ArticleLiterature Review

Substance abuse in patients with bipolar disorder: a systematic review and Meta-analysis

Authors:
  • Danuviusklinik
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Abstract

By considering the debilitating outcome of co-occurring of bipolar disorder (BD) and substance abuse, determination of risk factors of substance use disorders (SUD: abuse or dependence of drugs and/or alcohol) is essential to identify the susceptible patients. The purpose of this study was to clarify the major determinant factors of SUD among adults with BD by reviewing the relevant literature. We systematically searched electronic databases including PubMed (MEDLINE), EMBASE, OVID, Cochrane and Scopus for human studies addressing the co-existence of bipolar disorder and SUD. All potential published papers up to September 2016 have been reviewed. The statistical analysis was performed using Comprehensive Meta-analysis version 2. Male gender (Odds ratio: 2.191 (95% CI: 1.121–4.281), P 0.022), number of manic episodes (P: 0.001) and previous history of suicidality (Odds ratio: 1.758 (95% CI: 1.156–2.674), P: 0.008) were associated to SUD in patients with BD. SUD was not related to age, subtype of BD, hospitalization and co-existence of anxiety disorders or psychotic symptoms. SUD affects many aspects of BD regarding clinical course, psychopathology and prognosis. Our study demonstrates that male gender, history of higher number of manic episodes and suicidality are associated to higher susceptibility to SUD. Thus, assignment of more intensive therapeutic interventions should be considered in patients with increased risk of drug abuse to prevent development of SUD.

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... This is exacerbated by substance use, and several cross-sectional studies (7,(11)(12)(13) have found greater baseline impairment in occupational, relationship and cognitive function in co-morbid BD and SUD patients, both current and with a lifetime history. It is also well-established that co-morbid SUD leads to poorer clinical outcomes including unstable course of illness (1,14,15) decreased quality of life (16) and increased suicide attempts (17). When comparing co-morbid SUD in Schizophrenia, Major Depressive Disorder (MDD) and BD patients, Marquez-Arrico and Adan found BD patients with co-morbid SUD were more likely to be emotionally upset, worried, fearful, lacking self-confidence, and more sensitive to criticism, than patients with Schizophrenia or MDD, and co-morbid SUD (18). ...
... The traditional clinical emphasis on acute symptom reduction in BD has shifted to include longer-term focus on recovery of functioning in everyday life (20). Due to the high-level of functional and mood impairment in co-morbid BD and SUD, substance use-focused therapies have been suggested in this subpopulation (17,21,22). However, there is a paucity in structured trials of psychotherapy in this population and limited evidence regarding the most effective course of treatment. ...
... Previous studies have examined possible risk factors for comorbid BD and SUD which include earlier age of onset, male gender, presence of mixed mania, and family history of SUD (17,23,24). One potential mechanism for the higher rates of SUD in BD is that substance use provides a sense of "control" for patients, which provides stabilization of mood and daily rhythms (25,26). ...
Article
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Objectives: Research suggests that patients with co-morbid bipolar disorder (BD) and substance use disorder (SUD) have a poorer illness course and clinical outcome. The evidence is limited as SUD patients are often excluded from BD studies. In particular, evidence regarding long term outcomes from studies using psychotherapies as an adjunctive treatment is limited. We therefore examined data from two studies of Interpersonal Social Rhythm Therapy (IPSRT) for BD to determine whether lifetime or current SUD affected outcomes. Methods: Data were analyzed from two previous clinical trials of IPSRT for BD patients. Change in scores on the Social Adjustment Scale (SAS) from 0 to 78 weeks and cumulative mood scores from 0 to 78 weeks, measured using the Life Interval Follow-Up Evaluation (LIFE), were analyzed. Results: Of 122 patients (non-SUD n = 67, lifetime SUD but no current n = 43, current SUD n = 12), 79 received IPSRT and 43 received a comparison therapy—specialist supportive care—over 18 months. Lifetime SUD had a significant negative effect on change in SAS score but not LIFE score. There was no effect of current SUD on either change in score. Secondary analysis showed no correlation between symptom count and change in SAS total score or LIFE score. Conclusion: Current SUD has no impact on mood or functional outcomes, however, current SUD numbers were small, limiting conclusions. Lifetime SUD appears to be associated with impaired functional outcomes from psychotherapy. There is limited research on co-morbid BD and SUD patients undergoing psychotherapy.
... The reasons why patients with BD use illicit substances are different, including seeking relief by self-medication, improving psychic status, relieving tension and boredom, escaping from reality, achieving and/or maintaining elevated mood, and increasing energy (27). Furthermore, common genetic (i.e., polymorphism of the aldehyde hydrogenase and alcohol dehydrogenase, or 5HT 2C gene), socioeconomic, and environmental factors (i.e., access and availability of illicit drugs in the community, poverty), stressful events (i.e., trauma, physical, and sexual abuse), temperamental traits (i.e., a sensation of seeking behavior), lifetime suicide attempts, and psychiatric comorbidities (i.e., conduct disorder, cluster B personality disorder, and post-traumatic stress disorder) have been associated with SUD in patients with BD (24,28,29). ...
... The comorbidity between BD and SUD is associated with several detrimental clinical characteristics, such as an earlier onset of illness, greater severity of the disorder, more rapid cycling with a higher risk of switching into (hypo)manic or mixed phases and frequent affective relapses, increased risk of suicide attempts or suicide, and accelerated progression of BD with higher prevalence of negative and cognitive symptomatology. Furthermore, patients affected by BD and SUD are characterized by treatment delay due to possible misdiagnosis, reduced response to lithium and other pharmacological treatments with worsening of adherence, presence of medical comorbidities (hepatitis C, acquired immune deficiency syndrome, and others), increased psychosocial problems, and poorer social support (27,28,30). Finally, illicit substances, particularly cannabis, are considered risk factors for the onset of BD (31,32). ...
... In fact, a detailed characterization of the phenotype of patients with BD and polySUD may help the identification and prevention of risk factors for multidrug abuse. This may in turn improve the clinical course and outcomes of BD and may help the building of a meaningful therapeutic relationship and the choice of the most effective treatments (28). The inclusion criteria consisted of the following: (a) inpatient status; (b) ongoing major depressive or (hypo)manic episode into a primary diagnosis of BD type I and II, according to the DSM-5 criteria (1); (c) 18 years of age or older; and (d) written informed consent to participate in the study. ...
Article
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Introduction Patients with bipolar disorder (BD) often show comorbidity with substance use disorder (SUD) with a negative impact on clinical course, prognosis, and functioning. The role of polysubstance use disorder (polySUD) is understudied. The aim of the present paper is to evaluate the sociodemographic and clinical characteristics associated with BD and comorbid SUD, focusing on polySUD, in order to phenotype this specific group of patients and implement adequate treatment and prevention strategies. Methods A cross-sectional study was conducted involving 556 patients with a primary diagnosis of BD (376 without SUD, 101 with SUD, and 79 with polySUD). A semi-structured interview was administered to collect sociodemographic variables, clinical characteristics, and pharmacological treatment. ANOVA and chi-square tests were used to compare the three groups. Significantly different variables were then inserted in multivariate logistic regression. Results Patients affected by BD and polySUD were younger, and more frequently males and single, than patients with SUD or without SUD. Indeed, the prevalence of patients affected by BD and polySUD living in residential facilities was higher than in the other groups. Moreover, earlier age at onset, higher prevalence of psychotic and residual symptoms, involuntary hospitalization, and a family history of psychiatric disorders were associated with polySUD in patients suffering from BD. Lastly, patients with BD and polySUD were more likely to take four or more medications, particularly benzodiazepines and other drugs. At the multinomial regression, younger age, male gender, early age at onset, psychotic and residual symptoms, positive family history of psychiatric disorders, and use of benzodiazepines remained significantly associated with polySUD in patients with BD. Conclusion Our findings show a specific profile of patients with BD and polySUD. It is important to conduct research on this topic in order to adopt specific therapeutic strategies, minimize the use of polypharmacy, and aim at full remission and mood stabilization.
... Substance use in bipolar disorder may occur due to changes in mood, that is, in the context of a bipolar disorder episode, or more broadly, where habitual use may occur more frequently irrespective of mood. Men living with bipolar disorder are more at risk of abusing substances than women (Messer et al., 2017). ...
... Substance use in bipolar disorder may complicate the diagnosis and treatment of the condition, contributing to a more severe clinical course (Messer et al., 2017). In general, substance use may occur throughout the course of the illness, with a meta-analysis and systematic review finding that substance use was associated with more manic episodes and prior suicide attempts (Messer et al., 2017). ...
... Substance use in bipolar disorder may complicate the diagnosis and treatment of the condition, contributing to a more severe clinical course (Messer et al., 2017). In general, substance use may occur throughout the course of the illness, with a meta-analysis and systematic review finding that substance use was associated with more manic episodes and prior suicide attempts (Messer et al., 2017). ...
Chapter
Bipolar disorder is associated with two phases: mania (or hypomania) and depression. While bipolar disorder I is associated with mania, bipolar disorder II is associated with hypomania, which is a mild form of mania. In this chapter, we discuss topics related to the nature of depression in bipolar I and II disorder. Here, we review studies showing that unlike mania, depression in bipolar disorder is associated with worse occupational functioning. Further, in this chapter, we also discuss studies comparing the similarities and differences between both unipolar and bipolar depression. We also discuss how depression in bipolar disorder is closely associated with co-morbid psychiatric disorders such as anxiety disorders, substance abuse, and eating disorders. We will further discuss treatment plans for depression in bipolar I and II disorder, in comparison to unipolar depression.
... Approximately 50-60% of adults with bipolar disorders have a current, or lifetime, comorbid alcohol use disorder, a substance use disorder, or both. 33 Differentiation of bipolar disorders from alcohol use disorders and substance use disorders is done through patient observation during periods of sobriety (where possible). Clinicians are encouraged to be vigilant of the association between consumption of psychoactive substances and the presence of psychopathology. ...
... 50 About 30-50% of adults with bipolar disorders have either substance use disorder or alcohol use disorder and 25-45% meet the criteria for ADHD. 33,51 Personality disorders (20-40%) and binge eating disorder (10-20%) are also recognised as being common in people with bipolar disorders. 52 Taken together, the high prevalence of, and hazards posed by, psychiatric comorbidity in people with bipolar disorders invites the need for screening people with bipolar disorders for concurrent psychiatric conditions. ...
... 52 Taken together, the high prevalence of, and hazards posed by, psychiatric comorbidity in people with bipolar disorders invites the need for screening people with bipolar disorders for concurrent psychiatric conditions. 33,[50][51][52] The high prevalence of psychiatric comorbidity in bipolar disorders might, in some cases, reflect overlapping pathogenesis. For instance, brain regions implicated in affective instability and cognitive function in bipolar disorders are also implicated in ADHD and anxiety disorders. ...
Article
Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are associated with a loss of approximately 10–20 potential years of life. The mortality gap between populations with bipolar disorders and the general population is principally a result of excess deaths from cardiovascular disease and suicide. Bipolar disorder has a high heritability (approximately 70%). Bipolar disorders share genetic risk alleles with other mental and medical disorders. Bipolar I has a closer genetic association with schizophrenia relative to bipolar II, which has a closer genetic association with major depressive disorder. Although the pathogenesis of bipolar disorders is unknown, implicated processes include disturbances in neuronal-glial plasticity, monoaminergic signalling, inflammatory homoeostasis, cellular metabolic pathways, and mitochondrial function. The high prevalence of childhood maltreatment in people with bipolar disorders and the association between childhood maltreatment and a more complex presentation of bipolar disorder (eg, one including suicidality) highlight the role of adverse environmental exposures on the presentation of bipolar disorders. Although mania defines bipolar I disorder, depressive episodes and symptoms dominate the longitudinal course of, and disproportionately account for morbidity and mortality in, bipolar disorders. Lithium is the gold standard mood-stabilising agent for the treatment of people with bipolar disorders, and has antimanic, antidepressant, and anti-suicide effects. Although antipsychotics are effective in treating mania, few antipsychotics have proven to be effective in bipolar depression. Divalproex and carbamazepine are effective in the treatment of acute mania and lamotrigine is effective at treating and preventing bipolar depression. Antidepressants are widely prescribed for bipolar disorders despite a paucity of compelling evidence for their short-term or long-term efficacy. Moreover, antidepressant prescription in bipolar disorder is associated, in many cases, with mood destabilisation, especially during maintenance treatment. Unfortunately, effective pharmacological treatments for bipolar disorders are not universally available, particularly in low-income and middle-income countries. Targeting medical and psychiatric comorbidity, integrating adjunctive psychosocial treatments, and involving caregivers have been shown to improve health outcomes for people with bipolar disorders. The aim of this Seminar, which is intended mainly for primary care physicians, is to provide an overview of diagnostic, pathogenetic, and treatment considerations in bipolar disorders. Towards the foregoing aim, we review and synthesise evidence on the epidemiology, mechanisms, screening, and treatment of bipolar disorders.
