Publications by authors named "Giulio Perugi"

187 Publications

High exposure to pharmacological treatments is associated with limited efficacy of electroconvulsive therapy in bipolar depression.

Psychiatry Res 2021 Oct 17;304:114169. Epub 2021 Aug 17.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. Electronic address:

Episode chronicity and medication failure are considered robust predictors of poor response to electroconvulsive therapy (ECT). In this study we explored the associations between indexes of drug exposure during current episode and outcomes of ECT in 168 bipolar depressive patients. The association between response or remission and number of previous pharmacological trials, failure of treatment with antidepressants, antipsychotics or combinations, and sum of maximum Antidepressant Treatment History Form (ATHF) scores obtained in each pharmacological class were tested. 98 patients (58%) were considered responders and 21 remitters (13%). Number of trials, number of adequate trials, ATHF sum, antidepressant-antipsychotic combination therapy failure and failure of two adequate trials were significantly negatively associated with remission. The association with ATHF sum stayed significant when controlling for episode duration and manic symptoms and survived stepwise model selection. No significant associations with response were identified. In conclusion, a history of multiple drug treatments may be linked to a greater resistance to all types of therapies, including ECT. However, we could not exclude that, at least in some patients, a prolonged exposure to pharmacological treatments may be responsible for a greater chronicity and for the presence of residual symptoms, which would explain reduced remission after ECT.
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http://dx.doi.org/10.1016/j.psychres.2021.114169DOI Listing
October 2021

Clinical features and predictors of non-response in severe catatonic patients treated with electroconvulsive therapy.

Int J Psychiatry Clin Pract 2021 Sep 12;25(3):299-306. Epub 2021 Aug 12.

Psychiatry Unit 2, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Objective: To explore the demographic and clinical features of severe catatonic patients, comparing responders and non-responders to ECT in order to detect possible predictors of non-response.

Methods: This naturalistic study included 59 catatonic inpatients with a diagnosis of mood disorder according to DSM-IV-TR criteria. All patients were treated with bilateral ECT and evaluated before and after ECT course. The response to ECT was defined as a Clinical Global Impression (Improvement subscale) rating 1 'very much improved' or 2 'much improved'. Clinical variables were compared between responders and non-responders; logistic regression was used to predict the probability of non-response, with regard to the symptoms presented by the patients.

Results: The response rate was 83.1%. Non-responders ( = 10) to ECT showed neurological comorbidities, treatments with dopamine agonists and anticholinergic drugs, waxy flexibility, and echophenomena more frequently than respondents ( = 49). Echophenomena resulted a significant predictor of non-response in the multivariate analysis.

Conclusion: In line with previous reports, ECT resulted effective in the vast majority of severe catatonic patients. The association between ECT resistant catatonia and neurological comorbidity, use of dopamine-agonist and anticholinergic medications is consistent with the hypothesis that ECT is more effective in 'top-down' than in 'bottom-up' variant of catatonia.Key pointsCatatonic symptoms are frequently associated with severe and psychotic mood disorders.Electroconvulsive therapy is effective in treating most forms of severe catatonia.Neurological comorbidity and the presence of 'echopraxia/echolalia' could represent predictors of non-response to ECT.
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http://dx.doi.org/10.1080/13651501.2021.1951294DOI Listing
September 2021

Treatment adherence and tolerability of immediate- and prolonged-release lithium formulations in a sample of bipolar patients: a prospective naturalistic study.

Int Clin Psychopharmacol 2021 Sep;36(5):230-237

Psychiatry 2 Unit, Department of Clinical and Experimental Medicine, University of Pisa.

The aim of this study was to compare treatment adherence and tolerability of different lithium formulations in 70 bipolar patients receiving lithium therapy for the first time. During the 1-year follow-up, information was collected regarding patient's clinical course, therapeutic adherence, side effects of the treatment and serum levels of lithium, creatinine and thyroid-stimulating hormone. At baseline, 30 patients (43%) were on prolonged-release lithium formulations and 40 (57%) on immediate-release formulations. At the final evaluation, 37 patients (53%) were considered lost to follow-up. Both prolonged- and immediate-release patients showed significant improvement in the Functioning Assessment Short Test and in the Clinical Global Impressions for Bipolar Disorder scores during the follow-up. At the first follow-up visit, the mean plasma lithium level of prolonged-release patients was higher than immediate-release patients (0.61 vs. 0.47, respectively; P = 0.063), as well as the therapeutic adherence (85 vs. 64%, respectively; P = 0.089). Fine tremor and gastrointestinal symptoms were more frequent in immediate-release patients than in prolonged-release patients at each follow-up visit, with the sole exception of gastrointestinal symptoms at the last evaluation. Prolonged-release lithium therapy could provide potential advantages over immediate-release formulations. Future naturalistic studies and clinical trials with a longer follow-up duration are needed.
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http://dx.doi.org/10.1097/YIC.0000000000000373DOI Listing
September 2021

Development of bipolar disorder in patients with attention-deficit/hyperactivity disorder: A systematic review and meta-analysis of prospective studies.

J Affect Disord 2021 10 24;293:186-196. Epub 2021 Jun 24.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy.

Background: Increasing attention has been recently paid to precursors of bipolar disorder (BD). Symptoms of attention-deficit/hyperactivity disorder (ADHD) have been reported among the most common prodromes of BD. The aim of this study was to estimate the risk of BD in youths affected by ADHD based on prospective studies.

Methods: A systematic review was conducted according to the PRISMA guidelines. A meta-analysis of single proportions was performed to compute the overall occurrence of BD in ADHD individuals. Binary outcome data were used to calculate risk estimates of BD occurrence in ADHD subjects versus Healthy Controls (HC).

Results: An overall proportion of BD occurrence of 10.01% (95%-confidence interval [CI]: 6.47%-15.19%; I = 82.0%) was found among 1248 patients with ADHD over 10 prospective studies. A slightly higher proportion was found when excluding one study based on jack-knife sensitivity analysis (11.96%, 95%-CI: 9.15%-15.49%; I = 54.1%) and in three offspring studies (12.87%, 95%-CI: 8.91%-18.23%). BD occurrence was not significantly associated with mean follow-up duration (p-value = 0.2118). A greater risk of BD occurrence in ADHD versus HC from six studies was found (risk ratio: 8.97, 95%-CI: 4.26-18.87, p-value < 0.0001).

