Early experience with the new DORA daridorexant in patients with insomnia disorder and comorbid mental disturbances: Results of a naturalistic study with 3 months follow-up.

Insomnia disorder may affect mental health, increasing suicidal risk. Targeting insomnia is crucial in the clinical practice. Sixty-six consecutive patients with insomnia disorder according with the DSM-5-TR criteria were treated with the dual orexin receptor antagonist, daridorexant 50 mg. Baseline (T0), 1 month (T1) and 3 month (T2) evaluations were performed. Insomnia severity (Insomnia Severity Index), mood, anxiety symptoms and suicidal risk (Beck Depression Inventory-II, Young Mania Rating Scale, Self-Reported Anxiety Scale, Suicidal Ideation Scale), dysfunctional insomnia-cognitive factors and pre-sleep arousal (Dysfunctional Beliefs About Sleep, Pre-Sleep Arousal Scale) were evaluated. The final sample included 66 patients (n = 36, 54% females, mean age 60 ± 13.6 years). Most of them, 64%, suffered from insomnia disorder comorbid with unipolar/bipolar depression, anxiety disorders and substance use disorders. Repeated ANOVA analyses showed that Insomnia Severity Index, Dysfunctional Beliefs About Sleep and Pre-Sleep Arousal Scale total score decreased across time (F = 68.818, p < 0.001; F = 47.561, p < 0.001; F = 28.142, p < 0.001, respectively). Similarly, Beck Depression Inventory-II, Self-Reported Anxiety Scale, Young Mania Rating Scale, and Suicidal Ideation Scale significantly decreased over time (p < 0.001). Predictors of insomnia remission (Insomnia Severity Index < 8) at T1 were improvement of Insomnia Severity Index at T1 (F = 60.205, p < 0.001), and improvement of Dysfunctional Beliefs About Sleep at T1 (F = 4.432, p = 0.041). Insomnia remission at T2 was best predicted by improvement of Dysfunctional Beliefs About Sleep at T2 (F = 3.993, p = 0.023). Multiple-regression models showed that clinical improvement of Beck Depression Inventory-II was best predicted by improvement in Dysfunctional Beliefs About Sleep at T1 and T2, manic symptoms by Insomnia Severity Index at T2, anxiety symptoms by Dysfunctional Beliefs About Sleep, Insomnia Severity Index and somatic Pre-Sleep Arousal Scale at T1 and T2. With the caution of a naturalistic design, early experience with daridorexant showed that by targeting insomnia it may be possible to improve not only insomnia symptoms but also comorbid symptoms.

Response to electroconvulsive therapy in elderly patients with late-onset bipolar disorder: The impact of cerebral small vessel disease.

OBJECTIVES: Cerebral Small Vessel Disease (CSVD) is a chronic, progressive vascular disorder that confers increased vulnerability to psychiatric syndromes, including late-life mood disorders. In this study, we investigated the impact of CSVD on electroconvulsive therapy (ECT) outcomes in patients with late-onset bipolar disorder (BD). METHODS: A sample of 54 non-demented elderly patients (≥60 years) with late-onset BD and treatment-resistant major depression, mixed state, or catatonia who underwent bilateral ECT were included in this naturalistic observational study. A diagnosis of CSVD was established based on brain neuroimaging performed before ECT. All patients were evaluated before and after ECT using the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HAM-D), and the Clinical Global Impression scale (CGI). RESULTS: Of the total sample, 19 patients were diagnosed with CSVD (35.2%). No significant differences were observed at baseline between patients with and without CSVD. Overall, a response was obtained in 66%-68.5% of patients, with remission in 56.2%. No significant differences in ECT outcomes were found between those with and without CSVD, and both groups exhibited substantial improvements in symptom severity following ECT. CONCLUSIONS: The outcome of ECT in late-onset BD was not influenced by the presence of CSVD. This finding aligns with previous research on unipolar depression. Accordingly, ECT should be considered for elderly patients with late-onset BD, regardless of the presence of CSVD.

