Chronic Bipolar Disorder Research Articles

Nonseizure Response to ECT in Older Adults with Bipolar Depression on Bumetanide

Abstract: Psychiatric presentations in older adults are complicated by chronic comorbidities, polypharmacy, and older age-related psychosocial changes. This case report discusses an unusual treatment response to ECT in a 75-year-old man with chronic bipolar disorder. There was no seizure activity on EEG and upon direct observation in 3 out of 7 ECT sessions. After an in-depth medication review of its impact on ECT, we propose that bumetanide could likely have contributed to the nonseizure response. Bumetanide was proposed as a potential antiepileptic agent, but the evidence for its effect on ECT is sparse. A proportion of older adults receiving ECT are likely to be on this FDA-approved diuretic for cardiovascular comorbidities. This case highlights the need for further studies to test for ECT-modifying of bumetanide.

Patients with chronic bipolar disorder show impairments in interpreting literary fiction - A preliminary explorative study with the short story task

IntroductionTheory of mind (ToM) is a crucial skill in navigating and functioning in the social world. Significant ToM impairment was consistently found in bipolar disorder; it can be both a state and trait marker of the disorder. However, most of the ToM tests are not sensitive enough to detect subtle individual differences, which would be necessary for an individualized treatment plan. The Short Story Task (SST) is a new way to sensitively assess individual differences in ToM performance. The aim of the study was to test the feasibility of SST in patients with bipolar disorder. Method31 persons (11 male, 20 female) with bipolar I disorder and 31 healthy individuals (15 males and 16 females) as a control group were recruited. SST was used to evaluate ToM performance. The SST uses a Hemingway novel, in which the patient is presented with a realistic social situation, where the motivations of the characters and the underlying relationships of events are not explicitly described. ResultsIn the explicit mental state reasoning questions the CG (M = 8.06) had significantly higher (p < 0.001) scores than the persons with bipolar I disorder (M = 5.03). There was no ceiling effect for explicit ToM scores in either group. Participants in CG (M = 8.03) also significantly outperformed (p = 0.006) the BG participants (M = 6.55) in the comprehension questions. The spontaneous mental state inference question was performed equally (M = 0.23) in both groups. Group assignment (t = −3.503, p < 0.001), comprehension score (t = 2.864, p = 0.006), and spontaneous mentalization (t = 2.846, p = 0.006) significantly predicted the explicit ToM performance. ConclusionsOverall, we found that the Short Story Task is a promising tool for measuring ToM in patients with bipolar disorder without ceiling effect. Primarily explicit ToM was found to be deficient, which corresponds well with the ToM literature in bipolar disorder. Contrary to our hypothesis we could not detect impairment in spontaneous ToM and found that patients living with bipolar disorder also showed deficits in comprehension. The lack of assessment of neurocognitive skills is a significant limitation of the current study.

Diabetes mellitus in patients with chronic bipolar disorder: prevalence, clinical correlates and relationship with homocysteine.

Comorbid diabetes mellitus in patients with bipolar disorder may contribute to increased morbidity and mortality. To determine the prevalence of diabetes mellitus in bipolar disorder patients and its clinico-demographic and homocysteine correlates, we conducted a cross-sectional survey of 195 bipolar disorder inpatients. They received questionnaires, clinical measurements and laboratory tests to assess demographic characteristics, anthropometric variables, clinical variables and plasma homocysteine levels. The prevalence of diabetes mellitus (including type 1, type 2 and special types) in Chinese bipolar disorder patients was 14.9%. Analysis of variance or chi-square test showed that compared with non-diabetic bipolar disorder patients, diabetic bipolar disorder patients were older, more often married, had a longer duration of disease, took less olanzapine and had a higher frequency of hypertension. However, there were no significant differences in body mass index (BMI) and homocysteine levels between diabetic and non-diabetic bipolar disorder patients. Logistic regression analysis showed that marital status and duration of disease were independently associated with diabetes mellitus in patients with bipolar disorder after controlling for age, use of olanzapine, presence of hypertension, BMI and homocysteine levels. These findings shed light on the clinico-demographic correlates of the increased prevalence of diabetes mellitus in bipolar disorder patients, rather than the correlation with some metabolic risk factors.

