Substance use disorders in adults with attention-deficit/hyperactivity disorder: The role of affective temperament.

OBJECTIVE: Substance Use Disorders (SUD) are common in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Although predictors of SUD in this population are relevant for prevention and treatment, they need further clarification. Affective temperaments potentially associated with SUD in adult ADHD patients were explored. METHODS: ADHD patients with and without SUD were compared for sociodemographic, clinical, and psychological characteristics through: Adult ADHD Self-Report Scale; Wender Utah Rating Scale; Temperament Evaluation Memphis for Pisa, Paris, and San Diego-Autoquestionnaire. Logistic regression investigated factors associated with SUD. RESULTS: We included one-hundred and thirty-six ADHD patients with (n = 51, 37.5 %) and without SUD (n = 85, 62.5 %). The presence of SUD was associated with irritable temperament (p = 0.009), as well as more frequent school failure (p = 0.038), legal problems (p = 0.039), and lifetime suicide attempts (p = 0.014). LIMITATIONS: The cross-sectional design, the relatively small sample size, and the use of self-administered questionnaires. CONCLUSIONS: This study confirms the greater overall severity of adult ADHD-SUD compared with ADHD-only patients and suggests the potential role of irritable temperament as a predictor of substance-related problems.

Anxious distress in people with major depressive episodes: a cross-sectional analysis of clinical correlates.

OBJECTIVE: Most people with major depressive episodes meet the criteria for the anxious distress (AD) specifier defined by DSM-5 as the presence of symptoms such as feelings of tension, restlessness, difficulty concentrating, and fear that something awful may happen. This cross-sectional study was aimed at identifying clinical correlates of AD in people with unipolar or bipolar depression. METHODS: Inpatients with a current major depressive episode were included. Data on socio-demographic and clinical variables were collected. The SCID-5 was used to diagnose depressive episodes and relevant specifiers. The Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were used to assess the severity of depressive and manic (mixed) symptoms, respectively. Multiple logistic regression analyses were carried out to identify clinical correlates of AD. RESULTS: We included 206 people (mean age: 48.4 ± 18.6 yrs.; males: 38.8%) admitted for a major depressive episode (155 with major depressive disorder and 51 with bipolar disorder). Around two-thirds of the sample (N = 137; 66.5%) had AD. Multiple logistic regression models showed that AD was associated with mixed features, higher YMRS scores, psychotic features, and a diagnosis of major depressive disorder (p < 0.05). CONCLUSION: Despite some limitations, including the cross-sectional design and the inpatient setting, our study shows that AD is likely to be associated with mixed and psychotic features, as well as with unipolar depression. The identification of these clinical domains may help clinicians to better contextualize AD in the context of major depressive episodes.

Clinical correlates of comorbid attention deficit hyperactivity disorder in adults suffering from bipolar disorder: A meta-analysis.

OBJECTIVE: Attention deficit hyperactivity disorder is a frequent comorbid condition in adults with bipolar disorder. We performed a meta-analysis aimed at assessing sociodemographic and clinical correlates of attention deficit hyperactivity disorder in bipolar disorder. METHOD: We searched main electronic databases up to June 2021. Random-effects meta-analyses, with relevant meta-regression and quality-based sensitivity analyses, were carried out to estimate the association between attention deficit hyperactivity disorder and putative correlates, grading the quality of evidence. RESULTS: We included 43 studies, based on 38 independent samples. Attention deficit hyperactivity disorder participants were more likely to be males (odds ratio = 1.46; p < 0.001) and unemployed (odds ratio = 1.45; p = 0.045), and less likely to be married (odds ratio = 0.62; p = 0.014). They had an earlier onset of bipolar disorder (standardized mean difference = -0.36; p < 0.001); more mood episodes (standardized mean difference = 0.35; p = 0.007), particularly depressive (standardized mean difference = 0.30; p = 0.011) and mixed (standardized mean difference = 0.30; p = 0.031) ones; higher odds of using antidepressants (odds ratio = 1.80; p = 0.024) and attempted suicides (odds ratio = 1.83; p < 0.001) and lower odds of psychotic features (odds ratio = 0.63; p = 0.010). Moreover, they were more likely to have generalized anxiety disorder (odds ratio = 1.50; p = 0.019), panic disorder (odds ratio = 1.89; p < 0.001), social phobia (odds ratio = 1.61; p = 0.017), eating disorders (odds ratio = 1.91; p = 0.007), antisocial personality disorder (odds ratio = 3.59; p = 0.004) and substance (odds ratio = 2.29; p < 0.001) or alcohol (odds ratio = 2.28; p < 0.001) use disorders. Quality of the evidence was generally low or very low for the majority of correlates, except for bipolar disorder onset and alcohol/substance use disorders (high), and suicide attempts (moderate). CONCLUSION: Comorbid bipolar disorder/attention deficit hyperactivity disorder may have some distinctive clinical features including an earlier onset of bipolar disorder and higher comorbid alcohol/substance use disorder rates. Further research is needed to identify additional clinical characteristics of this comorbidity.

