Clinical Course Of Bipolar Disorder Research Articles

What Came First, Mania or Depression? Polarity at Onset in Bipolar I and II: Temperament and Clinical Course.

(1) Background: Bipolar disorder (BD) is divided into type I (BD-I) and type II (BD-II). Polarity at onset (PO) is a proposal to specify the clinical course of BD, based on the type of the first episode at disorder onset-depressive (D-PO) or manic (M-PO). At the same time, affective temperaments represent preexisting variants of the spectrum of affective disorders. Our objectives were to investigate the hypothesis that temperament may exert an influence on PO, and that this factor can serve as an indicator of the forthcoming course of the disorder, carrying significant therapeutic implications. (2) Methods: We included 191 patients with BD and examined clinical variables and temperament; the latter was assessed using the short version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Auto-questionnaire (TEMPS-A-39-SV). We tested the associations between these variables and PO using standard univariate/bivariate methods followed by multivariate logistic regression models. (3) Results: 52.9% of the sample had D-PO and 47.1% had M-PO. D-PO and M-PO patients scored higher for dysthymic and hyperthymic temperaments, respectively (p < 0.001). Also, they differed in BD subtypes, age at first affective episode, illness duration, number of depressive episodes, seasonality, suicide risk, substance use, lithium, and benzodiazepine use (p < 0.05). Only BD-II and age at first depressive episode were predictors of D-PO, whereas BD-I, age at first manic/hypomanic episode, and hyperthymic temperament were predictors of M-PO (p < 0.01). (4) Conclusions: Our findings point to the importance of carefully assessing temperament and PO in patients with BD, to better predict the clinical course and tailor therapeutic interventions to individual patients' needs.

Bipolar Disorder and Borderline Personality Disorder: A Diagnostic Challenge

IntroductionBipolar disorder (BD) and borderline personality disorder (BPD) appear as prevalent psychiatric conditions, with both being associated with increased morbidity and elevated suicide rates.Borderline personality disorder is characterized by emotional instability and impulsivity, and patients are susceptible to dangerous behaviors such as unsafe sexual behavior, eating disorders and substance abuse. On the other hand, mania in BD patients contributes to impulsivity, hypersexuality and poor judgment, as well as a lack of inhibition. In both cases, individuals are at a higher risk of committing suicide due to emotional dysregulation and impulsive behaviours.The symptomatic overlap in BPD and BD is prone to discussion and may lead to misdiagnosis. Some studies suggest that BPD and BD may lie on a spectrum, while others advocate them as separate entities that may coexist.ObjectivesTo explore the clinical challenges associated with both the differential diagnosis and the comorbidity of BD and BPD.MethodsWe performed a non-systematic review of the literature using the database PubMed and the following keywords: bipolar disorder borderline personality disorder comorbidityResultsPatients with borderline personality disorder seem to have significantly greater odds of a previous bipolar misdiagnosis, but no specific borderline criterion was shown unique in predicting this outcome.Nonetheless, research studies have reported that approximately 20% of BPD were also diagnosed with BD and, similarly, 10% of people with BD I and 20% with BD II were diagnosed with BPD.Comorbid BPD and BD are associated with marked psychosocial disability, with patients being more impulsive and aggressive than those with BPD and BD alone. They are also highly susceptible to anxiety disorders like obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and somatoform disorders. Studies have shown that comorbid BPD has a negative impact on the clinical course of Bipolar Disorder, as the patients have an unfavorable illness trajectory, with earlier onset of mood symptoms,higher likelihood of hospitalization, longer treatment duration and worse response to treatment. They are also at higher risk for depression and persistent unemployment, increased risk drug abuse, higher suicide risk, and greater utilization of ECT, compared to patients with BPD or BD alone.ConclusionsA careful review of the patient’s history must be done to properly distinguish between BPD and BD and to make the right diagnosis. Further studies are needed to clarify the risk factors associated with the comorbidity between these two disorders, in order to develop effective clinical strategies for optimal outcomes for patients with both disorders, improve their clinical course and prevent the increased risk of suicidality.Disclosure of InterestNone Declared

