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

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 P 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 (F = 4.36; P < 0.05) in outpatients (n = 97; mean = 3.8 ± 3.1) living in their own home during the quarantine compared with inpatients (n = 56; mean = 2.8 ± 2.8) in residential programs. Craving for tetrahydrocannabinol was the greatest (4.94, P < 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.

Hypomanic/manic switch after transcranial magnetic stimulation in mood disorders: A systematic review and meta-analysis.

BACKGROUND: Nowadays there is an increasing use of transcranial magnetic stimulation (TMS) both in neurological and psychiatric fields. After Food and Drug Administration approval of TMS for the therapy of treatment-resistant depression, TMS has been widely used in the context of mood disorders (MD). However, growing reports regarding the possibility of developing hypomanic/manic switch (HMS) have generated concern regarding its use in MDs. AIM: To investigate the actual risk of developing HMS due to TMS in the treatment of MD. METHODS: We led our research on PubMed, Scopus and Web of Science on March 22, 2020, in accordance to the PRISMA guidelines for systematic review. Only double blind/single blind studies, written in English and focused on the TMS treatment of MD, were included. A meta-analysis of repetitive TMS protocol studies including HMS was conducted using RevMan 5.4 software. The assessment of Risk of Bias was done using Cochrane risk of bias tool. This protocol was registered on PROSPERO with the CRD42020175811 code. RESULTS: Twenty-five studies were included in our meta-analysis: Twenty-one double blind randomized controlled trials (RCT) and four single blind-RCT (no. of subjects involved in active stimulation = 576; no. of subjects involved in sham protocol = 487). The most frequently treated pathology was major depressive episode/major depressive disorder, followed by resistant depression, bipolar depression and other MD. The majority of the studies used a repetitive TMS protocol, and the left dorsolateral prefrontal cortex was the main target area. Side effects were reported in eight studies and HMS (described as greater energy, insomnia, irritability, anxiety, suicidal attempt) in four studies. When comparing active TMS vs sham treatment, the risk of developing HMS was not significantly different between conditions. CONCLUSION: Applying the most usual protocols and the appropriate precautionary measures, TMS seems not to be related to HMS development.

Delirium in COVID-19 patients: a multicentric observational study in Italy.

INTRODUCTION: Although recent data show that SARS-CoV-2 infection seems to affect the central nervous system (CNS), little is known about the neuropsychiatric effects resulting from this condition. In addition to the well-known neurotrophism of coronaviruses, recent evidence shows also that the "cytokine storm" induced by the infection is at the basis of the neuroinflammation of the CNS. Furthermore, prolonged hospitalization, polypharmacotherapy, and isolation could be at the basis of the onset of delirium in hospitalized COVID patients. This multicentric observational study explores the incidence of the onset of delirium in an Italian cohort of SARS-CoV-2 positive inpatients. METHODS: Data were collected in the COVIDhospitals of Brescia, Bergamo, Chieti, and Genova. Different socio-demographic, medical, neurological, and pharmacological parameters were collected. As a rapid screening for delirium, the 4AT scale was used. Eighty COVID-19 inpatients (mean age 74.7 ± 14.5 years) met the inclusion criteria (confirmed positivity to the SARS-CoV-2 virus; the presence of delirium and/or psychomotor agitation and/or new onset of other neuropsychiatric symptoms during hospitalization). RESULTS: The majority of these patients (68.8%) had "hyperactive delirium" subtype. Polypharmacotherapy, current treatment with corticosteroids, and higher age were associated with delirium severity. CONCLUSION: These data provide an insight into the onset of delirium among COVID-19 patients underlining the need for monitoring, especially in elderly patients, the neuropsychiatric symptoms, and the therapy in order to have shorter hospitalization times and better outcomes.

Psychopathological Burden and Quality of Life in Substance Users During the COVID-19 Lockdown Period in Italy.

