Is there a relationship between morphological and functional platelet changes and depressive disorder?

BACKGROUND: Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral biomarker of neuronal activity. Therefore, the literature strongly focused on the investigation of eventual structural and functional platelet abnormalities in neuropsychiatric disorders, particularly in depressive disorder. Given their impact in biological psychiatry, the goal of the present paper was to review and critically analyze studies exploring platelet activity, functionality, and morpho-structure in subjects with depressive disorder. METHODS: According to the PRISMA guidelines, we performed a systematic review through the PubMed database up to March 2020 with the search terms: (1) platelets in depression [Title/Abstract]"; (2) "(platelets[Title]) AND depressive disorder[Title/Abstract]"; (3) "(Platelet[Title]) AND major depressive disorder[Title]"; (4) (platelets[Title]) AND depressed[Title]"; (5) (platelets[Title]) AND depressive episode[Title]"; (6) (platelets[Title]) AND major depression[Title]"; (7) platelet activation in depression[All fields]"; and (8) platelet reactivity in depression[All fields]." RESULTS: After a detailed screening analysis and the application of specific selection criteria, we included in our review a total of 106 for qualitative synthesis. The studies were classified into various subparagraphs according to platelet characteristics analyzed: serotonergic system (5-HT2A receptors, SERT activity, and 5-HT content), adrenergic system, MAO activity, biomarkers of activation, responsivity, morphological changes, and other molecular pathways. CONCLUSIONS: Despite the large amount of the literature examined, nonunivocal and, occasionally, conflicting results emerged. However, the findings on structural and metabolic alterations, modifications in the expression of specific proteins, changes in the aggregability, or in the responsivity to different pro-activating stimuli, may be suggestive of potential platelet dysfunctions in depressed subjects, which would result in a kind of hyperreactive state. This condition could potentially lead to an increased cardiovascular risk. In line with this hypothesis, we speculated that antidepressant treatments would seem to reduce this hyperreactivity while representing a potential tool for reducing cardiovascular risk in depressed patients and, maybe, in other neuropsychiatric conditions. However, the problem of the specificity of platelet biomarkers is still at issue and would deserve to be deepened in future studies.

Towards a psychopathology specific to Substance Use Disorder: Should emotional responses to life events be included?

INTRODUCTION: The severity of emotional responses to life events (PTSD spectrum) as part of Post Traumatic Stress Disorder (PTSD) in Substance Use Disorder (SUD) patients has often been considered from a unitary perspective. Light has also been shed on the possible definition of a specific psychopathology of SUD patients. This psychopathology has been proved to be independent of treatment choice, of being active in using substances, of lifetime psychiatric comorbidity and primary substance of abuse (heroin, alcohol, cocaine). METHODS: To further support this unitary perspective, in this study we have compared the severity and typology of the five psychopathological dimensions found in SUD patients, by dividing 93 HUD patients (77.4% males and 22.6% females), characterized by the lifetime absence of exposure to actual or threatened death, serious injury, or sexual violence, on the basis of the severity of their PTSD spectrum. We used the cut-off that differentiated people developing (High PTSD spectrum; H-PTSD/S) or not developing (Low PTSD spectrum; L-PTSD/S) a PTSD after the earthquake that hit L'Aquila, Italy, in April 2009. RESULTS: Using a canonical correlation analysis, the significant (p<0.001) canonical variate set-one (psychopathology) is saturated negatively by "panic anxiety" and positively by the "worthlessness-being trapped" and "violence-suicide" dimensions. Set-two (PTSD spectrum) is saturated negatively by "emotional, physical and cognitive responses to loss and traumas", and positively by "grief reactions", "re-experiencing numbing", "arousal symptoms" and "personality traits". When comparing the two groups, all five psychopathological dimensions were significantly more severe in H-PTSD/S patients, who were distinguished by higher values of worthlessness-being trapped, sensitivity-psychoticism and violence-suicide symptomatology. No differences were observed regarding the typology of psychopathology. CONCLUSIONS: This study further supports the SUD-PTSD spectrum unitary perspective and argues in favor of the inclusion of the PTSD spectrum in the psychopathology of SUD.

