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Search Results (28)

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Authors = Georgios D. Kotzalidis ORCID = 0000-0002-0281-6324

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31 pages, 638 KiB  
Systematic Review
Exploring the Autistic Brain: A Systematic Review of Diffusion Tensor Imaging Studies on Neural Connectivity in Autism Spectrum Disorder
by Giuseppe Marano, Georgios D. Kotzalidis, Maria Benedetta Anesini, Sara Barbonetti, Sara Rossi, Miriam Milintenda, Antonio Restaino, Mariateresa Acanfora, Gianandrea Traversi, Giorgio Veneziani, Maria Picilli, Tommaso Callovini, Carlo Lai, Eugenio Maria Mercuri, Gabriele Sani and Marianna Mazza
Brain Sci. 2025, 15(8), 824; https://doi.org/10.3390/brainsci15080824 - 31 Jul 2025
Viewed by 297
Abstract
Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific [...] Read more.
Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific to ASD. While grey matter has been the primary focus, white matter (WM) may be more specific in identifying the particular biological signature of the neurodiversity of ASD. Diffusion tensor imaging (DTI) is the more appropriate tool to investigate WM in ASD. Despite being introduced in 1994, its application to ASD research began in 2001. Studies employing DTI identify altered fractional anisotropy (FA), mean diffusivity, and radial diffusivity (RD) in individuals with ASD compared to typically developing (TD) individuals. Methods: We systematically reviewed literature on 21 May 2025 on PubMed using the following strategy: (“autism spectrum”[ti] OR autistic[ti] OR ASD[ti] OR “high-functioning autism” OR Asperger*[ti] OR Rett*[ti]) AND (DTI[ti] OR “diffusion tensor”[ti] OR multimodal[ti] OR “white matter”[ti] OR tractograph*[ti]). Our search yielded 239 results, of which 26 were adult human studies and eligible. Results: Analysing the evidence, we obtained regionally diverse WM alterations in adult ASD, specifically in FA, MD, RD, axial diffusivity and kurtosis, neurite density, and orientation dispersion index, compared to TD individuals, mostly in frontal and interhemispheric tracts, association fibres, and subcortical projection pathways. These alterations were less prominent than those of children and adolescents, indicating that individuals with ASD may improve during brain maturation. Conclusions: Our findings suggest that white matter alterations in adults with ASD are regionally diverse but generally less pronounced than in younger populations. This may indicate a potential improvement or adaptation of brain structure during maturation. Further research is needed to clarify the neurobiological mechanisms underlying these changes and their implications for clinical outcomes. Full article
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18 pages, 556 KiB  
Article
Clinical Outcomes in Patients with Schizophrenia Treated with Long-Acting Injectable vs. Oral Antipsychotics: A Naturalistic Study
by Francesca Bardi, Lorenzo Moccia, Georgios D. Kotzalidis, Gianluca Boggio, Andrea Brugnami, Greta Sfratta, Delfina Janiri, Gabriele Sani and Alessio Simonetti
Healthcare 2025, 13(14), 1709; https://doi.org/10.3390/healthcare13141709 - 16 Jul 2025
Viewed by 604
Abstract
Background/Objectives: Long-acting injectable antipsychotics (LAIs) represent a significant advancement in the treatment of schizophrenia (SCZ), particularly for improving adherence and long-term outcomes. This study aimed to assess the clinical outcomes of patients receiving atypical LAIs compared to those on various oral antipsychotics [...] Read more.
Background/Objectives: Long-acting injectable antipsychotics (LAIs) represent a significant advancement in the treatment of schizophrenia (SCZ), particularly for improving adherence and long-term outcomes. This study aimed to assess the clinical outcomes of patients receiving atypical LAIs compared to those on various oral antipsychotics over a one-year follow-up in a naturalistic setting. Methods: Sixty patients with SCZ were subdivided in two groups, those receiving LAIs (n = 25) and those receiving oral antipsychotics (n = 35). The groups were comparable for age, gender, educational attainment, employment status, marital status, smoking habits, and baseline SCZ severity, with no differences in baseline chlorpromazine equivalent dosages. Results: Over the follow-up period, patients in the LAI group discontinued treatment less frequently (χ2 = 4.72, p = 0.030), showed fewer suicide attempts (χ2 = 5.63, p = 0.018), fewer hospitalizations (χ2 = 4.95, p = 0.026), and fewer relapses (χ2 = 6.61, p = 0.010). Significant differences also emerged on the Drug Attitude Inventory (DAI-10) scores (F = 8.76, p = 0.005) and Body Mass Index (BMI) values (F = 8.32, p = 0.007), with the LAI group showing more favorable outcomes. Conclusions: LAIs, compared to oral antipsychotics, may promote treatment adherence, as shown by decreased hospitalization; furthermore, their use is related with better outcomes, like fewer relapses and less suicide attempts in individuals with SCZ in real-world settings. Full article
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29 pages, 2035 KiB  
Systematic Review
Dopamine Partial Agonists in Pregnancy and Lactation: A Systematic Review
by Alexia Koukopoulos, Delfina Janiri, Miriam Milintenda, Sara Barbonetti, Georgios D. Kotzalidis, Tommaso Callovini, Lorenzo Moccia, Silvia Montanari, Marianna Mazza, Lucio Rinaldi, Alessio Simonetti, Mario Pinto, Giovanni Camardese and Gabriele Sani
Pharmaceuticals 2025, 18(7), 1010; https://doi.org/10.3390/ph18071010 - 6 Jul 2025
Viewed by 708
Abstract
Background/Objectives: Dopamine partial agonists are drugs initially developed to treat schizophrenia, seeking a double effect of increased dopaminergic transmission in the prefrontal cortex and decrease in the accumbens/striatum. Of these drugs, aripiprazole, brexpiprazole, and cariprazine are currently marketed and used in schizophrenia [...] Read more.
