Evaluating the parent-of-origin effect in bipolar affective disorder. Is a more penetrant subtype transmitted paternally?

BACKGROUND: Numerous genetic mechanisms and modes of transmission underlying bipolar affective disorder (BPAD) have been postulated. Recently, the discovery of genomic imprinting and mitochondrial transmission of illness in humans has stimulated study of parent-of-origin effects in the transmission of BPAD. METHODS: We examined a large sample of families from an associated linkage study to search for a possible parent-of-origin effect. Selecting for unilineal families with at least one offspring and/or parent diagnosed with BPAD after structured interview, we conducted three analyses: (1) the rates of illness among mothers and fathers of offspring affected with BPAD; (2) the observed frequency of transmission and rates of illness among maternal and paternal lineages; and (3) the rates of affective illness among offspring of parents affected with BPAD. RESULTS: Our results indicate no significant differences in the rates of illness among mothers and fathers of offspring affected with BPAD. Also, the frequency of transmission and rates of illness among maternal and paternal lineages did not differ significantly. However, the rate of BPAD among the offspring of fathers affected with BPAD was significantly higher than for mothers with the illness. LIMITATIONS: Substantially more women than men, and maternal than paternal relatives were studied - introducing possible gender biases. CONCLUSIONS: These results suggest a possible paternal parent-of-origin effect.     

Anticipation in bipolar affective disorder: Is age at onset a valid criterion?

Anticipation has been suggested among the genetic mechanisms of bipolar disorder (BD), prompting the search for unstable DNA sequences. Past studies of anticipation in BD have generally relied on observed shift in the age at onset between parental and offspring generations. Such a shift, however, may be caused by a number of other factors difficult to correct for. We investigated age at onset distributions in a sample of 161 related subjects and in a sample of “pseudofamilies” consisting of 320 unrelated subjects selected from a large epidemiological cohort using Monte‐Carlo simulation to mimic the family sample. Comparison of age at onset distributions in both samples shows a difference between the generations, but of a similar magnitude in each sample. This suggests that age at onset alone may not be a sufficient criterion of anticipation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:804–807, 2000. © 2000 Wiley‐Liss, Inc.     

Anticipation in bipolar affective disorder: is age at onset a valid criterion?

Anticipation has been suggested among the genetic mechanisms of bipolar disorder (BD), prompting the search for unstable DNA sequences. Past studies of anticipation in BD have generally relied on observed shift in the age at onset between parental and offspring generations. Such a shift, however, may be caused by a number of other factors difficult to correct for. We investigated age at onset distributions in a sample of 161 related subjects and in a sample of "pseudofamilies" consisting of 320 unrelated subjects selected from a large epidemiological cohort using Monte-Carlo simulation to mimic the family sample. Comparison of age at onset distributions in both samples shows a difference between the generations, but of a similar magnitude in each sample. This suggests that age at onset alone may not be a sufficient criterion of anticipation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:804-807, 2000.     

Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university‐affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications. J. Med. Virol. 85:43–48, 2012. © 2012 Wiley Periodicals, Inc.     

Does the presence of a current psychiatric disorder in AIDS patients affect the initiation of antiretroviral treatment and duration of therapy?

