Annamaria Cattaneo

• University of Brescia

During pregnancy multiple biological systems undergo consistent modifications, in particular the hormonal axes and the immune system. Moreover, while it is well known that pregnant women suffering from depression show alterations in these systems, the exact underlying mechanisms are still not clear. For this reason, in this study, we explored the b...

Alzheimer’s disease is marked by cognitive and memory impairment, with early disruptions in the balance between excitatory and inhibitory neurotransmission, thought to be closely linked to co-occurrent brain changes. The posterior-to-anterior hypothesis posits that functional neurodegeneration begins in critical areas of the default mode network, p...

Background The mechanisms underlying the protective effect of the e2 variant of the APOE gene (APOEe2) against Alzheimer’s disease (AD) have not been elucidated. We altered the microbiota of 3xTgAD mice by fecal microbiota transplantation from a human APOEe2 donor (e2-FMT) and tested the effect of microbiota perturbations on brain AD pathology. Me...

It is well known that one third of depressed patients do not respond to two or more antidepressant treatments and the majority has a chronic or intermittent disease course, experiencing recurrent relapses, or developing physical comorbidity, such as cardiometabolic disorders. The biological underpinnings are multifaceted, complex, and not yet fully...

Human microbiota‐associated murine models, using fecal microbiota transplantation (FMT) from human donors, help explore the microbiome's role in diseases like Alzheimer's disease (AD). This study examines how gut bacteria from donors with protective factors against AD influence behavior and brain pathology in an AD mouse model. Female 3xTgAD mice r...

Purpose: Treatments for mental disorders, such as pharmacotherapy and psychosocial interventions, do not always guarantee symptomatic remission. The effectiveness of Physical Activity (PA) in improving the psychophysical health of individuals with various mental disorders is well-established; however, its effects on borderline personality disorder...

Background Developing interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is...

Background Current treatments for mental disorders, like pharmacotherapy or psychological approaches, do not lead to full remission in all individuals. Physical activity (PA) is effective at improving psycho-physical health in major depressive and anxiety disorders. However, the efficacy of PA as an adjunctive treatment for borderline personality d...

Objective An emerging marker of depression in the perinatal period is represented by a reduction in the autonomic nervous system (ANS) activity, reflected by heart rate variability (HRV). This scoping review aims to map the association between HRV and depression during the perinatal period and to understand its potential clinical implications. Int...

About one third of patients suffering from Major Depressive Disorder (MDD) do not respond to any antidepressant medications and 75% experience relapses and general health deterioration. Importantly, inflammation can contribute to such negative outcomes, as well as to cause depression in patients who have been exposed to adverse childhood experience...

Transcriptomic profiles are important indicators for molecular mechanisms and pathways involved in major depressive disorder (MDD) and its different phenotypes, such as immunometabolic depression. We performed whole-transcriptome and pathway analyses on 139 individuals from the observational, case-control, BIOmarkers in DEPression (BIODEP) study, 1...

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from...

The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world’s adolescents living in low- and middle-income countries (LMIC). Taking advantage of a uni...

Exposure to early-life stress (ELS) has been related to an increased susceptibility to psychiatric disorders later in life. Although the molecular mechanisms underlying this association are still under investigation, glucocorticoid signaling has been proposed to be a key mediator. Here, we used two preclinical models, the prenatal stress (PNS) anim...

Important sex-related differences have been observed in the onset, prevalence, and clinical phenotype of depression, based on several epidemiological studies. Social, behavioural, and educational factors have a great role in underlying this bias; however, also several biological factors are extensively involved. Indeed, sexually dimorphic biologica...

Background The ε4 allele of the Apolipoprotein E gene (APOE) is a well‐established risk factor for Alzheimer’s disease (AD), ε4 carriers showing earlier onset and more severe memory impairment than non‐carriers. Neuroimaging evidence suggests that APOEε4 may modulate neural activity in AD since early stages. The purpose of this study was to determi...

