Publications by authors named "Domenico De Berardis"

195 Publications

Relationship between Health-Anxiety and Cyberchondria: Role of Metacognitive Beliefs.

J Clin Med 2022 May 5;11(9). Epub 2022 May 5.

National Health Service, Department of Mental Health, ASL 4, 64100 Teramo, Italy.

Purpose: The current study was designed to examine the relationship between health anxiety, cyberchondria (its constructs), and metacognitive beliefs. In addition, it also evaluated the moderating role of metacognitive beliefs in this relationship.

Design And Method: The present study used the purposive sampling technique to acquire a sample of ( = 500) adults, among them ( = 256) women and ( = 244) men, and the age of the sample ranged from 20 to 50 years. Short Health Anxiety Inventory, Cyberchondria Severity Scale, and Metacognitions Questionnaire-Health Anxiety were used to operationalize the present study variables.

Findings: The descriptive statistics revealed that all instruments have good psychometric properties, as Cronbach's alpha coefficients for all scales are ≥0.70. In addition to this, the Pearson correlation showed that all variables of the present study have a significant positive correlation with each other. Furthermore, the regression analysis described that health anxiety and metacognitive beliefs (biased thinking and beliefs about uncontrollable thoughts) were the significant positive predictors of cyberchondria. Moreover, moderation analysis showed that metacognitive beliefs significantly strengthened the association between health anxiety and cyberchondria and its constructs.

Practical Implications: The present study will help medical practitioners to understand how metacognitive beliefs and health anxiety can cause an increase in cyberchondria. This will help them to design better treatment plans for people with cyberchondria.
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http://dx.doi.org/10.3390/jcm11092590DOI Listing
May 2022

Sick leave duration as a potential marker of functionality and disease severity in depression.

Int J Psychiatry Clin Pract 2022 Apr 2:1-11. Epub 2022 Apr 2.

Department of Psychiatry and Psychotherapy (Division of General Psychiatry), Medical University of Vienna, Vienna, Austria.

To discuss the impact of depression on work and how depression-related sick leave duration could be a potential indicator and outcome for measuring functionality in depression. Our review was based on a literature search and expert opinion that emerged during a virtual meeting of European psychiatrists that was convened to discuss this topic. Current evidence demonstrates that depression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditions. A wide variety of pharmacological and non-pharmacological treatments and work-based interventions are effective in reducing depression-related sick leave duration and/or facilitating return to work. Recent real-world evidence showed that patients treated with antidepressant monotherapy appear to recover their working life faster than those receiving combination therapy. Although depression-related sick leave duration was found to correlate with severity of depressive symptoms, it cannot be used alone as a viable marker for disease severity. Given its multifactorial nature, depression-related sick leave duration is not on its own a viable outcome measure of depression severity but could be used as a secondary outcome alongside more formal severity measures and may also represent a useful measure of functionality in depression. Key pointsDepression in the working population and depression-related sick leave have a profound economic impact on societyDepression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditionsA wide variety of pharmacological and non-pharmacological treatments and work-based interventions have been shown to be effective in reducing depression-related sick leave duration and/or facilitating return to workIn terms of pharmacological intervention, recent real-world evidence has shown that patients treated with antidepressant monotherapy are able to recover their working life faster than those treated with combination therapyAlthough depression-related sick leave duration has been shown to correlate with severity of depressive symptoms, it is not a viable outcome measure of depression severity on its own, but could be used as secondary outcome alongside more formal clinician- and patient-rated severity measuresDepression-related sick leave duration may, however, represent a viable outcome for measuring functionality in depression.
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http://dx.doi.org/10.1080/13651501.2022.2054350DOI Listing
April 2022

Brain Correlates of the Alcohol Use Disorder Pharmacotherapy Response: A Systematic Review of Neuroimaging Studies.

Brain Sci 2022 Mar 14;12(3). Epub 2022 Mar 14.

Department of Neuroscience, FMABC University Center, Santo André 09060-870, SP, Brazil.

Background: Although Alcohol Use Disorder (AUD) is highly prevalent worldwide, treating this condition remains challenging. Further, potential treatments for AUD do not fully address alcohol-induced neuroadaptive changes. Understanding the effects of pharmacotherapies for AUD on the human brain may lead to tailored, more effective treatments, and improved individual clinical outcomes.

Objectives: We systematically reviewed the literature for studies investigating pharmacotherapies for AUD that included neuroimaging-based treatment outcomes. We searched the PubMed, Scielo, and PsycINFO databases up to January 2021.

Study Eligibility Criteria, Participants, And Interventions: Eligible studies included those investigating pharmacotherapies for AUD and employing functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and/or proton magnetic resonance spectroscopy (H-MRS).

Study Appraisal And Synthesis Methods: Two independent reviewers screened studies' titles and abstracts for inclusion. Data extraction forms were shared among all the authors to standardize data collection. We gathered information on the following variables: sample size; mean age; sociodemographic and clinical characteristics; alcohol use status; study design and methodology; main neuroimaging findings and brain-regions of interest (i.e., brain areas activated by alcohol use and possible pharmacological interactions); and limitations of each study.

