Psychopharmacology of the psychiatric disorders of childhood and adolescence

The literature on the psychopharmacology of child and adolescent psychiatric disorders is reviewed. The scanty epidemiological data suggest that psychotherapeutic drugs are utilized more widely than research findings would warrant, especially in preschool-age children. With the exception of hyperactivity, the disorders of childhood and adolescence for which the use of psychopharmacological agents is well-established are rare. This highlights the need for careful prescribing, in which the child's rights, problems with compliance and developmental and behavioural adverse effects are important considerations.     

The response to DNA damage induced by 4-nitroquinoline-1-oxide or its 3-methyl derivative in xeroderma pigmentosum fibroblasts belonging to different complementation groups: evidence for different epistasis groups involved in the repair of large adducts in human DNA

The data in this paper show that when the inhibition of growthis measured, xeroderma pigmentosum (XP) complementation groupsA, G and D are very sensitive to 4-nitroquinoline-1-oxide (4NQO),whereas only XP groups G and D are very sensitive to 3-methyl-4NQO(3me4NQO). Cells belonging to XP-C group are not particularlysensitive to either agent. Thus there are different epistasisgroups for the excision repair of DNA adducts induced by theseagents as opposed to the repair of u.v. damage. DNA polymerase is involved in the repair of 4NQO-induced lesions because aphidicolinblocks their repair. XP cells from all the above groups aredefective to some extent in this repair. The degree of repairdefectiveness follows that seen after u.v., with even the XP-Ccell line used having reduced repair (despite the fact thatthe inhibition of growth by 4NQO in this cell line was not markedlydifferent from normal). Aphidicolin did not induce breaks inthe normal or XP cell lines exposed to 3me4NQO, thus the repairof lesions induced by 3me4NQO does not involve DNA polymerase in any of the cell lines. Finally, catalase reduces the alkalinelabile lesions induced by 4NQO, but not 3me4NQO, suggestingthe latter agent does not induce substantial amounts of DNAdamage by the generation of radicals.     

Effect of the catecholamine-depleting agent 1-phenyl-3-(2-thiazolyl)-2-thiourea (U-14,624) on drug metabolism in the rat

Male rats injected with 1-phenyl-3-(2-thiazolyl)-2-thiourea (U-14,624) (25 mg/kg/day i.p.) for 3 days prior to induction of anesthesia with pentobarbital (40 mg/kg, i.p.) slept significantly (P < 0.05) longer than control animals. Plasma and brain half-lives of pentobarbital were also prolonged in the treated animals, but both control and treated groups awakened with similar brain levels of pentobarbital. In addition, the plasma half-life of antipyrine in treated animals was also prolonged significantly. Subacute administration of U-14,624 (50 mg/kg/day i.p.) to male rats for 5–7 days suppressed the activities of aminopyrine N-demethylase, aniline hydroxylase and p-nitroanisole O-demethylase enzymes in vitro; this effect could not be demonstrated at lower doses. Single doses of U-14,624 (100–200 mg/kg, i.p.) also suppressed the activities of the three oxidative enzymes. The suppression was positively correlated with reduced levels of hepatic microsomal cytochrome P-450. Levels of cytochrome b₅ and NADPH-cytochrome c reductase activity were not affected consistently by acute dosage with U-14,624. The inhibitory effects of single doses (100–400 mg/kg, i.p.) on all enzymatic systems were reversible, and recovery was complete within 48 hr. Whereas all three oxidative drug-metabolizing enzymes were inhibited in a mixed manner by in vitro exposure to U-14,624 (10^?5–10^?2 M), neotetrazolium diaphorase was not inhibited by U-14,624 at concentrations as high as 5 mM. Inhibition of oxidative drug metabolism by U-14,624 is mechanistically related to depletion of cytochrome P-450, but inhibition of these enzymes in vitro indicates that a second inhibitory mechanism may also be operative.     

