Gender differences in clinical and biochemical parameters among patients hospitalized for schizophrenia: towards precision medicine.

BACKGROUND: The scientific literature shows some gender differences in the clinical course of schizophrenia. The aim of this study is to identify gender differences in clinical and biochemical parameters in subjects affected by schizophrenia. This would allow for the implementation of individualized treatment strategies. METHODS: We examined a large set of clinical and biochemical parameters. Data were obtained from clinical charts and blood analyses from a sample of 555 schizophrenia patients consecutively admitted for exacerbation of symptoms to the inpatient clinic of Fondazione IRCCS Policlinico (Milan) or ASST Monza in Italy from 2008 to 2021. Univariate analyses, binary logistic regression, and a final logistic regression model were performed with gender as dependent variable. RESULTS: The final logistic regression models showed that male patients (compared to females) were more prone to lifetime substance use disorders (p = 0.010). However, they also had higher GAF (global functioning) mean scores (p < 0.001) at the time of hospitalization. Univariate analyses showed that male patients (with respect to females) had an earlier age at onset (p < 0.001), a more frequent family history of multiple psychiatric disorders (p = 0.045), were more often smokers (p < 0.001), had a more frequent comorbidity with at least one psychiatric disorder (p = 0.001), and less often suffered from hypothyroidism (p = 0.011). In addition, men had higher levels of albumin (p < 0.001) and bilirubin (t = 2.139, p = 0.033), but lower levels of total cholesterol (t = 3.755, p < 0.001). CONCLUSIONS: Our analyses indicate a less severe clinical profile in female patients. This is evident especially in the early years of the disorder, as suggested by less comorbidity with psychiatric disorders or later age at onset; this is consistent with the related literature. In contrast, female patients seem to be more vulnerable to metabolic alterations as demonstrated by more frequent hypercholesterolemia and thyroid dysfunction. Further studies are needed to confirm these results in the framework of precision medicine.

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.

Which Clinical and Demographic Factors are Related to Incarceration in Male Patients With Antisocial Personality Disorder?

Antisocial Personality Disorder (APD) is a condition largely represented in detention centers where can reach a prevalence of 60% in male prisoners. The objective of this study is to identify the clinical and demographic factors that differentiate subjects with APD and hosted in penitentiary with respect to those are treated in outpatient psychiatric clinics. We recruited 65 male patients affected by APD, whose 26 were followed up in community mental health services and 39 were serving their sentence in a detention center located in Monza. Socio-demographic and clinical data were obtained through a review of the clinical charts, and interviews with patients or their relatives (if available). We performed descriptive analyses on the total sample, then we compared the two groups identified by the type of setting (outpatient clinic vs. penitentiary) by independent sample t tests (quantitative variables) or χ2 tests (qualitative ones). For qualitative variables odds ratios (ORs) were also calculated. Outpatients with APD (with respect to those hosted in the detention center) resulted: to be older (p = .02), to be less likely married (p = .01), to have more pre-onset psychiatric comorbidity (p = .05), to have more pre-onset substance poly-misuse (p = .01), to have more previous psychiatric hospitalizations (p < .01), and to be less likely to have received lifetime psychotherapy (p < .01). Globally, the results of this study show how the presence of psychiatric comorbidity or substance abuse (with the probable access to psychiatric services) before the onset of APD prevents imprisonment. This aspect is even more surprising when we consider that the two groups of patients show no differences in the frequency of crimes. Future research will have to confirm if early mental health care can really limit the access to penitentiary of subjects affected by APD.

High Rate of Discontinuation during Long-Acting Injectable Antipsychotic Treatment in Patients with Psychotic Disorders.

