Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19.

BACKGROUND: Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. METHODS: A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). RESULTS: Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. CONCLUSIONS: Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. TRIAL REGISTRATION: The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.

First episode psychosis during the Covid-19 pandemic in Milan, Italy: Diagnostic outcomes at 1-year follow-up.

An influence of the Covid-19 pandemic on First Episode Psychosis (FEP) has been hypothesized. We previously reported an increase of FEP during the early stages of the pandemic in Milan, Italy. Here we report a 1-year follow-up of the same cohort and comparison with a FEP cohort from 2019. The higher proportion of non-chronic psychoses observed during the pandemic (58.62% in 2020 vs 43,75% in 2019) should be confirmed in larger cohorts over a longer follow-up period.

ADHD and eating disorders in childhood and adolescence: An updated minireview.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders with overactivity, inattention, and impulsivity as core characteristics. Recent studies suggest that 20 % of children with ADHD also develop eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge eating disorder. However, little is still known about the association between ADHD and EDs through childhood and adolescence. Therefore, in the present work, we aimed at summarizing the studies investigating ADHD and EDs in childhood and adolescence over the last 10 years. METHODS: A bibliographic search on PubMed was performed and only studies that considered participants with a clinical diagnosis of ADHD, patients with an additional diagnosis of EDs and patients under 18 years old were included. A total of 7 studies were retrieved and included in the review. RESULTS: The majority of the reviewed studies (N = 5) found an association between ADHD and EDs, while the remaining, which focused on EDs symptomatology, reported either lower ED symptoms in ADHD sample or no association between ADHD and EDs. LIMITATIONS: the majority of studies were cross-sectional and therefore did not allow to explore the longitudinal casual relation between ADHD and EDs in the developmental age range considered. CONCLUSIONS: This review suggests that children and adolescents with ADHD should be monitored for EDs. However, more work is still needed to better understand the clinical implications of the comorbidity between ADHD and EDs and its prospective impact on the life of children and adolescents with ADHD.

The clinical utility of D-dimer/platelet count ratio in pregnant women.

OBJECTIVE: We performed a retrospective study to assess the clinical utility of a new index, D-dimer/platelet count (DD/PLT) ratio, in discriminating preeclampsia from normal pregnancy and gestational hypertension during third trimester, compared to the biomarkers currently used, such as D-dimer (DD), platelet (PLT), lymphocyte (LIN) and neutrophil (NEU) counts, fibrinogen (FIB), PLT/NEU, NEU/LIN and PLT/LIN ratios. STUDY DESIGN: We retrospectively included 213 subjects. Of them, 163 and 50 were singleton pregnant and healthy non-pregnant women, respectively. Among pregnant women, 105 had normal pregnancy, 33 had gestational hypertension, and 25 had preeclampsia. RESULTS: Using Receiver Operating Curve (ROC) analysis, DD/PLT ratio showed significant higher area under the curve (AUC) (0.90; 95% confidence interval (CI) 0.84-0.95) in discriminating preeclampsia from normal pregnancy compared to those of DD, NEU, FIB, LIN, PLT/NEU, NEU/LIN and PLT/LIN ratios (p < .03). In discriminating preeclampsia from gestational hypertension, the DD/PLT AUC (0.90; 95% CI 0.79-0.96) was significantly higher than those of DD, NEU, FIB, LIN, NEU/LIN and PLT/LIN ratios (p < .03), and not statistically different from those of PLT (p = .22) and PLT/NEU ratio (p = .46). CONCLUSIONS: This study shows that DD/PLT ratio helps to discriminate preeclampsia from normal pregnancy and gestational hypertension. Large-scale studies are needed to verify its clinical usefulness, and to suggest more appropriate cutoff values for a widespread use.

Imaging associations of self-injurious behaviours amongst patients with Borderline Personality Disorder: A mini-review.