Background/Objectives: Dopamine partial agonists are drugs initially developed to treat schizophrenia, seeking a double effect of increased dopaminergic transmission in the prefrontal cortex and decrease in the accumbens/striatum. Of these drugs, aripiprazole, brexpiprazole, and cariprazine are currently marketed and used in schizophrenia spectrum and mood disorders. It is debated whether patients with psychiatric disorders becoming pregnant should discontinue or continue their antipsychotic treatment despite some risks for the fetus, i.e., whether it is worse to have an untreated disorder or treating it with drugs. The safety of drugs for mother and baby extend from pregnancy to the postpartum, when breastfeeding assumes great importance. We set to investigate the use of dopamine partial agonists in pregnancy and lactation. Methods: On 23 June 2025, we used suitable strategies for identifying cases and studies of cariprazine, aripiprazole, brexpiprazole, dopamine partial agonists in pregnancy, perinatal period, and/or lactation on PubMed, CINAHL, PsycInfo/PsycArticles, Scopus, and ClinicalTrials.gov. We used the PRISMA Statement in developing our review. We included case reports and clinical studies. We excluded reports without pregnancy or focused on other drugs than the above. We reached consensus on eligibility with Delphi rounds among all authors. Results: Our searches produced 386 results on the above databases. We included 24 case reports/series and 15 studies. Most studies showed no negative pregnancy outcomes. There were serious concerns about the use of dopamine D2/D3 partial agonists during lactation. Conclusions: The use of dopamine partial agonists during pregnancy appears to be safe, but during breastfeeding they should be better avoided. Full article
(This article belongs to the Special Issue Pharmaceutical Strategy for Mood Disorders)
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16 pages, 634 KiB  
Systematic Review
Lurasidone for Pediatric Bipolar Disorder: A Systematic Review
by Alexia Koukopoulos, Claudia Calderoni, Georgios D. Kotzalidis, Tommaso Callovini, Lorenzo Moccia, Silvia Montanari, Gianna Autullo, Alessio Simonetti, Mario Pinto, Giovanni Camardese, Gabriele Sani and Delfina Janiri
Pharmaceuticals 2025, 18(7), 979; https://doi.org/10.3390/ph18070979 - 30 Jun 2025
Viewed by 857
Abstract
Background/Objectives: Lurasidone ((3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione) is a second-generation antipsychotic approved for schizophrenia and mood disorders. Adolescents and children with bipolar disorder receive treatments that expose them to weight gain and metabolic syndrome. Lurasidone is relatively free from such side effects, so it may constitute [...] Read more.