Effect of long-acting injectable antipsychotics on 1-year hospitalization in bipolar disorder: a mirror-image study.

Long-acting injectable (LAI) antipsychotics are often used for the long-term management also of bipolar disorder (BD). Nonetheless, evidence on their effect on pragmatic outcomes such as hospitalization risk in BD is inconsistent. We carried out a mirror-image study comparing rates and number of days of hospitalization, one year before and after the initiation of LAI treatment, in a sample of subjects with BD. Participants were selected from the STAR Network Depot Study, a pragmatic, observational, multicenter research involving a cohort of inpatients and outpatients consecutively started on LAI treatment. Variations in rates and in total number of days of hospitalization between the 12 months before and those after treatment initiation were analyzed. Among 461 individuals screened for eligibility, we included 71 adults with BD, initiated either on first- (FGA) or second-generation (SGA) LAIs. We found a significant decrease in terms of 12-month hospitalization rates (p < 0.001) and number of days (p < 0.001) after LAI initiation, without any effect by age, gender, alcohol/substance use disorders, and symptom severity. Subgroup analyses based on antipsychotic class, history of LAI treatment, and concomitant oral medications, confirmed the decreasing trend on both hospitalization rates and number of days. However, these reductions were not significant among participants who continued this treatment for less than 6 months. Comprehensively, this study supports the role of LAIs as effective maintenance treatment options for BD. Further research is needed to identify clinical characteristics of people with BD who would most benefit from long-acting formulations of antipsychotics.

The association of kynurenine pathway metabolites with symptom severity and clinical features of bipolar disorder: An overview.

BACKGROUND: The balance between neurotoxic and neuroprotective effects of kynurenine pathway (KP) components has been recently proposed as a key element in the pathophysiology of bipolar disorder (BD) and related mood episodes. This comprehensive overview explored the link of KP with symptom severity and other clinical features of BD. METHODS: We searched Medline, Embase, and PsycInfo electronic databases for studies assessing the association of peripheral and/or central concentrations of KP metabolites with putative clinical features, including symptom severity and other clinical domains in BD. RESULTS: We included the findings of 13 observational studies investigating the possible variations of KP metabolites according to symptom severity, psychotic features, suicidal behaviors, and sleep disturbances in BD. Studies testing the relationship between KP metabolites and depression severity generated mixed and inconsistent findings. No statistically significant correlations with manic symptoms were found. Moreover, heterogeneous variations of the KP across different clinical domains were shown. Few available studies found (a) higher levels of cerebrospinal fluid kynurenic acid and lower of plasma quinolinic acid in BD with psychotic features, (b) lower central and peripheral picolinic acid levels in BD with suicide attempts, and (c) no significant correlations between KP metabolites and BD-related sleep disturbances. CONCLUSIONS: An imbalance of KP metabolism toward the neurotoxic branches is likely to occur in people with BD, though evidence on variations according to specific clinical features of BD is less clear. Additional research is needed to clarify the role of KP in the etiopathogenesis of BD and related clinical features.