The role of NMDA receptors in bipolar disorder: A systematic review.

OBJECTIVES: Glutamatergic transmission and N-methyl-D-aspartate receptors (NMDARs) have been implicated in the pathophysiology schizophrenic spectrum and major depressive disorders. Less is known about the role of NMDARs in bipolar disorder (BD). The present systematic review aimed to investigate the role of NMDARs in BD, along with its possible neurobiological and clinical implications. METHODS: We performed a computerized literature research on PubMed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, using the following string: (("Bipolar Disorder"[Mesh]) OR (manic-depressive disorder[Mesh]) OR ("BD") OR ("MDD")) AND ((NMDA [Mesh]) OR (N-methyl-D-aspartate) OR (NMDAR[Mesh]) OR (N-methyl-D-aspartate receptor)). RESULTS: Genetic studies yield conflicting results, and the most studied candidate for an association with BD is the GRIN2B gene. Postmortem expression studies (in situ hybridization and autoradiographic and immunological studies) are also contradictory but suggest a reduced activity of NMDARs in the prefrontal, superior temporal cortex, anterior cingulate cortex, and hippocampus. CONCLUSIONS: Glutamatergic transmission and NMDARs do not appear to be primarily involved in the pathophysiology of BD, but they might be linked to the severity and chronicity of the disorder. Disease progression could be associated with a long phase of enhanced glutamatergic transmission, with ensuing excitotoxicity and neuronal damage, resulting into a reduced density of functional NMDARs.

Facts and myths about the use of lithium for bipolar disorder in routine clinical practice: an expert consensus paper.

BACKGROUND: Bipolar disorder is one of the most burdensome severe mental disorders, characterized by high levels of personal and social disability. Patients often need an integrated pharmacological and non-pharmacological approach. Lithium is one of the most effective treatments available not only in psychiatry, but in the whole medicine, and its clinical efficacy is superior to that of other mood stabilizers. However, a declining trend on lithium prescriptions has been observed worldwide in the last 20 years, supporting the notion that lithium is a 'forgotten drug' and highlighting that the majority of patients with bipolar disorder are missing out the best available pharmacological option. Based on such premises, a narrative review has been carried out on the most common "misconceptions" and "stereotypes" associated with lithium treatment; we also provide a list of "good reasons" for using lithium in ordinary clinical practice to overcome those false myths. MAIN TEXT: A narrative search of the available literature has been performed entering the following keywords: "bipolar disorder", "lithium", "myth", "mythology", "pharmacological treatment", and "misunderstanding". The most common false myths have been critically revised and the following statements have been proposed: (1) Lithium should represent the first choice for the treatment of patients with bipolar disorder; (2) lithium treatment is effective in different patients' groups suffering from bipolar disorder; (3) Drug-drug interaction risk can be easily managed during lithium treatment; (4) The optimal management of lithium treatment includes periodical laboratory tests; (5) Slow-release lithium formulation has advantages compared to immediate release formulation; (6) Lithium treatment has antisuicidal properties; (7) Lithium can be carefully managed during pregnancy. CONCLUSIONS: In recent years, a discrepancy between evidence-based recommendations and clinical practice in using lithium treatment for patients with bipolar disorder has been highlighted. It is time to disseminate clear and unbiased information on the clinical efficacy, effectiveness, tolerability and easiness to use of lithium treatment in patients with bipolar disorder. It is necessary to reinvigorate the clinical and academic discussion about the efficacy of lithium, to counteract the decreasing prescription trend of one of the most effective drugs available in the whole medicine.

Eating disorders and emotional dysregulation are associated with insufficient weight loss after bariatric surgery: a 1-year observational follow-up study.