BACKGROUND: Following the development of the COVID-19 pandemic, a rigid public health strategy of reduced social contact and shelter-in-place has been adopted by the Italian Government to reduce the spread of the virus. In this paper, we aim at evaluating the impact that the COVID-19 pandemic, and the relative containment measures, have had on a real-life sample of patients suffering from substance use disorders (SUDs) and/or behavioral addictions. METHODS: An anonymous questionnaire was filled out by 153 addicted patients, both outpatients and residential inpatients, recruited across Italy and highly representative of the current Italian population suffering from addictions. Psychopathological burden (anxiety and depressive symptomatology, somatization, irritability, and post-traumatic symptoms), quality of life, and craving changes in daily habits were assessed. RESULTS: In our sample, we found moderate rates of depression (22.9%), anxiety (30.1%), irritability (31.6%), and post-traumatic stress (5.4%) symptoms. Psychopathological burden was globally higher among residential patients. Reported levels of craving were generally low. DISCUSSION: This study is the first attempt to collect Italian data regarding the effects of the rigid quarantine period, during the COVID-19 pandemic, on patients suffering from a SUD and/or behavioral addictions. The presence of a moderate psychopathological burden correlated to poor quality of life and low craving scores represented the main outcomes. Long-term studies, with follow-up after the end of the restrictive measures, should be considered to implement our findings.

Corrigendum: Effects of Second Language Learning on the Plastic Aging Brain: Functional Connectivity, Cognitive Decline, and Reorganization.

[This corrects the article DOI: 10.3389/fnins.2019.00423.].

Comorbid Premenstrual Dysphoric Disorder in Women with Bipolar Disorder: Management Challenges.

Bipolar disorder (BD) and premenstrual dysphoric disorder (PMDD) are two cyclic mood illnesses, sometimes presenting together. Their comorbidity appears to be linked to common biological mechanisms and usually results in more severity of mood symptoms and a poorer long-term outcome. Nevertheless, the management of comorbid PMDD/BD has been scarcely studied. Therefore, the aim of the present paper was to review the published literature on the treatment of comorbid PMDD/BD and to provide point-by-point hypotheses to address these complex clinical cases. We searched PubMed to identify the studies focused on the treatment and management of comorbid PMDD/BD using the following search words, alone and in combination: premenstrual dysphoric disorder, bipolar disorder, comorbid, treatment, management, pharmacotherapy, psychotherapy. The search was conducted on the 1st of June 2019 and yielded 55 records. Four papers met our inclusion/exclusion criteria and were therefore included in our qualitative synthesis. Integrating the few data pertaining to the treatment of comorbid PMDD/BD with the large amount of published data on the two conditions separately, we can suggest that the management of comorbid PMDD/BD needs as a first step to stabilize the bipolar symptoms by means of optimal dosages of mood stabilizers. Then, in euthymic BD patients, the PMDD symptoms could be treated with estroprogestins (first-line treatment). On the contrary, during acute phases of BD, antidepressants (for major depressive episodes) and atypical antipsychotics/hormonal modulators (for manic episodes) could be considered as promising add-on treatments to mood stabilizers. In case of resistant PMDD/BD symptoms, combined strategies should be taken into account, as well as alternative treatments, such as lifestyle changes. In conclusion, RCTs on comorbid PMDD/BD are still lacking. The management of this complex condition is therefore challenging and it requires a tailored treatment.

Subjective Cognitive Decline and Nighttime Sleep Alterations, a Longitudinal Analysis.