Testing the Impact of Depressive and Anxiety Features on the Association between Attention-Deficit/Hyperactivity Disorder Symptoms and Academic Performance among University Students: A Mediation Analysis.

Attention deficit/hyperactivity disorder (ADHD) is associated with poor academic performance also among university students. This relationship may be made more complex by comorbid conditions. The aim of this study was to evaluate the mediating role of anxiety and depressive symptoms in the relationship between ADHD and academic performance. Data were drawn from the CAMPUS study (registration number: 0058642/21), an ongoing survey on university students' mental health. Using a logit model, mediation analyses were carried out to test whether the relationship between ADHD symptoms (assessed by ASRS-5) and academic performance might be mediated by depressive (assessed by PHQ-9) and anxiety (assessed by GAD-7) symptoms. Our results showed that worse academic performance is associated with ADHD symptoms (p < 0.001). However, about 24% of the overall association between ADHD symptoms and academic performance was mediated by depressive symptoms (indirect effect: 0.065, 95%CI 0.022; 0.100), whereas the contribution of anxiety symptoms to the model was not significant. Along with the association between ADHD symptoms and poor academic performance, our findings highlight the key mediating role of depressive symptoms, which may be targeted with tailored support, ultimately improving both the academic performance and the well-being of university students with ADHD.

Comparing 1-year effectiveness and acceptability of once-monthly paliperidone palmitate and aripiprazole monohydrate for schizophrenia spectrum disorders: Findings from the STAR Network Depot Study.

In this prospective study, we assessed the effectiveness and acceptability of paliperidone palmitate 1-month (PP1M) and aripiprazole monohydrate (AM) over 1-year follow-up. We included 195 subjects (117 treated with PP1M and 78 with AM) with schizophrenia spectrum disorders from real-world settings. We estimated no differences in hospitalization (Odds Ratio=1.59; p = 0.12), symptoms improvement (p = 0.90 adjusted for baseline severity), and discontinuation (Hazard Ratio=0.72; p = 0.20) at study endpoint. Although current evidence suggests the possible superiority of AM over PP1M, our findings showed comparable effectiveness between these drugs. Additional studies in real-world settings with direct comparisons between these two LAIs are needed.

The Impact of the COVID-19 Pandemic on Postpartum Maternal Mental Health.

OBJECTIVES: There are reports of mental health worsening during the COVID-19 pandemic. We aimed to assess whether this occurred in women who were pregnant at baseline (late 2019) and unaware of the pandemic, and who delivered after the implementation of COVID-19 restrictions and threat (March-April 2020). To compare the pandemic period with the pre-pandemic, we capitalized on a retrospective 2014-2015 perinatal sample which had had affective symptoms assessed. METHODS: The COVID sample were administered the Postnatal Depression Scale (EPDS), Zung Self-Rating Anxiety Scale (SAS), Hypomania Checklist-32 (HCL-32), Pittsburgh Sleep Quality Index (PSQI), and Perceived Stress Scale (PSS) at T0 (pregnancy) and T1 (post-delivery). The Non-COVID sample had completed EPDS and HCL-32 at the same timepoints. RESULTS: The COVID sample included 72 women, aged 21-46 years (mean = 33.25 years ± 4.69), and the Non-COVID sample included 68 perinatal women, aged 21-46 years (mean = 34.01 years ± 4.68). Our study showed greater levels of mild depression in T1 among the COVID sample compared to the Non-COVID sample. No significant differences in terms of major depression and suicidal ideation were found. The levels of hypomania were significantly different between the two groups at T1, with the COVID sample scoring higher than the Non-COVID sample. This may be related to the high levels of perceived stress we found during the postpartum evaluation in the COVID sample. LIMITATIONS: There was a relatively small sample size. CONCLUSIONS: New mothers responded to the pandemic with less mental health impairment than expected, differently from the general population. Women delivering amidst the pandemic did not differ in depressive and anxiety symptoms from their pre-pandemic scores and from pre-pandemic women. Because stress responses have high energy costs, it is optimal for maternal animals to minimize such high metabolic costs during motherhood. Evidence suggests that reproductive experience alters the female brain in adaptive ways. This maternal brain plasticity facilitates a higher purpose, the continuation of the species. This may point to the recruitment of motherhood-related resources, for potentially overcoming the effects of the pandemic on mental health.