Results: Out of 177 studies selected, 20 studies provided relevant data for the research topic. Findings indicate that: (1) Acamprosate and gabapentin may selectively modulate limbic regions and the anterior cingulate cortex; (2) Naltrexone and disulfiram effects may involve prefrontal, premotor, and cerebellar regions; (3) Pharmacotherapies acting on glutamate and GABA neurotransmission involve primarily areas underpinning reward and negative affective states, and; (4) Pharmacotherapies acting on opioid and dopamine systems may affect areas responsible for the cognitive and motor factors of AUD.

Limitations: Most of the studies were focused on naltrexone. A small number of studies investigated the action of disulfiram and gabapentin, and no neuroimaging studies investigated topiramate. In addition, the time between medication and neuroimaging scans varied widely across studies.

Conclusions: We identified key-brain regions modulated by treatments available for AUD. Some of the regions modulated by naltrexone are not specific to the brain reward system, such as the parahippocampal gyrus (temporal lobe), parietal and occipital lobes. Other treatments also modulate not specific regions of the reward system, but play a role in the addictive behaviors, including the insula and dorsolateral prefrontal cortex. The role of these brain regions in mediating the AUD pharmacotherapy response warrants investigation in future research studies.
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http://dx.doi.org/10.3390/brainsci12030386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946664PMC
March 2022

Brain Correlates of the Alcohol Use Disorder Pharmacotherapy Response: A Systematic Review of Neuroimaging Studies.

Brain Sci 2022 Mar 14;12(3). Epub 2022 Mar 14.

Department of Neuroscience, FMABC University Center, Santo André 09060-870, SP, Brazil.

Background: Although Alcohol Use Disorder (AUD) is highly prevalent worldwide, treating this condition remains challenging. Further, potential treatments for AUD do not fully address alcohol-induced neuroadaptive changes. Understanding the effects of pharmacotherapies for AUD on the human brain may lead to tailored, more effective treatments, and improved individual clinical outcomes.

Objectives: We systematically reviewed the literature for studies investigating pharmacotherapies for AUD that included neuroimaging-based treatment outcomes. We searched the PubMed, Scielo, and PsycINFO databases up to January 2021.

Study Eligibility Criteria, Participants, And Interventions: Eligible studies included those investigating pharmacotherapies for AUD and employing functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and/or proton magnetic resonance spectroscopy (H-MRS).

Study Appraisal And Synthesis Methods: Two independent reviewers screened studies' titles and abstracts for inclusion. Data extraction forms were shared among all the authors to standardize data collection. We gathered information on the following variables: sample size; mean age; sociodemographic and clinical characteristics; alcohol use status; study design and methodology; main neuroimaging findings and brain-regions of interest (i.e., brain areas activated by alcohol use and possible pharmacological interactions); and limitations of each study.

Results: Out of 177 studies selected, 20 studies provided relevant data for the research topic. Findings indicate that: (1) Acamprosate and gabapentin may selectively modulate limbic regions and the anterior cingulate cortex; (2) Naltrexone and disulfiram effects may involve prefrontal, premotor, and cerebellar regions; (3) Pharmacotherapies acting on glutamate and GABA neurotransmission involve primarily areas underpinning reward and negative affective states, and; (4) Pharmacotherapies acting on opioid and dopamine systems may affect areas responsible for the cognitive and motor factors of AUD.

Limitations: Most of the studies were focused on naltrexone. A small number of studies investigated the action of disulfiram and gabapentin, and no neuroimaging studies investigated topiramate. In addition, the time between medication and neuroimaging scans varied widely across studies.

Conclusions: We identified key-brain regions modulated by treatments available for AUD. Some of the regions modulated by naltrexone are not specific to the brain reward system, such as the parahippocampal gyrus (temporal lobe), parietal and occipital lobes. Other treatments also modulate not specific regions of the reward system, but play a role in the addictive behaviors, including the insula and dorsolateral prefrontal cortex. The role of these brain regions in mediating the AUD pharmacotherapy response warrants investigation in future research studies.
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http://dx.doi.org/10.3390/brainsci12030386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946664PMC
March 2022

Craving variations in patients with substance use disorder and gambling during COVID-19 lockdown: The Italian experience.

World J Clin Cases 2022 Jan;10(3):882-890

Department of Neuroscience, Imaging, Clinical Sciences, University G. d'Annunzio, Chieti-Pescara 66100, Italy.

Background: Following the development of the coronavirus disease-2019 (COVID-19) pandemic in Italy, a strict lockdown was imposed from March 9 to May 5, 2020. The risks of self-medication through alcohol or psychoactive substance abuse were increased, as well as the tendency to adopt pathological behaviors, such as gambling and internet addiction.

Aim: To evaluate the impact of the COVID-19 pandemic and associated containment measures on craving in a group of patients suffering from substance use disorder and/or gambling disorder who were in treatment in outpatient units or in residency programs as inpatients.

