Parent-of-origin effect in transmission of bipolar disorder

Recently, possible involvement of a parent-of-origin effect in the transmission of bipolar disorder has been suggested. We examined the possible contribution of parent-of-origin effect by using data from a large family and family history study of bipolar patients in the Collaborative Depression Study. In 276 probands with bipolar I disorder, family histories were examined using three diagnostic criteria: (1) bipolar I disorder, (2) bipolar I or bipolar II disorder, and (3) bipolar disorders or recurrent unipolar depression for parents and siblings. An excess of affected mothers was not observed when unipolar depression was excluded. Age-at-onset was significantly lower in probands having a father with bipolar disorders or recurrent unipolar depression than in probands with an affected mother. This difference was not observed when unipolar depression was excluded. There was no significant difference of prevalence rate in children of affected mothers and those with affected fathers. These data do not support the contribution of parent-of-origin effect in the transmission of bipolar disorder. © 1996 Wiley-Liss, Inc.     

Anticipation in Swedish families with bipolar affective disorder.

Anticipation describes an inheritance pattern within a pedigree with an increase in disease severity or decrease in age at onset or both in successive generations. The phenomenon of anticipation has recently been shown to be correlated with the expansion of trinucleotide repeat sequences in different disorders. We have studied differences of age at onset and disease severity between two generations in 14 families with unilinear inheritance of bipolar affective disorder (BPAD). There was a significant difference in age at onset (p < 0.008), in episodes per year with (p < 0.006) and without (p < 0.03) lithium treatment, and in total episodes per year (p < 0.002) between generations I and II. Furthermore, there was a highly significant correlation (p < 0.001) in age at onset between generations I and II. No evidence for specific paternal or maternal inheritance was found. We found evidence of anticipation and could rule out ascertainment bias or some other artefact. Anticipation is thus an inheritance pattern in BPAD which suggests that the expansion of trinucleotide repeat sequences is a possible mode of inheritance in BPAD.     

Parent-of-origin effect in panic disorder

Parent-of-origin effect was examined in a series of 64 pedigrees with panic disorder (PD) under both the narrow and broad diagnostic models. The narrow diagnostic model defined the affected phenotype to include only the "definite" and "probable" forms of PD, whereas the broad diagnostic model included the entire PD symptomatology. The pattern of maternal vs. paternal transmission of disease was analyzed through a number of comparisons. These comparisons were performed first on all pedigrees and then on a subset of "pure" pedigrees including only strictly maternal transmission or strictly paternal transmission of PD. There were no significant differences in the proportion of offspring born to transmitting mothers vs. transmitting fathers under either diagnostic model or pedigree set. When the difference in the sex ratio among affected offspring from both transmission types was considered, only the "pure" pedigree sample under the broad diagnostic model yielded nominally (i.e., not corrected for multiple tests) significant results (P < .05). Also, the comparisons of cumulative lifetime risk for PD between offspring of transmitting mothers and fathers gave some nominally significant results; when affected and unaffected offspring were considered, significant results were observed under the narrow and broad diagnostic models, P < .0005 and P < .05, respectively. These findings must be considered provisional until confirmed by further study.     

Gender differences in bipolar affective disorder

We report a study of gender differences in a sample of 111 manic patients. Female manics (N = 78) exhibited fewer manic and more depressive symptoms than males (N = 33). Although male manics had a more frequent history of delayed landmarks, the two groups did not differ in cortical function as measured by EEG and neuropsychological testing. There were no significant differences between male and female relatives of male and female probands for unipolar or bipolar affective disorder, alcoholism or sociopathy. Female relatives of both groups were at greater risk for total affective disorder and male relatives were at greater risk for alcoholism. Familial illness patterns indicated that male and female manics shared the same genetic liability for affective disorder and that X-linked transmission was unlikely.     

