Giulia Petrillo

RESEARCH, TEACHING, or OTHER INTERESTS

Psychiatry and Mental health, Biochemistry, Genetics and Molecular Biology

Scopus Publications

Immune dysregulation and neuroinflammation in bipolar disorder: Pathophysiological insights and therapeutic perspectives
Floriana De Cillis, Veronica Begni, Ilari D'Aprile, Giulia Petrillo, Marco Andrea Riva, Annamaria Cattaneo
Brain Behavior and Immunity Health, 2026
From Fat to Brain: Adiponectin as a Mediator of Neuroplasticity in Depression
Patrizia Genini, Ilari D’Aprile, Giulia Petrillo, Maria Grazia Di Benedetto, Veronica Begni, Nadia Cattane, Annamaria Cattaneo
Biomolecules, 2025
Depression is a leading cause of global disability and is increasingly recognized as a multifactorial disorder characterized by fundamental disruptions in neuroplasticity, including diminished hippocampal neurogenesis, impaired synaptic plasticity, and dysregulated stress-response systems. Given the limited efficacy of conventional pharmacological treatments, lifestyle-based interventions—most notably physical exercise—have gained considerable attention for their antidepressant effects, partly mediated by secreted exerkines. Among these, adiponectin has emerged as a particularly compelling candidate linking metabolic regulation to neuroplasticity and mood. Recent evidence suggests that adiponectin contributes to the antidepressant effects of exercise by modulating hippocampal neurogenesis, neuroinflammation, and brain-derived neurotrophic factor (BDNF) signalling. Despite these advances, the mechanisms by which adiponectin influences depression remain incompletely understood. This review synthesizes current knowledge on adiponectin’s role in depression pathophysiology, with emphasis on its capacity to enhance neuroplasticity and hippocampal neurogenesis, and its potential to mediate exercise-induced antidepressant effects via defined molecular pathways. Building on these insights, we discuss adiponectin’s translational promise as both a predictive biomarker of treatment response and a novel therapeutic target. By integrating preclinical and clinical evidence, this review offers a comprehensive perspective on adiponectin’s involvement in depression while identifying critical gaps to guide future mechanistic research.
Inflammatory status along the brain-liver axis in animals vulnerable to prenatal stress: sex-related implications for stress-induced comorbidities
Ilari D’Aprile, Giulia Petrillo, Veronica Begni, Kerstin Camile Creutzberg, Rodrigo Orso, Rodrigo Grassi-Oliveira, Marco Andrea Riva, Annamaria Cattaneo
Translational Psychiatry, 2025
The prevalence of mood disorders is constantly increasing, with exposure to stress early in life (ELS) as one of the major risk factors. Recent studies reported that ELS can increase the risk for mental disorders, but also for several cardiometabolic conditions, often in comorbidity. However, biological processes underlying these negative outcomes with a sex dependent effect are still poorly understood. Here, we used the preclinical model of prenatal stress (PNS) mimicking early in life adversities to investigate the presence of an abnormal inflammatory response as a possible mechanism leading to the onset of a vulnerable phenotype for mental and metabolic disorders in the offspring. We showed that adolescent male rats, classified as vulnerable to PNS by a two-step cluster analysis, based on three different behavioral tests, have brain microglia hyperactivation in the dorsal hippocampus. We then focused on liver, as a key organ involved in the development of several metabolic disorders and strictly communicating with the brain via immune-inflammatory pathways. We found that rats showing a vulnerable behavioral phenotype also showed abnormal inflammatory response in the liver. Moreover, liver inflammation is correlated with an increased expression of leptin receptor, an important adipokine involved in several metabolic processes. Overall, this study suggests that male but not female rats exposed to PNS and showing a vulnerable phenotype are characterized by brain and liver pro-inflammatory status, pointing out the need to target the inflammatory system via pharmacological or non-pharmacological strategies to reduce the risk for both mental and physical disorders in individuals exposed to ELS.