Management of Bipolar Disorder During the Perinatal Period

Bipolar disorder (BPD) is a lifelong mental health condition characterized by symptoms of mania, depression, and often anxiety. BPD can have detrimental consequences for individuals during pregnancy and the postpartum period, as well as for their offspring. This is often due to underdiagnosis and/or misdiagnosis as unipolar depression. There is a high incidence of first episodes of BPD in pregnant and postpartum persons. Perinatal care providers need to routinely screen for BPD and assess for relapse among those with a previous diagnosis during the pregnancy and postpartum periods. Medication management is complex and must be considered in the context of an individual’s risk factors and perceptions about treatment as well as the limited evidence regarding fetal safety, using a shared decision-making model. Collaboration, consultation, and/or referral to mental health care providers are essential for managing acute and chronic BPD symptoms.

Cognitive rehabilitation of attention and working memory in patients with chronic bipolar disorder using RehaCom software

Cognitive rehabilitation of attention and working memory in patients with chronic bipolar disorder using RehaCom software

Emotional intelligence: a comparison between patients after first episode mania and those suffering from chronic bipolar disorder type I.

Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients. The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model. In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (s.e.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, s.e. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (β = -0.293, p = 0.034) and verbal memory performance (β = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains. Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.

Vincent Van Gogh and the elusive diagnosis of vestibular migraine

Vincent Van Gogh (1853–1890) was a creative genius and one of the greatest painters in history. He was a troubled soul plagued with an inner turmoil driven by his social, financial, personality and medical/psychiatric afflictions. His life has fascinated academic scholars of many disciplines who have researched extensively on his life and works. From his voluminous correspondences and contemporary medical records, his medical/psychiatric illnesses have been analysed in detail and several diagnostic formulations proposed. These include temporal lobe epilepsy, intermittent acute porphyria, Meniere’s disease, lead poisoning, sexually transmitted diseases, terpene/absinthe/alcohol abuse, ophthalmological disorders in addition to chronic bipolar disorder, schizophrenia, personality and anxiety disorder and narcissism/neuroticism. We hypothesized a new diagnosis in the form of vestibular migraine for Van Gogh which is a migraine variant but distinct from the classical migraine variety. Our hypothesis is unique as it also considers that this condition due to its recognised associations with Van Gogh’s proposed illnesses could have influenced his other conditions and thus offers a common unifying factor to explain his illness symptoms. We tested our hypothesis by individually analysing all of Van Gogh’s correspondences in the original French and Dutch as well as English translations. Further, we considered the existing literature on Van Gogh’s other illnesses and contemporary medical records. Van Gogh fulfilled all the criteria for vestibular migraine as formulated by Barany Society and International Classification of Headache Disorders (ICHD) 3 with episodic dizziness, present or past history of classical migraine, headache, photophobia, phonophobia and visual and position triggered vertigo with no other otologial cause to explain his symptoms (including Meniere’s disease). Furthermore, it appears that vestibular migraine could have interacted with most of his other proposed illnesses. We also observed that this condition influenced his art following onset for example, in his use of colours and depiction of his subject matter with a consistent vertical tilt on the left. It is anticipated that our hypothesis will add a new dimension to the understanding of his illnesses and increase the awareness of the complex condition of vestibular migraine that to this day has limited awareness amongst the medical and general fraternity.

Decreased leucocyte telomere length in male patients with chronic bipolar disorder: lack of effect of long-term lithium treatment.