Methods: One hundred and fifty-three patients completed a structured questionnaire evaluating craving and other behaviors using a visual analogue scale (VAS). Forty-one subjects completed a pencil and paper questionnaire during the interview. The clinician provided an online questionnaire to 112 patients who had virtual assessments due to lockdown restrictions. Statistical analyses were performed using Statistica version 8.0. Quantitative parameters are presented as the mean ± SD and qualitative parameters as number and percentage per class. The Kolmogorov-Smirnov test was used to check for normality of distributions. Analysis of variance and Duncan post hoc test were employed to analyze differences among subgroup means. The associations between variables were measured using Pearson's correlation. A value of < 0.05 was considered significant.

Results: The variation in craving between the present and the month before showed VAS-related reductions of craving in 57%, increases in 24%, and no significant change in 19% of the sample. The level of craving was significantly higher ( = 4.36; < 0.05) in outpatients ( = 97; mean = 3.8 ± 3.1) living in their own home during the quarantine compared with inpatients ( = 56; mean = 2.8 ± 2.8) in residential programs. Craving for tetrahydrocannabinol was the greatest (4.94, < 0.001) among various preferred substances.

Conclusion: The unexpected result of this study may be explained by a perceived lack of availability of substances and gambling areas and/or decreased social pressure on a subject usually excluded and stigmatized, or the acquisition of a new social identity based on feelings of a shared common danger and fate that overshadowed the sense of exclusion and rejection in the abuser.
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http://dx.doi.org/10.12998/wjcc.v10.i3.882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790460PMC
January 2022

Psychosis in Women: Time for Personalized Treatment.

J Pers Med 2021 Dec 2;11(12). Epub 2021 Dec 2.

Department of Geriatrics, Neuroscience and Orthopedics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Early detection and prompt treatment of psychosis is of the utmost importance. The great variability in clinical onset, illness course, and response to pharmacological and psychosocial treatment is in great part gender-related. Our aim has been to review narratively the literature focusing on gender related differences in the psychoses, i.e., schizophrenia spectrum disorders. We searched the PubMed/Medline, Scopus, Embase, and ScienceDirect databases on 31 July 2021, focusing on recent research regarding sex differences in early psychosis. Although women, compared to men, tend to have better overall functioning at psychotic symptom onset, they often present with more mood symptoms, may undergo misdiagnosis and delay in treatment and are at a higher risk for antipsychotic drug-induced metabolic and endocrine-induced side effects. Furthermore, women with schizophrenia spectrum disorders have more than double the odds of having physical comorbidities than men. Tailored treatment plans delivered by healthcare services should consider gender differences in patients with a diagnosis of psychosis, with a particular attention to early phases of disease in the context of the staging model of psychosis onset.
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http://dx.doi.org/10.3390/jpm11121279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705671PMC
December 2021

Stress and Maladaptive Coping of Italians Health Care Professionals during the First Wave of the Pandemic.

Brain Sci 2021 Nov 30;11(12). Epub 2021 Nov 30.

Department of Territorial Assistance, ASL Teramo, 64100 Teramo, Italy.

Stress during the pandemic has had an impact on the mental health of healthcare professionals (HCPs). However, little is known about coping and "maladaptive" coping behaviours of this population. This study investigates "maladaptive" coping behaviours and their correlation with stress, anxiety and insomnia of Italian HCPs during the pandemic. It reports on a cross-sectional, descriptive and correlational study based on a survey of 1955 Italian HCPs. Overall participants reported increases in cigarette smoking, time spent online and video playing. Overall reported alcohol consumption decreased but increased in those reporting drinking more than once a week. Those reporting starting smoking during the pandemic were found to have higher SAS and PSS scores. Those reporting being online for 3 or more hours were found to have higher ISS scores. Doctors who reported playing video games were found to have higher PSS, ISS and SAS scores whilst nurses who reported playing video games were found to have higher ISS scores. Doctors who reported playing for longer than one hour had higher PSS scores. Online behaviours may be a coping behaviour of HCPs affected by the pandemic. However, this is an underexplored area for the wellbeing of HCPs. These deficits need to be addressed going forward.
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http://dx.doi.org/10.3390/brainsci11121586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699311PMC
November 2021

An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels.

Pharmacopsychiatry 2022 Mar 15;55(2):73-86. Epub 2021 Dec 15.

Department of Physical Medicine and Pharmacology, School of Medicine, Universidad de La Laguna, Canary Islands, Spain.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
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http://dx.doi.org/10.1055/a-1625-6388DOI Listing
March 2022

Duration of Untreated Disorder and Cannabis Use: An Observational Study on a Cohort of Young Italian Patients Experiencing Psychotic Experiences and Dissociative Symptoms.

Int J Environ Res Public Health 2021 11 30;18(23). Epub 2021 Nov 30.

Department of Neurosciences, Imaging and Clinical Sciences, Università degli Studi G. D'Annunzio Chieti-Pescara, 66100 Chieti, Italy.

Background: The Duration of Untreated Psychosis (DUP) is the time between the first-episode psychosis (FEP) and the initiation of antipsychotic treatment. It is an important predictor of several disease-related outcomes in psychotic disorders. The aim of this manuscript is investigating the influence of cannabis on the DUP and its clinical correlates.

