Factors associated with health-related quality of life in pediatric cancer survivors.

BACKGROUND: Childhood cancer survivors are at risk for late effects of disease and treatment that may be attributed to multiple causes. This study describes health-related quality of life (HRQOL) in childhood cancer survivors and identifies factors related to poor quality of life outcomes. PROCEDURE: Patients age 8-18 years, who attended the long-term information, follow-up, and evaluation (LIFE) clinic at Childrens Hospital Los Angeles during a 1-year time-period were eligible for the study. Eighty-six survivors (mean time off-treatment=7.8 years) completed the Pediatric Quality of Life Inventory 4.0 Generic Core Scales, a LIFE Clinic Intake Questionnaire and rated their fatigue using a 10-point scale. Oncology nurses independently rated subjects' late effects using a 3-point severity scale. Linear regression procedures were used to evaluate the association between demographic and medical factors and HRQOL. RESULTS: Fatigue and more severe late effects were associated with poorer physical functioning (fatigue, P<0.02; late effects, P<0.01). Fatigue, ethnic minority status, and a brain tumor diagnosis were associated with poorer psychosocial functioning (fatigue, P<0.0001; minority status, P<0.04; brain tumor, P<0.01). Fatigue was the only factor related to both poor physical and psychosocial HRQOL. CONCLUSIONS: Long-term follow-up clinics for childhood cancer survivors are in a unique position to monitor HRQOL over time. Factors associated with poorer HRQOL include fatigue, ethnic minority status, a brain tumor diagnosis, and more severe late effects. Future studies need to clarify relationships between ethnicity, socioeconomic status (SES), and HRQOL in cancer survivors.

Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats.

BACKGROUND: Brain phospholipid metabolism and membrane fluidity may be involved in the pathophysiology of mood disorders. We showed previously that cytidine, which increases phospholipid synthesis, has antidepressant-like effects in the forced swim test (FST) in rats, a model used in depression research. Because cytidine and uridine both stimulate synthesis of cytidine 5'-diphosphocholine (CDP-choline, a critical substrate for phospholipid synthesis), we examined whether uridine would also produce antidepressant-like effects in rats. We also examined the effects of omega-3 fatty acids (OMG), which increase membrane fluidity and reportedly have antidepressant effects in humans, alone and in combination with uridine. METHODS: We first examined the effects of uridine injections alone and dietary supplementation with OMG alone in the FST. We then combined sub-effective treatment regimens of uridine and OMG to determine whether these agents would be more effective if administered together. RESULTS: Uridine dose-dependently reduced immobility in the FST, an antidepressant-like effect. Dietary supplementation with OMG reduced immobility when given for 30 days, but not for 3 or 10 days. A sub-effective dose of uridine reduced immobility in rats given sub-effective dietary supplementation with OMG. CONCLUSIONS: Uridine and OMG each have antidepressant-like effects in rats. Less of each agent is required for effectiveness when the treatments are administered together.

Omega-3 fatty acid treatment and T(2) whole brain relaxation times in bipolar disorder.

OBJECTIVE: The authors hypothesized that changes in brain membrane composition resulting from omega-3 fatty acid administration in patients with bipolar disorder would result in greater membrane fluidity, as detected by reductions in T(2) values. METHOD: Women with bipolar disorder (N=12) received omega-3 fatty acids for 4 weeks. A cohort of bipolar subjects (N=9) and a group without bipolar disorder (N=12) did not receive omega-3 fatty acids. T(2) values were acquired at baseline and after 4 weeks. RESULTS: Bipolar subjects who received omega-3 fatty acids had significant decreases in T(2). There was a dose-dependent effect when the bipolar omega-3 fatty acid group was subdivided into high- and low-dose cohorts. CONCLUSIONS: Omega-3 fatty acids lowered T(2) values, consistent with the hypothesis that the fluidity of cell membranes was altered. Further studies are needed to clarify the significance of alterations in brain physiology induced by omega-3 fatty acids, as reflected in T(2) values.

Frontal lobe gray matter density decreases in bipolar I disorder.

BACKGROUND: This study was conducted to explore differences in gray and white matter density between bipolar and healthy comparison groups using voxel-based morphometry (VBM). METHODS: Brain magnetic resonance imaging was performed for 39 subjects with bipolar I disorder and 43 comparison subjects. Images were registered into a proportional stereotaxic space and segmented into gray matter, white mater, and cerebrospinal fluid. Statistical parametric mapping was used to calculate differences in gray and white matter density between groups. RESULTS: Bipolar subjects had decreased gray matter density in left anterior cingulate gyrus (Brodmann's area [BA] 32, 7.3% decrease), an adjacent left medial frontal gyrus (BA 10, 6.9% decrease), right inferior frontal gyrus (BA 47, 9.2% decrease), and right precentral gyrus (BA 44, 6.2% decrease), relative to comparison subjects. CONCLUSIONS: The observation of a gray matter density decrease in the left anterior cingulate, which processes emotions, in bipolar subjects is consistent with prior reports that used region-of-interest analytic methods. Decreased gray matter density in the right inferior frontal gyrus, which processes nonverbal and intrinsic functions, supports nondominant hemisphere dysfunction as a component of bipolar disorder.