Reliability and convergent validity of retrospective reports of childhood maltreatment by individuals with bipolar disorder

Childhood maltreatment is associated with the etiology and clinical course of bipolar disorder. Most studies employ retrospective maltreatment self-reports which are vulnerable to bias, raising questions about their validity and reliability. This study examined the test-retest reliability over 10 years, the convergent validity and the impact of current mood on retrospective reports of childhood maltreatment in a bipolar sample. 85 participants with bipolar I disorder completed the Childhood Trauma Questionnaire [CTQ] and the Parental Bonding Instrument [PBI] at baseline. Beck Depression Inventory and Self Report Mania Inventory assessed depressive and manic symptoms, respectively. 53 participants completed the CTQ at baseline and 10-year follow-up. Good levels of convergent validity were observed between the CTQ and PBI. Correlations ranged from rs= -0.35 (CTQ emotional abuse and PBI paternal care) to rs= -0.65 (CTQ emotional neglect and PBI maternal care). Good agreement between CTQ reports at baseline and 10-year follow-up were found (range: κ=0.41 for physical neglect to κ=0.83 for sexual abuse). Higher depression and mania scores were recorded among participants who reported abuse (but not neglect) compared to those without such reports. These findings support using this method in research and clinical practice, though current mood should be taken into account.

A review: Circadian Rhythm Dysfunction and Bipolar Disorder

IntroductionCircadian rhythm (CR) dysfunction is a prominent feature in bipolar disorder (BD) and sleep disturbances are characteristic, although not essential to the diagnosis.ObjectivesTo review the literature regarding the CR dysfunction and its impact on the onset and clinical course of BD.MethodsWe conducted a MEDLINE search using bipolar disorder, circadian rhythm and sleep as keywords, selecting studies written in English.ResultsCR dysfunction is a trait marker of BD. It’s known that during depressive episodes insomnia is present, with difficulty falling asleep/ maintaining sleep and early awakening. Regarding mania, decreased need for sleep is a critical marker. During the euthymic period significant alterations in sleep pattern have been described. It’s also known that changes in the sleep pattern occur prior to those in mood patterns, indicating that sleep dysregulation may trigger the onset of mood episodes or relapses. Therefore, CR disruption may be associated with the pathophysiology of BD and some factors have already been identified: irregularity of the sleep-wake rhythm, eveningness chronotype, abnormality of melatonin secretion, vulnerability of clock genes and the irregularity of social zeitgeber.ConclusionsDisturbances of sleep are pervasive, and an essential feature of BD, worse during mood episodes, but still present during euthymic periods. It remains to determine whether circadian rhythm dysfunction is a trait marker or mood state dependent. Further studies are warranted to clarify this association.DisclosureNo significant relationships.

Impact of childhood trauma on functioning of patients with bipolar disorder

IntroductionExposure to severe childhood trauma has been associated with the onset and the severity of bipolar disorder in adults.ObjectivesThe aim of this study was to examine the relationship between childhood trauma and functioning of patients suffering from bipolar disorder.MethodsWe conducted a cross-sectional, descriptive, and analytical study, including sixty-one remitted patients with BD. We used the Childhood Trauma Questionnaire (CTQ-SF) to measure history of traumatic childhood experiences and the Functioning Assessment Short Test (FAST) to assess functioning.ResultsThe mean age of patients was 43.4. The sex ratio was 2.4. Almost two-thirds of patients (64%) had experienced at least one type of childhood trauma. An overall functional impairment was found in 70.5% of participants. The CTQ total score was significantly associated with low educational level (p=0.001), low socio-economic status (P=0.034), a family history of psychosis (P=0.022), the number of mood episodes (P=0.001), the number of hospitalizations (P=0.04), the number of relapses with psychotic features (p=0.002) and that of depressive relapses (P&lt;0.001), rapid cycling (P=0.012), higher rates of suicide attempts (P=0.04) and poor functioning (P&lt;0.001).The logistic regression analyses showed a significant association of childhood trauma with low educational level (p=0.001), high number of depressive episodes (p=0.013) and poor functioning (p&lt;0.001).ConclusionsOur findings demonstrate that childhood abuse and neglect are risk factors associated with worsening clinical course of bipolar disorder and higher functional impairment. These findings press the urgency for preventive practices and early intervention strategies to diminish the prevalence of childhood trauma and minimize their impact.DisclosureNo significant relationships.

