Familial leukoencephalopathy in bipolar disorder

OBJECTIVE: Imaging studies of patients with bipolar disorder demonstrate changes in deep white matter and subcortical gray nuclei that are seen as focal hyperintensities on T2-weighted magnetic resonance imaging (MRI). The objective of this study was to examine MRIs in a family with a strong history of bipolar disorder to look for possible MRI abnormalities in members with and without affective illness. METHOD: The authors obtained MRIs of 21 members of a family with a strong history of bipolar disorder. Eight of the family members studied had bipolar illness, one had symptoms of bipolar disorder but did not meet full DSM-III-R criteria, two had unipolar disorder, and 10 did not have bipolar disorder. RESULTS: Fifteen of the 21 family members had MRI findings, including six of 10 family members who had no affective disorder and all of those with bipolar disorder. Lesions of both white matter and subcortical gray nuclei were found. CONCLUSIONS: Although the clinical significance of these MRI findings is unknown, the high prevalence of MRI findings in both affected and unaffected family members suggests that MRI findings may potentially serve as a biological marker for bipolar disorder. Recent genetic studies have established a link between familial leukoencephalopathy and chromosome 19. If leukoencephalopathy appears to be related to bipolar disorder, it may allow clearer characterization of the genetics of the disorder.     

Lamotrigine in rapid-cycling bipolar disorder

BACKGROUND: We evaluated the antidepressant and mood-stabilizing effects of lamotrigine, a novel anticonvulsant, in a group of rapid-cycling bipolar patients. Most were already nonresponders or poor partial responders to other conventional mood-stabilizing agents. METHODS: This open, naturalistic, and prospective study was conducted with five rapid-cycling bipolar patients (DSM-IV). Each received lamotrigine titrated to a minimum dose of 150 mg/day as monotherapy or in combination with other psychotropic agents. Patients were assessed with the Global Assessment Scale (GAS), Beck Depression Inventory (BDI), and Young Mania Rating Scale (YMRS) for evidence of cycling mood. RESULTS: Lamotrigine was used at a mean +/- SD dose of 185.0 +/- 33.5 mg/day for 225.8 +/- 28.0 days. Random regression modeling of data showed significant dose- and time-dependent improvements in depressive symptoms and social function of patients taking lamotrigine (Dose: z = 2.17, p < .03 for BDI, z = 4.44, p < .001 for GAS; Time: z = -3.79, p < .001 for BDI, z = 2.16, p < .03 for GAS). Further random regression modeling analysis of change over time in symptoms prior to lamotrigine compared with symptoms during lamotrigine treatment showed a significant treatment by time effect for GAS (z = 2.40, p < .016) and a trend for BDI scores (z = -1.79, p < .073). No significant time or dosage effect or time by treatment effect was observed for YMRS. Finally, t statistics showed a significant reduction in mean BDI scores following treatment with lamotrigine (t = -5.26, p < .006). Lamotrigine was well tolerated by all patients; only one patient experienced several side effects, which were probably due to interaction between several psychotropic medications. CONCLUSION: Lamotrigine augmentation therapy and monotherapy appeared to have mood-stabilizing and antidepressant efficacy in the treatment of five rapid-cycling bipolar patients. The effect persisted for an average of 7.5 months.     

Inducing lifestyle regularity in recovering bipolar disorder patients: results from the maintenance therapies in bipolar disorder protocol

On the basis of theories we articulated in earlier papers (Ehlers et al 1988: Arch Gen Psychiatry 45:948-952, 1993: Depression 1:285-293), we have developed an adjunctive psychosocial intervention for patients with bipolar 1 disorder. Central to this intervention is the establishment of regularity in daily routines. In this report, we present data from a controlled investigation comparing this new treatment, interpersonal and social rhythm therapy (IPSRT), with a conventional medication clinic approach. Despite comparable changes in symptomatology over a treatment period lasting up to 52 weeks, subjects assigned to IPSRT (n = 18) show significantly greater stability (p = .047) of daily routines with increasing time in treatment, while subjects assigned to the medication clinic condition (n = 20) show essentially no change in their social routines as measured by Social Rhythm Metric (SRM-Monk et al 1990: J Nerv Ment Dis 178(2):120-126) score. We conclude that IPSRT is capable of influencing lifestyle regularity in patients with bipolar 1 disorder, with the possible benefit of protection against future affective episodes.     

Misdiagnosis of bipolar affective disorder as personality disorder

Patients with longstanding recurrent behavioural disturbance, unstable interpersonal relationships and periodic affective symptoms are often diagnosed as having a cluster B personality disturbance using DSM-III-R criteria. Two women are described who were diagnosed as having a personality disorder on several admissions to hospital, but in whom closer inquiry revealed evidence of bipolar affective disorder. Since treatment with lithium and adjunctive mood-stabilizing drugs neither patient has required further admissions to hospital within the past five years.     

