Safety assessment of DHA-rich microalgae from Schizochytrium sp.

The purpose of this study was to determine the potential toxicity of docosahexaenoic acid-rich microalgae from Schizochytrium sp. (DRM), administered in the diet to rats for at least 13 weeks. DRM was administered in the diet to groups of 20 male and 20 female Sprague-Dawley derived rats (Crl:CD(SD)BR) to provide dosages of 0, 400, 1500, and 4000 mg/kg/day for at least 13 weeks. DRM contained high levels of fat (approximately 41% w/w) of which long-chain highly unsaturated fatty acids (PUFAs) were a major component. Vitamin E acetate was added to DRM at manufacture to provide supplementary dietary antioxidant given the highly unsaturated fat content of DRM. Untreated controls received the basal diet only. An additional group of 20 males and 20 females received basal diet mixed with fish oil (Arista) to provide a target dosage of 1628 mg/kg/day, an amount of fat comparable to that received by rats administered the highest dose of DRM. Vitamin E acetate was also added to the fish oil to provide a comparable level of dietary antioxidant provided to high-dose DRM rats. There were no treatment-related effects in clinical observations, body weights or weight gains, food consumption, hematologic or urinalysis values, gross necropsy findings, or organ weights and there were no deaths. The only treatment-related changes in clinical chemistry parameters were decreases in high-density lipoproteins and cholesterol in the DRM and fish oil groups when compared to the untreated controls. These changes were expected based on the high PUFA content of DRM and fish oil. There were no microscopic findings suggestive of toxicity. Periportal hepatocellular fat vacuolation (accumulation of fat) was observed only in the livers of female rats in both the DRM (all dosages) and fish oil groups. This finding was expected given the higher fat content of both the DRM and the fish oil diets compared to the basal diet fed to the untreated controls. A slight increase in the incidence, but not severity, of cardiomyopathy was observed only in the 4000 mg/kg/day DRM males. This finding was not considered adverse because cardiomyopathy occurs spontaneously in rats and especially male rats of the Sprague-Dawley strain when fed high levels of fat. Since cardiomyopathy does not develop in other species including primates fed high-fat diets, its occurrence in rats is considered to have little relevance to human health. This study demonstrates that administration of DRM did not produce any treatment-related adverse effects in Sprague-Dawley rats of relevance to humans at dosages up to 4000 mg/kg/day for 13 weeks.

Anxiety contributes to suicidality in depressed adolescents.

Several studies have suggested a positive association between anxiety symptoms and suicidality in adults. However, relatively little is known about this topic in adolescents. To investigate this issue, we examined a group of adolescents admitted to our psychiatric inpatient unit. Fifty-six adolescents (mean age = 14.8 +/- 1.4; females = 34, males = 22; race = 95% Caucasians) participated in the study. Diagnoses were made using the DSM-III-R criteria and a diagnostic interview. Anxiety was found to significantly correlate with depression (r = .60; P = < .05) and suicidality (r = .72; P < .05). A multiple regression analysis revealed that anxiety and depression together accounted for more than half (55%) of the variance in suicidal ideation [F(2,46) = 28.4; P < .0001]. In addition, anxiety had an independent ability to predict suicidality (t = 5.01; P < .0001). Self-rated but not clinician-rated suicidality was positively correlated with both anxiety and depression. Clinical and research implications of these findings are discussed.

The expressed protein in glyphosate-tolerant soybean, 5-enolpyruvylshikimate-3-phosphate synthase from Agrobacterium sp. strain CP4, is rapidly digested in vitro and is not toxic to acutely gavaged mice.

The safety of 5-enolpyruvylshikimate-3-phosphate synthase enzyme derived from Agrobacterium sp. strain CP4 (CP4 EPSPS) was assessed. CP4 EPSPS is the only protein introduced by genetic manipulation that is expressed in glyphosate-tolerant soybeans, which are being developed to provide new weed-control options for farmers. Expression of this protein in plants imparts high levels of glyphosate tolerance. The safety of CP4 EPSPS was ascertained by evaluating both physical and functional characteristics. CP4 EPSPS degrades readily in simulated gastric and intestinal fluids, suggesting that this protein will be degraded in the mammalian digestive tract upon ingestion as a component of food or feed, There were no deleterious effects due to the acute administration of CP4 EPSPS to mice by gavage at a high dosage of 572 mg/kg body wt, which exceeds 1000-fold tha anticipated consumption level of food products potentially containing CP4 EPSPS protein. CP4 EPSPS does not pose any important allergen concerns because this protein does not possess characteristics typical of allergenic proteins. These data, in combination with seed compositional analysis and animal feeding studies, support the conclusion that glyphosate-tolerant soybean are as safe and nutritious as traditional soybeans currently being marketed.