Methods: During years 2014-2019, sixty-two FEP patients with and without cannabis use disorder (CUD) were recruited from several Italian psychiatric hospitals. The subjects were then divided into two groups based on the duration of the DUP and assessed at the beginning of the antipsychotic treatment and after 3 and 6 months, using the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF) scale, and the Dissociative Experiences Scale (DES-II).

Results: As expected, a longer DUP was associated with worse symptoms and cannabis use did not seem to affect the DUP, but both were related with more dissociative symptoms at onset and over time.

Discussion: According to our study, cannabis use can be a predictor of FEP and DUP, and of disease outcome. However, several factors might influence the relationship between cannabis use and DUP. Preventing cannabis use and early diagnosis of psychotic disorders might impact the disease by reducing the persistence of symptoms and limiting dissociative experiences.
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http://dx.doi.org/10.3390/ijerph182312632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657003PMC
November 2021

Role and Perspectives of Inflammation and C-Reactive Protein (CRP) in Psychosis: An Economic and Widespread Tool for Assessing the Disease.

Int J Mol Sci 2021 Dec 2;22(23). Epub 2021 Dec 2.

Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", 66100 Chieti, Italy.

Schizophrenia is a major psychotic disorder affecting nearly 23.6 million people globally and greatly impacting the cognitive and social functioning of individuals. Multiple risk factors, including genetic, environmental, and epigenetic factors have been identified. However, the exact mechanism by which some factors aid in the development of schizophrenia is still uncertain. Acute and/or long-standing inflammation has been implicated as both a cause and effect of schizophrenia. Heightened immune responses have been documented in large cohorts of individuals with schizophrenia. While not completely known, multiple hypotheses, such as disruption of the blood-brain barrier, alterations in the kynurenine/tryptophan pathway, and increased microglial activation, have been presented to correlate inflammation with schizophrenic symptoms. Measurement of C-reactive protein (CRP) is a commonly performed and inexpensive test on patients' serum to determine levels of systemic inflammation in the body. Multiple studies have reported an elevated CRP level in different stages of schizophrenia, indicating its potential to be used as a viable biomarker in the diagnosis and monitoring of schizophrenia along with assessing treatment response to conventional and non-conventional treatment regimens. This review aims to evaluate the role of inflammation, in general, and CRP, in particular, in the pathogenesis of schizophrenia and its potential significance in diagnostic, therapeutic, and preventative approaches towards schizophrenia and psychosis.
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http://dx.doi.org/10.3390/ijms222313032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657450PMC
December 2021

Results of the COVID-19 mental health international for the general population (COMET-G) study.

Eur Neuropsychopharmacol 2022 01 15;54:21-40. Epub 2021 Oct 15.

Department of Psychiatry, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National Referral Hospital, Jakarta, Indonesia. Electronic address:

Introduction: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study.

Material And Methods: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively.

Statistical Analysis: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables.

Results: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed.

Conclusions: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them.
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http://dx.doi.org/10.1016/j.euroneuro.2021.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609892PMC
January 2022

Internet addiction and sleep quality among medical students during the COVID-19 pandemic: A multinational cross-sectional survey.

PLoS One 2021 5;16(11):e0259594. Epub 2021 Nov 5.

Department of Nursing, School of Health and Welfare, Jönköping University, Jönköping, Sweden.

Background: The emergence of the COVID-19 pandemic has affected the lives of many people, including medical students. The present study explored internet addiction and changes in sleep patterns among medical students during the pandemic and assessed the relationship between them.

Methods: A cross-sectional study was carried out in seven countries, the Dominican Republic, Egypt, Guyana, India, Mexico, Pakistan, and Sudan, using a convenience sampling technique, an online survey comprising demographic details, information regarding COVID-19, the Pittsburgh Sleep Quality Index (PSQI), and the Internet Addiction Test (IAT).

Results: In total, 2749 participants completed the questionnaire. Of the total, 67.6% scored above 30 in the IAT, suggesting the presence of an Internet addiction, and 73.5% scored equal and above 5 in the PSQI, suggesting poor sleep quality. Internet addiction was found to be significant predictors of poor sleep quality, causing 13.2% of the variance in poor sleep quality. Participants who reported COVID-19 related symptoms had disturbed sleep and higher internet addiction levels when compared with those who did not. Participants who reported a diagnosis of COVID-19 reported poor sleep quality. Those living with a COVID-19 diagnosed patient reported higher internet addiction and worse sleep quality compared with those who did not have any COVID-19 patients in their surroundings.

Conclusion: The results of this study suggest that internet addiction and poor sleep quality are two issues that require addressing amongst medical students. Medical training institutions should do their best to minimize their negative impact, particularly during the current COVID-19 pandemic.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259594PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570473PMC
November 2021

Actual Developments in the Antipsychotic Treatment of Psychiatric Disorders: Overcoming Challenges, Opening New Ways, and Looking at the Future.

Curr Pharm Des 2021 ;27(39):4031-4032

Department of Neuroscience and Imaging, University" G. D'Annunzio", Chieti, Italy.

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http://dx.doi.org/10.2174/138161282739211013094659DOI Listing
December 2021

COVID-19 Associated Mucormycosis: A Systematic Review from Diagnostic Challenges to Management.