Management of the depressive component of bipolar disorder

Acute bipolar depression (ABD) and breakthrough depression occurring during maintenance therapy of bipolar disorder are associated with significant morbidity and an increased risk of suicide. Lithium is an effective mood stabilizer for ABD, but its onset of antidepressant action is slow and additional antidepressant therapy is often prescribed. The extent to which other mood stabilizers (e.g., carbamazepine and valproate) have antidepressant activity is unclear. Preliminary initial research suggests three potential advantages that selective serotonin reuptake inhibitors have over tricyclic antidepressant for ABD: possibly greater efficacy, fewer adverse effects, and a lower frequency of antidepressant-induced mania. Bupropion may also have significant advantages. However, further research is needed to confirm these findings. Monoamine oxidase inhibitors are the antidepressant of choice for atypical bipolar depression. Electroconvulsive therapy (ECT) has the highest response rate of all treatments for ABD. Further research is needed to explore combination treatments with mood stabilizers and antidepressants for the effective treatment of ABD.     

Obsessive compulsive disorder. Clinical and epidemiologic studies

Until recently, Obsessive-Compulsive Disorder (OCD) was considered rare trouble with rather poor outcome. Currently progress in behavioral psychology, psychopharmacology and methodology of epidemiologic studies multiplying by 50 the traditional prevalence rates, give an impetus to the interest in this pathology. Recent clinical and epidemiologic data in OCD are reported in this paper. Multiple questions are evoked such as the issue of OCD homogeneity, the meaning of comorbidity with other psychological disorders: depression, panic attacks, schizophrenia, Gilles de la Tourette syndrome, the reality of OCD prevalence rate in general and psychiatric populations, the usefulness of classical demarcation between psychosis/neurosis in the treatment of OCD, and finally the search for a genetic diathesis and risk factors implicated in predisposition to OCD. A close relationship between clinical, epidemiologic and genetic approaches seems to be required in order to answer these questions and constitutes a first step prior to carrying on basic and applied research.     

Comorbidity of bipolar and personality disorder

Tuft cells, a widespread cell type that is present in the mucosal epithelia of hollow organs, including the main excretory duct (MED) epithelia of the rat salivary gland, are well documented morphologically. However, studies of their development are few. The purpose of the present study was to examine the perinatal and postnatal development of tuft cells in the main excretory duct of the rat submandibular gland. Main excretory ducts of the submandibular gland were obtained from five male Wistar rats at the ages of 0, 1, 7, 14, 17, 21, 23, 28, and 56 postnatal days and were prepared for scanning and transmission electron microscopy. The tuft cells, which are distinguished easily by their long microvilli protruding into the lumen, were recognizable first at 17 postnatal days. They showed a remarkable increase in number between 3 and 4 postnatal weeks. The percentages of tuft cells were 0.4% at 17 postnatal days and 0.8% at 3 postnatal weeks. The number of tuft cells represented approximately 5% of the total epithelial cells by 4 postnatal weeks. There was a significant difference between 3 and 4 postnatal weeks (P < 0.01). The microvilli of the tuft cells at the time of weaning had almost the same width as in the adult, but they were shorter. Microfilaments extending from the tips of the microvilli and microtubules and many electron-lucent vesicles in the supranuclear cytoplasm also were observed. These results indicate that tuft cells appeared in the MED of the submandibular gland during weaning and had abundant vesicles in their apical cytoplasm.     

Developmental subtypes of juvenile bipolar disorder

The incidence of hip fractures has increased over the past decades, and for patients with hip fractures, medical and social conditions have deteriorated during the same time. In this study the results of orthopaedic rehabilitation of patients with Parkinson's disease and a hip fracture are compared with those in all other hip fracture patients. A total of 74 patients with Parkinson's disease and hip fracture were compared with 1,361 patients without the disease. Prior to fracture, patients with Parkinson's disease were less likely to be living an independent life in their own homes. Postoperatively women with Parkinson's disease were hospitalized for a significantly longer period. Postoperative rehabilitation was significantly slower and less successful than among patients without the disease. Patients with Parkinson's disease comprise a subgroup of hip fracture patients who need more rehabilitation resources than can easily be provided at an ordinary orthopaedic ward. A team-work between an orthopaedic surgeon, a neurologist and a rehabilitation unit seems to be mandatory in order to achieve shorter hospitalization and earlier return to the pre-fracture environment.     

Family functioning in bipolar I disorder.

