Prevalence and Correlates of Self-Reported ADHD Symptoms in Bariatric Patients: Focus on Mood and Anxiety Comorbidity, Disordered Eating, and Temperamental Traits.

PURPOSE: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity. A positive association between ADHD and obesity has been observed, especially in adult samples. In this study, prevalence and correlates of self-reported symptoms indicative of a positive screening for ADHD were examined in patients seeking bariatric treatment. MATERIAL AND METHODS: The study sample was composed of 260 adult patients with obesity referred for bariatric surgery to the Obesity Center of the Endocrinology Unit in Pisa University Hospital between January 2006 and November 2016 (BMI ≥ 30 kg/m2; mean ± standard deviation = 46.27 ± 7.45 kg/m2). ADHD symptoms were identified using ADHD Symptom Check-List-90-R Screening Scale. Night-eating, binge-eating/purging behaviors, and temperamental and character traits were assessed in a subsample of 95 patients. RESULTS: Thirty participants had a positive screening for ADHD (11.5%, 95% CI = 7.9-16.1%). Patients with a positive screening showed significantly higher rates of anxiety disorders (40% vs. 16.5%, χ2 = 7.97, p = 0.005) panic disorder (40% vs. 14.3%, χ2 = 10.48, p = 0.001), and a higher severity of psychopathological symptoms and sleep disturbances than those without. In subsample analyses, ADHD symptoms severity was associated with more bulimic behaviors (r = 0.31-0.46), greater harm avoidance (r = 0.45-0.66), less self-directedness (r = - 0.44-0.63), and cooperativeness (r = - 0.26-0.42). CONCLUSION: ADHD symptoms may be common in patients with obesity seeking bariatric treatment and are positively associated with disordered eating, internalizing features, and maladaptive character traits. LEVEL OF EVIDENCE: V, cross sectional descriptive study.

Current nonstimulant medications for adults with attention-deficit/hyperactivity disorder.

INTRODUCTION: Stimulants, including methylphenidate and amphetamines, are the first-line pharmacological treatment of ADHD in adults. However, in patients who do not respond or poorly tolerate stimulants, non-stimulant medications are usually recommended. AREAS COVERED: The authors provide a narrative review of the literature on non-stimulant treatments for adult ADHD, including controlled and observational clinical studies conducted on adult samples. Atomoxetine has been extensively studied and showed significant efficacy in treating adult ADHD. Issues related to dosing, treatment duration, safety, and use in the case of psychiatric comorbidity are summarized. Among other compounds indicated for ADHD in adults, antidepressants sharing at least a noradrenergic or dopaminergic component, including tricyclic compounds, bupropion, and viloxazine, have shown demonstratable efficacy. Evidence is also available for antihypertensives, particularly guanfacine, as well as memantine, metadoxine, and mood stabilizers, while negative findings have emerged for galantamine, antipsychotics, and cannabinoids. EXPERT OPINION: While according to clinical guidelines, atomoxetine may serve as the only second-line option in adults with ADHD, several other nonstimulant compounds may be effectively used in order to personalize treatment based on comorbid conditions and ADHD features. Nevertheless, further research is needed to identify and test more personalized treatment strategies for adults with ADHD.

Pseudodementia in Patients with Unipolar and Bipolar Disorders: A Case Series and Literature Review.

Even though pseudodementia has been historically linked to depression, other psychiatric conditions may cause reversible cognitive alterations. The purpose of this study is to improve our understanding of pseudodementia occurring throughout the entire bipolar spectrum. A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched up to March 2023. Fifteen articles on patients with pseudodementia and bipolar disorder (BD), mania, hypomania, or mixed depression have been included. Moreover, seven female patients with mood disorders diagnosed with pseudodementia have been described. According to our research, pseudodementia in patients with BD mostly occurs during a depressive episode. However, pseudodementia has also been observed in the context of manic and mixed states. Psychomotor and psychotic symptoms were commonly associated. The most typical cognitive impairments were disorientation, inattention, and short-term memory deficits. Alterations in neuroimaging were frequently observed. Electroconvulsive therapy and lithium, either alone or in combination with antipsychotics, resulted in the most widely used therapies. Cognitive decline may occur in a substantial proportion of patients. Since pseudodementia can manifest along the entire mood spectrum, it should be taken into consideration as a possible diagnosis in BD patients showing cognitive deficits during manic, mixed, and depressive states.

The Role of Vortioxetine in the Treatment of Depressive Symptoms in General Hospital Psychiatry: A Case-Series and PRISMA-Compliant Systematic Review of the Literature.

Depressive symptoms are a customary finding in hospitalized patients, particularly those who are undergoing long hospitalizations, underwent major surgical procedures or suffer from high levels of multimorbidity and frailty. The patients included in this case series shared high degrees of frailty-complexity and were evaluated within the ordinary consultation and liaison psychiatry service of the University Hospital in Pisa, Italy, from September 2021 to June 2023. Patients were administered at least one follow-up evaluation after a week and before discharge. To relate this case series to the extant literature, a comprehensive systematic review of vortioxetine safety and efficacy was performed. None of the six patients included developed serious safety issues, but one patient complained of mild-to-moderate nausea for some days after the vortioxetine introduction. Five out of six patients exhibited at least a slight clinical benefit as measured by the clinical global impression scale. Of the 858 entries screened via Scopus and Medline/PubMed, a total of 134 papers were included in our review. The present case series provides preliminary evidence for vortioxetine's safety in this healthcare domain. The literature reviewed in this paper seems to endorse a promising safety profile and a very peculiar efficacy niche for vortioxetine in consultation and liaison psychiatry.

