Well-preserved aragonitic land snail shells (Vallonia) from late Pleistocene Eolian sediment in the Folsom archaeological site in New Mexico exhibit an overall decrease of δ18OPDB from maximum values of +2.7‰ (more positive than modern) to younger samples with lower average values of about −3.6‰ (within the modern range). The age of the samples (approximately 10,500 14C yr B.P.) suggests that the decrease in δ18O may manifest climatic changes associated with the Younger Dryas. Some combination of increased relative humidity and cooler temperatures with decreased δ18O of precipitation during the times of snail activity can explain the decrease in shell δ18O. A well-known Paleoindian bison kill occurred at the Folsom site during this inferred environmental transition.

Average δ13C values of the aragonite shells of the fossil Vallonia range from −7.3 to −6.0‰ among different archaeological levels and are not as negative as modern values. This suggests that the proportion of C4 vegetation at the Folsom site approximately 10,500 14C yr B.P. was greater than at present; a result which is consistent with other evidence for higher proportions of C4 plants in the region at that time.

Clozapine is a prototype atypical antipsychotic drug and displays efficacy in 30% to 60% of schizophrenia patients who do not respond to traditional antipsychotics. There is considerable evidence supporting a concentration-response relationship for clozapine. A plasma clozapine concentration >200 to 420 ng/mL increases the probability of antipsychotic effects. Approximately 70% to 80% of variability in clozapine plasma concentration can be attributed to variability in cytochrome P450 1A2 activity. Measurement of caffeine metabolites in plasma or urine can be used as an in vivo index of cytochrome P450 1A2 activity, since caffeine is primarily eliminated by oxidative metabolism through this cytochrome P450 enzyme. Caffeine-based tests may contribute to individualization of clozapine dosages and optimization of its antipsychotic effects in schizophrenia patieents There are several lines of evidence suggesting the potential involvement of the dopamine D4 receptor in pharmacodynamic effects of clozapine. Clozapine has a 10-fold higher affinity for the dopamine D4 receptor in comparison to the D2 and the D3 receptors. Moreover, the free plasma fluid concentration of clozapine is comparable to its binding affinity for the D4 receptor in vitro. Blockade of the D4 receptor in the mesocorticolimbic region, a brain area implicated in the pathogenesis of schizophrenia, may contribute to efficacy of clozapine in negative symptoms. Moreover, the dopamine D4 receptor gene (DRD4) displays an unusual degree of genetic variation (polymorphism). In a recent preliminary study, investigated the (G)n mononucleotide repeat polymorphism within the first intron of the D4 gene in 50 schizophrenia patients refractory to traditional antipsychotics. These patients were prospectively followed for antipsychotic response during clozapine treatment. Analysis of variance found significant differences in antipsychotic response as demonstrated by mean change in Brief Psychiatric Rating Scale scores among the genotype panels for this polymorphism F[3,49]=4.1 (P=0.01). Future studies investigating the mechanistic basis of variability in response to clozapine should focus on both pharmacokinetic and pharmacodynamic factors.

Background. Previous studies have examined suicidal ideation in older populations and emphasized the strong association with the presence of psychiatric disorder. However, associations with the presence of psychiatric disorder across the age range are unclear. Representative epidemiological estimates are needed.

Method. In a national survey of psychiatric morbidity in Great Britain, 8580 randomly selected adults were interviewed. Three questions were asked to assess suicidal ideation, and psychiatric disorder was identified using the revised Clinical Interview Schedule (CIS-R).

Results. Suicidal ideation was up to three times commoner in younger adults than in those aged 55–74 years but the odds of depression in those with suicidal thoughts was significantly greater in the older age group (p<0·01). Tiredness with life (p<0·01) and thoughts of death (p<0·01) were also more strongly associated with depression in the older age group. Other major associations of suicidal ideation for all ages were: smaller social support group, being divorced or separated, poor self-rated general health, and limitations in activities of daily living (ADL). Being single was an important factor for younger age groups, and widowhood for older people. Life events were also important in younger people, but not in those aged 55–74 years.

Conclusions. Suicidal thoughts and death wishes are comparatively more unusual in older people; however, they are more likely to be associated with clinical depression. In terms of suicide prevention this study emphasizes the importance of improving rates of recognition and treatment of depression in older people.