Limitations: Few prospective studies have been retrieved in our search and most were not specifically aimed at assessing BD in followed-up ADHD patients.

Conclusions: Greater clinical attention should be paid to ADHD as an early precursor of BD since a substantial proportion of ADHD patients is expected to be diagnosed with BD during the developmental age.
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http://dx.doi.org/10.1016/j.jad.2021.06.033DOI Listing
October 2021

Prevalence of mood, panic and eating disorders in obese patients referred to bariatric surgery: patterns of comorbidity and relationship with body mass index.

Eat Weight Disord 2021 Jun 16. Epub 2021 Jun 16.

Psychiatry 2 Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Via Savi 10, 56126, Pisa, Italia.

Purpose: We aimed at investigating the lifetime prevalence of mood, eating and panic disorders in a large sample of obese patients referred to bariatric surgery. We also explored the patterns of psychiatric comorbidity and their relationship with Body Mass Index (BMI).

Methods: The sample was composed of patients consecutively referred for pre-surgical evaluation to the Obesity Center of Pisa University Hospital between January 2004 and November 2016. Clinical charts were retrieved and examined to obtain sociodemographic information, anthropometric variables and lifetime psychiatric diagnoses according to DSM-IV criteria.

Results: A total of 871 patients were included in the study; 72% were females, and most patients had BMI ≥ 40 kg/m (81%). Overall, 55% of the patients were diagnosed with at least one lifetime psychiatric disorder. Binge eating disorder (27.6%), major depressive disorder (16%), bipolar disorder type 2 (15.5%), and panic disorder (16%) were the most common psychiatric diagnoses. Mood disorders showed associations with panic disorder (OR = 2.75, 95% CI = 1.90-3.99, χ = 41.85, p = 0.000) and eating disorders (OR = 2.17, 95% CI 1.64-2.88, χ = 55.54, p = 0.000). BMI was lower in patients with major depressive disorder (44.9 ± 7.89) than in subjects without mood disorders (46.75 ± 7.99, p = 0.017).

Conclusion: Bariatric patients show high rates of psychiatric disorders, especially binge eating and mood disorders. Longitudinal studies are needed to explore the possible influence of such comorbidities on the long-term outcome after bariatric surgery.

Level Of Evidence: V, cross sectional descriptive study.
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http://dx.doi.org/10.1007/s40519-021-01236-yDOI Listing
June 2021

There are no patients without comorbidity.

Eur Neuropsychopharmacol 2021 Sep 30;50:104-106. Epub 2021 May 30.

Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, Pisa 56126, Italy.

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http://dx.doi.org/10.1016/j.euroneuro.2021.05.002DOI Listing
September 2021

Prevalence and Clinical Correlates of Comorbid Anxiety and Panic Disorders in Patients with Parkinson's Disease.

J Clin Med 2021 May 25;10(11). Epub 2021 May 25.

2nd Psychiatric Unit, Department of Clinical and Experimental Medicine, Santa Chiara University Hospital, University of Pisa, 56100 Pisa, Italy.

Mood and anxiety disorders are the most common neuropsychiatric syndromes associated with Parkinson's disease (PD). The aim of our study was to estimate the prevalence of lifetime and current anxiety disorders in patients with Parkinson's Disease (PD), to explore possible distinctive neurological and psychiatric features associated with such comorbidity. One hundred patients were consecutively recruited at the Movement Disorders Section of the Neurological Outpatient Clinic of the University of Pisa. According to the MINI-Plus 5.0.0, 41 subjects were diagnosed with lifetime anxiety disorder (22 with panic disorder) and 26 were diagnosed with current anxiety disorders. Patients with anxiety disorders were more frequently characterized by psychiatric symptoms preceding PD, lifetime major depression and antidepressant treatments. They showed more anxious temperamental traits and scored higher at Parkinson Anxiety Scale (PAS) and persistent anxiety subscale. Current anxiety disorders were associated with more severe psychopathology, depressive symptomatology, and avoidant behavior. Among anxiety subtypes, patients with lifetime panic disorder showed higher rates of psychiatric symptoms before PD, lifetime unipolar depression, current psychiatric treatment, and a more severe psychopathology. Given the overall high impact of anxiety on patients' quality of life, clinicians should not underestimate the extent of different anxiety dimensions in PD.
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http://dx.doi.org/10.3390/jcm10112302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198165PMC
May 2021

Comparison of Emotional Dysregulation Features in Cyclothymia and Adult ADHD.

Medicina (Kaunas) 2021 May 12;57(5). Epub 2021 May 12.

Psychiatry 2 Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy.

: Emotional dysregulation is central to the problem of the overlap between attention-deficit/hyperactivity disorder (ADHD) and cyclothymia. The aim of the study was to evaluate comorbidity rates between ADHD and cyclothymic disorder and to explore demographic and clinical differences among the groups, focusing on affective temperament and emotional dysregulation. : One hundred sixty-five outpatients attending the Second Psychiatry Unit at the Santa Chiara University Hospital (Pisa) were consecutively recruited: 80 were diagnosed with ADHD, 60 with cyclothymic disorder, and 25 with both conditions. Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-M) and the 40-item version of Reactivity, Intensity, Polarity, and Stability questionnaire (RI-PoSt-40) were administered. : Cyclothymic patients were more frequently female and older with respect to the ADHD groups. Both comorbid and non-comorbid ADHD patients showed significantly lower educational attainment and more frequently had substance use disorders. Panic disorder was common in non-comorbid cyclothymic patients, who showed significantly higher rates of familial panic disorder, major depressive disorder and suicide attempts in comparison with patients only diagnosed with ADHD. Cyclothymic patients without ADHD were also characterized by fewer hyperthymic temperamental traits, higher depressive and anxious dispositions, and a greater negative emotionality. No significant differences among groups were observed for cyclothymic temperament and overall negative emotional dysregulation, but comorbid patients with both conditions scored the highest in these subscales. This group also showed significantly higher affective instability with respect to ADHD patients without cyclothymia and was less frequently diagnosed with bipolar disorder type II than patients from both the other groups. : ADHD and cyclothymia often co-occur and show similar levels of emotional dysregulation. However, cyclothymic patients may be more prone to negative emotionality in clinical settings. Subjects with "sunny" cyclothymic features might escape the attention of clinicians unless ADHD is present.
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http://dx.doi.org/10.3390/medicina57050489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151096PMC
May 2021

Influence of Substance Use Disorder on Treatment Retention of Adult-Attention-Deficit/Hyperactive Disorder Patients. A 5-Year Follow-Up Study.