Treatment discontinuation is a major challenge in routine clinical settings. Despite poor adherence to antipsychotic medication, long acting injectable (LAI) formulations are an underutilized option in psychotic disorders. Recently, an earlier and broader use of LAIs has been emphasized. However, few studies have evaluated the factors associated with LAI antipsychotic discontinuation in ordinary clinical practice. The main purpose of the present study was, therefore, to identify the factors associated with LAI discontinuation in a real-world setting. Patients in treatment with LAI antipsychotics were recruited. A Cox regression analysis was applied considering a 12-month follow-up period. Moreover, a Kaplan-Meier survival analysis was applied to compare the single treatment LAI antipsychotic groups in terms of time to discontinuation. Our analysis showed an LAI discontinuation rate at 12 months, corresponding to 28.8%, with olanzapine and aripiprazole having a longer time to discontinuation compared to zuclopenthixol. The results of the present study can help clinicians with their choice of LAI antipsychotic according to patients' characteristics and in a context of precision medicine. Increasing knowledge about factors affecting discontinuation of LAI antipsychotics can improve the prescribing practices of these compounds. Individualized approaches may ameliorate long-term patients' treatment adherence, thus preventing the long-term disability caused by psychotic disorders.

Which factors are associated with duration of untreated illness in borderline personality disorder?

AIM: Borderline personality disorder (BPD) is a prevalent condition associated with high rates of hospitalizations. The purpose of this manuscript was to detect the factors associated with duration of untreated illness (DUI) in BPD. METHODS: Through chart review, we identified 152 patients followed up by community psychiatry services in Milan and Monza, Italy. The association between DUI and socioeconomic and clinical variables was examined using Pearson correlation and analyses of variances. The statistically significant variables from univariate analyses were then inserted in regression models. RESULTS: A longer DUI was associated with several variables (substance misuse after the onset of BPD, older age, earlier age at onset, longer duration of illness), but these results were not maintained in the regression analyses. CONCLUSIONS: In conclusion, DUI does not seem to be significantly associated with specific clinical aspects of BPD, or significantly modify the course and outcome of the disorder. Studies with larger samples have to confirm these preliminary findings.

Malondialdehyde as a candidate biomarker for bipolar disorder: A meta-analysis.

Malondialdehyde (MDA) represents one of the final products of lipid peroxidation that is thought to be enhanced and accelerated in patients affected by bipolar disorder (BD). Purpose of the present article is to critically summarize the available data about MDA as a candidate biomarker for BD. First, we carried out a systematic review of the literature selecting those papers that evaluated MDA levels in BD. Then, we performed two separate meta-analyses: one of the studies that compared healthy controls (HC) with unmedicated BD and one with the studies that assessed MDA levels before and after treatment in BD, showing that bipolar patients experience more oxidative stress than healthy subjects and that treatment is effective in reducing MDA levels. In the first set of studies, we also explored through a meta-regression whether age, gender and experiencing an episode specifically influenced the difference between BD and HC in MDA levels. Bipolar patients compared to healthy subjects had higher MDA levels (SMD: 0.94, 95% CI: 0.23-1.64). Age (p < 0.01), gender (p < 0.01) and the presence of a current mood episode (p < 0.01) significantly influenced MDA plasma/serum levels. Specifically, studies that included more female, older subjects and more BD in euthymia were more likely to have higher MDA levels. Finally, patients after treatment had lower levels of MDA compared to baseline (SMD: -0.52, 95% CI: -0.85 -0.19). More studies are needed to draw definitive conclusions.

Biological Predictors of Treatment Response in Adult Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent condition with onset in childhood and in many cases persisting into adulthood. Even though an increasing number of studies have investigated the efficacy of pharmacotherapy in the management of adult ADHD, few authors have tried to identify the biological predictors of treatment response. OBJECTIVES: To summarize the available data about the biological markers of treatment response in adults affected by ADHD. METHODS: A search on the main biomedical and psychological archives (PubMed, Embase, Scopus, and PsycINFO) was performed. Manuscripts in English, published up to May 2022 and having the biological predictors of treatment response in adults with ADHD as their main topic, were included. RESULTS: A total of 3855 articles was screened. Twenty-two articles were finally included. Most of the manuscripts studied neuroimaging and electrophysiological factors as potential predictors of treatment response in adult ADHD patients. No reliable markers were identified until now. Promising findings on this topic regard genetic polymorphisms in snap receptor (SNARE) proteins and default mode network-striatum connectivity. CONCLUSIONS: Even though some biological markers seem promising for the prediction of treatment response in adults affected by ADHD, further studies are needed to confirm the available data in the context of precision medicine.