Diseases 2021 Sep 22;9(4). Epub 2021 Sep 22.

Department of Internal Medicine, Kabir Medical College, Gandhara University, Peshawar 25000, Pakistan.

The coronavirus disease 2019 (COVID-19) outbreak has caused significant destruction, claiming over three million lives worldwide. Post SARS-COV-2 invasion, immunosuppression with hyperglycemia and elevated ferritin levels along with steroidal treatment creates a perfect storm for opportunistic infections. There is increasing evidence of mucormycosis co-infection in COVID-19 patients, during or post-treatment. A worse prognosis, a late diagnosis, and limited guidelines of screening and management of COVID-19 associated mucormycosis have made healthcare professionals fear an epidemic alongside a pandemic. This review geographically reports cases of COVID-19 associated mucormycosis (CAM), evaluates characteristics, clinical manifestations, and outcomes of mucormycosis in COVID-19 active or recovered patients. It further describes preventive strategies and recommendations for optimal management therapy that can be adopted worldwide to curtail an impending threat to the healthcare system.
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http://dx.doi.org/10.3390/diseases9040065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544552PMC
September 2021

Trazodone Add-on in COVID-19-related Selective Serotonin Reuptake Inhibitor-resistant Post-traumatic Stress Disorder in Healthcare Workers: Two Case Reports.

Clin Psychopharmacol Neurosci 2021 Nov;19(4):780-785

Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", Chieti, Italy.

COVID-19 represents a significant stress factor for all people worldwide due to several factors, including quarantine, lockdowns, fear of contagion, deaths, and other traumatic events. However, the healthcare workers (HCWs) have paid the higher price of this pandemic in terms of fatalities, contagions, and psychological well-being. Studies suggest that this particular population is at increased risk of developing a severe post-traumatic stress disorder (PTSD). The early diagnosis and timely treatment of PTSD in HCWs may restore well-being and significantly impact health services functioning, reducing burnout, days spent far from work, disrupted personal and team empowerment, and worse job performances. In the present article, we reported on two cases of HCWs directly involved in the treatment of COVID-19 patients who showed selective serotonin reuptake inhibitor-resistant PTSD, which was successfully treated with extended-release trazodone TRZ Contramid add-on.
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http://dx.doi.org/10.9758/cpn.2021.19.4.780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553539PMC
November 2021

Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder.

Biomolecules 2021 10 10;11(10). Epub 2021 Oct 10.

Departamento de Medicina Legal e Ética Médica, Medicina Social e do Trabalho, Instituto Oscar Freire, LIM-40, Medical School, Universidade de São Paulo, São Paulo 05405-150, Brazil.

The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself or more severe clinical levels of AUD. Given the high association between alcohol metabolizing enzymes (AME) and the outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. We carried out a 12-week longitudinal clinical trial based on the treatment of AUD patients with naltrexone (N = 101), stratified by different alcohol metabolization genotypes. Genotyping was performed after the inclusion of the patients in the study, based on the individual presence of single nucleotide polymorphisms (SNPs) in the and , and genes. The outcome of alcohol use has been monitored employing the timeline follow-back during the treatment. The (Ile350Val, rs698) and (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the (Arg370Cys, rs2066702) allelic variant showed a negative outcome. The present study explores a genomic setting for the treatment of AUD with naltrexone. According to our findings, the association between and variants and better outcomes suggests a successful treatment, whereas the mutated allele might lead to an unsuccessful treatment. Further studies should be performed to investigate the relationship between alcohol metabolizing genotypes, the family history of alcohol use disorders and the effect of naltrexone on the outcomes. Genotyping may be a valuable tool for precision-medicine and individualized approach, especially in the context of alcohol use disorders. The small number of subjects was the main limitation of the present study.
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http://dx.doi.org/10.3390/biom11101495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533258PMC
October 2021

SARS-CoV-2 and the Brain: What Do We Know about the Causality of 'Cognitive COVID?

J Clin Med 2021 Aug 2;10(15). Epub 2021 Aug 2.

Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", 66100 Chieti, Italy.