Objective: The aim of this study was to analyze quantitative sleep changes and their implication on subjective cognitive decline (SCD). Objective sleep patterns were investigated by an actigraph and recorded at the baseline and 2-year after in order to examine specific sleep alterations in SCD. Background: Sleep disorders are very common among average elderly adults and an altered sleep pattern is known to be a risk factor for future development of mild cognitive impairment (MCI) and dementia. Recent studies have shown how sleep is objectively altered in average senior adults with SCD, without any other significant change in cognition and behavior or brain structure. Considering that both SCD and disrupted sleep are risk factors for future MCI and dementia, with sleep only as a modifiable risk factor, further research is required to deeply investigate the interaction between sleep and SCD. Methods: Among 70 community-dwelling elderly individuals who had been enrolled at baseline, 35 (64.6 ± 5.6 years, 15 M/20 F) underwent a complete neuropsychological battery and 1-week wrist actigraphy recording 2 years later during the follow-up stage. Individuals were divided into two groups according to their SCD Questionnaire (SCD-Q) score. Sleep hours, sleep efficiency and onset latency, napping and time awake after sleep onset (WASO) were collected. All individuals underwent structural magnetic resonance imaging (MRI) examination to exclude brain disorders. Data collection was performed at baseline and after 2 years at the follow-up phase. Results: A significantly different night sleep time between the two groups was observed: SCD showed a lower total sleep time (TST) than non-SCD subjects. Moreover, a total time spent in bed (TIB) was significantly lower in SCD subjects over 2 years of observation. Conclusions: Objective changes over time of the sleep pattern, specifically TIB and TST, are present in SCD individuals. The results of the study show that sleep alterations are common in SCD and underline the clinical importance of screening in order to assess sleep alterations as well as improve sleep in average adults with SCD complaints.

Effects of Second Language Learning on the Plastic Aging Brain: Functional Connectivity, Cognitive Decline, and Reorganization.

Learning a new language requires the use of extensive neural networks and can represent a powerful tool to reorganize brain neuroplasticity. In this study, we analyze how a 4 months long second language learning program (16, 2 h sessions) can lead to functional changes in the brain of healthy elderly individuals. A large number of studies point out a decline of brain-skills with age; here it is analyzed how cognition together with functional brain organization can be improved later in life. Twenty-six older adults (59-79 years old) were enrolled in the present study. A complete neuropsychological examination was administered before and after the intervention to measure global cognition levels, short- and long-term memory, attention, language access and executive functions. At the end of the program, in the intervention group, the results showed a significant improvement in global cognition together with an increased functional connectivity in the right inferior frontal gyrus (rIFG), right superior frontal gyrus (rSFG) and left superior parietal lobule (lSPL). These findings can be added to the current neurobiological breakthroughs of reshaping brain networks with a short language learning practice in healthy elderly subjects. Therefore, learning a foreign-language may represent a potentially helpful cognitive intervention for promoting healthy aging.

Transcranial Direct Current Stimulation Reduces Craving in Substance Use Disorders: A Double-blind, Placebo-Controlled Study.

OBJECTIVES: The use of transcranial direct current stimulation (tDCS) in addiction disorders is still on its rise in comparison with pharmacological and psychotherapeutic strategies that still show low level of evidence. In this study, we aimed to evaluate the efficacy of the anodic tDCS for the short-term treatment of substance craving and other psychiatric symptoms. METHODS: In this randomized, double-blind, sham-controlled trial, inclusion criteria included the diagnosis of substance use disorder and/or gambling disorder. The protocol includes 5 consecutive days of active or sham tDCS session. Cathode was placed over the left dorsolateral prefrontal cortex. Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Young Mania Rating Scale, Barratt Impulsiveness Scale, South Oaks Gambling Screen, and visual analog scale (VAS) 1 to 10 for craving were administered at the baseline (T0) and after 5 days of treatment (T1). RESULTS: Thirty-four treatment-seeking subjects were randomized to sham (n = 16) and active stimulation (n = 18) groups. A statistically significant reduction of values at T1 was found in all subjects considering VAS (P < 0.001), Hamilton Depression Rating Scale (P < 0.001), Hamilton Anxiety Rating Scale (P < 0.001), and Barratt Impulsiveness Scale 11 (P = 0.032). A significant reduction for VAS craving in favor of the active stimulation (P = 0.011) was found. CONCLUSIONS: Our findings reveal a statistically significant rapid reduction of craving in the active tDCS group on the right dorsolateral prefrontal cortex with respect to sham group, confirming the scientific literature trend. Large samples, with maintenance tDCS therapy and long-term follow-up, are required to establish the potential of this noninvasive and easily delivered brain stimulation strategy.

