Candidate Biological Markers for Social Anxiety Disorder: A Systematic Review.

Social anxiety disorder (SAD) is a common psychiatric condition associated with a high risk of psychiatric comorbidity and impaired social/occupational functioning when not promptly treated. The identification of biological markers may facilitate the diagnostic process, leading to an early and proper treatment. Our aim was to systematically review the available literature about potential biomarkers for SAD. A search in the main online repositories (PubMed, ISI Web of Knowledge, PsychInfo, etc.) was performed. Of the 662 records screened, 61 were included. Results concerning cortisol, neuropeptides and inflammatory/immunological/neurotrophic markers remain inconsistent. Preliminary evidence emerged about the role of chromosome 16 and the endomannosidase gene, as well as of epigenetic factors, in increasing vulnerability to SAD. Neuroimaging findings revealed an altered connectivity of different cerebral areas in SAD patients and amygdala activation under social threat. Some parameters such as salivary alpha amylase levels, changes in antioxidant defenses, increased gaze avoidance and QT dispersion seem to be associated with SAD and may represent promising biomarkers of this condition. However, the preliminary positive correlations have been poorly replicated. Further studies on larger samples and investigating the same biomarkers are needed to identify more specific biological markers for SAD.

Which clinical factors and biochemical parameters are associated with late-life major depression?

INTRODUCTION: Late-life major depression (MD) is a frequent and high-cost psychiatric disorder. Our purpose was to detect clinical and biological factors possibly associated with this condition to better prevent and treat it. METHODS: We recruited 343 patients, consecutively admitted for a Major Depressive Episode to the inpatient clinic of Policlinico of Milan and ASST Monza, Italy. A large set of clinical and biochemical variables was collected from clinical charts. Univariate analyses were performed both dividing the sample into two groups (age < or ≥65) and considering age as a continuous quantitative variable. Regression analyses were then performed considering as independent variables only those statistically significant at univariate analyses. RESULTS: Patients aged ≥ 65 resulted in having longer duration of illness, shorter duration of last antidepressant therapy, higher number of antidepressants assumed in the past, higher frequency of treatment-resistant depression, higher frequency of overweight/obesity and diabetes. As for biochemical parameters, patients ≥ 65 showed lower total plasmatic proteins and albumin, higher uric acid and creatinine. CONCLUSIONS: These preliminary results suggest less effectiveness of antidepressants, more susceptibility to metabolic disorders and poor nutritional status in patients with late-life depression; such aspects may consequently be taken into consideration for a proper therapeutic approach. KEY POINTSDepression in late life seems to be associated with poorer response to antidepressants;Clinicians should prefer compounds with minimal pharmacokinetic interactions and less risk of side effects including metabolic ones;The poor nutritional status and the higher risk of metabolic disorders in older patients points out the importance of proper diet and healthy lifestyle in this group of subjects;Further studies are needed to confirm the results of this research.

Psychological well-being and family distress of Italian caregivers during the COVID-19 outbreak.

The present study aimed to investigate the personal well-being and family distress of Italian caregivers during the lockdown. Five hundred sixty-five family caregivers and 638 age- and sex-matched noncaregivers completed a web-based survey. The following scales were administered to all participants: General Health Questionnaire-12 items (GHQ-12), Insomnia Severity Index (ISI), Brief Resilient Coping Scale (BRCS), and Family Distress Index (FDI). Caregivers were also asked to provide information about their family members with disabilities. Individual and family distress, as well as insomnia, were significantly higher in caregivers than controls. Contrariwise, caregivers reported lower resilience levels. Multiple linear regression showed that distress was higher in caregivers living in Central and Southern Italy. Individual well-being was negatively predicted by low independence measured by the activities of daily living (ADL). Family distress was higher in households of psychiatric patients. Finally, low resilience levels appeared as the strongest predictors of both individual and family distress. The lockdown caused severe distress among caregivers and families of people with disabilities. Support networks for people with disabilities and their families are fundamental to prevent severe consequences from a psychological, social, and economical point of view.

Factors Associated with Affective Symptoms and Quality of Life in Patients with Atopic Dermatitis.

