Thyroid autoimmunity in bipolar disorder: A systematic review

Background Accumulating evidence points to the pathophysiological relevance between immune dysfunction and mood disorders. High rates of thyroid dysfunction have been found in patients with bipolar disorder (BD), compared to the general population. A systematic review of the relationship between BD and thyroid autoimmunity was performed. Methods Pubmed, EMBASE and PsycINFO databases were searched up till January 28th, 2017. This review has been conducted according to the PRISMA statements. Observational studies clearly reporting data among BD patients and the frequency of autoimmune thyroid pathologies were included. Results 11 original studies met inclusion criteria out of 340 titles first returned from the global search. There is evidence of increased prevalence of circulating thyroid autoantibodies in depressed and mixed BD patients, while there is no evidence showing a positive relationship between BD and specific autoimmune thyroid diseases. There is a controversy about the influence of lithium exposure on circulating thyroid autoantibodies, even if most of studies seem not to support this association. A study conducted on bipolar twins suggests that autoimmune thyroiditis is related to the genetic vulnerability to develop BD rather than to the disease process itself. Females are more likely to develop thyroid autoimmunity. Limitations The samples, study design and outcomes were heterogeneous. Conclusion Thyroid autoimmunity has been suggested to be an independent risk factor for bipolar disorder with no clear association with lithium exposure and it might serve as an endophenotype for BD

A systematic review of manic/hypomanic and depressive switches in patients with bipolar disorder in naturalistic settings: The role of antidepressant and antipsychotic drugs

The present systematic review was aimed at critically summarizing the evidence about treatmentemergent manic/hypomanic and depressive switches during the course of bipolar disorder (BD). A systematic search of the MEDLINE, EMBASE, CINAHL, Web of Science, and PsycInfo electronic databases was conducted until March 24th , 2021, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Observational studies clearly reporting data regarding the prevalence of treatment-emergent mood switches in patients with BD were considered for inclusion. Thirty-two original studies met the inclusion criteria. In the majority of cases, manic switches were analyzed; only 3 papers investigated depressive switches in type I BD. Treatment-emergent mania/hypomania in BD subjects ranged from 17.3% to 48.8% and was more frequent with antidepressant monotherapy compared to combination treatment with mood stabilizers, especially lithium, or second-generation antipsychotics. A higher likelihood of mood switch has been reported with tricyclics and a lower rate with bupropion. Depressive switches were detected in 5-16% of type I BD subjects and were associated with first-generation antipsychotic use, the concomitant use of first- and second-generation antipsychotics, and benzodiazepines. The included studies presented considerable methodological heterogeneity, small sample sizes and comparability flaws. In conclusion, many studies, although heterogeneous and partly discordant, have been conducted on manic/hypomanic switches, whereas depressive switches during treatment with antipsychotics are poorly investigated. In BD subjects, both antidepressant and antipsychotic medications seems to play a role in the occurrence of mood switches, although the effects of different pharmacological compounds have yet to be fully investigated

The immunomodulatory effect of lithium as a mechanism of action in bipolar disorder

Bipolar disorder (BD) is a chronic mental disorder characterized by recurrent episodes of mania and depression alternating with periods of euthymia. Although environmental and genetic factors have been described, their pathogenesis is not fully understood. Much evidence suggests a role for inflammatory mediators and immune dysregulation in the development of BD. The first-line treatment in BD are mood-stabilizing agents, one of which is lithium (Li) salts. The Li mechanism of action is not fully understood, but it has been proposed that its robust immunomodulatory properties might be one of the mechanisms responsible for its effectiveness. In this article, the authors present the current knowledge about immune system changes accompanying BD, as well as the immunomodulatory effect of lithium. The results of studies describing connections between immune system changes and lithium effectiveness are often incoherent. Further research is needed to understand the connection between immune system modulation and the therapeutic action of lithium in BD

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

Aggressiveness in depression: a neglected symptom possibly associated with bipolarity and mixed features

OBJECTIVE: To evaluate aggressiveness during a major depressive episode (MDE) and its relationship with bipolar disorder (BD) in a post hoc analysis of the BRIDGE-II-MIX study. METHOD: A total of 2811 individuals were enrolled in this multicenter cross-sectional study. MDE patients with (MDE-A, n = 399) and without aggressiveness (MDE-N, n = 2412) were compared through chi-square test or Student's t-test. A stepwise backward logistic regression model was performed. RESULTS: MDE-A group was more frequently associated with BD (P < 0.001), while aggressiveness was negatively correlated with unipolar depression (P < 0.001). At the logistic regression, aggressiveness was associated with the age at first depressive episode (P < 0.001); the severity of mania (P = 0.03); the diagnosis of BD (P = 0.001); comorbid borderline personality disorder (BPD) (P < 0.001) but not substance abuse (P = 0.63); no current psychiatric treatment (P < 0.001); psychotic symptoms (P = 0.007); the marked social/occupational impairment (P = 0.002). The variable most significantly associated with aggressiveness was the presence of DSM-5 mixed features (P < 0.001, OR = 3.815). After the exclusion of BPD, the variable of lifetime suicide attempts became significant (P = 0.013, OR = 1.405). CONCLUSION: Aggressiveness seems to be significantly associated with bipolar spectrum disorders, independently from BPD and substance abuse. Aggressiveness should be considered as a diagnostic criterion for the mixed features specifier and a target of tailored treatment strategy

