Enhanced cancer risk among patients with bipolar disorder

BACKGROUND: In contrast to numerous epidemiological studies that explored the risk for cancer among persons with schizophrenic psychoses, analogous studies conducted on people with bipolar disorder are rarer, despite some commonalities in biological, treatment-related variables and unhealthy lifestyles. This study investigates the risk for cancer among psychiatric inpatients diagnosed with bipolar disorder. METHODS: Linkage analysis was conducted based on the psychiatric and the cancer national databases. Standardized incidence ratios (SIR) for both aggregated sites and for breast cancer were calculated by comparing the incidence rates among hospitalized patients with bipolar disorder with the incidence rates in the Jewish-Israeli general population. RESULTS: An enhanced cancer risk was found for bipolar disorder in both genders: men, SIR 1.59 (95% CI 1.01-2.17); women, SIR 1.75 (95% CI 1.31-2.18). The risk for breast cancer was higher, but not significantly, than in the general female population, SIR 1.70 (95% CI 0.99-2.41). LIMITATIONS: Our sample was derived from psychiatric inpatients, thus it is likely that the bipolar disorder cases had greater severity. Putative factors such as diet, smoking and medications were not investigated. CONCLUSIONS: Our study showed an enhanced risk for cancer among patients with bipolar disorder. Clinicians might note this risk for timely diagnosis and treatment.     

CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: a case-control study of female patients and several ethnic groups in the Israeli Jewish population.

The human small-conductance Ca(2+)-activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family-based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co-morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case-control analysis that has demonstrated a significant over-representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co-morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive-compulsive disorder (OCD) co-morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.     

Involvement of tumor necrosis factor alpha and interleukin-1beta in enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae

Neurologic manifestations, mainly convulsions, are the most frequent extraintestinal complications of shigellosis. We used an animal model to study the roles of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in Shigella-related seizures. Administration of Shigella dysenteriae 60R sonicate enhanced the sensitivity of mice to the proconvulsant pentylenetetrazole (PTZ) within 7 h. This was indicated by a significantly higher mean convulsion score and an increased number of mice responding with clonic-tonic seizures in the Shigella-pretreated group. Preinjection of mice with anti-murine TNF-alpha (anti-mTNF-alpha) or anti-murine IL-1beta (anti-mIL-1beta) 30 min prior to administration of Shigella sonicate abolished their enhanced response to PTZ at 7 h. Mean convulsion scores were reduced by anti-mTNF-alpha from 1.2 to 0.8 (P = 0.017) and by anti-mIL-1beta from 1.3 to 0.7 (P = 0.008). Preinjection of anti-mTNF-alpha also reduced the percentage of mice responding with clonic-tonic seizures, from 48 to 29% (P = 0.002), and preinjection of anti-mIL-1beta reduced it from 53 to 21% (P = 0. 012). Neutralization of TNF-alpha or IL-1beta did not protect the mice from death due to S. dysenteriae 60R. These findings indicate that TNF-alpha and IL-1beta play a role in the very early sensitization of the central nervous system to convulsive activity after S. dysenteriae administration. Similar mechanisms may trigger neurologic disturbances in other infectious diseases.     

Group cognitive behavioral treatment in female soldiers diagnosed with binge/purge eating disorders

ABSTRACT

Cognitive behavioral treatment (CBT) is the recommended intervention in bulimia nervosa (BN) and eating disorders not otherwise specified with binge/purge (EDNOS-B/P) symptoms. There are fewer data on its application in a group format. We sought to investigate the effect of group CBT in female soldiers with B/P symptomatology in an open trial design. For this purpose we assessed 64 female soldiers serving in the Israeli Defense Force diagnosed with BN and EDNOS-B/P who participated in a group CBT format of 16 weekly sessions and one follow-up session. In this study, 42 participants (65.6%) completed treatment and 22 participants (34.4%) did not. A total of 39 treatment completers (92.8% of treatment completers) and 19 non-completers (86.4% of treatment non-completers) were assessed around 12 months after treatment. Participants completed at baseline and following treatment questionnaires assessing eating-related symptoms, depression, anxiety, and overall functioning. At follow-up they were assessed for eating-related symptoms. Our findings show only minimal baseline differences between treatment completers and non-completers. Significant improvement from baseline to post-treatment was shown for B/P and restrictive symptoms, depression, anxiety, and overall functioning. At that time, more than a third of treatment completers were abstinent from binging and more than a half from vomiting. The improvement in B/P and restricting symptoms was maintained at 1 year follow-up for treatment completers. At that time around 60% were abstinent from binging and more than 70% from vomiting. Participants not completing treatment were also improved at follow-up but to a lesser extent. The findings of the present study suggest that group CBT may be effective for the treatment of female soldiers with BN and EDNOS-B/P.     