J Clin Med 2021 May 5;10(9). Epub 2021 May 5.

Association for the Application of Neuroscientific Knowledge to Social Aims (AU-CNS), 55045 Pietrasanta, Italy.

Attention-Deficit/Hyperactivity Disorder (ADHD) is the most widespread neurodevelopmental disorder, and it still persists into adulthood in 2-6% of the population. Psychiatric comorbidities are very common in adult ADHD (A-ADHD) patients; in particular, Substance Use Disorder (SUD) is found in 40% of these patients. Co-occurrence of ADHD and SUD is described as detrimental to clinical outcome by many authors, while only a few studies describe good clinical results in A-ADHD-SUD patients when they were treated for ADHD, both for the efficacy and the compliance of patients. In this study we tested to determine whether SUD can influence the treatment outcome of A-ADHD patients by correlating lifetime, past and current substance use in A-ADHD patients with their outcome (retention rate) during a 5-year follow-up of patients treated with stimulant and non-stimulant medications, using Kaplan-Meier survival analysis with overall and pairwise comparison. The association between demographic, symptomatological and clinical aspects with retention in treatment, adjusting for potential confounding factors, was summarized using Cox regression. After 5 years of observation, the cumulative treatment retention was 49.0%, 64.3% and 41.8% for A-ADHD patients without lifetime SUD (NSUD/A-ADHD), A-ADHD with past SUD (PSUD/A-ADHD) and A-ADHD with current SUD (CSUD/A-ADHD), respectively. Overall comparisons were not significant (Wilcoxon Rank-Sum (statistical) Test = 1.48; df = 2; = 0.477). The lack of differences was confirmed by a Cox regression demonstrating that the ADHD diagnosis according to DIVA, gender, education, civil status, presence of psychiatric comorbidity, and psychiatric and ADHD familiarity; severity of symptomatological scales as evaluated by WHODAS, BPRS, BARRAT, DERS, HSRS, and ASRS did not influence treatment drop-out (χ2 22.30; df = 20 = 0.324). Our A-ADHD-SUD patients have the same treatment retention rate as A-ADHD patients without SUD, so it seems that substance use comorbidity does not influence this clinical parameter.
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http://dx.doi.org/10.3390/jcm10091984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124852PMC
May 2021

Does Cannabis, Cocaine and Alcohol Use Impact Differently on Adult Attention Deficit/Hyperactivity Disorder Clinical Picture?

J Clin Med 2021 Apr 2;10(7). Epub 2021 Apr 2.

Association for the Application of Neuroscientific Knowledge to Social Aims (AU-CNS), Pietrasanta, 55045 Lucca, Italy.

While the association between adult Attention Deficit/Hyperactivity Disorder (A-ADHD) and Substance Use Disorders (SUDs) has been widely explored, less attention has been dedicated to the various substance use variants. In a previous paper, we identified two variants: type 1 (use of stimulants/alcohol) and type 2 (use of cannabinoids). In this study, we compared demographic, clinical and symptomatologic features between Dual Disorder A-ADHD (DD/A-ADHD) patients according to our substance use typology, and A-ADHD without DD (NDD/A-ADHD) ones. NDD patients were more frequently diagnosed as belonging to inattentive ADHD subtype compared with type 1 DD/A-ADHD patients, but not with respect to type 2 DD/ADHD. NDD/A-ADHD patients showed less severe symptoms of hyperactivity/impulsivity than DD/A-ADHD type 1, but not type 2. Type 1 and type 2 patients shared the feature of displaying higher impulsiveness than NDD/A-ADHD ones. General psychopathology scores were more severe in type 2 DD/ADHD patients, whereas type 1 patients showed greater similarity to NDD/A-ADHD. Legal problems were more strongly represented in type 1 than in type 2 patients or NDD/A-ADHD ones. Our results suggest that type 1 and type 2 substance use differ in their effects on A-ADHD patients-an outcome that brings with it different likely implications in dealing with the diagnostic and therapeutic processes.
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http://dx.doi.org/10.3390/jcm10071481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038274PMC
April 2021

Transitions: Hagop Souren Akiskal.

J Affect Disord 2021 04 8;284:201-202. Epub 2021 Feb 8.

International Consortium for Mood & Psychotic Disorder Research, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Lucio Bini Mood Disorder Centers, Cagliari & Rome, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jad.2021.02.025DOI Listing
April 2021

Symptomatological Variants and Related Clinical Features in Adult Attention Deficit Hyperactive Disorder.

Int J Environ Res Public Health 2021 01 21;18(3). Epub 2021 Jan 21.

2nd Psychiatric Unit, Department of Clinical and Experimental Medicine, Santa Chiara University Hospital, University of Pisa, 56100 Pisa, Italy.

A large amount of the current literature has focused on the characteristic symptoms of attention deficit hyperactivity disorder (ADHD) in children and adolescents. In contrast, less attention has been devoted to ADHD clinical subtypes in adult patients. We evaluated 164 consecutive adult ADHD (A-ADHD) outpatients using DSM-5 criteria and many specific rating scales and questionnaires. A principal component factor analysis was performed on clinical and symptomatological variables to describe potential clinical variants. We sought to determine different A-ADHD variants focusing on demographic and clinical features. A four-factor solution was identified, and patients were clustered, according to their z-score, in 4 subgroups. The first was marked out by Emotional Dysregulation (ED), the second by Substance Use (SU), the third by Core-ADHD Symptoms (Co-ADHD) and the fourth by Positive Emotionality (PE). Predominantly ED patients showed worse overall function, early treatment with antidepressants and a greater presence of borderline personality disorder than predominantly Co-ADHD patients. Predominantly SU patients reported high rates of bipolar disorder and severe general psychopathology. The PE factor was related to hyperthymic temperament and hypomania and showed a higher level of functioning. Females with A-ADHD showed a lower risk of being included in SU, and A-ADHD patients with co-occurring delayed sleep phase had less risk of being included in the SU factor than the prevailing Co-ADHD group. Our empirically based description of four clinical A-ADHD variants shows several aspects beyond the definition given by the DSM-5 diagnostic criteria.
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http://dx.doi.org/10.3390/ijerph18030922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908530PMC
January 2021

Insomnia, sleep loss, and circadian sleep disturbances in mood disorders: a pathway toward neurodegeneration and neuroprogression? A theoretical review.