The Relevance of Insomnia in the Diagnosis of Perinatal Depression: Validation of the Italian Version of the Insomnia Symptom Questionnaire.

BACKGROUND: Sleep disorders are common in perinatal women and may underlie or trigger anxiety and depression. We aimed to translate and validate and evaluate the psychometric properties of the Italian version of the Insomnia Symptom Questionnaire (ISQ), in a sample of women during late pregnancy and 6-months postpartum according to the DSM-5 criteria. METHODS: The ISQ was administered to 292 women prenatally along with other measures of sleep quality, depression, and anxiety, to examine its construct and convergent validity. Women were readministered the ISQ six months postdelivery to assess test-retest reliability. Women were divided into DSM-5 No-Insomnia (N = 253) and Insomnia (N = 39) groups. RESULTS: The insomnia group had received more psychopharmacotherapy, had more psychiatric family history, increased rates of medically assisted reproduction, of past perinatal psychiatric disorders, and scored higher on almost all TEMPS-A dimensions, on the EPDS, HCL-32, PSQI, and on ISQ prenatally and postnatally. ISQ scores correlated with all scales, indicating adequate convergent and discriminant validity; furthermore, it showed antenatal-postnatal test-retest reliability, 97.5% diagnostic accuracy, 79.5% sensitivity, 94.9% specificity, 70.5% positive predictive power, and 92.8% negative predictive power. CONCLUSIONS: The ISQ is useful, valid, and reliable for assessing perinatal insomnia in Italian women. The Italian version showed equivalent properties to the original version.

Some of us are most at risk: Systematic review and meta-analysis of correlates of depressive symptoms among healthcare workers during the SARS-CoV-2 outbreak.

The COVID-19 pandemic has had a severe psychosocial impact on healthcare workers (HCWs). This systematic review and meta-analysis aimed at evaluating the association between individual features and depressive symptoms reported by HCWs during the pandemic. We searched Medline, Embase, and PsycInfo up to 23 June 2020. We included cross-sectional studies testing the association between individual correlates and depressive symptoms in HCWs during the SARS-CoV-2 outbreak. Fourteen studies met inclusion criteria, involving 14,173 HCWs (3,070 with depressive symptoms). Women (OR = 1.50; 95 %CI: 1.28-1.76; I2 = 40.0 %), individuals with suspected/confirmed COVID-19 (OR = 2.10; 95 %CI: 1.64-2.69; I2 = 0 %), and those with an infected family member or friend (OR = 1.67; 95 %CI: 1.37-2.04; I2 = 0%) were more likely to report depressive features, which, instead, were less frequent among doctors (compared with nurses) (OR = 0.80; 95 %CI: 0.66-0.98; I2 = 48.2 %) and HCWs who felt adequately protected (OR = 0.48; 95 %CI: 0.32-0.72; I2 = 36.3 %). Our study provided timely evidence on the correlates of depressive symptoms among HCWs during the pandemic. Early screening is crucial to develop tailored health interventions, redesigning the response to COVID-19.

Disentangling the Association between ADHD and Alcohol Use Disorder in Individuals Suffering from Bipolar Disorder: A Systematic Review and Meta-Analysis.