In a sample of 62 patients with Bipolar I disorder, the authors used a repeated measures longitudinal design to examine whether global family functioning was associated with the presence of a concurrent bipolar episode as well as whether global family functioning was associated with the presence of manic and depressive episodes in the following 3 months. Participants were recruited for a randomized clinical trial examining the efficacy of family treatments combined with pharmacotherapy for bipolar disorder. Global family functioning was repeatedly measured with both clinician-rated and patient-rated assessment instruments over the 28-month study period. Results indicated that mood episodes were associated with concurrent global family functioning within individuals, but global family functioning was not associated with episode status in the subsequent 3 months. The repeated measures nature of these results suggests that global family functioning and bipolar episodes may fluctuate in concert with each other but that global family functioning is not associated with subsequent change in episode status. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social support and the course of bipolar disorder.

The current study prospectively examined the impact of social support on symptom severity and recovery from episodes in bipolar disorder, both as a direct influence and as a buffer of life events. Fifty-nine individuals with Bipolar I disorder were followed longitudinally with monthly symptom severity interviews. Social support was measured by the Interpersonal Support Evaluation List and the Interview Schedule for Social Interaction, and life events were assessed using the Life Events and Difficulties Schedule. Individuals with low social support took longer to recover from episodes and were more symptomatic across a 6-month follow-up. Results suggest a polarity-specific effect, in that social support influences depression but not mania. Discussion focuses on theoretical implications of a series of polarity-specific findings within the field. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thought suppression in patients with bipolar disorder.

Suppression of negative thoughts has been observed under experimental conditions among patients with major depressive disorder (MDD) but has never been examined among patients with bipolar disorder (BD). Patients with BD (n = 36), patients with MDD (n = 20), and healthy controls (n = 20) completed a task that required unscrambling 6-word strings into 5-word sentences, leaving out 1 word. The extra word allowed the sentences to be completed in a negative, neutral, or “hyperpositive” (manic/goal-oriented) way. Participants completed the sentences under conditions of cognitive load (rehearsing a 6-digit number), reward (a bell tone), load and reward, or neither load nor reward. We hypothesized that patients with BD would engage in more active suppression of negative and hyperpositive thoughts than would controls, as revealed by their unscrambling more word strings into negative or hyperpositive sentences. Under conditions of load or reward and in the absence of either load or reward, patients with BD unscrambled more negative sentences than did controls. Under conditions of reward, patients with BD unscrambled more negative sentences than did patients with MDD. Patients with BD also reported more use of negative thought suppression than did controls. These group differences in negative biases were no longer significant when current mood states were controlled. Finally, the groups did not differ in the proportion of hyperpositive sentence completions in any condition. Thought suppression may provide a critical locus for psychological interventions in BD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological profiles in bipolar affective disorder and complex partial seizure disorder.

Compared neuropsychological profiles of bipolar patients, complex partial seizure disorder patients, and normal controls. Complex partial seizure patients performed worse than bipolar patients or normal controls in 1 of 5 neuropsychological domains examined in an ANOVA (focusing-execution) and on delayed verbal recall; they performed worse than bipolar patients in the verbal domain. Bipolar patients performed worse than normal controls in focusing-execution and showed clinical elevation on 1 scale of the MMPI. The data suggest both similarities and differences in the neuropsychological profiles of patients with bipolar affective disorder and patients with complex partial seizure disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A 'sticky' interhemispheric switch in bipolar disorder?

Despite years of research into bipolar disorder (manic depression), its underlying pathophysiology remains elusive. It is widely acknowledged that the disorder is strongly heritable, but the genetics are complex with less than full concordance in monozygotic twins and at least four susceptibility loci identified. We propose that bipolar disorder is the result of a genetic propensity for slow interhemispheric switching mechanisms that become 'stuck' in one or the other state. Because slow switches are also 'sticky' when compared with fast switches, the clinical manifestations of bipolar disorder may be explained by hemispheric activation being 'stuck' on the left (mania) or on the right (depression). Support for this 'sticky' interhemispheric switching hypothesis stems from our recent observation that the rate of perceptual alternation in binocular rivalry is slow in euthymic subjects with bipolar disorder (n = 18, median = 0.27 Hz) compared with normal controls (n = 49, median = 0.60 Hz, p < 0.0005). We have presented evidence elsewhere that binocular rivalry is itself an interhemispheric switching phenomenon. The rivalry alternation rate (putative interhemispheric switch rate) is robust in a given individual, with a test-retest correlation of more than 0.8, making it suitable for genetic studies. The interhemispheric switch rate may provide a trait-dependent biological marker for bipolar disorder.     

Parental sex effects in bipolar affective disorder pedigrees

Measurements of transepithelial electrical resistance (TEER), the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) test and monitoring of poly(ethylene glycol) (PEG) transport have been used to study the effects of the non-ionic surfactants Solulan C24 and Solulan 16, either free in solution or as an integral part of niosome bi-layers, on intestinal epithelial cells from man (Caco-2 cell monolayers). The effects on epithelial integrity and on the transport of the hydrophilic drug metformin depend on the concentration of the surfactants. At concentrations above 1% the effect on TEER of the surfactant in niosomal form and free in solution were equivalent whereas cell viability was preserved to a higher concentration of Solulans when the Solulans were present in the niosomal form. It was concluded that the toxic effect of niosomes arises from free surfactant present in the niosome suspension.     