CNS Spectr 2021 Jan 11:1-11. Epub 2021 Jan 11.

Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

The present paper aims at reviewing and commenting on the relationships between sleep and circadian phasing alterations and neurodegenerative/neuroprogressive processes in mood disorder. We carried out a systematic review, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, in PubMed, PsycINFO, and Embase electronic databases for literature related to mood disorders, sleep disturbances, and neurodegenerative/neuroprogressive processes in relation to (1) neuroinflammation, (2) activation of the stress system, (3) oxidative stress, (4) accumulation of neurotoxic proteins, and (5) neuroprotection deficit. Seventy articles were collectively selected and analyzed. Experimental and clinical studies revealed that insomnia, conditions of sleep loss, and altered circadian sleep may favor neurodegeneration and neuroprogression in mood disorders. These sleep disturbances may induce a state of chronic inflammation by enhancing neuroinflammation, both directly and indirectly, via microglia and astrocytes activation. They may act as neurobiological stressors that by over-activating the stress system may negatively influence neural plasticity causing neuronal damage. In addition, sleep disturbances may favor the accumulation of neurotoxic proteins, favor oxidative stress, and a deficit in neuroprotection hence contributing to neurodegeneration and neuroprogression. Targeting sleep disturbances in the clinical practice may hold a neuroprotective value for mood disorders.
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http://dx.doi.org/10.1017/S1092852921000018DOI Listing
January 2021

Survey on centres and procedures for the diagnosis and treatment of adult ADHD in public services in Italy.

Riv Psichiatr 2020 Nov-Dec;55(6):355-365

Department of Mental Health and Addiction, ASST Papa Giovanni XXIII Bergamo, Italy.

Attention deficit/hyperactivity disorder (ADHD) often persists into adulthood. Although its persistence and relative high prevalence, ADHD in adults is often underdiagnosed and undertreated in Italy, leading to poor clinical and functional outcomes, and higher costs of illness. The aims of the study were to identify the Italian mental health services for ADHD in adults, describe the diagnostic and treatment procedures they follow, and compare this offer with the recommendations of the German and English guidelines. The centres, that adopt a clinical and assessment protocol for adult ADHD diagnosis (carried out by specifically trained personnel) and prescribe pharmacological treatment for adult ADHD, were selected from the list of accredited services provided by the Appendix B.2 of the ISTISAN 16/37 Reports of the ISS. An ad-hoc survey including open-ended and close-ended questions was sent to each selected centre in February 2020. The overall picture resulting from the data analysis was compared with the recommendations of the German and English guidelines. The present survey shows that only a few centres are specialised in the diagnosis and treatment of ADHD in adults in Italy. Furthermore, there are no national guidelines for adult ADHD in Italy. The collected data also suggest that there is no a unified practice shared by the Centres both for the patient's transition from child and adolescent to adult mental health services and for the diagnostic-therapeutic process. It is therefore crucial to create specific protocols and develop national guidelines to better identify and diagnose ADHD in adults and provide targeted and more efficient multimodal treatments.
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http://dx.doi.org/10.1708/3503.34894DOI Listing
December 2020

The shocking attitude toward electroconvulsive therapy in Italy.

CNS Spectr 2020 Dec 4:1-3. Epub 2020 Dec 4.

Psychiatry 2 Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy.

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http://dx.doi.org/10.1017/S1092852920002059DOI Listing
December 2020

Bipolar Spectrum disorders in Parkinson's disease: a systematic evaluation.

CNS Spectr 2020 Dec 7:1-7. Epub 2020 Dec 7.

Department of Clinical and Experimental Medicine-Psychiatry Unit, University of Pisa, Pisa, Italy.

Objective: Psychiatric disorders are very common in patients affected by Parkinson's disease (PD). However, comorbidity with Bipolar Spectrum disorders is understudied. The aim of this study is to explore the clinical correlates of PD associated with Bipolar Spectrum disorders.

Methods: One hundred PD patients were screened for psychiatric comorbidities, cognitive profile, motor, and non-motor symptoms. The sample was divided into three groups: PD-patients with Bipolar Spectrum disorders (bipolar disorder type I, type II, and spontaneous or induced hypomania; N = 32), PD-patients with others psychiatric comorbidities (N = 39), PD-patients without psychiatric comorbidities (N = 29). Clinical features were compared among the groups using analysis of variance and chi-square test. A logistic regression was performed to evaluate the association between Bipolar Spectrum disorders and early onset of PD (≤50 years) controlling for lifetime antipsychotic use.

Results: In comparison with PD patients with and without other psychiatric comorbidity, subjects affected by Bipolar Spectrum disorders were younger, showed more frequently an early onset PD, reported more involuntary movements and a higher rate of impulse control disorders and compulsive behaviors. No differences were observed in indexes of exposure to dopamine agonist treatments. The early onset of PD was predicted by Bipolar Spectrum comorbidity, independently from lifetime antipsychotic use.

Conclusion: Bipolar Spectrum disorders are common in early onset PD. The presence of bipolar comorbidity could identify a particular subtype of PD, showing higher rates of neurological and psychiatric complications and deserving further investigation.
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http://dx.doi.org/10.1017/S1092852920002126DOI Listing
December 2020

Exploring the Role of Caffeine Use in Adult-ADHD Symptom Severity of US Army Soldiers.

J Clin Med 2020 Nov 23;9(11). Epub 2020 Nov 23.