Attention Deficit-Hyperactivity disorder (ADHD) may influence rates of Alcohol Use Disorder (AUD) among individuals suffering from Bipolar Disorder (BD). The aim of this systematic review and meta-analysis was to estimate the strength and consistency of the potential association between ADHD and AUD in BD. We searched main electronic databases for studies indexed up to November 2020. We included observational studies investigating the association between ADHD and AUD among individuals with BD. The association between ADHD and AUD was estimated using odds ratios (ORs) with 95% Confidence Intervals (CIs). Eleven studies, involving 2734 individuals with BD (516 with ADHD), were included in the meta-analysis. Individuals with both BD and ADHD had higher rates of AUD as compared with subjects with BD only (34.0% vs. 18.3%). The estimated OR of AUD for ADHD was 2.50 (95% CI: 1.91 to 3.27; I2 = 13.0%). Study-level characteristics did not influence the effect size. No risk of publication bias was estimated. Despite some limitations, this meta-analysis estimated an association between ADHD and AUD among individuals suffering from BD. At least a portion of the high rates of AUD in BD may, thereby, be related to comorbid ADHD. Longitudinal studies are needed to clarify the nature of this relationship.

Treatment of CSF leakage and infections of dural substitute in decompressive craniectomy using fascia lata implants and related anatomopathological findings.

PURPOSE: Decompressive craniectomy (DC) is widely used to treat raised intracranial pressure (ICP) in cranial trauma and stroke. It is accompanied by numerous complications. The aim of our study is to assess the surgical treatment of infections related to the use of a dural substitute with concurrent CSF leakage performed at our institution. MATERIAL AND METHODS: A retrospective analysis of a series of 72 patients who underwent DC between 2011 and 2017 was performed. Seven cases (9%) showed infection related to the use of xenograft (bovine pericardium) and coexisting CSF leakage. Epidural/subdural empyemas were observed in seven cases; three in conjunction with an intracerebral abscess. For reconstruction, free anterolateral thigh fascia lata flaps were used, based on the size of the defect. RESULTS: After removal of the dural substitute and the implant of free fascia lata, infection and CSF leaks resolved in all. An anatomopathological examination of the implant at the later time of cranioplasty (CP) showed the tissue had become vascularized exhibiting integration with the native dura. No complications related to the harvesting of the fascia lata were observed. CONCLUSIONS: Fascia lata is a validated source of autologous grafts; it is cost-free and would appear to be the biological material most similar to the dura mater. The implanted material appears to maintain a lasting vitality when covered over with a well-vascularized scalp, even after a period of months, achieving a successful suppression of infection. Subsequent skull reconstruction is performed safely and easily using artificial bone.

The kynurenine pathway in bipolar disorder: a meta-analysis on the peripheral blood levels of tryptophan and related metabolites.

Growing evidence suggests that a dysregulation of the kynurenine pathway (KP) occurs in bipolar disorder (BD). This systematic review and meta-analysis aimed at assessing the possible differences in peripheral blood levels of KP metabolites between individuals with BD and healthy controls. We searched Medline, Embase, and PsycInfo electronic databases for articles indexed up to February 2020. We included any observational study comparing the peripheral blood levels of at least one KP metabolite between adults with BD and healthy controls. Random-effects meta-analyses were carried out generating pooled standardized mean differences (SMDs). Heterogeneity between studies was estimated using the I2 index. Meta-regression and sensitivity analyses were conducted. Sixteen studies met inclusion criteria and were included in our study. Meta-analyses showed that individuals with BD have lower peripheral blood levels of tryptophan (SMD = -0.29), kynurenine (SMD = -0.28), kynurenic acid (SMD = -0.30), and xanthurenic acid (SMD = -0.55), along with lower kynurenic acid to kynurenine (SMD = -0.60) and kynurenic acid to quinolinic acid (SMD = -0.37) ratios, than healthy controls. Individuals with a manic episode showed the greatest reductions in tryptophan levels (SMD = -0.51), whereas kynurenic acid levels were more reduced among subjects in a depressive phase (SMD = -0.70). Meta-regression and sensitivity analyses confirmed our results. The findings of the present meta-analysis support the hypothesis of an abnormality of the KP in BD. Considering the partial inconsistency of the findings and the small-to-medium magnitude of the estimated effect sizes, additional research assessing possible mediators or confounders is needed.

Pre-Discharge Predictors of 1-Year Rehospitalization in Adolescents and Young Adults with Severe Mental Disorders: A Retrospective Cohort Study.