Background/Objectives: Lurasidone ((3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione) is a second-generation antipsychotic approved for schizophrenia and mood disorders. Adolescents and children with bipolar disorder receive treatments that expose them to weight gain and metabolic syndrome. Lurasidone is relatively free from such side effects, so it may constitute a useful alternative for the treatment of these patients. We focused on the use of lurasidone in children and adolescents with bipolar disorder. Methods: On 11 June 2025, we used the following strategy on PubMed: lurasidone AND (“bipolar disorder” OR “bipolar depression” OR mania OR manic). We filtered for humans and ages 0–18 years and included case reports and clinical studies. Similar strategies adapted to each database were used to carry out our systematic review on CINAHL, PsycINFO/PsycARTICLES, Scopus, and the ClinicalTrials.gov register on the same date. We excluded reports without children/adolescent participants, those grouping adult participants with children/adolescents without providing data separately, reviews, and opinions/editorials with no data. Eligibility was determined through Delphi rounds; it was required that consensus was reached among all authors. We followed the PRISMA-2020 Statement. Results: Our search produced 38 results on PubMed on 11 June 2025. We included four case reports/series and five studies. One additional eligible study emerged from our Scopus inquiry, raising the number of eligible studies to six. One case series was moderately positive; one case report was neutral, another was positive, and one reported the induction of mania. The six longitudinal studies involved 16,735 participants and showed generally good efficacy. Conclusions: The use of lurasidone in adolescents/children with bipolar disorder obtains favorable results regarding the excitatory and depressive symptoms of bipolar disorder with no significant side effects. Full article
(This article belongs to the Special Issue Pediatric Drug Therapy: Safety, Efficacy, and Personalized Medicine)
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13 pages, 1170 KiB  
Article
Gender Differences in Alexithymia, Emotion Regulation, and Impulsivity in Young Individuals with Mood Disorders
by Luca Di Benedetto, Mario Pinto, Valentina Ieritano, Francesco Maria Lisci, Laura Monti, Elisa Marconi, Daniela Pia Rosaria Chieffo, Silvia Montanari, Georgios D. Kotzalidis, Gabriele Sani and Delfina Janiri
J. Clin. Med. 2025, 14(6), 2030; https://doi.org/10.3390/jcm14062030 - 17 Mar 2025
Viewed by 1656
Abstract
Background/Objectives: Alexithymia, emotion regulation, and impulsivity are key factors in youths with mood disorders. However, gender differences within these dimensions remain insufficiently studied in this population. This study seeks to explore these dimensions in a sample of adolescents and young adults with mood [...] Read more.
Background/Objectives: Alexithymia, emotion regulation, and impulsivity are key factors in youths with mood disorders. However, gender differences within these dimensions remain insufficiently studied in this population. This study seeks to explore these dimensions in a sample of adolescents and young adults with mood disorders, aiming to identify gender-specific characteristics with important clinical implications. Methods: We assessed 115 outpatients aged 13 to 25 years with a DSM-5 diagnosis of mood disorder. The evaluation included the Toronto Alexithymia Scale (TAS-20), the Difficulties in Emotion Regulation Scale (DERS), and the UPPS-P Impulsive Behavior Scale. The associations with suicidal ideation were tested using two different multivariate models. Results were controlled for age and intelligence measures. Results: The first model (Wilks’ Lambda = 0.720, p < 0.001) revealed significantly higher scores in women than men for TAS-20 (p < 0.001), DERS (p < 0.001), and the UPPS-P subscales “Lack of Premeditation” (p = 0.004) and “Lack of Perseverance” (p = 0.001). Regression analyses confirmed gender as a significant predictor of these variables, also controlling for age and intelligence. Furthermore, intelligence measure influenced Lack of Premeditation and age influenced Lack of Perseverance. Conclusions: Women with mood disorders exhibit greater alexithymia, emotional dysregulation, and impulsivity, particularly in difficulties with planning and task persistence. These findings highlight the need for gender-sensitive interventions that address emotional awareness and impulse control to improve clinical outcomes. Full article
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27 pages, 1361 KiB  
Review
The Neuroscience Behind Writing: Handwriting vs. Typing—Who Wins the Battle?
by Giuseppe Marano, Georgios D. Kotzalidis, Francesco Maria Lisci, Maria Benedetta Anesini, Sara Rossi, Sara Barbonetti, Andrea Cangini, Alice Ronsisvalle, Laura Artuso, Cecilia Falsini, Romina Caso, Giuseppe Mandracchia, Caterina Brisi, Gianandrea Traversi, Osvaldo Mazza, Roberto Pola, Gabriele Sani, Eugenio Maria Mercuri, Eleonora Gaetani and Marianna Mazza
Life 2025, 15(3), 345; https://doi.org/10.3390/life15030345 - 22 Feb 2025
Cited by 4 | Viewed by 12809
Abstract
Background: The advent of digital technology has significantly altered ways of writing. While typing has become the dominant mode of written communication, handwriting remains a fundamental human skill, and its profound impact on cognitive processes continues to be a topic of intense scientific [...] Read more.
