Phenotypic clustering of bipolar disorder supports stratification by lithium responsiveness over diagnostic subtypes

Introduction: The aim of this study was to determine whether the clinical profiles of bipolar disorder (BD) patients could be differentiated more clearly using the existing classification by diagnostic subtype or by lithium treatment responsiveness. Methods: We included adult patients with BD-I or II (N = 477 across four sites) who were treated with lithium as their principal mood stabilizer for at least 1 year. Treatment responsiveness was defined using the dichotomized Alda score. We performed hierarchical clustering on phenotypes defined by 40 features, covering demographics, clinical course, family history, suicide behaviour, and comorbid conditions. We then measured the amount of information that inferred clusters carried about (A) BD subtype and (B) lithium responsiveness using adjusted mutual information (AMI) scores. Detailed phenotypic profiles across clusters were then evaluated with univariate comparisons. Results: Two clusters were identified (n = 56 and n = 421), which captured significantly more information about lithium responsiveness (AMI range: 0.033 to 0.133) than BD subtype (AMI: 0.004 to 0.011). The smaller cluster had disproportionately more lithium responders (n = 47 [83.8%]) when compared to the larger cluster (103 [24.4%]; p = 0.006). Conclusions: Phenotypes derived from detailed clinical data may carry more information about lithium responsiveness than the current classification of diagnostic subtype. These findings support lithium responsiveness as a valid approach to stratification in clinical samples

Development of a self-report screening instrument for emotional dysregulation: the Reactivity, Intensity, Polarity and Stability questionnaire, screening version (RIPoSt-SV)

Background: Emotional dysregulation (ED) refers to the inability to effectively manage emotional experiences or expressions that hinder appropriate goal-oriented behavior. Moderate impairment on at least two domains among temper control, affective lability, and emotional over-reactivity has been proposed to identify ED in adults with attention-deficit/hyperactivity disorder (ADHD). No screening measure designed for use in diverse psychiatric samples currently exists. Aims: This study aimed to develop a self-report screening tool for ED based on the 40-item version of the Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-40). Criteria for identifying ED were predefined based on the previously suggested approach in adults with ADHD. Methods: 150 adult outpatients were enrolled between February and July 2023 at the Second Psychiatry Unit of Pisa University Hospital. Differences between patients with and without ED were tested. To develop our screening instrument, a decision tree algorithm was trained by hyperparameter tuning through 5-fold cross-validation in 120 subjects and tested on the remaining 30. Results: 75 subjects met criteria for ED (50%). ED was associated with lower age and higher prevalence of psychiatric conditions, including minor mood disorders, ADHD, cannabis use disorders, and eating disorders. We identified a decision tree consisting of six items from RIPoSt-40 that effectively detected ED. The algorithm exhibited accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 80% or higher in both the training and testing sets. Conclusion: The screening version of the Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-SV) demonstrates promise as a valuable tool for ED screening in clinical settings

Neuroanatomical correlates of criminal psychopathy: a person-centered approach

Background: Psychopathy is a personality disorder characterized by core emotional deficits, such as guilt reduction and low empathy, impulsivity and an increased risk for antisocial behaviour. Past research has successfully adopted clustering algorithms to distinguish between different psychopathic traits profiles among offenders. Such a person-centered approach has been suggested as a useful framework to identify specific neurobiological correlates of psychopathy. Methods: We computed seven morphology measures of 31 cortical ROIs per hemisphere, in a sample of 89 Caucasian male offenders, that were subdivided into four clusters using a k-means clustering algorithm based on PCL-R facets scores. Results: No correlation between morphology measures and PCL-R scores reached statistical significance after Bonferroni correction, nor did the comparisons between groups of participants based on the standard cut-offs of PCL-R total score. In contrast, comparisons between clusters produced significant results. Prototypical psychopaths showed a significantly increased left retrosplenial cortex volume, compared with each of the other clusters, but also increased surface area and folding index in the same area and increased folding index in the pars orbitalis of the right inferior frontal gyrus, when compared to antisocial offenders. Conclusions: Our findings support the hypothesis of a neurovelopmental origin of psychopathy and highlight the utility of a person-centered approach to identify its neurobiological correlates

Psychiatric Symptoms in Patients with Cerebral Endometriosis: A Case Report and Literature Review