... In this study, using drugs was associated with early onset of the disorder and the prevalence increased over time. Meta-analysis on bipolar disorder have also shown a high comorbidity of more than 40%; however, specific risk factors has remained controversial (2,13,14). Such correlations and controversies around risk factors highlights the importance of addressing the factors associated with substance use in high-risk groups . ...
... In this study, bipolar disorder, substance induced psychotic disorder, and schizophrenia were the most prevalent diagnostic groupings, respectively. We detected a high prevalence of substance use among all patients with psychotic, which is in line with the preceding studies in both clinical and community settings (2,13,14). The most common type of used substance was opioids in all forms. ...
... The rate of alcohol drinking was well below the global epidemiological studies. Worldwide, 25% of patient with schizophrenia (1) and bipolar disorder (13) are prone to develop an alcohol use disorder at some life stage. Alcohol consumption is much less prevalent in Asia (21,22), including Iran (15,23). ...
Article
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Objective: Although comorbidity of psychotic disorders and substance use can lead to increase in mortality, less is known about the outbreak and predictors. Psychotic patients tend to be overlooked during assessment; hence, the possibility of an undertreated or missed condition such as increasing substance use. This investigation aimed to measure the prevalence of substance use in psychotic patients and to survey the powerful predictors. Method: In a 1-year cross-sectional study, 311 psychotic patients were assessed using the Structured Interview Based on DSM-5 for diagnostic confirmation as well as questions surveying prevalence and possible predictors of substance use. Results: Prevalence of substance use among psychotic patients was 37.9%. Several variables were identified as factors associated with drug abuse among the psychotic patients. These included male gender, younger age, being currently homeless, a history of imprisonment, and having family history of drug use. The strongest predictors of substance use, however, were family history of drug use, male gender, and being currently homelessness. Conclusion: Policymakers should note the importance of substance use among psychotic patients. Developing active screening strategies and comprehensive preventive plans, especially in the high-risk population, is suggested.
... To improve clinical relevance and interpretability of SMDs -immune associations, we propose to analyze distinct groups in terms of illness course characteristics not dependent on current clinical state. Severity of illness course is often described quantitatively by number of illness episodes (Coulon et al., 2020;Immonen et al., 2017;Kennedy et al., 2015) together with qualitative markers of comorbid substance use disorder (Kendler et al., 2019;Messer et al., 2017), history of suicidality (Yates et al., 2019), and in bipolar disorders, presence of psychotic episodes (Burton et al., 2018;Keck et al., 2003). A more severe illness course also seems to be related to an earlier age at onset (Cirone et al., 2021;Coulon et al., 2020;Hanssen et al., 2015). ...
... On the basis of the inflammatory model of SMDs, a set of generally stable and abundantly expressed immune markers encompassing novel markers and markers with established link to SMDs, representing pathways of potential pathophysiological relevance, including neuroinflammation, blood-brain barrier (BBB) function, inflammasome activation and immune cell orchestration, were chosen. Commonly used illness course characteristics were analyzed, including number of illness episodes (Häfner, 2019;Luciano et al., 2021;Peters et al., 2016;Provenzani et al., 2021), suicide attempts (Black and Miller, 2015;Yates et al., 2019), comorbid substance use disorder (Kendler et al., 2019;Messer et al., 2017) and for bipolar disorder presence of psychotic features (Burton et al., 2018;Keck et al., 2003). ...
Article
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Background Low-grade inflammation has been implicated in the pathophysiology of severe mental disorders (SMDs) and a link between immune activation and clinical characteristics is suggested. However, few studies have investigated how patterns across immune markers are related to diagnosis and illness course. Methods A total of 948 participants with a diagnosis of schizophrenia (SCZ, N = 602) or bipolar (BD, N = 346) spectrum disorder, and 814 healthy controls (HC) were included. Twenty-five immune markers comprising cell adhesion molecules (CAMs), interleukin (IL)-18-system factors, defensins, chemokines and other markers, related to neuroinflammation, blood-brain barrier (BBB) function, inflammasome activation and immune cell orchestration were analyzed. Eight immune principal component (PC) scores were constructed by PC Analysis (PCA) and applied in general linear models with diagnosis and illness course characteristics. Results Three PC scores were significantly associated with a SCZ and/or BD diagnosis (HC reference), with largest, however small, effect sizes of scores based on CAMs, BBB markers and defensins (p < 0.001, partial η² = 0.02–0.03). Number of psychotic episodes per year in SCZ was associated with a PC score based on IL-18 system markers and the potential neuroprotective cytokine A proliferation-inducing ligand (p = 0.006, partial η² = 0.071). Conclusion Analyses of composite immune markers scores identified specific patterns suggesting CAMs-mediated BBB dysregulation pathways associated with SMDs and interrelated pro-inflammatory and neuronal integrity processes associated with severity of illness course. This suggests a complex pattern of immune pathways involved in SMDs and SCZ illness course.
... Of course the presence of comorbid conditions may have important implications for treatment and prognosis. 35,36 The fact that they have not been recorded at a rate that could be expected may suggest that they have not been elicited and may have important clinical implications and may suggest the need to raise awareness regarding comorbidity among clinicians treating bipolar disorder. ...
... 37 The higher rates of psychoses and hospital admission may also be because men are more likely to have comorbid substance use disorder, which is associated with higher rates of manic psychosis and consequently higher rates of admission. 36 The higher rates of forensic service admissions for men may be reflective of the higher rates of arrest for men with psychotic disorders 38 and criminal activity. 15 The higher rates of substance use disorder treatment in our study is probably reflective of the higher rates of comorbid substance use in men in general and in this sample. ...
Article
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Background Despite evidence of gender differences in bipolar disorder characteristics and comorbidity, there is little research on the differences in treatment and service use between men and women with bipolar disorder. Aims To use routine data to describe specialist mental health service contact for bipolar disorder, including in-patient, community and support service contacts; to compare clinical characteristics and mental health service use between men and women in contact with secondary services for bipolar disorder. Method Cross-sectional analysis of mental health patients with bipolar disorder in New Zealand, based on complete national routine health data. Results A total of 3639 individuals were in contact with specialist mental health services with a current diagnosis of bipolar disorder in 2015. Of these 58% were women and 46% were aged 45 and over. The 1-year prevalence rate of bipolar disorder leading to contact with specialist mental health services was 1.56 (95% CI 1.50–1.63) per 100 000 women and 1.20 (95% CI 1.14–1.26) per 100 000 men. Rates of bipolar disorder leading to service contact were 30% higher in women than men (rate ratio 1.30, 95% CI 1.22–1.39). The majority (68%) had a diagnosis of bipolar I disorder. Women were more likely to receive only out-patient treatment and have comorbid anxiety whereas more men had substance use disorder, were convicted for crimes when unwell, received compulsory treatment orders and received in-patient treatment. Conclusions Although the prevalence of bipolar disorder is equal between men and women in the population, women were more likely to have contact with specialist services for bipolar disorder but had a lower intensity of service interaction.
... Aproximadamente el 70-90 % de las personas con TB cumplen los criterios para el trastorno de ansiedad generalizada, el trastorno de ansiedad social o el trastorno de pánico (Yapici Eser et al., 2018). Alrededor del 30-50 % de los adultos con TB tienen un trastorno por consumo de sustancias o un trastorno por consumo de alcohol, y el 25-45 % cumplen los criterios para el TDAH (Messer et al., 2017;Onyeka et al., 2019). Los trastornos de la personalidad (20-40 %) y el trastorno por atracón (10-20 %) también se reconocen como comunes en las personas con TB (McElroy, et al., 2018). ...
... Aproximadamente un 23,1 % de la muestra forense de este estudio, presentaba comorbilidad relacionada con abuso de sustancias (EJE I). En muestras clínicas, la Guía Clínica sobre Trastorno Bipolar (2012) obtiene hallazgos que coinciden con estudios más recientes, entre el 30 y el 50% de los adultos con TB tienen un trastorno por consumo de sustancias(Messer et al., 2017;Onyeka et al., 2019).Según la Guía de Práctica Clínica sobre Trastorno Bipolar (2012), las tasas de comorbilidad para trastornos del eje II, varían drásticamente dependiendo de qué instrumentos de medida se usen y en qué episodio se encuentren los pacientes con TB. Así, la comorbilidad para trastornos del EJE II puede pasar de un 38 % para los pacientes eutímicos, hasta un 89 % para aquellos en un episodio afectivo agudo. ...
Article
Full-text available
Resumen El trastorno bipolar (TB) es un trastorno crónico con importantes repercusiones funcionales y psicojurídicas. El objetivo del presente estudio es examinar la consideración del TB en el contexto pericial forense español, su asociación con otras patologías y con el tipo criminológico, así como el impacto jurídico en términos de imputabilidad. Se ha realizado un análisis sistemático de la jurisprudencia de los últimos 30 años en España, obteniéndose una muestra de 52 sentencias relevantes del Tribunal Supremo. Los resultados muestran una gran diferencia entre el sexo de los encausados, un 88,5 % hombres frente a un 11,5 % mujeres. Además, un 34,6 % de los encausados mostraba comorbilidad. En el TB se debe tener en cuenta la capacidad de los encausados para tomar conciencia de su trastorno, la gravedad de este, la interferencia que el trastorno ejerce sobre el funcionamiento diario en las diferentes áreas vitales, la afectación en la esfera cognoscitiva y/o volitiva y la intensidad de esta, sobre todo con relación a aspectos como la impulsividad o el fracaso de los frenos inhibitorios. Abstract Bipolar disorder forensic implications in the criminal field thirty years of review Bipolar disorder (BD) is a chronic disorder that has significant functional and psycholegal implications. This study aims to examine the consideration of TB in the Spanish forensic expert context, its association with other pathologies and the criminological type, as well as its legal impact in terms of imputability. A systematic analysis of the jurisprudence over the last 30 years in Spain has been carried out, obtaining a sample of 52 relevant Supreme Court rulings. The results show a notable difference between the gender of the defendants, since 88.5% were men, compared with 11.5% of women. In addition, 34.6% of the defendants showed comorbidity. Regarding TB, the ability of the defendants to be aware of their disorder should be take into account, as well as its severity, the interference that this condition exerts on the person's daily functioning in different areas of life, the affectation of cognitive and/or volitional functions and its intensity, especially concerning to individual factors such as the impulsivity or the failure of inhibitory brakes.
... Substance use induces higher rates of psychiatric crises in vulnerable individuals (Leon et al., 1998). It is also well-known that psychiatric users with a comorbid substance-related disorder are more likely to have poorer social support, lack of therapeutic compliance and worse physical conditions, contributing to the overall complexity of the clinical presentation (Messer et al., 2017;Š prah et al., 2017). The potential interaction between psychoactive drugs and therapeutic psychoactive agents should be also considered (Davis et al., 1995), as it was found to increase therapeutic resistance (Sokolski et al., 1994). ...
