Combining Mini-Mental State Examination and Montreal Cognitive Assessment for assessing the clinical efficacy of cholinesterase inhibitors in mild Alzheimer's disease: a pilot study.

Current drugs for Alzheimer's Disease (AD), such as cholinesterase inhibitors (ChEIs), exert only symptomatic activity. Different psychometric tools are needed to assess cognitive and non-cognitive dimensions during pharmacological treatment. In this pilot study, we monitored 33 mild-AD patients treated with ChEIs. Specifically, we evaluated the effects of 6 months (Group 1 = 17 patients) and 9 months (Group 2 = 16 patients) of ChEIs administration on cognition with the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Frontal Assessment Battery (FAB), while depressive symptoms were measured with the Hamilton Depression Rating Scale (HDRS). After 6 months (Group 1), a significant decrease in MoCA performance was detected. After 9 months (Group 2), a significant decrease in MMSE, MoCA, and FAB performance was observed. ChEIs did not modify depressive symptoms. Overall, our data suggest MoCA is a potentially useful tool for evaluating the effectiveness of ChEIs.

Impact of Stress during COVID-19 Pandemic in Italy: A Study on Dispositional and Behavioral Dimensions for Supporting Evidence-Based Targeted Strategies.

The COVID-19 pandemic caused critical mental health issues and lifestyle disruptions. The aim of this study was to explore, during the lockdown of second-wave contagions in Italy, how stress was affected by dispositional (personality factors and intolerance to uncertainty) and behavioral (coping strategies) dimensions, how these variables differed among sex, age, educational, professional, and health groups, and how the various changes in work and daily routine intervened in the psychological impact of the emergency. Our results highlight that women, the youngs, students/trainees, those with chronic diseases, those who stopped their jobs due to restrictions, and those who left home less than twice a week were more stressed, while health professionals showed lower levels of the same construct. Those with higher levels of stress used more coping strategies based on avoidance, which positively correlated with age, agreeableness, conscientiousness, and intolerance to uncertainty, and negatively with openness. Stress levels also positively correlated with agreeableness, conscientiousness, intolerance to uncertainty, and seeking of social support, and negatively with openness, a positive attitude, and a transcendent orientation. Finally, stress was predicted mainly by behavioral dimensions. Our results are discussed and framed within the literature, as important insights for targeted intervention strategies to promote health even in emergencies.

Successes and challenges in the development of BD1-selective BET inhibitors: a patent review.

INTRODUCTION: Bromodomain and ExtraTerminal (BET) domain proteins are transcriptional cofactors that, recognizing acetylated lysines of histone and non-histone proteins, can modulate gene expression. The BET family consists of four members, each of which contains two bromodomains (BD1 and BD2) able to recognize the acetylated mark. Pan-BET inhibitors (BETi) have shown a promising anticancer potential in many clinical trials; however, their further development has been in part hampered by the side effects due to their lack of selectivity. Mounting evidence suggests that BD1 is primarily involved in cancer and that its selective inhibition can phenocopy the anticancer effects of pan-BETi with increased tolerability. Therefore, the development of BD1 selective inhibitors is highly pursed in both academia and industry. AREAS COVERED: This review aims at giving an overview of the patent literature of BD1-selective BETi between 2014 and 2023. WIPO, USPTO, EPO, and SciFinder® databases were used for the search of patents. EXPERT OPINION: The development of BD1-selective BETi, despite challenging, is highly desirable as it could have a great impact on the development of new safer anticancer therapeutics. Several strategies could be applied to discover potent and selective compounds with limited side effects.

A narrative review on insomnia and hypersomnolence within Major Depressive Disorder and bipolar disorder: A proposal for a novel psychometric protocol.

