Rapid cycling bipolar affective disorder in people with intellectual disability: a systematic review

Rapid cycling bipolar affective disorder has attracted renewed interest in the general adult psychiatric literature, particularly as the response to lithium prophylaxis is poor in this subgroup of patients. The present paper describes a systematic Medline/Psyclit review of case studies and small series of patients with rapid cycling bipolar affective disorder in people with intellectual disability (ID). Rapid cycling bipolar affective disorder in people with ID may differ from its occurrence in the non-ID population in terms of a relative preponderance of males, an increased likelihood of rapid cycling onset in those with an early (prepubertal) onset of affective disorder and a different response to prophylactic drugs. The efficacy of treatment and prophylaxis of rapid cycling illnesses needs further investigation in the population with ID.     

Lamotrigine therapy in treatment-resistant menstrually-related rapid cycling bipolar disorder: a case report

AIMS/OBJECTIVES: To evaluate lamotrigine in a woman with a 30-year history of treatment-resistant menstrually-entrained rapid cycling bipolar II disorder with follicular phase depressive and luteal phase mood elevation symptoms. METHODS: Lamotrigine was started at 5 mg/day and gradually increased up to 300 mg/day, while venlafaxine was tapered gradually and discontinued, and divalproex sodium 500 mg/day and levothyroxine 175 mcgm/day were continued. Daily self-reported mood ratings were obtained from the patient, using ChronoRecord software. RESULTS: As lamotrigine was increased gradually, mood cycle amplitude attenuated. There was notable decrease in the severity and duration of depressive symptoms specifically during the follicular phase of the menstrual cycle. At the time of submission of this paper, the subject had remained euthymic for a total of 12 months. CONCLUSION: This case suggests the potential utility of lamotrigine in treatment-resistant menstrually-related rapid cycling bipolar disorder, and raises the possibility that lamotrigine might be able to treat pathological entrainment of mood with the menstrual cycle. Both of these issues merit systematic assessment.     

Validation of the hypomania interview guide-seasonal affective disorder (HIGH-SAD) version in patients with rapid cycling bipolar disorder

We validated the Hypomania Interview Guide-Seasonal Affective Disorder (HIGH-SAD) version in patients with rapid cycling bipolar disorder (RCBD). Fourteen outpatients were rated on six separate occasions (total= 84 visits). On each visit the patients were rated with the HIGH-SAD and the Young Mania Rating Scale (YMRS) in a counterbalanced order. Clinical assessment was completed at the end of the visit by the treating psychiatrist. Patients were assessed as hypomanic/manic on 22 of the visits. Pearson correlation coefficient between the YMRS total scores and the HIGH-SAD total scores for those 22 visits in which patients were hypomanic/manic was r= 0.629 (P< 0.05) and for all visits was r= 0.769 (P<0.0001). Analysis with only one rating per patient yielded a Pearson correlation coefficient of r=0.792 (P<0.0004). We found that the HIGH-SAD was a valid scale for the measurement of hypomania in patients with RCBD. However, the scale does not differentiate hypomania from mania in this group of patients. Depression and Anxiety 8:166–168, 1998. Published 1998 Wiley-Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.     

Quetiapine in the treatment of rapid cycling bipolar disorder

Vieta E, Parramon G, Padrell E, Nieto E, Martinez‐Arán A, Corbella B, Colom F, Reinares M, Goikolea JM, Torrent C. Quetiapine in the treatment of rapid cycling bipolar disorder. Bipolar Disord 2002: 4: 335–340. © Blackwell Munksgaard, 2002 Introduction: This prospective open‐label study assessed the impact of add‐on quetiapine in the treatment of rapid cycling bipolar patients. Methods: Fourteen rapid cycling bipolar patients were treated with quetiapine, which was added to their ongoing medication regimen for 112 ± 33 days. At the beginning of the study, five were manic, three were in a mixed state, three were depressed, two hypomanic and one was euthymic. Patients were assessed prospectively with a modified version of the Clinical Global Impression Scale for Bipolars (CGI‐BP), the Young Scale for mania (YMRS) and the Hamilton Scale for Depression (HDRS). Results: A significant reduction of the following scale scores was observed: ? a 1.8 point reduction for the general CGI‐BP (p=0.013), ? a –1.3 point for the mania subscale (p=0.016), ? a –1.01 point for the YMRS (p=0.025). Improvement in depressive symptoms was not significant, neither in the CGI‐BP (–1 point, p=0.074) nor in the HDRS (–5.2 points, p=NS). The most common side‐effect was sedation (n=6, 43%). Doses of quetiapine were significantly reduced by the end of the study (443 ± 235 mg/day versus 268 ± 190 mg/day, p=0.008) and they also differed according to the initial episode to be treated (720 ± 84 mg/day for mania, and 183 ± 29 mg/day for depression, p=0.023). Conclusions: Quetiapine could possibly be an effective treatment for rapid cycling bipolar patients. Adequate doses for acute episodes could significantly differ according to the episode polarity and the length of treatment.     

