Reduced left anterior cingulate volumes in untreated bipolar patients.

BACKGROUND: Functional and morphologic abnormalities of the cingulate cortex have been reported in mood disorder patients. To examine the involvement of anatomic abnormalities of the cingulate in bipolar disorder, we measured the volumes of this structure in untreated and lithium-treated bipolar patients and healthy control subjects, using magnetic resonance imaging (MRI). METHODS: The volumes of gray matter at the right and left anterior and posterior cingulate cortices were measured in 11 bipolar patients not taking any psychotropic medications (aged 38 +/- 11 years, 5 women), 16 bipolar patients treated with lithium monotherapy (aged 33 +/- 11 years, 7 women), and 39 healthy control subjects (aged 37 +/- 10 years, 14 women). Volumetric measurements were made with T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5T, and were done blindly. RESULTS: Using analysis of covariance with age and intracranial volume as covariates, we found that untreated bipolar patients had decreased left anterior cingulate volumes compared with healthy control subjects [2.4 +/-.3 cm3 and 2.9 +/-.6 cm3, respectively; F(1,58) = 6.4, p =.042] and compared with lithium-treated patients [3.3 +/-.5 cm3; F(1,58) = 11.7, p =.003]. The cingulate volumes in lithium-treated patients were not significantly different from those of healthy control subjects. CONCLUSIONS: Our findings indicate that anatomic abnormalities in left anterior cingulate are present in bipolar patients. Furthermore, our results suggest that lithium treatment might influence cingulate volumes in bipolar patients, which could possibly reflect postulated neuroprotective effects of lithium.     

Cross-sectional study of abnormal amygdala development in adolescents and young adults with bipolar disorder.

BACKGROUND: In vivo imaging studies in adult bipolar patients have suggested enlargement of the amygdala. It is not known whether this abnormality is already present early in the illness course or whether it develops later in life. We conducted a morphometric MRI study to examine the size of specific temporal lobe structures in adolescents and young adults with bipolar disorder and healthy control subjects, as well as their relationship with age, to examine possible neurodevelopmental abnormalities. METHODS: Subjects included 16 DSM-IV bipolar patients (16 +/- 3 years) and 21 healthy controls (mean age +/- SD = 17 +/- 4 years). Measures of amygdala, hippocampus, temporal gray matter, temporal lobe, and intracranial volumes (ICV) were obtained. RESULTS: There was a trend to smaller left amygdala volumes in patients (mean volumes +/- SD = 1.58 +/- .42 mL) versus control subjects (1.83 +/- .4 mL; F = 3.87, df = 1,32, p = .06). Bipolar patients did not show significant differences in right or left hippocampus, temporal lobe gray matter, temporal lobe, or right amygdala volumes (analysis of covariance, age, gender, and ICV as covariates, p > .05) compared with healthy control subjects. Furthermore, there was a direct correlation between left amygdala volumes and age (r =. 50, p = .047) in patients, whereas in healthy controls there was an inverse correlation (r = -.48, p = .03). CONCLUSIONS: The direct correlation between left amygdala volumes and age in bipolar patients, not present in healthy control subjects, may reflect abnormal developmental mechanisms in bipolar disorder.     

Magnetic resonance imaging study of corpus callosum abnormalities in patients with bipolar disorder.

BACKGROUND: This study was conducted to further examine the hypothesis of abnormalities in size of corpus callosum in subjects with bipolar disorder. METHODS: Sixteen right-handed DSM-IV bipolar I patients and 27 right-handed healthy control subjects were studied. A 1.5-T GE Signa magnet was used, and three-dimensional gradient echo imaging (spoiled gradient recall acquisition) was conducted. Area measurements of corpus callosum were obtained blindly, with a semi-automated software, by a well-trained rater. RESULTS: Right-handed bipolar I patients had significantly smaller total corpus callosum, genu, posterior body, and isthmus areas compared with right-handed healthy control subjects (analysis of covariance with age, gender, and intracranial volume as covariates, p <.05). Partial correlation analyses, controlled for intracranial volumes, found a significant inverse relationship between age and total callosal, genu, anterior body, isthmus, and circularity in healthy control subjects (p <.05) but not in bipolar patients (p >.05). CONCLUSIONS:Smaller callosal areas may lead to altered inter-hemispheric communication and be involved in the pathophysiology and cognitive impairment found in bipolar disorder.     

