Medical and substance-related comorbidity in bipolar disorder: translational research and treatment opportunities

It is well established that individuals with bipolar disorder are differentially affected by substance-related as well as medical disorders (ie, cardiometabolic disorders, respiratory disorders, neurological disorders, and infectious diseases). Emerging evidence indicates that some comorbid conditions (eg, diabetes mellitus) in bipolar individuals may be subserved by overlapping neurobiological networks. Disturbances in glucocorticoid/insulin signaling and immunoinflammatory effector systems are points of pathophysiological commonality between bipolar disorder and "stress-sensitive" medical disorders. Subphenotyping bipolar disorder as a function of comorbidity and temporality of onset may provide an opportunity for refining disease pathophysiological models and developing innovative disease-modifying therapies.     

Recent advances in the genetics of recurrent vertigo and vestibulopathy

PURPOSE OF REVIEW: To focus on recent advances in the genetics of recurrent vertigo, with an overview on episodic ataxia, benign recurrent vertigo (mainly migraine-associated vertigo), bilateral vestibulopathy, and Ménière's disease. RECENT FINDINGS: Since the identification more than a decade ago of the genetic causes of episodic ataxia type 1 with myokymia caused by KCNA1 mutations and episodic ataxia type 2 with nystagmus caused by CACNA1A mutations, the list of episodic ataxia syndromes with distinct clinical features and genetic loci is slowly expanding, now up to episodic ataxia type 7. There is growing recognition for a correlation between benign recurrent vertigo and migraine, and acceptance for vertigo as a manifestation of migraine; efforts to identify susceptibility loci for migraine and migraine-associated vertigo are underway. A handful of families with vestibulopathy spanning several generations have been identified. Although no gene has yet been found, vestibulopathy with normal hearing variably associated with migraine is likely monogenic and heterogeneous, similar to nonsydromic deafness. There is also continuing effort to identify genetic causes of familial Ménière's disease. SUMMARY: Overlapping clinical features among different familial syndromes of recurrent vertigo and strong association with migraine suggest shared mechanisms. Collaborative efforts in patient identification and recruitment will facilitate progress in understanding disease mechanisms to improve diagnosis and treatment of recurrent vertigo.     

Ultrastructure of the blood-brain barrier of the gyrus hippocampal cortex in an experimental model of febrile seizures and with the use of a new generation antiepileptic drug--topiramate

The ultrastructure of the blood-brain barrier (BBB) of the gyrus hippocampal cortex in an experimental model of febrile seizures in rats and the effect of a new generation antiepileptic drug, topiramate, on the morphological status of this barrier were investigated. Advanced changes indicating a substantial increase in BBB permeability were observed in the animals with induced febrile seizures (FS), with approximately 2/3 of capillaries and perivascular astroglial processes being affected. Almost total occlusion of the capillary lumen was frequently seen, caused by damaged endothelial lining and by external pressure from markedly swollen perivascular astrocytic processes. Mitochondrial changes predominated among the abnormalities found in endoplasmic organelles of endothelial cells. Lesions in the BBB coexisted with damage to pyramidal neurons, mainly with features of aponecrosis ("dark neurons"). The study on topiramate seems to demonstrate its protective action on the BBB components of the ammonal cortex in the group receiving the drug as prevention, i.e. against febrile seizures. It was found to prevent marked BBB damage in over half of the capillaries. However, the application of topiramate directly after FS induction had no distinct beneficial effect on the structural BBB components.     

The Childhood Autism Spectrum Test (CAST): Sex Differences

The Childhood Autism Spectrum Test (CAST) (formally known as the Childhood Asperger Screening Test) identifies autism spectrum conditions by measuring social and communication skills. The present study explored the sex distribution of scores. The CAST was distributed to 11,635 children aged 4–9 years in Cambridgeshire primary schools (UK). 3,370 (29%) were returned. The median score was significantly higher in boys (median test, P < 0.001) (Boys, median = 5 (IQR: 3,8); girls, median = 4 (IQR: 2,6)). There was a predominance of boys (n = 81 (79.4%) over girls (n = 21 (20.6%)) amongst those scoring ≥ 15. Exclusion of children with ASC did not significantly affect the results. We conclude that different profiles of social and communication skills in boys and girls must be taken into account when measuring these skills in the general population. Fiona Scott is now freelance.     

POLG1 mutations manifesting as autosomal recessive axonal Charcot-Marie-Tooth disease

BACKGROUND: Although a molecular diagnosis is possible in most patients having Charcot-Marie-Tooth disease (CMT), recessively inherited and axonal neuropathies still present a diagnostic challenge. OBJECTIVE: To determine the cause of axonal CMT type 2 in 3 siblings. DESIGN: Case report. SETTING: Academic research. PARTICIPANTS: Three siblings who subsequently developed profound cerebellar ataxia. MAIN OUTCOME MEASURES: Muscle biopsy specimen molecular genetic analysis of the POLG1 (polymerase gamma-1) gene, as well as screening of control subjects for POLG1 sequence variants. RESULTS: Cytochrome c oxidase deficient fibers and multiple deletions of mitochondrial DNA were detected in skeletal muscle. Three compound heterozygous substitutions were detected in POLG1. CONCLUSION: Even in the absence of classic features of mitochondrial disease, POLG1 should be considered in patients having axonal CMT that may be associated with tremor or ataxia.     