The implications of hypersomnia in the context of major depression: Results from a large, international, observational study

According to the DSM-5, 'reduction in the need for sleep' is the only sleep-related criteria for mixed features in depressive episodes. We aimed at studying the prevalence, clinical correlates and the role of hypersomnia in a sample of acutely depressed patients. Secondarily, we factors significantly increasing the odds of hypersomnia were studied. We conducted a post-hoc analysis of the BRIDGE-II-Mix study. Variables were compared between patients with hypersomnia (SLEEP+) and with insomnia (SLEEP-) with standard bivariate tests. A stepwise backward logistic regression model was performed with SLEEP+ as dependent variable. A total of 2514 subjects were dichotomized into SLEEP+ (n = 423, 16.8%) and SLEEP- (n = 2091, 83.2%). SLEEP+ had significant higher rates of obese BMI (p < 0.001), BD diagnosis (p = 0.027), severe BD (p < 0.001), lifetime suicide attempts (p < 0.001), lower age at first depression (p = 0.004) than SLEEP-. Also, SLEEP+ had significantly poorer response to antidepressants (AD) such as (hypo)manic switches, AD resistance, affective lability, or irritability (all 0<0.005). Moreover, SLEEP+ had significantly higher rates of mixed-state specifiers than SLEEP- (all 0 < 0.006). A significant contribution to hypersomnia in our regression model was driven by metabolic-related features, such as 'current bulimia' (OR = 4.21) and 'overweight/obese BMI (OR = 1.42)'. Globally, hypersomnia is associated with poor outcome in acute depression. Hypersomnia is strongly associated with mixed features and bipolarity. Metabolic aspects could influence the expression of hypersomnia, worsening the overall clinical outcome. Along with commonly used screening tools, detection of hypersomnia has potential, costless discriminative validity in the differential diagnosis unipolar and bipolar depression

Trattamento chirurgico del cancro del retto in un centro ad alto volume: analisi di 24 mesi di attività

Il cancro del colon-retto è un patologia tumorale molto frequente a livello mondiale. Mentre dal punto di vista epidemiologico i tumori del colon e del retto non differiscono significativamente, pur essendo il tumore del retto meno frequente, da un punto di vista chirurgico invece il trattamento per il carcinoma rettale è molto più complesso: si hanno difficoltà tecniche maggiori dovute alla sede tumorale, si ha il problema del salvataggio dello sfintere quando le neoplasie sono molto distali, si ha infine il problema delle complicanze locali, non avendo il retto distale e medio un rivestimento peritoneale che ne limiti l’insorgenza. Per questo si enfatizza la necessità di eseguire interventi per carcinoma rettale in strutture ad alto volume, ovvero dove l’esperienza chirurgica è maggiore grazie ad un maggior numero di interventi svolti. Lo scopo di questo studio è valutare la gestione e la qualità del trattamento dei pazienti con cancro rettale che afferiscono ad un'unità chirurgica ad alto volume, ovvero l’U.O. Chirurgia generale colon rettale diretta dal Prof. Buccianti dell’Azienda Ospedaliero Universitaria Pisana. Abbiamo analizzato i dati riguardanti l'intero percorso diagnostico-terapeutico di una serie consecutiva di 105 pazienti, operati per cancro rettale tra il gennaio 2010 e il dicembre 2011. I risultati maggiormente correlati alla qualità del trattamento sono: il tasso di conversione intraoperatoria, il tasso di complicanze post-chirurgiche (soprattutto infezione della ferita chirurgica, deiescenza dell'anastomosi e mortalità) e i risultati oncologici a lungo termine (comparsa di recidive locali e sistemiche). Confrontando i dati ottenuti con quelli riportati in letteratura, possiamo concludere che l'unità operativa in esame ha conseguito ottimi risultati, sia dal punto di visto chirurgico che oncologico. L'ottima gestione dei pazienti riscontrata è da imputare non solo all'alta esperienza chirurgica, ma anche alla presenza di un gruppo oncologico multidisciplinare che affianca l'unità operativa

Recurrency in mood disorders is related to bipolar course: pooled analysis of the BRIDGE and BRIDGE-II-Mix cohorts