Stress predicts depression symptoms for women living with bipolar disorder during the menopause transition.

Although sleep disturbance is an important feature in bipolar disorder, the relationship between mood symptoms, sleep disturbances, and hot flash symptom severity during menopause for women with bipolar disorder is largely unknown. Women with bipolar disorder (n = 100) who were categorized as perimenopausal using the STRAW and Monash criteria took part in an international online survey. The survey contained questions on history of reproductive health; the clinical course of bipolar disorder; menopausal symptoms (Menopause Rating Scale [MRS]); depression, anxiety, and stress (Depression Anxiety and Stress Scale-21) and the Altman Mania Rating Scale. MRS sleep problems and hot flash severity were positively correlated with each other and with depression, anxiety, and stress symptoms. Mania scores were not significantly correlated with sleep or hot flash severity scores. A stepwise regression analysis on depression symptoms, using MRS sleep disturbance and MRS hot flash severity scores as predictors with anxiety and stress symptoms in the model, found that stress alone predicted 40% of the variance in total depression scores. Stress plays an important role in the experience of depression for women living with bipolar disorder during the perimenopausal phase. More research is needed to determine if stress management programs may be helpful for women living with bipolar disorder during this time of life and if these in turn, may improve depressive symptoms.

Recent Perceived Stress, Amygdala Reactivity to Acute Psychosocial Stress, and Alcohol and Cannabis Use in Adolescents and Young Adults With Bipolar Disorder.

Background: Psychosocial stress negatively affects the clinical course of bipolar disorder. Studies primarily focused on adults with bipolar disorder suggest the impact of stress is progressive, i.e., stress response sensitizes with age. Neural mechanisms underlying stress sensitization are unknown. As stress-related mechanisms contribute to alcohol/substance use disorders, variation in stress response in youth with bipolar disorder may contribute to development of co-occurring alcohol/substance use disorders. This study investigated relations between psychosocial stress, amygdala reactivity, and alcohol and cannabis use in youth with bipolar disorder, compared to typically developing youth.Methods: Forty-two adolescents/young adults [19 with bipolar disorder, 23 typically developing, 71% female, agemean ± SD = 21 ± 2 years] completed the Perceived Stress Scale (PSS), Daily Drinking Questionnaire modified for heaviest drinking week, and a modified Montreal Imaging Stress functional MRI Task. Amygdala activation was measured for both the control and stress conditions. Main effects of group, condition, total PSS, and their interactions on amygdala activation were modeled. Relationships between amygdala response to acute stress with recent alcohol/cannabis use were investigated.Results: Greater perceived stress related to increased right amygdala activation in response to the stress, compared to control, condition in bipolar disorder, but not in typically developing youth (group × condition × PSS interaction, p = 0.02). Greater amygdala reactivity to acute stress correlated with greater quantity and frequency of alcohol use and frequency of cannabis use in bipolar disorder.Conclusion: Recent perceived stress is associated with changes in amygdala activation during acute stress with amygdala reactivity related to alcohol/cannabis use in youth with bipolar disorder.

Substance Misuse Trajectories and Risk of Relapse in the Early Course of Bipolar Disorder.

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.