EEG abnormalities in bipolar affective disorder

Forty-six patients with bipolar illness were evaluated with scalp-recorded electroencephalograms. Familial pattern of psychopathology was evaluated between groups with clinically normal and abnormal EEG tracings. Those with abnormal EEGs were noted to have a significantly negative family history of affective disorder when compared to the EEG normal group. These results may support the concept of some patients with mania having an acquired illness which occurs independent from its genetic loading.     

Parental bonding in bipolar affective disorder

When the Parental Bonding Instrument was administered to 58 bipolar affective disorder patients and 100 general practice patients no difference was found in reports of parental characteristics. Among the female patients there was an association between poor parental bonding and increased number of hospitalisations.     

Mutational analysis of the Wolfram syndrome gene in two families with chromosome 4p‐linked bipolar affective disorder

Bipolar affective disorder (BPAD) is a complex disease with a significant genetic component. Heterozygous carriers of Wolfram syndrome (WFS) are at increased risk of psychiatric illness. A gene for WFS (WFS1) has recently been cloned and mapped to chromosome 4p, in the general region we previously reported as showing linkage to BPAD. Here we present sequence analysis of the WFS1 coding sequence in five affected individuals from two chromosome 4p‐linked families. This resulted in the identification of six polymorphisms, two of which are predicted to change the amino acid sequence of the WFS1 protein, however none of the changes segregated with disease status. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:158–160, 2000. © 2000 Wiley‐Liss, Inc.     

Psychotherapeutic case conceptualization using plan analysis for bipolar affective disorder

Valid individualized case conceptualization methodologies, such as plan analysis, are rarely used for the psychotherapeutic treatment conceptualization and planning of bipolar affective disorder (BD), even if data do exist showing that psychotherapy interventions might be enhanced by applying such analyses for treatment planning for several groups of patients. We applied plan analysis as a research tool (Caspar, 1995) to N=30 inpatients presenting BD, who were interviewed twice. Our study aimed at producing a prototypical plan structure encompassing the most relevant data from the 30 individual case conceptualizations. Special focus was given to links with emotions and coping plans. Inter‐rater reliability of these plan analyses was considered sufficient. Results suggest the presence of two subtypes based on plananalytic principles: emotion control and relationship control, along with a mixed form. These subtypes are discussed with regard to inherent plananalytic conflicts, specific emotions and coping plans, as well as symptom level and type. Finally, conclusions are drawn for enhancing psychotherapeutic practice with BD patients, based on the motive‐oriented therapeutic relationship. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65: 1–16, 2009.     

Theory of mind deficits in bipolar affective disorder

BACKGROUND: Bipolar affective disorder patients often show cognitive deficits that are similar to those found in schizophrenia patients. Theory of mind (the ability to understand others' mental states) is compromised in currently ill schizophrenia patients. This study aimed to establish whether similar deficits are found in bipolar patients. METHODS: We measured theory of mind ability in 20 bipolar-manic patients, 15 bipolar-depressed patients, 13 bipolar patients in remission and 15 normal controls. The task, which controlled for memory and comprehension, had previously been used in a study of schizophrenia patients. RESULTS: Impaired performance on theory of mind was found for both bipolar-depressed and bipolar-manic patients, even when memory was controlled for. No impairment was observed in the remitted patients. LIMITATIONS: The manic patients scored lower than the remitted patients on a brief measure of intelligence; no other group differences in IQ were significant. CONCLUSIONS: Theory of mind deficits are found in currently symptomatic bipolar patients. These findings add to growing evidence that common mechanisms may contribute to bipolar affective disorder and schizophrenia.     

