Which Factors Are Associated With Comorbid Psychiatric Conditions in Patients Affected by Substance Use Disorders? The Impact of COVID-19 Pandemic on Dual-Diagnosis Subjects.

OBJECTIVE: To investigate demographic/cinical variables associated to dual diagnosis and the psychological reaction of dual-diagnosis patients to COVID-19 pandemic. METHODS: Information was collected at the Addiction Service of Monza, Italy. The Impact of Event Scale-Revised (IES-R), a self-report questionnaire measuring the subjective response to a traumatic event, was administered. Univariate analyses and binary logistic regression were performed. IES-R scores were compared between groups defined by qualitative variables through one-way analyses of variance (ANOVA). RESULTS: 118 outpatients were included, 48.3% with dual diagnosis. Alcohol use disorder and being female were associated to dual diagnosis. IES-R scores were significantly higher in the dual-diagnosis group, especially for personality disorders (PDs). IES-R scores were higher in patients taking treatment for substance use disorder (SUD). CONCLUSIONS: Females and alcohol abusers were at-risk subjects for dual diagnosis. Patients with SUD and PDs may benefit from additional support, especially when traumatic life events occur. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04694482.

Infrared nanospectroscopy depth-dependent study of modern materials: morpho-chemical analysis of polyurethane/fibroin binary meshes.

Infrared scattering-type scanning near-field optical microscopy (IR s-SNOM) and imaging is here exploited together with attenuated total reflection (ATR) IR imaging and scanning electron microscopy (SEM) to depict the chemical composition of fibers in hybrid electrospun meshes. The focus is on a recently developed bio-hybrid material for vascular tissue engineering applications, named Silkothane®, obtained in the form of nanofibrous matrices from the processing of a silk fibroin-polyurethane (SFPU) blend via electrospinning. Morphology and chemistry of single fibers, at both surface and subsurface level, have been successfully characterized with nanoscale resolution, taking advantage of the IR s-SNOM capability to portray the nanoscale depth profile of this modern material working at diverse harmonics of the signal. The applied methodology allowed to describe the superficial characteristics of the mesh up to a depth of about 100 nm, showing that SF and PU do not tend to co-aggregate to form hybrid fibers, at least at the length scale of hundreds of nanometers, and that subdomains other than the fibrillar ones can be present. More generally, in the present contribution, the depth profiling capabilities of IR s-SNOM, so far theoretically predicted and experimentally proven only on model systems, have been corroborated on a real material in its natural conditions with respect to production, opening the room for the exploitation of IR s-SNOM as valuable technique to support the production and the engineering of nanostructured materials by the precise understanding of their chemistry at the interface with the environment.

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.

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.

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.

Profile of patients attending psychiatric emergency care during the coronavirus 2019 (COVID 19) pandemic: a comparative cross-sectional study between lockdown and post-lockdown periods in Lombardy, Italy.

OBJECTIVE: To assess the long-term impact of early COVID-19 lockdown phase on emergency psychiatric consultations in two psychiatric emergency departments located in Italy. METHODS: We conducted a cross-sectional study comparing the number and characteristics of emergency psychiatric consultations during post-lockdown with respect to the lockdown period. Sociodemographic data, clinical characteristics, referred symptoms, diagnosis, information on multiple psychiatric consultations and hospitalisation were collected. RESULTS: A rise of almost 60% in emergency psychiatric consultations during the post-lockdown compared to the lockdown period was observed. Emergency psychiatric consultations in the post-lockdown period were associated with lower rates of cannabis (aOR = 0.42, p = 0.011) and cocaine use (aOR = 0.39, p = 0.011). Despite a lower occurrence of two or more psychiatric consultations was observed during post-lockdown phase (aOR = 0.44, p = 0.008), subjects who had anxiety disorders (aOR = 3.91, p = 0.000) and substance intoxication or withdrawal (aOR = 6.89, p = 0.000) were more likely to present to emergency psychiatric consultations during post-lockdown period compared to the lockdown one. CONCLUSIONS: Substance intoxication or withdrawal and anxiety disorders increased after the COVID-19 lockdown. The findings of this study suggest to address more economic and professional sources to the mental health areas potentially more affected by the different phases of a pandemic.KEYPOINTSCOVID-19 pandemic and lockdown measures increased mental health unmet needs.According to our findings, a rise in emergency psychiatric consultations during the post-lockdown compared to the lockdown period was observed.Patients with substance intoxication or withdrawal syndrome and anxiety disorders were significantly more likely to present to emergency psychiatric consultations during post-lockdown.Lockdown was associated with higher rates of both cannabis and cocaine use disorders as well as of multiple psychiatric consultations.Alternative strategies to improve mental health such as e-health technologies should be promoted.