Recent Perceived Stress, Amygdala Reactivity to Acute Psychosocial Stress, and Alcohol Use in Adolescents/Young Adults With Bipolar Disorder

Psychosocial stress negatively effects the clinical course of bipolar disorder. Studies primarily focused on adults with bipolar disorder suggest that the impacts of stress are progressive, i.e., response sensitizes with age. The neural mechanisms underlying stress sensitization are not yet known, nor how those mechanisms impact the clinical course of bipolar disorder, e.g., underlie the high rates of alcohol use disorders. This study investigated how acute psychosocial stress effects amygdala reactivity and alcohol misuse in youth with bipolar disorder, compared to typically developing youth.

Orexins in the clinical course of bipolar disorder

IntroductionOrexins are involved in the regulation of circadian rhythms which play an important role in mood regulation(1,2), and are hypothesised to be associated with major depressive disorder(3). However, scarce studies analyse their relationship with bipolar disorder (BD).ObjectivesTo evaluate the relationship of orexin-A and the clinical course of BDMethods95 BD patients were tested for serum orexin-A. The clinical course was analysed through number of depressive, manic/mixed episodes. HDRS and YMRS were used to assess severity of current episode. Statistics: Spearman correlations, U Mann-Whitney, linear regression analysis.ResultsMean age was 50.03 (SD=12.87) and 64.2% were women. 63.2% had BD-type I. Mean number of manic, depressive and mixed episodes was 2.32 (SD=3.07), 7.28 (SD=12.37), and 3.01 (SD=9.06), respectively. Mean age of onset was 26.09 (SD=10.50). Mean concentration of orexin-A was 21.78 pg/ml (SD=15.41), with no differences in sex, body mass index, age at onset or presence of insomnia(ICD-10). A correlation with age was observed; r=0.24 (p=0.019). No association was identified between orexin-A and severity of current episode. In relation to clinical course, no correlation was found with manic or mixed episodes. However, a negative correlation was identified between orexin-A levels and number of depressive episodes; r=-0.36 (p=0.001). When linear regression (orexin-A as dependent variable) was used to control for age, only this covariate (B=0.304) entered in the model (R2=0.067, F=6.045, p=0.015).ConclusionsNo relationship between orexin-A and number of manic/mixed episodes were detected. The association of orexin-A with number of depressive episodes dissappeared when age was controlled.DisclosureNo significant relationships.

Antisocial Personality Disorder in Bipolar Disorder: A Systematic Review.

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.

The effects of childhood emotional maltreatment and alexithymia on depressive and manic symptoms and suicidal ideation in females with bipolar disorder: emotion dysregulation as a mediator

Objectives The relations of childhood emotional maltreatment and alexithymia to the clinical course of bipolar disorder (BD) have been widely recognised. Difficulties in regulating emotions may explain these relationships. The current study evaluated the effects of childhood emotional maltreatment and alexithymia on depressive and manic symptoms as well as suicidal ideation in female patients with BD. Emotion dysregulation was evaluated as a mediating factor. Methods Three hundred hospitalised female patients with a diagnosis of BD provided information regarding their history of childhood emotional maltreatment, alexithymia, difficulties in emotion regulation, depressive and manic symptoms, and suicidal ideation. A series of structural equation models (SEMs) were calculated to assess the associations between these variables. Results Childhood emotional abuse and difficulty in identifying feelings were indirectly associated with depressive and manic symptoms as well as suicidal ideation. This association was mediated by emotion dysregulation. This association remained significant after depressive and manic symptoms were controlled in the model. Conclusions This study indicates that patients with BD who experienced emotional abuse during childhood and have difficulties identifying emotions report greater emotion dysregulation. These individuals, in turn, are more likely to experience more severe depressive and manic symptoms as well as suicidal ideation. Key points Childhood emotional maltreatment and emotional and clinical factors in bipolar disorder were assessed. Childhood emotional abuse indirectly affected clinical factors via emotion dysregulation. Difficulty in identifying feelings was linked to clinical factors via emotional dysregulation. Emotional dysregulation affected the links of childhood emotional maltreatment and difficulty in identifying feelings on suicidal ideation after controlling for clinical symptoms. Emotional dysregulation dimensions of impulse, strategies, and goals emerge in relation to suicidal ideation.