Cognitive impairment in remission in bipolar affective disorder

BACKGROUND: Although the traditional view of bipolar affective disorder is that the majority of patients have full remission between episodes, recent evidence suggests that residual cognitive deficits are present. The aim of this study was to determine whether memory and executive deficits were present in a well-defined clinically remitted group of patients. METHODS: This was a case-control study of bipolar patients in remission (N = 18). Subjects had to fulfil stringent clinical criteria for inclusion into the study and had to have been in remission for at least 4 months. Subjects also had no history of substance dependence. The cognitive battery examined memory and executive function. RESULTS: Patients in excellent clinical remission and who reported good social adaptation showed imipairment on tests of visuospatial recognition memory. Accuracy on four tests of executive function was not impaired in patients in remission compared with controls, although response latency on these executive tests was still impaired. CONCLUSIONS: As our group and others have shown, patients with mania and unipolar depression show generalized impairment on tests of memory and executive function. In comparison, this study has demonstrated that patients in remission show a relatively specific impairment in memory with recovery of accuracy measures on executive function task. The increased response latency on the executive tasks suggests a possible small residual impairment. These findings suggest that in netIroanatomical terms, more posterior cortical function (temporal lobe) has not improved but there is at least some recovery of frontal lobe function in remission.     

Illness behaviour and rehospitalization in bipolar affective disorder

Fifty hospitalized patients with bipolar affective disorder were interviewed on discharge from hospital. Over the subsequent 12 months, 36 of these patients were readmitted to hospital. Compared with the remainder, those readmitted had had more past hospital admissions and on interview were rated as being less able to recognize and respond to early symptoms of relapse and were less accepting of medication.     

No association of the tryptophan hydroxylase gene with bipolar affective disorder,unipolar affective disorder,or suicidal behaviour in major affective disorder

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of 5-hydroxytryptamine (5-HT). An association study in bipolar affective disorder I or unipolar major affective disorder was performed by using a Bfa I restriction site polymorphism within intron 7 of the tryptophan hydroxylase gene. A total of 118 bipolar, 125 unipolar, and 437 control subjects were used in the study (1:3.7 bipolar:control, 1:3.5 unipolar:control). There were no significant differences in TPH allele or genotype frequencies between the affective disorder and control groups. In addition, bipolar and/or unipolar subjects with or without a history of suicide attempts were compared for the TPH polymorphism. No significant differences were found between suicidal and nonsuicidal groups in major affective disorder, in contrast to a previous study suggesting an association of this polymorphism with a history of suicide attempts among alcoholic violent offenders. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:245–247, 1998. © 1998 Wiley-Liss, Inc.     

Indirect measurement of dysfunctional attitudes in bipolar affective disorder

Objective. The present study uses an indirect measure to explore whether dysfunctional attitudes are characteristic of all phases of bipolar disorder. Previous studies with bipolar patients using indirect measurements have uncovered depression‐like responses that were otherwise undetected. Design. A cross‐sectional study design was adopted to explore the presence of dysfunctional attitudes within each phase of the illness. Method. Manic patients, depressed bipolar patients, remitted bipolar patients, and healthy controls were compared on a sentence stem completion task designed to implicitly assess dysfunctional attitudes. Results. The manic, depressed, and remitted patients all exceeded the controls on implicit measures of dysfunctional attitudes. Conclusions. The findings are consistent with the hypothesis that all phases of bipolar disorder are associated with depressogenic dysfunctional attitudes.     

Analysis of GNAZ gene polymorphism in bipolar affective disorder

Evidence for a bipolar disorder (BPD) susceptibility locus on chromosome 22q11 has been provided in several studies. One candidate gene that maps to this region is the G-protein α subunit gene Gαz (GNAZ). We have identified a common silent polymorphism in GNAZ exon 2 by single strand conformation polymorphism analysis. The frequency of this polymorphism was determined in a control population (n=84) and in patients with BPD (n=88). The data showed a statistical trend toward a difference in the distribution of alleles in patients with BPD compared with control subjects (chi square=3.2, 1 df, P=0.073, two-tailed). No significant difference was detected when the GNAZ polymorphism was analyzed in control subjects and schizophrenia patients (n=63, P=0.92). These data continue to provide some support for a BPD susceptibility gene on 22q11, possibly in linkage disequilibrium with the GNAZ 309 polymorphism. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:324–328, 1999. © 1999 Wiley-Liss, Inc.