Article
The revolving door (RD) phenomenon refers to subjects who undergo frequent rehospitalizations in psychiatric units. The main aim of this study was to analyze clinical factors associated with RD in acute inpatient psychiatric ward. In a 5-year cohort study, subjects hospitalized three or more times in 12 months (revolving door subjects-RDS) were identified. A total of 1,324 subjects were hospitalized. RDS represented 6.3% (n = 84) of the entire sample with a total of 337 RD hospitalizations (revolving door hospitalizations-RDH) (16.7% of all admissions). RDS were younger, unmarried, with comorbid substance related disorders, with mood or psychotic disorders and affected by comorbid medical conditions. After controlling for age, sex and marital status, the most strongly associated variable with RDH was the comorbidity between mood and substance use disorders. Other associated factors were the presence of a comorbid medical condition and a longer length of stay. The commitment to community residential facilities and the treatment with a first generation long-acting antipsychotic were also associated with RDH. On the contrary, admissions to the psychiatric unit for manic/hypomanic episode or for self-directed harmful behavior were inversely associated with RDH. Attention should be given to these clinical variables in order to reduce RD.
... 11 The unmet psychosocial needs in LMICs Studies conducted globally have identified potential mediators and moderators of bipolar disorder treatment outcomes, such as treatment adherence, 12 knowledge about the disorder 13 and sleep hygeine. 14 Moreover, social factors, including stigma and discrimination, 15 stressful life events 16 and substance use, 17 may influence the course and outcome of the disorder. In LMICS, inadequate care for people with bipolar disorder contributes to functional impairment, stigma, discrimination, human rights violence and premature death. ...
Article
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Background Evidence from high- and middle-income countries indicates that psychological interventions (PSIs) can improve the well-being of people with bipolar disorder. However, there is no evidence from low-income countries. Cultural and contextual adaptation is recommended to ensure that PSIs are feasible and acceptable when transferred to new settings, and to maximise effectiveness. Aims To develop a manualised PSI for people with bipolar disorder in rural Ethiopia. Method We used the Medical Research Council framework for the development and evaluation of complex interventions and integrated a participatory theory-of-change (ToC) approach. We conducted a mental health expert workshop ( n = 12), four independent ToC workshops and a final workshop with all participants. The four independent ToC workshops comprised people with bipolar disorder and caregivers ( n = 19), male community leaders ( n = 8), female community leaders ( n = 11) and primary care workers ( n = 21). Results During the workshops, participants collaborated on the development of a ToC roadmap to achieve the shared goal of improved quality of life and reduced family burden for people with bipolar disorder. The developed PSI had five sessions: needs assessment and goal-setting; psychoeducation about bipolar disorder and its causes; treatment; promotion of well-being, including sleep hygiene and problem-solving techniques; and behavioural techniques to reduce anxiety and prevent relapse. Participants suggested that the intervention sessions be linked with patients’ monthly scheduled healthcare follow-ups, to reduce economic barriers to access. Conclusions We developed a contextually appropriate PSI for people with bipolar disorder in rural Ethiopia. This intervention will now be piloted for feasibility and acceptability before its wider implementation.
... Mood symptoms in BD are primarily outcomes of AUD [19]. Also, more severe BD may be a risk factor for alcohol and other substance related disorders, a point that might have an impact on cognition [20]. ...
Article
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The purpose of this study was to explore the association of cognition with hazardous drinking and alcohol-related disorder in persons with bipolar disorder (BD). The study population included 1268 persons from Finland with bipolar disorder. Alcohol use was assessed through hazardous drinking and alcohol-related disorder including alcohol use disorder (AUD). Hazardous drinking was screened with the Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) screening tool. Alcohol-related disorder diagnoses were obtained from the national registrar data. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on A tablet computer: the 5-choice serial reaction time task, or reaction time (RT) test and the Paired Associative Learning (PAL) test. Depressive symptoms were assessed with the Mental Health Inventory with five items (MHI-5). However, no assessment of current manic symptoms was available. Association between RT-test and alcohol use was analyzed with log-linear regression, and eβ with 95% confidence intervals (CI) are reported. PAL first trial memory score was analyzed with linear regression, and β with 95% CI are reported. PAL total errors adjusted was analyzed with logistic regression and odds ratios (OR) with 95% CI are reported. After adjustment of age, education, housing status and depression, hazardous drinking was associated with lower median and less variable RT in females while AUD was associated with a poorer PAL test performance in terms of the total errors adjusted scores in females. Our findings of positive associations between alcohol use and cognition in persons with bipolar disorder are difficult to explain because of the methodological flaw of not being able to separately assess only participants in euthymic phase.
... The rates of comorbidities of BD are also distinct between the sexes: male sex is associated with over two times the risk of alcohol use disorder (8,9), and females have 0.3 times lower substance use disorder compared to males (10). Females in turn are nearly 6 more times likely to have comorbid eating disorders (10,11), and potentially, more than double the risk of anxiety disorders, such as agoraphobia and specific phobias (11). ...
Article
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Bipolar disorder (BD) differs in its clinical presentation in females compared to males. A number of clinical characteristics have been associated with BD in females: more rapid cycling and mixed features; higher number of depressive episodes; and a higher prevalence of BD type II. There is a strong link between BD and risk for postpartum mood episodes, and a substantial percentage of females with BD experience premenstrual mood worsening of varying degrees of severity. Females with premenstrual dysphoric disorder (PMDD)—the most severe form of premenstrual disturbances—comorbid with BD appear to have a more complex course of illness, including increased psychiatric comorbidities, earlier onset of BD, and greater number of mood episodes. Importantly, there may be a link between puberty and the onset of BD in females with comorbid PMDD and BD, marked by a shortened gap between the onset of BD and menarche. In terms of neurobiology, comorbid BD and PMDD may have unique structural and functional neural correlates. Treatment of BD comorbid with PMDD poses challenges, as the first line treatment of PMDD in the general population is selective serotonin reuptake inhibitors, which produce risk of treatment-emergent manic symptoms. Here, we review current literature concerning the clinical presentation, illness burden, and unique neurobiology of BD comorbid with PMDD. We additionally discuss obstacles faced in symptom tracking, and management of these comorbid disorders.
... Substance use disorders (SUDs) are one of the most common psychiatric comorbidities seen in patients diagnosed with bipolar disorder (BD). It has been reported that more than half of US patients with BD had at least 1 SUD (1). The data from large-sample epidemiological studies has indicated that the risk of a SUD among patients with BD is higher than that of the general population. ...
... BD is highly comorbid with addictions [52], Bipolar disorders are highly associated with alcohol use disorder [53], and generally, substance abuse is a major comorbidity in BD [54]. Lack of these two comorbidities was acknowledged in this study. ...
Article
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Social cognition might be impaired in first degree relatives (FDR) of BD but existing research shows controversial results about social cognitive impairments in this population. The aim of this study was to assess Theory of Mind (ToM) and nonverbal sensitivity in FDR of BD and compare the results with those of two groups of persons with remitted bipolar disorder (BD), type I and II, and a control group. Social cognitive ability was examined in first degree relatives of BD, with a biological parent, offspring or sibling diagnosed with the disorder. For this study, 37 FDRs of bipolar patients, 37 BD I, 40 BD II and 40 control participants were recruited. Social cognition was explored by means of the Reading the Mind in the Eyes Test and the MiniPONS. Results showed a significant impairment in FDR of BD in the ToM task, but not in nonverbal sensitivity. Performance of FDRs in social cognition is better than that of BDs (either type I or type II) but worse when compared with that of healthy individuals without a family history of psychiatric disorders. Nevertheless, no differences were found between BD I and BD II groups. Males and older participants showed a worse performance in all groups. Group family therapy with FDRs of BD might include training in the recognition of nonverbal cues, which might increase the understanding of their familiars with BD, in order to modify communication abilities.
... In this case, surely the duration of the episode is not to be attributed only to the severity of the condition of abuse but also to the presence of the patient's previous psychiatric disorder. In fact, the previous diagnosis of bipolar disorder may have affected both the emotional instability, which pushed the patient toward the abuse of phenibut, and the severity of the consequent psychopathological picture (10). Moreover, in this patient, it seems that the abuse was not determined by a sensation-seeking modality but by the inability to manage feelings of emptiness and fear due to the COVID-19 pandemic emergency that recently occurred in northern Italy (11,12). ...
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Background and Objectives: Phenibut (4-amino-3-phenyl-butyric acid), acting as a GABA-B receptor agonist, has a beneficial effect on anxiety. Although its medical use is not approved in western countries, it can be easily obtained worldwide via the Internet, so it spread as a substance of abuse. In recent years, some case reports have, therefore, highlighted episodes of acute toxicity or withdrawal, but it is still a largely unknown phenomenon. Methods: In this case report, a 50-year-old woman was admitted to the emergency room with psychomotor agitation, psychotic symptoms, and insomnia, and was non-responsive to treatment. She was hospitalized at the psychiatry ward for 25 days and gave her consent for the publication of the present case report. Results: The suspicion of phenibut withdrawal allowed to establish the appropriate management, leading to the restitutio ad integrum of the psychopathological case. Conclusions: In the face of an incoercible psychomotor agitation case, the knowledge of the so-called novel psychoactive substances allows for more appropriate clinical management of intoxication and withdrawal syndromes. This is a scientifically significant report as it provides therapeutic and outcome data concerning a syndrome that is still quite unfamiliar.
... The family does not know how to deal with the patient. Patients with bipolar disorder have a higher prevalence of substance abuse (24,25). They also may attempt or commit suicide (26). ...
... Substance misuse, especially of cannabis but also of alcohol, is associated with more severe clinical characteristics in BD including earlier onset of the disorder, increased suicide risk and increased rates of rapid cycling (3,7,8). As these associations have mainly been established in cross-sectional studies, the current understanding of the direction of the relationship between substance misuse and BD illness severity is limited. ...
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Substance misuse is highly prevalent in bipolar disorder even in the early illness phases. However, the trajectories of misuse of different substances after treatment initiation is not well-studied. Also, knowledge on how substance misuse trajectories influence the early course of bipolar disorder is limited. We recruited 220 individuals in first treatment of bipolar disorder of which 112 participated in a 1-year follow-up study at the NORMENT center in Oslo, Norway. Misuse was defined as having scores above cut-off for harmful use on the Alcohol or Drug Use Disorders Identification Tests (AUDIT or DUDIT). We investigated rates of stopping and continuing misuse of alcohol, cannabis and other illicit substances and daily nicotine use over the follow-up period, and whether such misuse trajectories predicted the risk for affective relapse. The prevalence of cannabis misuse was reduced from 29 to 15% and alcohol misuse was reduced from 39 to 21% during follow-up. Continuing alcohol misuse significantly and independently predicted affective relapse, whereas there was no difference in relapse risk between individuals stopping alcohol misuse and never misusing alcohol. Cannabis misuse trajectories did not significantly predict relapse risk although we cannot exclude interactions with alcohol misuse. In conclusion, substance misuse decreased in the early phase of bipolar disorder treatment but should be further reduced with interventions specifically addressing substance misuse. Stopping alcohol misuse is likely to yield substantial benefit on the clinical course of bipolar disorder.
... Bipolar disorder (BD) is a widespread and severe psychiatric condition associated with reduced psychosocial functioning and a loss of life expectancy of about 10-20 years with respect to healthy general population, particularly due to suicide and cardiovascular diseases [1]. Different factors were identified as predictors of chronic course and poor outcome in BD, including among others delayed treatment [2], lifetime presence of psychotic symptoms [3,4], rapid cycling [5][6][7], concomitant substance misuse [8], and psychiatric/ medical comorbidity such as borderline personality disorder [9], obesity [10] or diabetes [11]. The identification of clinical predictors of illness severity allowed to a better management of BD, and to develop targeted prevention strategies [12]. ...