Bipolar disorder (BD) may be connected with accelerated aging, the marker of this can be shorter telomere length (TL). Some data suggest that lithium may exert a protective effect against telomere shortening. The study aimed to compare the TL between patients with BD and control subjects. The effect of long-term lithium treatment was also assessed. The study group comprised 41 patients with BD, including 29 patients treated longitudinally with lithium (mean 16.5 years) and 20 healthy people. TL was assessed by the quantitative polymerase chain reaction (qPCR). In the control group, the TL was significantly longer in males than in females. Male bipolar patients had significantly shorter TL compared with the control male group. In bipolar patients, there was no correlation between TL and duration of treatment. The TL was negatively correlated with age in male bipolar patients. The study did not confirm the lithium effect on TL in bipolar patients. TL showed gender differences, being shorter in BD males, compared to control males, and longer in healthy males, compared to control females.

Individualized identification of first-episode bipolar disorder using machine learning and cognitive tests

Identifying cognitive dysfunction in the early stages of Bipolar Disorder (BD) can allow for early intervention. Previous studies have shown a strong correlation between cognitive dysfunction and number of manic episodes. The objective of this study was to apply machine learning (ML) techniques on a battery of cognitive tests to identify first-episode BD patients (FE-BD). Two cohorts of participants were used for this study. Cohort #1 included 74 chronic BD patients (CHR-BD) and 53 healthy controls (HC), while the Cohort #2 included 37 FE-BD and 18 age- and sex-matched HC. Cognitive functioning was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The tests examined domains of visual processing, spatial memory, attention and executive function. We trained an ML model to distinguish between chronic BD patients (CHR-BD) and HC at the individual level. We used linear Support Vector Machines (SVM) and were able to identify individual CHR-BD patients at 77% accuracy. We then applied the model to Cohort #2 (FE-BD patients) and achieved an accuracy of 76% (AUC=0.77). These results reveal that cognitive impairments may appear in early stages of BD and persist into later stages. This suggests that the same deficits may exist for both CHR-BD and FE-BD. These cognitive deficits may serve as markers for early BD. Our study provides a tool that these early markers can be used for detection of BD.

Global DNA hypomethylation and its correlation to the betaine level in peripheral blood of patients with schizophrenia

Accumulating evidence suggests that aberrant epigenetic regulation is involved in the pathophysiology of major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). We previously showed that the plasma level of betaine (N,N,N-trimethylglycine), a methyl-group donor, was significantly decreased in patients with first episode schizophrenia (FESZ). In this study, we identified decrease of global DNA methylation level in FESZ (N = 24 patients vs N = 42 controls), and found that global DNA methylation level was inversely correlated with scores on the global assessment of functioning (GAF) scale, and positively correlated with plasma betaine level. Notably, correlations between levels of betaine and its metabolites (N,N-dimethylglycine and sarcosine, N-methylglycine) were lower or lost in FESZ plasma, but remained high in controls. We further examined global DNA methylation levels in patients with chronic SZ (N = 388) and BD (N = 414) as well as controls (N = 430), and confirmed significant hypomethylation and decreased betaine level in SZ. We also found that patients with BD type I, but not those with BD type II, showed significant global hypomethylation. These results suggest that global hypomethylation associated with decreased betaine level in blood cells is common to SZ and BD, and may reflect common pathophysiology such as psychotic symptoms.

Inflammation and Neurodegeneration in Patients with Early-Stage and Chronic Bipolar Disorder

The increase in the circulatory cytokine levels observed in patients with bipolar disorder (BD) may imply involvement of inflammation in the pathogenesis of mood disorders. However, the association between the inflammatory process and the stage and severity of illness is not well understood. In this study, our aim was to investigate the association between neuroinflammation and disease progression in the clinical course of BD. IL-6, TNF-α, IL-1 receptor antagonist (IL-1RA), neuronspecific enolase (NSE) and S100B were measured by ELISA in plasma samples of patients at early-stage BD (n=30), chronic BD (n=77) and healthy controls (n=30). Chronic BD patients showed significantly increased levels of all measured inflammatory markers as compared to early-stage BD patients and the healthy controls. IL-6 and IL-1RA levels correlated with NSE and/or S100B levels and TNF-α levels correlated with Montgomery- Asberg Depression Rating Scale scores and Clinical Global Impression Scale scores. Our results indicate that inflammation appears to be particularly associated with IL-1RA and IL-6 activity, progressing at later stages of BD and possibly associated with gliosis and neuronal loss.