PURPOSE: Subjects with obesity, especially those seeking bariatric surgery, exhibit high rates of mental disorders and marked psychopathological traits. The primary objective of this prospective, non-interventional study was to investigate whether the presence of different psychiatric disorders, attention deficit/hyperactivity disorder (ADHD) symptomatology and emotional dysregulation influenced weight loss at 1-year follow-up after surgery. METHODS: Subjects consecutively referred for pre-surgical evaluation at the Obesity Center of Pisa University Hospital were recruited. Psychiatric diagnoses were made through the Mini-International Neuropsychiatric Interview (MINI) and ADHD symptomatology was assessed with the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS). Emotional dysregulation was investigated through the WRAADDS and self-report questionnaires. After surgery, weight and obesity-related comorbidities were monitored during follow-up. RESULTS: Of the 99 participants recruited, 76 underwent surgery and 65 could be reevaluated 1 year after surgery. Subjects with insufficient weight loss (excess body mass index loss ≤ 53%, n = 15) had more frequent lifetime binge eating disorder (BED) and BED-mood disorders comorbidity than subjects with favorable post-surgical outcome. Additionally, they scored higher on both physician-administered and self-report scales assessing emotional dysregulation, which represents a nuclear symptom of ADHD in adults. At the logistic regression analysis, older age, higher preoperative excess body mass index and greater affective instability were predictors of reduced weight loss at 1-year follow-up. CONCLUSION: Emotional dysregulation seems to be associated with a worse outcome after bariatric surgery. Further studies with larger samples and longer follow-up are needed to confirm the influence of different psychiatric disorders and psychopathological traits on post-surgical outcome. LEVEL OF EVIDENCE: V, prospective descriptive study.

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

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.

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

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.

Prevalence and psychiatric comorbidities of night-eating behavior in obese bariatric patients: preliminary evidence for a connection between night-eating and bipolar spectrum disorders.

PURPOSE: The co-occurrence of obesity, eating and mood disorders has been frequently reported in clinical and epidemiological settings. This study aimed to explore the prevalence of night-eating obese patients referred for bariatric surgery and to identify associated psychopathology and psychiatric comorbidity. METHODS: The sample was composed of 121 obese patients consecutively enrolled between November 2010 and May 2012 during psychiatric evaluations for bariatric intervention. Clinical features and psychiatric diagnoses were collected. Night-eating was investigated through the administration of the Night-eating Questionnaires (NEQ) and was defined as the presence of self-reported evening hyperphagia and/or nocturnal ingestions. Binge-eating and purging behaviors and general psychopathology were respectively assessed using the Bulimic Investigatory Test, Edinburgh and the Symptom Checklist-90-Revised. RESULTS: Night-eating was reported by twenty subjects (16.5%). Patients with night-eating behavior were significantly more frequently diagnosed with bipolar spectrum disorders and with comorbid eating and mood disorders in comparison with other patients. Night-eating patients showed significantly more binging/purging behaviors and greater severity of somatization, obsessive-compulsive symptoms, phobic anxiety, psychoticism and sleep disorders. Patients with bipolar disorder type 1 or 2 scored significantly higher than those without mood disorders at NEQ total score, mood/sleep and nocturnal ingestions subscales, but also scored significantly higher than other patients with mood disorders at the latter subscale. CONCLUSION: Patients with evening hyperphagia and/or nocturnal ingestions should be carefully evaluated to detect possible bipolar spectrum disorders and other eating disorders. Prompt management of these conditions should be provided before bariatric interventions. LEVEL OF EVIDENCE: V, cross-sectional descriptive study.

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

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/m2 (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, χ2 = 41.85, p = 0.000) and eating disorders (OR = 2.17, 95% CI 1.64-2.88, χ2 = 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, padj = 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.

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

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.

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

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 (n = 10) to ECT showed neurological comorbidities, treatments with dopamine agonists and anticholinergic drugs, waxy flexibility, and echophenomena more frequently than respondents (n = 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.

Comparison of Emotional Dysregulation Features in Cyclothymia and Adult ADHD.

Background and Objectives: 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. Materials and Methods: 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. Results: 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. Conclusions: 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.

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

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.

The role of different patterns of psychomotor symptoms in major depressive episode: Pooled analysis of the BRIDGE and BRIDGE-II-MIX cohorts.