Efficacy and Safety of Atypical Antipsychotics in Bipolar Disorder With Comorbid Substance Dependence: A Systematic Review.

OBJECTIVES: Bipolar disorder (BD) patients with a comorbid substance use disorder (SUD) are notoriously difficult to treat. Atypical antipsychotics (AAPs) are widely prescribed in BD, but their efficacy in patients with comorbid SUD is still debated. The aim of the present article is to systematically review the literature findings on the efficacy and safety of AAPs in BD patients with comorbid SUD. METHODS: We searched PubMed to identify original studies focused on the treatment of dual diagnosed BD with AAPs. RESULTS: Ten articles met our inclusion/exclusion criteria, involving a total of 969 subjects, 906 affected by BD and 793 with comorbid SUD: 4 were randomized controlled trials, 4 were open label trials and 2 were observational studies, published between 2002 and 2017. The most commonly abused substances were alcohol and cocaine. The AAPs used to treat patients were quetiapine (n = 337), asenapine (n = 119), olanzapine (n = 80), risperidone (n = 62), and aripiprazole (n = 48). In terms of safety, AAPs were usually well tolerated. Atypical antipsychotics were usually efficacious on acute mood symptoms, whereas their impact on substance-related issues was reported only in those studies without a placebo comparison. CONCLUSIONS: According to our results, even though AAPs are widely used and efficacious in treating the clinical symptoms of BD, there are not enough data to suggest their adjunctive benefit on craving and substance consumption.

Pathological Gambling among Italian Nursing Students.

PURPOSE: To investigate the role of psychiatric dimensions, behavioral or substance addictions and demographical variables as determinants of pathological gambling among nursing students. DESIGN: Multicenter cross-sectional study. METHODS: From June to October 2015 a survey was carried out among Italian Nursing students. Data were collected using a six-section tool. FINDINGS: Nursing students who completed the survey numbered 1083, 902 (83.3%) had some problems with gambling and 29 (2.7%) showed pathological gambling. Percentage of pathological gambling was significantly associate with illicit drug/alcohol use (65.5%; p=0.001) and with male gender (58.6%) comparing to student nurse with non-pathological gambling (20%) and those with some problem (24.2%). Significant main effect was observed for IAT score (Beta=0.119, t=3.28, p=0.001): higher IAT scores were associated with higher SOGS scores. CONCLUSIONS: Italian nursing students have some problems with gambling and pathological gambling problem, and males are those who have more problems. Results might be useful for faculties of health professionals to identify students at risk in an early stage, to direct prevention tailored interventions. CLINICAL RELEVANCE: Nursing faculties should be aware of the prevalence of Gambling among students. Prevention interventions should be planned to minimize the risk of gambling behavior in the future nurses' health care workers.

Bupropion Augmentation in a Case of Compulsive Buying Disorder.

BACKGROUND: Compulsive buying disorder (CBD) is a condition characterized by excessive preoccupations, impulses, and behaviors regarding buying, resulting in serious psychological, social, and financial problems. Even though it has not been included in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, "behavioral addictions" section, CBD is a hot topic in current clinical psychiatry, because of its relevant prevalence (at least 5% in adult populations) and severe effect on quality of life.The CBD shares some clinical features with substance-related and behavioral addictions, impulse control disorders, and obsessive compulsive disorder, and it is often comorbid with other psychiatric illnesses (especially depressive and anxiety disorders). The treatment of CBD is therefore difficult, and clear therapeutic guidelines are not yet available. Treating the comorbid disorders as the first-line approach, or combining drugs with different pharmacodynamic profiles, has been suggested to address this challenging condition. CASE: A 60-year-old woman affected by a severe form of CBD with comorbid major depressive disorder, resistant/intolerant to previous selective serotonin reuptake inhibitor treatments and only partially responder to mirtazapine, achieved a good clinical improvement adding bupropion. CONCLUSIONS: Combining 2 agents with different pharmacological profiles and mechanisms of action, such as bupropion and mirtazapine, could be a useful strategy in the management of complex CBD cases.