The feeding value of soybeans fed to rats, chickens, catfish and dairy cattle is not altered by genetic incorporation of glyphosate tolerance.

Animal feeding studies were conducted with rats, broiler chickens, catfish and dairy cows as part of a safety assessment program for a soybean variety genetically modified to tolerate in-season application of glyphosate. These studies were designed to compare the feeding value (wholesomeness) of two lines of glyphosate-tolerant soybeans (GTS) to the feeding value of the parental cultivar from which they were derived. Processed GTS meal was incorporated into the diets at the same concentrations as used commercially; diary cows were fed 10 g/100 g cracked soybeans in the diet, a level that is on the high end of what is normally fed commercially. In a separate study, laboratory rats were fed 5 and 10 g unprocessed soybean meal 100 g diet. The study durations were 4 wk (rats and dairy cows), 6 wk (broilers) and 10 wk (catfish). Growth, feed conversion (rats, catfish, broilers), fillet composition (catfish), and breast muscle and fat pad weights (broilers) were compared for animals fed the parental and GTS lines. Milk production, milk composition, rumen fermentation and nitrogen digestibility were also compared for dairy cows. In all studies, measured variables were similar for animals fed both GTS lines and the parental line, indicating that the feeding value of the two GTS lines is comparable to that of the parental line. These studies support detailed compositional analysis of the GTS seeds, which showed no meaningful differences between the parental and GTS lines in the concentrations of important nutrients and antinutrients. They also confirmed the results of other studies that demonstrated the safety of the introduced protein, a bacterial 5-enolpyruvyl-shikimate-3-phosphate synthase from Agrobacterium sp. strain CP4.

Electroconvulsive treatment in adolescents with pharmacotherapy-refractory depression.

The effectiveness and safety of ECT in pharmacotherapy-refractory depression was examined in 11 hospitalized adolescents (ages 16.3 +/- 1.7 years, 10 females) with a primary DSM-III-R diagnosis of mood disorder, which had failed to respond to three or more adequate trials of antidepressant pharmacotherapy. After a thorough diagnostic evaluation, patients received a course of ECT involving 11.2 +/- 2.0 (range 8-15) administrations. ECT was commenced with bilateral treatment in 2 adolescents and nondominant right electrode placement in 9 patients; 5 of the 9 patients were subsequently changed to bilateral treatment. All 11 patients improved to a clinically significant degree. Significant improvements were noted in scores on the Children Depression Rating Scale-Revised (CDSR-R) and the Global Assessment of Functioning Scale (GAF) (p < 0.05). Euthymia, defined as CDRS-R score < or = 40, was achieved by 64% (7/11) of patients. The Mini-Mental State Examination showed no significant decline in cognitive functioning. Neuropsychological testing completed in 5 subjects both before ECT and 1-5 days after the last treatment, indicated a significant decline in attention, concentration, and long-term memory search. Minor side effects, experienced within the first 12 hours of treatment, were headache (80% of patients) and nausea/vomiting (64%). The potentially serious complication of tardive seizure (after full recovery of consciousness) occurred in 1 adolescent. Prolonged seizures (> 2.5 minutes) were noted in 7 of the 11 patients (9.6% of the 135 ECT administrations). Pending further research on ECT in youth, it is recommended that ECT should only be administered to youth in hospital settings, that all regularly administered psychotropic medications (including antidepressants) be discontinued before ECT and restarted after the final administration of ECT, and that physicians be aware that 12 treatments are usually sufficient, but that 15 treatments may occasionally be necessary for treating depressed adolescents. With the understanding that scientific evaluation of ECT in youth is lacking, it appears that ECT can be an effective and relatively safe treatment for depressed adolescents who have failed to respond to antidepressant pharmacotherapy.

Parents' marital functioning and adolescent psychopathology.

Parents' marital functioning and adolescent psychopathology were investigated in 2 studies. The first study compared parents' marital satisfaction, conflict over childrearing, affective communication, and traditional role orientation in matched samples of psychiatric inpatient and control-group adolescents. The second study examined associations between specific dimensions of marital functioning and adolescent depression severity, suicidal ideation, and social adjustment in a larger sample of adolescent inpatients. In Study 1, parents of inpatients reported less marital satisfaction and more conflicts over childrearing than parents of control-group adolescents. In Study 2, marital conflicts over childrearing were associated with a less active or involved father-adolescent relationship and more severe school behavior and spare time problems. Marital functioning was not associated with depression severity or suicidal ideation.

Suicide contagion among adolescents during acute psychiatric hospitalization.