BACKGROUND: Psychomotor agitation (PA) or retardation (PR) during major depressive episodes (MDEs) have been associated with depression severity in terms of treatment-resistance and course of illness. OBJECTIVES: We investigated the possible association of psychomotor symptoms (PMSs) during a MDE with clinical features belonging to the bipolar spectrum. METHODS: The initial sample of 7689 MDE patients was divided into three subgroups based on the presence of PR, PA and non-psychomotor symptom (NPS). Univariate comparisons and multivariate logistic regression models were performed between subgroups. RESULTS: A total of 3720 patients presented PR (48%), 1971 showed PA (26%) and 1998 had NPS (26%). In the PR and PA subgroups, the clinical characteristics related to bipolarity, along with the diagnosis of bipolar disorder (BD), were significantly more frequent than in the NPS subgroup. When comparing PA and PR patients, the former presented higher rates of bipolar spectrum features, such as family history of BD (OR = 1.39, CI = 1.20-1.61), manic/hypomanic switches with antidepressants (OR = 1.28, CI = 1.11-1.48), early onset of first MDE (OR = 1.40, CI = 1.26-1.57), atypical (OR = 1.23, CI = 1.07-1.42) and psychotic features (OR = 2.08, CI = 1.78-2.44), treatment with mood-stabilizers (OR = 1.39, CI = 1.24-1.55), as well as a BD diagnosis according to both the DSM-IV criteria and the bipolar specifier criteria. When logistic regression model was performed, the clinical features that significantly differentiated PA from PR were early onset of first MDE, atypical and psychotic features, treatment with mood-stabilizers and a BD diagnosis according to the bipolar specifier criteria. CONCLUSIONS: Psychomotor symptoms could be considered as markers of bipolarity, illness severity, and treatment complexity, particularly if PA is present.

Insomnia symptoms predict emotional dysregulation, impulsivity and suicidality in depressive bipolar II patients with mixed features.

INTRODUCTION: Insomnia symptoms are very common in Bipolar Disorder. Our aim was to assess the potential association between insomnia, emotion dysregulation and suicidality in subjects with Bipolar Disorder. METHODS: Seventy-seven subjects with Bipolar Disorder type II with a depressive episode with mixed features were recruited. Patients were assessed with SCID-DSM-5, the Insomnia Severity Index (ISI), the Difficulties in Emotion Regulation Scale (DERS), the Scale for Suicide Ideation (SSI) while evaluating manic and depressive symptoms. RESULTS: Subjects with insomnia symptoms compared to those without showed higher scores in the DERS scale and subscales, including impulsivity, and in the SSI scale. Insomnia symptoms significantly predicted the severity of depressive symptoms, emotion dysregulation, and suicidality in subjects with bipolar disorder. In particular, insomnia was related to difficulties in some areas of emotion regulation including impulsivity. Emotion dysregulation significantly mediated the association between insomnia and depressive symptoms (Z = 2.9, p = 0.004). Furthermore, emotional impulsivity mediated the association between insomnia symptoms and suicidality (Z = 2.2, p = 0.03). CONCLUSION: In our study, subjects with bipolar disorder suffering from insomnia experienced a greater severity of depressive symptoms and suicidality compared to subjects without insomnia. Insomnia was associated with emotion dysregulation, impulsivity and suicidality. Further research is necessary to investigate if these latter features may benefit from early insomnia treatment in subjects with bipolar disorder.

Towards a psychopathology specific to Substance Use Disorder: Should emotional responses to life events be included?