Affective Temperaments and Clinical Course of Bipolar Disorder: An Exploratory Study of Differences among Patients with and without a History of Violent Suicide Attempts.

Background and Objectives: Suicide is the leading cause of death in patients with Bipolar Disorder (BD). In particular, the high mortality rate is due to violent suicide attempts. Several risk factors associated with suicide attempts in patients with BD have been identified. Affective temperaments are associated with suicidal risk, but their predictive role is still understudied. The aim of this study is to assess the relationship between affective temperaments and personal history of violent suicide attempts. Materials and Methods: 74 patients with Bipolar Disorder type I (BD-I) or II (BD-II) were included. All patients filled in the short version of Munster Temperament Evaluation of the Memphis, Pisa, Paris and San Diego (short TEMPS-M) and the Temperament and Character Inventory, revised version (TCI-R). The sample was divided into two groups on the basis of a positive history for suicidal attempts and the suicidal group was further divided into two subgroups according to violent suicide attempts. Results: Violent suicide attempts were positively associated with the cyclothymic temperament and inversely to the hyperthymic one. BD-I patients and patients with a clinical history of rapid cycling were significantly more represented in the group of patients with a history of violent suicide attempts. Conclusions: Our study highlights that several clinical and temperamental characteristics are associated with violent suicide attempts, suggesting the importance of affective temperaments in the clinical management of patients with BPI.

Diet quality and eating patterns in euthymic bipolar patients.

As mood disorders and obesity are interrelated, and both are linked to increased morbidity and mortality, risk factors for obesity should be identified and closely monitored in patients with bipolar disorder (BD). The aim of this study was to determine the diet quality of BD patients and to investigate its putative associations with comorbid obesity and disorders of carbohydrate metabolism, as well as the relationship between diet and clinical features of BD. Eating patterns in 113 euthymic BD patients and 160 healthy control subjects were assessed using data obtained from a food frequency questionnaire. Associations of diet quality with subjects' weight, waist circumference (WC), insulin resistance index and clinical features of BD were also analyzed. BD patients had lower Mediterranean Diet Score than controls. Using principal analysis, four dietary patterns were revealed in the BD group (western-type, pro-healthy carbohydrates, unhealthy snacks, and meats and potatoes). Over 70% of patients with BD had Body Mass Index above 25kg/m2. The values of Fasting Triglycerides Glucose Index and WC were significantly higher in BD patients than in the control group. No significant association between diet quality indices and the clinical course of BD was found. In our work, euthymic bipolar patients showed unhealthy dietary patterns and had lower adherence to the Mediterranean diet than the controls. Increased values of insulin resistance indicators in the BD group point to the necessity of monitoring glucose and triglycerides levels and measurement of waist circumference in bipolar patients in the routine clinical practice. The cooperation between psychiatrists, dieticians and other medical professionals are necessary to develop dietary recommendations for patients with bipolar disorder.

Circadian rhythm in bipolar disorder: A review of the literature.

Sleep disturbances and circadian rhythm dysfunction have been widely demonstrated in patients with bipolar disorder (BD). Irregularity of the sleep-wake rhythm, eveningness chronotype, abnormality of melatonin secretion, vulnerability of clock genes, and the irregularity of social time cues have also been well-documented in BD. Circadian rhythm dysfunction is prominent in BD compared with that in major depressive disorders, implying that circadian rhythm dysfunction is a trait marker of BD. In the clinical course of BD, the circadian rhythm dysfunctions may act as predictors for the first onset of BD and the relapse of mood episodes. Treatments focusing on sleep disturbances and circadian rhythm dysfunction in combination with pharmacological, psychosocial, and chronobiological treatments are believed to be useful for relapse prevention. Further studies are therefore warranted to clarify the relation between circadian rhythm dysfunction and the pathophysiology of BD to develop treatment strategies for achieving recovery in BD patients.