Affected-sib-pair analyses of bipolar disorder using data on chromosome 18

Our aim was to analyze the GAW10 bipolar data on chromosome 18, using three well-known affected-sib-pair methods. Analyses were carried out on both individual and combined data sets. In these analyses we defined the affected phenotype to include only individuals with diagnosis of bipolar I. We observed suggestive evidence for linkage to a few markers on the peri-centromeric region of chromosome 18. In the COLUMBIA data set, D18S45 showed statistically significant results (p-value < or = 0.001). Also for the combined analyses, D18S53 gave a consistently significant linkage signal.     

Genetic linkage study of bipolar disorder and the serotonin transporter

Administration of a low sub-immunosuppressive dose of cyclophosphamide (CY) to naive mice induced a marked increase in the number of splenic cells forming natural antibodies against unrelated antigens such as foot-and-mouth disease virus, keyhole limpet hemocyanin, horseradish peroxidase, or bovine serum albumin, as determined by an enzyme-linked immunosorbent assay spot technique. These results suggest that in mice there exists a repertoire of B cells forming natural antibodies which is restrained by an unknown mechanism and that CY is able to interfere with that restriction.     

Cyclothymia in the adolescent offspring of parents with bipolar affective disorder.

Explored the prevalence and types of psychopathology exhibited by the adolescent and young adult offspring (n?=?37, aged 15–21 yrs) of 24 patients (mean age 48.4 yrs) with bipolar affective disorder and by the age-matched offspring (n?=?22) of 14 patients (mean age 46.7 yrs) with nonaffective psychiatric disorders. It was hypothesized that the offspring of bipolar Ss would be characterized by an increased rate of cyclothymia. Offspring received structured diagnostic interviews conducted by interviewers unaware of parental diagnosis. Anonymous diagnoses were derived based on Research Diagnostic Criteria. It was found that the offspring of bipolar Ss exhibited significantly higher rates of affective disorder in general and cyclothymia in particular than the offspring of the nonaffective controls, a finding concordant with the proposed hypothesis. The offspring groups did not differ on rates of nonaffective disorders. Results support a continuum model of bipolar disorder in which cyclothymia is viewed as a mild form of full syndromal bipolar illness. (84 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Primary structure of the serotonin transporter in unipolar depression and bipolar disorder

Genetic factors have been implicated in the etiology of affective disorders but due to the complex inheritance patterns of these disorders, identification of the responsible gene(s) has so far been unsuccessful. Decreased platelet serotonin (5-HT) transport and reduced binding of imipramine or paroxetine to brain and platelet 5-HT uptake sites/transporters in patients with depression and suicide victims define the 5-HT transporter (5-HTT) as a candidate gene. The primary structure of the 5-HTT was analyzed in 17 patients meeting DSM-III-R diagnostic criteria for major depressive or bipolar disorder and in 4 healthy controls using polymerase chain reaction (PCR-) amplification and sequencing of complementary deoxyribose nucleic acid (cDNA) synthesized from platelet 5-HTT messenger ribose nucleic acid (mRNA). Direct PCR sequencing of the protein coding region failed to reveal changes in the deduced amino acid sequence of the platelet/brain 5-HTT (40,000 base pairs sequence screened), although a conservative single-base substitution representing a silent polymorphism was found. The results provide preliminary evidence that alterations in the primary structure of 5-HTT are not generally involved in the pathogenesis of unipolar depression and manic-depressive illness.     

Differential response to lithium and carbamazepine in the prophylaxis of bipolar disorder

The relation between selected indicator foods, alcohol and coffee intake, and the risk of pancreatic cancer was evaluated in a case-control study conducted between 1983 and 1992 in northern Italy on 362 patients with histologically confirmed, incident cancers of the pancreas, and 1,552 controls in hospital for acute, non-neoplastic diseases. Odds ratios (ORs) for subsequent tertiles of intake were computed after allowance for sociodemographic factors and tobacco smoking. Pancreatic cancer risk was directly associated with consumption of meat (OR for the highest frequency tertile = 1.43), liver (OR = 1.43) and ham and sausages (OR = 1.64), and inversely with consumption of fresh fruit (OR = 0.59), fish (OR = 0.65) and olive oil (OR = 0.58). No appreciable association was found with coffee (OR = 1.21) and alcohol consumption (OR = 1.20). A summary score was derived by summing the six related food items; compared to the lowest level, the OR was 2.7 for the highest quintile, and the population attributable risk was 36% (95% confidence interval, 15-57%), indicating the scope of diet for the prevention of this common neoplasm in the Italian population.