Giuseppe Fanelli

• Clinical lecturer at University of Bologna

Up to 60% of patients with major depressive disorder (MDD) do not respond to the first treatment with antidepressants. Response to antidepressants is a polygenic trait, although its underpinning genetics has not been fully clarified. This study aimed to investigate if Polygenic Risk Scores (PRSs) for major psychiatric disorders and trait neuroticis...

About two-thirds of patients with major depressive disorder (MDD) fail to achieve symptom remission after the initial antidepressant treatment. Despite a role of genetic factors was proven, the specific underpinnings are not fully understood yet. Polygenic risk scores (PRSs), which summarise the additive effect of multiple risk variants across the...

Abstract The prevalence of somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), is higher in Alzheimer’s disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared gene...

Suicide is the second cause of death among youths. Genetics may contribute to suicidal phenotypes and their co‐occurrence in other neuropsychiatric and medical conditions. Our study aimed to investigate the association of polygenic risk scores (PRSs) for 24 neuropsychiatric, inflammatory, and cardio‐metabolic traits/diseases with suicide attempt (S...

Clinical and genomic studies have shown an overlap between neuropsychiatric disorders and insulin resistance (IR)-related somatic conditions, including obesity, type 2 diabetes, and cardiovascular diseases. Impaired cognition is often observed among neuropsychiatric disorders, where multiple cognitive domains may be affected. In this review, we aim...

The relationship between major depressive disorder (MDD) and mild motor signs (MMS) remains to be elucidated. The present study aims to assess the association between neurological symptoms and medications and treatment response. Neurological signs in 790 patients with MDD were correlated with treatment outcome. Three hundred ten (39.2%) were respon...

The co-occurrence of insulin resistance (IR)-related metabolic conditions with neuropsychiatric disorders is a major public health challenge. Evidence of the genetic links between these phenotypes is emerging, but little is currently known about the genomic regions and biological functions that are involved. To address this, we performed Local Anal...

Background Personality plays an important role in the clinical presentation, the course and the prognosis of psychotic disorders (1) also influencing the outcome of cognitive performances (2). However, there is a paucity of studies exploring personality domains in patients with recent onset of psychosis, particularly looking at their relationship w...

Background Personality traits in patients with schizophrenia influence various aspects of psychosis, including treatment response, cognitive functioning and the symptomatological profile (1). Negative symptoms in particular may represent an intensification of premorbid personality traits (2). However, the relationship between personality domains an...

Background Cognitive impairment is observed across all stages of schizophrenia, including the high-risk state and the first-episode psychosis (FEP) (1). While higher cognitive impairment is typically associated with deficit schizophrenia (2), there is inconclusive evidence regarding the specific cognitive dysfunction associated with psychotic sympt...

This state-of-the-art review explores the relationship between depression and diabetes, highlighting the two-way influences that make treatment challenging and worsen the outcomes of both conditions. Depression and diabetes often co-occur and share genetic, lifestyle, and psychosocial risk factors. Lifestyle elements such as diet, physical activity...

The revival of psilocybin in psychopharmacological research heralds a potential paradigm shift for treating mood and anxiety disorders, and other psychiatric conditions beyond the psychotic spectrum. This critical review evaluates current evidence on psilocybin’s efficacy, juxtaposing potential benefits with the practical aspects of psychedelic-ass...

Deficits in social cognition may impair emotional processing and facial emotional recognition (FER) in patients with bipolar disorder (BD) and schizophrenia. FER is generally explored using photographs or images of static faces that do not fully capture the complexity of real-life facial stimuli. To overcome this limitation, we developed a set of d...

Background Anhedonic features within major depressive disorder (MDD) have been associated with worse course and outcome and may predict non-response to treatment. However a detailed clinical profile of anhedonia in MDD is still lacking. Materials and Methods One thousand two hundred ninety-four patients with MDD were selected from the cross-sectio...