Background: The advent of digital technology has significantly altered ways of writing. While typing has become the dominant mode of written communication, handwriting remains a fundamental human skill, and its profound impact on cognitive processes continues to be a topic of intense scientific scrutiny. Methods: This paper investigates the neural mechanisms underlying handwriting and typing, exploring the distinct cognitive and neurological benefits associated with each. By synthesizing findings from neuroimaging studies, we explore how handwriting and typing differentially activate brain regions associated with motor control, sensory perception, and higher-order cognitive functions. Results: Handwriting activates a broader network of brain regions involved in motor, sensory, and cognitive processing. Typing engages fewer neural circuits, resulting in more passive cognitive engagement. Despite the advantages of typing in terms of speed and convenience, handwriting remains an important tool for learning and memory retention, particularly in educational contexts. Conclusions: This review contributes to the ongoing debate about the role of technology in education and cognitive development. By understanding the neural differences between handwriting and typing, we can gain insights into optimal learning strategies and potential cognitive advantages, in order to optimize educational, cognitive, and psychological methodologies. Full article
(This article belongs to the Special Issue Advances in Brain-Machine Interfaces)
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57 pages, 1065 KiB  
Systematic Review
Pharmacological Interventions for Negative Symptoms in Schizophrenia: A Systematic Review of Randomised Control Trials
by Lorenzo Moccia, Francesca Bardi, Maria Benedetta Anesini, Sara Barbonetti, Georgios D. Kotzalidis, Sara Rossi, Romina Caso, Flavia Grisoni, Giuseppe Mandracchia, Stella Margoni, Tommaso Callovini, Delfina Janiri, Marianna Mazza, Alessio Simonetti, Silvia Montanari, Gianna Autullo, Giovanni Camardese, Maria Pepe, Marco Di Nicola, Vassilij Di Giorgio, Fabio Conti, Gabriele Sani and on behalf of the Gemelli RePsy Study Groupadd Show full author list remove Hide full author list
Biomedicines 2025, 13(3), 540; https://doi.org/10.3390/biomedicines13030540 - 21 Feb 2025
Cited by 1 | Viewed by 2120
Abstract
Background/Objectives: While positive symptoms of schizophrenia are often satisfactorily controlled, negative symptoms are difficult to treat, persisting despite treatment. Different strategies have been devised to deal with this problem. We aimed to review drug treatment for negative symptoms of schizophrenia in controlled trials [...] Read more.
Background/Objectives: While positive symptoms of schizophrenia are often satisfactorily controlled, negative symptoms are difficult to treat, persisting despite treatment. Different strategies have been devised to deal with this problem. We aimed to review drug treatment for negative symptoms of schizophrenia in controlled trials of marketed drugs. Methods: We searched the PubMed database and the resulting records’ reference lists to identify eligible trials using schizophrenia[ti] AND “negative symptom*”[ti] as a search strategy. We determined eligibility through Delphi rounds among all authors. Results: On 11 February 2025, we identified 1485 records on PubMed and 3 more from reference lists. Eligible were 95 records. Most studies were double-blind, randomized controlled trials, carried-out in add-on in patients stabilized with antipsychotics. Other antipsychotics were the most frequent comparators, followed by antidepressants, and recently, antioxidants are gaining importance in trials. Many trials, especially those conducted in the Western world, found no significant effects compared to placebo, while most Iranian studies were positive, although not with a strong effect size. Conclusions: Current research has contributed little to progress in the treatment of the negative symptoms of schizophrenia. The reason might reside in the absence of knowledge of the mechanisms whereby these symptoms are generated, which prevents us from designing possibly effective treatment strategies, and/or to the chronicity of negative symptoms, as they are the first to be established even when they do not become fully apparent. Full article
(This article belongs to the Special Issue Advanced in Schizophrenia Research and Treatment)
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18 pages, 465 KiB  
Article
Optimising Aripiprazole Long-Acting Injectable: A Comparative Study of One- and Two-Injection Start Regimens in Schizophrenia with and Without Substance Use Disorders and Relationship to Early Serum Levels
by Giada Trovini, Ginevra Lombardozzi, Georgios D. Kotzalidis, Luana Lionetto, Felicia Russo, Angela Sabatino, Elio Serra, Simone Castorina, Giorgia Civita, Sara Frezza, Donatella De Bernardini, Giuseppe Costanzi, Marika Alborghetti, Maurizio Simmaco, Ferdinando Nicoletti and Sergio De Filippis
Int. J. Mol. Sci. 2025, 26(3), 1394; https://doi.org/10.3390/ijms26031394 - 6 Feb 2025
Cited by 2 | Viewed by 3367
Abstract
Aripiprazole as a long-acting injectable (LAI) is initiated in oral aripiprazole-stabilised patients and needs, after first injection, 14 days supplementation of oral aripiprazole (one-injection start, OIS). Recently, an alternative two-injection start (TIS) was advanced, involving two 400 mg injections with a single 20 [...] Read more.