Sleep disorders have become increasingly prevalent, with many adults worldwide reporting sleep dissatisfaction. Major Depressive Disorder (MDD) and Bipolar Disorder (BD) are common conditions associated with disrupted sleep patterns such as insomnia and hypersomnolence. These sleep disorders significantly affect the progression, severity, treatment, and outcome of unipolar and bipolar depression. While there is evidence of a connection between sleep disorders and depression, it remains unclear if sleep features differ between MDD and BD. In light of this, this narrative review aims to: (1) summarize findings on common sleep disorders like insomnia and hypersomnolence, strongly linked to MDD and BD; (2) propose a novel psychometric approach to assess sleep in individuals with depressive disorders. Despite insomnia seems to be more influent in unipolar depression, while hypersomnolence in bipolar one, there is no common agreement. So, it is essential adopting a comprehensive psychometric protocol for try to fill this gap. Understanding the relationship between sleep and MDD and BD disorders are crucial for effective management and better quality of life for those affected.

DMSO-Related Effects on Ligand-Binding Properties of Lysine Methyltransferases G9a and SETD8.

Being the standard solvent for preparing stock solutions of compounds for drug discovery, DMSO is always present in assay buffers in concentrations ranging from 0.1 % to 5 % (v/v). Even at the lowest concentrations, DMSO-containing solutions can have significant effects on individual proteins and possible pitfalls cannot be eliminated. Herein, we used two protein systems, the lysine methyltransferases G9a/KMT1 C and SETD8/KMT5 A, to study the effects of DMSO on protein stability and on the binding of the corresponding inhibitors, using different biophysical methods such as nano Differential Scanning Fluorimetry (nanoDSF), Differential Scanning Fluorimetry (DSF), microscale thermophoresis (MST), and surface plasmon resonance (SPR), all widely used in drug discovery screening campaigns. We demonstrated that the effects of DMSO are protein- and technique-dependent and cannot be predicted or extrapolated on the basis of previous studies using different proteins and/or different assays. Moreover, we showed that the application of orthogonal biophysical methods can lead to different binding affinity data, thus confirming the importance of using at least two different orthogonal assays in screening campaigns. This variability should be taken into account in the selection and characterization of hit compounds, in order to avoid data misinterpretation.

Solubilizer Tag Effect on PD-L1/Inhibitor Binding Properties for m-Terphenyl Derivatives.

Although heavily studied, the subject of anti-PD-L1 small-molecule inhibitors is still elusive. Here we present a systematic overview of the principles behind successful anti-PD-L1 small-molecule inhibitor design on the example of the m-terphenyl scaffold, with a particular focus on the neglected influence of the solubilizer tag on the overall affinity toward PD-L1. The inhibitor developed according to the proposed guidelines was characterized through its potency in blocking PD-1/PD-L1 complex formation in homogeneous time-resolved fluorescence and cell-based assays. The affinity is also explained based on the crystal structure of the inhibitor itself and its costructure with PD-L1 as well as a molecular modeling study. Our results structuralize the knowledge related to the strong pharmacophore feature of the m-terphenyl scaffold preferential geometry and the more complex role of the solubilizer tag in PD-L1 homodimer stabilization.

Mediterranean Diet and Sleep Features: A Systematic Review of Current Evidence.

The prevalence of sleep disorders, characterized by issues with quality, timing, and sleep duration is increasing globally. Among modifiable risk factors, diet quality has been suggested to influence sleep features. The Mediterranean diet is considered a landmark dietary pattern in terms of quality and effects on human health. However, dietary habits characterized by this cultural heritage should also be considered in the context of overall lifestyle behaviors, including sleep habits. This study aimed to systematically revise the literature relating to adherence to the Mediterranean diet and sleep features in observational studies. The systematic review comprised 23 reports describing the relation between adherence to the Mediterranean diet and different sleep features, including sleep quality, sleep duration, daytime sleepiness, and insomnia symptoms. The majority of the included studies were conducted in the Mediterranean basin and reported a significant association between a higher adherence to the Mediterranean diet and a lower likelihood of having poor sleep quality, inadequate sleep duration, excessive daytime sleepiness or symptoms of insomnia. Interestingly, additional studies conducted outside the Mediterranean basin showed a relationship between the adoption of a Mediterranean-type diet and sleep quality, suggesting that biological mechanisms sustaining such an association may exist. In conclusion, current evidence suggests a relationship between adhering to the Mediterranean diet and overall sleep quality and different sleep parameters. The plausible bidirectional association should be further investigated to understand whether the promotion of a healthy diet could be used as a tool to improve sleep quality.