Alzheimer’s disease (AD) is a multifactorial disease with both genetic and environmental factors contributing to its etiology. Previous evidence has implicated disturbed insulin signaling as a key mechanism that plays a role in both neurodegenerative diseases such as AD and comorbid somatic diseases such as diabetes mellitus type 2 (DM2). In this s...

Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are heritable disorders that frequently co-occur with insulin resistance (IR)-related conditions. Traditional genetic case-control comparisons are challenged by the extent of heterogeneity and comorbidity within and across these...

Psychiatric disorders frequently co-occur with insulin resistance (IR)-related conditions, including obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS). Although pairwise genetic correlations have been observed, the shared genetics underlying this multimorbidity remains underexplored. Here, we investigate the joint genetic arch...

Objective: Therapeutic drug monitoring (TDM) is an important tool for treatment optimisation. Its usefulness has recently been demonstrated for some first-line antidepressants; however, few studies have been reported on the relationship between blood levels of mirtazapine and its antidepressant effects. The aim of this study was to investigate the...

Sociability is relevant for most mental health conditions and their prognosis. The classic "social brain" maps mainly to the default mode (DMN) and salience networks (SN). Recent studies also suggest involvement of other brain regions, but results are not yet fully consistent and interpretable. We conducted a fully data-driven resting-state connect...

Treatment response and resistance in major depressive disorder (MDD) show a significant genetic component, but previous studies had limited power also due to MDD heterogeneity. This literature review focuses on the genetic factors associated with treatment outcomes in MDD, exploring their overlap with those associated with clinically relevant sympt...

Background Psychiatric disorders and type 2 diabetes mellitus (T2DM) are heritable, polygenic, and often comorbid conditions, yet knowledge about their potential shared familial risk is lacking. We used family designs and T2DM polygenic risk score (T2DM-PRS) to investigate the genetic associations between psychiatric disorders and T2DM. Methods We...

The brain's default mode network (DMN) plays a role in social cognition, with altered DMN function being associated with social impairments across various neuropsychiatric disorders. In the present study, we examined the genetic relationship between sociability and DMN-related resting-state functional magnetic resonance imaging (rs-fMRI) traits. To...

The co-occurrence of insulin resistance (IR)-related metabolic conditions with neuropsychiatric disorders is a complex public health challenge. Evidence of the genetic links between these phenotypes is emerging, but little is currently known about the genomic regions and biological functions that are involved. To address this, we performed Local An...

Background There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network meta-analysis to assess and compare the efficacy and safety of pharmacological treatments for psychotic depression. Methods In this systematic review and network meta-analysis, we...

This review synthesizes the evidence on associations between antidepressant use and gut microbiota composition and function, exploring the microbiota’s possible role in modulating antidepressant treatment outcomes. Antidepressants exert an influence on measures of gut microbial diversity. The most consistently reported differences were in β-diversi...

A significant proportion of patients with major depressive disorder (MDD) do not experience remission after one or more pharmacological treatments. Research has explored brain structural measures, particularly hippocampal volume, as potential predictors of treatment response, as well as genetic factors. This study investigated the association of po...

Autism spectrum disorder (ASD) is a common and complex neurodevelopmental condition. The pathophysiology of ASD is poorly defined; however, it includes a strong genetic component and there is increasing evidence to support a role of immune dysregulation. Nonetheless, it is unclear which immune phenotypes link to ASD through genetics. Hence, we inve...

Autism spectrum disorder (ASD) is a common and complex neurodevelopmental condition. The pathophysiology of ASD is poorly defined; however, it includes a strong genetic component and there is increasing evidence to support a role of immune dysregulation. Nonetheless, it is unclear which immune phenotypes link to ASD through genetics. Hence, we inve...

Background: Emotion dysregulation (ED) is a transdiagnostic construct characterized by difficulties regulating intense emotions. People with bipolar disorder (BD) are more likely to show ED and use maladaptive emotion regulation strategies than adaptive ones. However, little is known about whether ED in BD is a trait or it is rather an epiphenomeno...