Resilience and cross-network connectivity: A neural model for post-trauma survival.

Literature on the neurobiological bases of Post-Traumatic Stress Disorder (PTSD) considers medial Prefrontal cortex (mPFC), a core region of the Default Mode Network (DMN), as a region involved in response regulation to stressors. Disrupted functioning of the DMN has been recognized at the basis of the pathophysiology of a number of mental disorders. Furthermore, in the evaluation of the protective factors to trauma consequence, an important role has been assigned to resilience. Our aim was to investigate the specific relation of resilience and PTSD symptoms severity with resting state brain connectivity in a traumatized population using magnetoencephalography (MEG), a non-invasive imaging technique with high temporal resolution and documented advantages in clinical applications. Nineteen Trauma Exposed non-PTSD (TENP) and 19 PTSD patients participated to a resting state MEG session. MEG functional connectivity of mPFC seed to the whole brain was calculated. Correlation between mPFC functional connectivity and Clinician Administered PTSD Scale (CAPS) or Connor-Davidson Resilience Scale (CD-RISC) total score was also assessed. In the whole group, it has been evidenced that the higher was the resilience, the lower was the cross-network connectivity between DMN and Salience Network (SN) nodes. Contrarily, in the TENP group, the negative correlation between resilience and DMN-SN cross-interaction disappeared, suggesting a protective role of resilience for brain functioning. Regarding our findings as a continuum between healthy and pathological after trauma outcomes, we could suggest a link between resilience and the good dialogue between the networks needed to face a traumatic event and its long-term consequence on individuals' lives.

A Case of Resistant Schizophrenia Successfully Treated With Clozapine/Long-acting Injectable Aripiprazole Combination.

BACKGROUND: Treatment-resistant schizophrenia (TRS) is a condition characterized by intense symptom severity and poor response to different antipsychotic agents. The first therapeutic option in TRS is clozapine, but often high/medium doses are not tolerated. Adding an oral antipsychotic to low doses of clozapine is a promising strategy in the management of TRS. On the contrary, there are few data on combined clozapine/long-acting injectable (LAI) medications, and none on clozapine/LAI-aripiprazole. CASE: A 21-year-old male schizophrenic patient, resistant to several oral and LAI medications, partially improved after clozapine 300 mg/d treatment. Unfortunately, he also reported excessive sedation and an episode of myoclonus, so clozapine was reduced to 150 mg/d, but no additional benefits were observed. Subsequently, LAI-aripiprazole (first 200 mg/mo, then 400 mg/mo) was added, and the patient's conditions dramatically improved over time. After 1 year of observation, symptoms reduction was 50% or greater, without significant adverse events. CONCLUSIONS: Clozapine use in TRS is often reduced or delayed due to the fear of serious adverse effects. Adding LAI-aripiprazole to low doses of clozapine may be a useful therapeutic option to obtain a good efficacy/tolerability balance.

Premenstrual Dysphoric Disorder Without Comorbid Psychiatric Conditions: A Systematic Review of Therapeutic Options.