Initiation of psychotropic medication in hospitalized patients with COVID-19: Association with clinical and biological characteristics.

INTRODUCTION: Inpatients with coronavirus disease 2019 (COVID-19) show a high rate of neuropsychiatric manifestations, possibly related to a higher risk of serious illness or death. Use of psychotropic medications (PMs) indicates the presence of neuropsychiatric symptoms in COVID-19 patients. So far, potential clinical predictors of use of PMs have not been much investigated. In order to extend research in this area, we aimed to investigate the prevalence of PM prescription among a sample of inpatients with COVID-19 and to find potential predictors of initiation of PMs in these individuals. METHODS: This is a cross-sectional single-center study, conducted during the first outbreak peak in a hospital of northern Italy. Information on socio-demographic characteristics, comorbidities, routine blood test, use of potential COVID-19 treatments, and length of stay were retrieved from medical records. RESULTS: Data were available for 151 inpatients. Forty-seven of them (31.1%) started at least one prescription of a PM. PM prescription was significantly inversely associated with lymphocyte and platelet counts. A significant association was also found for lactate dehydrogenase (LDH). CONCLUSION: Our findings suggest that the initiation of PMs could be common among COVID-19 inpatients. Lymphocyte and platelet counts as well as LDH levels may reflect neuropsychiatric complications of COVID-19.

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.

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.

A miRNome analysis of drug-free manic psychotic bipolar patients versus healthy controls.

The lifetime presence of psychotic symptoms is associated with more clinical severity, poorer outcome and biological changes in patients affected by bipolar disorder (BD). Epigenetic mechanisms have been evoked to explain the onset of psychotic symptoms in BD as well as the associated biological changes. The main objective of the present study was to evaluate the expression profiles of circulating microRNAs (miRNAs) in drug-free manic psychotic bipolar patients versus healthy controls (HC), to identify possible non-invasive molecular markers of the disorder. 15 drug-free manic psychotic bipolar patients and 9 HC were enrolled and 800 miRNAs expression profile was measured by Nanostring nCounter technology on plasma samples and validated through qPCR. Overall, twelve miRNAs showed a significantly altered expression between the two groups (p < 0.05). Functional annotation of predicted miRNAs targets by MultiMIR R tool showed repression in bipolar patients of genes with a role in neurodevelopment and neurogenesis, and upregulation of genes involved in metabolism regulation. We identified a signature of circulating miRNA characteristic of manic psychotic bipolar patients, suggesting a possible role in neurodevelopment and metabolic processes regulation.

Is trazodone more effective than clomipramine in major depressed outpatients? A single-blind study with intravenous and oral administration.

OBJECTIVE: Some antidepressants, such as trazodone or clomipramine, can be administered intravenously in patients with major depressive disorder (MDD), with potential benefits compared to the standard oral treatment, but available data about their efficacy are limited. The present study was aimed to compare the effectiveness of trazodone and clomipramine (intravenous [i.v.] followed by oral administration). METHODS: Some 42 patients with a diagnosis of MDD according to the DSM-5 were selected and treated with i.v. trazodone or clomipramine according to clinical judgment. The Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Montgomery-Åsberg Depression Rating Scale were administered at baseline, after 2 weeks, and after 6 weeks, as well as after 1 week of intravenous antidepressant administration. Raters were blinded to type of treatment. RESULTS: No significant differences were found between treatment groups in terms of effectiveness at endpoint. Borderline statistical significance was found in terms of number of responders in favor of trazodone. In addition, patients treated with trazodone reported fewer total side effects than those treated with clomipramine. CONCLUSION: Both i.v. trazodone and clomipramine are rapid and effective options for improving depressive symptoms, although trazodone appears to be tolerated better. Further studies with larger samples and double-blind conditions are warranted to confirm our results.

Is Internet Addiction a Clinical Symptom or a Psychiatric Disorder? A Comparison With Bipolar Disorder.