The aim of this study was to detect demographic and clinical factors associated with affective symptoms and quality of life in patients with severe atopic dermatitis. First, one-way analyses of variance and correlations were performed to compare a large set of qualitative and quantitative clinical variables. Three final multivariable regression models were performed, with depression/anxiety subscales and Dermatology Life Quality Index scores as dependent variables, and the factors that were statistically significant on univariate analyses as independent ones. More severe anxiety symptoms and poorer quality of life (p < 0.01) were significantly associated with more severe depressive symptoms. Female sex and disturbed sleep (p = 0.03) were significantly associated with more severe anxiety. Finally, previous treatment with cyclosporine (p = 0.03) or methotrexate (p = 0.04), more severe depressive symptoms (p < 0.01), itch (p = 0.03), impaired sleep (p < 0.01) and perceived severity of dermatological illness (p < 0.01) were significant predictors of low quality of life. This study shows a complex interplay between the severity of atopic dermatitis, poor quality of life and presence of clinically relevant affective symptoms. These results will help dermatologists to identify patients who need psychiatric consultation within the framework of a multidisciplinary approach.

Lifetime prevalence of suicidal ideation and suicidal behaviors in gender non-conforming youths: a meta-analysis.

Gender identity represents a topic of growing interest in mental health research. People with non-conforming gender identity are prone to suffer from stigmatization and bullying and often present psychiatric issues, which may in turn lead to a high prevalence of suicidal ideation and behaviors. The present meta-analysis aimed to estimate the prevalence of suicidal ideation and suicidal behaviors in gender non-conforming children, adolescents and young adults. A systematic search was performed in Web of Science and PsycINFO from inception to December 2018. We selected cross-sectional and cohort studies including youths (up to 25 years) with a diagnosis confirmed by a clinician according to international classifications, or after a direct interview with a peer. A random-effects meta-analysis was computed for the following outcomes: non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. Overall, we found a mean prevalence of NSSI of 28.2% (9 studies, 3057 participants, 95% CI 14.8-47.1). A similar prevalence (28%) was found for suicidal ideation (6 studies, 2249 participants, 95% CI 15-46.3), while the prevalence of suicide attempts was 14.8% (5 studies, 1039 participants, 95% CI 7.8-26.3). Subgroup analyses revealed no significant differences according to biological sex. Given the prevalence of suicidal behaviors in gender non-conforming youths, it appears desirable to implement therapeutic and support strategies for this population. Moreover, educational interventions directed to parents, teachers, mental health professionals and general community should be promoted to struggle against stigma and social isolation, factors that may contribute to increasing the risk of suicidal behaviors.

A new approach for seasonal pattern: is it related to bipolarity dimension? Findings from an Italian multicenter study.

OBJECTIVE: The aims of this study were to assess the impact of seasonal pattern on several clinical dimensions in inpatients with a current major depressive episode and to evaluate clinical differences between unipolar and bipolar depression according to seasonal pattern. METHODS: Study participants were 300 patients affected by major depressive disorder (MDD) or bipolar disorder (BD) currently experiencing a major depressive episode (MDE) and were recruited at three University Medical Centres in Italy. All study subjects completed several evaluation scales for depressive and hypomanic symptoms, quality of life and functioning, impulsiveness, and seasonal pattern. RESULTS: Several differences between BD with and without seasonal pattern, MDD with and without seasonal pattern but in particular between BD and MDD with seasonal pattern were found. Patients with MDE with seasonal pattern had more frequently received a longitudinal diagnosis of BD. CONCLUSIONS: A large number of patients with BD and seasonal pattern, but also a considerable number of patients with MDD and seasonal pattern, endorsed manic items during a current MDE. Seasonal pattern should be associated with a concept of bipolarity in mood disorders and not only related to bipolar disorder. A correct identification of seasonal patterns may lead to the implementation of personalised pharmacological treatment approaches.KEY POINTSHigh prevalence of mixed features in mood disorders with seasonal pattern, supporting the need for a dimensional approach to major depressive disorder and bipolar disorder.Significant percentage of patients with a primary diagnosis of major depressive disorder had seasonal pattern.Significant percentage of patients with a primary diagnosis of major depressive disorder reported (hypo)manic symptomatology.