Endometriosis is a systemic medical condition characterized by endometrial tissue that is abnormally implanted in extrauterine sites, including the central nervous system. In this article, we reported the case of a patient with presumed cerebral endometriosis who was diagnosed with bipolar disorder and panic disorder and systematically reviewed the literature for previously reported neuropsychiatric symptoms in patients with cerebral and cerebellar endometriosis. The PubMed, Scopus, and Web of Science bibliographic databases were searched according to the PRISMA guidelines. Seven previous case reports were found and described. While neurological disturbances dominated the clinical picture in the cases retrieved from the literature, our patient represented the first case to show both neurological and psychiatric manifestations. Atypical features of bipolar disorder including chronic mood instability, mixed episodes, and excitatory interepisodic symptoms were highlighted. During the neuropsychological evaluation, a dysexecutive profile consistent with frontal lobe pathology was evidenced. We hypothesized that the course and features of the illness were largely influenced by the presence of documented brain lesions compatible with endometrial implants, especially in the frontal region. Accordingly, patients with endometriosis who exhibit neurological as well as mental symptoms should be investigated for cerebral lesions

Revisiting stimulant use for emotional dysregulation in attention-deficit/hyperactivity disorder (ADHD)

IntroductionEmotional dysregulation (ED) symptoms are present in a considerable portion of patients with attention-deficit/hyperactivity disorder (ADHD). In recent years, an increasing number of studies investigated the effects of stimulant medications on ED in patients with ADHD.Areas coveredA narrative review of the literature on stimulant treatment for ED is provided, including controlled and observational clinical studies conducted on pediatric and adult samples and neurobiological investigations. Positive effects of stimulants on irritability have been demonstrated in children. Comorbidity with disruptive behavior disorders (DBD) and disruptive mood dysregulation disorder does not prevent stimulant effectiveness. Methylphenidate has also been found to reduce temper problems, affective instability, and emotional over-reactivity in adults with ADHD, although with variable effect sizes. A variety of adverse emotional effects have been reported, especially at high doses and in special populations. However, several possible confounders of treatment-emergent ED have been highlighted. Finally, according to neuroimaging studies, stimulants may mitigate emotional processing anomalies associated with ADHD.Expert opinionThe findings are consistent with models including ED within the core features of ADHD. Stimulant treatment should be prioritized over antipsychotics in ADHD-DBD. It remains to be elucidated whether other medications may be more effective in specific populations with ADHD and/or ED

Risk of conversion to bipolar disorder in patients with late-onset major depression

To evaluate the impact of age at onset on late-life depression course and on risk of conversion to bipolar disorder (BD). A retrospective chart review of 100 elderly patients (age ≥ 65 years) diagnosed with a moderate-to-severe depressive episode and followed up for at least 18 months was conducted. Among patients affected by major depressive disorder ( N = 57), follow-up morbidity differences between those with typical onset depression (TOD) (<60 years) and those with late-onset depression (LOD) (≥60 years) were investigated using Wilcoxon rank-sum test and Cox proportional hazard model. Patients belonging to the LOD group had a significantly lower percentage of follow-up time spent with depressive symptoms compared with patients with TOD ( r = 0.36; P = 0.006), but significantly more time spent with (hypo)manic episodes ( r = -0.31; P = 0.021). Moreover, LOD was significantly associated with a faster conversion to BD (hazard ratio = 3.05; P = 0.037). Depression first emerging in late life may represent an unstable condition with a high risk to convert to BD. Given the potential clinical implications, further studies on the course of LOD are required

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40519-021-01306-1

Bipolar Disorder and Manic-like Symptoms in Alzheimer's, Vascular and Frontotemporal Dementia: A Systematic Review

An increased risk of manic episodes has been reported in patients with neurodegenerative disorders, but the clinical features of bipolar disorder (BD) in different subtypes of dementia have not been thoroughly investigated

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

ObjectivesCerebral 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).MethodsA 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).ResultsOf 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.ConclusionsThe 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.CSVD was found in 19 out of 54 (35.2%) elderly with late-onset BD referred to ECT. Response to ECT was achieved in about two-thirds of patients with late-onset BD. ECT was equally effective in patients with and without CSVD

History of Childhood/Adolescence Referral to Speciality Care or Treatment in Adult Patients with Attention-Deficit/Hyperactivity Disorder: Mutual Relations with Clinical Presentation, Psychiatric Comorbidity and Emotional Dysregulation

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that only rarely remits in adulthood. While several studies underlined differences between child and adult ADHD, the relationship between adult clinical presentation and early referral/treatment has been rarely investigated. In our study, 100 adults with ADHD were recruited and subdivided according to a history of referral to speciality care or treatment with methylphenidate (MPH) during childhood/adolescence. The early referral was associated with a history of disruptive behaviors during childhood/adolescence. Current ADHD symptoms were more pronounced in patients first referred during childhood/adolescence but never treated with MPH. Early MPH treatment was associated with lower rates of mood disorders and lower severity of emotional dysregulation at the time of assessment. Negative emotionality mediated the relationship between MPH treatment and mood disorders comorbidity. ADHD patients first referred during childhood/adolescence are characterized by more externalizing features than those first referred in adulthood. MPH treatment during the developmental age may have a role in preventing mood disorders in patients with ADHD, possibly by reducing emotional dysregulation