INTRODUCTION: The severity of emotional responses to life events (PTSD spectrum) as part of Post Traumatic Stress Disorder (PTSD) in Substance Use Disorder (SUD) patients has often been considered from a unitary perspective. Light has also been shed on the possible definition of a specific psychopathology of SUD patients. This psychopathology has been proved to be independent of treatment choice, of being active in using substances, of lifetime psychiatric comorbidity and primary substance of abuse (heroin, alcohol, cocaine). METHODS: To further support this unitary perspective, in this study we have compared the severity and typology of the five psychopathological dimensions found in SUD patients, by dividing 93 HUD patients (77.4% males and 22.6% females), characterized by the lifetime absence of exposure to actual or threatened death, serious injury, or sexual violence, on the basis of the severity of their PTSD spectrum. We used the cut-off that differentiated people developing (High PTSD spectrum; H-PTSD/S) or not developing (Low PTSD spectrum; L-PTSD/S) a PTSD after the earthquake that hit L'Aquila, Italy, in April 2009. RESULTS: Using a canonical correlation analysis, the significant (p<0.001) canonical variate set-one (psychopathology) is saturated negatively by "panic anxiety" and positively by the "worthlessness-being trapped" and "violence-suicide" dimensions. Set-two (PTSD spectrum) is saturated negatively by "emotional, physical and cognitive responses to loss and traumas", and positively by "grief reactions", "re-experiencing numbing", "arousal symptoms" and "personality traits". When comparing the two groups, all five psychopathological dimensions were significantly more severe in H-PTSD/S patients, who were distinguished by higher values of worthlessness-being trapped, sensitivity-psychoticism and violence-suicide symptomatology. No differences were observed regarding the typology of psychopathology. CONCLUSIONS: This study further supports the SUD-PTSD spectrum unitary perspective and argues in favor of the inclusion of the PTSD spectrum in the psychopathology of SUD.

The long-term outcome of patients with heroin use disorder/dual disorder (chronic psychosis) after admission to enhanced methadone maintenance.

BACKGROUND: Over-standard methadone doses are generally needed in the treatment of heroin use disorder (HUD) patients that display concomitant high-severity psychopathological symptomatology. A flexible dosing regimen may lead to higher retention rates in dual disorder (DD), as we demonstrated in bipolar 1 HUD patients, leading to outcomes that are as satisfactory as those of HUD patients without high-severity psychopathological symptomatology. OBJECTIVE: This study aimed to compare the long-term outcomes of treatment-resistant chronic psychosis HUD patients (PSY-HUD) with those of peers without dual disorder (HUD). METHODS: 85 HUD patients who also met the criteria for treatment resistance-25 of them affected by chronic psychosis and 60 without DD-were monitored prospectively for up to 8 years while continuing to receive enhanced methadone maintenance treatment. RESULTS: The rates of endurance in the treatment of PSY-HUD patients were 36%, compared with 34% for HUD patients (p = 0.872). After 3 years of treatment, these rates tended to become progressively more stable. PSY-HUD patients showed better outcome results than HUD patients regarding CGI severity (p < 0.001) and DSM-IV-GAF (p < 0.001). No differences were found regarding good toxicological outcomes or the methadone dosages used to achieve stabilization. The time required to stabilize PSY-HUD patients was shorter (p = 0.034). CONCLUSIONS: An enhanced methadone maintenance treatment seems to be equally effective in patients with PSY-HUD and those with HUD.

Psychopathology of addiction: Can the SCL90-based five-dimensional structure differentiate Heroin Use Disorder from a non-substance-related addictive disorder such as Gambling Disorder?