Mood disorders and outcomes in lung cancer patients undergoing surgery: a brief summery.

Cancer is a leading cause of death worldwide. Literature reports depression and anxiety are the most common psychiatric symptoms in cancer patients. Notably, lung cancer is associated with major depressive disorder in 5-13% of cases. The present article aims to give an overview regarding the impact of mood disorders on the outcomes of patients affected by lung cancer. Our review showed that pharmacological treatment and psychotherapy can be useful to improve the quality of life of patients with lung cancer. Moreover, the treatment of depression and anxiety can be associated with a reduced mortality. In conclusion, it is important to consider psychiatric care as important as other adjuvant oncologic therapies in patients with cancer.

Is Pilates effective in improving depressive disorders? A comprehensive overview.

Depressive disorders are disabling conditions that account for high social costs. Pilates demonstrated to have several beneficial effects on health. Objective of this manuscript was to systematically review the literature about the effects of Pilates on depressive disorders. A bibliographic search was conducted in the main database sources (Pubmed, Medline, and Scopus). The inclusion criteria consisted of articles written in English language about the effectiveness of Pilates on depressive symptoms. Most of included studies are randomized controlled trials (10 out of 12). The available literature agrees in indicating that Pilates is effective in improving depressive symptoms especially when compared to inactivity and when this practice is administered for a medium-long period (8-16 weeks). In addition, Pilates seems to have at least comparable effectiveness than aerobic exercise. Pilates can be considered a reliable complementary treatment for people with depressive disorders. These findings should be interpreted considering the different types of practice administered as well as the different duration of the programs or rating scales used to assess mood symptoms. Studies with a more homogenous design are needed to confirm and make generalizable the results presented in this review.

Novel pharmacotherapy targeting the positive symptoms of schizophrenia.

INTRODUCTION: The severity of positive symptoms in schizophrenia is associated with poor prognosis. About one-third of schizophrenia patients partially respond to treatment with available antipsychotics. The purpose of the present manuscript is to provide an updated overview of novel pharmacotherapy targeting positive symptoms in schizophrenia. AREAS COVERED: A comprehensive research on the main database sources (PubMed, PsychINFO, Isi Web of Knowledge, MEDLINE, and EMBASE) was performed to obtain original articles published till 31st January 2023 about new pharmacological strategies for the treatment of positive symptoms in schizophrenia. EXPERT OPINION: The most promising compounds include: lamotrigine, pro-cognitive-compounds (donepezil - in the short term, idazoxan and piracetam) and drugs acting partially or totally outside the Central Nervous System (CNS) (anti-inflammatory drugs: celecoxib, methotrexate; cardiovascular compounds: L-theanine, mononitrate isosorbide, propentofylline, sodium nitroprusside; metabolic regulators: diazoxide, allopurinol; others: bexarotene, raloxifene [in women]). The effectiveness of the latter compounds indicates that other biological systems, such as immunity or metabolism can be object of future research to identify pharmacological targets for positive symptoms of schizophrenia. Mirtazapine could be useful for treating negative symptoms without increasing the risk of a worsening of delusions/hallucinations. Nevertheless, the lack of replication of studies prevents to draw definitive conclusions and future studies are needed to confirm the findings presented in this overview.

Sociodemographic and clinical factors associated with prescription of first- versus second-generation long-acting antipsychotics in incarcerated adult males.

Information on patterns of prescription of long-acting injection (LAI) antipsychotics among people who are incarcerated is lacking. Therefore, we aimed to evaluate prescribing rates for first-generation antipsychotic (FGA)-LAI versus second-generation antipsychotic (SGA)-LAI and to identify the factors associated with the prescription of one of the two classes of LAI. A cross-sectional study was conducted among incarcerated adult males hosted in Monza detention center between January 2013 and April 2023. Socio-demographic and clinical data were retrospectively collected. Descriptive and univariate statistics as well as logistic regression analyses were performed. Data were available for 135 consecutive incarcerated adult males with different mental disorders who received a LAI as part of their treatment. 75.6% of our sample was treated with FGA-LAIs, with haloperidol as the most commonly prescribed drug, followed by zuclopentixol and aripiprazole. Diagnosis of bipolar disorder and concomitant administration of antidepressants were statistically significant predictors of SGA-LAI prescription. Some patients' characteristics may influence prescription patterns in prison. Further longitudinal studies with larger samples should confirm these findings.