Exposure to early-life stress uncovers shared biological signatures underlying vulnerability in the habenula and insular cortex of male and female adult rats
Valentina Zonca, Moira Marizzoni, Samantha Saleri, Monica Mazzelli, Giulia Petrillo, Maria Grazia Di Benedetto, Floriana De Cillis, Marco Andrea Riva, Annamaria Cattaneo
Neurobiology of Stress, 2025
Early-life stress (ELS) is a well-known risk factor for the development of several mental disorders later in life. The effect of ELS can be twofold: resilient individuals adapt by perceiving stress as minimal, while vulnerable ones struggle to cope with it and are predisposed to the onset of psychopathology. Although it is known that different brain regions play a role in determining ELS resilience or vulnerability, the specific mechanisms remain unclear. This preclinical study examines the effects of prenatal stress (PNS) on the functional connectivity of habenula (Hb) and insular cortex (IC) and whether these alterations predispose to stress vulnerability in adulthood. PNS was associated with reduced social interaction in both male and female animals, suggesting the onset of a potentially altered behavioral phenotype. Transcriptomic analysis of vulnerable and resilient animals revealed profound PNS-induced gene expression changes in both Hb and IC, with sex-specific patterns. In vulnerable males, pathway analysis identified a shared molecular signature between Hb and IC primarily involving the activation of inflammation and collagen-related processes. In females, vulnerability was linked to downregulation of serotonin signaling, indicating an alternative pathway to stress susceptibility compared with males. Co-expression network analysis confirmed these findings, highlighting sex-dependent biological mechanisms underlying vulnerability. These results suggest that vulnerability to stress may emerge from functional interactions between Hb and IC, mediated by distinct and sex-specific pathways. • Prenatal stress can induced social impairments in both male and female adult animals. • PNS alters gene expression profile in the habenula and insular cortex with sex-specific patterns. • Functional interactions between the habenula and insular cortex may underlie prenatal stress response, mediated by sex-dependent mechanisms. • Vulnerability to stress is linked to upregulation of inflammation and collagen pathways in males in both habenula and insular cortex. • Vulnerability is linked to downregulation of serotonin signalling in females in both regions.
Systemic Inflammation at the Crossroad of Major Depressive Disorder and Comorbidities: A Narrative Review
Erika Vitali, Nadia Cattane, Ilari D’Aprile, Giulia Petrillo, Annamaria Cattaneo
International Journal of Molecular Sciences, 2025
Major Depressive Disorder (MDD) represents a global challenge due to its high prevalence worldwide. Inflammation is the most extensively studied and plausible biological pathway involved in the onset of MDD. Individuals with MDD often exhibit low-grade inflammation, characterized by immune system dysregulation and activation of pro-inflammatory pathways. Elevated inflammation is also associated with a reduced response to antidepressant therapies, suggesting that targeting inflammation could represent a promising therapeutic approach for MDD. MDD frequently co-occurs with other pathological conditions, including cardiometabolic, autoimmune, and chronic pain disorders. These comorbidities further complicate MDD treatment and contribute to reduced antidepressant efficacy. Like MDD, these disorders are characterized by a strong inflammatory component, and several cytokines and pro-inflammatory mechanisms altered in MDD are also found in these comorbid conditions. This narrative review explores inflammation as a shared biological mechanism in MDD and its most frequent comorbidities, to provide a comprehensive understanding of the interplay between inflammation and these comorbid conditions. Persistent low-grade inflammation may help explain the high rate of bidirectional co-occurrence between MDD and its comorbidities. Moreover, it may represent a target for better understanding the molecular mechanisms driving this co-occurrence, potentially contributing to the development of tailored treatment and improving antidepressants response rates.