Aripiprazole as a long-acting injectable (LAI) is initiated in oral aripiprazole-stabilised patients and needs, after first injection, 14 days supplementation of oral aripiprazole (one-injection start, OIS). Recently, an alternative two-injection start (TIS) was advanced, involving two 400 mg injections with a single 20 mg oral supplementation of aripiprazole. We tested the two regimens in patients with schizophrenia (SCZ, n = 152, 90 men and 62 women) with (SUD+; n = 93) or without (SUD; n = 59) substance use disorders (SUDs), comparing OIS (n = 66) with TIS (n = 86) and SUD+ vs. SUD. For 26 patients, we measured weekly for one month, aripiprazole + dehydroaripiprazole (active moiety) levels. Patients were followed for three months after LAI with psychopathology and quality-of-life scales (BPRS, CGI-S, ACES, BIS-11, and WHOQOL). All groups improved in psychopathology with no differences between OSI and TIS and between SCZ–SUD+ and SCZ–SUD. The TIS group was associated with serum blood levels of the active moiety within the therapeutic window, while the OIS group showed peaks above the window, possibly exposing patients to toxicity. Treatments were well-tolerated. Here we showed no disadvantages for TIS vs. OIS and possibly increased safety. Shifting the initiation of aripiprazole LAIs to the TIS modality may be safe and pharmacokinetically advantageous. Full article
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20 pages, 299 KiB  
Review
Psychological Sequelae of Dog Bites in Children: A Review
by Laura Monti, Georgios D. Kotzalidis, Valentina Arcangeli, Camilla Brozzi, Rossella Iacovino, Cristina Giansanti, Daniela Belella, Elisa Marconi, Silvia Maria Pulitanò, Marianna Mazza, Giuseppe Marano, Giorgio Conti, Delfina Janiri, Gabriele Sani and Daniela Pia Rosaria Chieffo
Children 2024, 11(10), 1218; https://doi.org/10.3390/children11101218 - 7 Oct 2024
Cited by 2 | Viewed by 2540
Abstract
Background/Objectives: Although rare in the Western world, dog bites may be lethal or lead to physically severe outcomes. However, little attention is given to their psychological consequences. We aimed to review their psychological consequences in children 1–14 years of age, focusing on the [...] Read more.
Background/Objectives: Although rare in the Western world, dog bites may be lethal or lead to physically severe outcomes. However, little attention is given to their psychological consequences. We aimed to review their psychological consequences in children 1–14 years of age, focusing on the prevalence and nature of psychological disorders, evaluating the impact on future mental health of children and their families, and assessing the effectiveness of preventive interventions and measures. Methods: On 23 May 2024, we investigated the PubMed, CINAHL, and PsycINFO/PsycARTICLES databases using (“dog bite” OR animal-induced OR animal-caused) AND (psychol* OR mental OR psychiatr* OR anxiety OR anxious OR depress* OR obsess* OR trauma* OR psychosis OR psychotic OR schizophren* OR schizoaffect*) filtered for ages 0–18 years. This resulted in 311 records, of which 50 were eligible. These included original research, case reports, patient surveys, and reviews/meta-analyses. Results: Findings indicate that younger children are particularly vulnerable, often suffering head/neck bites, leading to severe injuries and psychological distress, with post-traumatic stress disorder (PTSD) being a common outcome. Symptoms such as nightmares, flashbacks, anxiety, and social withdrawal were frequently reported. Positive parental support and timely psychological interventions were found to mitigate these effects. Conclusions: Interdisciplinary approaches integrating education, cognitive restructuring, and behaviour modification are needed to effectively prevent and address the psychological impacts of dog bites. Summarising, dog bites in children result in substantial psychological sequelae, necessitating robust prevention and intervention strategies to improve their quality of life and reduce the risk of chronic mental conditions. Full article
26 pages, 1460 KiB  
Systematic Review
Obstetric Outcomes in Women on Lithium: A Systematic Review and Meta-Analysis
by Tommaso Callovini, Silvia Montanari, Francesca Bardi, Sara Barbonetti, Sara Rossi, Romina Caso, Giuseppe Mandracchia, Stella Margoni, Andrea Brugnami, Marco Paolini, Giovanni Manfredi, Luca Lo Giudice, Daniele Segatori, Andrea Zanzarri, Luca Onori, Claudia Calderoni, Elisabetta Benini, Giuseppe Marano, Marco Massetti, Federica Fiaschè, Federica Di Segni, Delfina Janiri, Alessio Simonetti, Lorenzo Moccia, Flavia Grisoni, Sara Ruggiero, Giovanni Bartolucci, Marco Biscosi, Ottavia Marianna Ferrara, Evelina Bernardi, Leonardo Monacelli, Alessandro Michele Giannico, Domenico De Berardis, Giulia Battisti, Michele Ciliberto, Caterina Brisi, Francesco Maria Lisci, Antonio Maria D’Onofrio, Antonio Restaino, Luca Di Benedetto, Maria Benedetta Anesini, Gianluca Boggio, Elettra Specogna, Arianna Crupi, Emanuela De Chiara, Emanuele Caroppo, Valentina Ieritano, Laura Monti, Daniela Pia Rosaria Chieffo, Lucio Rinaldi, Giovanni Camardese, Ilaria Cuomo, Roberto Brugnoli, Georgios D. Kotzalidis, Gabriele Sani and Marianna Mazzaadd Show full author list remove Hide full author list
J. Clin. Med. 2024, 13(16), 4872; https://doi.org/10.3390/jcm13164872 - 18 Aug 2024
Cited by 4 | Viewed by 2366
Abstract
Background/Objectives: Lithium taken during pregnancy was linked in the past with increased risk for foetal/newborn malformations, but clinicians believe that it is worse for newborn children not to treat the mothers’ underlying psychiatric illness. We set to review the available evidence of [...] Read more.