Efficacy of antipsychotics to reverse phencyclidine-induced social interaction deficits in female rats--a preliminary investigation

Sub-chronic phencyclidine (PCP) treatment mimics certain aspects of schizophrenia symptomology in rats. However, there is a marked lack of attempts to model negative symptomology such as social behaviour deficits in female rats. This study was conducted to assess whether sub-chronic PCP treatment produces social interaction deficits in female rats and to ascertain if these deficits can be reversed by either typical (haloperidol) or atypical (clozapine and ziprasidone) antipsychotics.     

The Desire for Body Contouring Surgery after Bariatric Surgery

Background  Obesity has become far more prevalent over the last few decades. In parallel, bariatric surgery has been increasingly utilized as a method of treatment. This appears to be having an impact on the rate of body contouring surgery for hanging redundant skin after the massive weight loss that usually results from bariatric surgery. Little literature is available addressing how frequently patients who have undergone bariatric surgery receive or desire body contouring surgery or regarding how satisfied these patients are with the hanging skin in certain body areas. Methods  Seventy individuals (out of 250 who were mailed the questionnaire) who had undergone Roux-en-Y gastric bypass surgery 6–10 years previously completed a questionnaire, which obtained information regarding their experiences with as well as their desire for body contouring surgery and more general body area satisfaction. Results  Thirty three of the seventy patients reported having undergone a total of 38 body contouring procedures. The most common were abdominoplasties (24.3%), breast lifts (8.6%), and thigh lifts (7.1%). However, subjects were not uniformly satisfied with body areas that had undergone body contouring surgery; some found the areas unattractive. The majority of patients, at least to some extent, desired body contouring surgery, often in several areas, most notably the waist/abdomen, rear/buttock, upper arms, and chest/breast. Conclusion  Paralleling the increasing use of bariatric surgery is an increasing desire for body contouring surgery. Most patients desire body contouring surgery after bariatric surgery. However, third party payors usually do not reimburse for such procedures.     

Early and late outcomes of cardiac surgery in patients with moderate to severe preoperative renal dysfunction without dialysis

It is well known that end-stage renal failure requiring dialysis negatively impacts early and late outcome of cardiac surgery. However, data with respect to non-dialysis-dependent renal failure patients (NDRF) are limited. We retrospectively analyzed 6940 consecutive patients undergoing cardiac surgery from January 1998 to September 2006. Patients undergoing cardiac transplantation and ventricular assist device implantation (n=246) and dialysis dependent patients (n=245) were excluded. NDRF was present in 135 (2.1%) patients (mean age 64+/-14, 38% female). NRDF patients were more likely to present with cardiac related risk factors including ejection fraction <30% (P<0.001), prior myocardial infarction (P<0.001), congestive heart failure (P<0.001), active endocarditis (P<0.001) and hemodynamic instability (P<0.001). The estimated odds (OR) of hospital mortality in NDRF patients was 6.6 (P<0.001). Multivariate analysis retained NDRF as an independent factor for increasing the risk of hospital mortality among patients undergoing cardiac surgery (OR=5.1, P<0.001). Patients with NDRF were more likely to experience major postoperative complications when compared to the control group. One- and 5-year survival in NDRF patients was 82+/-4% and 63+/-6%, respectively, and significantly reduced compared to the control group. NDRF is a strong independent predictor of hospital mortality and morbidity in patients undergoing cardiac surgery. Preoperative renal dysfunction also adversely affects long-term survival in these patients.     

Prevalence of autism spectrum phenomenology in Cornelia de Lange and Cri du Chat syndromes

Autism spectrum disorder characteristics have not been evaluated in Cornelia de Lange and Cri du Chat syndromes using robust assessments. The Autism Diagnostic Observation Schedule and Social Communication Questionnaire were administered to 34 participants with Cornelia de Lange syndrome and a comparison group of 23 participants with Cri du Chat syndrome (M ages 12.4 [SD = 3.8] and 10.3 years [SD = 3.6], respectively). Twenty-one participants with Cornelia de Lange syndrome (61.8%) scored above the autism cut-off on the Autism Diagnostic Observation Schedule compared to 9 with Cri du Chat syndrome (39.2%). Prevalence of autism spectrum disorder characteristics is heightened in Cornelia de Lange syndrome. The profile of characteristics is atypical to that of idiopathic autism.     

Religious activity and lifetime prevalence of psychiatric disorder

BACKGROUND: There is growing evidence that current religious activity is associated with less psychological distress, yet research on clinical levels of psychopathology along with lifetime patterns of religious activity remains limited. METHOD: In this study, we used data on 718 participants from the Providence, RI, cohort of the National Collaborative Perinatal Project, to test for the association between lifetime patterns of religious service attendance frequency, subjective religiosity, and lifetime psychiatric diagnosis. RESULTS: For women, but not men, a changing pattern of service attendance (having stopped or started attending services since childhood) was associated with increased lifetime rates of generalized anxiety, and marginally increased rates of alcohol abuse/dependence (OR for generalized anxiety: 2.71, 95% CI: 1.11-6.62; OR for alcohol abuse/dependence=1.97, 95% CI: 0.92-4.20) compared to a stable pattern of continuous religious service attendance. Conversely, men who changed their frequency of religious service attendance were less likely to have ever met diagnostic criteria for major depression (OR=0.50, 95% CI: 0.31-0.83) as compared to those who had always been religiously active. The rates of psychiatric illness among those who reported never attending religious services were not statistically different from those who either had always been religiously active or those who reported changing patterns of attendance. CONCLUSION: These findings suggest that lifetime religious activity patterns are associated with psychiatric illnesses, with different patterns observed for men and women.