Prenatal Stress Rewires the Gut–Brain Axis: Long-Term, Sex-Specific Effects on Microbiota, Intestinal Barrier, and Hippocampal Inflammation †
Floriana De Cillis, Giulia Petrillo, Ilari D’Aprile, Moira Marizzoni, Samantha Saleri, Monica Mazzelli, Valentina Zonca, Maria Grazia Di Benedetto, Marco Andrea Riva, Annamaria Cattaneo
Nutrients, 2025
Background: The gut microbiota and the gut epithelium play a central role in maintaining systemic and brain homeostasis from early life. Stressful experiences during sensitive developmental windows can disrupt this balance, increasing long-term susceptibility to psychiatric disorders. However, the mechanisms through which early-life alterations in the microbiota influence brain development and function remain poorly understood. Here, the sex-specific impact of prenatal stress (PNS) on gut integrity and microbial composition in adult offspring was explored. Methods: Thirty dams were mated and randomly assigned to PNS or control. Offspring microbiota was analysed through 16S rRNA sequencing, intestinal morphology with morphometric analyses, and tight junctions using qPCR and immunofluorescence. Results: Exposure to PNS was associated with reduced intestinal surface area in males and shortened crypts in females. In both sexes, PNS caused a decrease in the expression of ZO-1, suggesting impaired gut barrier integrity. 16S rRNA sequencing revealed, furthermore, that PNS exposure was associated with a decrease in beneficial genera, including Akkermansia in males and Clostridia vadinBB60 in females, along with an increase in the pro-inflammatory genus Anaerotruncus, regardless of sex. Notably, some of these alterations were more pronounced in PNS-exposed animals that showed impaired sociability, highlighting gut microbiota inter-individual variability in the response to early-life adversity. Moreover, selected microbial changes show significant correlations with the behavioural outcomes, as well as with intestinal morphology or brain inflammatory markers. Conclusions: Together, these findings pinpoint the gut as a central player in stress vulnerability and highlight specific microbial signatures as promising biomarkers and therapeutic targets for stress-related disorders.
Sex-specific metabolic and inflammatory alterations in adult animals vulnerable to prenatal stress exposure
Ilari D'Aprile, Giulia Petrillo, Valentina Zonca, Monica Mazzelli, Floriana De Cillis, Maria Grazia Di Benedetto, Marco Andrea Riva, Annamaria Cattaneo
Progress in Neuro Psychopharmacology and Biological Psychiatry, 2025
Early life stress (ELS) is a significant risk factor for the development of mood and metabolic disorders later in life, which are often in comorbidity. Although it is well known that not all the exposed individuals develop these conditions, the mechanisms leading to a vulnerable or a resilient phenotype for mood and metabolic disorders , as consequences of ELS exposure, are still not fully understood. In this study, we used a prenatal stress (PNS) model, mimicking perinatal adversities, to investigate the impact of ELS on metabolic function, stress-related and inflammatory markers in adult male and female offspring, with a particular focus on vulnerable or resilient phenotypes. PNS exposure was associated with a dysregulation of stress-related and metabolic markers both in the liver and also in the ventral hippocampus , with vulnerable males exhibiting increased insulin receptor levels and dysregulated expression of adipokine receptors (such as leptin and adiponectin). In contrast, female animals did not exhibit these changes. Additionally, PNS induced a pronounced neuroinflammatory response in the ventral hippocampus of vulnerable male rats, characterized by an upregulation of microglial activation markers. Interestingly, a similar pro-inflammatory status was observed in the liver of PNS-exposed males regardless of the pathologic phenotype; however, anti-inflammatory markers were upregulated only in resilient animals, suggesting an active mechanism of resilience. These findings suggest that specific metabolic and inflammatory changes underlie, with a sex-specific effect, the onset of a vulnerable phenotype to PNS and highlight the importance of targeting these pathways in the treatment of mood disorders and metabolic comorbidities. • Prenatal stress causes social deficits in 30 % of adult animals. • Vulnerable rats present metabolic alterations in the ventral hippocampus and liver. • Vulnerable rats exhibit a proinflammatory status in the ventral hippocampus and liver. • Increased hepatic adiponectin and anti-inflammatory signaling correlate with resilience. • Female rats show no changes, suggesting a possible role of sex hormones in stress response.