Background/Objectives: Lithium taken during pregnancy was linked in the past with increased risk for foetal/newborn malformations, but clinicians believe that it is worse for newborn children not to treat the mothers’ underlying psychiatric illness. We set to review the available evidence of adverse foetal outcomes in women who received lithium treatment for some time during their pregnancy. Methods: We searched four databases and a register to seek papers reporting neonatal outcomes of women who took lithium during their pregnancy by using the appropriate terms. We adopted the PRISMA statement and used Delphi rounds among all the authors to assess eligibility and the Cochrane Risk-of-Bias tool to evaluate the RoB of the included studies. Results: We found 28 eligible studies, 10 of which met the criteria for inclusion in the meta-analysis. The studies regarded 1402 newborn babies and 2595 women exposed to lithium. Overall, the systematic review found slightly increased adverse pregnancy outcomes for women taking lithium for both the first trimester only and any time during pregnancy, while the meta-analysis found increased odds for cardiac or other malformations, preterm birth, and a large size for gestational age with lithium at any time during pregnancy. Conclusions: Women with BD planning a pregnancy should consider discontinuing lithium when euthymic; lithium use during the first trimester and at any time during pregnancy increases the odds for some adverse pregnancy outcomes. Once the pregnancy has started, there is no reason for discontinuing lithium; close foetal monitoring and regular blood lithium levels may obviate some disadvantages of lithium administration during pregnancy. Full article
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13 pages, 698 KiB  
Systematic Review
Examining the Myth of Prescribed Stimulant Misuse among Individuals with Attention-Deficit/Hyperactivity Disorder: A Systematic Review
by Tommaso Callovini, Delfina Janiri, Daniele Segatori, Giulia Mastroeni, Georgios D. Kotzalidis, Marco Di Nicola and Gabriele Sani
Pharmaceuticals 2024, 17(8), 1076; https://doi.org/10.3390/ph17081076 - 16 Aug 2024
Cited by 1 | Viewed by 3002
Abstract
The literature emphasizes the importance of addressing the misuse of ADHD medications as a potential significant healthcare issue within the general population. Nevertheless, there are no systematic reviews that specifically examine whether the misuse of psychostimulant medication among clinical populations diagnosed with ADHD [...] Read more.
The literature emphasizes the importance of addressing the misuse of ADHD medications as a potential significant healthcare issue within the general population. Nevertheless, there are no systematic reviews that specifically examine whether the misuse of psychostimulant medication among clinical populations diagnosed with ADHD who are undergoing prescribed stimulant therapy is a rational concern or a false myth. This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. We searched PubMed databases for articles indexed up to 12th July 2023, without language restrictions. Our systematic search generated 996 unique articles. After a full-text revision, 13 studies met the eligibility criteria and were included in the systematic review. In the 50% of the study on the adult population, the reported prevalence of stimulant misuse was 0%. In other studies, the range of stimulant misuse rates varied from 2% to 29%, with no available data specifically focusing on the youth population. It has been noted that misuse of prescribed stimulant treatment is linked with particular subject characteristics, such as older age, prior or more frequent use of ADHD medication, use of short-acting medication, and a history of alcohol/substance misuse diagnosis. Despite certain limitations, our study highlights that while a significant proportion of individuals undergoing psychostimulant treatment for ADHD follow their prescribed medication regimens without resorting to misuse behaviors, there is variability in adherence, with occurrences of misuse behaviors. The misuse of prescribed ADHD treatment appears to be associated with distinct subject characteristics, underscoring the importance for tailored interventions addressing the specific requirements of these individuals to attain optimal treatment outcomes while mitigating misuse risks. Full article
(This article belongs to the Special Issue Advances in Neuropharmacology of Drug Abuse)
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21 pages, 502 KiB  
Article
Effect of Anti-Interleukin-6 Agents on Psychopathology in a Sample of Patients with Post-COVID-19 Syndrome: An Observational Study
by Alessio Simonetti, Antonio Restaino, Evelina Bernardi, Ottavia Marianna Ferrara, Stella Margoni, Antonio Maria D’Onofrio, Federica Ranieri, Delfina Janiri, Vincenzo Galluzzo, Matteo Tosato, Georgios D. Kotzalidis, Francesco Landi and Gabriele Sani
Brain Sci. 2024, 14(1), 47; https://doi.org/10.3390/brainsci14010047 - 3 Jan 2024
Cited by 1 | Viewed by 2947
Abstract
Interleukin 6 (IL-6) receptor inhibitors tocilizumab and sarilumab have recently been approved for severe coronavirus disease 2019 (COVID-19). They also affect mood, even though their effect on the post-COVID-19 syndrome-related psychopathology still has to be investigated. The aim of this study was to [...] Read more.