Psychiatric Illness and Parasomnias: a Systematic Review

Purpose of Review

Little is known about the presence of parasomnias such as nightmare disorder, sleep paralysis, REM sleep behavior disorder (RBD), and sleep-related eating disorders (SRED) in people with mental illness. A predominant view suggests that psychotropic medications might be contributing to parasomnias. This article summarizes knowledge regarding the relationships between psychiatric disorders and parasomnias, and possible confounds. A systematic search of the literature in the past 10 years identified 19 articles.

Recent Findings

There were significantly elevated rates of parasomnias in psychiatric disorders (average prevalence of nightmares was 38.9%, sleep paralysis 22.3%, SRED 9.9%, sleepwalking 8.5%, and RBD 3.8%). Medication usage was only one of many risk factors (other sleep disorders, medical comorbidities, and substance abuse) which were associated with parasomnias.

Summary

A strong association exists between mental illness and parasomnias which is not fully explained by medications. Prospective longitudinal studies are needed to develop a better understanding of the unique and shared variance from multiple risk factors.

     

Gene Expression of CYP1A1 and its Possible Clinical Application in Thyroid Cancer Cases

Background: Thyroid cancer is the most common endocrine malignancy, and exact causes remain unknown. The role of CYP450 1A1 (CYP1A1) in cancer initiation and progression has been investigated. The aim of this work was to analyze, for the first time, CYP1A1 gene expression and its relationship with several clinicopathological factors in Mexican patients diagnosed with thyroid cancer. Materials and Methods: Realtime PCR analysis was conducted on 32 sets of thyroid tumors and benign pathologies. Expression levels were tested for correlations with clinical and pathological data. All statistical analysis were performed using GraphPad Prism version 3.0 software. Results: We found that female gender was associated with thyroid cancer risk (P<0.05). A positive relationship was identified between CYP1A1 mRNA levels and the presence of chronic disease, alcohol use, tumor size, metastasis and an advanced clinical stage (P<0.05). Conclusions: The results suggest that CYP1A1 gene expression could be used as a marker for thyroid cancer.     

Risk estimates from an online risk calculator are more believable and recalled better when expressed as integers

Background

Online risk calculators offer different levels of precision in their risk estimates. People interpret numbers in varying ways depending on how they are presented, and we do not know how the number of decimal places displayed might influence perceptions of risk estimates.

Objective

The objective of our study was to determine whether precision (ie, number of decimals) in risk estimates offered by an online risk calculator influences users’ ratings of (1) how believable the estimate is, (2) risk magnitude (ie, how large or small the risk feels to them), and (3) how well they can recall the risk estimate after a brief delay.

Methods

We developed two mock risk calculator websites that offered hypothetical percentage estimates of participants’ lifetime risk of kidney cancer. Participants were randomly assigned to a condition where the risk estimate value rose with increasing precision (2, 2.1, 2.13, 2.133) or the risk estimate value fell with increasing precision (2, 1.9, 1.87, 1.867). Within each group, participants were randomly assigned one of the four numbers as their first risk estimate, and later received one of the remaining three as a comparison.

Results

Participants who completed the experiment (N = 3422) were a demographically diverse online sample, approximately representative of the US adult population on age, gender, and race. Participants whose risk estimates had no decimal places gave the highest ratings of believability (F _3,3384 = 2.94, P = .03) and the lowest ratings of risk magnitude (F _3,3384 = 4.70, P = .003). Compared to estimates with decimal places, integer estimates were judged as highly believable by 7%–10% more participants (χ² ₃ =17.8, P < .001). When comparing two risk estimates with different levels of precision, large majorities of participants reported that the numbers seemed equivalent across all measures. Both exact and approximate recall were highest for estimates with zero decimals. Odds ratios (OR) for correct approximate recall (defined as being within 50% of the original estimate) were, for one decimal place, OR = 0.65 (95% CI 0.49–0.86), for two decimal places, OR = 0.70 (95% CI 0.53–0.94), and for three decimal places, 0.61 (95% CI 0.45–0.81). Exact recall showed a similar pattern, with larger effects.

Conclusions

There are subtle but measurable differences in how people interpret risk estimates of varying precision. Adding decimal places in risk calculators offers little to no benefit and some cost. Rounding to the nearest integer is likely preferable for communicating risk estimates via risk calculators so that they might be remembered correctly and judged as believable.