Clinical Markers of Panic and Generalized Anxiety Disorder: Overlapping Symptoms, Different Course and Outcome.

Generalized Anxiety Disorder (GAD) and Panic Disorder (PD) share underlying neurobiological mechanisms and several clinical features which, with medical comorbidities, may increase misdiagnosis and delay proper treatment. The aim of the study was to evaluate the association between clinical/socio-demographic markers and GAD/PD diagnosis. Outpatients (N = 290) with PD or GAD were identified in mental health services in Monza and Milan (Italy). Descriptive analyses and a binary logistic regression model were performed. Post-onset psychiatric (p = 0.05) and medical (p = 0.02) multiple co-morbidities were associated with GAD; treatment with selective serotonin reuptake inhibitors (SSRIs) was associated with PD, while GAD diagnosis was associated with treatment with atypical antipsychotics or GABAergic drugs (p = 0.03), as well as psychodynamic psychotherapy (p < 0.01). Discontinuation of the last pharmacological treatment was associated with GAD diagnosis rather than the PD one (p = 0.02). GAD patients may have a worse prognosis than PD patients because of more frequent multiple co-morbidities, relapses and poorer treatment compliance. The different treatment approaches were consistent with the available literature, while the association between GAD and psychodynamic psychotherapy is an original finding of our study. Further studies on larger samples are necessary to better characterize clinical factors associated with GAD or PD.

Air Pollution and Perinatal Mental Health: A Comprehensive Overview.

BACKGROUND: The aim of the present study was to summarise the available data about the link between air pollution exposure and the new-onset and severity of psychiatric disorders in pregnant women during the perinatal period. MATERIALS AND METHODS: We selected articles published until June 2022 on PubMed and the Web of Science. Pollutants included were PM2.5 (particulate matter 2.5 micrometres and smaller), PM10 (particulate matter 10 micrometres and smaller), NO2 (nitrogen dioxide), O3 (ozone), SO2 (sulphur dioxide), CO (carbon monoxide), PBDEs (polybrominated diphenyl ethers), PFAS (per- and polyfluoroalkyl substances), lead, and cadmium. The perinatal period was considered as the time of pregnancy until one year after childbirth. RESULTS: Nine studies were included; most of them evaluated the association between exposure to air pollutants and the onset of Postpartum Depression (PPD). Two studies showed an association between, respectively, only PM2.5 and both PM2.5 and NO2 exposure and PPD onset 12 months after childbirth, while another study found a significant association between NO2 exposure and PPD occurrence 6 months after childbirth. PBDE blood levels were associated with more severe depressive symptoms. Lastly, one study observed a link between stressful symptoms and exposure to PM2.5, PM10 during pregnancy. CONCLUSION: More comprehensive and uniform studies are required to make a roadmap for future interventions, given the growing relevance of issues such pollution and mental health, particularly during the perinatal period.

Are There Any Differences in Clinical and Biochemical Variables between Bipolar Patients with or without Lifetime Psychotic Symptoms?

INTRODUCTION: Psychotic symptoms occur in more than half of patients affected by Bipolar Disorder (BD) and are associated with an unfavorable course of the disorder. The objective of this study is to identify the differences in the clinical and biochemical parameters between bipolar patients with or without psychotic symptoms. METHODS: A total of 665 inpatients were recruited. Demographic, clinical, and biochemical data related to the first day of hospitalization were obtained via a screening of the clinical charts and intranet hospital applications. The two groups identified via the lifetime presence of psychotic symptoms were compared using t tests for quantitative variables and χ2 tests for qualitative ones; binary logistic regression models were subsequently performed. RESULTS: Patients with psychotic BD (compared to non-psychotic ones) showed a longer duration of hospitalization (p < 0.001), higher Young Mania Rating Scale scores (p < 0.001), lower Global Assessment of Functioning scores (p = 0.002), a less frequent history of lifetime suicide attempts (p = 0.019), less achievement of remission during the current hospitalization (p = 0.028), and a higher Neutrophile to Lymphocyte Ratio (NLR) (p = 0.006), but lower total cholesterol (p = 0.018) and triglycerides (p = 0.013). CONCLUSIONS: Patients with psychotic BD have a different clinical and biochemical profile compared to their counterparts, characterized by more clinical severity, fewer metabolic alterations, and a higher grade of inflammation. Further multi-center studies have to confirm the results of this present study.