The second year of the COVID-19 (coronavirus disease) pandemic has seen the need to identify and assess the long-term consequences of a SARS-CoV-2 infection on an individual's overall wellbeing, including adequate cognitive functioning. 'Cognitive COVID' is an informal term coined to interchangeably refer to acute changes in cognition during COVID-19 and/or cognitive sequelae with various deficits following the infection. These may manifest as altered levels of consciousness, encephalopathy-like symptoms, delirium, and loss of various memory domains. Dysexecutive syndrome is a peculiar manifestation of 'Cognitive COVID' as well. In the previous major outbreaks of viruses like SARS-CoV, MERS-CoV and Influenza. There have been attempts to understand the underlying mechanisms describing the causality of similar symptoms following SARS-CoV-2 infection. This review, therefore, is attempting to highlight the current understanding of the various direct and indirect mechanisms, focusing on the role of neurotropism of SARS-CoV-2, the general pro-inflammatory state, and the pandemic-associated psychosocial stressors in the causality of 'Cognitive COVID.' Neurotropism is associated with various mechanisms including retrograde neuronal transmission via olfactory pathway, a general hematogenous spread, and the virus using immune cells as vectors. The high amounts of inflammation caused by COVID-19, compounded with potential intubation, are associated with a deleterious effect on the cognition as well. Finally, the pandemic's unique psychosocial impact has raised alarm due to its possible effect on cognition. Furthermore, with surfacing reports of post-COVID-vaccination cognitive impairments after vaccines containing mRNA encoding for spike glycoprotein of SARS-CoV-2, we hypothesize their causality and ways to mitigate the risk. The potential impact on the quality of life of an individual and the fact that even a minor proportion of COVID-19 cases developing cognitive impairment could be a significant burden on already overwhelmed healthcare systems across the world make it vital to gather further evidence regarding the prevalence, presentation, correlations, and causality of these events and reevaluate our approach to accommodate early identification, management, and rehabilitation of patients exhibiting cognitive symptoms.
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http://dx.doi.org/10.3390/jcm10153441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347421PMC
August 2021

Treating Postpartum Depression: What Do We Know about Brexanolone?

Diseases 2021 Jul 12;9(3). Epub 2021 Jul 12.

NHS, Department of Mental Health, Psychiatric Service for Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4, 64100 Teramo, Italy.

Postpartum depression (PPD) is defined as the onset of major depressive disorder in mothers, occurring during pregnancy or within 4 weeks post-delivery. With 7% of pregnancy-related death in the United States owing to mental health conditions, including PPD, and a global prevalence of 12%, PPD is a growing public health concern. In 2019, the Food and Drug Administration (FDA) approved brexanolone, an exogenous analog of allopregnanolone, as the first ever drug to be specifically indicated for treating patients with PPD. This approval was preceded by an open-label study and three randomized placebo-controlled trials, each assessing the safety, tolerability, and efficacy of brexanolone, using mean Hamilton Rating Scale for Depression (HAM-D) score reduction as the primary outcome. In each randomized controlled trial, the drug was administered as an intravenous infusion given over 60 h. Enrolled participants were followed up on days 7 and 30 to evaluate the sustained effect. A statistically significant reduction in mean HAM-D score compared to placebo was observed in all three studies, supporting brexanolone's use in treating moderate-to-severe PPD. Therefore, this article attempts to briefly review the pharmacology of brexanolone, evaluate the latest available clinical data and outcomes concerning its use, reevaluate its position as a 'breakthrough' in managing PPD, and review the cost-related barriers to its worldwide standardized use.
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http://dx.doi.org/10.3390/diseases9030052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293057PMC
July 2021

Oxidative Stress in the Early Stage of Psychosis.

Curr Top Med Chem 2021 Oct;21(16):1457-1470

Department of Mental Health, ASL Teramo, Teramo, Italy.

Background: In the past few decades, increasing evidence in the literature has appeared describing the role of the antioxidant defense system and redox signaling in the multifactorial pathophysiology of psychosis. It is of interest to clinicians and researchers alike that abnormalities of the antioxidant defense system are associated with alterations of cellular membranes, immune functions and neurotransmission, all of which have some clinical implications.

Methods: This narrative review summarizes the evidence regarding oxidative stress in the early stages of psychosis. We included 136 peer-reviewed articles published from 2007 to 2020 on PubMed EMBASE, The Cochrane Library and Google Scholar.

Results: Patients affected by psychotic disorders show a decreased level of non-enzymatic antioxidants, an increased level of lipid peroxides, nitric oxides, and a homeostatic imbalance of purine catabolism. In particular, a significantly reduced antioxidant defense has been described in the early onset first episode of psychosis, including reduced levels of glutathione. Also, it has been shown that a decreased basal low-antioxidant capacity correlates with cognitive deficits and negative symptoms, mostly related to glutamate-receptor hypofunction. In addition, atypical antipsychotic drugs seem to show significant antioxidant activity. These factors are critical in order to treat cases of first-onset psychosis effectively.

Conclusion: This systematic review indicates the importance that must be given to anti-oxidant defense systems.
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http://dx.doi.org/10.2174/1568026621666210701105839DOI Listing
October 2021

New Pharmacological Targets for the Treatment of Schizophrenia: A Literature Review.

Curr Top Med Chem 2021 Oct;21(16):1500-1516

Department of Mental Health, ASL Teramo, Teramo, Italy.

Background: The pharmacological treatment of schizophrenia is currently based on the employment of antipsychotic medications showing an antagonism of dopaminergic and serotoninergic inhibitors. 20-40% of patients are drug-resistant or residually symptomatic in the long-term antipsychotic treatment, and new strategies are needed for improving their functional and cognitive impairment.

Methods: This systematic review has summarized evidences from the literature regarding the newer pharmacological targets proposed for the treatment of psychosis. We included 128 peer-reviewed articles and 5 other relevant sources published from 2002 to 2020 on PubMed EMBASE, The Cochrane Library, and Google Scholar.