Chronic Cocaine Use and Parkinson's Disease: An Interpretative Model.

Over the years, the growing "epidemic" spread of cocaine use represents a crucial public health and social problem worldwide. According to the 2023 World Drug Report, 0.4% of the world's population aged 15 to 64 report using cocaine; this number corresponds to approximately 24.6 million cocaine users worldwide and approximately 1 million subjects with cocaine use disorder (CUD). While we specifically know the short-term side effects induced by cocaine, unfortunately, we currently do not have exhaustive information about the medium/long-term side effects of the substance on the body. The scientific literature progressively highlights that the chronic use of cocaine is related to an increase in cardio- and cerebrovascular risk and probably to a greater incidence of psychomotor symptoms and neurodegenerative processes. Several studies have highlighted an increased risk of antipsychotic-induced extrapyramidal symptoms (EPSs) in patients with psychotic spectrum disorders comorbid with psychostimulant abuse. EPSs include movement dysfunction such as dystonia, akathisia, tardive dyskinesia, and characteristic symptoms of Parkinsonism such as rigidity, bradykinesia, and tremor. In the present paper, we propose a model of interpretation of the neurobiological mechanisms underlying the hypothesized increased vulnerability in chronic cocaine abusers to neurodegenerative disorders with psychomotor symptoms. Specifically, we supposed that the chronic administration of cocaine produces significant neurobiological changes, causing a complex dysregulation of various neurotransmitter systems, mainly affecting subcortical structures and the dopaminergic pathways. We believe that a better understanding of these cellular and molecular mechanisms involved in cocaine-induced neuropsychotoxicity may have helpful clinical implications and provide targets for therapeutic intervention.

Silent Infections are not So Silent: The Emerging Role of Combined Infections, Inflammation, and Vitamin Levels in OCD.

Objective: Recent evidence highlights that different agents may trigger immune-mediated processes involved in the pathophysiology of different neuropsychiatric conditions. Given the limited information on obsessive-compulsive disorder (OCD), the present study aimed at assessing current/past infections and plasma levels of vitamin D, vitamin B12, folic acid, homocysteine and common peripheral inflammatory markers in a group of OCD outpatients. Method: The sample included 217 adult outpatients with an OCD diagnosis according to the DSM-5 criteria. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to assess the clinical phenotype and symptom severity. Laboratory blood tests measured levels of vitamin D, vitamin B12, folic acid, homocysteine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count and antibodies titers for cytomegalovirus (CMV), Epstein Barr virus (EBV), Toxoplasma gondii and antistreptolysin titer. Results: Sixty-one patients had a previous EBV infection, 46 were seropositive for CMV IgG, 24 showed positive antistreptolysin titer, 14 were seropositive for Toxoplasma gondii IgG, and four for CMV IgM. More than a half of patients showed vitamin D insufficiency. Compared to seronegative patients, patients with a past EBV infection displayed significantly higher scores on the Y-BOCS total score and compulsion subscale, and other symptoms. Vitamin D was negatively correlated with both the Y-BOCS total score and the subscales scores. Folic acid was negatively correlated with the Y-BOCS total and obsessions subscale score. Conclusions: The findings of our study show an association between Epstein-Barr infection and hypovitaminosis D and the overall severity and specific symptom patterns of OCD. The laboratory measures used in this study are useful, cheap and easy parameters that should be routinely assessed in patients with OCD. Further studies are needed to clarify their role in OCD pathophysiology and outcomes, as well as the potential therapeutic impact of vitamins and antibiotics/immunomodulatory agents in OCD and other psychiatric conditions.

A Critical Review of the Psychomotor Agitation Treatment in Youth.