The general purpose of this review is to present an updated literature overview of neurobiological/clinical aspects of Internet addiction (IA), particularly of overlaps and differences with bipolar affective disorder (BPAD). Articles with clinical/neurobiological aspects of IA or similarities/differences with BPAD as main topics, from 1990 to present and written in English language, were included. Comorbidity between IA and other psychiatric disorders, including BPAD, is common. Dysfunctions in dopaminergic pathways have been found both in IA and in mood disorders. Most of investigations in IA support a chronic hypodopaminergic dysfunctional state in brain reward circuit and an excessive reward experience during mood elevation. Neuroimaging studies show prefrontal cortex abnormalities shared between addictive and bipolar patients. BPAD and IA present numerous overlaps, such as polymorphisms in nicotinic receptors genes, anterior cingulate/prefrontal cortex abnormalities, serotonin/dopamine dysfunctions, and good response to mood stabilizers. The future is to clarify diagnostic criteria to better define the IA/BPAD relationship.

Pharmacological Management of Psychiatric Symptoms in Frontotemporal Dementia: A Systematic Review.

Psychiatric symptoms in patients with frontotemporal dementia (FTD) are highly prevalent and may complicate clinical management of these patients. Purpose of the present article is to present and discuss available data about the pharmacological treatment of psychiatric symptoms in patients with FTD. A research in the main database sources has been conducted to obtain an overview of the pharmacological management of psychiatric symptoms in patients with FTD. The search strategy included the following terms-"FTD and psychiatry," "FTD and behavioural disturbances," and "FTD and treatment". Pathophysiology of psychiatric symptoms in FTD is different from other types of dementia. Although drugs for Alzheimer disease appear to be ineffective for the treatment of psychiatric symptoms of FTD, preliminary evidence supports a possible usefulness of serotonergic antidepressants for these patients. Data are too scanty to draw definitive conclusions, but antidepressant treatment, particularly with serotonergic compounds, may improve psychiatric symptoms in patients with FTD. Large observational studies are needed to confirm this preliminary evidence, and a lot of effort and collaboration between neurologists and psychiatrists will be definitely crucial for future research of effective treatments for FTD.

Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

Sex Steroids and Major Psychoses: Which Role for DHEA-S and Progesterone.

OBJECTIVE: Endocrine pathways seem to play a role in the etiology of major psychoses. The identification of biomarkers associated with psychotic symptoms in schizophrenia (SKZ) and mood disorders would allow the identification of high-risk subjects for delusions and hallucinations. The aim of this study was to evaluate dehydroepiandrosterone sulfate (DHEA-S) and progesterone plasma levels in drug-free patients with major psychoses and their relation with the diagnosis and history of psychotic symptoms. METHODS: Eighty-nine consecutive drug-free male inpatients with SKZ or mood disorders were recruited, and DHEA-S and progesterone plasma levels were measured. The groups, divided according to pathological/normal-range hormone levels, were compared in terms of clinical variables using x03C7;2 tests with Bonferroni's corrections or multivariate analyses of variance. The same analyses were performed for groups divided according to the presence/absence of lifetime psychotic symptoms. Binary logistic regression analysis was performed using hormone levels as independent variables and history of lifetime psychotic symptoms as a dependent one. RESULTS: A higher number of patients with abnormal DHEA-S levels was found to have a family history of major depressive disorder (p < 0.05). Higher DHEA-S levels (F = 8.31; p = 0.005) were found in patients with a history of psychotic symptoms. In addition, binary logistic regression confirmed that DHEA-S levels were associated with a higher probability of lifetime psychotic symptoms (p = 0.037). CONCLUSIONS: Our results confirm previous data about the role of endocrine factors in the etiology of major psychoses. A high DHEA-S level might be a risk factor for psychotic symptoms. Studies with larger samples are needed to confirm these data.

Psychiatric Conditions in Parkinson Disease: A Comparison With Classical Psychiatric Disorders.

Psychiatric conditions often complicate the outcome of patients affected by Parkinson disease (PD), but they differ from classical psychiatric disorders in terms of underlying biological mechanisms, clinical presentation, and treatment response. The purpose of the present review is to illustrate the biological and clinical aspects of psychiatric conditions associated with PD, with particular reference to the differences with respect to classical psychiatric disorders. A careful search of articles on main databases was performed in order to obtain a comprehensive review about the main psychiatric conditions associated with PD. A manual selection of the articles was then performed in order to consider only those articles that concerned with the topic of the review. Psychiatric conditions in patients with PD present substantial differences with respect to classical psychiatric disorders. Their clinical presentation does not align with the symptom profiles represented by Diagnostic and Statistical Manual for Mental Disorders and International Classification of Diseases. Furthermore, psychiatry treatment guidelines are of poor help in managing psychiatric symptoms of patients with PD. Specific diagnostic tools and treatment guidelines are needed to allow early diagnosis and adequate treatment of psychiatric conditions in comorbidity with PD.

