoactive substance abuse were increased, as well as the tendency to adopt pathological behaviors, such as gambling and internet addiction. AIM: To evaluate the impact of the COVID-19 pandemic and associated containment measures on craving in a group of patients suffering from substance use disorder and/or gambling disorder who were in treatment in outpatient units or in residency programs as inpatients. METHODS: One hundred and fifty-three patients completed a structured questionnaire evaluating craving and other behaviors using a visual analogue scale (VAS). Forty-one subjects completed a pencil and paper questionnaire during the interview. The clinician provided an online questionnaire to 112 patients who had virtual assessments due to lockdown restrictions. Statistical analyses were performed using Statistica version 8.0. Quantitative parameters are presented as the mean ± SD and qualitative parameters as number and percentage per class. The Kolmogorov-Smirnov test was used to check for normality of distributions. Analysis of variance and Duncan post hoc test were employed to analyze differences among subgroup means. The associations between variables were measured using Pearson's correlation. A P value of < 0.05 was considered significant. RESULTS: The variation in craving between the present and the month before showed VAS-related reductions of craving in 57%, increases in 24%, and no significant change in 19% of the sample. The level of craving was significantly higher (F = 4.36; P < 0.05) in outpatients (n = 97; mean = 3.8 ± 3.1) living in their own home during the quarantine compared with inpatients (n = 56; mean = 2.8 ± 2.8) in residential programs. Craving for tetrahydrocannabinol was the greatest (4.94, P < 0.001) among various preferred substances. CONCLUSION: The unexpected result of this study may be explained by a perceived lack of availability of substances and gambling areas and/or decreased social pressure on a subject usually excluded and stigmatized, or the acquisition of a new social identity based on feelings of a shared common danger and fate that overshadowed the sense of exclusion and rejection in the abuser.

Intimate partner violence: A loop of abuse, depression and victimization.

Intimate partner violence has been recognized as a serious public health issue. Exposure to violence contributes to the genesis of, and exacerbates, mental health conditions, and existing mental health problems increase vulnerability to partner violence, a loop that imprisons victims and perpetuates the abuse. A recently described phenomenon is when male violence against females occurs within intimate relationships during youth, and it is termed adolescent or teen dating violence. In this narrative review, factors associated with intimate partner violence and consequences of exposure of children to parental domestic violence are discussed, along with possible intensification of violence against women with the spread of coronavirus disease 2019 pandemic and subsequent lockdown. Intervention programs with a multicomponent approach involving many health care settings and research have a pivotal role in developing additional strategies for addressing violence and to provide tailored interventions to victims. Prevention policy with a particular attention on healthy child and adolescent development is mandatory in the struggle against all forms of violence.

Not Only Mania or Depression: Mixed States/Mixed Features in Paediatric Bipolar Disorders.

Background: early onset is frequent in Bipolar Disorders (BDs), and it is characterised by the occurrence of mixed states (or mixed features). In this systematic review, we aimed to confirm and extend these observations by providing the prevalence rates of mixed states/features and data on associated clinical, pharmacological and psychopathological features. Methods: following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched from inception to 9 February 2021 for all studies investigating mixed states/mixed features in paediatric BD. Data were independently extracted by multiple observers. The prevalence rates of mixed states/features for each study were calculated. Results: eleven studies were included in our review, involving a total patient population of 1365 individuals. Overall, of the patients with paediatric age BD, 55.2% had mixed states/features (95% CI 40.1-70.3). Children with mixed states/features presented with high rates of comorbidities, in particular, with Attention Deficit Hyperactivity Disorder (ADHD). Evidences regarding the psychopathology and treatment response of mixed states/features are currently insufficient. Conclusions: our findings suggested that mixed states/features are extremely frequent in children and adolescents with BD and are characterised by high levels of comorbidity. Future investigations should focus on the relationship between mixed states/features and psychopathological dimensions as well as on the response to pharmacological treatment.

Neuropsychiatric Symptoms in Elderly With Dementia During COVID-19 Pandemic: Definition, Treatment, and Future Directions.