(1) Background: To systematically review evidence on the safety and efficacy of psychopharmacological treatments available for psychomotor agitation (PA) in children and adolescents. (2) Methods: Studies assessing the safety and efficacy of psychopharmacological treatments for acute PA in children and adolescents that were published between January 1984 and June 2022 on PubMed were systematically reviewed. We included: (i) papers that presented a combination of the search terms specified in the "Search strategy" sub-paragraph; (ii) manuscripts in English; (iii) original papers; (iv) prospective or retrospective/observational studies and experimental or quasi-experimental reports. The exclusion criteria were: (i) review papers; (ii) non-original studies including editorials and book reviews; (iii) studies not specifically designed and focused on the selected topic. (3) Results: We selected 42 papers: 11 case series (11/42, 26.19%), 8 chart reviews (8/42, 19.05%), 8 case reports (8/42, 19.05%), 6 double-blind placebo-controlled randomized studies (6/42, 14.29%), 4 double-blind controlled randomized studies (4/42, 9.52%), 4 open-label trials (4/42, 9.52%) and 1 case control (1/42, 2.38%). (4) Conclusions: The drugs most frequently used to treat agitation in children and adolescents were ziprasidone, risperidone, aripiprazole, olanzapine and valproic acid. Further studies are needed to evaluate the efficacy/safety ratio, considering the limited number of observations in this field.

A Case of Delirious Mania Treated with Electroconvulsive Therapy.

(1) Background: Delirious mania is a neuropsychiatric condition characterized by the rapid onset of delirium, psychosis, and mania. Due to the presence of catatonic signs and symptoms, some authors considered this syndrome to be a specific excited catatonia subtype. Usually, delirious mania is responsive to intravenous benzodiazepines (BZDs) or to electroconvulsive therapy (ECT). (2) Methods: In the present study, we describe the case of a 64-year-old woman with a diagnosis of recurrent major depressive disorder. We assessed the severity of the clinical picture and the response to ECT treatment with the Bush-Francis Catatonia Rating Scale (BFCRS). (3) Results: After eleven sessions of ECT, the patient presented a reduced BFCRS total score, with a resolution of the autonomic abnormalities (temperature, respiratory, and heart rate). (4) Conclusions: These data demonstrate how important it is to diagnose this syndrome as soon as possible to set up an effective therapy, avoiding the use of antipsychotic drugs and preventing potentially fatal complications. The initial administration of BZDs IV and the subsequent ECT application, associated with intensive care of life-threatening general medical conditions, guaranteed us a good level of efficacy in obtaining a complete resolution of the clinical picture.

Depression and Pseudodementia: Decoding the Intricate Bonds in an Italian Outpatient Setting.

In spite of the uncertainties of its diagnostic framework, pseudodementia may be conceptualized as a condition characterized by depressive symptoms and cognitive impairment in the absence of dementia. Given the controversies on this topic, the aim of the present study was to assess neurological and cognitive dysfunctions in a sample of elderly depressed subjects, and the eventual relationship between cognitive impairment and depressive symptoms. Fifty-seven elderly depressed outpatients of both sexes were included in the study. A series of rating scales were used to assess diagnoses, depressive and cognitive impairment. Comparisons for continuous variables were performed with the independent-sample Student's t-test. Comparisons for categorical variables were conducted by the χ2 test (or Fisher's exact test when appropriate). The correlations between between socio-demographic characteristics and clinical features, as well as between cognitive impairment and depressive symptoms were explored by Pearson's correlation coefficient or Spearman's rank correlation. Our data showed the presence of a mild-moderate depression and of a mild cognitive impairment that was only partially related to the severity of depression. These dysfunctions became more evident when analyzing behavioral responses, besides cognitive functions. A high educational qualification seemed to protect against cognitive decline, but not against depression. Single individuals were more prone to cognitive disturbance but were similar to married subjects in terms of the severity of depressive symptoms. Previous depressive episodes had no impact on the severity of depression or cognitive functioning. Although data are needed to draw firm conclusions, our findings strengthen the notion that pseudodementia represents a borderline condition between depression and cognitive decline that should be rapidly identified and adequately treated.