Background Recent studies reported microstructural alterations in the locus coeruleus ‐ transentorhinal cortex (LC‐TEC) pathway in patients with Alzheimer’s disease (AD) but data in subjects at risk of AD (i.e., cognitively intact APOEε4 carriers) are missing. In this study, we apply in‐vivo diffusion weighted images (DWI) to study the effect of AP...

Background Recent studies reported microstructural alterations in the locus coeruleus ‐ transentorhinal cortex (LC‐TEC) pathway in patients with Alzheimer’s disease (AD) but data in subjects at risk of AD (i.e., cognitively intact APOEe4 carriers) are missing. In this study, we apply in‐vivo diffusion weighted images (DWI) to study the effect of AP...

Background The e4 allele of the Apolipoprotein E gene (APOE) is a well‐established risk factor for Alzheimer’s disease (AD), e4 carriers showing earlier onset and more severe memory impairment than non‐carriers. Neuroimaging evidence suggests that APOEe4 may modulate neural activity in AD since early stages. The purpose of this study was to determi...

Exposure to stress can lead to long lasting behavioral and neurobiological consequences, which may enhance the susceptibility for the onset of mental disorders. However, there are significant individual differences in the outcome of stress exposure since only a percentage of exposed individuals may show pathological consequences, whereas others app...

Background The workload associated with caring for a person with dementia (PwD) could negatively affect informal caregivers’ physical and mental health. According to the recent literature, there is a need for studies testing the implementation of affordable and accessible interventions for improving caregivers’ well-being. Aims This study aimed to...

Alzheimer’s disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer’s disease by showing specific alterations in the gut microbiome composition of Alzheimer’s patients and in rodent models. Howev...

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual data from 13 clinical studies o...

Early life stress (ELS) is associated with treatment-resistant depression (TRD), and trauma-focused psychotherapy benefits TRD patients exposed to ELS. We explored peripheral modulations of stress-response genes (nuclear receptor subfamily 3 group C member 1 [NR3C1] , FK506-binding protein 5 [FKBP5] , and serum/glucocorticoid-regulated kinase 1 [ S...

Although the association between cognitive performances and the onset of psychiatric disorders has been widely investigated, limited research on the role of childhood trauma or early life stress (CT/ELS), and whether this role differs between clinical and non-clinical cohorts is available. This systematic review aims at filling this gap, testing wh...

Background Microbiota‐derived short chain fatty acids (SCFA) and liposaccharide (LPS) could modulate astrocyte and neuronal activity. Glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) are markers of astroglial activation and neuronal damage, can be measured in blood samples and have been associated with Alzheimer’s disease (AD) p...

Abstract Compelling evidence demonstrates that some individuals suffering from major depressive disorder (MDD) exhibit increased levels of inflammation. Most studies focus on inflammation-related proteins, such as serum or plasma C-reactive protein (CRP). However, the immune-related modifications associated with MDD may be not entirely captured by...

Abstract Background Increasing evidence links the gut microbiota (GM) to Alzheimer’s disease (AD) but the mechanisms through which gut bacteria influence the brain are still unclear. This study tests the hypothesis that GM and mediators of the microbiota-gut-brain axis (MGBA) are associated with the amyloid cascade in sporadic AD. Methods We includ...

Neuroinflammation is an important component of many neurodegenerative diseases, whether as a primary cause or a secondary outcome. For that reason, either as diagnostic tools or to monitor progression and/or pharmacological interventions, there is a need for robust biomarkers of neuroinflammation in the brain. Mitochondrial TSPO (18 kDa Translocato...

Major depressive disorder is a leading cause of disability worldwide; therefore, effective treatment options are crucial. However, due to the highly heterogeneous nature of depression, a comprehensive understanding of the disease is lacking and treatment options are limited. Whilst the pathology of depression is complex, neuroendocrine–immune inter...