An emotional Stroop functional MRI study of euthymic bipolar disorder

Objective:  To identify the brain regions associated with emotional processing in euthymic bipolar patients.
Methods:  The study examined 12 euthymic bipolar patients using functional magnetic resonance imaging (fMRI) while performing an emotional Stroop (eStroop) task. The task comprised emotionally valent and neutral words presented in alternating blocks that was designed to implicitly induce affect. In conjunction with fMRI, galvanic skin responses (GSR) were measured to monitor arousal.
Results:  Euthymic bipolar patients had diminished activation in response to the affective stimuli in both cortical and subcortical brain regions when compared with healthy subjects. In particular, patients had less activation in the left ventral prefrontal cortex suggesting a potential trait deficit. Patients were slower to react than healthy controls, but did not differ with respect to accuracy.
Conclusions:  Euthymic bipolar patients are perhaps constrained in their ability to engage affective processing. Diminished ventral prefrontal cortex activation corroborates previous reports of a potential trait deficit, suggesting that 'all is not well in euthymia', although the effects of medication cannot be overlooked.     

Gender differences in bipolar disorder type I and II

Objective: We investigated gender differences in bipolar disorder (BD) type I and II in a representative cohort of secondary care psychiatric in‐ and out‐patients. Method: In the prospective, naturalistic Jorvi Bipolar Study of 191 secondary care psychiatric in‐ and out‐patients, 160 patients (85.1%) could be followed up for 18 months with a life chart. Results: After adjusting for confounders, no marked differences in illness‐related characteristics were found. However, female patients with BD had more lifetime comorbid eating disorders (P < 0.001, OR = 5.99, 95% CI 2.12–16.93) but less substance use disorders (P < 0.001, OR = 0.29, 95% CI 0.16–0.56) than males. Median time to recurrence after remission was 3.1 months longer among men than women, female gender carrying a higher hazard of recurrence (P = 0.006, HR = 2.00, 95% CI 1.22–3.27). Conclusion: Men and women with type I and II BD have fairly similar illness‐related clinical characteristics, but their profile of comorbid disorders may differ significantly, particularly regarding substance use and eating disorders. In medium‐term follow‐up, females appear to have a higher hazard of recurrence than males.     

Comorbidity of attention deficit hyperactivity disorder in juvenile bipolar disorder

OBJECTIVE: There is some evidence to suggest that attention deficit hyperactivity disorder (ADHD) and juvenile bipolar disorder could be related. This is based on studies of comorbidity and some preliminary family study data. However, doubts continue to be raised about the relationship between the two disorders. This study examined the comorbidity of disruptive behavior disorders (DBD) that include ADHD, oppositional defiant disorder (ODD) and conduct disorder (CD) in juvenile bipolar disorder. METHOD: Seventy-three subjects with onset of bipolar disorder at age 18 years or younger were evaluated using structured interviews (Missouri Assessment of Genetics Interview for Children, Structured Clinical Interview for DSM-IV Axis I disorders--Clinician Version, and Operational Criteria Checklist for Psychotic Disorders version 3.4). Information was collected from subjects as well as from their parents. Patients with comorbid DBD were compared with patients without DBD. RESULTS: Ten subjects (14%) had one or more comorbid DBD. ADHD, CD, and ODD were present in three (4%), two (3%), and eight (11%) subjects, respectively. Those with DBD had earlier onset of bipolar disorder and spent more time ill compared to those without DBD. CONCLUSIONS: The rates of comorbid DBD in juvenile bipolar disorder are low. The study does not support a definite relationship between ADHD and juvenile bipolar disorder. Higher rates reported previously may be due to differing methods of subject ascertainment. Samples recruited from community and general psychiatric settings may help to clarify the relationship between bipolar disorder and ADHD.     