BACKGROUND: In the Gambling Disorder (GD), there is no exogenous drug administration that acts as the central core of the traditional meaning of addiction. A specific psychopathology of Substance Use Disorders has been proposed recently. In a sample of Heroin Use Disorder (HUD) patients entering opioid agonist treatment, it became possible to identify a group of 5 mutually exclusive psychiatric dimensions: Worthlessness-Being trapped (W-BT), Somatic Symptoms (SS), Sensitivity-Psychoticism (SP), Panic Anxiety (PA) and Violence-Suicide (VS). The specificity of these dimensions was suggested by the absence of their correlations with treatment choice, active substance use, psychiatric comorbidity and the principal substance of abuse and by the opportunity, through their use, of fully discriminating HUD from Major Depression patients and, partially, from obese non-psychiatric patients. To further support this specificity in the present study, we tested the feasibility of discriminating HUD patients from those affected by a non-substance-related addictive behaviour, such as GD. In this way, we also investigated the psychopathological peculiarities of GD patients. METHODS: We compared the severity and frequency of each of the five aspects found by us, in 972 (83.5% males; mean age 30.12 ± 6.6) HUD and 110 (50% males; average age 30.12 ± 6.6) GD patients at univariate (T test; Chi square) and multivariate (discriminant analysis and logistic regression) level. RESULTS: HUD patients showed higher general psychopathology indexes than GD patients. The severity of all five psychopathological dimensions was significantly greater in HUD patients. Discriminant analysis revealed that SS and VS severity were able to discriminate between HUD (higher severity) and GD patients (lower severity), whereas PA and SP could not. W-BT severity was negatively correlated with SS and VS; GD patients were distinguished by low scores for SS and VS low scores associated with high ones for W-BT. Psychopathological subtypes characterized by SS and VS symptomatology were better represented in HUD patients, whereas PA symptomatology was more frequent in GD individuals. No differences were observed regarding the W-BT and SP dimensions. At multivariate level, the one prominent characteristic of HUD patients was the presence of SS (OR = 5.43) as a prominent qualification for psychopathological status. CONCLUSIONS: Apart from the lower severity of all psychopathological dimensions, only the lower frequency of SS typology seems to be the prominent factor in GD patients. The SCL90-defined structure of opioid addiction seems to be useful even in non-substance-related addictive disorders, as in the case of GD patients, further supporting the possible existence of a psychopathology specific to addiction.

Obesity in patients with major depression is related to bipolarity and mixed features: evidence from the BRIDGE-II-Mix study.

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. The present post-hoc analysis evaluated the association between obesity and the presence of mixed features and bipolarity. METHODS: A total of 2811 MDE subjects were enrolled in a multicenter cross-sectional study. In 2744 patients, the body mass index (BMI) was evaluated. Psychiatric symptoms, and sociodemographic and clinical variables were collected, comparing the characteristics of MDE patients with (MDE-OB) and without (MDE-NOB) obesity. RESULTS: Obesity (BMI ≥30) was registered in 493 patients (18%). In the MDE-OB group, 90 patients (20%) fulfilled the DSM-IV-TR criteria for bipolar disease (BD), 225 patients (50%) fulfilled the bipolarity specifier criteria, 59 patients (13%) fulfilled DSM-5 criteria for MDEs with mixed features, and 226 patients (50%) fulfilled Research-Based Diagnostic Criteria for an MDE. Older age, history of (hypo)manic switches during antidepressant treatment, the occurrence of three or more MDEs, atypical depressive features, antipsychotic treatment, female gender, depressive mixed state according to DSM-5 criteria, comorbid eating disorders, and anxiety disorders were significantly associated with the MDE-OB group. Among (hypo)manic symptoms during the current MDE, psychomotor agitation, distractibility, increased energy, and risky behaviors were the variables most frequently associated with MDE-OB group. CONCLUSIONS: In our sample, the presence of obesity in patients with an MDE seemed to be associated with higher rates of bipolar spectrum disorders. These findings suggest that obesity in patients with an MDE could be considered as a possible marker of bipolarity.

Use of Stimulants in Bipolar Disorder.

Several international guidelines indicate stimulants, including methylphenidate (MPH), amphetamines and derivatives, modafinil, and armodafinil among the second-third-line choices for bipolar depression. Efficacy of stimulants has been also reported for the management of residual depressive symptoms such as fatigue and sleepiness and for the management of affective, cognitive, and behavioral symptoms in children and adult bipolar patients with comorbid ADHD. Few case reports show positive results with MPH in the treatment of resistant mania. Finally, MPH might be an option in some bipolar forms observed in psychiatric presentations of frontotemporal dementia and traumatic brain injury. In spite of these preliminary observations, the use of stimulants in bipolar patients is still controversial. Potential of misuse and abuse and mood destabilization with induction of (hypo)manic switches, mixed states, and rapid cycling are the concerns most frequently reported. Our aims are to summarize available literature on this topic and discuss practical management implications.