Results: The possible role of glutamate and its receptors as targets of the antipsychotic mechanism of action has been described. Glutamatergic neurotransmission and NMDA receptors hypofunction are involved in the neurobiological explanatory model of psychosis and possibly targeted for the successful treatment of cognitive and residual symptoms. Results show an efficacy of D-cycloserine (antagonist at the Glycine site of the NMDA-R) in the treatment of negative symptoms of schizophrenia as well as Memantine (NMDA- Receptor antagonist) for cognition and psychopathology. The putative antipsychotic effect of cannabidiol on positive symptoms and cognition will also be discussed. The action on serotoninergic and GABAergic receptors will be considered as a new pharmacological target, with a possible efficacy of Vabicaserin on symptoms of psychosis. Mynocicline has shown to induce improvements in cognitive symptoms in schizophrenia, as well as Erythropoietin. Oxytocin has been reported to have an antipsychotic-like effect; moreover, COX-2 inhibitors lead to a reduction in positive symptoms of psychosis, specifically in the first episode of illness.

Conclusion: This narrative report suggests a promising role of new agents in the treatment of Schizophrenia; however, more research is needed to approve their clinical employment.
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http://dx.doi.org/10.2174/1568026621666210701103147DOI Listing
October 2021

New Pharmacological Targets for the Treatment of Schizophrenia: A Literature Review.

Curr Top Med Chem 2021 Oct;21(16):1500-1516

Department of Mental Health, ASL Teramo, Teramo, Italy.

Background: The pharmacological treatment of schizophrenia is currently based on the employment of antipsychotic medications showing an antagonism of dopaminergic and serotoninergic inhibitors. 20-40% of patients are drug-resistant or residually symptomatic in the long-term antipsychotic treatment, and new strategies are needed for improving their functional and cognitive impairment.

Methods: This systematic review has summarized evidences from the literature regarding the newer pharmacological targets proposed for the treatment of psychosis. We included 128 peer-reviewed articles and 5 other relevant sources published from 2002 to 2020 on PubMed EMBASE, The Cochrane Library, and Google Scholar.

Results: The possible role of glutamate and its receptors as targets of the antipsychotic mechanism of action has been described. Glutamatergic neurotransmission and NMDA receptors hypofunction are involved in the neurobiological explanatory model of psychosis and possibly targeted for the successful treatment of cognitive and residual symptoms. Results show an efficacy of D-cycloserine (antagonist at the Glycine site of the NMDA-R) in the treatment of negative symptoms of schizophrenia as well as Memantine (NMDA- Receptor antagonist) for cognition and psychopathology. The putative antipsychotic effect of cannabidiol on positive symptoms and cognition will also be discussed. The action on serotoninergic and GABAergic receptors will be considered as a new pharmacological target, with a possible efficacy of Vabicaserin on symptoms of psychosis. Mynocicline has shown to induce improvements in cognitive symptoms in schizophrenia, as well as Erythropoietin. Oxytocin has been reported to have an antipsychotic-like effect; moreover, COX-2 inhibitors lead to a reduction in positive symptoms of psychosis, specifically in the first episode of illness.

Conclusion: This narrative report suggests a promising role of new agents in the treatment of Schizophrenia; however, more research is needed to approve their clinical employment.
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http://dx.doi.org/10.2174/1568026621666210701103147DOI Listing
October 2021

Homophobia and mental health: a scourge of modern era.

Epidemiol Psychiatr Sci 2021 Jun 29;30:e52. Epub 2021 Jun 29.

Institute of Psychiatry, King's College, London, UK.

Homophobia is still a scourge in the modern era. Despite a greater acceptance of sexual variations and same-sex marriage in many countries, homophobia is widely sustained by religious, political and cultural values and beliefs at individual and social level. Most of homophobic attitudes are based on the principle of heteronormativity according to which heterosexuality is the standard for legitimating social and sexual relationships and homosexuality is considered as an abnormal variant. Homophobia may be also recognised at institutional level (state-sponsored homophobia, social homophobia) and supported by laws or religious beliefs. Moreover, internalised homophobia (IH) is defined as the inward direction of societal homophobic behaviours at individual level and refers to the subjective psychological impact of these negative attitudes. In fact, IH is significantly associated with a high prevalence of internalising mental disorders such as depression, anxiety, stress/trauma-related disorders, etc. We believe that a set of immediate actions are needed in order to contrast homophobia and its impact on mental health, in particular political initiatives, educational trainings and scientific research should be promoted with a specific focus on mental health needs of people target of homophobia.
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http://dx.doi.org/10.1017/S2045796021000391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264802PMC
June 2021

Homophobia and mental health: a scourge of modern era.

Epidemiol Psychiatr Sci 2021 Jun 29;30:e52. Epub 2021 Jun 29.

Institute of Psychiatry, King's College, London, UK.