Tardive dyskinesia (TD) is a side-effect of chronic antipsychotic medication. Abnormalities in dopaminergic activity in the nigrostriatal system have been most often suggested to be involved because the agents which cause TD share in common potent antagonism of dopamine D2 receptors (DRD2), that notably is not balanced by effects such as more potent serotonin (5-HT)2A antagonism. Thus, a number of studies have focused on the association of dopamine system gene polymorphisms and TD. The most consistent findings have been found with the Ser9Gly polymorphism of the DRD3 gene. Although DRD2 has long been hypothesized to be the main target for antipsychotics, only a few polymorphisms in DRD2 have been investigated for their potential involvement in the aetiology of TD. In the present study, we investigated 12 polymorphisms spanning the DRD2 gene and their association with TD in our European Caucasian (n=202) and African–American (n=30) samples. Genotype frequencies for a functional polymorphism, C957T (Duan et al., 2003; Hirvonen et al., 2004), and the adjacent C939T polymorphism were found to be significantly associated with TD (p=0.013 and p=0.022 respectively). DRD2 genotypes were not significantly associated with TD severity as measured by AIMS (Abnormal Involuntary Movement Scale) with the exception of a trend for C939T (p=0.071). Both TD and total AIMS scores were found to be significantly associated with two-marker haplotypes containing C939T and C957T (p=0.021 and p=0.0087 respectively). Preliminary results indicated that C957T was also associated with TD in our African–American sample (p=0.047). Taken together, the present study suggests that DRD2 may be involved in TD in the Caucasian population, although further studies are warranted.

Background. Previous studies suggest that worry content and prevalence may vary as a function of age, but evidence is limited.

Method. Cross-sectional national survey of 8580 householders in Great Britain aged between 16 and 74 years. This analysis examined the relationship between age, worry content (relationships/family, financial/housing, work, health, miscellaneous), common mental disorders, and functional limitation, adjusting for other sociodemographic factors.

Results. Overall, the prevalence of worries declined with age. However, with the exception of worry about relationships, the strength of associations between worry types and mental disorder either remained constant or increased in the older age groups. Compared to the 16–24 years reference group, worries about relationships/family, finances/housing and work were lower in the 55–74 years age groups. Financial/housing worries were increased in the 25–44 years group, and health worries were increased in the 25–64 years groups. There were independent associations between all worry items and the categories of mental disorder. All worry types apart from miscellaneous worries were independently associated, positively or negatively, with functional limitation.

Conclusions. Worry content in the general population varies as a function of age, gender, marital status, and educational attainment. All categories of worry are more prevalent in individuals with common mental disorders. The lower prevalence of worries and their stronger association with mental disorder in old age emphasize the clinical significance of these symptoms in this age group.

The last decades of fieldwork have not decisively upset the long-held view that the settlement of the Americas occurred in the very latest Pleistocene, as marked in North America by the Clovis archaeological horizon at about 11,200 years ago, and by a variety of contemporaneous South American industries. Yet there are several sites that may prove to be older, among them Pedra Furada, in the thorn forest of northeastern Brazil, a large and remarkable rock-shelter, whose Pleistocene deposits have been interpreted as containing clear evidence of human occupation.

This paper offers a considered view of Pedra Furada from three archaeologists with a wide range of experiences in sites of all ages in the Americas and elsewhere, but who also share a special interest and expertise in the issues Pedra Furada has raised: Meltzer from long study of the peopling of the Americas and the frame of thinking within which we address that issue (Meltzer 1993a; 1993b); Adovasio from his intensive excavations and analysis of the Meadowcroft Rockshelter in Pennsylvania, the prime North American pre-Clovis candidate (Adovasio et al. 1990; Donahue & Adovasio 1990); and Dillehay from his work at the Monte Verde site in Chile, a site in which extraordinary preservation has produced a rich archaeological record with radiocarbon ages in excess of 12,500 years b.p. (Dillehay 1989a; in press). At the invitation of the Pedra Furada team, the three travelled to Brazil last December to participate in an international conference on the peopling of the Americas, and see first-hand the evidence from Pedra Furada.

The Holly Oak pendant is a shaped piece of marine whelk (Busycon sinistrum) shell with two holes drilled in one end that bears an incised depiction of an extinct proboscidean (woolly mammoth or mastodon). It allegedly was recovered in 1864 from an archaeological site in Delaware. There was speculation in the 1970s as to its age and significance, and it was illustrated and cited as a Paleoindian artifact of Pleistocene age. Subsequent analyses indicated the artifact was fraudulent: The engraving probably was done in the 1880s on a shell recovered from an archaeological site. This has been confirmed by a recently obtained AMS radiocarbon date. The Holly Oak pendant is a modern forgery.