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The purpose of the present study was to detect demographic and clinical factors associated with lifetime suicide attempts in Bipolar Disorder (BD). A total of 1673 bipolar patients from different psychiatric departments were compared according to the lifetime presence of suicide attempts on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (presence of suicide attempts) at the univariate analyses, preliminary multiple logistic regression analyses were realized. A final multivariable logistic regression was then performed, considering the presence of lifetime suicide attempts as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. The final multivariable logistic regression analysis showed that an earlier age at first contact with psychiatric services (odds ratio [OR] = 0.97, p < 0.01), the presence of psychotic symptoms (OR = 1.56, p < 0.01) or hospitalizations (OR = 1.73, p < 0.01) in the last year, the attribution of symptoms to a psychiatric disorder (no versus yes: OR = 0.71, partly versus yes OR = 0.60, p < 0.01), and the administration of psychoeducation in the last year (OR = 1.49, p < 0.01) were all factors associated with lifetime suicide attempts in patients affected by BD. In addition, female patients resulted to have an increased association with life-long suicidal behavior compared to males (OR: 1.02, p < 0.01). Several clinical factors showed complex associations with lifetime suicide attempts in bipolar patients. These patients, therefore, require strict clinical monitoring for their predisposition to a less symptom stabilization. Future research will have to investigate the best management strategies to improve the prognosis of bipolar subjects presenting suicidal behavior.
... In fact, the prevalence of ASPD can be up to five times higher (4.1%) [36] and appears to be more frequently identified in BD I than BD II [37]. ASPD and BD are both characterized by impulsive behaviors [38,39] and substance use disorder [40][41][42] that frequently lead to trouble with the law [43,44] and suicidal behavior [45,46]. Studies suggested that impulsivity and the frequent abuse of drugs, especially alcohol, cannabis and amphetamines, is associated with sensation seeking and a lack of premeditation in ASPD and that when ASPD is co-morbid with BD it is associated with significant deficits in the ability to delay reward [47][48][49] and greater gray matter volume in the mesolimbic reward system [50]. ...
Article
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Background and Objectives: Bipolar Disorder (BD) is a severe psychiatric disorder that worsens quality of life and functional impairment. Personality disorders (PDs), in particular Cluster B personality, have a high incidence among BD patients and is considered a poor prognostic factor. The study of this co-morbidity represents an important clinical and diagnostic challenge in psychiatry. Particularly, clinical overlap has been shown between antisocial personality disorder (ASPD) and BD that could worsen the course of both disorders. We aimed to detect the frequency of ASPD in bipolar patients with greater accuracy and the impact of ASPD on the clinical course of BD. Materials and Methods: A systematic literature search was conducted in PubMed, Embase, MEDLINE and the Cochrane Library through December 2020 without language or time restriction, according to PRISMA statement guidelines. Results: Initially, 3203 items were identified. After duplicates or irrelevant paper deletion, 17 studies met the inclusion criteria and were included in this review. ASPD was more frequent among BD patients, especially in BD type I. BD patients with ASPD as a comorbidity seemed to have early onset, higher number and more severe affective episodes, higher levels of aggressive and impulsive behaviors, suicidality and poor clinical outcome. ASPD symptoms in BD seem to be associated with a frequent comorbidity with addictive disorders (cocaine and alcohol) and criminal behaviors, probably due to a shared impulsivity core feature. Conclusions: Considering the shared symptoms such as impulsive and dangerous behaviors, in patients with only one disease, misdiagnosis is a common phenomenon due to the overlapping symptoms of ASPD and BD. It may be useful to recognize the co-occurrence of the disorders and better characterize the patient with ASPD and BD evaluating all dysfunctional aspects and their influence on core symptoms.
... often associated with prominent social dysfunction (Kjaerstad et al., 2019), cognitive impairment (Buoli, Caldiroli, Caletti, Zugno, & Altamura, 2014) and disability (Grande, Berk, Birmaher, & Vieta, 2016). Different factors have been associated with poor prognosis in BD including: duration of illness Melloni et al., 2019), lifetime presence of psychotic symptoms (Ahn et al., 2017;Altamura et al., 2019), rapid-cycling 2019; Perlis et al., 2010), prevalent manic polarity (Belizario, Silva, & Lafer, 2018), concomitant substance abuse (Messer, Lammers, Müller-Siecheneder, Schmidt, & Latifi, 2017), lack of treatment compliance (Fuentes, Rizo-Méndez, & Jarne-Esparcia, 2016) and psychiatric/medical comorbidity (Forty et al., 2014;Passos et al., 2016). ...
Article
Aim The aim of the present study was to detect factors associated with duration of untreated illness (DUI) in bipolar disorder (BD). Method A total of 1575 patients were selected for the purposes of the study. Correlation analyses were performed to analyse the relation between DUI and quantitative variables. The length of DUI was compared between groups defined by qualitative variables through one‐way analyses of variance or Kruskal‐Wallis's tests according to the distribution of the variable. Linear multivariable regressions were used to find the most parsimonious set of variables independently associated with DUI: to this aim, qualitative variables were inserted with the numeric code of their classes by assuming a proportional effect moving from one class to another. Results An inverse significant correlation between length of DUI and time between visits in euthymic patients was observed (r = −.52, P < .001). DUI resulted to be longer in patients with: at least one lifetime marriage/partnership (P = .009), a first psychiatric diagnosis of major depressive disorder or substance abuse (P < .001), a depressive polarity of first episode (P < .001), no lifetime psychotic symptoms (P < .001), BD type 2 (P < .001), more lifetime depressive/hypomanic episodes (P < .001), less lifetime manic episodes (P < .001), presence of suicide attempts (P = .004), depressive episodes (P < .001), hypomanic episodes (P = .004), hospitalizations (P = .011) in the last year. Conclusions Different factors resulted to increase the length of DUI in a nationwide sample of bipolar patients. In addition, the DUI was found to show a negative long‐term effect in terms of more suicidal behaviour, more probability of hospitalization and depressive/hypomanic episodes.
... For example, several meta-analyses report the lifetime rates of different psychiatric disorders in BD populations and some explore comorbidities in those at high risk of developing BD in the future (e.g., Lau et al. 2018;Pavlova et al. 2015;Messer et al. 2017). Whilst these confirm high rates of mood and non-mood disorders, the sequence of onset of the different comorbidities has only been examined consistently in prospective studies of offspring of parents with BD (e.g., Duffy et al. 2019;Mesman et al. 2013;Hafeman et al. 2017). ...
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Background Major contributors to the global burden of bipolar disorders (BD) are the early age at onset (AAO) and the co-occurrence of non-mood disorders before and after the onset of BD. Using data from two independent cohorts from Europe and the USA, we investigated whether the trajectories of BD-I onset and patterns of psychiatric comorbidities differed in (a) individuals with or without a family history (FH) of BD, or (b) probands and parents who both had BD-I. Methods First, we estimated cumulative probabilities and AAO of comorbid mental disorders in familial and non-familial cases of BD-I (Europe, n = 573), and sex-matched proband-parent pairs of BD-I cases (USA, n = 194). Then we used time to onset analyses to compare overall AAO of BD-I and AAO according to onset polarity. Next, we examined associations between AAO and polarity of onset of BD-I according to individual experiences of comorbidities. This included analysis of the density of antecedent events (defined as the number of antecedent comorbidities per year of exposure to mental illness per individual) and time trend analysis of trajectory paths plotted for the subgroups included in each cohort (using R² goodness of fit analysis). Results Earlier AAO of BD-I was found in FH versus non-FH cases (log rank test = 7.63; p = 0.006) and in probands versus parents with BD-I (log rank test = 15.31; p = 0.001). In the European cohort, AAO of BD-I was significantly associated with factors such as: FH of BD (hazard ratio [HR]: 0.60), earlier AAO of first non-mood disorder (HR: 0.93) and greater number of comorbidities (HR: 0.74). In the USA cohort, probands with BD-I had an earlier AAO for depressive and manic episodes and AAO was also associated with e.g., number of comorbidities (HR: 0.65) and year of birth (HR: 2.44). Trajectory path analysis indicated significant differences in density of antecedents between subgroups within each cohort. However, the time trend R² analysis was significantly different for the European cohort only. Conclusions Estimating density of antecedent events and comparing trajectory plots for different BD subgroups are informative adjuncts to established statistical approaches and may offer additional insights that enhance understanding of the evolution of BD-I.
... A high rate of psychiatric comorbidity observed in the LAI-BPN cohort is a notable finding, particularly when considering the well-known association of dual diagnosis with poorer health outcomes. [11][12][13] It is recommended that this is considered in the development of individualised, patientcentred treatment plans, as well as in-service planning. ...
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Objective: Long-acting injectable buprenorphine (LAI-BPN) was introduced in recent years as a novel treatment for opioid use disorder. Despite growing evidence-base of its effectiveness, there is limited research on the relationship between this treatment and patient characteristics. Methods: This descriptive, retrospective cohort study compared sociodemographic and clinical variables between patients treated with SL-BPN and those treated with LAI-BPN at a large metropolitan health service in Queensland, Australia. Results: Patients that transitioned to LAI-BPN were more likely to be single, have a comorbid mental illness, untreated hepatitis C infection and longer duration of unsanctioned opioid use. Patients continuing treatment with SL-BPN were more likely to fail to attend appointments and have urine drug screen results positive for gabapentinoids. Conclusions: The results of this study contribute to currently limited literature on this novel treatment option in an Australian context, highlighting factors which may influence patient and prescriber treatment choices. Clinicians may be more inclined to prescribe LAI-BPN to patients with higher psychosocial comorbidity to facilitate engagement in treatment.
... Substance use is increased in BD patients compared to the general population, with the current prevalence of comorbid substance use disorders in BD being as high as 61% in BD type I 46 . In addition, a meta-analysis revealed that increased substance abuse is correlated with a higher number of manic episodes in BD patients (Messer et al., 2017). Of note, there is evidence that drugs of abuse are associated with significant disrupting effects on the BBB, impacting BMECs and many aspects of the NVU (Sajja et al., 2016). ...
Article
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Bipolar disorder (BD) is a severe psychiatric disorder affecting approximately 1–3% of the population and characterized by a chronic and recurrent course of debilitating symptoms. An increasing focus has been directed to discover and explain the function of Blood-Brain Barrier (BBB) integrity and its association with a number of psychiatric disorders; however, there has been limited research in the role of BBB integrity in BD. Multiple pathways may play crucial roles in modulating BBB integrity in BD, such as inflammation, insulin resistance, and alterations of neuronal plasticity. In turn, BBB impairment is hypothesized to have a significant clinical impact in BD patients. Based on the high prevalence of medical and psychiatric comorbidities in BD and a growing body of evidence linking inflammatory and neuroinflammatory mechanisms to the disorder, recent studies have suggested that BBB dysfunction may play a key role in BD's pathophysiology. In this comprehensive narrative review, we aim to discuss studies investigating biological markers of BBB in patients with BD, mechanisms that modulate BBB integrity, their clinical implications on patients, and key targets for future development of novel therapies.
... Comorbidity with other psychiatric disorders is seen in over 50% of patients with BD, particularly with anxiety, attention-deficit/hyperactivity and substance use disorders (2). The presence of comorbid diagnoses in BD is associated with poorer treatment response and a more severe illness course; patients with these diagnoses often require more intensive or complex treatment regimens (3)(4)(5)(6). ...
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Dissociative disorders are an important group of trauma-related disorders associated with significant disability. The co-occurrence of dissociative disorders (DD) and symptoms (DS) in bipolar disorder has been relatively understudied, but there is some evidence that this comorbidity may have significant mechanistic and clinical implications. This paper presents the results of a scoping review of the frequency and correlates of DS and DD in bipolar disorder. Based on the available evidence, DS/DD are more common in bipolar disorder than in healthy controls or in unipolar depression, are related to childhood trauma, and are associated with psychotic symptoms, suicide attempts, and a poorer response to treatment in patients with bipolar disorder. The implications of these findings, and possible mechanistic pathways underlying them, are discussed based on the current literature. Clinicians should be aware of the frequent occurrence of significant DS or DD when treating patients with bipolar disorder. A tentative future research agenda for this field, based on clinical, risk factor-related and neurobiological considerations, is outlined.
... Cariprazine also demonstrated anti-abuse potential by reducing the rewarding effect of cocaine in rats (20). Since BD is frequently linked to substance use disorders (21), this finding warrants further investigation in clinical trials. Animal models have suggested a role of D3 receptors in mood regulation, and that partial agonism at D3 receptors may have antidepressant effects (22). ...