The Impact of Covid-19 Pandemic on Mental Health Services: A Comparison Between First Psychiatric Consultations Before and After the Pandemic.

Objective: A high rate of onset or exacerbation of several mental disorders has been observed during the COVID-19 pandemic. However, the risk contributing to mental distress during the pandemic remains unclear. The study aims to evaluate the risk of the onset of mental disorders by comparing the number of requests for the first psychiatric consultation before and after the COVID-19 pandemic at the psychiatric outpatient services of Varese, a small town in Northern Italy. Method: This observational retrospective study aims to compare the requests for the first psychiatric consultation at the outpatient services of Varese during the 14-month period before COVID-19 pandemic (from 1st January 2019 to 28th February 2020) versus the 14-month period after the pandemic (from 1st March 2020 to 31st May 2021) extracted from the server SIPRL-Psicheweb database (Sistema Informativo della Psichiatria, Lombardy Region). For each patient, socio-demographic features and clinical data (psychiatric diagnosis, psychiatric comorbidities, previous psychiatric records, and previous hospitalization in the psychiatric ward) were collected. Results: Three hundred ninety-five consultations were made during the pre-COVID period and 346 during the post-COVID period. No statistically significant difference was found between the number of first consultation requests in the two periods evaluated but a slight decrease in the total number during the pandemic period (395 vs 346; p=0.07) can be noticed. In the subjects of the pre-COVID group, a statistically significant association was detected with no previous psychiatric records ("absent") and with stressor-related disorders. In the post-COVID group, a statistically significant correlation between "present" previous records and anxiety-depressive disorders emerged. Conclusions: It has been observed that anxiety-depressive disorders increased in the post-COVID-19 period compared to the pre-COVID-19, instead of stressor-related disorders. This might be because stressor-related disorders may be treated by general practitioners with no psychiatric interventions. Most of the first consultations during the period of the COVID-19 pandemic were for patients who already had contact with psychiatric services.The study shows an increasing request for care by more severe patients in the first phase of the SARS-CoV-2 pandemic. Further research is needed to investigate the long-term impact of the COVID-19 pandemic on emergency departments and hospital services.

Relationship between BDNF and oxytocin.

Converging, albeit scattered data mainly gathered in animals indicate that the neurotrophin brain-derived neurotrophic factor (BDNF) and the nonapeptide oxytocin (OT) interact in a cooperative way. Data in humans are really limited and indirect. Therefore, the aim of the present study was to explore the possible existence of a link between OT and BDNF in humans, by means of two peripheral markers, the platelet-poor-plasmatic-BDNF (PPP-BDNF) and the platelet BDNF (PLT-BDNF) and OT levels. Twenty-six young healthy controls of both sexes who volunteered for the study were included in the study. Fifty ml of peripheral venous blood were drawn from one-night fasting subjects between 8.00 and 9.00 a.m. The BDNF and OT assays were carried out according to common methods. Comparisons for continuous variables were performed by the Student's t-test for variables that follow a normal distribution, and by the Wilcoxon-Mann-Whitney test for variables not normally distributed. The correlations between biological markers were explored by calculating the Pearson's correlation coefficient or Spearman's rank correlation. The results showed that PLT-BDNF (pg/mg proteins, mean ± SD) and PPP-BDNF (pg/ml, mean ± SD) were 1546 ± 1844 and 10111 ± 1892, respectively. The OT levels (pg/ml, mean ± SD) were 13.92 ± 4.54. The OT levels were significantly higher in women than in men. The Spearman's analysis revealed a statistically significant and negative correlation between OT levels and PLT-BDNF (R = -0.543, p = 0.004). The findings of this study highlight the presence of a significant and negative correlation between OT and PLT-BDNF in a small group of healthy controls of both sexes. In any case, despite all the limits of peripheral biomarkers, they suggest that this reciprocal influence might have a downstream homeostatic function dampening one activity when the other is activated or no longer necessary, maybe at the level of the stress and/or immune systems.