Screening for ADHD Symptoms among Criminal Offenders: Exploring the Association with Clinical Features.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a disabling disorder. High rates of ADHD have been consistently reported among prisoners. The main objectives were (1) to estimate the prevalence of ADHD symptoms in a sample of male inmates and (2) to investigate the relationship between ADHD symptoms and socio-demographic/clinical features. According to the high prevalence of childhood trauma among inmates, we assessed whether exposition to childhood trauma can be related to the presence of ADHD symptoms. METHODS: A total of 159 male prisoners admitted to Monza prison between January 2020 and June 2021 were included. Both Wender Utah ADHD rating scale and adult ADHD self-report scale were administered to assess ADHD symptoms. Moreover, inmates completed the childhood trauma questionnaire. RESULTS: Data were available for 108 inmates. Thirty-five prisoners (32.4%) were found on screening to meet the criteria for symptoms of ADHD. Cocaine use disorder, prescription of mood stabilizers and a history of emotional abuse significantly increased the likelihood of having clinically significant ADHD symptoms. Furthermore, patients who experienced physical neglect resulted in meeting the criteria for ADHD symptoms. CONCLUSIONS: ADHD symptoms are widespread among inmates and are associated with specific risk factors. Screening for ADHD should be done to provide appropriate intervention strategies.

Is there an association between inflammatory/anti-oxidant markers and the presence of psychotic symptoms or severity of illness in mood and psychotic disorders? A multi-centric study on a drug-free sample.

The immune and antioxidant systems are intimately connected and their role in the etiology of major psychiatric disorders is currently under study. The aim of this study was to evaluate the potential associations between inflammatory/antioxidant peripheral markers and presence of psychotic symptoms or severity of illness in patients affected by major psychiatric disorders. One hundred and twenty-six drug-free patients were included. A blood sample was collected to measure total/B/T lymphocytes and plasma levels of albumin, total bilirubin, uric acid, C-reactive protein, and vitamins A and E. Severity of illness was assessed using psychometric scales. Groups of patients divided according to diagnosis were compared in terms of measured markers using multivariate analyses of variance (MANOVAs). Linear and logistic regression analyses were performed to investigate the potential association between markers and severity of illness or presence/absence of psychotic symptoms. Albumin plasma levels were higher in patients with substance-induced psychotic disorder (SIPD) than subjects affected by schizophrenia (F â€‹= â€‹4.923; p â€‹= â€‹0.003). Lower vitamin E (OR â€‹= â€‹0.81; p â€‹= â€‹0.014) and T lymphocyte (OR â€‹= â€‹0.99; p â€‹= â€‹0.048) plasma levels were predictive of lifetime psychotic symptoms. Lower vitamin A levels were associated with higher Montgomery-Åsberg Depression Rating Scale scores (ߠ​= â€‹-24.26; p â€‹= â€‹0.029), independent of diagnosis. Patients with SIPD may be less vulnerable to oxidative stress. The severity of depressive symptoms, inversely associated with vitamin A plasma levels, is likely to be modulated by the degree of inflammation. Patients presenting with lifetime psychotic symptoms may be more vulnerable to oxidative stress and may have a higher activation of humoral immunity.

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.

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.

Malondialdehyde and bipolar disorder: A short comprehensive review of available literature.

BACKGROUND: The pathogenetic mechanisms of Bipolar Disorder (BD) have not been totally clarified. Oxidative stress seems to be involved in the etiology of BD, and malondialdehyde (MDA) represents a candidate biomarker for monitoring this aspect in different medical conditions including mood disorders. This article has the objective to critically summarize the available data about the association between MDA and BD. METHODS: A research in Pubmed, PsycINFO and Isi Web of Knowledge was fulfilled to identify studies in which MDA levels were measured in BD patients for the purpose of securing a comprehensive review concerning the issue. RESULTS: We detected 20 articles that satisfied the inclusion criteria: most of them observed higher MDA levels (or Thiobarbituric acid-reactive substances-TBARS) in BD patients compared to healthy controls (HC), although there are some contrasting results, depending in particular on the phase of illness or the inclusion criteria or the methodological differences. LIMITATIONS: We included studies, exclusively in English, that used different laboratory methods to measure MDA. CONCLUSIONS: The analysed articles suggest that MDA or TBARS are increased in BD patients with respect to HC, thus supporting the hypothesis that MDA may be a promising and potential biomarker to monitor the course of BD, although further studies are needed to confirm this hypothesis.