Type 2 diabetes mellitus is associated with manic morbidity in elderly patients with mood disorders.

The association between mood disorders, especially bipolar disorder (BD), and metabolic disorders, is long known. However, to which extent metabolic disorders affect the course of mood disorders in late life is still open to inquiring. To assess the impact of type 2 diabetes mellitus (T2DM) on late-life mood disorders a retrospective chart review was performed. Elderly depressive patients (≥ 65 years) diagnosed with Major Depressive Disorder (N = 57) or BD (N = 43) and followed up for at least 18 months were included and subdivided according to the presence of T2DM comorbidity. Vascular encephalopathy (39.1% vs. 15.6%, P  = 0.021) and neurocognitive disorders (21.7% vs. 5.2%, P  = 0.028), were more frequently reported in patients with T2DM than in those without. Patients with T2DM showed a greater percentage of follow-up time in manic episodes (r = -0.23, P  = 0.020) and a higher rate of manic episode(s) during follow-up (21.7% vs. 5.2%, P  = 0.028) than those without. When restricting longitudinal analyses to patients with bipolar spectrum disorders, results were confirmed. In line with the well-known connection between BD and metabolic disorders, our data support an association between T2DM and unfavorable course of illness in the elderly with BD.

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.

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.

Pharmacological Strategies for Bipolar Disorders in Acute Phases and Chronic Management with a Special Focus on Lithium, Valproic Acid, and Atypical Antipsychotics.

Bipolar disorders (BDs) are a heterogeneous group of severe affective disorders generally described by the alternation of (hypo)manic, depressive, and mixed phases, with euthymic intervals of variable duration. BDs are burdened with high psychiatric and physical comorbidity, increased suicide risk and reduced life expectancy. In addition, BDs can progress into complicated forms (e.g., mixed states, rapid/irregular cycling), which are more difficult to treat and often require personalized pharmacological combinations. Mood stabilizers, particularly Lithium and Valproic acid (VPA), still represent the cornerstones of both acute and chronic pharmacotherapies of BDs. Lithium is the gold standard in BD-I and BDII with typical features, while VPA seems more effective for atypical forms (e.g., mixed-prevalence and rapid-cycling). However, despite appropriate mood stabilization, many patients show residual symptoms, and more than a half recur within 1-2 years, highlighting the need of additional strategies. Among these, the association of atypical antipsychotics (AAPs) with mood stabilizers is recurrent in the treatment of acute phases, but it is also being growingly explored in the maintenance pharmacotherapy. These combinations are clinically more aggressive and often needed in the acute phases, whereas simplifying pharmacotherapies to mood stabilizers only is preferable in the long-term, whenever possible. When mood stabilizers are not enough for maintenance treatment, Quetiapine and, less consistently, Aripiprazole have been proposed as the most advisable adjunctive strategies, for their safety and tolerability profiles. However, in view of the increased risk of serious adverse effects, a careful patient-centered balance between costs and benefits is mandatory.

Triple Diagnosis of Attention-Deficit/Hyperactivity Disorder with Coexisting Bipolar and Alcohol Use Disorders: Clinical Aspects and Pharmacological Treatments.

Attention-Deficit/Hyperactivity Disorder (ADHD), Bipolar Disorder (BD) and Alcohol Use Disorder (AUD) are common medical conditions often coexisting and exerting mutual influence on disease course and pharmacological treatment response. Each disorder, when considered separately, relies on different therapeutic approaches, making it crucial to detect the plausible association between them. Treating solely the emerging condition (e.g., alcoholism) and disregarding the patient's whole psychopathological ground often leads to treatment failure and relapse. Clinical experience and scientific evidence rather show that tailoring treatments for these three conditions considering their co-occurrence as a sole complex disorder yields more fulfilling and durable clinical outcomes. In light of the above considerations, the purpose of the present review is to critically discuss the pharmacological strategies in the personalized treatment of complex conditions defined by ADHD-bipolarityalcoholism coexistence.

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.

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.

Microsurgical anatomy of the amygdaloid body and its connections.

The amygdaloid body is a limbic nuclear complex characterized by connections with the thalamus, the brainstem and the neocortex. The recent advances in functional neurosurgery regarding the treatment of refractory epilepsy and several neuropsychiatric disorders renewed the interest in the study of its functional Neuroanatomy. In this scenario, we felt that a morphological study focused on the amygdaloid body and its connections could improve the understanding of the possible  implications in functional neurosurgery. With this purpose we performed a morfological study using nine formalin-fixed human hemispheres dissected under microscopic magnification by using the fiber dissection technique originally described by Klingler. In our results the  amygdaloid body presents two divergent projection systems named dorsal and ventral amygdalofugal pathways connecting the nuclear complex with the septum and the hypothalamus. Furthermore, the amygdaloid body is connected with the hippocampus through the amygdalo-hippocampal bundle, with the anterolateral temporal cortex through the amygdalo-temporalis fascicle, the anterior commissure and the temporo-pulvinar bundle of Arnold, with the insular cortex through the lateral olfactory stria, with the ambiens gyrus, the para-hippocampal gyrus and the basal forebrain through the cingulum, and with the frontal cortex through the uncinate fascicle. Finally, the amygdaloid body is connected with the brainstem through the medial forebrain bundle. Our description of the topographic anatomy of the amygdaloid body and its connections, hopefully represents a useful tool for clinicians and scientists, both in the scope of application and speculation.

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

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.

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

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.