Lithium alone or in combination with carbamazepine for the treatment of rapid-cycling bipolar affective disorder

The authors retrospectively examined the clinical outcome (after 1, 2 and 5 years of beginning the therapeutic protocols) for 16 rapid-cycling bipolar affective disorder patients given either lithium alone or lithium plus carbamazepine. The results suggest that both therapeutic protocols have been safe and clinically effective. However, improvement was observed earlier in the patients given lithium and carbamazepine.     

Treatment‐emergent mania/hypomania during antidepressant monotherapy in patients with rapid cycling bipolar disorder

Objective: To study treatment‐emergent mania/hypomania (TEM) associated with second‐generation antidepressant monotherapy in patients with rapid cycling bipolar disorder (RCBD). Methods: Data of patients with RCBD (n = 180) enrolled into two clinical trials were used to study the risk for TEM during second‐generation antidepressant monotherapy. History of TEM was retrospectively determined at the initial assessment by asking patients whether they were exposed to second‐generation antidepressants and if a hypomania/mania episode emerged during the first four weeks of treatment. Data were analyzed using t‐test, chi‐square, and logistic regression. Results: Of the 180 patients (bipolar I disorder, n = 128; bipolar II disorder, n = 52) with RCBD, 85% (n = 153) had at least one antidepressant treatment. Among these patients, 94.1% (144/153) had at least one antidepressant monotherapy treatment. Overall, 49.3% of patients had at least one TEM and 29.1% (116/399) of treatment trials were associated with TEM. In regression analysis, an inverse association between the number of mood episodes in the last 12 months and TEM was observed with an odds ratio of 0.9. However, gender, bipolar subtype, a lifetime history of comorbid anxiety disorder, substance use disorder, or psychosis, and age of mood disorder onset were not associated with TEM. For individual antidepressants, the rates of TEM varied from 42.1% for fluoxetine to 0% for fluvoxamine and mirtazapine. As a group, there was no difference between selective serotonin reuptake inhibitors and venlafaxine or bupropion in the incidence of TEM. Conclusions: Use of second‐generation antidepressants as monotherapy in RCBD is accompanied by clinically relevant rates of TEM. Even in patients with RCBD, differential vulnerabilities to antidepressant TEM may exist.     

Pharmacologic treatment of rapid cycling and mixed states in bipolar disorder: an argument for the use of lithium

Lithium has long been considered as less than ideal in the management of rapid cycling and mixed states in bipolar disorder. However, these forms of bipolarity represent a generally more difficult phase of the illness to treat with any medication. Increasing knowledge about lithium's other beneficial effects, including protection against suicide and neuromodulatory effects which may protect the brain, make it a first-line treatment for any form of bipolar disorder. As newer therapies become available or receive further exploration, we should look to the past and re-embrace lithium as a core therapeutic modality for bipolarity as we move forward in the field, particularly for forms of the disorder such as rapid cycling and mixed states, historically thought to be more treatment resistant.     

Neuroimaging in bipolar disorder

Objective: The authors reviewed neuroimaging studies of bipolar disorder in order to evaluate how this literature contributes to the current understanding of the neurophysiology of the illness.

Method: Papers were reviewed as identified, using the NIMH PubMed literature search systems that reported results of neuroimaging studies involving a minimum of five bipolar disorder patients compared with healthy comparison subjects.

Results: Structural neuroimaging studies report mixed results for lateral and third ventriculomegaly. Recent studies suggest subcortical structural abnormalities in the striatum and amygdala, as well as the prefrontal cortex. Proton spectroscopic studies suggest that abnormalities in choline metabolism exist in bipolar disorder, particularly in the basal ganglia. Additionally, phosphorous MRS suggests that there may be abnormalities in frontal phospholipid metabolism in bipolar disorder. Functional studies have identified affective state‐related changes in cerebral glucose metabolism and blood flow, particularly in the prefrontal cortex during depression, but no clear abnormalities specific to bipolar disorder have been consistently observed.