Dietary (Poly)phenols and Cognitive Decline: A Systematic Review and Meta-Analysis of Observational Studies.

SCOPE: This study aims to systematically review observational studies investigating the relation between dietary (poly)phenol consumption and various cognitive outcomes. METHODS AND RESULTS: Embase and PubMed databases are searched from inception to April 2023 for observational studies investigating the relation between dietary (poly)phenol intake and cognitive outcomes. For quantitative analyses, random effects models, subgroup analyses, and dose-response analyses are performed. A total of 37 studies are included in the systematic review. Among (poly)phenols, a higher intake of flavonoids is associated with better cognitive function and lower odds of cognitive decline (although with some exceptions). A quantitative meta-analysis shows an overall inverse association with cognitive impairment and reduced association with the incidence of dementia or related disorders for total flavonoids (relative risk (RR) = 0.83, 95% confidence interval (CI): 0.76, 0.89), anthocyanins (RR = 0.73, 95% CI: 0.60, 0.89), flavones (RR = 0.77, 95% CI: 0.63, 0.94), flavan-3-ols (RR = 0.86, 95% CI: 0.82, 0.91), and flavonols (RR = 0.88, 95% CI: 0.80, 0.96). Data on other (poly)phenolic compounds (i.e., phenolic acids) are promising but too preliminary. CONCLUSION: Habitual inclusion of flavonoids in the diet may play a preventive role against cognitive disorders.

A combined approach of structure-based virtual screening and NMR to interrupt the PD-1/PD-L1 axis: Biphenyl-benzimidazole containing compounds as novel PD-L1 inhibitors.

Immunotherapy has emerged as a game-changing approach for cancer treatment. Although monoclonal antibodies (mAbs) targeting the programmed cell death protein 1/programmed cell death protein 1 ligand 1 (PD-1/PD-L1) axis have entered the market revolutionizing the treatment landscape of many cancer types, small molecules, although presenting several advantages including the possibility of oral administration and/or reduced costs, struggled to enter in clinical trials, suffering of water insolubility and/or inadequate potency compared with mAbs. Thus, the search for novel scaffolds for both the design of effective small molecules and possible synergistic strategies is an ongoing field of interest. In an attempt to find novel chemotypes, a virtual screening approach was employed, resulting in the identification of new chemical entities with a certain binding capability, the most versatile of which was the benzimidazole-containing compound 10. Through rational design, a small library of its derivatives was synthesized and evaluated. The homogeneous time-resolved fluorescence (HTRF) assay revealed that compound 17 shows the most potent inhibitory activity (IC50 ) in the submicromolar range and notably, differently from the major part of PD-L1 inhibitors, exhibits satisfactory water solubility properties. These findings highlight the potential of benzimidazole-based compounds as novel promising candidates for PD-L1 inhibition.

A network study to differentiate suicide attempt risk profiles in male and female patients with major depressive disorder.