OBJECTIVE: The study investigated whether exposure to other suicidal adolescents led to suicide contagion among patients hospitalized on an acute adolescent psychiatry unit. It also examined whether some adolescents express more suicidality during hospitalization than before admission. METHODS: Fifty-seven adolescents with a range of diagnoses admitted to a university-based psychiatric inpatient unit were assessed for suicidality at hospital admission and discharge using the Spectrum of Suicide Behavior scale and the Suicidal Ideation Questionnaire-Jr. Suicidal intent or behavior was the primary reason for admission of 58 percent of the patients. RESULTS: Despite many patients' severe suicide risk at hospital admission, 94 percent expressed no active suicidal intent and engaged in no behavior that could be considered suicidal during hospitalization. Four patients engaged in possibly suicidal, self-cutting behaviors; however, these incidents did not cluster in time. Fourteen patients (26 percent) expressed a significant increase in suicidal ideation during hospitalization, but the increase was not associated with study measures of exposure to other suicidal adolescents. CONCLUSIONS: Contagion of suicidal behaviors may not be a frequent or significant problem on acute adolescent inpatient units, although the phenomenon of increased suicidal ideation among some inpatients warrants further study.

Psychosocial functioning of severely disturbed adolescents after short-term hospitalization.

Forty-two severely emotionally disturbed adolescents discharged after a brief hospitalization for an acute psychiatric episode were assigned to two groups--one for whom clinicians recommended continued intensive treatment in an inpatient, residential, or day treatment setting, even though such services were not available, and the other for whom clinicians recommended only outpatient treatment. The two groups were compared on rates of rehospitalization, self-harmful actions, and suicide attempts and on severity of problems with peers during the six months after discharge. The two groups showed significant differences only in the extent of their problems with peers.

A prospective study of adolescent suicidal behavior following hospitalization.

Identification of factors associated with adolescent suicidal behavior following psychiatric hospitalization would facilitate development of effective aftercare interventions. This prospective study identified specific predictors of suicidal behavior in 100 adolescents during a 6-month follow-up period. Standardized baseline assessments and structured follow-up telephone interviews were conducted with adolescents and their guardians. Eighteen percent of adolescents reported suicidal behavior during the follow-up period, primarily of low medical lethality and minimal or ambivalent suicidal intent. This behavior was associated with suicidal thoughts, family dysfunction, and dysthymia. It was not associated with initial posthospitalization treatment compliance. Implications of these findings are discussed.

Language disorders and learning disabilities in school-refusing adolescents.

OBJECTIVE: We undertook this study to test the hypothesis that school-refusing adolescents hospitalized on an inpatient psychiatric unit have more language and learning disabilities than diagnosis-, age-, and sex-matched psychiatric controls. METHOD: The Woodcock-Johnson Tests of Achievement-Revised (WJTA-R), the WISC-R, the Adolescent Language Screening Test, the Clinical Evaluation of Language Fundamentals-Revised, and the Test of Language Competence (TLC) were given to a group of well-characterized, primarily depressed school refusers and matched psychiatric controls. RESULTS: We found that school-refusing adolescents had significantly lower WISC-R verbal intelligence scores, lower Math and Written Language subscale scores on the WJTA-R, and lower scores on the TLC than nonrefusers. School refusers were found to have a significantly higher incidence of both language impairments and learning disabilities than controls. CONCLUSIONS: We infer that academic and communicative frustration and the adolescent's resulting inability to meet the academic and social demands in the school environment may play a role in the etiology of school refusal.

Update on lithium carbonate therapy in children and adolescents.

The use of lithium to treat child and adolescent psychiatric disorders is becoming more common. Since the publication of the report of The Committee on Biological Aspects of Child Psychiatry of the American Academy of Child Psychiatry in 1978, a considerable body of literature has accumulated on the efficacy of lithium in treating adolescent bipolar disorders, childhood aggression, and behavioral disorders associated with mental retardation and developmental disorders. Efforts to understand lithium's mechanism(s) and refinements in psychiatric diagnosis have contributed to its growing use.

Safety assessment of the neomycin phosphotransferase II (NPTII) protein.

Two approaches were used to assess the safety of the NPTII protein for human consumption using purified E. coli produced NPTII protein that was shown to be chemically and functionally equivalent to the NPTII protein produced in genetically engineered cotton seed, potato tubers and tomato fruit. The NPTII protein was shown, as expected, to degrade rapidly under simulated mammalian digestive conditions. An acute mouse gavage study confirmed that the NPTII protein caused no deleterious effects when administered by gavage at a cumulative target dosage of up to 5000 mg/kg of body weight. This dosage correlates to at least a million fold safety factor relative to the average daily consumption of potato or tomato, assuming all the potatoes or tomatoes consumed contained the NPTII protein. These results, along with previously published information, confirm that ingestion of genetically engineered plants expressing the NPTII protein poses no safety concerns.