S-adenosyl-L-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects.

BACKGROUND: S-adenosyl-L-methionine is an effective treatment for clinical depression, although the mechanism underlying this effect is unclear. Presently, in vivo phosphorus magnetic resonance spectroscopy (31P MRS) and brain transverse relaxometry were employed to test if S-adenosyl-L-methionine supplementation alters brain bioenergetics and/or transverse relaxation time (T2RT) in a nondepressed cohort. If these magnetic resonance techniques are sensitive to S-adenosyl-L-methionine induced alterations in neurochemical processes, these methods may be used in cases of clinical depression to elucidate the mechanism underlying the antidepressant effect of S-adenosyl-L-methionine. METHODS: Twelve subjects self-administered 1600 mg of oral S-adenosyl-L-methionine daily. Phosphorus spectra and transverse relaxation time were acquired at baseline and after treatment using a 1.5 Tesla scanner. RESULTS: Phosphocreatine levels were significantly higher after treatment, whereas beta nucleoside triphosphate levels, predominantly adenosine triphosphate in brain, were significantly lower after treatment. A surprising gender difference in T2RT emerged after supplementation, with women exhibiting significantly lower T2RT than men. CONCLUSIONS: Alterations in phosphocreatine and beta nucleoside triphosphate are consistent with the report that S-adenosyl-L-methionine is involved in the production of creatine, which in turn is phosphorylated to phosphocreatine using adenosine triphosphate. These findings suggest that S-adenosyl-L-methionine alters parameters associated with cerebral bioenergetic status and that some effects of S-adenosyl-L-methionine (T2RT) occur in a gender-specific manner.

Phosphorous31 magnetic resonance spectroscopy after total sleep deprivation in healthy adult men.

STUDY OBJECTIVES: To investigate chemical changes in the brains of healthy adults after sleep deprivation and recovery sleep, using phosphorous magnetic resonance spectroscopy. DESIGN: Three consecutive nights (baseline, sleep deprivation, recovery) were spent in the laboratory. Objective sleep measures were assessed on the baseline and recovery nights using polysomnography. Phosphorous magnetic resonance spectroscopy scans took place beginning at 7 am to 8 am on the morning after each of the 3 nights. SETTING: Sleep laboratory in a private psychiatric teaching hospital. PARTICIPANTS: Eleven healthy young men. INTERVENTIONS: Following a baseline night of sleep, subjects underwent a night of total sleep deprivation, which involved supervision to ensure the absence of sleep but was not polysomnographically monitored. MEASUREMENTS AND RESULTS: No significant changes in any measure of brain chemistry were observed the morning after a night of total sleep deprivation. However, after the recovery night, significant increases in total and beta-nucleoside triphosphate and decreases in phospholipid catabolism, measured by an increase in the concentration of glycerylphosphorylcholine, were observed. Chemical changes paralleled some changes in objective sleep measures. CONCLUSIONS: Significant chemical changes in the brain were observed following recovery sleep after 1 night of total sleep deprivation. The specific process underlying these changes is unclear due to the large brain region sampled in this exploratory study, but changes may reflect sleep inertia or some aspect of the homeostatic sleep mechanism that underlies the depletion and restoration of sleep. Phosphorous magnetic resonance spectroscopy is a technique that may be of value in further exploration of such sleep-wake functions.

Antidepressant-like effects of cytidine in the forced swim test in rats.

BACKGROUND: Altered brain phospholipid metabolism may be involved in the pathophysiology of cocaine dependence and mood disorders. Evidence suggests that citicoline, a rate-limiting metabolite for phospholipid synthesis, reduces cocaine craving in human addicts. Because antidepressants can reduce cocaine craving, we explored in rats the possibility that citicoline has antidepressant effects. We also tested the primary metabolites of citicoline, cytidine and choline. METHODS: We examined if citicoline or metabolites alter immobility in the forced swim test. We used two scoring methods: latency to become immobile, a simple method that identifies antidepressants, and behavioral sampling, a complex method that differentiates antidepressants according to pharmacological mechanisms. RESULTS: Over a range of doses, citicoline did not affect behavior in the forced swim test. At molar equivalent doses, cytidine dramatically decreased immobility, whereas choline tended to increase immobility. The effects of cytidine resemble those of desipramine, a standard tricyclic antidepressant. None of the treatments affected locomotor activity, and cytidine did not establish conditioned place preferences. CONCLUSIONS: Citicoline does not have effects in the forced swim test, but its primary metabolites have opposing effects: cytidine has antidepressant-like actions, whereas choline has prodepressant-like actions. At antidepressant doses, cytidine lacks stimulant and rewarding properties. This is the first report of potential antidepressant effects of cytidine.