Background and objectives: Readmissions of youths hospitalized for a severe mental disorder are common events and bear a remarkable human, social, and economic burden. The current study aimed at evaluating predictors of 1-year rehospitalization in a sample of adolescents and young adults with severe mental disorders. Materials and Methods: Data for ≤25-year-old inpatients with a severe mental disorder and consecutively admitted between 1 January 2016 and 30 June 2019 were collected. Subjects were retrospectively assessed over a follow-up period of one year after the index discharge to track readmissions-i.e., the primary outcome variable. Standard descriptive statistics were used. The association between variables and 1-year rehospitalization was estimated using the univariate Cox proportional hazards regression model. We then carried out a multivariable Cox regression model, also estimating the covariate-adjusted survivor function. Hazard ratios (HRs) with related 95% confidence intervals (95% CIs) were provided. Results: The final sample included 125 individuals. The multivariable Cox regression model estimated that co-occurring substance use disorders (HR = 2.14; 95% CI: 1.08 to 4.26; p = 0.029) and being admitted for a suicide attempt (HR = 2.49; 95% CI: 1.13 to 5.49; p = 0.024) were both significant predictors of 1-year rehospitalization. Conclusions: Our study showed that comorbid substance use disorders and being admitted for a suicide attempt were predictors of early readmission in youths with severe mental disorders. Although their generalizability is limited, our findings could contribute to improve the quality of young patients' mental health care by identifying vulnerable subjects who may benefit from tailored interventions to prevent rehospitalizations.

How is stereotactic brain biopsy evolving? A multicentric analysis of a series of 421 cases treated in Rome over the last sixteen years.

OBJECTIVE: In recent decades, frame-based (FBB) and frame-less stereotactic brain biopsy (FLB) have played a crucial role in defining the diagnosis and management of expanding intracranial lesions in critical areas. During the same period, there have been significant advances in diagnostic imaging, a shift in surgical strategies towards extensive resection in gliomas and new molecular classification of brain tumors. Taking these advances into account, we have evaluated whether significant changes have occurred over the last sixteen years of our clinical practice in terms of frequency, indications, target selection, and the histologic results of stereotactic brain biopsy (SBB) procedures. PATIENTS AND METHODS: We analyzed a series of 421 SBB cases treated between January 2002 and June 2017 in three major neurosurgical institutes in Rome, serving a total of 1.5 million people. Within this series, 94.8% of patients underwent FBB, while, more recently, FLB was performed in 5.2% of cases. The entire period under consideration, running from 2002 to 2017, has been further stratified into four-year time-frames (2002-2005, 2006-2009, 2010-2013, 2014-2017) for the purpose of analysis. RESULTS: The diagnostic yield was 97%. Final diagnoses revealed tumors in 90% of cases and non-neoplastic masses in 7%, while 3% of cases were not conclusive. The morbidity rate was 3% (12 cases) and mortality was 0.7% (3 cases). Intra-operative frozen sections were made in 78% of biopsies. In our three institutes, the number of SBBs decreased steadily throughout the time-frames under consideration. We have also observed a statistically significant reduction in biopsy procedures in lobar lesions, while those performed on the basal ganglia increased and the number of SBBs of multiple masses and lesions of the corpus callosum remained stable. Primary central nervous system diagnosis of lymphomas (PCNSL) was the sole diagnosis whose incidence increased significantly. CONCLUSIONS: Over the last sixteen years, we have witnessed a significant decrease in SBB procedures and a modification in target selection and histologic results. Despite the significant evolution of neuroimaging, an accurate non-invasive diagnosis of intracranial expanding lesions has not yet been achieved. Furthermore, the most recent WHO classification of brain tumors (2016), which incorporates molecular and morphological features, has boosted the need for molecular processing of tissue samples in all expanding brain lesions. For these reasons, it is likely that SBBs will continue to be performed in specific cases, playing a significant role in diagnostic confirmation by providing tissue samples, so as to better assess the biology and the prognosis of cerebral lesions, as well as their sensitivity to standard radio-chemotherapy or to new molecular target therapies.