Emotional dysregulation following prenatal stress is associated with altered prefrontal cortex responsiveness to an acute challenge in adolescence
Rodrigo Orso, Kerstin Camile Creutzberg, Veronica Begni, Giulia Petrillo, Annamaria Cattaneo, Marco Andrea Riva
Progress in Neuro Psychopharmacology and Biological Psychiatry, 2025
Exposure to prenatal stress (PNS) has the potential to elicit multiple neurobiological alterations and increase the susceptibility to psychiatric disorders. Moreover, gestational stress may sensitize the brain toward an altered response to subsequent challenges. Here, we investigated the effects of PNS in rats and assessed whether these animals exhibit an altered brain responsiveness to an acute stress (AS) during adolescence. From gestational day 14 until delivery, Sprague Dawley dams were exposed to PNS or left undisturbed. During adolescence (PND38 to PND41), offspring were tested in the social interaction and splash test. At PND44 half of the animals were exposed to 5 min of forced swim stress. Males and Females exposed to PNS showed reduced sociability and increased anhedonic-like behavior. At the molecular level, exposure of adolescent rats to AS produced increased activation of the amygdala and ventral and dorsal hippocampus. Regarding the prefrontal cortex (PFC), we observed a pronounced activation in PNS males exposed to AS. Cell-type specific transcriptional analyses revealed a significant imbalance in the activation of PFC excitatory and inhibitory neurons in PNS males and females exposed to AS. Furthermore, stressed males exhibited disrupted HPA-axis function, while females showed impairments in the modulation of antioxidant genes. Our study shows that PNS induces emotional dysregulation and alters the responsiveness of the PFC to an acute stressor. Moreover, the disruption of excitatory and inhibitory balance during adolescence could influence the ability to respond to challenging events that may contribute to precipitate a full-blown pathologic condition.
Conservation of mechanisms regulating emotional-like responses on spontaneous nicotine withdrawal in zebrafish and mammals
Luisa Ponzoni, Gloria Melzi, Laura Marabini, Andrea Martini, Giulia Petrillo, Muy-Teck Teh, Jose V. Torres-Perez, Stefano Morara, Cecilia Gotti, Daniela Braida, Caroline H. Brennan, Mariaelvina Sala
Progress in Neuro Psychopharmacology and Biological Psychiatry, 2021

RECENT SCHOLAR PUBLICATIONS

Immune Dysregulation and Neuroinflammation in Bipolar Disorder: Pathophysiological Insights and Therapeutic Perspectives
F De Cillis, V Begni, I D’Aprile, G Petrillo, MA Riva, A Cattaneo
Brain, Behavior, & Immunity-Health, 101155 , 2025
2025
Citations: 3
From Fat to Brain: Adiponectin as a Mediator of Neuroplasticity in Depression
P Genini, I D’Aprile, G Petrillo, MG Di Benedetto, V Begni, N Cattane, ...
Biomolecules 15 (12), 1642 , 2025
2025
Citations: 1
Inflammatory status along the brain-liver axis in animals vulnerable to prenatal stress: sex-related implications for stress-induced comorbidities
I D’Aprile, G Petrillo, V Begni, KC Creutzberg, R Orso, R Grassi-Oliveira, ...
Translational Psychiatry 15 (1), 392 , 2025
2025
Citations: 2
Systemic Inflammation at the Crossroad of Major Depressive Disorder and Comorbidities: A Narrative Review
E Vitali, N Cattane, I D’Aprile, G Petrillo, A Cattaneo
International Journal of Molecular Sciences 26 (19), 9382 , 2025
2025
Citations: 8
Exposure To Early-Life Stress Uncovers Shared Biological Signatures Underlying Vulnerability In The Habenula And Insular Cortex Of Male And Female Adult Rats
V Zonca, M Marizzoni, S Saleri, M Mazzelli, G Petrillo, MG Di Benedetto, ...
Neurobiology of Stress, 100761 , 2025
2025
Citations: 2
Prenatal Stress Rewires the Gut–Brain Axis: Long-Term, Sex-Specific Effects on Microbiota, Intestinal Barrier, and Hippocampal Inflammation
F De Cillis, G Petrillo, I D’Aprile, M Marizzoni, S Saleri, M Mazzelli, ...
Nutrients 17 (17), 2812 , 2025
2025
Citations: 3
Sex-specific metabolic and inflammatory alterations in adult animals vulnerable to prenatal stress exposure
I D'Aprile, G Petrillo, V Zonca, M Mazzelli, F De Cillis, MG Di Benedetto, ...