Vitamin B12, homocysteine, and folic acid in patients suffering from bipolar disorders: Relationship with suicide.

OBJECTIVES: Vitamin B12, folic acid, and homocysteine play a key role in 'one-carbon metabolism', involved in different brain processes. Altered levels have been reported in mood disorders (MDs), particularly in major depression (MDD), while the information in bipolar disorders (BDs) is limited. The present study aimed at assessing vitamin B12, homocysteine, and folic acid in 69 bipolar inpatients. METHODS: Twenty-seven patients were diagnosed with BDI, 15 BDII, 16 schizoaffective disorders, and 11 MDD, according to DSM-5 criteria. The clinical picture was assessed by the MINI, HRSD, YMRS, and CGI. The blood parameters were measured according to common clinical-chemical methods. RESULTS: Thirty-four patients had significantly lower vitamin B12, and 14 higher homocysteine levels than normative values. Folic acid levels were normal in the majority of the sample. Patients with a family history of suicide showed significantly lower levels of vitamin B12. CONCLUSIONS: Our results underline the utility of assessing vitamin B12, homocysteine, and folic acid in patients with BD. Although other studies are necessary, the present findings that lower levels of vitamin B12 seem typical of patients with a family history of suicide independently from the phase of illness suggest that they might constitute a possible predictor of suicide.

Internet Use Amongst Professional Tennis Players.

Objective: Next to its well-known benefits, Internet may trigger harmful consequences due to its abuse, thus delineating clinical pictures that are similar to abuse disorders, such as Problematic Internet Use (PIU). The matter becomes more elusive for sportsmen, as data regarding PIU in this specific group are scarce, particularly for tennis players. Therefore, our aim was to assess the prevalence and the features of PIU in a sample of either in current activity or retired professional tennis players, as compared with healthy controls. Method: Twenty-five professional tennis players were evaluated during two events held in two different European countries and were matched to an equal number of healthy subjects who were not performing any agonistic sport. The characteristics of Internet use were assessed by a specific instrument we developed (QUNT). Statistical analyses were carried out to evaluate both demographic and QUNT features and the possible intergroup differences. Results: Retired athletes presented statistically significant lower scores compared to both athletes in current activity and control subjects in the "Time spent online" and in the "Addiction to pornography" domains. Athletes in current activity presented statistically significant higher scores compared to retired athletes in the "Ludopathy" and Total score domains. Male athletes had a statistically significant lower score in the "Addiction to pornography" domain compared to both female and male healthy controls. Conclusions: Tennis players frequently indulge in the use of Internet facilities, particularly those in current activity, thus potentially being more vulnerable to PIU. Men and women seem to use Internet for different activities. The lifestyle that professional tennis players are obliged to follow might provide an explanation of our findings.

Decreased Levels of Vitamin D in Bipolar Patients.

Recently, vitamin D is considered a pleiotropic hormone, and as such, it has also become a topic of renewed interest in neuropsychiatry for its proposed role in the aetiology and pathophysiology of different psychiatric conditions, including mood disorders (MDs). This seems particularly crucial while considering the relatively high and often neglected prevalence of hypovitaminosis D in the general population and in specific groups, such as patients suffering from the most common type of MDs, which are major depression (MDD) and bipolar disorders (BDs). Therefore, in view of the controversial literature and findings on this topic and its potential therapeutic implications, the present study aimed at evaluating vitamin D levels in the plasma of a sample of inpatients fulfilling the DSM-5 criteria for mood episodes within BDs. The clinical picture was assessed by means of specific rating scales. The results showed that the vitamin D levels (mean ± SD, nM/L) of the bipolar patients of our sample were significantly lower (14.58 ± 11.27 nmol/L) than the normative values (>30 nmol/L). Eleven patients had sufficient values and only 4 had optimal, while 19 showed insufficient, 18 critical, and 17 severely critical levels. No differences emerged according to different socio-demographic or clinical features. In our opinion, the present findings strengthen previous research highlighting decreased vitamin D levels in bipolar patients and support the role of this pleiotropic hormone in BDs. Nevertheless, further studies should follow to corroborate the data of this preliminary study and to address the potential benefits of vitamin D supplementation in the treatment of MDs.