A significant proportion of patients with major depressive disorder (MDD) do not experience remission after one or more pharmacological treatments. Research has explored brain structural measures, particularly the hippocampus, as potential predictors of treatment response in MDD, as well as genetic factors. This study investigated the association o...

Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants are not effective in all patients and often show a relevant response latency, with a range of adverse events, including weight gain and sexual dysfunction. Novel rapid agents were developed with the aim of overcoming at least in part thes...

Mood disorders and type 2 diabetes mellitus (T2DM) are prevalent conditions that often co-occur. We reviewed the available evidence from longitudinal and Mendelian randomisation (MR) studies on the relationship between major depressive disorder (MDD), bipolar disorder and T2DM. The clinical implications of this comorbidity on the course of either c...

Background: Individuals with major depressive disorder (MDD) are at higher risk for obesity. In turn, weight gain is a predisposing factor for depression. Although clinical data are sparse, suicide risk also appears to be elevated in obese patients. This study used data from the European Group for the Study of Resistant Depression (GSRD) to invest...

In late-life depression (LLD), several differences between patients whose first episode is reported after age 65 (late-onset depression, LOD) and those with early-onset depression (EOD) might reflect the effects of brain ageing. To test this hypothesis, we analysed the impact of current age and age at illness onset on a number of clinical and cogni...

Background: Serotonin-norepinephrine reuptake inhibitors (SNRIs) are among the most frequently prescribed antidepressants (ADs) for major depressive disorder (MDD), with an increasing trend in the last decade. Given the relative dearth of information regarding rationales for their preferred use as first-line ADs in the broad clinical routine, the...

Suicidal ideation (SI) is a risk factor for suicidal behaviour. To ascertain the clinical correlates and prognostic impact of severe SI, we analysed 249 outpatients with major depressive disorder (MDD) and suicidal thoughts included in the COmbining Medications to Enhance Depression outcome (CO-MED) trial. Patients with severe SI (36%) were younger...

The relationship between psychiatric symptoms and thyroid function has been well known and studied since antiquity. The common view is that clinical hypothyroidism is associated with depressive symptoms, whereas the psychiatric manifestations of hyperthyroidism are agitation, emotional lability, hyperexcitability, occasionally accompanied by angry...

Background: Multimorbidity of somatic insulin resistance (IR)-related diseases, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), and neuropsychiatric disorders, including Alzheimer's disease (AD), neurodevelopmental, mood, and psychotic disorders, is frequently observed. Significant global genetic correlations were foun...

Background Major depressive disorder (MDD) is a highly prevalent psychiatric condition characterised by a heterogeneous clinical presentation and an estimated twin-based heritability of ~40–50 %. Different clinical MDD subtypes might partly reflect distinctive underlying genetics. This study aims to investigate if polygenic risk scores (PRSs) for d...

Antipsychotic polypharmacy (APP) in patients with schizophrenia spectrum disorders (SSDs) is usually not recommended, though it is very common in clinical practice. Both APP and SSDs have been linked to worse health outcomes and decreased levels of physical activity, which in turn is an important risk factor for cardiovascular diseases and prematur...

Background Type 2 diabetes mellitus (T2DM) is linked with several neurodegenerative and psychiatric disorders, either as a comorbid condition or as a risk factor. We aimed to expand the evidence by examining associations with a broad range of brain disorders (psychiatric and neurological disorders, excluding late-onset neurodegenerative disorders),...

Human beings are social animals, and social psychiatry is a key discipline within psychiatry around the world. The impact of social factors on the genesis and perpetuation of mental illnesses and maintenance of well-being of individuals and families is well recognized. Exploring social factors is the key to understanding aetiology and developing th...

Binge-eating (BE) symptoms are relatively common in major depressive disorder (MDD), but their prognostic role is not fully understood. This study compared two groups of patients with MDD experiencing or not BE symptoms to ascertain differences in terms of clinical manifestations, presence of bipolar features, and antidepressant treatment outcomes....