BACKGROUND: Borderline Personality Disorder (BPD) is a severe and disabling psychiatric syndrome, frequently associated with self-injurious behaviours (SIB). In recent years, functional magnetic resonance imaging (fMRI) investigations have tried to identify alterations associated with SIB amongst BPD patients, in order to better delineate possible neurobiological underpinnings of these manifestations. In this mini-review, we aimed at summarizing fMRI studies exploring patterns of neural activation associated with SIB in BPD patients. METHODS: Literature searches on PubMed, Psych-Info and Embase databases were performed for all fMRI studies including adult patients with BPD and SIB undergoing different tasks, including painful or thermic stimulation, affective stimulation through the presentation of picturesor the recollection of personal memories as well as tasks that evaluate sustained attention and impulsivity, and reward processing. Thirteen relevant papers were considered eligible for the present review. RESULTS: Patients with BPD and SIB, compared to HC, showed prefrontal, nucleus accumbens overactivation and amygdala deactivation during pain stimulation. During negative affective stimulation, BPD patients showed a hyperactivation of the amygdala and a hypoactivation of the orbitofrontal cortex (OFC), which was also found to be enhanced during a gambling task and during a recalling of aversive memories. In contrast, during cognitive tasks with negative affective interference, BPD patients showed hypoactivation of OFC, anterior cingulated cortex, and basal ganglia. LIMITATIONS: The limited number of studies and the heterogeneity regarding the fMRI tasks employed allowed only suggestive conclusions. CONCLUSIONS: The reviewed fMRI studies highlighted that BPD patients with a history of SIB showed altered brain activity, compared to HC, in regions involved in inhibitory cognitive processes and affect regulation, which may in turn, explain the overwhelming emotional experiences eliciting SIB in these patients.

Hospital workers mental health during the COVID-19 pandemic: methods of data collection and characteristics of study sample in a university hospital in Milan (Italy).

BACKGROUND: The COVID-19 pandemic is currently a severe challenge for healthcare workers, with a considerable impact on their mental health. In order to focus preventive and rehabilitation measures it's fundamental to identify risk factors of such psychological impairment. We designed an observational longitudinal study to systematically examine the psychological wellbeing of all employees in a large University Hospital in Italy, using validated psychometric scales in the context of the occupational physician's health surveillance, in collaboration with Psychiatric Unit. METHODS: The study started after ethical approval in August 2020. For each worker, the psychological wellbeing is screened in two steps. The first level questionnaire collects sociodemographic characteristics, personal and occupational COVID-19 exposure, worries and concerns about COVID-19, general psychological discomfort (GHQ-12), post-traumatic stress symptoms (IES-R) and anxiety (GAD-7). Workers who score above the cut-off in at least one scale are further investigated by the second level questionnaire composed by PHQ-9, DES-II and SCL-90. If second level shows psychological impairments, we offer individual specialist treatment (third level). We plan to follow-up all subjects to monitor symptoms and possible chronicization; we aim to investigate potential risk factors through univariate analysis and multivariate logistic regressions. RESULTS: Preliminary results refer to a sample of 550 workers who completed the multi-step evaluation from August to December 2020, before vaccination campaign started. The participation rate was 90%. At first level screening, 39% of the subjects expressed general psychological discomfort (GHQ-12), 22% post-traumatic stress symptoms (IES-R), and 21% symptoms of anxiety (GAD-7). Women, nurses, younger workers, subjects with COVID-19 working exposure and with an infected family member showed significantly higher psychological impairment compared to colleagues. After the second level screening, 12% and 7% of all workers showed, respectively, depressive and dissociative symptoms; scorings were significantly associated with gender and occupational role. We are currently extending sample size and evaluating subjects over a period of further 12 months. CONCLUSIONS: The possibility to perform a systematic follow-up of psychological wellbeing of all hospital workers, directly or indirectly exposed to pandemic consequences, constitutes a unique condition to detect individual, occupational, and non-occupational risk factors for psychological impairment in situations of prolonged stress, as well as variables associated with symptoms chronicization.

Olfactory and gustatory dysfunctions in SARS-CoV-2 infection: A systematic review.

BACKGROUND: Among Coronavirus Disease 2019 (COVID-19) manifestations, Olfactory (OD) and Gustatory (GD) Dysfunctions (OGD) have drawn considerable attention, becoming a sort of hallmark of the disease. Many have speculated on the pathogenesis and clinical characteristics of these disturbances; however, no definite answers have been produced on the topic. With this systematic review, we aimed to collect all the available evidence regarding the prevalence of OGD, the timing of their onset and their resolution, their rate of recovery and their role as diagnostic and prognostic tools for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. METHODS: A systematic review comprising all the observational studies that reported the prevalence and/or the longitudinal trajectories of OGD in COVID-19 patients, as self-reported by patients or measured through objective psychophysical tests. RESULTS: After the selection process, 155 studies were included, with a total of 70,920 patients and 105,291 not-infected individuals. Prevalence reports were extremely variable across studies, with wide ranges for OD (0%-98%) and GD (0-89%) prevalence. OGD occurred early during the disease course and only rarely preceded other symptoms; out of 30 studies with a follow-up time of at least 20 days, only in 5 studies OGD fully resolved in more than 90% of patients. OGD had low sensitivity and high specificity for SARS-CoV-2 infection; accuracy of OD and GD for infection identification was higher than 80% in 10 out of 33 studies and in 8 out of 22 studies considered, respectively. 28 out of 30 studies that studied the association between OGD and disease severity found how OGD were associated with lower rates of severe pneumonia, hospitalization and mortality. CONCLUSIONS: OGD seem to be highly prevalent in SARS-CoV-2 infection. They occur early, concomitantly with other symptoms and often persist after recovery, in some cases for months; whether a full recovery eventually occurs in all cases is not clear yet. OGD are good predictors of SARS-CoV-2 infection and are associated with a milder disease course.