BACKGROUND: Psychiatric disorders are common in HIV patients, and previous work suggests that these patients experience delays in treatment with highly active antiretroviral therapy (HAART). We investigated whether a current psychiatric disorder (1) affected the time to initiation of HAART, (2) predicted the likelihood of being prescribed HAART for at least 6 months, and (3) affected survival in urban AIDS patients. METHODS: We conducted a retrospective cohort study of AIDS patients with no prior history of HAART who were enrolled and followed at the Johns Hopkins University HIV clinic between January 1996 and January 2002. Patients were stratified based on the presence of a psychiatric disorder. Cox proportional hazards regression models estimated the relative risk of receiving HAART and survival, whereas multivariate logistic regression models estimated the relative odds of remaining on HAART. RESULTS: During the study period, 549 patients with AIDS and no prior antiretroviral treatment were enrolled in the clinic. Eighteen percent (n = 100) were defined as having a current psychiatric disorder, 39% (n = 215) were defined as having no psychiatric disorder, and 43% (n = 34) were indeterminate. Patients with a psychiatric disorder were 37% more likely to receive HAART (Cox adjusted hazard ratio [95% confidence interval (CI)]: 1.37 [1.01-1.87]), had greater than twice the odds of being prescribed HAART for at least 6 months (adjusted odds ratio [95% CI]: 2.14 [1.24-3.69]), and were 40% more likely to survive (Cox adjusted hazard ratio [95% CI]: 0.61[0.37-0.99]) as compared with those without a psychiatric disorder. CONCLUSION: Patients with psychiatric disorders are receiving HAART and are able to reap the survival benefit by remaining on it.     

Is bipolar II disorder misdiagnosed as major depressive disorder in children?

OBJECTIVES: To estimate the lifetime prevalence of bipolar II disorder in children and adolescents presenting with DSM-IV major depressive disorder (MDD). METHODS: Sixty-one consecutive subjects aged < or =18 years attending the outpatient services of the Child and Adolescent Psychiatric (CAP) services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India with a diagnosis of MDD were evaluated using the Missouri Assessment of Genetics Interview for children (MAGIC). Two psychiatrists, one of whom was a child psychiatrist diagnosed hypomania by consensus. RESULTS: Twelve children had a past episode of hypomania (20%), which was hitherto undiagnosed clinically. LIMITATIONS: We recruited subjects from a psychiatric hospital, thus limiting the generalizability of the finding. Sample size was relatively small and assessments were cross-sectional. CONCLUSIONS:: Our study shows that bipolar II disorder is often misdiagnosed as MDD in children. The study also highlights that the chance of diagnosing bipolarity is enhanced by using semi-structured interview in routine clinical practice.     

Major depressive disorder with anger: a bipolar spectrum disorder?

BACKGROUND: Depression with anger may be more common in bipolar disorders. The aim of the study was to assess whether major depressive disorder (MDD) with anger could be included in the bipolar spectrum, by comparing it to MDD without anger and to bipolar II disorder. METHODS: Consecutive outpatients (281 bipolar II disorder and 202 MDD) presenting for major depressive episode (MDE) treatment were interviewed with the DSM-IV structured clinical interview. Clinical variables used to support the inclusion of MDD with anger in the bipolar spectrum were age of onset, many MDE recurrences, atypical features of depression, depressive mixed state (an MDE plus some concurrent hypomanic symptoms), and bipolar family history. RESULTS: Frequency of MDE with anger was 50.5% [61.2% in bipolar II, and 35.6% in MDD (z = 5.5, p = 0.0000, 95% CI 16.8-43.3%)]. Logistic regression of MDE with anger (dependent variable) versus bipolar variables showed that MDE with anger was significantly associated with all bipolar variables, apart from recurrences. MDD with anger, compared with MDD without anger, had significantly lower age of onset, more marked depressive mixed state, a bipolar family history with more cases, but comparable atypical features and Global Assessment of Functioning scores. MDD with anger, compared with bipolar II disorder, had significantly higher age of onset, less atypical features, and a bipolar family history with less cases. CONCLUSIONS: MDE with anger was common in outpatients (more in bipolar II disorder). MDD with anger may be midway between MDD without anger and bipolar II disorder, and might be included into the bipolar spectrum. However, MDD with anger does not appear to be associated with the often reported negative response to monotherapy with antidepressants.     

Seasonal affective disorder: a vestigial evolutionary advantage?