Association for the Application of Neuroscientific Knowledge to Social Aims (AU-CNS), 55045 Pietrasanta, Lucca, Italy.

There is a growing trend of using energy drinks and caffeinated beverages to improve cognitive performance that is widespread and well-studied among children and teenagers with Attention Deficit Hyperactive Disorder (ADHD), but little is known about adult ADHD (A-ADHD). As a consequence, the use of highly caffeinated drinks and their impact on ADHD symptoms are poorly understood. This is especially true in populations where A-ADHD and the use of these beverages are largely represented, such as in military samples. From the All Army Study (AAS) of the Army Study to Assess Risk and Resilience in Service members (STARRS) data, 1,239 A-ADHD soldiers and 17,674 peers without any psychiatric comorbidity were selected. The two groups were compared on: (1) the presence of substance use disorder (SUD) diagnosis both over their lifetime and in the previous 30 days; (2) patterns of alcohol and caffeine use using chi-square analyses. Lastly, the relationship between substance use and severity of A-ADHD symptoms was assessed using Pearson's correlations. Soldiers with a diagnosis of A-ADHD had a higher prevalence of SUD diagnosis compared to their peers without psychiatric comorbidity. They also tended to use more alcohol, caffeine pills, energy drinks, and other caffeinated drinks. Alcohol use was positively correlated with A-ADHD symptoms; on the contrary, energy drinks, caffeine pills and other caffeinated drinks showed negative correlations with some aspects of A-ADHD symptomatology. The use of caffeinated compounds appears to be increased among military soldiers with ADHD, and they may help reducing A-ADHD symptoms and improve cognitive performance. These results suggest a possible role for caffeine as a potential pharmacological tool in the treatment of adult ADHD.
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http://dx.doi.org/10.3390/jcm9113788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700297PMC
November 2020

Mood disorders comorbidity in obese bariatric patients: the role of the emotional dysregulation.

J Affect Disord 2021 01 6;279:46-52. Epub 2020 Oct 6.

Psychiatry 2 Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy. Electronic address:

Background: Obese patients seeking bariatric surgery are known to show high rates of mental disorders, mainly mood and eating disorders. The aim of the present study is to evaluate psychiatric comorbidities, affective temperamental dimensions, emotional dysregulation and impulsivity in a sample of obese bariatric patients, exploring the differences between obese patients with and without mood disorders (MD).

Methods: A total of 69 obese patients were consecutively enrolled between March and November 2019 during the presurgical evaluation routinely performed before the bariatric intervention. Sociodemographic and clinical features were collected by psychiatrists during a single consultation. Affective temperaments, emotional dysregulation and impulsivity were also investigated through self-report questionnaires. Epidemiological and clinical variables were compared between patients with and without MD.

Results: In our sample, almost 3 out of 4 patients presented a lifetime psychiatric disorder, mainly MD (n=33, 48%), binge eating disorder (BED) (n=34, 49%) and anxiety disorders (n=30, 43%). Compared to N-MD patients, those with MD showed higher rates of psychiatric comorbidity with BED, bulimia and panic disorder. In addition, obese patients with MD showed more frequently cyclothymic, depressive and anxious temperaments, and higher mean scores on the psychometric questionnaires assessing emotional dysregulation and impulsivity compared to obese subjects without MD.

Limitations: the small sample size, the retrospectively assessment of psychiatric disorders and the self-report questionnaires.

Conclusions: A subgroup of obese patients, especially among those with MD, show high emotional dysregulation, affective lability and impulsiveness that could represent suitable substrates for the development of compulsive and addictive eating habits.
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http://dx.doi.org/10.1016/j.jad.2020.09.128DOI Listing
January 2021

Characterization of rapid cycling bipolar patients presenting with major depressive episode within the BRIDGE-II-MIX study.

Bipolar Disord 2021 06 8;23(4):391-399. Epub 2020 Oct 8.

University of Pisa, Pisa, Italy.

Objectives: The "Bipolar Disorders: Improving Diagnosis, Guidance, and Education" (BRIDGE-II-Mix) study aimed to estimate the frequency of mixed states in patients with a major depressive episode (MDE) according to different definitions and to compare their clinical validity, looking into specific features such as rapid cycling (RC).

Methods: Psychiatric symptoms, socio-demographic, and clinical variables were collected from a sample of 2811 MDE patients, of which 726 (25.8%) were diagnosed with bipolar disorder (BD). The characteristics of bipolar patients with RC (BD-RC) and without (BD-NRC) RC were compared.

Results: Of 726 BD patients, 159 (21.9%) met DSM-5 criteria for RC. BD-RC group presented a higher number of lifetime depressive episodes (p < 0.001) with shorter duration of depressive episodes, and more psychiatric comorbidities, as well as higher rates of atypical features (p = 0.016) and concomitant (hypo)manic symptoms (irritable mood (p = 0.001); risky behavior (p = 0.005); impulsivity (p = 0.006); and psychomotor agitation (p = 0.029)). Patients with RC had a worse functioning (p = 0.033), more obesity (p = 0.003), and were significantly more likely to be treated with three or more drugs (p = 0.007).

Conclusions: Important clinical differences between bipolar patients with and without a RC include more depressive morbidity, higher incidence of anxiety disorders, addiction, bulimia, and borderline personality disorder, as well as atypical features during depression and symptoms such as irritability, risky behavior, impulsivity, and agitation. RC patients had poorer functioning than patients without RC, more obesity, and had to be treated with more drugs.
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http://dx.doi.org/10.1111/bdi.12994DOI Listing
June 2021

Characterization of rapid cycling bipolar patients presenting with major depressive episode within the BRIDGE-II-MIX study.

Bipolar Disord 2021 06 8;23(4):391-399. Epub 2020 Oct 8.

University of Pisa, Pisa, Italy.

Objectives: The "Bipolar Disorders: Improving Diagnosis, Guidance, and Education" (BRIDGE-II-Mix) study aimed to estimate the frequency of mixed states in patients with a major depressive episode (MDE) according to different definitions and to compare their clinical validity, looking into specific features such as rapid cycling (RC).