Monoclonal free light chain detection and quantification: Performances and limits of available laboratory assays.

The detection and quantification of immunoglobulin free light chains in serum and urine is recommended for the diagnosis and monitoring of monoclonal gammopathies according to the guidelines of the International Myeloma Working Group (IMWG). Several tests are currently available in the clinical laboratory to detect and quantify free light chains but although quality, efficiency, and effectiveness have been improved, the results are still variable and poorly harmonized and standardized. The present review article wants to analyze these aspects, with a keen eye on techniques, such as mass spectrometry, that could replace in the practical clinical laboratory the current methods including Bence-Jones protein assay and free light chain immunoassays.

Classification of first-episode psychosis using cortical thickness: A large multicenter MRI study.

Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.

Multiple retrospective analysis of survival and evaluation of cardiac death predictors in a population of dogs affected by degenerative mitral valve disease in ACVIM class C treated with different therapeutic protocols.

Clinical records of dogs with spontaneous degenerative mitral valve disease (DMVD) with clinical signs related to congestive heart failure (CHF) recruited during routine clinical practice between 2001 and 2018 at the Cardiology Unit of the Veterinary Teaching Hospital (University of Milan) were included in this retrospective cohort study. Baseline echocardiographic data were evaluated. Median survival time (MST) was calculated. Data on therapeutic treatment, ISACHC (International Small Animal Cardiac Health Council) or ACVIM (American College of Veterinary Internal Medicine) classes were reviewed based on the inclusion period and type of endpoint (i.e. cardiac death or death for other causes). A univocal classification was needed, and the patients classified in ISACHC classes II, IIIa and IIIb, visited before 2009, were reallocated to ACVIM class C. The main goal of this data review was to retrospectively evaluate 259 clinical records of subjects belonging to ACVIM C class examined between 2001 to 2018 and 202 dogs examined between 2010 to 2018. In this way, in the second group, the bias of the reclassification was avoided. The MST (median survival time) of these subjects was 531 d (2001-2018) and 335.5 d (2010-2018), respectively. Univariate survival regression analysis for subjects included from 2010 to 2018 showed as significantly related to cardiac death (CD): left atrium to aorta ratio (LA/Ao) (HR 2.754, p=0.000), E wave (HR 2.961, p=0.000), E/A ratio (HR 1.372, p=0.000), end-diastolic (HR 1.007, p=0.000) (EDVI) and end-systolic (HR 1.012, p=0.026) (ESVI) volume indexes, allometric diastolic (HR 4.018, p=0.000) (LVIDdN) and systolic (HR 2.674, p=0.049) (LVIDsN) left ventricular internal diameters, age (HR 1.006, p=0.009) and pulmonary hypertension severity (HR=1.309, p=0.012) (PH). Multivariate analysis, adjusted for age, showed that the only variable that determined a statistically significant difference in MST was PH severity (HR 1.334, p=0.033). The type of therapeutic treatment within this class was not significant for the MST of the subjects.

A significant decreased in the frequency of Clostridioides difficile infection at the Italian Hospital of Desio over the last decade.

Clostridiodes difficile infection (CDI) is the most important cause of healthcare-associated diarrhea. The decreasing trend of CDI from 15% to 4% observed at the Italian Hospital of Desio over a 10-year period is due to prevention strategies. Our data highlight the importance of surveillance studies to control CDI.

Impact of the first Covid-19 pandemic wave on first episode psychosis in Milan, italy.

The ongoing Corona Virus Disease 2019 (COVID-19) pandemic appears to increase risk for mental illness, either directly due to inflammation caused by the virus or indirectly due to related psychosocial stress, resulting in the development of both anxious-depressive and psychotic symptoms. The purpose of the present study was to assess the frequency and characteristics of all patients with First Episodes Psychosis (FEP) without COVID-19 infection hospitalized in the first four months since lockdown in Milan. We recruited sixty-two patients hospitalized between March 8 to July 8, 2020 versus those first  hospitalized in the same period in 2019. The two subgroups were compared for sociodemographic variables and clinical characteristics of the episodes. Patients with FEP in 2020 were significantly older than patients with FEP in 2021, and presented with significantly less substances abuse. Interestingly, patients presenting with FEP in 2020 were significantly older than patients with FEP in 2019. These data are compatible with the greater vulnerability to stressful factors during the pandemic, as well as with the greater concern regarding a possible COVID-19 infection producing brain damage causing the FEP.