Patients with chronic bipolar disorder exhibit widespread increases in extracellular free water.

Bipolar disorder (BP) is a debilitating psychiatric disease that is not well understood. Previous diffusion magnetic resonance imaging (dMRI) studies of BP patients found prominent microstructural white matter (WM) abnormalities of reduced fractional anisotropy (FA). Because FA is a nonspecific measure, relating these abnormalities to a specific pathology is difficult. Here, dMRI specificity was increased by free water (FW) imaging, which allows identification of changes in extracellular space (FW) from neuronal tissue (fractional anisotropy of tissue [FA-t]). Previous studies identified increased FW in early schizophrenia (SZ) stages which was replaced by widespread decreased FA-t in chronic stages. This is the first analysis utilizing this method to compare BP patients and controls. 3 Tesla diffusion weighted imaging (3T DWI) data were acquired for 17 chronic BP and 28 healthy control (HC) participants at Oxford University. Tract-based spatial statistics was utilized to generate a WM skeleton. FW imaging deconstructed the diffusion signal into extracellular FW and tissue FA-t maps. These maps were projected onto the skeleton and FA, FA-t, and FW were compared between groups. We found significantly lower FA in BP patients when compared to HC in areas that overlapped with extensive FW increases. There were no FA-t differences. Our study suggests that chronic BP shows similar WM changes to early SZ, suggesting that extracellular FW increases could be a transient indication of recent psychotic episodes. Since FW increase in SZ has been suggested to be related to neuroinflammation, we theorize that neuroinflammation might be a shared pathology between chronic BP and early SZ.

The barriers to participation in leisure time physical activities among Iranian women with severe mental illness: A qualitative study

Background and objectivesSedentary behavior and physical inactivity are known risk factors for poor health and increased mortality in patients with severe mental illness. Identifying the barriers to participation in leisure-time physical activities among these patients can be helpful in planning effective interventions aimed at increasing activity level. Prior to the present study, the barriers experienced by female patients in Iran were unknown. Materials and methodsThis was a qualitative study using conventional content analysis. Participants were 32 women with severe mental illness who were hospitalized at women's psychiatric wards of Farabi Teaching Hospital in Kermanshah, Iran, from September 2015 to March 2016. Data were collected through four focus group discussion sessions and were then analyzed. ResultsParticipants had a mean age of 42 (SD = 7.8) and an active diagnosis of schizoaffective disorder (n = 10), schizophrenia (n = 8), a chronic bipolar disorder (n = 8), or major depression disorder (n = 6). Two main barrier categories emerged: Personal experience of disease and Non-supportive context. Within the former, stigma of disease, signs and symptoms of disease, and medication side effects were the constituent subcategories. Non-supportive context subcategories consisted of family, cultural, environmental, and medical staff barriers that influenced non-participation in leisure-time physical activities. ConclusionIranian women with severe mental illness face a number of barriers to participation in leisure-time physical activities including the stigma, symptoms, and treatment of mental illness; and contextual barriers such as family expectations, societal perceptions, environmental factors, and lack of medical staff support. It is recommended that providers consider these factors when developing therapeutic plans for similar patient populations.

Bipolar disorder patients display reduced serum complement levels and elevated peripheral blood complement expression levels.