Background: Current classifications of mood disorders focus on polarity rather than recurrency, thus separating Bipolar Disorder (BD) from Major Depressive Disorder (MDD). There is though increasing evidence that a course of MDD characterized by high number and frequency of major depressive episodes (MDEs) is related to a bipolar diathesis, regardless the occurrence of hypomanic/manic episodes, with implication for clinical practice. Objective: The aim of the present study is to explore the possible relationships between number and frequency of the depressive episodes and clinical variables associated to bipolarity in a sample of MDD patients. Method: The present study is a post-hoc analysis, based on a pooled cohort of MDD patients resulting from the combination of two international, naturalistic and transversal studies, the BRIDGE and the BRIDGE-II-Mix studies. The final total sample included 7055 patients, divided in 4 groups: patients at first mood episode, patients with 1 previous MDE, patients with 2 or 3 MDEs in the past, patients with at least 4 previous MDEs. Patients in the latter group (n= 2977) were in turn subdivided in patients with 1 or less MDE in the last 365 days (low-frequency) and patients with 2 or more MDEs in the last year (high-frequency). Sociodemographic and clinical variables were compared between groups through Chi-square and Student’s t-test. Two stepwise backward logistic regression model were used to identify the predictive value of clinical features on the presence of high number (≥2) and high frequency (≥2) of depressive recurrences. Results: In comparison with low-recurrency patients (≤ 1 MDE in the past), subjects with greater number and frequency of MDEs showed earlier depressive onset, greater burden of BD family history, more atypical and psychotic features, more suicide attempts, more antidepressant (AD) treatment resistance and more hypomanic/manic switches when treated with ADs. Furthermore, highly recurrent patients were more frequently treated with mood-stabilizers and presented higher rates of bipolarity diagnosis, according to Angst criteria. Similarly, high-frequency patients were more related than low-frequency subjects with a bipolar diathesis in terms of BD family history, briefer duration of current MDE, higher rates of mood switches under AD treatment and greater comorbidity, in particular with alcohol-substance use disorders. Among the above-mentioned bipolar features, logistic regression showed that a previous history of AD-induced mania/hypomania, the prescription of mood-stabilizers and a diagnosis of bipolarity according to Angst criteria were variables associated with both high-recurrency and high-frequency depression. Conclusions: High-recurrency and high-frequency MDD patients differed from those with lower number and frequency of MDEs for several clinical variables usually associated with bipolarity. These results support the need to identify, within the wide and heterogeneous range of MDD patients, a subpopulation of subjects with high recurrence and frequency of the episodes. Even in the absence of hypomanic/manic episodes, these patients seem to be similar to those belonging to bipolar spectrum in terms of clinical features and, perhaps, treatment response. The current diagnostic classification of mood disorders based on the polarity of affective episodes, neglects the importance of recurrency and cyclicity (frequency) which are core features of the disease. Future research focusing on the identification of highly recurrent MDD patients may be relevant for the definition of appropriate treatment strategies

Mood and eating disorders in obese patients referred for bariatric surgery: prevalence rates and impact on post-surgical outcome.

Introduction Obese patients seeking bariatric intervention exhibit high rates of mental disorders and psychopathological traits that could impact weight and mental health outcomes after bariatric surgery. Objectives The first objective of these two studies was to report the lifetime prevalence of mood, eating, and anxiety disorders in two Italian samples of obese patients seeking bariatric surgery. In addition, we aimed to investigate in a prospective and naturalistic setting whether the presence of different psychiatric disorders or certain psychopathological traits were associated with post-surgical outcome. Methods In the first prospective study, clinical data and psychiatric comorbidities of obese bariatric patients (n=99) were collected during the presurgical evaluation by participating psychiatrists. After surgery, weight, obesity-related comorbidities and psychiatric status were monitored during a 1-year follow-up. In the second study, medical records from a different and larger sample of pre-bariatric patients (n=871) were retrieved and reviewed for psychiatric diagnoses and clinical information. Subsequently, patients will be contacted by telephone for a follow-up survey to collect data on post-surgical weight and psychiatric outcomes 5-15 years after surgery. Results The prevalence of psychiatric disorders was 80% in the first and 55% in the second study. Binge eating disorder (BED) was the most frequent single diagnosis in both studies (52% and 28%), followed by mood disorders, especially belonging to the bipolar spectrum (40% and 33%), and panic disorder (37% and 16%). In the first study, 34 patients completed follow-up; of these, 24% showed inadequate weight loss (i.e., excess BMI loss ≤53%) at 1 year. These patients had more frequent lifetime mood disorders (p=0.011) and BED (p=0.044) than subjects with adequate weight loss, and they scored higher on both clinician-administered and self-report scales assessing impulsivity and emotional dysregulation. The latter two psychopathological traits were found to be predictors of reduced weight loss at 1-year after surgery on logistic regression analysis. Conclusion Our study confirms the high rates of psychiatric comorbidities in bariatric patients. After surgery, patients with mood disorders and BED have been shown to exhibit worse weight outcomes than patients without these comorbidities. Furthermore, this is the first study to show an association between the presence of marked impulsivity, emotional dysregulation and inadequate weight loss after bariatric surgery. Future longer follow-up studies with larger samples are urgently needed.

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