Prostate cancer (PCa) is a leading cause of death in the male population commonly treated with androgen deprivation therapy that often relapses as androgen-independent and aggressive castration-resistant prostate cancer (CRPC). Ferroptosis is a recently described form of cell death that requires abundant cytosolic labile iron to promote membrane li...

The gut microbiome is emerging as an important susceptibility factor in Alzheimer’s disease (AD) possibly due to the increased prevalence of pro-inflammatory genera in gut microbiota of AD participants. Microbiota-mediated changes in cognition and adult hippocampal neurogenesis (AHN), an important process for memory which is altered in AD, position...

The gut microbiome is emerging as an important susceptibility factor in Alzheimers disease (AD) possibly due to the increased prevalence of pro-inflammatory genera in gut microbiota of AD participants. Microbiota-mediated changes in cognition and adult hippocampal neurogenesis (AHN), an important process for memory which is altered in AD, position...

Background Bipolar Disorder (BD) is a complex mental disease characterized by recurrent episodes of mania and depression. Lithium (Li) represents the mainstay of BD pharmacotherapy, despite the narrow therapeutic index and the high variability in treatment response. However, although several studies have been conducted, the molecular mechanisms und...

Background Treatment-resistant depression (TRD) results in huge healthcare costs and poor patient clinical outcomes. Most studies have adopted a “candidate mechanism” approach to investigate TRD pathogenesis, however this is made more challenging due to the complex and heterogeneous nature of this condition. High-throughput “omics” technologies can...

CYP2D6 is a widely expressed human xenobiotic metabolizing enzyme, best known for its role in the hepatic phase I metabolism of up to 25% of prescribed medications, which is also expressed in other organs including the brain, where its potential role in physiology and mental health traits and disorders is under further investigation. Owing to the p...

Early-life stress (ELS) exposure increases the risk for mental disorders, including cognitive impairments later in life. We have previously demonstrated that a dietary low ω6/ω3 polyunsaturated fatty acid (PUFA) ratio protects against ELS-induced cognitive impairments. Several studies have implicated the neuroimmune system in the ELS and diet media...

Background: Adolescents have been deeply exposed to negative consequences of social distancing imposed by Covid-19. There is a lack of longitudinal studies regarding the impact on adolescents of this unfavorable condition, and their results are controversial. The aim of the present prospective study is to assess psychopathological symptoms in adol...

Animal models are useful preclinical tools for studying the pathogenesis of mental disorders and the effectiveness of their treatment. While it is not possible to mimic all symptoms occurring in humans, it is however possible to investigate the behavioral, physiological and neuroanatomical alterations relevant for these complex disorders in control...

Background Exposure to traumatic experience represents one of the key environmental factors influencing the risk for several psychiatric disorders, in particular when suffered during childhood, a critical period for brain development, characterized by a high level of neuroplasticity. Abnormalities affecting neurotrophic factors, might play a fundam...

Background Emotional dysregulation (ED) constitutes a relevant factor involved in the onset and maintenance of many mental disorders. Targeting ED during adolescence could be a determinant both to identify high-risk individuals and to promote preventive interventions. This study will aim to evaluate the impact of a brief Dialectical Behavioral Ther...

Background: Human microbiota-associated (HMA) murine models are developed by gavaging mice with human bacteria or stools and are increasingly used to study the relation between the human microbiota and disease. The aim of this study is to evaluate the effect of gut bacteria isolated from donors with or without Alzheimer's dementia on behavior in A...

Background: Although recent data support an association between certain bacterial strains and Alzheimer's Disease (AD), it is not clear how these alterations contribute to different aspects of the disease. Increasing evidences also from our group (Cattaneo, AAIC 2020), suggest that endothelial dysfunction, reflected by the upregulation of cell adh...

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of beta-amyloid (Aβ42) and phosphorylated tau (P-tau) deposits in the brain, neurodegeneration in specific brain regions, and inflammation. This study aimed at investigating the association of periferal inflammatory signaling with brain structural al...