Safety and efficacy of long-term low-dose clozapine aftercare treatment in a patient with learning difficulties who suffered from neuroleptic malignant syndrome

INTRODUCTION : Antipsychotic medication continues to be an essential component in the treatment of schizophrenia. Neuroleptic malignant syndrome (NMS) is one of the most serious complications of neuroleptic treatment and the optimal therapeutic aftercare regimen for patients is unclear. Also, it is not clear if low-dose neuroleptic maintenance in such patients is safe and efficient enough over time. METHOD : We present a case of a 56-year-old woman suffering from schizoaffective disorder, who was successfully treated with a low dosage of clozapine for 6.5 years following a NMS episode. RESULT : To the best of our knowledge this is the first report of such a long-term beneficial use of low-dose clozapine in a patient who previously underwent such a serious complication. CONCLUSION : Large-scale studies are needed to substantiate this observation. (Int J Psych Clin Pract 2002; 6: 121-123)     

Impact of Gastric Banding on Plasma Adiponectin Levels

Background: Several endocrine abnormalities are reported in obesity. In an earlier study, we found that the changes in BMI following laparoscopic adjustable gastric banding (LAGB) were associated with changes in hormone profiles such as insulin and proinsulin. In the current study, we explored the changes in plasma adiponectin levels in morbidly obese subjects who lost abundant weight following LAGB. Methods: 23 adult morbidly obese patients (15 females), aged 21-56 years, were studied. Blood samples were collected before, and 6 and 14 months after LAGB. The plasma adiponectin levels were determined by commercial kit (B-Bridge International, Inc). Statistical analysis was based on one-way repeated measures ANOVA, followed by Student-NewmanKeuls post-hoc test. Regression model was used to look for predictors of adiponectin change after LAGB. Results: Mean BMI before surgery was 46.04±4.44 kg/m², and decreased significantly by 18% 6 months after surgery to 37.67±4.47 kg/m². BMI further decreased by 32% 14 months after surgery to a mean of 31.30±4.65 kg/m² (P =.000). The mean adiponectin level before surgery was 3997±1766 μg/ml, and increased significantly by 16% to 4763±1776 μg/ml 6 months after surgery, and to 6336±3292 μg/ml (37%) 14 months after surgery. Although BMI persistently decreased, while adiponectin persistently increased, BMI did not correlate with adiponectin. Conclusion: In morbidly obese patients who underwent LAGB, adiponectin levels persistently increased, probably due to the reduction of visceral fat mass. Adiponectin plasma increase was correlated with proinsulin levels prior to the surgery. The interaction between adiponectin, proinsulin and BMI change in morbid obesity merits further investigation.     

Adherence to antidepressant medications is associated with reduced premature mortality in patients with cancer: A nationwide cohort study

Background: Depression and anxiety are common in cancer and antidepressants (AD) are efficacious treatment. The relationship between AD adherence and mortality in cancer is unclear. This study aimed to evaluate the association between adherence to AD and all‐cause mortality in a population‐based cohort of patients with cancer. Materials and Methods: We conducted a 4‐year historical prospective cohort study including 42,075 patients with cancer who purchased AD at least once during the study period. Adherence to AD was modeled as nonadherence (<20%), poor (20–50%), moderate (50–80%), and good (>80%) adherence. We conducted multivariable survival analyses adjusted for demographic and clinical variables that may affect mortality. Results: During 1,051,489 person‐years at risk follow‐up, the adjusted hazard ratios (HR) for mortality were 0.89 (95% confidence interval [CI]: 0.83–0.95), 0.77 (95% CI: 0.66–0.72), and 0.80 (95% CI: 0.76–0.85) for the poor, moderate, and good adherence groups, respectively, compared to the nonadherent group. Analysis of the entire sample and a subgroup with depression, for cancer subtypes, revealed similar patterns for breast, colon, lung, and prostate cancers, but not for melanoma patients. Multivariate predictors of premature mortality included male gender (HR 1.48 [95% CI: 1.42–1.55]), current/past smoking status (HR 1.1, [95% CI: 1.04–1.15]; P < .0001), low socioeconomic status (HR 1.1, [95% CI: 1.03–1.17]; P < .0001) and more physical comorbidities. Conclusions: The present study is the first to demonstrate that higher adherence to AD is associated with a decrease of all‐cause mortality in a large nationwide cohort of cancer patients. Our data add to the pressing need to encourage adherence to AD among cancer patients.     

Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes

22q11.2 deletion syndrome (22q11.2DS) is a common genetic risk factor for the development of schizophrenia. We investigated two neurophysiological endophenotypes of schizophrenia – P50 sensory gating and mismatch negativity in 22q11.2DS subject and evaluated their association with catechol O-methyltransferase (COMT) and proline dehydrogenase (PRODH) genetic variants. We also assessed the association of neurophysiological measures with schizophrenia-like symptomatology in 22q11.2DS. Fifty-nine subjects, 41 with 22q11.2DS and 18 typically developing controls, participated in the study. The participants with 22q11.2DS were genotyped for the COMT Val¹⁵⁸Met (rs4680) and PRODH Gln¹⁹Pro (rs2008720) and Arg¹⁸⁵Trp (rs4819756) polymorphisms. Following psychiatric evaluation, all the participants underwent neurophysiological recordings and executive function assessment. The 22q11.2DS group showed poorer sensory gating of the P50 response than the controls. Within the 22q11.2DS group, the COMT Met allele was associated with poorer sensory gating, while both the COMT Met allele and the PRODH Pro-Arg haplotype were associated with smaller mismatch negativity amplitudes. Smaller mismatch negativity amplitudes predicted greater impairment of executive functions and greater severity of schizophrenia-like negative symptoms in 22q11.2DS. The current study demonstrates that sensory gating impairments that are typical of schizophrenia are found in 22q11.2DS subjects. Our results further suggest that COMT and PRODH genetic variations contribute to sensory gating and mismatch negativity schizophrenia-like impairments in 22q11.2DS, possibly via dopaminergic/glutamatergic networks. The associations of mismatch negativity impairments with increased severity of schizophrenia-like negative symptoms and poorer executive functions performance in our 22q11.2DS sample suggest that mismatch negativity is a potential endophenotype for schizophrenia in 22q11.2DS.