Clinical course predicts long-term outcomes in bipolar disorder.

The long-term outcomes of bipolar disorder range from lasting remission to chronic course or frequent recurrences requiring admissions. The distinction between bipolar I and II disorders has limited utility in outcome prediction. It is unclear to what extent the clinical course of bipolar disorder predicts long-term outcomes. A representative sample of 191 individuals diagnosed with bipolar I or II disorder was recruited and followed for up to 5 years using a life-chart method. We previously described the clinical course over the first 18 months with dimensional course characteristics and latent classes. Now we test if these course characteristics predict long-term outcomes, including time ill (time with any mood symptoms) and hospital admissions over a second non-overlapping follow-up period in 111 individuals with available data from both 18 months and 5 years follow-ups. Dimensional course characteristics from the first 18 months prospectively predicted outcomes over the following 3.5 years. The proportion of time depressed, the severity of depressive symptoms and the proportion of time manic predicted more time ill. The proportion of time manic, the severity of manic symptoms and depression-to-mania switching predicted a greater likelihood of hospital admissions. All predictions remained significant after controlling for age, sex and bipolar I v. II disorder. Differential associations with long-term outcomes suggest that course characteristics may facilitate care planning with greater predictive validity than established types of bipolar disorders. A clinical course dominated by depressive symptoms predicts a greater proportion of time ill. A clinical course characterized by manic episodes predicts hospital admissions.

Circadian Rhythm Sleep-Wake Disorders Predict Shorter Time to Relapse of Mood Episodes in Euthymic Patients With Bipolar Disorder: A Prospective 48-Week Study.

Circadian rhythm dysfunction has been considered to be common in bipolar disorder (BD) and plays an important role in mood dysregulation in this disorder. However, no study has investigated whether circadian rhythm dysfunction would affect the clinical course of BD. The aim of this study was to test the hypothesis that circadian rhythm dysfunction could be a predictor of relapse in euthymic BD patients. One hundred four euthymic outpatients with BD diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), participated in this prospective follow-up study from August 2014 to April 2015. At baseline, data on demographic variables and clinical descriptive variables of bipolar disorder were ascertained via clinical interviews. The diagnoses of circadian rhythm sleep-wake disorders (CRSWDs) were made based on participants' sleep logs for 4 weeks and according to the International Classification of Sleep Disorders, Third Edition (ICSD-3). The BD symptoms of the subjects were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) scores every 4 weeks throughout the 48-week study period. Relapse of BD was defined as scores higher than the cutoff points (MADRS score ≥ 13 and YMRS score ≥ 7). The primary outcome was time to relapse of mood episodes. Thirty-four subjects met criteria for CRSWD at baseline, most frequently delayed sleep-wake phase disorder (n = 27). Of the total 104 subjects, 51 (49.0%) experienced relapse during the 48-week follow-up period. Multivariate Cox hazard regression analyses revealed that 2 or more previous mood episodes within the past year and comorbidity of CRSWD were significantly associated with the time to relapse of mood episodes (P < .001). Comorbid CRSWD, mainly delayed sleep-wake phase disorder, could be a significant predictor of relapse in BD patients.