Multifamily psychoeducation groups (MFPG) for families of children with bipolar disorder

Objectives: Multi‐family psychoeducation groups (MFPG) have been developed and tested for adults, but not for children with bipolar disorder (BPD). We present data from a pilot study of our manual‐driven MFPG treatment for families of children with mood disorders and address two questions: Do families of children with BPD and families of children with major depressive disorder/dysthymic disorder (MDD/DD): 1) differ at treatment entry?; 2) benefit equally from intervention? Method: A total of 35 children (n=16, BPD; n=19, MDD/DD) aged 8–11 years and their parents were randomized into immediate MFPG plus treatment as usual (TAU) or wait‐list + TAU and assessed periodically. Results: At baseline, there was a trend toward parents in BPD families being more knowledgeable about mood symptoms than parents in MDD/DD families (p < 0.04). Additionally at baseline, children with BPD evidenced greater mood severity historically and a trend toward more hospitalizations, day treatment, outpatient treatment, medication trials, and placement in special education classrooms than children with MDD/DD. Immediately following and 4 months post‐treatment, both BPD and MDD/DD families described having gained knowledge, skills, support, and positive attitudes during treatment. MDD/DD families increased their knowledge of symptoms to the same level as BPD families. Conclusions: While BPD families enter treatment with more impaired children and more extensive treatment histories, both BPD and MDD/DD families benefit from intervention. The clinical issues concerning combining families of children with bipolar and depressive spectrum illnesses in groups are discussed. Clinical impressions suggest that such combinations are clinically feasible and potentially beneficial.     

Cortical magnetic resonance imaging findings in familial pediatric bipolar disorder.

BACKGROUND: Morphometric magnetic resonance imaging (MRI) studies of pediatric bipolar disorder (BD) have not reported on gray matter volumes but have reported increased lateral ventricular size and presence of white matter hyperintensities (WMH). We studied gray matter volume, ventricular-to-brain ratios (VBR), and number of WMH in patients with familial, pediatric BD compared with control subjects. METHODS: Twenty subjects with BD (aged 14.6 +/- 2.8 years; 4 female) according to the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, each with a parent with BD, and 20 age-, gender-, and intelligence quotient-matched healthy control subjects (aged 14.1 +/- 2.8 years; 4 female) were scanned at 3 T. Most subjects were taking psychotropic medications. A high-resolution T1-weighted spoiled gradient echo three-dimensional MRI sequence was analyzed by BrainImage for volumetric measurements, and T2-weighted images were read by a neuroradiologist to determine presence of WMH. RESULTS: After covarying for age and total brain volume, there were no significant differences between subjects with BD and control subjects in volume of cerebral (p = .09) or prefrontal gray matter (p = .34). Subjects with BD did not have elevated numbers of WMH or greater VBR when compared with control subjects. CONCLUSIONS: Children and adolescents with familial BD do not seem to have decreased cerebral grey matter or increased numbers of WMH, dissimilar to findings in adults with BD. Gray matter decreases and development of WMH might be later sequelae of BD or unique to adult-onset BD.     

Lateral ventricle differences between first-episode schizophrenia and first-episode psychotic bipolar disorder: A population-based morphometric MRI study

Abstract

Objectives. The extent to which psychotic disorders fall into distinct diagnostic categories or can be regarded as lying on a single continuum is controversial. We compared lateral ventricle volumes between a large sample of patients with first-episode schizophrenia or bipolar disorder and a healthy control group from the same neighbourhood. Methods. Population-based MRI study with 88 first-episode psychosis (FEP) patients, grouped into those with schizophrenia/schizophreniform disorder (N=62), bipolar disorder (N=26) and 94 controls. Results. Right and left lateral ventricular and right temporal horn volumes were larger in FEP subjects than controls. Within the FEP sample, post-hoc tests revealed larger left lateral ventricles and larger right and left temporal horns in schizophrenia subjects relative to controls, while there was no difference between patients with bipolar disorder and controls. None of the findings was attributable to effects of antipsychotics. Conclusions. This large-sample population-based MRI study showed that neuroanatomical abnormalities in subjects with schizophrenia relative to controls from the same neighbourhood are evident at the first episode of illness, but are not detectable in bipolar disorder patients. These data are consistent with a model of psychosis in which early brain insults of neurodevelopmental origin are more relevant to schizophrenia than to bipolar disorder.     