Suicide attempts are a possible consequence of Major Depressive Disorder (MDD), although their prevalence varies across different epidemiological studies. Suicide attempt is a significant predictor of death by suicide, highlighting its importance in understanding and preventing tragic outcomes. Researchers are increasingly recognizing the need to study the differences between males and females, as several distinctions emerge in terms of the characteristics, types and motivations of suicide attempts. These differences emphasize the importance of considering gender-specific factors in the study of suicide attempts and developing tailored prevention strategies. We conducted a network analysis to represent and investigate which among multiple neurocognitive, psychosocial, demographic and affective variables may prove to be a reliable predictor for identifying the 'suicide attempt risk' (SAR) in a sample of 81 adults who met DSM-5 criteria for MDD. Network analysis resulted in differences between males and females regarding the variables that were going to interact and predict the SAR; in particular, for males, there is a stronger link toward psychosocial aspects, while for females, the neurocognitive domain is more relevant in its mnestic subcomponents. Network analysis allowed us to describe otherwise less obvious differences in the risk profiles of males and females that attempted to take their own lives. Different neurocognitive and psychosocial variables and different interactions between them predict the probability of suicide attempt unique to male and female patients.

The dynamic interaction between symptoms and pharmacological treatment in patients with major depressive disorder: the role of network intervention analysis.

INTRODUCTION: The Major Depressive Disorder (MDD) is a mental health disorder that affects millions of people worldwide. It is characterized by persistent feelings of sadness, hopelessness, and a loss of interest in activities that were once enjoyable. MDD is a major public health concern and is the leading cause of disability, morbidity, institutionalization, and excess mortality, conferring high suicide risk. Pharmacological treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Noradrenaline Reuptake Inhibitors (SNRIs) is often the first choice for their efficacy and tolerability profile. However, a significant percentage of depressive individuals do not achieve remission even after an adequate trial of pharmacotherapy, a condition known as treatment-resistant depression (TRD). METHODS: To better understand the complexity of clinical phenotypes in MDD we propose Network Intervention Analysis (NIA) that can help health psychology in the detection of risky behaviors, in the primary and/or secondary prevention, as well as to monitor the treatment and verify its effectiveness. The paper aims to identify the interaction and changes in network nodes and connections of 14 continuous variables with nodes identified as "Treatment" in a cohort of MDD patients recruited for their recent history of partial response to antidepressant drugs. The study analyzed the network of MDD patients at baseline and after 12 weeks of drug treatment. RESULTS: At baseline, the network showed separate dimensions for cognitive and psychosocial-affective symptoms, with cognitive symptoms strongly affecting psychosocial functioning. The MoCA tool was identified as a potential psychometric tool for evaluating cognitive deficits and monitoring treatment response. After drug treatment, the network showed less interconnection between nodes, indicating greater stability, with antidepressants taking a central role in driving the network. Affective symptoms improved at follow-up, with the highest predictability for HDRS and BDI-II nodes being connected to the Antidepressants node. CONCLUSION: NIA allows us to understand not only what symptoms enhance after pharmacological treatment, but especially the role it plays within the network and with which nodes it has stronger connections.

Mediterranean diet and chronotype: Data from Italian adults and systematic review of observational studies.

Scientific evidence suggests a relation between dietary factors and sleep. Several studies show that higher adherence to the Mediterranean diet is associated with better sleep quality, but the relation with chronotype has been only recently explored. The aim of this study was to better understand the relation between chronotype and Mediterranean diet adherence. For this purpose, an analysis of 1936 adults (age 18-90 y) living in Italy was performed to investigate the association between chronotype (assessed with a short form of the morningness-eveningness questionnaire) and adherence to the Mediterranean diet (assessed through a 110-item food frequency questionnaire and the Medi-Lite literature-based Mediterranean adherence score). A multivariate logistic regression analysis was conducted to calculate odds ratios (OR) and 95 % confidence intervals (CIs) describing the association between chronotypes and high adherence to the Mediterranean diet (>14 points). Moreover, a systematic review of other observational studies published so far was performed. Individuals reporting having intermediate (n = 614) and evening (n = 173) chronotypes were less likely to have high adherence to the Mediterranean diet compared to morning chronotype (OR = 0.28, 95 % CI: 0.18, 0.42 and OR = 0.08, 95 % CI: 0.03, 0.27, respectively). When the analysis was conducted in subgroups of age, the results were similar in mid-age (>50 y) participants (for intermediate and evening chronotypes, OR = 0.21, 95 % CI: 0.10, 0.43 and OR = 0.92, 95 % CI: 0.01, 0.69, respectively) while the association with high adherence to the Mediterranean diet of evening compared to morning chronotype lost significance in older (>60 y) participants (for intermediate and evening chronotypes, OR = 0.27, 95 % CI: 0.09, 0.82 and OR = 0.22, 95 % CI: 0.02, 1.92, respectively). Out of 10 studies (date range of publication 2020-2022) included in the systematic review, there was a general consistence of findings showing higher adherence to the Mediterranean diet among morning chronotypes, although few studies reported null results. In conclusion, current evidence suggests that an intermediate and evening chronotype could be associated with lower adherence to a Mediterranean diet, but the association could be modified by other factors when considering older individuals.

NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors.

NADPH oxidases (NOXs) form a family of electron-transporting membrane enzymes whose main function is reactive oxygen species (ROS) generation. Strong evidence suggests that ROS produced by NOX enzymes are major contributors to oxidative damage under pathologic conditions. Therefore, blocking the undesirable actions of these enzymes is a therapeutic strategy for treating various pathological disorders, such as cardiovascular diseases, inflammation, and cancer. To date, identification of selective NOX inhibitors is quite challenging, precluding a pharmacologic demonstration of NOX as therapeutic targets in vivo. The aim of this Perspective is to furnish an updated outlook about the small-molecule NOX inhibitors described over the last two decades. Structures, activities, and in vitro/in vivo specificity are discussed, as well as the main biological assays used.

Identification of a Protein Arginine Methyltransferase 7 (PRMT7)/Protein Arginine Methyltransferase 9 (PRMT9) Inhibitor.

Less studied than the other protein arginine methyltransferase isoforms, PRMT7 and PRMT9 have recently been identified as important therapeutic targets. Yet, most of their biological roles and functions are still to be defined, as well as the structural requirements that could drive the identification of selective modulators of their activity. We recently described the structural requirements that led to the identification of potent and selective PRMT4 inhibitors spanning both the substrate and the cosubstrate pockets. The reanalysis of the data suggested a PRMT7 preferential binding for shorter derivatives and prompted us to extend these structural studies to PRMT9. Here, we report the identification of the first potent PRMT7/9 inhibitor and its binding mode to the two PRMT enzymes. Label-free quantification mass spectrometry confirmed significant inhibition of PRMT activity in cells. We also report the setup of an effective AlphaLISA assay to screen small molecule inhibitors of PRMT9.

Physical Activity, Sun Exposure, Vitamin D Intake and Perceived Stress in Italian Adults.

The last decades of global development have, due to rapid urbanization, pressuring entire populations to changes in lifestyle and dietary habits, led to an increase in the prevalence of mental disorders, including stress. This study explored how lifestyle and dietary factors, such as physical activity, sun exposure, and vitamin D intake are related to perceived stress in a Mediterranean-based population. Physical activity level was evaluated using the international physical activity questionnaires (IPAQ), sun exposure was evaluated using the sunlight exposure measurement questionnaire (SEM-Q), and validated food frequency questionnaires (FFQs) were used to assess dietary intakes. The perceived stress of the study participants was evaluated using the perceived stress scale (PSS). Multivariate logistic regression models were used to test for potential associations. In the most adjusted model, an inverse association between physical activity level, sunlight exposure, vitamin D intake, and high perceived stress was found (OR = 0.72, 95% CI: 0.51, 1.00, OR = 0.72, 95% CI: 0.52, 0.99, OR = 0.69, 95% CI: 0.53, 0.89, respectively). However, when stratifying the population by level of physical activity, the retrieved associations with sunlight exposure and dietary vitamin D intake were significant only among those individuals reporting being moderately to highly physically active (OR = 0.16, 95% CI: 0.08, 0.33 and OR = 0.46, 95% CI: 0.28, 0.76, respectively), while results on low physically active participants were null. In conclusion, this study demonstrated that higher dietary intake of vitamin D and sunlight exposure are associated with a lower likelihood of having high perceived stress among physically active individuals.