Homophobia is still a scourge in the modern era. Despite a greater acceptance of sexual variations and same-sex marriage in many countries, homophobia is widely sustained by religious, political and cultural values and beliefs at individual and social level. Most of homophobic attitudes are based on the principle of heteronormativity according to which heterosexuality is the standard for legitimating social and sexual relationships and homosexuality is considered as an abnormal variant. Homophobia may be also recognised at institutional level (state-sponsored homophobia, social homophobia) and supported by laws or religious beliefs. Moreover, internalised homophobia (IH) is defined as the inward direction of societal homophobic behaviours at individual level and refers to the subjective psychological impact of these negative attitudes. In fact, IH is significantly associated with a high prevalence of internalising mental disorders such as depression, anxiety, stress/trauma-related disorders, etc. We believe that a set of immediate actions are needed in order to contrast homophobia and its impact on mental health, in particular political initiatives, educational trainings and scientific research should be promoted with a specific focus on mental health needs of people target of homophobia.
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http://dx.doi.org/10.1017/S2045796021000391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264802PMC
June 2021

Identification of clinical phenotypes in schizophrenia: the role of lurasidone.

Ther Adv Psychopharmacol 2021 10;11:20451253211012250. Epub 2021 May 10.

NHS, Department of Mental Health, Hospital "G. Mazzini", ASL 4, Teramo, 64100, Italy.

The treatment of schizophrenia includes the control of symptoms, the prevention of relapses, and amelioration of adaptive skills for patient re-integration into society. Antipsychotic drugs are the agents of choice for the treatment of schizophrenia, as they reduce the positive symptoms of psychosis. Lurasidone is a second-generation antipsychotic drug representing a novel and useful clinical tool for the management of schizophrenia. A board consisting of a panel of Italian expert psychiatrists was organized with the following aims: (a) defining the current modalities of use of lurasidone, highlighted through 17 specific questions; (b) defining and agreeing the main features of the drug and the principal reasons to suggest its administration. We established that lurasidone is suggested at any age, with no gender difference, at all stages of the disease. The switch from previous treatments is done primarily because of lack of efficacy as well as poor adherence/tolerability. Lurasidone is among the best-tolerated antipsychotics, and its use is indicated in the presence of different comorbidities. A wide range of dosages is available, allowing safe titration in particular cases, with the highest dose (148 mg) generally used for the treatment of the acute phase. The discontinuation rate due to poor tolerability, low compliance, and interactions with other drugs is very low. Akathisia is the most reported adverse event, but it may be controlled by dose reduction. Lurasidone does not possess a marked sedative action but, in agitated patients, can be associated with sedative drugs, such as benzodiazepines. The most frequent reason for switching to other therapies is the need for long-acting formulations, as in patients at risk of very low adherence or suicide. Lurasidone does not strongly impact metabolism or the cardiovascular system (QT interval), and does not influence the metabolism of other drugs, showing good efficacy and tolerability.
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http://dx.doi.org/10.1177/20451253211012250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120523PMC
May 2021

Publish or perish: Panic publishing a danger to science during COVID-19.

Aust N Z J Psychiatry 2021 07 2;55(7):733. Epub 2021 May 2.

Department of Mental Health, Psychiatric Service for Diagnosis and Treatment, Hospital 'G. Mazzini', NHS, Teramo, Italy.

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http://dx.doi.org/10.1177/00048674211009624DOI Listing
July 2021

The Management of Psychomotor Agitation Associated with Schizophrenia or Bipolar Disorder: A Brief Review.

Int J Environ Res Public Health 2021 04 20;18(8). Epub 2021 Apr 20.

Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", National Health Service (NHS), ASL 4 Teramo, 64100 Teramo, Italy.

The early and correct assessment of psychomotor agitation (PMA) is essential to ensure prompt intervention by healthcare professionals to improve the patient's condition, protect healthcare staff, and facilitate future management. Proper training for recognizing and managing agitation in all care settings is desirable to improve patient outcomes. The best approach is one that is ethical, non-invasive, and respectful of the patient's dignity. When deemed necessary, pharmacological interventions must be administered rapidly and avoid producing an excessive state of sedation, except in cases of severe and imminent danger to the patient or others. The purpose of this brief review is to raise awareness about best practices for the management of PMA in emergency care situations and consider the role of new pharmacological interventions in patients with agitation associated with bipolar disorder or schizophrenia.
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http://dx.doi.org/10.3390/ijerph18084368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074323PMC
April 2021

The Management of Psychomotor Agitation Associated with Schizophrenia or Bipolar Disorder: A Brief Review.

Int J Environ Res Public Health 2021 04 20;18(8). Epub 2021 Apr 20.

Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", National Health Service (NHS), ASL 4 Teramo, 64100 Teramo, Italy.

The early and correct assessment of psychomotor agitation (PMA) is essential to ensure prompt intervention by healthcare professionals to improve the patient's condition, protect healthcare staff, and facilitate future management. Proper training for recognizing and managing agitation in all care settings is desirable to improve patient outcomes. The best approach is one that is ethical, non-invasive, and respectful of the patient's dignity. When deemed necessary, pharmacological interventions must be administered rapidly and avoid producing an excessive state of sedation, except in cases of severe and imminent danger to the patient or others. The purpose of this brief review is to raise awareness about best practices for the management of PMA in emergency care situations and consider the role of new pharmacological interventions in patients with agitation associated with bipolar disorder or schizophrenia.
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http://dx.doi.org/10.3390/ijerph18084368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074323PMC
April 2021
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