Conclusions: The current literature examining the neurophysiology of bipolar disorder using neuroimaging is limited. Nonetheless, abnormalities in specific frontal‐subcortical brain circuits seem likely. Additional targeted studies are needed to capitalize on this burgeoning technology to advance our understanding of the neurophysiology of bipolar disorder.     

Sleep and sleep-wake cycle in an 81-year-old patient with de novo ultra-rapid cycling bipolar disorder

This is a case report of an 81-year-old man who developed de novo bipolar disorder with ultra-rapid cycling at the age of 80. Mood was self-rated daily over a period of ten weeks; in addition, polysomnographic and motor activity recordings were performed during a drug-free baseline period. Both depressive and hypomanic episodes had an average duration of about 30 hours; the affective cycle was thus independent from the sleep-wake cycle. When mood shifts occurred during nighttime, sleep was different in nights following depression than in nights following hypomania. Positron emission tomography revealed a moderate bilateral frontal hypermetabolism in the hypomanic phase and yielded normal findings for the depressive stage. In contrast to what is usually expected in ultra-rapid cycling bipolar disorder, this case demonstrates an unusual sleep-unrelated cycle duration in the oldest reported patient so far. Received: 29 June 1999 / Accepted: 16 January 2001     

A case of temporal lobe epilepsy with improvement of clinical symptoms and single photon emission computed tomography findings after treatment with clonazepam

A 26-year-old female presented psychomotor seizures, deja vu and amnestic syndrome after meningitis at the age of 14 years. Repeated electroencephalograms (EEG) demonstrated occasional spikes localized in the right temporal region in addition to a considerable amount of theta waves mainly in the right fronto-temporal region. Single photon emission computed tomography (SPECT) showed a marked hypoperfusion corresponding to the region in which the EEG showed abnormal findings, although magnetic resonance imaging (MRI) demonstrated no abnormal findings associated with the clinical features. Treatment with clonazepam in addition to sodium valproate resulted in a remarkable improvement of clinical symptoms (i.e. psychomotor seizures and deja vu), as well as of the EEG and SPECT findings. The present study suggests that SPECT is a useful method not only to determine the localization of regions associated with temporal lobe epilepsy but also to evaluate the effect of treatment in temporal lobe epilepsy.     

A case of psychotic disorder associated with a right temporal lesion: a special reference to magnetic resonance imaging and single photon emission computed tomography findings

A case of psychotic disorder with a right temporal lesion was reported. The patient, a 19 year old male, who underwent a brain surgery to remove the trigeminal Schwannoma, occupying from the right cerebellopontine angle to the right middle cranial fossa. One year postoperatively, he presented with a psychotic disorder, including auditory hallucinations, delusions of persecution and reference, thought hearing, thought insertion and passive experiences. T1-weighted images on magnetic resonance imaging (MRI) demonstrated a low intensity signal area in the right temporal cortex and white matter. T2-weighted images demonstrated a high intensity signal within the same region. Single photon emission computed tomograghy (SPECT) demonstrated a severe low perfusion corresponding to the region in which the MRI demonstrated the abnormalities. The clinical and neuroimaging studies of this case suggest that psychotic disorder may occur in association with a right temporal lesion and MRI and SPECT are useful to evaluate an organic basis for the psychotic disorder.     

Neuropsychological impairment in bipolar disorder: the relationship with glucocorticoid receptor function

OBJECTIVE: Basal levels of glucocorticoids, such as cortisol, are generally unaltered in bipolar disorder. However, neuroendocrine tests of glucocorticoid receptor (GR) function such as the dexamethasone suppression test (DST) are frequently abnormal. Neuropsychological impairment is well documented in healthy volunteers after administration of glucocorticoids and in patients with bipolar affective disorder. This suggests a potential link between neuropsychological and hypothalamic-pituitary-adrenal axis function. We examined the hypothesis that neuropsychological impairment in bipolar disorder is associated with abnormal GR function. METHODS: Seventeen euthymic bipolar patients and 16 controls completed tests of verbal declarative and working memory (WM) tests and the DST. The correlation between neuroendocrine and neuropsychological function was examined. RESULTS: Bipolar patients made significantly more errors of omission and commission on the WM paradigm and demonstrated impaired verbal recognition memory. Patients' post-dexamethasone cortisol correlated with WM commission errors (r(s) = 0.64, p = 0.0006). No such relationship was evident in controls. CONCLUSION: Deficits in declarative memory and WM are evident in patients with bipolar disorder. The deficit in retrieval accuracy from WM appears to be correlated with abnormal GR function.     