The Psychological Impact of the COVID-19 Lockdown: A Comparison between Caregivers of Autistic and Non-Autistic Individuals in Italy.

The COVID-19 outbreak has disrupted the daily routine of the population worldwide, including autistic people and their caregivers, with severe consequences on mental health. On one hand, the reduced social contacts and the interruption of outpatient and daycare services during the lockdown have represented a real challenge for autistic people and their caregivers. On the other hand, confinement has allowed individuals to spend more time pursuing their interests and stay home with their family members without feeling the pressure of social expectations. The present study aimed to compare the levels of personal wellbeing, family distress, insomnia, and resilience between caregivers of autistic people and caregivers of people with other neurodevelopmental, psychiatric, or relational disabilities. A web survey was completed by 383 participants, of which 141 were primary caregivers of autistic people. We did not find any significant difference between caregivers of autistic and non-autistic people in any of the considered psychological variables. Lower age of the autistic family member and lower resilience levels were significantly associated with higher individual distress in the group of caregivers of autistic people. Our findings do not corroborate the hypothesis that caregivers of autistic individuals have had more severe consequences than other caregivers during the lockdown. However, they confirm the importance of promoting resilient coping strategies in autistic people and their caregivers.

Gender differences in clinical and biochemical parameters of patients consecutively hospitalized for unipolar depression.

Major Depressive Disorder (MDD) is a medical illness twice as common in women than in men lifetime. Purpose of this study is to identify gender differences in clinical and biochemical parameters in subjects affected by MDD to implement individualized treatment strategies. We recruited 234 patients (112 males and 122 females) consecutively hospitalized for MDD in Milan (Italy). Data were obtained through a screening of the clinical charts and blood analyses. Univariate analyses, binary logistic regressions and a final logistic regression model were performed. The final logistic regression model showed that female patients (compared to males) had lower plasmatic levels of hemoglobin (p = 0.020) and uric acid (p = 0.002), higher levels of cholesterol (p < 0.001), had been treated with a lower number of antidepressants (p = 0.011), presented lower red blood cells (p < 0.001) and showed more frequently comorbidity with hypothyroidism (p = 0.036). Univariate analyses identified also that women had an earlier age at onset (p = 0.043), were less likely to have comorbidity with diabetes (p = 0.002) and were less frequently treated with a psychiatric polytherapy (p < 0.001). Finally, female patients had achieved more frequently remission in the last depressive episode (p = 0.001) and were more likely to have family history for psychiatric disorders (p < 0.001) than males. Female patients globally have a better response to treatments, but they seem to be more vulnerable to specific metabolic abnormalities as showed by more frequent hypercholesterolemia and lower plasma levels of uric acid. These results have to be confirmed by further studies.

Which Clinical and Biochemical Parameters Are Associated with Lifetime Suicide Attempts in Bipolar Disorder?