Neuropsychiatric Manifestations of Fahr's Disease, Diagnostic and Therapeutic Challenge: A Case Report and a Literature Review.

Objective: Calcifications in basal ganglia could be an incidental finding up to 20% of asymptomatic patients undergoing computed tomography (CT) or magnetic resonance imaging (MRI) scan. The presence of neuropsychiatric symptomatology associated with basal ganglia calcifications identifies a clinical entity defined as Fahr's Disease. This term is used in presence of calcifications secondary to a specific cause, but the variability of etiology, pathogenesis, and clinical picture underlying this condition have raised the question of the real existence of a syndrome. Several classifications based on the etiology, the location of brain calcifications and the clinical presentation have been proposed. Method: In the present study, we describe the case of a 52 years old man with a Bipolar I disorder diagnosis and a recent onset of behavioral disinhibition and alcohol misuse. The patient came to our center, specialized for bipolar disorder, as a consequence of a progressive worsening of the clinical picture associated to behavioral disturbances (sexual disinhibition, episodes of binge-eating, alcohol misuse), initial degrees of deterioration in cognitive function, peculiar psychotic symptoms and a resistance to various psychopharmacological treatment. The patient underwent neuro-psychologic evaluation, laboratory examinations and neuroimaging. Results and Conclusions: CT and MRI revealed basal ganglia calcification and, in presence of normal blood tests, a diagnosis of Fahr's syndrome was suggested. During the hospitalization, the patient showed a good clinical response to a psychopharmacological therapy constituted by two mood stabilizers (lithium carbonate and oxcarbazepine) and mild antipsychotics doses (quetiapine and aripiprazole). Finally, we performed a literature review on the complex and multifaceted neuropsychiatric clinical manifestations of Fahr's disease in order to provide useful elements in terms of etiology, clinical manifestation, diagnosis, and treatment.

Psychomotor Symptoms in Chronic Cocaine Users: An Interpretative Model.

According to the latest estimates, there are around 24.6 million cocaine users worldwide, and it is estimated that around a quarter of the population worldwide has used cocaine at some point in their lifetime. It follows that such widespread consumption represents a major risk for public health. Long-term use of cocaine, in addition to being related to many cerebral and cardiovascular diseases, is increasingly associated with a higher incidence of psychomotor symptoms and neurodegenerative disorders. In recent years, numerous studies have shown an increased risk of antipsychotic-induced extrapyramidal symptoms (EPSs) in patients with psychotic spectrum disorders comorbid with psychostimulant misuse, particularly of cocaine. In the present paper, we describe the case of a young patient on his first entry into a psychiatric setting with previous cocaine misuse who rapidly presented psychomotor symptoms and was poorly responsive to symptomatic therapy consisting of benzodiazepines and anticholinergics, in relation to the introduction of various antipsychotics (first, second, and third generation). Furthermore, we propose neurobiological mechanisms underlying the hypothesized increased vulnerability to psychomotor symptoms in chronic cocaine abusers. Specifically, we supposed that the chronic administration of cocaine produces important neurobiological changes, causing a complex dysregulation of various neurotransmitter systems, mainly affecting subcortical structures and the dopaminergic and glutamatergic pathways. We believe that a better understanding of these neurochemical and neurobiological processes could have useful clinical and therapeutic implications by providing important indications to increase the risk-benefit ratio in pharmacological choice in patients with psychotic spectrum disorders comorbid with a substance use disorder.