Methods: Psychiatric symptoms, socio-demographic, and clinical variables were collected from a sample of 2811 MDE patients, of which 726 (25.8%) were diagnosed with bipolar disorder (BD). The characteristics of bipolar patients with RC (BD-RC) and without (BD-NRC) RC were compared.

Results: Of 726 BD patients, 159 (21.9%) met DSM-5 criteria for RC. BD-RC group presented a higher number of lifetime depressive episodes (p < 0.001) with shorter duration of depressive episodes, and more psychiatric comorbidities, as well as higher rates of atypical features (p = 0.016) and concomitant (hypo)manic symptoms (irritable mood (p = 0.001); risky behavior (p = 0.005); impulsivity (p = 0.006); and psychomotor agitation (p = 0.029)). Patients with RC had a worse functioning (p = 0.033), more obesity (p = 0.003), and were significantly more likely to be treated with three or more drugs (p = 0.007).

Conclusions: Important clinical differences between bipolar patients with and without a RC include more depressive morbidity, higher incidence of anxiety disorders, addiction, bulimia, and borderline personality disorder, as well as atypical features during depression and symptoms such as irritability, risky behavior, impulsivity, and agitation. RC patients had poorer functioning than patients without RC, more obesity, and had to be treated with more drugs.
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http://dx.doi.org/10.1111/bdi.12994DOI Listing
June 2021

Relationships Among Delayed Sleep Phase Disorder, Emotional Dysregulation, and Affective Temperaments in Adults With Attention Deficit Hyperactivity Disorder and Cyclothymia.

J Nerv Ment Dis 2020 11;208(11):857-862

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

This study aims to explore the relationships between delayed sleep phase disorder (DSPD) and emotional dysregulation in 240 patients (134 with cyclothymia, 81 with attention deficit hyperactivity disorder [ADHD] and 25 with both conditions). DSPD was assessed using the Morningness-Eveningness Questionnaire, followed by a clinical evaluation. Affective temperaments and emotional dysregulation were also investigated through the brief version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego and the Reactivity, Intensity, Polarity, Stability questionnaires, respectively. Clinical variables were compared in patients with and without DSPD, and a logistic regression model was used to identify the predictive value of the clinical characteristics on the presence of DSPD. DSPD patients (19% of the total sample) were significantly younger than patients without DSPD, showed an about 4 times higher lifetime history of comorbid ADHD and cyclothymia, and reported higher scores in the irritable and cyclothymic temperamental subscales and in the affective instability and impulsivity dimensions. In the multiple logistic regression, we found a negative predictive value of increasing age on the presence of DSPD, whereas comorbid cyclothymia and ADHD and cyclothymic temperament seem to represent risk factors for DSPD.
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http://dx.doi.org/10.1097/NMD.0000000000001209DOI Listing
November 2020

Psychiatric Aspects of Obesity: A Narrative Review of Pathophysiology and Psychopathology.

J Clin Med 2020 Jul 23;9(8). Epub 2020 Jul 23.

2nd Psychiatric Unit, Department of Clinical and Experimental Medicine, Santa Chiara University Hospital, University of Pisa, 56100 Pisa, Italy.

In the last decades, obesity has become a major concern for clinical and public health. Despite the variety of available treatments, the outcomes remain-by and large-still unsatisfactory, owing to high rates of nonresponse and relapse. Interestingly, obesity is being associated with a growing surge of neuropsychiatric problems, certainly related to the pathogenesis of this condition, and likely to be of great consequence as for its treatment and prognosis. In a neurobiologic direction, a sturdy body of evidence has recently shown that the immune-metabolic-endocrine dyscrasias, notoriously attached to excess body weight/adiposity, affect and impair the morpho-functional integrity of the brain, thus possibly contributing to neuroprogressive/degenerative processes and behavioral deviances. Likewise, in a neuropsychiatric perspective, obesity displays complex associations with mood disorders and affective temperamental dimensions (namely cyclothymia), eating disorders characterized by overeating/binge-eating behaviors, ADHD-related executive dysfunctions, emotional dysregulation and motivational-addictive disturbances. With this review, we attempt to provide the clinician a synoptic, yet exhaustive, tool for a more conscious approach to that subset of this condition, which could be reasonably termed "psychiatric" obesity.
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http://dx.doi.org/10.3390/jcm9082344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463475PMC
July 2020

Deconstructing major depressive episodes across unipolar and bipolar depression by severity and duration: a cross-diagnostic cluster analysis on a large, international, observational study.

Transl Psychiatry 2020 07 19;10(1):241. Epub 2020 Jul 19.

Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.

A cross-diagnostic, post-hoc analysis of the BRIDGE-II-MIX study was performed to investigate how unipolar and bipolar patients suffering from an acute major depressive episode (MDE) cluster according to severity and duration. Duration of index episode, Clinical Global Impression-Bipolar Version-Depression (CGI-BP-D) and Global Assessment of Functioning (GAF) were used as clustering variables. MANOVA and post-hoc ANOVAs examined between-group differences in clustering variables. A stepwise backward regression model explored the relationship with the 56 clinical-demographic variables available. Agglomerative hierarchical clustering with two clusters was shown as the best fit and separated the study population (n = 2314) into 65.73% (Cluster 1 (C1)) and 34.26% (Cluster 2 (C2)). MANOVA showed a significant main effect for cluster group (p < 0.001) but ANOVA revealed that significant between-group differences were restricted to CGI-BP-D (p < 0.001) and GAF (p < 0.001), showing greater severity in C2. Psychotic features and a minimum of three DSM-5 criteria for mixed features (DSM-5-3C) had the strongest association with C2, that with greater disease burden, while non-mixed depression in bipolar disorder (BD) type II had negative association. Mixed affect defined as DSM-5-3C associates with greater acute severity and overall impairment, independently of the diagnosis of bipolar or unipolar depression. In this study a pure, non-mixed depression in BD type II significantly associates with lesser burden of clinical and functional severity. The lack of association for less restrictive, researched-based definitions of mixed features underlines DSM-5-3C specificity. If confirmed in further prospective studies, these findings would warrant major revisions of treatment algorithms for both unipolar and bipolar depression.
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http://dx.doi.org/10.1038/s41398-020-00922-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370235PMC
July 2020

Adult attention-deficit hyperactivity disorder and clinical correlates of delayed sleep phase disorder.