Bipolar disorder (BD) patients have recently been shown to exhibit increased proinflammatory cytokine levels indicating the role of inflammation in this disease. As inflammatory responses often include complement level alterations and complement production is influenced by cytokines, we aimed to find out whether complement system is activated in BD in a time-dependent manner and complement factors are involved in BD pathogenesis. Serum C4, factor B, sC5b-9 and neuron-specific enolase levels were measured by enzyme-linked immunosorbent assay, whereas peripheral blood mononuclear cell messenger RNA (mRNA) expression levels of C1q, C4, factor B and CD55 were measured by real-time polymerase chain reaction in chronic BD patients (n=22), first episode BD patients (n=24) and healthy controls (n=19). Serum complement levels were significantly reduced in chronic BD patients as compared with first episode BD patients and healthy controls. Serum levels of complement factors showed significant inverse correlation with disease duration, severity of manic symptoms and serum neuron-specific enolase levels. In chronic BD patients, peripheral blood mononuclear cell mRNA expression levels of C1q, C4 and factor B were significantly elevated, whereas the mRNA expression level of the complement inhibitor CD55 was significantly reduced. Our results suggest that complement factor levels are reduced in BD presumably due to overconsumption of the complement system and complement production is increased at mRNA level possibly as a compensation measure. Complement factors might potentially be used as indicators of disease severity, neuronal loss and cognitive dysfunction.

Mind: explore the space inside.

When caught in the dilemma of career choice, a critical conversation helped the writer crystallize the decision to plunge into the field of mental health. The decision just not only kindled interest in psychiatry but passion to study the science of the mind despite the fact that in earlier times psychiatry mainly catered to patients with chronic schizophrenia and uncontrolled bipolar disorder. Weathering the curious glances of colleagues the writer pursued to explore the field of the science of the mind. Not restricting himself to classical trends in private practice, he explored every opportunity to reach out to the common man through writing articles in popular newspapers and also ran a TV Show to respond to people's queries on mental health. He further ventured into training and development of young MBA aspirants and trained himself into an international coach and facilitator. The science of Behavioural Economics beckons him now.

Differentiating Between the Course of Illness in Bipolar 1 and Chronic-Psychotic Heroin-Dependent Patients at Their First Agonist Opioid Treatment

In an effort to inquiry the “self-medication hypothesis” in heroin-dependent patients suffering from chronic psychosis and bipolar disorder, a naturalistic comparative cohort study was designed with the aim of comparing, according to the presence of dual diagnosis, the clinical characteristics of heroin-dependent patients presenting for their first agonist opioid treatment. The main finding was that addictive (heroin) illness was more severe in bipolar 1 patients and less severe in chronic psychotic patients when compared with heroin-dependent patients without dual diagnoses. In the case of chronic psychotic patients, these differences do not allow us to exclude a therapeutic heroin use, at least at the beginning of their toxicomanic career, with limited progression of their addictive disease. This occurrence seems to be excluded for bipolar 1 heroin-dependent patients, who come to their first agonist opioid treatment with a more severe addictive disease.

Evaluation of the acceptability and usefulness of an information website for caregivers of people with bipolar disorder

BackgroundBipolar disorder is associated with extreme mood symptoms, disability and suicide risk. Close family or friends often have a primary role in supporting an adult with bipolar disorder. However, not all support is helpful and there is little publicly accessible evidence-based information to guide caregivers. Caregiver burden increases the risk of caregiver depression and health problems. To help fill the information gap, expert clinicians, caregivers and consumers contributed to the development of guidelines for caregivers of adults with bipolar disorder using the Delphi consensus method. This paper reports on an evaluation of the acceptability and usefulness of the online version of the guidelines, http://www.bipolarcaregivers.org.MethodsVisitors to the website responded to an initial online survey about the usefulness of the information (N = 536). A more detailed follow-up feedback survey was emailed to web users who were adult caregivers of adults with bipolar disorder a month later (N = 121). The feedback was analyzed quantitatively and qualitatively to establish user appraisals of the online information, whether and how caregivers applied the information and ways it could be improved.ResultsThe majority of users (86.4% to 97.4%) found the various sections of the website useful. At follow-up, nearly 93% of caregivers reported that the information was relevant to them and 96% thought it would help others. Most respondents said that the information was supportive and encouraged adaptive control appraisals. However, a few respondents who were experiencing complex family problems, or who cared for a person with severe chronic bipolar disorder did not appraise it as positively. Nevertheless, over two-thirds of the caregivers reported using the information. Optional interactive features were recommended to maximize benefits.ConclusionsOverall, http://www.bipolarcaregivers.org was appraised positively and used. It appears useful to close family and friends seeking basic information and reassurance, and may be an inexpensive way to disseminate guidelines for caregivers. Those who care for people with more severe and chronic bipolar disorder, or who have complex family problems might benefit from more specialized interventions, suggesting the importance of a stepped-care approach to supporting caregivers. The potential of evidence-based, collaboratively developed information websites to enhance caregiver and consumer outcomes merits further investigation.