Association between alcoholic (poly)phenol-rich beverage consumption and cognitive status in older adults living in a Mediterranean area.

The prevalence of cognitive disorders is growing and evidence suggests the putative role of plant-based foods and beverages containing (poly)phenols. The aim of this study was to explore the association between the consumption of (poly)phenol-rich beverages, including wine and beer, resveratrol intake, and cognitive status in a cohort of older adults. The dietary intakes were assessed using a validated food frequency questionnaire, and cognitive status using the Short Portable Mental Status Questionnaire. Multivariate logistic regression analyses showed that individuals in the second and third tertile of red wine consumption were less likely to have cognitive impairment than those in the first tertile. In contrast, only individuals in the highest tertile of white wine intake were having lower odds of cognitive impairment. No significant results were found for beer intake. Individuals with higher resveratrol intake were less likely to have cognitive impairment. In conclusion, consumption of (poly)phenol-rich beverages may potentially affect cognition among older adults.

Dietary Fats and Cognitive Status in Italian Middle-Old Adults.

The increase in life expectancy led to a significant rise in the prevalence of age-related neurological diseases, such as cognitive impairment, dementia, and Alzheimer's disease. Although genetics certainly play a role, nutrition emerged as a key factor in maintaining optimal cognitive function among older adults. Therefore, the study aimed to investigate whether specific categories and subcategories of dietary fats, based on carbon-chain length, are associated with cognitive status in a cohort of 883 Italian participants over the age of 50. METHODS: The intake of total, single class of dietary fat, such as saturated fatty acids (SFA), monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA), and also single fatty acids grouped according to carbon-chain length, were evaluated by food frequency questionnaires (FFQs). Cognitive health was assessed using the short portable mental status questionnaire (SPMSQ). RESULTS: After adjustment for potential confounding factors subjects with a moderate consumption of both short-chain SFA (for Q2 vs. Q1, OR = 0.23, 95% CI: 0.08, 0.66) and middle-chain SFA specifically lauric acid (C12:0) intake (for Q2 vs. Q1, OR = 0.27, 95% CI: 0.09, 0.77) were less likely to suffer from cognitive impairment. Among single MUFAs, erucic acid (C22:1) intake resulted in an inverse association, in a linear way, with cognitive impairment (for Q4 vs. Q1, OR = 0.04, 95% CI: 0.00, 0.39). Conversely, moderate intake of linoleic acid (C18:2) was associated with cognitive impairment (Q3 vs. Q1, OR = 4.59, 95% CI: 1.51, 13.94). Regarding other PUFAs, individuals consuming moderate intake alpha linolenic acid (C18:3) were less likely to have cognitive impairment (for Q3 vs. Q1, OR = 0.19, 95% CI: 0.06, 0.64). CONCLUSIONS: Total SFA intake appeared to be inversely associated with cognitive impairment. Regarding specific subtypes of fatty acids, the results mostly referred to short- and middle-chain SFA. Further studies are needed to validate the results of the present study.

Mediterranean diet, mental health, cognitive status, quality of life, and successful aging in southern Italian older adults.