Psychiatry Res 2020 09 3;291:113162. Epub 2020 Jun 3.

Department of Experimental and Clinic Medicine, Section of Psychiatry, University of Pisa, Italy; Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. Electronic address:

The purpose of the study was to assess the prevalence and clinical correlates of Delayed Sleep Phase Disorder (DSPD) in adults with Attention-Deficit/Hyperactivity Disorder. Participants were 102 adults (Female= 27), aged 18-65 (mean age= 28.2 years), with ADHD diagnosed in adulthood. ADHD and DSPD diagnosis were made according to DSM-5 criteria. Assessing instruments included the Morningness-Eveningness Questionnaire, the brief Temperament Evaluation of Memphis, Pisa, Paris and San Diego Questionnaire, the Barratt Impulsiveness Scale, the Reactivity Intensity Polarity Stability Questionnaire-40 and the World Health Organization Disability Assessment Schedule 2.0. Epidemiological and Clinical features were compared in patients with and without DSPD. 34 out of 102 patients were classified as having a Delayed Sleep Phase Disorder. As expected, DSPD patients reported a more frequent evening chronotype. In the multivariate logistic regression analysis, Delayed Sleep Phase Disorder was significantly associated with young age, cannabis use, cyclothymic temperamental traits and severe global impairment. An early diagnosis with a proper treatment targeted to both disorders may be fundamental in order to improve the overall functioning and the outcome of adult ADHD patients.
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http://dx.doi.org/10.1016/j.psychres.2020.113162DOI Listing
September 2020

Predictors of Depressive Switch in Patients With Bipolar I Disorder Who Initiated or Changed Pharmacologic Treatment for Mania or Mixed-Mania: A Prospective Observational Study.

J Clin Psychiatry 2020 06 2;81(4). Epub 2020 Jun 2.

Clinica Psichiatrica, Università di Pisa, Via Roma 67, 56100, Pisa, Italy.

Objective: To evaluate the prevalence and the predictors of depressive switch in patients with bipolar I disorder (BD-I) requiring the initiation or change (but not a dose change) of treatment with oral antipsychotics or mood stabilizers for mania or mixed-mania.

Methods: This was a 3-month, prospective, noninterventional study conducted in 34 Italian psychiatric centers from April 2012 to April 2013. The study sample comprised 234 patients aged 18 years or older presenting with a manic episode according to DSM-IV-TR criteria. Patients were assessed at baseline and at follow-up visits by a variety of measures, including the Clinical Global Impressions scale for use in bipolar illness (CGI-BP). The primary outcome measure was depressive switch, which was defined a posteriori on the basis of a Montgomery-Åsberg Depression Rating Scale total score ≥ 15 and a Young Mania Rating Scale total score < 10 at week 12. A stepwise backward logistic regression model was used to explore the effect of clinical variables on the occurrence of depressive switch.

Results: According to the definition used in this study, 26 (11.1%) of 234 patients switched to depression. The variables associated with a depressive switch were prescription of both first- and second-generation antipsychotics (P = .017), depressive-predominant polarity (P = .012), CGI-BP total score at baseline evaluation (P = .024), depressive temperament (P = .063), and age at evaluation (P = .020).

Conclusions: Depressive switch was observed in about 1 of 10 of the BD-I patients. Our results suggest an association between the depressive switch and treatment with both first- and second-generation antipsychotics, depressive-predominant polarity, greater severity of the symptomatology, and older age at evaluation. Further randomized controlled studies are needed to confirm possible predictors of a depressive switch during mania.
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http://dx.doi.org/10.4088/JCP.19m12896DOI Listing
June 2020

Association of treatment facets, severity of manic symptoms, psychomotor disturbances and psychotic features with response to electroconvulsive therapy in bipolar depression.

World J Biol Psychiatry 2021 03 3;22(3):194-202. Epub 2020 Jun 3.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Objectives: Clinically useful predictors of response to electroconvulsive therapy (ECT) are warranted, especially in the case of bipolar depression. The aim of this study was to explore the associations between response and its known and putative correlates.

Methods: Six hundred seventy bipolar depressive patients treated with ECT were included in the study. The association between response (CGI-I ≤ 2) and mean seizure duration, number of treatments, age, sex, bipolar subtype, episode duration, HAM-D and YMRS scores, psychomotor disturbances and psychotic symptoms assessed through BPRS-EV were evaluated by means of univariate and multivariate logistic regression models, including quadratic and/or linear effects of continuous variables.

Results: Four hundred eighty three patients (72%) were responders. Among known correlates of response, significant quadratic effects were found for seizure duration and number of treatments, while a linear association was confirmed for episode duration. Among putative correlates, severe motor retardation, tension or agitation, hyperactivity and delusions of guilt were significantly associated with response (<.01) and a significant quadratic effect was found for YMRS score (<.01).

Conclusion: Bipolar depressive patients with severe psychomotor disturbances, mood-congruent delusions and severe mixed features are highly responsive to ECT. A significant improvement in response prediction is expected when considering those clinical characteristics.
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http://dx.doi.org/10.1080/15622975.2020.1770860DOI Listing
March 2021

Naturalistic follow-up in bipolar patients after successful electroconvulsive therapy.

J Affect Disord 2020 06 11;271:152-159. Epub 2020 Apr 11.

Psychiatry Unit 2, Azienda Ospedaliero-Universitaria Pisana, Italy; Department of Clinical and Experimental Medicine, University of Pisa, Italy. Electronic address:

Background: Electroconvulsive therapy (ECT) is an effective treatment for acute depression, mania and mixed states. We evaluated the long-term outcome of patients with bipolar depression or mixed state, responsive to ECT.

Methods: this observational follow-up study was conducted in 70 patients with Bipolar Disorder: 36 patients met DSM-IV-TR criteria for a major depressive episode (MDE) and 34 for a mixed episode (MXE). During the follow-up after ECT, the relapse rates and the duration of response and remission periods were recorded.