INTRODUCTION: Bipolar Disorder (BD) is a disabling condition with suicidal behavior as one of the most common adverse outcomes. The purpose of the present research is to investigate the relationship between lifetime suicide attempts and the clinical factors/biochemical parameters in a large sample of bipolar patients. METHODS: A total of 561 patients, consecutively hospitalized for BD in Milan and Monza (Italy), were recruited. Data about the demographic and clinical variables, as well as the values of blood analyses, were collected. The groups identified according to the presence/absence of lifetime suicide attempts were compared using univariate analyses. Then, three preliminary binary logistic regressions and a final logistic regression model were performed to identify the clinical and biochemical parameters associated with lifetime suicide attempts in BD. RESULTS: Lifetime suicide attempts in BD were predicted by a longer duration of untreated illness (DUI) (p = 0.005), absence of lifetime psychotic symptoms (p = 0.025), presence of poly-substance use disorders (p = 0.033), comorbidity with obesity (p = 0.022), a last mood episode of manic polarity (p = 0.044), and lower bilirubin serum levels (p = 0.002); higher total cholesterol serum levels showed a trend toward statistical significance (p = 0.058). CONCLUSIONS: BD patients with lifetime suicide attempts present unfavorable clinical features. Some specific biochemical characteristics of bipolar patients may represent potential markers of suicidal behavior and need to be better investigated to identify new targets of treatment in the framework of personalized medicine. These preliminary findings have to be confirmed by further studies in different clinical settings.

Clinical and Biological Factors Are Associated with Treatment-Resistant Depression.

BACKGROUND: Treatment-resistant depression (TRD) is a debilitating condition associated with unmet clinical needs. Few studies have explored clinical characteristics and serum biomarkers associated with TRD. AIMS: We investigated whether there were differences in clinical and biochemical variables between patients affected by TRD than those without. METHODS: We recruited 343 patients (165 males and 178 females) consecutively hospitalized for MDD to the inpatient clinics affiliated to the Fondazione IRCCS Policlinico, Milan, Italy (n = 234), and ASST Monza, Italy (n = 109). Data were obtained through a screening of the clinical charts and blood analyses conducted during the hospitalization. RESULTS: TRD versus non-TRD patients resulted to be older (p = 0.001), to have a longer duration of illness (p < 0.001), to be more currently treated with a psychiatric poly-therapy (p < 0.001), to have currently more severe depressive symptoms as showed by the Hamilton Depression Rating Scale (HAM-D) scores (p = 0.016), to have lower bilirubin plasma levels (p < 0.001). In addition, more lifetime suicide attempts (p = 0.035), more antidepressant treatments before the current episode (p < 0.001), and a lower neutrophil to lymphocyte ratio at borderline statistically significant level (p = 0.060) were all associated with the TRD group. CONCLUSION: We identified candidate biomarkers associated with TRD such as bilirubin plasma levels and NLR, to be confirmed by further studies. Moreover, TRD seems to be associated with unfavorable clinical factors such as a predisposition to suicidal behaviors. Future research should replicate these results to provide robust data in support of the identification of new targets of treatment and implementation of prevention strategies for TRD.

The effect of adjunctive nutraceuticals in bipolar disorder: A systematic review of randomized placebo-controlled trials.

BACKGROUND: Nutraceuticals are a group of compounds of growing interest for mental health professionals. Given the implication of certain nutrients in the onset of bipolar disorder, it has been hypothesized that nutraceuticals might be effective in improving symptoms of the condition (i.e. mania or depression). Our systematic review aimed to evaluate the effectiveness of adjunctive nutraceuticals compared to placebo. METHODS: We searched the following databases from inception to February 2019: Web of Science, CINAHL, Embase, and PsycINFO. We included only original randomized controlled trials written in English, testing the efficacy of nutraceuticals in add-on to standard care, compared to placebo, in patients with bipolar disorder. RESULTS: After identifying 6584 potentially relevant publications, we finally included 25 studies, among which six used fatty acids, seven micronutrients, seven amino acids. One study tested probiotics, while in four trials a combination of different types of nutraceuticals was used. Even if some compounds have shown promising results (i.e. fatty acids and N-acetyl cysteine for depression, amino acid drinks and folic acid for mania), the majority of nutraceuticals did not cause significant improvements in comparison to placebo. LIMITATIONS: We could not perform a meta-analysis due to the high heterogeneity of trials, which were also affected by some methodological caveats. CONCLUSIONS: Evidence regarding the efficacy of adjunctive nutraceuticals in bipolar disorder is inconsistent. Nevertheless, they appear generally free from relevant side effects. Well-designed trials are needed to further explore the potential role of nutraceuticals in different mood episodes.