Rapid cycling depression in adolescence. A case treated with family therapy and carbamazepine

This report aims at alerting the clinician to the existence of rapid cycling depression in adolescence. The importance of integrating psychodynamic, social and pharmacological modalities in evaluation and treatment is emphasized.     

Prefrontal and paralimbic metabolic dysregulation related to sustained attention in euthymic older adults with bipolar disorder

Brooks JO III, Bearden CE, Hoblyn JC, Woodard SA, Ketter TA. Prefrontal and paralimbic metabolic dysregulation related to sustained attention in euthymic older adults with bipolar disorder.
Bipolar Disord 2010: 12: 866–874. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objective: Reports of sustained attention deficits in the euthymic phase of bipolar disorder have been variable, and have yet to be related to cerebral metabolism. In the present study, we evaluated relationships between cognitive performance deficits and resting cerebral metabolism in euthymic older adults with bipolar disorder. Methods: Sixteen older (mean age 58.7 years) euthymic outpatients with bipolar disorder (10 type I, 6 type II; 44% female) and 11 age‐matched healthy controls received resting positron emission tomography with ¹⁸fluorodeoxyglucose and, within 10 days, the Conners’ Continuous Performance Test‐II, a commonly used measure of sustained attention and inhibitory control. Results: Bipolar disorder patients had significantly more omission errors (z = 2.53, p = 0.01) and a trend toward more commission errors (z = 1.83, p < 0.07) than healthy controls. Relative to healthy controls, among bipolar disorder subjects commission errors were more strongly related to inferior frontal gyrus [Brodmann area (BA) 45/47] hypometabolism and paralimbic hypermetabolism. In bipolar disorder subjects, relative to controls, omission errors were more strongly related to dorsolateral prefrontal (BA 9/10) hypometabolism and greater paralimbic, insula, and cingulate hypermetabolism. Conclusions: In older adults with bipolar disorder, even during euthymia, resting‐state corticolimbic dysregulation was related to sustained attention deficits and inhibitory control, which could reflect the cumulative impact of repeated affective episodes upon cerebral metabolism and neurocognitive performance. The relative contributions of aging and recurrent affective episodes to these differences in bipolar disorder patients remain to be established.     

Thyroid hypofunction in patients with rapid-cycling bipolar disorder after lithium challenge.

BACKGROUND: There is debate whether patients with rapid-cycling bipolar disorder (BD) are predisposed to thyroid axis abnormalities and whether this may contribute to development of rapid mood shifts. Using lithium carbonate as a challenge to the hypothalamic-pituitary-thyroid (HPT) system, we determined whether patients with rapid-cycling BD are sensitive to the "antithyroid" properties of lithium. METHODS: We studied the response to thyrotropin-releasing hormone (TRH) of HPT system hormones in 20 medication-free patients with rapid-cycling BD and compared these measurements with those of 20 healthy age- and gender-matched control subjects. The same measurements were repeated after both groups had received lithium carbonate for 4 weeks in sufficient doses to maintain blood levels between.7-1.2 mEq/L. RESULTS: At baseline, the results of thyroid function tests, including the TRH challenge test, did not differ between patients and control subjects. After treatment with lithium, serum concentrations of thyroxine significantly decreased, whereas basal thyrotropin (TSH) and DeltaTSH(max) significantly increased in both patients and control subjects; however, patients had significantly higher DeltaTSH(max) after TRH stimulation. More patients than control subjects developed laboratory evidence consistent with grade III hypothyroidism after lithium treatment. CONCLUSIONS: Rapid-cycling BD is associated with a latent hypofunction of the HPT system. This dysfunction becomes manifest with short-term lithium challenge.     

Regional cerebral blood flow changes in patients with idiopathic REM sleep behavior disorder

Background: Recent studies have shown an association between rapid eye movement sleep behavior disorder (RBD) and neurodegenerative disorders, especially alpha‐synucleinopathies. Objective: We investigated regional cerebral blood flow (rCBF) changes using single photon emission computed tomography (SPECT) in patients with idiopathic RBD (iRBD), to determine functional brain alterations associated with the disorder. Methods: The SPECT data of 24 patients with iRBD were compared with those of 18 age‐matched normal controls using statistical parametric mapping 2. Results: We found decreased rCBF in the parietooccipital lobe (precuneus), limbic lobe, and cerebellar hemispheres in patients with iRBD, which is commonly seen in patients with Lewy body disease (Parkinson’s disease and dementia with Lewy bodies) or multiple system atrophy. Conclusion: Our SPECT study suggests that iRBD can be a presymptomatic stage of alpha‐synucleinopathies.