Many antidepressants, atomoxetine, and several antipsychotics are metabolized by the cytochrome P450 enzymes CYP2D6 and CYP2C19, and guidelines for prescribers based on genetic variants exist. Although some laboratories offer such testing, there is no consensus regarding validated methodology for clinical genotyping of CYP2D6 and CYP2C19. The aim o...

Major depressive disorder (MDD) is a complex mental disorder where the neurochemical, neuroendocrine, immune, and metabolic systems are impaired. The microbiota-gut-brain axis is a bidirectional network where the central and enteric nervous systems are linked through the same endocrine, immune, neural, and metabolic routes dysregulated in MDD. Thus...

Antenatal psychopathology negatively affects obstetric outcomes and exerts long-term consequences on the offspring’s wellbeing and mental health. However, the precise mechanisms underlying these associations remain largely unknown. Here, we present a novel model system in mice that allows for experimental investigations into the effects of antenata...

The default mode (DMN) and the salience (SN) networks show functional hypo-connectivity in Alzheimer's disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD), respectively, along with patterns of hyper-connectivity. We tested the clinical and neurobiological effects of non-invasive stimulation over these networks in 45 patients...

Extensive research suggests a role for the innate immune system in the pathogenesis of depression, but most of the studies are conducted in adult populations, in high-income countries and mainly focus on the study of inflammatory proteins alone, which provides only a limited understanding of the immune pathways involved in the development of depres...

Exposure to early adverse experiences induces persistent changes in physiological, emotional and behavioural functions predisposing the individual to an enhanced vulnerability to develop different disorders during lifespan. The adverse outcomes depend upon the timing of the stressful experiences, and in this contest, adolescence represents a key se...

Background Exposure to early adverse experiences induces persistent changes predisposing the individual to an enhanced vulnerability to develop physical and mental disorders during lifespan. The adverse outcomes depend upon the timing of the stressful experiences, which may differentially influence specific brain regions and biological systems. Me...

Background Antidepressants are a first line treatment for depression. However, only a third of individuals remit after the first treatment. Common genetic variation likely regulates, in part, antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic...

A combination of different risk factors, such as genetic, environmental and psychological factors, together with immune system, stress response, brain neuroplasticity and the regulation of neurotransmitters, is thought to lead to the development of major depressive disorder (MDD). A growing number of studies have tried to investigate the underlying...

Background: Emotional dysregulation (ED) constitutes a relevant factor involved in the onset and maintenance of many mental disorders. Targeting ED during adolescence could be determinant both to identify high risk individuals and to promote preventive interventions. This study will aim to evaluate the impact of a brief Dialectical Behavioral Thera...

Background: No study investigated the association between stress exposure in different stages of life and metabolic dysfunction. Aim: We explore the association between stress exposure and several biomarkers related to glucose metabolism (insulin, c-peptide, GIP, GLP-1, glucagon) in a group of 72 healthy individuals. Method: We used the Childhood E...

Background Physical activity promotes resilience and reduces stress. Here we aimed to clarify the impact of physical activity and childhood trauma experiences on current mood and cognitive function in patients with schizophrenia (SZ) or bipolar disorders (BD). Methods Three-hundred-and-six patients with a DSM-IV schizophrenia (SZ) or bipolar disor...

Prenatal stress (PNS) affects foetal programming and, through an interaction with subsequent challenges, can increase vulnerability to mood and metabolic disorders. We have previously shown that, following PNS, adult male rats are characterised by increased vulnerability to a metabolic stressor experienced at adulthood (8‐week‐high‐fat diet ‐ HFD)....

[This corrects the article DOI: 10.3389/fpsyt.2020.00389.].

A Correction to this paper has been published: https://doi.org/10.1038/s41380-020-01014-9

Introduction Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the de...

There are some data associating variants in the CYP2D6 and/or CYP2C19 genes with concentration-to-dose ratios, efficacy, and retention in treatments. However, much of the above arises from relatively small studies or large datasets with limited genotyping methodologies. Our aim was to develop and validate comprehensive and accurate genotyping metho...