Peripheral oxidative damage in early-stage mood disorders: a nested population-based case-control study

Systemic toxicity is a relevant dimension of pathophysiology in bipolar disorder, and oxidative damage is one potential link between central and peripheral pathology. Although there is mounting evidence that chronic bipolar disorder is associated with oxidative stress, studies in the early stages of bipolar disorder are scarce, and heavily reliant on clinical in lieu of population studies. The objective of this study was to confirm leading hypotheses about the role of oxidative damage in bipolar disorder. To that end, we nested a case-control study in a population-based study of young adults aged 18-24 yr. After an initial psychopathology screen, all people with a lifetime history of (hypo)mania and matched controls underwent a structured diagnostic interview. This yielded a sample of 231 participants, in whom we measured serum protein carbonyl content (PCC) and thiobarbituric acid reactive substances (TBARS). People with bipolar disorder had higher PCC levels than healthy subjects. Those with major depression were not different from control subjects in either PCC or TBARS levels. Both bipolar disorder and major depression were associated with higher PCC levels in the a priori regression model controlling for possible confounders. These findings indicate that protein oxidative damage is present from early stages and can be seen as a sign of early illness activity in mood disorders.

Different gray matter patterns in chronic schizophrenia and chronic bipolar disorder patients identified using voxel-based morphometry

Gray matter (GM) volume deficits have been described in patients with schizophrenia (Sz) and bipolar disorder (BD), but to date, few studies have directly compared GM volumes between these syndromes with methods allowing for whole-brain comparisons. We have used structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) to compare GM volumes between 38 Sz and 19 BD chronic patients. We also included 24 healthy controls. The results revealed a widespread cortical (dorsolateral and medial prefrontal and precentral) and cerebellar deficit as well as GM deficits in putamen and thalamus in Sz when compared to BD patients. Besides, a subcortical GM deficit was shown by Sz and BD groups when compared to the healthy controls, although a putaminal reduction was only evident in the Sz patients. In this comparison, the BD patients showed a limited cortical and subcortical GM deficit. These results support a partly different pattern of GM deficits associated to chronic Sz and chronic BD, with some degree of overlapping.

Cortical and subcortical white matter abnormalities in adults with remitted first‐episode mania revealed by Tract‐Based Spatial Statistics

Abnormalities of brain white matter have been noted in structural magnetic resonance imaging and diffusion tensor imaging (DTI) studies of bipolar disorder, but there are fewer investigations specifically examining white matter integrity early in the course of illness. In this study, we employed DTI to elucidate white matter changes in adult patients with remitted first-episode mania and hypothesized that first-episode mania was associated with decreased fractional anisotropy in cortical (frontal) and subcortical (thalamus, striatum) white matter as well as white matter tracts (cingulum, corpus callosum). Diffusion tensor images were acquired from 16 patients with remitted first-episode mania and 16 healthy controls matched for age, gender, handedness, and years of education. Fractional anisotropy and radial and axial diffusivities were analyzed using Tract-Based Spatial Statistics. Patients had lower fractional anisotropy and higher radial diffusivity in the left anterior frontal white matter, right posterior thalamic radiation, left cingulum, and bilateral sagittal striatum. In addition, increased radial diffusivity was found in the left corpus callosum. Our findings highlighted that white matter abnormalities were present by the time of remission of first-episode mania. The widespread occurrence of these white matter abnormalities both in first-episode mania and chronic bipolar disorder suggested that disruption of white matter cortical-subcortical networks as well as projection, associative, and commissural tracts is a hallmark of the illness.