Interleukin 6 (IL-6) receptor inhibitors tocilizumab and sarilumab have recently been approved for severe coronavirus disease 2019 (COVID-19). They also affect mood, even though their effect on the post-COVID-19 syndrome-related psychopathology still has to be investigated. The aim of this study was to investigate their effect on psychopathology in a sample of patients with post-COVID-19 syndrome. We included 246 patients (34% female, 66% male) aged 18–75 years who had been hospitalized for COVID. Patients were split into those who received anti-IL-6 receptor agents (Anti-IL-6-R, N = 88) and those who did not (Ctrl, N = 158). The former group was further split into those receiving tocilizumab (TOC, N = 67) and those receiving sarilumab (SAR, N = 21). Groups were compared based on clinical characteristics before and during COVID-19 as well as on physical and psychiatric symptoms after COVID-19. Ctrl had less psychiatric and physical symptoms during hospitalization and more post-COVID-19 diarrhea, headache, cough, and dyspnea upon exertion than those receiving IL-6-receptor inhibitors. Ctrl also showed greater difficulties in emotion regulation. These differences were driven by TOC vs. Ctrl, whereas differences between SAR and Ctrl or TOC did not reach significance. IL-6 receptor inhibitors are related to a lower post-COVID-19 illness burden and seem to be effective in emotion regulation. Further research is needed to confirm these findings. Full article
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12 pages, 616 KiB  
Article
What Came First, Mania or Depression? Polarity at Onset in Bipolar I and II: Temperament and Clinical Course
by Delfina Janiri, Alessio Simonetti, Lorenzo Moccia, Daniele Hirsch, Silvia Montanari, Marianna Mazza, Marco Di Nicola, Georgios D. Kotzalidis and Gabriele Sani
Brain Sci. 2024, 14(1), 17; https://doi.org/10.3390/brainsci14010017 - 23 Dec 2023
Cited by 1 | Viewed by 2301
Abstract
(1) Background: Bipolar disorder (BD) is divided into type I (BD-I) and type II (BD-II). Polarity at onset (PO) is a proposal to specify the clinical course of BD, based on the type of the first episode at disorder onset—depressive (D-PO) or manic [...] Read more.
(1) Background: Bipolar disorder (BD) is divided into type I (BD-I) and type II (BD-II). Polarity at onset (PO) is a proposal to specify the clinical course of BD, based on the type of the first episode at disorder onset—depressive (D-PO) or manic (M-PO). At the same time, affective temperaments represent preexisting variants of the spectrum of affective disorders. Our objectives were to investigate the hypothesis that temperament may exert an influence on PO, and that this factor can serve as an indicator of the forthcoming course of the disorder, carrying significant therapeutic implications. (2) Methods: We included 191 patients with BD and examined clinical variables and temperament; the latter was assessed using the short version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego—Auto-questionnaire (TEMPS-A-39-SV). We tested the associations between these variables and PO using standard univariate/bivariate methods followed by multivariate logistic regression models. (3) Results: 52.9% of the sample had D-PO and 47.1% had M-PO. D-PO and M-PO patients scored higher for dysthymic and hyperthymic temperaments, respectively (p < 0.001). Also, they differed in BD subtypes, age at first affective episode, illness duration, number of depressive episodes, seasonality, suicide risk, substance use, lithium, and benzodiazepine use (p < 0.05). Only BD-II and age at first depressive episode were predictors of D-PO, whereas BD-I, age at first manic/hypomanic episode, and hyperthymic temperament were predictors of M-PO (p < 0.01). (4) Conclusions: Our findings point to the importance of carefully assessing temperament and PO in patients with BD, to better predict the clinical course and tailor therapeutic interventions to individual patients’ needs. Full article
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18 pages, 680 KiB  
Article
Association of Delirium and Depression with Respiratory and Outcome Measures in COVID-19 Inpatients
by Alessio Simonetti, Cristina Pais, Vezio Savoia, Maria Camilla Cipriani, Matteo Tosato, Delfina Janiri, Evelina Bernardi, Ottavia Marianna Ferrara, Stella Margoni, Georgios D. Kotzalidis, Daniela Chieffo, Massimo Fantoni, Rosa Liperoti, Francesco Landi, Roberto Bernabei and Gabriele Sani
J. Pers. Med. 2023, 13(8), 1207; https://doi.org/10.3390/jpm13081207 - 29 Jul 2023
Viewed by 1705
Abstract
Delirium (DEL) and depression (DEP) may impair the course and severity of acute respiratory illness. The impact of such syndromes on respiratory and outcome parameters in inpatients with COVID-19 needs clarification. To clarify the relationship between DEL and DEP and respiratory outcome measures, [...] Read more.