The typical symptoms of recurrent winter depression include lowered mood, lethargy, hypersomnia, social withdrawal, decreased libido, increased appetite and weight gain. Mild hypomania often occurs in spring and summer. It is argued that this pattern of attenuated hibernation constituted an adaptive evolutionary mechanism which enhanced the likelihood of reproductive success, most notably for females, among populations living at temperate latitudes. Women were more likely to become pregnant in the summer and thus to give birth at a time of year when their babies had a higher chance of survival. Winter depression symptoms also promoted healthier pregnancies and gave rise to enhanced female-male pair-bonding which improved the survival chances of both mothers and babies. Hypomania in spring and summer also served to increase the likelihood of procreation at the optimal time of year. In the modern era, it is probable that recurrent winter depression is becoming a reproductive disadvantage.     

Is there a relationship between attention deficit hyperactivity disorder and bipolar disorder?

With the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults and psychotic disorders in children and adolescents, the possibility of a relationship between bipolar disorder (BP) and ADHD has attracted growing interest. This paper critically reviews the scientific literature concerning this postulated relationship by examining evidence from clinico-epidemiological, follow up, family and laboratory studies, including neuroimaging, neuropsychology and genetic studies. The evidence suggests that although the diagnostic categories of BP and ADHD appear to be unrelated, there is support for a possible relationship between some ADHD and manic-like symptoms. However, several fundamental methodological issues require rectification in future research in order to further elucidate the relationship between these disorders.     

Is the perimenopause a time of increased risk of recurrence in women with a history of bipolar affective postpartum psychosis? A case series

Summary There is increasing awareness of the influence of female reproductive life events on the course of bipolar disorder. Here, we describe the case histories of 5 women diagnosed with postpartum psychosis who subsequently experienced major mood disorders in relation to the perimenopause. This case series suggests that (a) the perimenopause may be a time of increased risk for women who experienced postpartum bipolar episodes and (b) periods of hormonal change represent a major trigger for bipolar episodes in some women. Correspondence: Ian Jones Ph.D., MRCPsych, Department of Psychological Medicine, Henry Wellcome Building for Biomedical Research in Wales, Cardiff University, Heath Park, Cardiff CF14 4XN, U.K.     

Does sphingosine 1-phosphate play a protective role in the course of pulmonary tuberculosis?

Sphingosine 1-phosphate (S1P) has recently been reported to induce antimycobacterial activity in vitro and in a mouse model of in vivo Mycobacterium tuberculosis infection. However, its role in the course of pulmonary tuberculosis in humans is still not known. This study shows that S1P levels in airway surface fluid of tuberculosis (TB) patients are significantly less than those observed in non-TB control patients. Moreover, the in vitro stimulation of bronchoalveolar lavage cells coming from TB patients with S1P significantly reduces intracellular growth of endogenous mycobacterial isolates. These results show that, in the course of pulmonary TB, airway epithelial fluid-associated S1P may play a protective role in the containment of intracellular mycobacterial growth and that its decrease may represent a novel pathogenic mechanism through which M. tuberculosis favors its replication.     

Does family interrelating change over the course of individual treatment?

Interrelating is a combination of each person's relating towards a specified other and each person's view of the other's relating towards him/her. Negative interrelating is a maladaptive form of interrelating. The study aims to (1) compare the negative interrelating within the families of neurotic and psychotic psychotherapy outpatients; (2) examine whether individual treatment has a beneficial effect upon negative interrelating; (3) examine whether the improvement extends beyond the patients' interrelating with their parents (i.e., between the parents and the patients' sibling and between the parents themselves); and (4) make similar comparisons within a sample of non‐patients. The negative interrelating between the psychotic patients and their parents was more marked than that between the neurotic patients and their parents. The negative interrelating between the patients and their parents dropped significantly over the course of therapy. There were also significant changes in the interrelating between the patients' siblings and their parents and between the parents themselves even though they had not been involved in the therapy. Many of the end of therapy scores of the patients and their parents approached more those of the non‐patients. Copyright © 2010 John Wiley & Sons, Ltd. Key Practitioner Message: ? It is useful to measure both the negative relating of patients and the negative interrelating between patients and other family members. ? The patients' therapy appears also to benefit the interrelating between those family members who were not involved in the therapy. ? These findings may be more marked in Greek families, in which young adults stay closer to their parents.     