OBJECTIVES: Premenstrual dysphoric disorder (PMDD) is a disabling condition affecting approximately 2% to 8% of women during reproductive age. It has been recently included in the mood disorder section of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, but its treatment as a primary psychiatric illness is still debated, because of the high prevalence of other mental disturbances in PMDD patients. On the other hand, clear clinical guidelines for PMDD patients not suffering from comorbid mental conditions are not yet available. The aim of the present study was therefore to systematically review the original articles pertaining to the treatment of PMDD in adult women free of any current or previous psychiatric comorbidity. METHODS: We searched PubMed to identify published studies on PMDD, including randomized controlled trials, open-label trials, and case series or case reports involving adult women with no history of comorbid mental conditions. The search was conducted in April 2015. RESULTS: We found 55 studies fulfilling our inclusion criteria, 49 of them focused on pharmacological/chemical agents and the remaining 6 on nonpharmacological interventions. CONCLUSIONS: Based on the results of our qualitative synthesis, the best therapeutic option in the treatment of adult PMDD patients free of other mental disorders are selective serotonin reuptake inhibitor antidepressants (especially paroxetine and fluoxetine) and low doses of oral estroprogestins. Other interventions, such as light therapy, cognitive behavioral therapy, food supplements, and herbal medicines, showed promising effects, but other investigations are needed to confirm their efficacy.

The Novel Antipsychotic Cariprazine (RGH-188): State-of-the-Art in the Treatment of Psychiatric Disorders.

Cariprazine (RGH-188) is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to D3 receptor, antagonism of 5HT2B receptors and partial agonism of 5HT1A. Currently, cariprazine is in late-stage clinical development (phase III clinical trials) in patients with schizophrenia (S) and in patients with bipolar disorder (BD), as well as an adjunctive treatment in patients with Major Depressive Disorder (MDD) and drug-resistant MDD. Cariprazine has completed phase III trials for the acute treatment of schizophrenia and bipolar mania, phase II trials for the bipolar depression and MDD whilst it is undergoing phase III trials as an adjunct to antidepressants. The present review aims at proving a comprehensive summary of the current evidence on the safety, tolerability and efficacy of cariprazine in the treatment of schizophrenia, BD (manic/mixed/ depressive episode) and MDD. A systematic search was conducted on PubMed/Medline/ Scopus and the database on Clinical Trials from inception until April 2015 by typing a set of specified keywords. Available evidence seems to support cariprazine efficacy in the treatment of cognitive and negative symptoms of schizophrenia. Preliminary findings suggest its antimanic activity whilst it is still under investigation its efficacy in the treatment of bipolar depression and MDD. Furthermore, the available data seems not to allow judgements about its antipsychotic potential in comparison with currently prescribed antipsychotics. Further studies should be carried out to better investigate its pharmacodynamic and clinical potential, particularly as alternative to current antipsychotic drugs.

GABA levels in the ventromedial prefrontal cortex during the viewing of appetitive and disgusting food images.

Characterizing how the brain appraises the psychological dimensions of reward is one of the central topics of neuroscience. It has become clear that dopamine neurons are implicated in the transmission of both rewarding information and aversive and alerting events through two different neuronal populations involved in encoding the motivational value and the motivational salience of stimuli, respectively. Nonetheless, there is less agreement on the role of the ventromedial prefrontal cortex (vmPFC) and the related neurotransmitter release during the processing of biologically relevant stimuli. To address this issue, we employed magnetic resonance spectroscopy (MRS), a non-invasive methodology that allows detection of some metabolites in the human brain in vivo, in order to assess the role of the vmPFC in encoding stimulus value rather than stimulus salience. Specifically, we measured gamma-aminobutyric acid (GABA) and, with control purposes, Glx levels in healthy subjects during the observation of appetitive and disgusting food images. We observed a decrease of GABA and no changes in Glx concentration in the vmPFC in both conditions. Furthermore, a comparatively smaller GABA reduction during the observation of appetitive food images than during the observation of disgusting food images was positively correlated with the scores obtained to the body image concerns sub-scale of Body Uneasiness Test (BUT). These results are consistent with the idea that the vmPFC plays a crucial role in processing both rewarding and aversive stimuli, possibly by encoding stimulus salience through glutamatergic and/or noradrenergic projections to deeper mesencephalic and limbic areas.