Delirium (DEL) and depression (DEP) may impair the course and severity of acute respiratory illness. The impact of such syndromes on respiratory and outcome parameters in inpatients with COVID-19 needs clarification. To clarify the relationship between DEL and DEP and respiratory outcome measures, we enrolled 100 inpatients from COVID-19 units of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome. Participants were divided into those with DEL, DEP, or absence of either delirium or depression (CONT). Delirium severity was assessed with the Neelson and Champagne Confusion Scale (NEECHAM). Psychopathology was assessed with the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), and the Brief Psychiatric Rating Scale (BPRS). Dependent variables include: (a) respiratory parameters, i.e., partial pressure of oxygen in arterial blood (PaO2), oxygen saturation (SpO2), ratio between arterial partial pressure of oxygen (PaO2), and fraction of inspired oxygen (PaO2/FiO2); (b) outcome parameters, i.e., duration of hospitalization and number of pharmacological treatments used during the hospitalization. We investigated between-group differences and the relationships between severity of delirium/depression and the dependent variables. Duration of hospitalization was longer for DEL than for either DEP or CONT and for DEP compared to CONT. NEECHAM and HAM-D scores predicted lower PaO2 and PaO2/FiO2 levels in the DEL and DEP groups, respectively. In DEP, BPRS scores positively correlated with duration of hospitalization. Delirium impacted the course of COVID-19 more severely than depression. The mechanisms by which delirium and depression worsen respiratory parameters differ. Full article
(This article belongs to the Section Epidemiology)
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29 pages, 762 KiB  
Systematic Review
Are the Post-COVID-19 Posttraumatic Stress Disorder (PTSD) Symptoms Justified by the Effects of COVID-19 on Brain Structure? A Systematic Review
by Georgios D. Kotzalidis, Ottavia Marianna Ferrara, Stella Margoni, Valentina Ieritano, Antonio Restaino, Evelina Bernardi, Alessia Fischetti, Antonello Catinari, Laura Monti, Daniela Pia Rosaria Chieffo, Alessio Simonetti and Gabriele Sani
J. Pers. Med. 2023, 13(7), 1140; https://doi.org/10.3390/jpm13071140 - 15 Jul 2023
Cited by 8 | Viewed by 2727
Abstract
COVID-19 affects brain function, as deduced by the “brain fog” that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a patient in the post-COVID-19 period. Approximately one-third of patients, even when they have recovered from the [...] Read more.
COVID-19 affects brain function, as deduced by the “brain fog” that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a patient in the post-COVID-19 period. Approximately one-third of patients, even when they have recovered from the acute somatic disease, continue to show posttraumatic stress disorder (PTSD) symptoms. We hypothesized that the persistent changes induced by COVID-19 on brain structure would overlap with those associated with PTSD. We performed a thorough PubMed search on 25 April 2023 using the following strategy: ((posttraumatic OR PTSD) AND COVID-19 AND (neuroimaging OR voxel OR VBM OR freesurfer OR structural OR ROI OR whole-brain OR hippocamp* OR amygd* OR “deep gray matter” OR “cortical thickness” OR caudate OR striatum OR accumbens OR putamen OR “regions of interest” OR subcortical)) OR (COVID-19 AND brain AND (voxel[ti] OR VBM[ti] OR magnetic[ti] OR resonance[ti] OR imaging[ti] OR neuroimaging[ti] OR neuroimage[ti] OR positron[ti] OR photon*[ti] OR PET[ti] OR SPET[ti] OR SPECT[ti] OR spectroscop*[ti] OR MRS[ti])), which produced 486 records and two additional records from other sources, of which 36 were found to be eligible. Alterations were identified and described and plotted against the ordinary PTSD imaging findings. Common elements were hypometabolism in the insula and caudate nucleus, reduced hippocampal volumes, and subarachnoid hemorrhages, while white matter hyperintensities were widespread in both PTSD and post-COVID-19 brain infection. The comparison partly supported our initial hypothesis. These data may contribute to further investigation of the effects of long COVID on brain structure and function. Full article
(This article belongs to the Special Issue Novel Advance in COVID-19 and Neuroscience)
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