Circadian rhythm sleep-wake disorders predict shorter time to relapse of mood episodes in euthymic patients with bipolar disorder: a prospective 48-week study

OBJECTIVE Circadian rhythm dysfunction has been considered to be common in bipolar disorder (BD) and plays an important role in mood dysregulation in this disorder. However, no study has investigated whether circadian rhythm dysfunction would affect the clinical course of BD. The aim of this study was to test the hypothesis that circadian rhythm dysfunction could be a predictor of relapse in euthymic BD patients. METHODS One hundred four euthymic outpatients with BD diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), participated in this prospective follow-up study from August 2014 to April 2015. At baseline, data on demographic variables and clinical descriptive variables of bipolar disorder were ascertained via clinical interviews. The diagnoses of circadian rhythm sleep-wake disorders (CRSWDs) were made based on participants' sleep logs for 4 weeks and according to the International Classification of Sleep Disorders, Third Edition (ICSD-3). The BD symptoms of the subjects were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) scores every 4 weeks throughout the 48-week study period. Relapse of BD was defined as scores higher than the cutoff points (MADRS score ≥ 13 and YMRS score ≥ 7). The primary outcome was time to relapse of mood episodes. RESULTS Thirty-four subjects met criteria for CRSWD at baseline, most frequently delayed sleep-wake phase disorder (n = 27). Of the total 104 subjects, 51 (49.0%) experienced relapse during the 48-week follow-up period. Multivariate Cox hazard regression analyses revealed that 2 or more previous mood episodes within the past year and comorbidity of CRSWD were significantly associated with the time to relapse of mood episodes (P < .001). CONCLUSIONS Comorbid CRSWD, mainly delayed sleep-wake phase disorder, could be a significant predictor of relapse in BD patients.

Increased illness burden in women with comorbid bipolar and premenstrual dysphoric disorder: data from 1 099 women from STEP-BD study.

The impact of comorbid premenstrual dysphoric disorder (PMDD) in women with bipolar disorder (BD) is largely unknown. We compared illness characteristics and female-specific mental health problems between women with BD with and without PMDD. A total of 1 099 women with BD who participated in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were studied. Psychiatric diagnoses and illness characteristics were assessed using the Mini International Neuropsychiatric Interview. Female-specific mental health was assessed using a self-report questionnaire developed for STEP-BD. PMDD diagnosis was based on DSM-5 criteria. Women with comorbid BD and PMDD had an earlier onset of bipolar illness (P < 0.001) and higher rates of rapid cycling (P = 0.039), and increased number of past-year hypo/manic (P = 0.003), and lifetime/past-year depressive episodes (P < 0.05). Comorbid PMDD was also associated with higher proportion of panic disorder, post-traumatic stress disorder, generalized anxiety disorder, bulimia nervosa, substance abuse, and adult attention deficit disorder (all P < 0.05). There was a closer gap between BD onset and age of menarche in women with comorbid PMDD (P = 0.003). Women with comorbid PMDD reported more severe mood symptoms during the perinatal period and while taking oral contraceptives (P < 0.001). The results from this study is consistent with research suggesting that sensitivity to endogenous hormones may impact the onset and the clinical course of BD. The comorbidity between PMDD and BD is associated with worse clinical outcomes and increased illness burden.

A longitudinal mirror-image assessment of morbidity in bipolar disorder

BackgroundEvidence about the clinical course of bipolar disorder is inconsistent and limited. The aim of this study was to assess changes in morbidity in patients with bipolar disorder along a mean follow-up period of 80months. MethodsBased on a mirror-image design, the follow-up period of each patient was divided into two halves. Then, three measures of morbidity — number of affective episodes, time spent ill, and cycle length — were recorded and compared between each half of the follow-up period. ResultsOn average, there was a trend to a smaller amount of time spent with subclinical symptomatology during the second half of the follow-up period. In contrast, there were no differences in terms of number of episodes, time spent with clinical symptoms, or cycle length between the first and second half of the follow-up period. A subgroup analysis identified 21.9% of patients with consistent data of a worsening during follow-up. ConclusionsThe results suggest that, on average, there is stability or slight improvement of clinical morbidity over the course of BD. Then, worsening of the clinical course may be a feature of a subgroup of patients rather than an inherent characteristic of the disorder. These subgroups or patient profiles could represent an opportunity for further studies to assess clinical, pathophysiologic, and therapeutic features associated with them.