Oxytocin: An Old Hormone, a Novel Psychotropic Drug and its Possible Use in Treating Psychiatric Disorders.

BACKGROUND: Oxytocin is a nonapeptide synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Historically, this molecule has been involved as a key factor in the formation of infant attachment, maternal behavior and pair bonding and, more generally, in linking social signals with cognition, behaviors and reward. In the last decades, the whole oxytocin system has gained a growing interest as it was proposed to be implicated in etiopathogenesis of several neurodevelopmental and neuropsychiatric disorders. METHODS: With the main goal of an in-depth understanding of the oxytocin role in the regulation of different functions and complex behaviors as well as its intriguing implications in different neuropsychiatric disorders, we performed a critical review of the current state of the art. We carried out this work through the PubMed database up to June 2021 with the search terms: 1) "oxytocin and neuropsychiatric disorders"; 2) "oxytocin and neurodevelopmental disorders"; 3) "oxytocin and anorexia"; 4) "oxytocin and eating disorders"; 5) "oxytocin and obsessive- compulsive disorder"; 6) "oxytocin and schizophrenia"; 7) "oxytocin and depression"; 8) "oxytocin and bipolar disorder"; 9) "oxytocin and psychosis"; 10) "oxytocin and anxiety"; 11) "oxytocin and personality disorder"; 12) "oxytocin and PTSD". RESULTS: Biological, genetic, and epigenetic studies highlighted quality and quantity modifications in the expression of oxytocin peptide or in oxytocin receptor isoforms. These alterations would seem to be correlated with a higher risk of presenting several neuropsychiatric disorders belonging to different psychopathological spectra. Collaterally, the exogenous oxytocin administration has shown to ameliorate many neuropsychiatric clinical conditions. CONCLUSION: Finally, we briefly analyzed the potential pharmacological use of oxytocin in a patient with severe symptomatic SARS-CoV-2 infection due to its anti-inflammatory, antioxidative and immunoregulatory properties.

Different Sides of Depression in the Elderly: An In-depth View on the Role of Aß Peptides.

BACKGROUND: Late-onset depression (LOD) is the most common neuropsychiatric disorder associated with Alzheimer's disease (AD), often associated with structural and functional brain changes, neuropsychological impairments and negative family history for affective disorders. LOD could be a risk factor or a prodromal phase of AD; this has led to the investigation of the link between depression and amyloid-ß (Aß) peptides by measuring Aß levels in plasma, cerebrospinal fluid (CSF) and brains of elderly depressed subjects. OBJECTIVE: This study aims to clarify the complex relationship between depression, Aß peptides and AD. METHODS: We evaluated all articles published up to 2019 in PubMed in which Aß was measured in serum (or plasma), CSF or brain in elderly with Major Depressive Disorder or depressive symptoms evaluated with standard scales. RESULTS: Low plasma Aß42 levels are strongly associated with depression severity. Plasma Aß40 levels are higher in younger depressed, drug-resistant and those with more severe symptoms. CSF Aß42 levels are lower in depressed than controls. PET-detected global and region-specific increases in Aß deposition are sometimes associated with LOD, cognitive impairment, anxiety but not with Cardiovascular Diseases (CVDs)/CVD risk factors. Elderly depressed with CVDs/CVD risk factors have more frequently high plasma Aß40 levels and drug-resistance; those without Conclusion: Two specific Aß profiles emerge in the depressed elderly. One is associated with Aß42 reductions in plasma and CSF, possibly reflecting increased brain amyloid deposition and prodromal AD. The other one is characterized by high plasma Aß40 levels, cerebrovascular disease and is clinically associated with increased AD risk.

Type 2 Diabetes Mellitus, Platelet Activation and Alzheimer's Disease: A Possible Connection.