Article
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Bipolar disorder (BD) is chronic psychiatric disorder associated with significant impairment in psychosocial functioning and quality of life. Although current pharmacological treatments for BD have improved its clinical management, many patients do not achieve remission, particularly those suffering from bipolar depression. In addition, available treatments are associated with a myriad of potential adverse effects, which highlights the need for novel therapeutic agents that can be effective for both phases of the illness with a reduced side effect burden. Cariprazine is a novel antipsychotic that is a dopamine D2/D3 partial agonist with a preference for D3 receptors. In this review, we examine the pharmacological properties, clinical efficacy and tolerability profile of cariprazine in patients with BD, taking into account the latest clinical trials data. We also review post hoc analyses addressing clinically relevant subgroups and symptom domains in BD. Current evidence suggests efficacy for cariprazine 3–12 mg/day in the treatment of acute manic and mixed episodes; for bipolar depression, the efficacy of cariprazine appears to be dose-related, with doses of 1.5–3 mg/day beneficial as monotherapy. Cariprazine is overall well-tolerated by patients in both manic and depressive episodes. Its most common side effects relative to placebo include akathisia, extrapyramidal symptoms and nausea. There are no metabolic concerns reported with cariprazine use. In summary, the latest evidence suggests that cariprazine is an effective and safe treatment option for BD.
... Finally, the perpetuation of a SUD results from an interplay between positive rewarding effects (pleasure, relaxation, euphoria) and negative aversive effects that the affected individual will try to avoid (withdrawal symptoms, negative emotions). AUD has well-described harmful effects on the course of BD with an earlier onset of mood episodes [5], prolonged recovery after mood episodes, more frequent mood switches including development of rapid cycling, increased episodes of mixed states, higher severity of depression and more frequently suicidal ideation [20][21][22][23][24]. The UK Bipolar Disorder Research Network, (BDRN) reported that among their almost 1900 participants with BD odds of increasing levels of alcohol consumption were significantly associated with a history of suicide attempts [24]. ...
Article
Introduction: Comorbidity of bipolar disorder (BD) and alcohol use disorder (AUD) is very frequent resulting in detrimental outcomes, including increased mortality. Diagnosis of AUD in BD and vice versa is often delayed as symptoms of one disorder mimic and obscure the other one. Evidence for pharmacotherapies for people with comorbid BD and AUD remains limited, and further proof-of-concept studies are urgently needed. Areas covered: This paper explores the currently available pharmacotherapies for AUD, BD and their usefulness for comorbid BD and AUD. It also covers to some degree the epidemiology, diagnosis, and potential common neurobiological traits of comorbid BD and AUD. Expert opinion: The authors conclude that more controlled studies are needed before evidence-based guidance can be drawn up for clinician's use. Since there are no relevant pharmacological interactions, approved medications for AUD can also be used safely in BD. For mood stabilization, lithium should be considered first in adherent persons with BD and comorbid AUD. Alternatives include valproate, lamotrigine and some atypical antipsychotics, with partial D2/D3 receptor agonism possibly being beneficial in AUD, too.
... Further, fragmented profiles of activity as measured by RA and rest duration, were shown to be associated with higher systolic blood pressure (92) and increased alcohol consumption (85). Thus, disrupted daytime activity levels could be indicators of risk for worsening outcomes not only of BD but also the wellestablished links with cardiovascular disease (101) and substance use disorders (102). These associations with comorbid conditions warrant further investigation through longitudinal studies. ...
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Background Disruptions in rest and activity patterns are core features of bipolar disorder (BD). However, previous methods have been limited in fully characterizing the patterns. There is still a need to capture dysfunction in daily activity as well as rest patterns in order to more holistically understand the nature of 24-h rhythms in BD. Recent developments in the standardization, processing, and analyses of wearable digital actigraphy devices are advancing longitudinal investigation of rest-activity patterns in real time. The current systematic review aimed to summarize the literature on actigraphy measures of rest-activity patterns in BD to inform the future use of this technology. Methods A comprehensive systematic review using PRISMA guidelines was conducted through PubMed, MEDLINE, PsycINFO, and EMBASE databases, for papers published up to February 2021. Relevant articles utilizing actigraphy measures were extracted and summarized. These papers contributed to three research areas addressed, pertaining to the nature of rest-activity patterns in BD, and the effects of therapeutic interventions on these patterns. Results Seventy articles were included. BD was associated with longer sleep onset latency and duration, particularly during depressive episodes and with predictive value for worsening of future manic symptoms. Lower overall daily activity was also associated with BD, especially during depressive episodes, while more variable activity patterns within a day were seen in mania. A small number of studies linked these disruptions with differential patterns of brain functioning and cognitive impairments, as well as more adverse outcomes including increased suicide risk. The stabilizing effect of therapeutic options, including pharmacotherapies and chronotherapies, on activity patterns was supported. Conclusion The use of actigraphy provides valuable information about rest-activity patterns in BD. Although results suggest that variability in rhythms over time may be a specific feature of BD, definitive conclusions are limited by the small number of studies assessing longitudinal changes over days. Thus, there is an urgent need to extend this work to examine patterns of rhythmicity and regularity in BD. Actigraphy research holds great promise to identify a much-needed specific phenotypic marker for BD that will aid in the development of improved detection, treatment, and prevention options.
... Other clinical features that could identify a subgroup of patients with higher severity of the clinical presentation appeared to be more prevalent in the SUD-BD population, confirming that this comorbidity may underpin worse illness course and poor prognosis (Zamora-Rodríguez, 2018). Particularly, SUD was linked to the development of suicidal behaviors, as already detected by previous studies (Gordon-Smith et al., 2020;Icick et al., 2019;Messer et al., 2017;Oquendo et al., 2010;Østergaard et al., 2017). Due to the burden that suicidality exerts in BD, identifying modifiable risk factors that may predict the occurrence of such behaviors represents a crucial unmet need for this population. ...
Article
Background Substance use disorders (SUD) in bipolar disorders (BD) present relevant impact on psychopathological features and illness course. The present study was aimed at analyzing the clinical correlates of this comorbidity. Methods In- and outpatients suffering from BD were recruited. Socio-demographic and clinical characteristics were collected. Subjects underwent a psychopathological assessment evaluating affective temperaments and impulsiveness. The appraisal of treatment response to mood stabilizers was conducted with the Alda Scale. Bivariate analyses were used to compare subjects suffering from BD with (SUD-BD) or without comorbid SUD (nSUD-BD) (p<0.05). A logistic regression model was performed to identify specific correlates of SUD in BD. Results Among the 161 included subjects, 63 (39.1%) were diagnosed with comorbid SUD. SUD-BD subjects showed younger age at onset (p=0.003) and higher prevalence of BD type I diagnosis (BDI) (p<0.001). Furthermore, lifetime mixed features (p<0.001), psychotic symptoms (p<0.001), suicide attempts (p=0.002), aggression (p=0.003), antidepressant-induced manic switch (p=0.003), and poor treatment response (p<0.001) were more frequent in the SUD-BD subgroup. At the logistic regression, SUD revealed a positive association with BD type I diagnosis (Odds Ratio (OR) 4.77, 95% CI 1.66-13.71, p=0.004) and mixed features (OR 2.54, 95% CI 1.17-5.53, p=0.019). Limitations The cross-sectional study design and the relatively small sample size may limit the generalizability of the findings. The retrospective evaluation of comorbid SUD could have biased the outcome assessment. Conclusions Subjects with BD and SUD are characterized by higher clinical severity and require careful assessment of treatment response.
... Alcohol use/disorders are highly prevalent in mood disorders [1]. Co-occurring mood and alcohol use/disorders are associated with worse clinical outcomes [2][3][4][5][6] characterized by more frequent and severe mood episodes [7][8][9][10], greater cognitive deficits [11,12], increased impulsivity [13], and an elevated risk for suicide [14][15][16][17][18]. Even moderate levels of alcohol consumption are associated with worse clinical outcomes [8]. ...
Article
(1) Background: Alcohol use in the course of mood disorders is associated with worse clinical outcomes. The mechanisms by which alcohol use alters the course of illness are unclear but may relate to prefrontal cortical (PFC) sensitivity to alcohol. We investigated associations between alcohol use and PFC structural trajectories in young adults with a mood disorder compared to typically developing peers. (2) Methods: 41 young adults (24 with a mood disorder, agemean = 21 ± 2 years) completed clinical evaluations, assessment of alcohol use, and two structural MRI scans approximately one year apart. Freesurfer was used to segment PFC regions of interest (ROIs) (anterior cingulate, orbitofrontal cortex, and frontal pole). Effects of group, alcohol use, time, and interactions among these variables on PFC ROIs at baseline and follow-up were modeled. Associations were examined between alcohol use and longitudinal changes in PFC ROIs with prospective mood. (3) Results: Greater alcohol use was prospectively associated with decreased frontal pole volume in participants with a mood disorder, but not typically developing comparison participants (time-by-group-by-alcohol interaction; p = 0.007); however, this interaction became a statistical trend in a sensitivity analysis excluding one outlier in terms of alcohol use. Greater alcohol use and a decrease in frontal pole volume related to longer duration of major depression during follow-up (p's < 0.05). (4) Conclusion: Preliminary findings support more research on alcohol use, PFC trajectories, and depression recurrence in young adults with a mood disorder including individuals with heavier drinking patterns.
... In summary, these findings confirmed the high prevalence of psychiatric comorbidities, in particular substance use disorders, as well as suicide attempts in individuals with BD (Messer et al., 2017;Dong et al., 2019). We further demonstrate the existence of some dimensional mediators making the links between early life stress and these associated conditions, that has been further replicated (Marwaha et al., 2020). ...
Article
Background The FACE-BD cohort is an observational cohort of individuals with bipolar disorders (BD) who benefited from a systematic evaluation with evidence-based treatment recommendations and who were followed-up every year for 3 years in France. The objectives were to describe the lifetime course of BD, associated psychiatric and somatic comorbidities, and cognition profile. This cohort aims to identify clinical/biological signatures of outcomes, trajectories of functioning and transition between clinical stages. This article summarizes 10 years of findings of the FACE-BD cohort. Method & results We included 4422 individuals, all having a baseline assessment, among which 61.2% had at least one follow-up visit at either one, two or three years. A subsample of 1200 individuals had at least one biological sample (serum, plasma, DNA). Assessments include family history of psychiatric disorders, psychiatric diagnosis, current mood symptoms, functioning, hospitalizations, suicidal attempts, physical health, routine blood tests, treatment history, psychological dimensions, medico-economic data and a cognitive assessment. Studies from this cohort illustrate that individuals with BD display multiple coexistent psychiatric associated conditions including sleep disturbances, anxiety disorders, substance use disorders and suicide attempts as well as a high prevalence of metabolic syndrome. During follow-up, we observed a 55% reduction of the number of days of hospitalization and a significant improvement in functioning. Conclusions The FACE-BD cohort provides a strong research infrastructure for clinical research in BD and has a unique position among international cohorts because of its comprehensive clinical assessment and sustainable funding from the French Ministry of Health.
... 19) times higher odds of mortality than those patients who were non-smokers [89]. In line with this, a two-fold increased odds of substance abuse disorders were correlated with male sex [114]. And, the risk of mortality was 1.4 (95% CI: 1.1-1.7) ...