Toward a definition of a cyclothymic behavioral endophenotype: which traits tap the familial diathesis for bipolar II disorder?

BACKGROUND: Although the cyclothymic temperament appears to be related to the familial diathesis of bipolar disorder, exhibiting high sensitivity for bipolar II (BP-II) disorder, it is presently uncertain which of its constituent traits are specific for this disorder. METHODS: In a sample of 446 major depressive patients (BP-II and unipolar), in the French National EPIDEP study, the cyclothymic temperament was assessed by using clinician- and self-rated scales. We computed the frequency of individual traits and relative risk for family history of bipolarity. RESULTS: From both clinician- and self-rated scales, four items related to mood reactivity, energy, psychomotor and mental activity were significantly highly represented in the subgroup with positive family history of bipolarity. The item "rapid shifts in mood and energy" obtained the highest relative risk (OR=3.42) for positive family history of bipolarity. CONCLUSION: These findings delineate those cyclothymic traits which are most likely to tap a familial-genetic diathesis for BP-II, thereby identifying traits which can best serve as a behavioral endophenotype for this bipolar subtype. Such an endophenotype might underlie the cyclic course of bipolar disorder first described in France 150 years ago by Falret and Baillarger.     

In your eyes: Does theory of mind predict impaired life functioning in bipolar disorder?

Background

Deficits in emotion perception and social functioning are strongly implicated in bipolar disorder (BD). Examining theory of mind (ToM) may provide one potential mechanism to explain observed socio-emotional impairments in this disorder. The present study prospectively investigated the relationship between theory of mind performance and life functioning in individuals diagnosed with BD compared to unipolar depression and healthy control groups.

Methods

Theory of mind (ToM) performance was examined in 26 individuals with remitted bipolar I disorder (BD), 29 individuals with remitted unipolar depression (UD), and 28 healthy controls (CTL) using a well-validated advanced theory of mind task. Accuracy and response latency scores were calculated from the task. Life functioning was measured during a 12 month follow-up session.

Results

No group differences for ToM accuracy emerged. However, the BD group exhibited significantly shorter response times than the UD and CTL groups. Importantly, quicker response times in the BD group predicted greater life functioning impairment at a 12-month follow-up, even after controlling for baseline symptoms.

Limitations

The stimuli were static representations of emotional states and do not allow for evaluating the appropriateness of context during emotional communication; due to sample size, neither specific comorbidities nor medication effects were analyzed for the BD and UD groups; preliminary status of theory of mind as a construct.

Conclusions

Results suggest that quickened socio-emotional decision making may represent a risk factor for future functional impairment in BD.     

Is there a familial overlap between schizophrenia and bipolar disorder?

BACKGROUND: Most investigators accept that schizophrenia and bipolar disorders are distinct entities. The proponents of continuum model have challenged this dichotomy model. METHODS: Information about the first-degree relatives of probands with DSM-IV diagnosis of schizophrenia (n=90), bipolar disorder (n=90), and epilepsy (n=60) was collected by using the Family Interview for Genetic Studies (FIGS). A trained psychiatrist blind to the status of index probands obtained the information. Morbid risk in relatives was calculated using abridged Weinberg's method of age correction. RESULTS: Rates of schizophrenia and bipolar disorder were elevated in the relatives of schizophrenia and bipolar probands, but there was no evidence of coaggregation. The risk for major depression was significantly elevated in the relatives of schizophrenia probands and was comparable to the risk in the relatives of bipolar probands. LIMITATIONS: Family history method was used to obtain information about relatives. Schizoaffective disorder patients were not included in the study and this may have amplified the distinction between schizophrenia and bipolar disorder. CONCLUSIONS: The findings suggest that schizophrenia and bipolar disorders are familially independent, but there could be a familial relationship between the predisposition to schizophrenia and to major depression.