BACKGROUND: Neuropsychiatric symptoms (NPS) of dementia, such as anxiety, depression, agitation, and apathy, are complex, stressful, and costly aspects of care, and are associated to poor health outcomes and caregiver burden. A steep worsening of such symptoms has been reported during Coronavirus Disease 2019 (COVID-19) pandemic. However, their causes, their impact on everyday life, and treatment strategies have not been systematically assessed. Therefore, the aim of this review is to provide a detailed description of behavioral and psychopathological alterations in subjects with dementia during COVID-19 pandemic and the associated management challenges. METHODS: A PubMed search was performed focusing on studies reporting alterations in behavior and mood and treatment strategies for elderly patients with dementia, in accordance with PRISMA guidelines. The following search strategy was utilized: (COVID* OR coronavirus OR "corona vir*" OR SARS-CoV-2) AND (dementia OR demented OR dement* OR alzheimer* OR "pick's disease" OR "lewy body" OR "mild cognitive" OR mild cognitive impairment OR MCI). RESULTS: Apathy, anxiety and agitation are the most frequently NPS during the COVID-19 pandemic and are mainly triggered by protracted isolation. Most treatment strategies rely on pharmacotherapy; technology is increasingly utilized with mixed results. CONCLUSIONS: NPS of dementia during COVID-19 appear to arise from social restrictions occurring as a consequence of the pandemic. Implementation of caregiver support and the presence of skilled nursing home staff are required to restore social interaction and adjust technological support to the patients' needs.

How to communicate with families living in complete isolation.

IMPORTANCE: During the SARS-CoV-2 pandemic, a complete physical isolation has been worldwide introduced. The impossibility of visiting their loved ones during the hospital stay causes additional distress for families: in addition to the worries about clinical recovery, they may feel exclusion and powerlessness, anxiety, depression, mistrust in the care team and post-traumatic stress disorder. The impossibility of conducting the daily meetings with families poses a challenge for healthcare professionals. OBJECTIVE: This paper aims to delineate and share consensus statements in order to enable healthcare team to provide by telephone or video calls an optimal level of communication with patient's relatives under circumstances of complete isolation. EVIDENCE REVIEW: PubMed, Cochrane Database of Systematic Reviews, Database of Abstracts and Reviews of Effectiveness and the AHCPR Clinical Guidelines and Evidence Reports were explored from 1999 to 2019. Exclusion criteria were: poor or absent relevance regarding the aim of the consensus statements, studies prior to 1999, non-English language. Since the present pandemic context is completely new, unexpected and unexplored, there are not randomised controlled trials regarding clinical communication in a setting of complete isolation. Thus, a multiprofessional taskforce of physicians, nurses, psychologists and legal experts, together with some family members and former intensive care unit patients was established by four Italian national scientific societies. Using an e-Delphi methodology, general and specific questions were posed, relevant topics were argumented, until arriving to delineate position statements and practical checklist, which were set and evaluated through an evidence-based consensus procedure. FINDINGS: Ten statements and two practical checklists for phone or video calls were drafted and evaluated; they are related to who, when, why and how family members must be given clinical information under circumstances of complete isolation. CONCLUSIONS AND RELEVANCE: The statements and the checklists offer a structured methodology in order to ensure a good-quality communication between healthcare team and family members even in isolation, confirming that time dedicated to communication has to be intended as a time of care.

Antimicrobial Role of RNASET2 Protein During Innate Immune Response in the Medicinal Leech Hirudo verbana.

The innate immune response represents a first-line defense against pathogen infection that has been widely conserved throughout evolution. Using the invertebrate Hirudo verbana (Annelida, Hirudinea) as an experimental model, we show here that the RNASET2 ribonuclease is directly involved in the immune response against Gram-positive bacteria. Injection of lipoteichoic acid (LTA), a key component of Gram-positive bacteria cell wall, into the leech body wall induced a massive migration of granulocytes and macrophages expressing TLR2 (the key receptor involved in the response to Gram-positive bacteria) toward the challenged/inoculated area. We hypothesized that the endogenous leech RNASET2 protein (HvRNASET2) might be involved in the antimicrobial response, as already described for other vertebrate ribonucleases, such as RNase3 and RNase7. In support of our hypothesis, HvRNASET2 was mainly localized in the granules of granulocytes, and its release in the extracellular matrix triggered the recruitment of macrophages toward the area stimulated with LTA. The activity of HvRNASET2 was also evaluated on Staphylococcus aureus living cells by means of light, transmission, and scanning electron microscopy analysis. HvRNASET2 injection triggered the formation of S. aureus clumps following a direct interaction with the bacterial cell wall, as demonstrated by immunogold assay. Taken together, our data support the notion that, during the early phase of leech immune response, granulocyte-released HvRNASET2 triggers bacterial clumps formation and, at the same time, actively recruits phagocytic macrophages in order to elicit a rapid and effective eradication of the infecting microorganisms from inoculated area.