Article
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Background Drug resistance remains from among the most feared public health threats that commonly challenges tuberculosis treatment success. Since 2010, there have been rapid evolution and advances to second-line anti-tuberculosis treatments (SLD). However, evidence on impacts of these advances on incidence of mortality are scarce and conflicting. Estimating the number of people died from any cause during the follow-up period of SLD as the incidence proportion of all-cause mortality is the most informative way of appraising the drug-resistant tuberculosis treatment outcome. We thus aimed to estimate the pooled incidence of mortality and its predictors among persons receiving the SLD in sub-Saharan Africa. Methods We systematically identified relevant studies published between January, 2010 and March, 2020, by searching PubMed/MEDLINE, EMBASE, SCOPUS, Cochrane library, Google scholar, and Health Technology Assessment. Eligible English-language publications reported on death and/or its predictors among persons receiving SLD, but those publications that reported death among persons treated for extensively drug-resistant tuberculosis were excluded. Study features, patients’ clinical characteristics, and incidence and/or predictors of mortality were extracted and pooled for effect sizes employing a random-effects model. The pooled incidence of mortality was estimated as percentage rate while risks of the individual predictors were appraised based on their independent associations with the mortality outcome. Results A total of 43 studies were reviewed that revealed 31,525 patients and 4,976 deaths. The pooled incidence of mortality was 17% (95% CI: 15%-18%; I ² = 91.40; P = 0.00). The studies used varied models in identifying predictors of mortality. They found diagnoses of clinical conditions (RR: 2.36; 95% CI: 1.82–3.05); excessive substance use (RR: 2.56; 95% CI: 1.78–3.67); HIV and other comorbidities (RR: 1.96; 95% CI: 1.65–2.32); resistance to SLD (RR: 1.75; 95% CI: 1.37–2.23); and male sex (RR: 1.82; 95% CI: 1.35–2.44) as consistent predictors of the mortality. Few individual studies also reported an increased incidence of mortality among persons initiated with the SLD after a month delay (RR: 1.59; 95% CI: 0.98–2.60) and those persons with history of tuberculosis (RR: 1.21; 95% CI: 1.12–1.32). Conclusions We found about one in six persons who received SLD in sub-Saharan Africa had died in the last decade. This incidence of mortality among the drug-resistant tuberculosis patients in the sub-Saharan Africa mirrors the global average. Nevertheless, it was considerably high among the patients who had comorbidities; who were diagnosed with other clinical conditions; who had resistance to SLD; who were males and substance users. Therefore, modified measures involving shorter SLD regimens fortified with newer or repurposed drugs, differentiated care approaches, and support of substance use rehabilitation programs can help improve the treatment outcome of persons with the drug-resistant tuberculosis. Trial registration number CRD42020160473 ; PROSPERO
Article
Bipolar disorder is heterogeneous in phenomenology, illness trajectory, and response to treatment. Despite evidence for the efficacy of multimodal­ity interventions, the majority of persons affected by this disorder do not achieve and sustain full syndromal recovery. It is eagerly anticipated that combining datasets across various information sources (e.g., hierarchical “multi‐omic” measures, electronic health records), analyzed using advanced computational methods (e.g., machine learning), will inform future diagnosis and treatment selection. In the interim, identifying clinically meaningful subgroups of persons with the disorder having differential response to specific treatments at point‐of‐care is an empirical priority. This paper endeavours to synthesize salient domains in the clinical characterization of the adult patient with bipolar disorder, with the overarching aim to improve health outcomes by informing patient management and treatment considerations. Extant data indicate that characterizing select domains in bipolar disorder provides actionable information and guides shared decision making. For example, it is robustly established that the presence of mixed features – especially during depressive episodes – and of physical and psychiatric comorbidities informs illness trajectory, response to treatment, and suicide risk. In addition, early environmental exposures (e.g., sexual and physical abuse, emotional neglect) are highly associated with more complicated illness presentations, inviting the need for developmentally‐oriented and integrated treatment approaches. There have been significant advances in validating subtypes of bipolar disorder (e.g., bipolar I vs. II disorder), particularly in regard to pharmacological interventions. As with other severe mental disorders, social functioning, interpersonal/family relationships and internalized stigma are domains highly relevant to relapse risk, health outcomes, and quality of life. The elevated standardized mortality ratio for completed suicide and suicidal behaviour in bipolar disorder invites the need for characterization of this domain in all patients. The framework of this paper is to describe all the above salient domains, providing a synthesis of extant literature and recommendations for decision support tools and clinical metrics that can be implemented at point‐of‐care.
Article
Objective Few instruments measuring life events over the course of bipolar disorder distinguish the valence of events or consider cumulative stress burden. In the current study, we used a valence-focused life event questionnaire to assess stress in the last 12 months in patients with bipolar I (n = 863) and bipolar II (n = 362) disorder. Methods Associations between recent stress and lifetime illness severity features were evaluated via linear and logistic regression, adjusting for age and gender. We additionally investigated the feasibility of quantifying recent stress burden by measuring methylation at a known bipolar susceptibility locus, SLC1A2 in a subset of bipolar I patients (n = 150) with or without comorbid substance use. Results Bipolar II patients endorsed higher total, negative, and positive stress burden than their bipolar I counterparts, but the latter displayed more significant stress-illness severity associations, notably to all forms of substance abuse (e.g., alcohol, nicotine, food, other drugs). Irrespective of bipolar subtype, negative stress burden was significantly associated with illness severity features. High versus low total stress predicted hypomethylation of the SLC1A2 promoter (p < 0.05). Conclusion Together, these findings reveal substantial differences in how bipolar subtypes experience and perceive stress. The observed degree of association between recent stress and substance abuse in bipolar I lend further support to the multidirectional effects of stress, affective episodes, and substance abuse on illness severity. Quantification of recent total stress using the methylation status of the SLC1A2 promoter is feasible, although a whole-methylome approach will likely prove more effective in disaggregating other environmental influences.
Article
Background The comorbidities associated with bipolar disorder (BD) can worsen patients’ prognosis and increase economic costs to society. Currently, efforts are being made to identify new endophenotypes characterized by the presence of BD and another concomitant condition. Methods We performed a search on PubMed and GWAS catalog databases to find genome-wide association studies carried out on patients with BD with any other comorbid condition. We extracted the associated SNPs that attained statistical significance and listed them to appraise their potential to define new BD endophenotypes based on the presence of comorbidities. Results Six articles fulfilled the inclusion criteria, and all included only patients with BD type-I (BDI). The identified comorbid conditions were migraine, externalizing disorders and eating disorders. BDI with comorbid migraine was associated with rs1160720 in the NBEA gene. BDI with comorbid anorexia or bulimia nervosa was associated with rs4854912 and rs13100379 in the SOX2-OT gene. BDI with comorbid substance abuse was associated with rs1039002 in the PDE10A gene, rs12563333 upstream of the MARK1 gene, and rs13220542 downstream of the MAP3K7 gene. BDI with comorbid alcohol dependence and substance abuse was associated with rs2727943, which is located between CNTN4 and CNTN6. However, such associations were not strong enough to replicate. Limitations The main limitations are the small size and poor description of the samples used in the included articles. Conclusions Some genes involved in neurotransmission, stress response, neurogenesis and synaptic plasticity may be associated with comorbid BDI. However, evidence is too weak to consider new endophenotypes in BDI.
Article
Background and Objectives Evidence indicates that mood disorders often co-occur with substance-related disorders. However, pooling comorbidity estimates can be challenging due to heterogeneity in diagnostic criteria and in the overall study design. The aim of this study was to systematically review and, where appropriate, meta-analyse estimates related to the pairwise comorbidity between mood disorders and substance-related disorders, after sorting these estimates by various study designs. Methods We searched PubMed (MEDLINE), Embase, CINAHL and Web of Science for publications between 1980 and 2017 regardless of geographical location and language. We meta-analysed estimates from original articles in 4 broadly defined mood and 35 substance-related disorders. Results After multiple eligibility steps, we included 120 studies for quantitative analysis. In general, regardless of variations in diagnosis type, temporal order or use of adjustments, there was substantial comorbidity between mood and substance-related disorders. We found a sixfold elevated risk between broadly defined mood disorder and drug dependence (odds ratio = 5.7) and fivefold risk between depression and cannabis dependence (odds ratio = 4.9) while the highest pooled estimate, based on period prevalence risk, was found between broadly defined dysthymic disorder and drug dependence (odds ratio = 11.3). Based on 56 separate meta-analyses, all pooled odds ratios were above 1, and 46 were significantly greater than 1 (i.e. the 95% confidence intervals did not include 1). Conclusion This review found robust and consistent evidence of an increased risk of comorbidity between many combinations of mood and substance-related disorders. We also identified a number of under-researched mood and substance-related disorders, suitable for future scrutiny. This review reinforces the need for clinicians to remain vigilant in order to promptly identify and treat these common types of comorbidity.
Chapter
The use of substances that modify the psychic functioning involved in the search for pleasure, relief of discomfort, and ritual/religious activities and also with the potential to cause harm to users and people around them has been reported for a long time in the history of mankind. Eventually it is possible to characterize pathologies related to the consumption of alcohol and other drugs called substance use disorders. These disorders often coexist with other pathological conditions in the same individual which increases the potential for damage and treatment difficulties. The concepts of comorbidity and multimorbidity can be applied in these situations. The recognition of comorbidities and multimorbidities and the development of strategies for their management are fundamental for individual therapeutic projects or the elaboration of public health policies. This chapter deals with this subject with the description of concepts and addresses issues associated with multimorbidity in the presence of a substance use disorder.
Article
Bipolar disorder (BD) is a complex and dynamic condition with a typical onset in late adolescence or early adulthood followed by an episodic course with intervening periods of subthreshold symptoms or euthymia. It is complicated by the accumulation of comorbid medical and psychiatric disorders. The etiology of BD remains unknown and no reliable biological markers have yet been identified. This is likely due to lack of comprehensive ontological framework and, most importantly, the fact that most studies have been based on small non‐representative clinical samples with cross‐sectional designs. We propose to establish large, global longitudinal cohorts of BD studied consistently in a multidimensional and multidisciplinary manner to determine etiology and help improve treatment. Herein we propose collection of a broad range of data that reflect the heterogenic phenotypic manifestations of BD that include dimensional and categorical measures of mood, neurocognitive, personality, behavior, sleep and circadian, life‐story, and outcomes domains. In combination with genetic and biological information. such an approach promotes the integrating and harmonizing of data within and across current ontology systems supporting a paradigm shift that will facilitate discovery and become the basis for novel hypotheses.
Article
Objectives Emergent literature reports that confirmed or suspected cases of COVID-19 can lead to severe psychological stress. However, a small but growing number of studies have consistently suggested that individuals exhibit significant coping capability facing the pandemic. The main objective of this study was to describe the effects of the pandemic, during and after the lockdown periods, on mood, anxiety and chronobiological rhythms in a cohort of bipolar patients. Material and methods We conducted a prospective and descriptive study on patients with a DSM‐5 diagnosis of bipolar I disorder or bipolar II disorder and evaluated the Perceived Stress Scale (a 10-item self-administered questionnaire) at two times: 1) during the period of the French first lockdown (N = 159 patients); and 2) from one week to six weeks after the lockdown period (N = 94 patients). Our primary objective was composite and focused on the mood levels and the perceived stress during these two periods. Results This study shows that the mood is stable, and perceived stress scores decrease between the lockdown and the post-lockdown periods. Moreover, regarding the patient's living space, we found a significant (positive) correlation between the number of rooms and the mood, as well as a significant influence on the mood by the number of residents living with the patient during the lockdown. Conclusion These results suggest that our cohort of bipolar patients could have good coping abilities under extraordinary stressful situations. In the future, it could be relevant to monitor the long-term potential impact of such stress.
Article
За время проведения клинического исследования выполнена оценка коморбидности биполярного аффективного расстройства с зависимостью от алкоголя, развившейся на фоне биполярного расстройства и предшествовавшей биполярному расстройству, с целью определения особенностей течения заболевания. В исследование вошли 120 пациентов в возрасте от 18 до 65 лет (75 мужчин, 45 женщин) с биполярным аффективным расстройством первого типа, которые проходили стационарное лечение в ГБУЗ «СКПБ № 1» (Краснодар) в период с 2013 по 2018 г. During the course of the clinical study, the comorbidity of bipolar disorder (BD) with alcohol addiction following BD (BD-A) and preceding BD was assessed in order to determine the features of the course of the disorder. The study involved 120 patients aged from 18 to 65 years (75 men, 45 women) with bipolar disorder of the first type, who underwent inpatient treatment at State budgetary institution of health care “Specialized Clinical Psychiatric Hospital No. 1” (Krasnodar) in the period from 2013 to 2018.