General and social cognition in remitted first-episode schizophrenia patients: a comparative study.

The aim of this paper was to investigate whether both neurocognitive and social cognitive performances were different between remitted first-episode schizophrenia patients, non-remitters and healthy controls (HC). We assessed social cognition (Degraded Facial Affect Recognition Task-DFAR and Emotional Mentalizing Task-EMT) and neurocognition (Wechsler Adult Intelligence Scale and Word Learning Test-WLT) in 174 remitted first-episode schizophrenia patients, 110 non-remitted first-episode schizophrenia patients and 320 HC. Multivariate analyses of variance with age, gender and IQ as covariates (MANCOVA) were performed to compare mean cognitive test scores between the three groups. Remitted first-episode schizophrenia patients performed significantly worse than HC only in one verbal memory task (WLT immediate recall; p = 0.004); in the same test, they were significantly better than non-remitters (p = 0.027). Non-remitted first-episode schizophrenia patients, differently from remitters, performed significantly worse than HC in terms of social cognition (EMT-p < 0.05 and DFAR-p < 0.05). Remitted first-episode schizophrenia patients presented worse cognitive performance than HC in verbal memory tasks, but not in facial affect recognition and in ToM, while non-remitters did; these results suggest that neurocognitive deficits are the core hallmark of schizophrenia and that social cognition is relatively unaffected in remitted patients after their first episode.

Biological aspects and candidate biomarkers for psychotic bipolar disorder: A systematic review.

AIM: We carried out a systematic review of the available literature about potential biomarkers of psychotic bipolar disorder (BD-P), a specific subset presenting worse outcome and greater risk of relapse than non-psychotic bipolar disorder (BD-NP). METHODS: We searched the main psychiatric databases (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles with the main topic of BD-P compared to schizophrenia/BD-NP/healthy controls (HC) written in English from 1994 to 2015 were included. RESULTS: BD-P patients presented higher kynurenic acid levels in the cerebrospinal fluid, elevated anti- S accharomyces cerevisiae antibodies levels, and lower serum levels of dehydroepiandrosterone sulfate and progesterone than BD-NP/HC. Event-related potentials abnormalities have been identified in BD-P with respect to BD-NP. BD-P patients also presented bigger ventricles but similar hippocampal volumes compared to BD-NP/HC. Although the results are contrasting, some cognitive deficits seemed to be related to the psychotic dimension of bipolar affective disorder, such as impairment in verbal/logical memory, working memory, verbal and semantic fluency and executive functioning. Finally, polymorphisms of genes, such as NRG1, 5HTTLPR (s), COMT, DAOA and some chromosome regions (16p12 and 13q), were positively associated with BD-P. CONCLUSION: Data about the identification of specific biomarkers for BD-P are promising, but most of them have not yet been replicated. They could lead the clinicians to an early diagnosis and proper treatment, thus ameliorating outcome of BD-P and reducing the biological changes associated with a long duration of illness. Further studies with bigger samples are needed to detect more specific biological markers of the psychotic dimension of bipolar affective disorder.

Are antidepressants equally effective in the long-term treatment of major depressive disorder?

OBJECTIVE: Few studies have compared simultaneously different antidepressants in long-term treatment of major depressive disorder (MDD). Long-term prevention of recurrences should be the main goal of MDD treatment. The purpose of this study was to compare antidepressants of different pharmacological classes in terms of retention in treatment (no discontinuation for recurrences, hospitalizations, side effects). METHODS: One hundred and fifty outpatients with an MDD diagnosis, treated with antidepressants in mono-therapy, were included. Follow-up period was set at 24 months, and information have been obtained from charts, interviews with patients and their relatives, and from the Lombardy regional register. A survival analysis (Kaplan-Meier) was performed, considering recurrences, hospitalizations, or discontinuation due to side effects as 'death' events. RESULTS: In our sample, 48.7% of the patients presented a recurrence within the first 2 years of treatment. Bupropion appears less effective in long-term treatment of MDD than the other compared antidepressants, with exception of fluoxetine (p = 0.09), amitriptyline (p = 0.13), fluvoxamine (p = 0.83), venlafaxine (p = 0.5), and trazodone (p = 0.58). Fluvoxamine appears to be less effective than citalopram (p = 0.036), paroxetine (p = 0.037), clomipramine (p = 0.05), sertraline (p = 0.011), and duloxetine (p = 0.024). CONCLUSIONS: Bupropion and fluvoxamine appear less effective in long-term treatment of MDD. These results should be confirmed by randomized placebo-controlled prospective studies with larger samples.