Results: the mean duration of the follow-up was 57 weeks. 93% of the patients maintained at least a partial therapeutic response for more than 90% of the follow-up period. 73% of patients fulfilled the criteria for a full remission, 33% showed a depressive relapse and 10% a mixed relapse. No manic relapses occurred but almost 1/3 of the sample presented hypomanic episodes. MDE patients presented higher rates of remission compared to MXE ones. Patients with anxiety disorders reported earlier relapses than those without this comorbidity. Relapsed-patients showed higher functional impairment at baseline evaluation, compared to non-relapsed ones.

Limitations: nonrandom allocation, limited sample size, possible influence of psychopharmacological treatment.

Conclusions: Given several methodological limitations, this study cannot draw definite conclusions but could suggest that in treatment-resistant bipolar patients with severe depression or mixed state, ECT may represent a useful treatment option. Patients with mixed features, comorbid anxiety disorders and higher functional impairment present less favorable outcome. Future research on long-term efficacy of ECT and on clinical predictors of relapse is needed.
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http://dx.doi.org/10.1016/j.jad.2020.03.079DOI Listing
June 2020

Substance Use Disorder in Adult-Attention Deficit Hyperactive Disorder Patients: Patterns of Use and Related Clinical Features.

Int J Environ Res Public Health 2020 05 17;17(10). Epub 2020 May 17.

Association for the Application of Neuroscientific Knowledge to Social Aims (AU-CNS), 55045 Pietrasanta, Lucca, Italy.

Background: While a large amount of medical literature has explored the association between Attention Deficit/Hyperactivity Disorder (ADHD) and Substance Use Disorders (SUDs), less attention has been dedicated to the typologies of SUD and their relationships with ADHD-specific symptomatology and general psychopathology in dual disorder patients.

Methods: We selected 72 patients (aged 18-65) with a concomitant SUD out of 120 adults with ADHD (A-ADHD). Assessment instruments included the Diagnostic Interview for ADHD in adults (DIVA 2.0), Conner's Adult ADHD Rating Scales-Observer (CAARS-O:S): Short Version, the Structured Clinical Interview for Axis I and II Disorders (SCID-I), the Barratt Impulsiveness Scale (BIS-11), the Brief Psychiatric rating scale (BPRS), the Reactivity Intensity Polarity Stability Questionnaire (RIPoSt-40), the World Health Organization Disability Assessment Schedule (WHODAS 2.0) and the Morningness-Eveningness Questionnaire (MEQ). A factorial analysis was performed to group our patients by clusters in different typologies of substance use and correlations between SUDs, as made evident by their typological and diagnostic features; in addition, specific ADHD symptoms, severity of general psychopathology and patients' functionality were assessed.

Results: Two patterns of substance use were identified: the first (type 1) characterized by stimulants/alcohol and the second (type 2) by the use of cannabinoids (THC). Type 1 users were significantly younger and had more legal problems. The two patterns were similar in terms of ADHD-specific symptomatology and its severity at treatment entry. No differences were found regarding the other scales assessed, except for lower scores at MEQ in type 1 users.

Conclusions: At treatment entry, the presence of different comorbid SUD clusters do not affect ADHD-specific symptomatology or severity.
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http://dx.doi.org/10.3390/ijerph17103509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277475PMC
May 2020

Symptom networks in acute depression across bipolar and major depressive disorders: A network analysis on a large, international, observational study.

Eur Neuropsychopharmacol 2020 06 12;35:49-60. Epub 2020 May 12.

Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain.

Major Depressive Episode (MDE) is a transdiagnostic nosographic construct straddling Major Depressive (MDD) and Bipolar Disorder (BD). Prognostic and treatment implications warrant a differentiation between these two disorders. Network analysis is a novel approach that outlines symptoms interactions in psychopathological networks. We investigated the interplay among depressive and mixed symptoms in acutely depressed MDD/BD patients, using a data-driven approach. We analyzed 7 DSM-IV-TR criteria for MDE and 14 researched-based criteria for mixed features (RBDC) in 2758 acutely depressed MDD/BD patients from the BRIDGE-II-Mix study. The global network was described in terms of symptom thresholds and symptom centrality. Symptom endorsement rates were compared across diagnostic subgroups. Subsequently, MDD/BD differences in symptom-network structure were examined using permutation-based network comparison test. Mixed symptoms were the most central and highly interconnected nodes in the network, particularly agitation followed by irritability. Despite mixed symptoms, appetite gain and hypersomnia were significantly more endorsed in BD patients, associations between symptoms were highly correlated across MDD/BD (Spearman's r = 0.96, p<0.001). Network comparison tests showed no significant differences among MDD/BD in network strength, structure, or specific edges, with strong edges correlations (0.66-0.78). Upstream differences in MDD/BD may produce similar symptoms networks downstream during acute depression. Yet, mixed symptoms, appetite gain and hypersomnia are associated to BD rather than MDD. Symptoms during mixed-MDE might aggregate according to 2 different clusters, suggesting a possible stratification within mixed states. Future symptom-based studies should implement clinical, longitudinal, and biological factors, in order to establish tailored therapeutic strategies for acute depression.
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http://dx.doi.org/10.1016/j.euroneuro.2020.03.017DOI Listing
June 2020

Mixed Features in Depression: The Unmet Needs of Diagnostic and Statistical Manual of Mental Disorders Fifth Edition.

Psychiatr Clin North Am 2020 03 28;43(1):59-68. Epub 2019 Nov 28.

Barcelona Bipolar and Depressive Disorders Program, Hospital Clinic, University of Barcelona, Institute of Neuroscience, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, Barcelona, Catalonia 08036, Spain.

The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition introduced the specifier "with mixed features" including 3 or more nonoverlapping typical manic symptoms during a major depressive episode in bipolar disorder type I or II or unipolar major depressive disorder. Excluding overlapping excitatory symptoms, which are frequently observed in mixed depression, leaves many patients with mixed depression undiagnosed. As a consequence, alternative diagnostic criteria have been proposed, claiming for the inclusion in the rubric of mixed features the following symptoms: psychomotor agitation, mood lability, and aggressiveness. A deeper diagnostic reconsideration of mixed features in depression should be provided by the new nosologic classification systems.
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http://dx.doi.org/10.1016/j.psc.2019.10.006DOI Listing
March 2020
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