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.

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.

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.

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.

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.

Exploring the role of serum lipid profile and neutrophil-to-lymphocyte ratio in violent suicide attempters: a cross sectional study.

BACKGROUND: Suicidality is one of the most common complications of mental disorders, so that the identification of potential biomarkers may be relevant in clinical practice. To date, the role of serum lipids and neutrophil/lymphocyte ratio (NLR) has been explored albeit with conflicting results. To the best of our knowledge, no study has explored lipid levels concomitantly with NLR in relation to violent suicide attempts. Therefore, we aimed to investigate whether serum lipid levels and NLR might be associated with the violent method of suicide attempts. METHODS: The study group consisted of 163 inpatients who attempted suicide. Blood samples were collected at the beginning of hospitalization to measure total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, very-low-density lipoprotein (VLDL), triglycerides, and NLR. Descriptive analyses of the total sample were performed. The included patients were divided into two groups according to violent/nonviolent method. Groups were compared in terms of lipid (MANCOVAs). RESULTS: Plasma levels of total cholesterol (F = 5.66; P = .02), LDL (F = 4.94; P = .03), VLDL (F = 5.66; P = .02), and NLR (F = 8.17; P < .01) resulted to be significantly lower in patients that used a violent method compared to patients who attempted suicide with a nonviolent method. CONCLUSIONS: Low cholesterol, LDL, and VLDL levels as well as low NLR value were associated with a violent method of suicide attempt in patients with mental disorders. Further studies are needed to confirm these results.

Augmentative Pharmacological Strategies in Treatment-Resistant Major Depression: A Comprehensive Review.

Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best pharmacological augmentation strategy to antidepressants (AD). In the present review, we identify the available literature regarding the pharmacological augmentation to AD in TRD. Research in the main psychiatric databases was performed (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles in English with the main topic being pharmacological augmentation in TRD and presenting a precise definition of TRD were included. Aripiprazole and lithium were the most investigated molecules, and aripiprazole presented the strongest evidence of efficacy. Moreover, olanzapine, quetiapine, cariprazine, risperidone, and ziprasidone showed positive results but to a lesser extent. Brexpiprazole and intranasal esketamine need further study in real-world practice. Intravenous ketamine presented an evincible AD effect in the short-term. The efficacy of adjunctive ADs, antiepileptic drugs, psychostimulants, pramipexole, ropinirole, acetyl-salicylic acid, metyrapone, reserpine, testosterone, T3/T4, naltrexone, SAMe, and zinc cannot be precisely estimated in light of the limited available data. Studies on lamotrigine and pindolol reported negative results. According to our results, aripiprazole and lithium may be considered by clinicians as potential effective augmentative strategies in TRD, although the data regarding lithium are somewhat controversial. Reliable conclusions about the other molecules cannot be drawn. Further controlled comparative studies, standardized in terms of design, doses, and duration of the augmentative treatments, are needed to formulate definitive conclusions.

Long-Term Efficacy of Intranasal Esketamine in Treatment-Resistant Major Depression: A Systematic Review.

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.

Gender Differences in Misdiagnosis and Delayed Diagnosis among Adults with Autism Spectrum Disorder with No Language or Intellectual Disability.

Autism Spectrum Disorder (ASD) is often unrecognized, especially in mild forms and in women. Studies evaluating features associated with missed/misdiagnosis in men and women with ASD are warranted. 61 subjects (22 females, 39 males, age 28.5 ± 10.8 years) with ASD with no language/intellectual deficit were enrolled in the service for the treatment of psychiatric comorbidities in adults with ASD of the ASST Fatebenefratelli-Sacco in Milan (Italy). A detailed clinical history was gathered, and two self-report questionnaires (Autism Spectrum Quotient-AQ and Adult Autism Subthreshold Spectrum-AdAS Spectrum) were administered. 75.4% received their ASD diagnosis average eight years later than the first evaluation by mental health services. Compared to males, females showed a significantly greater delay in referral to mental health services and a significantly higher age at diagnosis of ASD. Among men, diagnostic delay inversely correlated with scores on the AdAS Spectrum total, Verbal communication, Empathy and Inflexibility and adherence to routine domains. Among women, diagnostic delay positively correlated with the Attention to detail score while the age at diagnosis of ASD positively correlated with the AdAS Spectrum Verbal communication and Restricted interests and rumination domain scores. Females were less likely to be correctly diagnosed and more likely to be misdiagnosed at first evaluation than men. Females reported significantly higher scores than men in the Hyper/Hyporeactivity to sensory input domain only among subjects who were misdiagnosed. Our findings provide gender-specific information about ASD patients seeking help for comorbid conditions and might be a primary ground for future research.