Type 2 diabetes mellitus DM (T2DM) is associated with a 70% increased risk for dementia, including Alzheimer's disease (AD). Insulin resistance has been proposed to play a pivotal role in both T2DM and AD and the concept of "brain insulin resistance" has been suggested as an interpretation to the growing literature regarding cognitive impairment and T2DM. Subjects with T2DM present an abnormal platelet reactivity that together with insulin resistance, hyperglycaemia and dyslipidaemia effect the vascular wall by a series of events including endothelial dysfunction, oxidative stress and low-grade inflammation. Activated platelets directly contribute to cerebral amyloid angiopathy (CAA) by promoting the formation of ß-amyloid (Aß) aggregates and that Aß, in turn, activates platelets, creating a feed-forward loop suggesting the involvement of platelets in the AD pathogenesis. Moreover, islet amyloid polypeptide deposition, co-localized with Aß deposits, is a common finding in the brain of patients with T2DM. These observations raise the intriguing prospect that traditional or novel antiplatelet therapeutic strategies may alleviate fibril formation and could be used in the prevention or treatment of AD subjects with diabetes.

Platelet APP Processing: Is It a Tool to Explore the Pathophysiology of Alzheimer's Disease? A Systematic Review.

The processing of the amyloid precursor protein (APP) is a critical event in the formation of amyloid plaques. Platelets contain most of the enzymatic machinery required for APP processing and correlates of intracerebral abnormalities have been demonstrated in platelets of patients with AD. The goal of the present paper was to analyze studies exploring platelet APP metabolism in Alzheimer's disease patients trying to assess potential reliable peripheral biomarkers, to offer new therapeutic solutions and to understand the pathophysiology of the AD. According to the PRISMA guidelines, we performed a systematic review through the PubMed database up to June 2020 with the search terms: "((((((APP) OR Amyloid Precursor Protein) OR AbetaPP) OR Beta Amyloid) OR Amyloid Beta) OR APP-processing) AND platelet". Thirty-two studies were included in this systematic review. The papers included are analytic observational studies, namely twenty-nine cross sectional studies and three longitudinal studies, specifically prospective cohort study. The studies converge in an almost unitary way in affirming that subjects with AD show changes in APP processing compared to healthy age-matched controls. However, the problem of the specificity and sensitivity of these biomarkers is still at issue and would deserve to be deepened in future studies.

The Importance of a Multi-Disciplinary Approach to the Endometriotic Patients: The Relationship between Endometriosis and Psychic Vulnerability.

Endometriosis is a chronic inflammatory condition, which is distinguished by the presence of the endometrial-like glands and stroma outside the uterine cavity. Pain and infertility are the most commonly expressed symptoms, occurring in 60% and 40% of cases, respectively. Women with endometriosis, especially those with pelvic pain, also have a greater vulnerability to several psychiatric disorders. There is, in particular, a tendency to contract affective or anxiety disorders as well as panic-agoraphobic and substance use disorders. Endometriosis with pelvic pain, infertility and psychic vulnerability usually leads to disability and a markedly lower quality of life for women of reproductive age. Thus, the burden of endometriosis is not limited to the symptoms and dysfunctions of the disease; it extends to the social, working and emotional spheres, leading to a severe impairment of global functioning. An analysis of scientific literature revealed a close relationship between specific temperamental traits, the expression of several psychiatric symptoms, chronicity of pain, risk of substance use and lower probability of a positive outcome. Endometriosis symptoms and the impact of related psychological consequences, increased vulnerability and the possible onset of psychiatric symptoms may influence coping strategies and weaken resilience, so triggering a vicious cycle leading to a marked deterioration in the quality of life. A multidisciplinary approach consisting of a medical team composed of gynecologists, psychologists, psychiatrists, experts in Dual Disorder, algologists and sexologists, would guarantee the setting of a target and taking the best decision on a personalized treatment plan. That approach would allow the prompt detection of any psychopathological symptoms and improve the endometriosis-related physical symptoms, bringing a healthier quality of life and a greater likelihood of a positive outcome.