Antipsychotic polypharmacy in psychotic disorders is widespread despite international guidelines favoring monotherapy. Previous evidence indicates the utility of low-dose partial dopamine agonist (PDAs) add-ons to mitigate antipsychotic-induced metabolic adverse effects or hyperprolactinemia. However, clinicians are often concerned about using PDAs...

Substance use disorder (SUD) is a common comorbidity in individuals with bipolar disorder (BD), and it is associated with a severe course of illness, making early identification of the risk factors for SUD in BD warranted. We aimed to identify, through machine-learning models, the factors associated with different types of SUD in BD. We recruited 5...

Major depressive disorder (MDD) and diseases linked to insulin resistance (IR), including obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome, are among the leading causes of disability worldwide, and their incidence continues to grow to epidemic proportions. A number of epidemiological studies have shown that the risk of IR-related di...

Parenthood age may affect the risk for the development of different psychiatric disorders in the offspring, including bipolar disorder (BD). The present systematic review and meta-analysis aimed to appraise the relationship between paternal age and risk for BD and to explore the eventual relationship between paternal age and age at onset of BD. We...

Objectives Cognitive deficits in Bipolar Disorder (BD) are significant enough to have an impact on daily functioning. Therefore, appropriate cognitive tools must be used to improve our understanding of the nature and severity of cognitive deficits in BD. In this study, we aimed to compare the cognitive profiles of patients with BD and healthy contr...

Introduction Due to favorable antidepressant (AD) efficacy and tolerability, selective-serotonin reuptake inhibitors (SSRIs) are consistently recommended as substances of first choice for the treatment of major depressive disorder (MDD) in international guidelines. However, little is known about the real-world clinical correlates of patients primar...

Since selective serotonin reuptake inhibitors, that are recommended as first-line antidepressant psychopharmacotherapy for major depressive disorder (MDD), may not be the optimal choice for every patient, antidepressants with different modes of action exerting a distinct set of expectant effects, represent a valuable alternative. Despite the previo...

Obsessive-compulsive symptoms (OCS) are often reported in patients with bipolar disorder. The aim of this study was to investigate OCS and their related clinical features in major depressive disorder (MDD). The analysis involved 482 outpatients with MDD collected within the Combining Medications to Enhance Depression outcomes trial, who were assess...

Social withdrawal is an early manifestation of several neuropsychiatric disorders, and it is characterised by a gradual disengagement from social interactions, potentially leading to complete isolation. This study investigated the association between social withdrawal at baseline and short-term symptom remission in five independent cohorts, includi...

About two thirds of the patients with major depressive disorder (MDD) do not sufficiently respond to monotherapy with antidepressants (ADs) which makes them reliant on further treatment approaches. Hereby, combination of different ADs and augmentation with second-generation antipsychotics (SGAs) are widely used and recommended psychopharmacotherape...

Background Psychiatric disorders are complex, multifactorial illnesses with a demonstrated biological component in their etiopathogenesis. Epigenetic modifications, through the modulation of DNA methylation, histone modifications and RNA interference, tune tissue-specific gene expression patterns and play a relevant role in the etiology of psychiat...

About two-thirds of patients with major depressive disorder (MDD) fail to achieve symptom remission after the initial antidepressant treatment. Despite a role of genetic factors was proven, the specific underpinnings are not fully understood yet. Polygenic risk scores (PRSs), which summarise the additive effect of multiple risk variants across the...

The prevalence of Alzheimer's disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) is higher among patients with somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shar...

Suicide is the second leading cause of death among young people. Genetics may contribute to suicidal phenotypes and their co-occurrence in other psychiatric and medical conditions. Our study aimed to investigate the association of polygenic risk scores (PRSs) for 22 psychiatric, inflammatory, and cardio-metabolic traits and diseases with suicide at...

Gastrointestinal side effects (SEs) are frequently observed in patients with major depressive disorder (MDD) while taking antidepressants and may lead to treatment discontinuation. The aim of this meta-analysis is to provide quantitative measures on short-term rates of gastrointestinal SEs in MDD patients treated with second-generation antidepressa...