Progress in Neuro-Psychopharmacology and Biological Psychiatry 138, 111344 , 2025
2025
Citations: 8
Emotional dysregulation following prenatal stress is associated with altered prefrontal cortex responsiveness to an acute challenge in adolescence
R Orso, KC Creutzberg, V Begni, G Petrillo, A Cattaneo, MA Riva
Progress in Neuro-Psychopharmacology and Biological Psychiatry 136, 111162 , 2025
2025
Citations: 8
A Spatial Dispersion Approach Qualifies to Quantify Vascular Alterations in a Swine Amyotrophic Lateral Sclerosis Model
R Marco, M Stefano, P Giulia, P Andrea, C Giulia, C Cristiano
Medical Research Archives 10 (9) , 2022
2022
Conservation of mechanisms regulating emotional-like responses on spontaneous nicotine withdrawal in zebrafish and mammals
L Ponzoni, G Melzi, L Marabini, A Martini, G Petrillo, MT Teh, ...
Progress in Neuro-Psychopharmacology and Biological Psychiatry 111, 110334 , 2021
2021
Citations: 13

MOST CITED SCHOLAR PUBLICATIONS

Conservation of mechanisms regulating emotional-like responses on spontaneous nicotine withdrawal in zebrafish and mammals
L Ponzoni, G Melzi, L Marabini, A Martini, G Petrillo, MT Teh, ...
Progress in Neuro-Psychopharmacology and Biological Psychiatry 111, 110334 , 2021
2021
Citations: 13
Systemic Inflammation at the Crossroad of Major Depressive Disorder and Comorbidities: A Narrative Review
E Vitali, N Cattane, I D’Aprile, G Petrillo, A Cattaneo
International Journal of Molecular Sciences 26 (19), 9382 , 2025
2025
Citations: 8
Sex-specific metabolic and inflammatory alterations in adult animals vulnerable to prenatal stress exposure
I D'Aprile, G Petrillo, V Zonca, M Mazzelli, F De Cillis, MG Di Benedetto, ...
Progress in Neuro-Psychopharmacology and Biological Psychiatry 138, 111344 , 2025
2025
Citations: 8
Emotional dysregulation following prenatal stress is associated with altered prefrontal cortex responsiveness to an acute challenge in adolescence
R Orso, KC Creutzberg, V Begni, G Petrillo, A Cattaneo, MA Riva
Progress in Neuro-Psychopharmacology and Biological Psychiatry 136, 111162 , 2025
2025
Citations: 8
Immune Dysregulation and Neuroinflammation in Bipolar Disorder: Pathophysiological Insights and Therapeutic Perspectives
F De Cillis, V Begni, I D’Aprile, G Petrillo, MA Riva, A Cattaneo
Brain, Behavior, & Immunity-Health, 101155 , 2025
2025
Citations: 3
Prenatal Stress Rewires the Gut–Brain Axis: Long-Term, Sex-Specific Effects on Microbiota, Intestinal Barrier, and Hippocampal Inflammation
F De Cillis, G Petrillo, I D’Aprile, M Marizzoni, S Saleri, M Mazzelli, ...
Nutrients 17 (17), 2812 , 2025
2025
Citations: 3
Inflammatory status along the brain-liver axis in animals vulnerable to prenatal stress: sex-related implications for stress-induced comorbidities
I D’Aprile, G Petrillo, V Begni, KC Creutzberg, R Orso, R Grassi-Oliveira, ...
Translational Psychiatry 15 (1), 392 , 2025
2025
Citations: 2
Exposure To Early-Life Stress Uncovers Shared Biological Signatures Underlying Vulnerability In The Habenula And Insular Cortex Of Male And Female Adult Rats
V Zonca, M Marizzoni, S Saleri, M Mazzelli, G Petrillo, MG Di Benedetto, ...
Neurobiology of Stress, 100761 , 2025
2025
Citations: 2
From Fat to Brain: Adiponectin as a Mediator of Neuroplasticity in Depression
P Genini, I D’Aprile, G Petrillo, MG Di Benedetto, V Begni, N Cattane, ...
Biomolecules 15 (12), 1642 , 2025
2025
Citations: 1
A Spatial Dispersion Approach Qualifies to Quantify Vascular Alterations in a Swine Amyotrophic Lateral Sclerosis Model
R Marco, M Stefano, P Giulia, P Andrea, C Giulia, C Cristiano
Medical Research Archives 10 (9) , 2022
2022