Global self-worth, specific self-perceptions of competence, and depression in adolescents.

OBJECTIVE: The purpose of this research was (1) to study adolescent depression severity in relation to global self-worth and specific self-perceptions of competence, and (2) to determine whether improvement in depression during hospitalization is accompanied by improvement in global self-worth and specific self-perceptions. METHOD: A within-subject longitudinal design with cross-sectional control subjects was used. Thirty depressed adolescent inpatients participated in assessments of depression severity (Hamilton Rating Scale for Depression) and self-perceptions of global self-worth and domain-specific competencies (Self-Perception Profile for Adolescents) at hospital admission and discharge (mean hospitalization: 59 days). A demographically similar group of 30 normal comparison subjects participated in the baseline assessment. RESULTS: Global self-worth was negatively associated with inpatients' depression severity and differentiated inpatients from normal comparison subjects. Self-perceptions of specific competencies were differentially related to depression severity, with perceived social acceptance being most clearly related to depression severity. Among the subgroup of inpatients showing clear and significant improvement in depression across hospitalization, increases in global self-worth and perceived social acceptance were also evident. CONCLUSIONS: Findings underscore the importance of considering global self-worth and self-perceptions of specific competencies in developmentally significant areas when assessing and treating adolescents.

Sleep deprivation in depressed adolescents and psychiatric controls.

Up to 70% of depressed adults have an antidepressant response to sleep deprivation. To study the effects of sleep deprivation on depression severity and level of arousal in psychiatrically disturbed adolescents, we deprived 17 patients of sleep for 36 hours. Severity of depression and subjective arousal were assessed at baseline, during sleep deprivation, and after 1 night's recovery sleep. We found that severely depressed adolescents showed a significant decrease in depression severity, whereas depressed patients in remission and psychiatric controls worsened after sleep deprivation. Patients with depression in remission showed a significant decrease in subjective arousal after sleep deprivation. In contrast to findings in depressed adults, the effects of sleep deprivation persisted after 1 night of recovery sleep, and diurnal variation of mood did not predict response to sleep deprivation. These findings are consistent with those reported in the adult literature, and suggest a common psychophysiology between adult and adolescent depression.

Capgras syndrome in adolescence.

Capgras syndrome, the delusion of substitution, has rarely been reported in adolescents. The etiology is unknown, and intense controversy surrounds the debate over the relative importance of biological versus psychological factors. Presented here are two cases of Capgras syndrome in adolescents and a review of the relevant biological, neuropsychological, and psychodynamic literature. The authors suggest that the psychological processes underlying the Capgras delusion are mediated by neuroanatomical connections between various brain areas and hypothesize that the fundamental lesion in Capgras syndrome may be the patient's inability or failure to acknowledge the authenticity of a person they clearly recognize.

Mania associated with fluoxetine treatment in adolescents.

Fluoxetine, a selective serotonin reuptake inhibitor, is gaining increased acceptance in the treatment of adolescent depression. Generally safe and well tolerated by adults, fluoxetine has been reported to induce mania. The cases of five depressed adolescents, 14-16 years of age, who developed mania during pharmacotherapy with fluoxetine, are reported here. Apparent risk factors for the development of mania or hypomania during fluoxetine pharmacotherapy in this population were the combination of attention-deficit hyperactivity disorder and affective instability; major depression with psychotic features; a family history of affective disorder, especially bipolar disorder; and a diagnosis of bipolar disorder. Further study is needed to determine the optimal dosage and to identify risk factors that increase individual vulnerability to fluoxetine induced mania in adolescents.

Suicidal adolescents' perceptions of their family environment.

This study examined the extent to which adolescents' perceptions of their family environments were associated with suicidal behavior. Fifteen suicidal adolescents, 14 psychiatric controls, and 14 normal controls rated their families on cohesiveness, adaptability, parent-adolescent communication, parental caring, and parental over-protectiveness. Suicidal adolescents rated their families as the least cohesive and most rigid of the 3 groups, suggesting that adolescent suicidal behavior may occur when isolation is experienced within an inflexible family system. Suicidal and psychiatric control adolescents rated their families as similarly dysfunctional along the remaining variables, and as more dysfunctional than families of normal control adolescents. The implications of these findings are discussed, and it is suggested that several characteristics commonly attributed to families of suicidal adolescents may actually be general risk factors for adolescent psychopathology, rather than for suicidal behavior specifically.