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Background Psychiatric comorbidities and suicide attempts are highly prevalent in Bipolar Disorders (BD). We examined the associations between childhood maltreatment, psychiatric comorbidities, and suicide attempts, in terms of lifetime prevalence, sequence of onset, and current symptoms. Methods We assessed 3,047 individuals with BD for suicide attempts, anxiety disorders, substance use disorders, and eating disorders. Participants completed a self-report for the assessment of childhood maltreatment. Associations between childhood maltreatment and characteristics of comorbidities (lifetime prevalence, current symptoms, and age at onset) were examined using logistic regressions and network analyses. Results Psychiatric comorbidities were frequent with a mean number per individual of 1.23 (SD = 1.4). Most comorbidities occurred prior to the onset of BD. Participants who reported higher levels of childhood maltreatment had more frequent and multiple comorbidities, which were also more currently active at inclusion. Childhood maltreatment did not decrease the age of onset of comorbidities, but was associated with a faster accumulation of comorbidities prior to the onset of BD. Logistic regression and network analyses showed that emotional abuse and sexual abuse might play a prominent role in the lifetime prevalence of psychiatric comorbidities and suicide attempts. Conclusions Childhood maltreatment was associated with suicide attempts, and with frequent, multiple, and persistent psychiatric comorbidities that accumulated more rapidly prior to the onset of BD. Hence, childhood maltreatment should be systematically assessed in individuals with BD, in particular when the course of the disorder is characterized by a high comorbid profile or by a high suicidality.
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Objetivo: Analisar a concepção dos profissionais acerca das ações de cuidado compartilhadas entre Centros de Atenção Psicossocial Adulto (CAPS Adulto) e Álcool e Drogas (CAPS AD). Métodos: Estudo qualitativo, interpretativo, realizado com 10 profissionais, seis de um CAPS Adulto e quatro de um CAPS AD de uma região de São Paulo. Aplicou-se questionário digital semiestruturado e utilizou-se a abordagem de análise temática do conteúdo. Os dados foram coletados em dezembro de 2018, atendendo todas as recomendações éticas. Resultados: Os dados foram organizados nas categorias temáticas: 1) o problema de saúde mental e o uso de álcool e outras drogas; 2) o Projeto Terapêutico Singular (PTS) de casos com duplo diagnóstico; 3) dificuldades e potencialidades no compartilhamento de casos entre CAPS Adulto e CAPS AD. Conclusão: Observou-se que o uso de álcool e outras drogas é negativamente associado aos problemas de saúde mental e que esta concepção interfere na organização do projeto terapêutico compartilhado entre os serviços. Além disso, a concepção dos profissionais é de que as ações compartilhadas entre os CAPS ampliam as possibilidades de cuidado, mas demandam trabalho em rede.
Article
Background The quality of life and lifespan are greatly reduced among individuals with mental illness. To improve prognosis, the nascent field of precision psychiatry aims to provide personalized predictions for the course of illness and response to treatment. Unfortunately, the results of precision psychiatry studies are rarely externally validated, almost never implemented in clinical practice, and tend to focus on a few selected outcomes. To overcome these challenges, we have established the PSYchiatric Clinical Outcome Prediction (PSYCOP) cohort, which will form the basis for extensive studies in the upcoming years. Methods PSYCOP is a retrospective cohort study that includes all patients with at least one contact with the psychiatric services of the Central Denmark Region in the period from January 1, 2011 to October 28, 2020 (n=119,291). All data from the electronic health records (EHR) are included, spanning diagnoses, information on treatments, clinical notes, discharge summaries, laboratory tests etc. Based on these data, machine learning methods will be used to make prediction models for a range of clinical outcomes, such as diagnostic shifts, treatment response, medical comorbidity, and premature mortality, with an explicit focus on clinical feasibility and implementation. Discussion We expect that studies based on the PSYCOP cohort will advance the field of precision psychiatry through the use of state-of-the-art machine learning methods on a large and representative dataset. Implementation of prediction models in clinical psychiatry will likely improve treatment and, hopefully, increase the quality of life and lifespan of those with mental illness.
Chapter
Mood, anxiety, and psychotic disorders commonly occur with alcohol and substance use disorders; such comorbidity is often associated with higher disease severity, lower functioning, and poorer treatment response. This high prevalence of substance and non-substance use disorders points to a common etiology with shared genetic and neurobiological features. It is recognized that environmental factors of low parental monitoring and trauma play a contributory role in this shared etiology. Given the high prevalence of dual-diagnosis disorders, patients presenting for treatment of one category of disorder should be carefully evaluated for the presence of the other. Empirically validated screening and diagnostic instruments may be combined with the clinical interview for a comprehensive assessment of psychiatric and substance use disorders, as well as their temporal relation to each other. Treatment of co-occurring disorders often includes a combination of pharmacotherapy and psychotherapy, to improve symptom management and treatment adherence. While pharmacotherapies are often more effective in targeting the non-substance-related comorbidity, available medications which specifically target reducing substance use should be included in the treatment plan as needed. Timely identification and treatment of one disorder with evidence-based psychotherapies and behavioral therapies often leads to an improved prognosis for the other disorder. In sum, the integration of psychiatric and substance use disorder treatment has demonstrated efficacy for the treatment of a wide spectrum of these frequently co-occurring conditions.
Article
Background: Taking care of patients with bipolar disorder (BD) makes critical challenges for their informal caregivers (ICGs) and forces them to tolerate considerable burden. This qualitative study explored the dimensions of ICGs' care burden (CB) based on their own experiences and the patients' therapists. Materials and methods: This is a qualitative study which was conducted based on conventional content analysis through semistructured and in-depth interviews. Purposive sampling was used to select the participants including 13 ICGs and 14 therapists (2 psychiatrists, 10 psychiatric nurses, and 2 clinical psychologists). Interviews were audiotaped, transcribed verbatim, and analyzed using Graneheim's 2004 principles. Results: Qualitative analyses yielded three major themes: "challenges associated with the nature of BD," "challenges related to the ICGs," and "challenges related to interventions." The categories of the first theme entailed "individual-oriented characteristics of BD" and "social-oriented characteristics of BD." The categories of the second theme consisted of "social stigma," "psychiatric problems and helplessness of ICGs," "financial costs related to providing cares," and "insufficient self-efficacy of ICGs in cares provision." The categories of the last theme included "educational interventions" and "organizational interventions." Conclusions: This study showed that the burden of ICGs have individual, social, and organizational aspects. Every one of them impacts the severity of their burden remarkably. The depth of the therapists' experiences has a significant role in designing the interventions to reduce this burden. The present investigation emphasized the constitution of a comprehensive framework related to all factors affecting burden in a developing country.
Article
Although the etiopathogenesis of mental disorders is not fully understood, accumulating evidence support that clinical symptomatology cannot be assigned to a single gene mutation, but it involves several genetic factors. More specifically, a tight association between genes and environmental risk factors, which could be mediated by epigenetic mechanisms, may play a role in the development of mental disorders. Several data suggest that epigenetic modifications such as DNA methylation, post-translational histone modification and interference of microRNA (miRNA) or long non-coding RNA (lncRNA) may modify the severity of the disease and the outcome of the therapy. Indeed, these changes may help to identify patients particularly vulnerable to mental disorders and may have potential utility as biomarkers to facilitate diagnosis and treatment of psychiatric disorders. This article summarizes the most relevant preclinical and human data showing how epigenetic modifications can be central to the therapeutic efficacy of antidepressant and/or antipsychotic agents, as possible predictor of drugs response.
Article
Background: Women with bipolar disorder (BD) may continue psychotropics during pregnancy. The association of exposure to antidepressant, antipsychotics, and mood stabilizers with offspring risks of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) remains unexplored in mothers with BD. Methods: A total of 5669 pregnant women with BD and 5669 psychiatrically healthy controls were identified between 2002 and 2011 from the Taiwan Longitudinal Health Insurance Database. We analyzed the odds ratios (ORs) of psychotropic types and exposure periods (3 months before pregnancy [3MbPreg] and first, second, and third trimesters [T1, T2, T3, respectively]) on the risk of ADHD and ASD by using adjusted logistic regression analyses. Results: Antidepressant exposure during 3MbPreg (OR=2.15, 95% CI=1.45-3.20), T1 (OR=2.62, 95% CI=1.68-4.09), T2 (OR=2.33, 95% CI=1.18-4.63), and T3 (OR=2.33, 95% CI=1.67-6.61) was associated with increased offspring risk of ADHD, particularly for selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor. Mood stabilizer exposure during 3MbPreg increased the risks of ADHD (OR=2.39, 95% CI=1.45-3.95) and ASD (OR=3.89, 95% CI=1.30-11.65); a higher ADHD risk was associated with valproic acid (OR=2.43, 95% CI=1.32-4.47) and lamotrigine exposure (OR=8.24, 95% CI = 1.49-45.67); ASD risk was higher for lithium exposure (OR=6.75, 95% CI=1.41-32.28). Limitation: In claims-data analyses, several clinical parameters or potential confounders may be incompletely captured. Conclusions: Antidepressants were associated with higher offspring risk of ADHD over all gestation periods among mothers with BD than psychiatrically healthy controls, while mood stabilizers were associated with higher risk of ADHD and ASD during 3MbPreg.
Article
This review summarizes evidence on the effects of cannabis use on the development of adolescents and young adults. It draws on epidemiological studies, neuroimaging studies, case-control studies, and twin and Mendelian randomization studies. The acute risks include psychiatric symptoms associated with the use of high THC (tetrahydrocannabinol) products and motor vehicle accidents. Daily cannabis use during adolescence is associated with cannabis dependence and poor cognitive function, which may affect educational attainment and occupational choice. Daily use of highly potent cannabis is associated with more severe psychological symptoms, such as psychoses, mania, and suicidality. There are more mixed findings on depressive symptoms, anxiety, and violence and debates about the interpretation of these associations. Legalization of adult cannabis use may increase cannabis use and dependence among adolescents and young adults. The regulation of cannabis after legalization needs to minimize adolescent uptake and cannabis-related adverse developmental outcomes. Expected final online publication date for the Annual Review of Developmental Psychology, Volume 2 is December 15, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Given its prevalence and impact on public health, the comorbidity of bipolar and substance use disorders is one of the most relevant of dual diagnoses. The objective was to evaluate the characteristics of patients from community mental health and substance abuse centres in Madrid. The sample consisted of 837 outpatients from mental health and substance abuse centres. We used the Mini International Neuropsychiatric Interview (MINI) and Personality Disorder Questionnaire (PDQ4+) to evaluate axis I and II disorders. Of these patients, 174 had a lifetime bipolar disorder, 83 had bipolar disorder type I and 91 had type II. Most patients had dual pathology. Of the 208 participants from the mental health centres, 21 had bipolar disorder and 13 (61.9%) were considered dually-diagnosed patients, while 33.2% of non-bipolar patients had a dual diagnoses (p = 0.03). Of the 629 participants from the substance abuse centres, 153 patients (24.3%) had a bipolar diagnosis. Bipolar dual patients had higher rates of alcohol and cocaine dependence than non-bipolar patients. Moreover, age at onset of alcohol use was earlier in bipolar duallydiagnosed patients than in other alcoholics. Bipolar dually-diagnosed patients had higher personality and anxiety disorder comorbidities and greater suicide risk. Thus, alcohol and cocaine are the drugs most associated with bipolar disorder. Given the nature of the study, the type of relationship between these disorders cannot be determined.