A rare case of cutaneous Papiliotrema (Cryptococcus) laurentii infection in a 23-year-old Caucasian woman affected by an autoimmune thyroid disorder with hypothyroidism.

In recent years, the frequency of infections due to saprophytic fungi has increased. Cryptococcus laurentii, recently classified as Papiliotrema laurentii, is responsible for fungemia, meningitis, and superficial infections. Here, we report the first case of cutaneous Papiliotrema (Cryptococcus) laurentii infection in a 23-year-old Caucasian woman affected by an autoimmune thyroiditis with hypothyroidism. Impairments of the immune system are often associated with unusual fungal infections, which cannot be neglected. The isolate strain was susceptible to Amphotericin B while resistant to fluconazole, itraconazole, voriconazole, and terbinafine. The patient was successfully treated with Amphotericin B.

Effect of childhood physical abuse on social anxiety is mediated via reduced frontal lobe and amygdala-hippocampus complex volume in adult clinical high-risk subjects.

BACKGROUND: Childhood adverse experiences (CAE) are associated with clinical psychiatric disorders and symptoms, and with volumetric abnormalities in the amygdala-hippocampus complex (AmHiC) and frontal lobe (FroL) in adulthood. AIM: To study whether CAE are associated with reduced AmHiC and FroL and whether these structures mediate the effect of CAE on social anxiety and depression. METHOD: In seven European centres, 374 patients with recent onset of psychosis (n = 127), clinical high-risk to psychosis (n = 119) or recent onset of depression (n = 128) were scanned with MRI and their FroL and AmHiC volumes were measured. They all completed self-report scales for assessment of CAE, social anxiety and depression. RESULTS: Of the CAE domains, physical abuse was associated specifically with reduced grey and white matter volumes of FroL and AmHiC in psychotic and high-risk patients. After controlling intracranial volume, PhyAb associated significantly with FroL and its grey matter volume in high-risk patients only. In mediation analyses, the effect of physical abuse on social anxiety was mediated via reduced FroL grey mater volume in high-risk patients. In them, when the effects of AmHiC and depression were controlled, the effect of physical abuse on social anxiety was mediated via FroL grey matter volume reduction. CONCLUSIONS: Childhood physical abuse is associated with reduced frontal lobe and amygdala-hippocampus complex volume in adult subjects with psychotic symptoms. Reduced frontal lobe and amygdala-hippocampus complex volume mediate the effect of physical abuse on social anxiety in high-risk patients. The effect of physical abuse on depression-independent social anxiety is mediated via reduced frontal lobe.

A rare case of Clostridium paraputrificum bacteremia in a 78-year-old Caucasian man diagnosed with an intestinal neoplasm.

Clostridium like species, particularly Clostridium perfrigens, are the second most common causes of human anaerobic infections, including myonecrosis and bacteremia. Clostridium paraputrificum is an infrequent isolate, which has been identified in only 1% of reported cases of clostridial infections. We herein report a rare case of C. paraputrificum bacteremia in a 78-year-old Caucasian man diagnosed with an intestinal carcinoma and liver neoplastic lesions. The isolate was susceptible to chloramphenicol, meropenem, metronidazole, vancomycin, and resistant to clindamycin and penicillin, and the patient was successfully treated with metronidazole. Malignancy and inflammatory bowel diseases are often associated with clostridial bacteremia, which cannot be neglected.

A novel spatiotemporal tool for the automatic classification of fMRI noise based on Independent Component Analysis.

In this study, a semi-automatic, easy-to-use classification method for the identification and removal of fMRI noise is proposed and tested. The method relies on subject-level spatial independent component analysis (ICA) of fMRI data. Starting from a reference set of labeled independent components (ICs), novel ICs are classified as physiological/artefactual by combining a spatial correlation (SC) analysis with the reference ICs and relative power spectral (PS) analysis. Here, ICs from a task-based fMRI dataset were used as reference. SC and SP thresholds were set using a test dataset (5 subjects, same fMRI protocol) based on Receiving Operating Characteristic curves. The tool performance and versatility were measured on a resting-state fMRI dataset (5 subjects). Our results show that the method can automatically identify noise-related ICs with accuracy, specificity and sensitivity higher than 80% across different fMRI protocols. These findings also suggest that the reference set provided in the present study might be used to mark ICs coming from independent taskrelated or resting-state fMRI datasets.Clinical relevance- The new method will be included in a userfriendly, open-source tool for removal of noisy contributions from fMRI datasets to be used in clinical and research practices.