Healthy successful aging with preserved mental and cognitive health is expected to be one of the most important challenges of the growing old population globally. Studies investigating these multi-dimensional aspects of senescence are important to identify potential targets for early prevention. The aim of this study was to investigate the relation between adherence to the Mediterranean diet and mental and cognitive health, quality of life, and successful aging in middle-age and older adults living in Sicily, southern Italy. Data from a sample of 883 individuals was collected including information on food intake (through a 110-item food frequency questionnaire), sleep quality (through the Pittsburgh sleep quality index) depressive symptoms (through the Center for the Epidemiological Studies of Depression Short Form), quality of life (through the Manchester Short Assessment of Quality of Life), cognitive status (through the Short Portable Mental Status Questionnaire), and overall successful aging (through the Successful Aging Index). Multivariate logistic regression analyses were conducted to assess the association between adherence to the Mediterranean diet and the outcomes investigated. After adjustment for potential confounding factors, individuals in the highest quartile of adherence to the Mediterranean diet were less likely to have cognitive impairment (OR = 0.19, 95 % CI: 0.04, 0.86), depressive symptoms (OR = 0.19, 95 % CI: 0.08, 0.46) and more likely to have good quality of life (OR = 14.04, 95 % CI: 6.81, 28.93); significant results were also found for individuals in the third quartile of Mediterranean diet adherence and good sleep quality (OR = 1.65, 95 % CI: 1.03, 2.64). Moreover, individuals in the highest quartile of adherence were more likely to have a successful aging (OR = 1.65, 95 % CI: 1.01, 2.68). In conclusion, this study supports the hypothesis that adherence to the Mediterranean diet provides a positive trajectory toward a healthy successful aging, with major potential benefits toward mental and cognitive health.

Predictors of functional outcome in patients with major depression and bipolar disorder: A dynamic network approach to identify distinct patterns of interacting symptoms.

The purpose of this study is to use a dynamic network approach as an innovative way to identify distinct patterns of interacting symptoms in patients with Major Depressive Disorder (MDD) and patients with Bipolar Type I Disorder (BD). More precisely, the hypothesis will be testing that the phenotype of patients is driven by disease specific connectivity and interdependencies among various domains of functioning even in the presence of underlying common mechanisms. In a prospective observational cohort study, hundred-forty-three patients were recruited at the Psychiatric Clinic "Villa dei Gerani" (Catania, Italy), 87 patients with MDD and 56 with BD with a depressive episode. Two nested sub-groups were treated for a twelve-week period, which allowed us to explore differences in the pattern of symptom distribution (central vs. peripheral) and their connectedness (strong vs weak) before (T0) and after (T1) treatment. All patients underwent a complete neuropsychological evaluation at baseline (T0) and at T1. A network structure was computed for MDD and BD patients at T0 and T1 from a covariance matrix of 17 items belonging to three domains-neurocognitive, psychosocial, and mood-related (affective) to identify what symptoms were driving the networks. Clinically relevant differences were observed between MDD and BD, at T0 and after 12 weeks of pharmacological treatment. At time T0, MDD patients displayed an affective domain strongly connected with the nodes of psychosocial functioning, while direct connectivity of the affective domain with the neurocognitive cluster was absent. The network of patients with BD, in contrast, revealed a cluster of highly interconnected psychosocial nodes but was guided by neurocognitive functions. The nodes related to the affective domain in MDD are less connected and placed in the periphery of the networks, whereas in BD they are more connected with psychosocial and neurocognitive nodes. Noteworthy is that, from T0 to T1 the "Betweenness" centrality measure was lower in both disorders which means that fewer "shortest paths" between nodes pass through the affective domain. Moreover, fewer edges were connected directly with the nodes in this domain. In MDD patients, pharmacological treatment primarily affected executive functions which seem to improve with treatment. In contrast, in patients with BD, treatment resulted in improvement of overall connectivity and centrality of the affective domain, which seems then to affect and direct the overall network. Though different network structures were observed for MDD and BD patients, data suggest that treatment should include tailored cognitive therapy, because improvement in this central domain appeared to be fundamental for better outcomes in other domains. In sum, the advantage of network analysis is that it helps to predict the trajectory of future phenotype related disease manifestations. In turn, this allows new insights in how to balance therapeutic interventions, involving different fields of function and combining pharmacological and non-pharmacological treatment modalities.