Post-traumatic stress disorder among adolescents with bipolar disorder and its relationship to suicidality

OBJECTIVES: The aims of this cross-sectional pilot study were to ascertain the rates of post-traumatic stress disorder (PTSD) among adolescents with bipolar disorder (BPD) and major depressive disorder (MDD) relative to a comparison group comprised of non-affectively ill patients, and to determine whether PTSD is related to suicidal ideation and attempts. The impetus for the study was born of clinical impressions derived in the course of routine clinical practice. METHODS: Patients were screened by a single interviewer for BPD, MDD and PTSD, panic disorder, obsessive-compulsive disorder (OCD) and social phobia using the apposite modules from the Structured Clinical Interview for DSM-IV (SCID) and histories of suicidal ideation and attempts. The data were subjected to analysis using a logistic regression model. RESULTS: The database included 34 patients with BPD, 79 with MDD and 26 with a non-affective disorder. The risk for PTSD for a patient with BPD significantly exceeded that for a patient with MDD [odds ratio (OR) = 4.9, 95% confidence interval (CI) = 1.9-12.2, p = 0.001]. Patients with PTSD had an insignificantly increased risk for suicidal ideation (OR = 2.8, 95% CI = 0.9-8.9, p = 0.069), and a 4.5-fold significantly increased risk of having had a suicide attempt (OR = 4.5, 95% CI = 1.7-11.7, p = 0.002). The relationship between PTSD and suicide attempts remained significant even after controlling for the confounding effects of concurrent panic disorder, OCD and social phobia (OR = 3.4, 95% CI = 1.1-10.0, p = 0.023). CONCLUSIONS: Patients with BPD have a greater risk for PTSD than those with MDD. Post-traumatic stress disorder is significantly related to history of suicide attempts.     

Increased risk of hyperthyroidism among patients hospitalized with bipolar disorder

OBJECTIVES: Hyperthyroidism has been associated with affective disorder in many cross-sectional studies, but longitudinal studies in this connection are scarce. We assessed whether hospitalization with depressive disorder or bipolar disorder was a risk factor for development of hyperthyroidism. METHODS: We conducted a historical cohort study using the Danish register data. The observational period was 1977--99. Three study cohorts were identified: all patients with a first hospital admission with resulting index discharge diagnoses of depression, bipolar disorder, or osteoarthritis. The risks of subsequently being readmitted with a resulting discharge diagnosis of hyperthyroidism were estimated in survival analyses. RESULTS: A study sample of 133,570 patients discharged with an index diagnosis was identified. Exactly 610 patients were later readmitted following diagnoses of hyperthyroidism. Patients with depressive disorder did not have an increased risk of hyperthyroidism, whereas patients with bipolar disorder had an increased of risk on the margin of statistical significance, when compared to patients with osteoarthritis. Patients with bipolar disorder had a significantly increased risk of hyperthyroidism when compared to patients with depression. Limitations: The results apply only to hospitalized patients. Diagnoses are not validated for research purposes. CONCLUSION: Patients hospitalized with bipolar disorder tend to be at greater risk of readmission with hyperthyroidism than suitable control patients.     

MRI study of thalamic volumes in bipolar and unipolar patients and healthy individuals

The thalamus is a key structure in brain anatomic circuits potentially involved in the pathophysiology of mood disorders. Available findings from studies that examined this brain region in mood disorder patients have been conflicting. To examine the hypothesis of anatomical abnormalities in the thalamus in patients with mood disorders, we conducted a magnetic resonance imaging (MRI) study in 25 bipolar patients (mean age±S.D.=34.4±9.8 years), 17 unipolar patients (mean age±S.D.=42.8±9.2 years), and 39 healthy control subjects (mean age±S.D.=36.6±9.7 years). Thalamic volumes Gray Matter were measured blindly with a semi-automated technique. Multivariate analysis of variance, with age and gender as covariates, revealed no significant differences in left or right thalamic volumes among bipolar patients, unipolar patients and healthy individuals. There were no significant effects of gender, age at illness onset, episode type, number of episodes, length of illness, or family history of mood disorders on thalamic measurements. Although functional abnormalities in the thalamus are likely to be implicated in the pathophysiology of mood disorders, no abnormalities in thalamic size appear present in bipolar or unipolar individuals.     

Long-term prognosis of bipolar I disorder

This study examined the contribution of demographic, syndromal and longitudinal course variables to the long-term prognosis of 165 bipolar patients prospectively observed over 10 years as part of the National Institute of Mental Health Collaborative Study of Depression. Although most baseline clinical and demographic variables were not strong prognostic indicators, switching polarity within episodes was. Most episodes among the poor-prognosis patients were polyphasic, while most episodes among the comparison group with a better prognosis were monophasic. There was no evidence of shortening of cycle lengths over follow-up for either the poor-prognosis group or the entire sample. The relevance of these findings to the 'kindling' model is discussed.     