The association between childhood trauma and lifetime suicide attempts among a sample of male prisoners: A pilot observational study.

BACKGROUND: Prisoners have higher rates of suicide attempts compared with general population. A history of childhood trauma (CT) is common among incarcerated subjects and it is a well-known risk factor for lifetime suicide attempts. Therefore, the purpose of the study was to investigate whether lifetime suicide attempts may be related to the exposition to CT among male prisoners. METHOD: We conducted a cross sectional study recruiting newly arrived inmates in an Italian jail, between January 2017 and June 2018. Prisoners were interviewed to collect socio-demographic and clinical information. Moreover, inmates completed the Childhood Trauma Questionnaire. We excluded prisoners unable to speak or read Italian, with learning disabilities or current severe psychiatric symptoms. RESULTS: A total of 215 consecutive male inmates were included. Fifty-one prisoners (23.7%) had a history of attempted suicide. The most reported CT was physical neglect. Multivariate logistic regression analysis showed that a history of childhood sexual abuse, emotional neglect and psychiatric diagnosis significantly increased the likelihood of lifetime suicide attempt. CONCLUSIONS: A previous history of suicide attempt is highly prevalent among inmates. In agreement with previous findings, lifetime suicide attempts seem to be associated with the presence of CT and psychiatric diagnosis. Therefore, CT should be considered as a relevant variable to improve the programs for the prevention of suicide in prison.

Biomarkers of suicidal behaviors: A comprehensive critical review.

Suicide is a relevant worldwide public health problem. Many studies have shown that different demographic and clinical factors are potentially associated with suicidal behavior. Other studies have reported data about the role of biomarkers in the onset of suicidal behaviors. Specifically, researchers have found that suicidal risk may be increased by abnormalities in serotonergic system, hypothalamic-pituitary-adrenal axis, lipid metabolism, immune system and neuronal plasticity. The identification of specific biological parameters associated with self-harm may be helpful to implement prevention strategies and also to detect new therapeutic strategies. In this review, we summarize and analyze the results of main studies about neurobiological mechanisms related to suicidal behavior, also exploring the possible interconnection between the different biological systems.

Monocyte count in schizophrenia and related disorders: a systematic review and meta-analysis.

OBJECTIVE: Increasing evidence suggests that immunological and inflammatory dysfunctions may play an important role in predisposition, onset, and progression of schizophrenia and related psychosis. The activation of cells of the mononuclear phagocyte system, especially microglia and monocytes, has been reported in schizophrenia. We carried out this systematic review and meta-analysis to investigate if there are significant differences in monocyte count comparing healthy controls with people suffering from schizophrenia and related disorders. METHODS: We searched main electronic databases; nine records met all our criteria and were included in the meta-analysis. Meta-analyses based on random effects models have been carried out generating pooled standardised mean differences (SMDs) of monocyte count in peripheral blood between schizophrenia and related psychosis and healthy controls. Heterogeneity was estimated. Relevant sensitivity and subgroup analyses were conducted. RESULTS: Patients showed higher monocyte count as compared with healthy control (SMD = 0.393; p = 0.001). Heterogeneity across studies was from moderate to high (I2 = 65.952%); sensitivity analysis leaving out two studies responsible for most of the heterogeneity showed a slightly higher SMD. Subgroup analyses confirmed this result, showing no significant differences in the effect size across different study characteristics. CONCLUSIONS: Monocyte count can be considered an indirect marker of microglia activation in the central nervous system. Thus, the observed higher monocyte count in patients could be considered as a possible peripheral marker of microglia's activation in schizophrenia disorder.