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Background: Approximately 30%-60% of adults diagnosed with bipolar disorder (BD) report onset between the ages 15 and 19 years; however, a correct diagnosis is often delayed by several years. Therefore, investigations of the early features of BD are important for adequately understanding the prodromal stages of the illness. Methods: A complete review of the medical records of 46 children and adolescents who were hospitalized for BD at two psychiatric teaching centers in Prague, Czech Republic was performed. Frequency of BD in all inpatients, age of symptom onset, phenomenology of mood episodes, lifetime psychiatric comorbidity, differences between very-early-onset (<13 years of age) and early-onset patients (13-18 years), and differences between the offspring of parents with and without BD were analyzed. Results: The sample represents 0.83% of the total number of inpatients (n=5,483) admitted during the study period at both centers. BD often started with depression (56%), followed by hypomania (24%) and mixed episodes (20%). The average age during the first mood episode was 14.9 years (14.6 years for depression and 15.6 years for hypomania). Seven children (15%) experienced their first mood episode before age 13 years (very early onset). Traumatic events, first-degree relatives with mood disorders, and attention deficit hyperactivity disorder were significantly more frequent in the very-early-onset group vs the early-onset group (13-18 years) (P≤0.05). The offspring of bipolar parents were significantly younger at the onset of the first mood episode (13.2 vs 15.4 years; P=0.02) and when experiencing the first mania compared to the offspring of non-BD parents (14.3 vs 15.9 years; P=0.03). Anxiety disorders, substance abuse, specific learning disabilities, and attention deficit hyperactivity disorder were the most frequent lifetime comorbid conditions. Conclusion: Clinicians must be aware of the potential for childhood BD onset in patients who suffer from recurrent depression, who have first-degree relatives with BD, and who have experienced severe psychosocial stressors.
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Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words "bipolar disorder," "suicide attempts," "cannabis," "marijuana," "early age at onset," and "early onset." Results. The following percentages in bipolar patients were found: suicide attempts 3.6-42%; suicide attempts and substance use 5-60%; suicide attempts and cannabis use 15-42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.
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To compare the prevalence and pattern of comorbid substance use disorders (SUD) between patients with schizophrenia, bipolar disorder, and depressive illness. Data on presence of alcohol use disorder (AUD) and non-alcohol drug use disorder (DUD) were retrieved from the Norwegian Patient Register for individuals born between 1950 and 1989 who in the period 2009-2013 were diagnosed with schizophrenia, bipolar disorder or depressive illness according to the 10th version of the WHO International Classification of Diseases. The prevalence of AUD only, DUD only, or both was compared between men and women across age and diagnostic groups. The prevalence of SUD was 25.1 % in schizophrenia (AUD: 4.6 %, DUD: 15.6 %, AUD and DUD: 4.9 %), 20.1 % in bipolar disorder (AUD: 8.1 %, DUD: 7.6 %, AUD and DUD: 4.4 %), and 10.9 % in depressive illness (AUD: 4.4 %, DUD: 4.3 %, AUD and DUD: 2.2 %). Middle-aged men with bipolar disorder had the highest prevalence of AUD (19.1 %) and young men with schizophrenia had the highest prevalence of DUD (29.6 %). Of the specific DUDs, all but sedative use disorder were more prevalent in schizophrenia than the other groups. Cannabis and stimulant use disorder was found among 8.8 and 8.9 %, respectively, of the men with schizophrenia. The alarmingly high prevalence of DUD among young patients with severe mental disorders should encourage preventive efforts to reduce illicit drug use in the adolescent population.
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It is clinically important to recognize both bipolar disorder and borderline personality disorder (BPD) in patients seeking treatment for depression, and it is important to distinguish between the two. The most studied question on the relationship between BPD and bipolar disorder is their diagnostic concordance. Across studies approximately 10 % of patients with BPD had bipolar I disorder and another 10 % had bipolar II disorder. Likewise, approximately 20 % of bipolar II patients were diagnosed with BPD, though only 10 % of bipolar I patients were diagnosed with BPD. While the comorbidity rates are substantial, each disorder is, nonetheless, diagnosed in the absence of the other in the vast majority of cases (80-90 %). In studies examining personality disorders broadly, other personality disorders were more commonly diagnosed in bipolar patients than was BPD. Likewise, the converse is also true: other axis I disorders such as major depression, substance abuse, and post-traumatic stress disorder are more commonly diagnosed in patients with BPD than is bipolar disorder. Studies comparing patients with BPD and bipolar disorder find significant differences on a range of variables. These findings challenge the notion that BPD is part of the bipolar spectrum. While a substantial literature has documented problems with the under-recognition and under-diagnosis of bipolar disorder, more recent studies have found evidence of bipolar disorder over-diagnosis and that BPD is a significant contributor to over-diagnosis. Re-conceptualizing the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, diagnostic criteria for bipolar disorder as a type of test, rather than the final word on diagnosis, shifts the diagnostician from thinking solely whether a patient does or does not have a disorder to considering the risks of false-positive and false-negative diagnoses, and the ease by which each type of diagnostic error can be corrected by longitudinal observation.
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It is clinically important to recognize both bipolar disorder and borderline personality disorder (BPD) in patients seeking treatment for depression, and it is important to distinguish between the two. Research considering whether BPD should be considered part of a bipolar spectrum reaches differing conclusions. We reviewed the most studied question on the relationship between BPD and bipolar disorder: their diagnostic concordance. Across studies, approximately 10% of patients with BPD had bipolar I disorder and another 10% had bipolar II disorder. Likewise, approximately 20% of bipolar II patients were diagnosed with BPD, though only 10% of bipolar I patients were diagnosed with BPD. While the comorbidity rates are substantial, each disorder is nontheless diagnosed in the absence of the other in the vast majority of cases (80% to 90%). In studies examining personality disorders broadly, other personality disorders were more commonly diagnosed in bipolar patients than was BPD. Likewise, the converse is also true: other axis I disorders such as major depression, substance abuse, and post-traumatic stress disorder are also more commonly diagnosed in patients with BPD than is bipolar disorder. These findings challenge the notion that BPD is part of the bipolar spectrum.
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Heterogeneity has a key role in meta-analysis methods and can greatly affect conclusions. However, true levels of heterogeneity are unknown and often researchers assume homogeneity. We aim to: a) investigate the prevalence of unobserved heterogeneity and the validity of the assumption of homogeneity; b) assess the performance of various meta-analysis methods; c) apply the findings to published meta-analyses. We accessed 57,397 meta-analyses, available in the Cochrane Library in August 2012. Using simulated data we assessed the performance of various meta-analysis methods in different scenarios. The prevalence of a zero heterogeneity estimate in the simulated scenarios was compared with that in the Cochrane data, to estimate the degree of unobserved heterogeneity in the latter. We re-analysed all meta-analyses using all methods and assessed the sensitivity of the statistical conclusions. Levels of unobserved heterogeneity in the Cochrane data appeared to be high, especially for small meta-analyses. A bootstrapped version of the DerSimonian-Laird approach performed best in both detecting heterogeneity and in returning more accurate overall effect estimates. Re-analysing all meta-analyses with this new method we found that in cases where heterogeneity had originally been detected but ignored, 17-20% of the statistical conclusions changed. Rates were much lower where the original analysis did not detect heterogeneity or took it into account, between 1% and 3%. When evidence for heterogeneity is lacking, standard practice is to assume homogeneity and apply a simpler fixed-effect meta-analysis. We find that assuming homogeneity often results in a misleading analysis, since heterogeneity is very likely present but undetected. Our new method represents a small improvement but the problem largely remains, especially for very small meta-analyses. One solution is to test the sensitivity of the meta-analysis conclusions to assumed moderate and large degrees of heterogeneity. Equally, whenever heterogeneity is detected, it should not be ignored.
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Background: Family history and adversity in childhood are two replicated risk factors for early onset bipolar disorder. However, their combined impact has not been adequately studied. Methods: Based on questionnaire data from 968 outpatients with bipolar disorder who gave informed consent, the relationship and interaction of: 1) parental and grandparental total burden of psychiatric illness; and 2) the degree of adversity the patient experienced in childhood on their age of onset of bipolar disorder was examined with multiple regression and illustrated with a heat map. Results: The familial loading and child adversity vulnerability factors were significantly related to age of onset of bipolar and their combined effect was even larger. A heat map showed that at the extremes (none of each factor vs high amounts of both) the average age of onset differed by almost 20 years (mean = 25.8 vs 5.9 years of age). Limitations: The data were not based on interviews of family members and came from unverified answers on a patient questionnaire. Conclusions: Family loading for psychiatric illness and adversity in childhood combine to have a very large influence on age of onset of bipolar disorder. These variables should be considered in assessment of risk for illness onset in different populations, the need for early intervention, and in the design of studies of primary and secondary prevention.
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Background: Cognitive impairment is a well-established feature of bipolar disorder (BD). Comorbid BD and substance use leads to poor psychosocial and clinical outcomes. However, knowledge on the neurocognitive functioning of individuals with dual diagnosis is limited. The aim of this study is to assess the cognitive performance of subjects with BD, BD with comorbid alcohol use disorder (AUD), and BD with comorbid illicit substance use disorders (SUD) as compared to healthy individuals. Methods: We included 270 inpatients and outpatients with BD and 211 healthy controls. The diagnostic of BD and substance use disorder was assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Axis I. Demographic and clinical information were also collected. The cognitive assessment included the Wechsler Test of Adult Reading (WTAR), and a revised version of the California Verbal Learning Test (CVLT) as part of the South Texas Assessment of Neurocognition (STAN). Results: The STAN was administered to 134 BD patients (100 female, M±SD: 37.37±12.74 years), 72 BD patients with AUD (40 female, M±SD: 38.42±11.82), 64 BD patients with SUD (39 female, M±SD: 34.50±10.57), and 211 healthy controls with no lifetime history of mental illness and substance use (127 female, M±SD: 34.80±12.57 years). In terms of clinical characteristics, BD+SUD showed a marginally earlier onset of illness compared to BD. Compared to HC, BD performed poorly in the immediate recall and short-delay free tests of the CVLT, while BD patients with AUD and SUD showed significant memory deficits in both the immediate recall and recognition components of the CVLT. There were no differences in memory performance between BD and BD with either AUD or SUD. Conclusions: A history of substance use disorders is associated with an earlier onset of BD. BD has marked effects on processes underlying the encoding of new information, while comorbid substance use in BD impairs more specifically the recognition of previously presented information. Future longitudinal studies should evaluate the effects of AUD and SUD on illness progression and therapeutic outcomes.
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Background. High rates of substance abuse have been reported in the general population, with males more often affected than females. Although high rates of substance abuse have also been reported in bipolar patients, the relationship between substance abuse and bipolar disorder has not been well characterized. Methods: Substance abuse histories were obtained in 392 patients hospitalized for manic or mixed episodes of bipolar disorder and rates of current and lifetime abuse calculated. Analyses comparing sex, subtype (manic vs. mixed) and clinical history variables were conducted. Results: Rates of lifetime substance abuse were high for both alcohol (48.5%) and drugs (43.9%). Nearly 60% of the cohort had a history of some lifetime substance abuse. Males had higher rates of abuse than females, but no differences in substance abuse were observed between subjects in manic and mixed bipolar states. Rates of active substance abuse were lower in older age cohorts. Subjects with a comorbid diagnosis of lifetime substance abuse had more psychiatric hospitalizations. Conclusions: Substance abuse is a major comorbidity in bipolar patients. Although rates decrease in older age groups, substance abuse is still present at clinically important rates in the elderly. Bipolar patients with comorbid substance abuse may have a more severe course. These data underscore the significance of recognition and treatment of substance abuse in bipolar disorder patients.
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Mental illness and substance use are overrepresented within urban homeless populations. This paper compared substance use patterns between homeless individuals diagnosed with schizophrenia spectrum (SS) and bipolar disorders (BD) using the Mini-International Neuropsychiatric Interview. From a sample of 497 subjects drawn from Vancouver, Canada who participated in the At Home/Chez Soi study, 146 and 94 homeless individuals were identified as BD and SS, respectively. In the previous 12 months, a greater proportion of BD homeless reported greater use of cocaine (χ = 20.0, p = 0.000), amphetamines (χ = 13,8, p = 0.000), opiates (χ = 24.6, p = 0.000), hallucinogens (χ = 11.7, p = 0.000), cannabinoids (χ = 5.05, p = 0.034), and tranquilizers (χ = 7.95, p = 0.004) compared to SS. Cocaine and opiates were significantly associated with BD homeless (χ = 39.06, df = 2, p < 0.000). The present study illustrates the relationship between substance use and BD in a vulnerable urban population of homeless, affected by adverse psychosocial factors and severe psychiatric conditions.