拉莫三嗪治疗双相心境障碍对照研究

目的：探讨拉莫三嗪治疗双相情感障碍的疗效与安全性。方法：双相心境障碍患者135例,其中双相抑郁78例,躁狂57例。将患者随机分为3组,每组抑郁相26例,躁狂相19例。疗程32周。前8周为急性期治疗阶段,对照组抑郁相只服选择性5-羟色胺回收抑制剂（SSRI）类抗抑郁剂,躁狂相只服利培酮;拉莫三嗪组在对照组用药的基础上加服拉莫三嗪;碳酸锂组在对照组用药的基础上加服碳酸锂。后24周为巩固治疗阶段,所有患者随机分为两组,只服拉莫三嗪或碳酸锂。采用汉密尔顿抑郁量表（HAMD）、Young躁狂评定量表（YMRS）、治疗中出现的症状量表（TESS）评定疗效及安全性。结果：急性期治疗结束后,无论躁狂相还是抑郁相,拉莫三嗪组和碳酸锂组的临床疗效显著高于对照组（P〈0．01或〈0．05）。巩固治疗阶段两组相比,拉莫三嗪的抗抑郁作用较好,碳酸锂的抗躁狂作用较强。不良反应发生率,碳酸锂组40％,拉莫三嗪组22％。巩固治疗阶段病情复发率,拉莫三嗪组8％,碳酸锂组11％,两组差异无显著性（P〉0．05）。结论：拉莫三嗪作为心境稳定剂治疗双相情感障碍疗效可靠,不良反应小,与碳酸锂相比,抗抑郁作用更强。     

Statins and cognition in late‐life bipolar disorder

Objectives

Recent data suggests that statins have positive effects on cognition in older adults. Studies in patients with mood disorders have found contradicting positive and negative effects of statins on mood and cognition, with limited data in bipolar disorder (BD). The objective of this study was to assess the association between statin use and cognition in older adults with BD.

Methods

In a cross‐sectional sample of 143 euthymic older adults with BD (age ≥ 50), statin users (n = 48) and nonusers (n = 95) were compared for cognitive outcomes: Global and cognitive domain z‐scores were calculated from detailed neuropsychological batteries using normative data from healthy comparators (n = 87).

Results

The sample had a mean age of 64.3 (±8.9) years, 65.0% were female, with an average of 15.1 (±2.79) years of education. Statin users did not differ from nonusers on global (?0.60 [±0.69] vs ?0.49 [±0.68], t[127] = 0.80, P = .42) or individual cognitive domains z‐score.

Conclusions

In older patients with BD, statin use is not independently associated with cognitive impairment. This suggests that in older BD patients, the cognitive dysfunction associated with BD trumps the potential cognitive benefit that is associated with statins in older adults without a psychiatric disorder. Further, statins do not seem to exacerbate this cognitive dysfunction. Future longitudinal studies are needed to confirm these findings.     

Developmental abnormalities in striatum in young bipolar patients: a preliminary study

OBJECTIVES: Anatomical abnormalities in the basal ganglia of adult mood disorder patients have been reported. To investigate whether these abnormalities are present early in illness course, we compared the volume of striatal structures in young bipolar patients and healthy controls. METHODS: Brain magnetic resonance images of 15 children and adolescents who met DSM-IV criteria for bipolar disorders and 21 healthy controls were obtained. Measurements were performed manually, by trained evaluators, who were blind to subjects' diagnosis. The volumes of caudate and putamen were compared in patients and controls. RESULTS: The volumes of striatal structures were not significantly different in patients and controls (ANCOVA, p > 0.05). However, we found a significant inverse relationship between age and the volumes of left caudate (r = -0.72, p < 0.01), right caudate (r = -0.66, p = 0.02) and left putamen (r = -0.71, p = 0.01) in bipolar patients, not present in healthy controls. CONCLUSIONS: Abnormalities in striatal development may be involved in the pathophysiology of bipolar disorder.     