Microstructural white matter alterations in borderline personality disorder: A minireview.

BACKGROUND: Borderline personality disorder (BPD) affects 1-5% of the population and is characterized by a complex symptomatology and selective functional impairments. Although brain imaging studies have contributed to better characterizing the pathophysiological mechanisms underlying BPD, the white matter (WM) deficits associated with this disorder are still unclear. Therefore, the present review aims at providing an overview of the findings emerged from the available diffusion tensor imaging (DTI) studies on BPD. METHODS: From a bibliographic research in PubMed until May 2019, we collected 12 studies that fulfilled our inclusion criteria, including a total sample of 291 BPD subjects and 293 healthy controls. RESULTS: Overall, the DTI studies reviewed showed impairments in selective WM tracts that are part of the prefronto-limbic system, including frontal WM (short and long tracts), anterior cingulate cortex, corpus callosum, corona radiata, hippocampal fornix and thalamic radiation, in BPD patients compared to healthy controls. LIMITATIONS: Few DTI studies with heterogeneous findings. CONCLUSIONS: Overall these results reported that BPD is characterized by selective structural connectivity alterations in prefronto-limbic structures, further supporting the neurobiological model of BPD that suggests the presence of an abnormal modulation of frontal regions over limbic structures. Finally, the results also highlighted that the disrupted WM integrity in selective brain regions may also explain key-aspects of BPD symptomatology, including emotional dysregulation, ambivalence, contradictory behaviors and cognitive dysfunctions.

A focus on valproate and cognitive deficits in Bipolar Disorders: A mini-review: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD.

BACKGROUND: Cognitive deficits represent a core feature of Bipolar Disorder (BD), which seem to characterize this disorder regardless of the mood phase. However, the role of pharmacological treatment in determining cognitive alterations is still not clear. Indeed, although drugs improve cognition by targeting mood symptoms, they could also carry their own cognitive side effects. This is true especially for mood stabilizers as they are the most commonly prescribed drugs in patients affected by BD and they are usually administered also during euthymic phases. METHODS: In this context, the present review aimed at summarizing the results of the studies evaluating the impact of valproate on cognitive functions in patients suffering from BD, as primary or secondary results. The inclusion criteria were met by ten studies. Specifically, we included one double-blind quasi-randomized study and nine cross-sectional or naturalistic studies, which a) used healthy subjects as control group (N = 1), b) compared valproate treated patients with healthy individuals and other treatments (N = 5), and c) compared valproate treated patients just with other treatments, with a specific focus on lithium (N = 3). RESULTS: Overall the results suggested a negative effect of valproate on cognitive functions in chronically-treated patients affected by BD. Notably, it has been found that the working memory was the most affected cognitive domain. LIMITATIONS: Few studies directly explored the effect of valproate on cognition in BD. CONCLUSIONS: These findings seem to suggest that valproate might have a negative effect on cognitive functions, especially on working memory domain. However, the results should be taken cautiously since the limited number of available studies published so far. In conclusion, these evidences seem to point out that the possible cognitive side effects of pharmacological treatments should be carefully taken into account, especially in chronic patients.

Association between serum BDNF levels and maternal perinatal depression: A review: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD.

INTRODUCTION: A large amount of studies demonstrated reduced serum Brain-Derived Neurotrophic Factor (BDNF) levels in stress-related and depressive disorders. However, it is still unclear if a similar deficit in BDNF concentrations might also characterize maternal perinatal depression. METHODS: We performed a bibliographic search on PUBMED of all the studies investigating the association between maternal BDNF levels and perinatal depression. The inclusion criteria were met by thirteen studies. RESULTS: Overall, the majority of the studies reported a significant reduction in serum BDNF levels among depressed mothers compared to healthy mothers either during pregnancy or in the postpartum period. Moreover, some studies also demonstrated that the BDNF reduction could be more evident in those depressed mothers with perinatal stressful life events and suicide risk. LIMITATIONS: BDNF were collected at different time points across the studies. Potential confounding factors, including the clinical characteristics of the samples employed by the original studies, might have influenced the results. CONCLUSIONS: So far, the evidences suggested the presence of decreased BDNF concentrations in perinatal depressive disorders. However, further studies are needed in order to confirm the role of BDNF in this disorder.