Pituitary volumes in relatives of bipolar patients

BACKGROUND: Increased, decreased, as well as unchanged pituitary volumes have been reported in bipolar disorders (BD). It is unclear, whether abnormal pituitary volumes increase vulnerability for BD (primary vulnerability marker), or are secondary to burden of illness. To address this question, we performed the first high-risk study of pituitary volumes in affected and unaffected relatives of bipolar subjects. METHOD: High-risk participants (age range 15-30 years) were recruited from families multiply affected with BD and included 24 unaffected, 19 affected subjects with first or second degree bipolar I or II relative, matched by age and sex with 31 controls without a personal or family history of psychiatric disorders. Pituitary volumes were measured on 1.5 T 3D anatomical MRI images using standard methods. RESULTS: We found comparable pituitary volumes among unaffected, affected relatives of bipolar patients and controls. There were no differences in pituitary volumes between male and female subjects nor was there any sex by group interaction. Analyzing 26 participants with bipolar I parent or excluding 5 medicated subjects did not change the results. There were no differences between subjects from families containing bipolar I versus families containing only bipolar II subjects. CONCLUSIONS: The lack of abnormalities in unaffected and also affected subjects early in the course of illness in our study, as well as previous investigations of bipolar and familial unipolar children and adolescents, suggest that pituitary volume abnormalities are unlikely to be a primary risk factor for mood disorders.     

The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review

Objectives: To present a comprehensive review of the existing neuropsychological and neuroimaging literature on bipolar affective disorder. This review critically evaluates two common conceptions regarding the neuropsychology of bipolar disorder: 1) that, in contrast to schizophrenia, bipolar affective disorder is not associated with general cognitive impairment independent of illness episodes, and 2) relative right hemisphere (RH) dysfunction is implicated in bipolar illness patients, supported by reports of relatively greater impairment in visuospatial functioning, lateralization abnormalities, and mania secondary to RH lesions.

Methods: The major computerized databases (Medline and PSYCInfo) were consulted in order to conduct a comprehensive, integrated review of the literature on the neuropsychology and neuroanatomy of bipolar disorder. Articles meeting specified criteria were included in this review.

Results: In a critical evaluation of the above notions, this paper determines that: 1) while there is little evidence for selective RH dysfunction, significant cognitive impairment may be present in bipolar illness, particularly in a subgroup of chronic, elderly or multiple‐episode patients, suggesting a possible toxic disease process, and 2) the underlying functional correlate of these cognitive deficits may be white matter lesions (‘signal hyperintensities’) in the frontal lobes and basal ganglia, regions critical for executive function, attention, speeded information processing, learning and memory, and affect regulation. While this hypothesized neural correlate of cognitive impairment in bipolar disorder is speculative, preliminary functional neuroimaging evidence supports the notion of frontal and subcortical hypometabolism in bipolar illness.

Conclusions: The etiology of the structural brain abnormalities commonly seen in bipolar illness, and their corresponding functional deficits, remains unknown. It is possible that neurodevelopmental anomalies may play a role, and it remains to be determined whether there is also some pathophysiological progression that occurs with repeated illness episodes. More research is needed on first‐episode patients, relatives of bipolar probands, and within prospective longitudinal paradigms in order to isolate disease‐specific impairments and genetic markers of neurocognitive function in bipolar disorder.     

Neurocysticercosis presenting as bipolar disorder: a case report

Neurocysticercosis is the most common neuro-parasitosis caused by the larval stage of Taenia solium. The most common manifestations include seizures and hydrocephalus. Psychiatric abnormalities are relatively rare but depressive symptoms are frequent in patients with neurocysticercosis. However, mania as a presentation is relatively rare. Pregnancy and the postpartum period are relatively vulnerable times and they can lead to reactivation of existing neurocysterci lesions. We are discussing the case of a 23-year-old female patient with neurocysticercosis leading to the reactivation of lesions in the peripartum and postpartum period leading to bipolar affective disorder. Improvement in the patient was seen with a combination of antipsychotics, antihelmintics, antiepileptics and steroids, along with improved radiological signs of neurocysterci lesions. Although neurocysticercosis is a common illness, its prevalence presenting as a manic episode is merely 2.6% and, hence, missed easily. Therefore, it is important to rule out organic aetiology in patients even with a classic presentation of bipolar affective disorder and those having any other neurological symptoms and signs.