Neuroticism mediates the association of the serotonin transporter gene with lifetime major depression.

BACKGROUND AND OBJECTIVES: An association between a polymorphism in the serotonin transporter gene (5HTT-LPR) and the personality trait of neuroticism has been reported. We sought to address the question of whether trait neuroticism mediates the putative association between this polymorphism and lifetime major depression in adults drawn from the general population. METHODS: Two hundred and fifty-one participants completed the Eysenck Personality Questionnaire and an adapted version of the depression section of the Structured Clinical Interview for DSM-III-R diagnosis, modified for implementation by a self-report questionnaire. A path method was applied to assess the mediator effect of neuroticism on the association between 5HTT-LPR genotype and lifetime major depression. RESULTS: 5HTT-LPR genotype was significantly associated with both neuroticism (p=0.02) and lifetime major depression (p=0.04), and neuroticism with lifetime major depression (p<0.001). Neuroticism accounted for 42.3% of the effect of 5HTT-LPR genotype on lifetime major depression, indicating possible mediation (p<0.001). CONCLUSIONS: These results suggest that neuroticism mediates the association between 5HTT-LPR genotype and lifetime major depression, consistent with models of the aetiology of depression which suggest that anxiety-related personality traits represent a substantial risk factor for affective disorder.

Longitudinal analysis of the effect of prenatal nicotine exposure on subsequent smoking behavior of offspring.

We explored the influence of maternal smoking during pregnancy on the likelihood of smoking among offspring in adolescence and adulthood using data from two similar British birth cohort surveys, the 1958 National Child Development Study and the 1970 British Birth Survey. Similar information was available in each cohort on maternal age at delivery, offspring sex, maternal smoking during pregnancy, parental and offspring socioeconomic status, and parental smoking at the time offspring smoking was assessed at age 16 years. Offspring smoking at 16 years and at 30/33 years were the primary outcomes of interest. Our data support an association between maternal smoking during pregnancy and an increased risk of offspring smoking later in life among female offspring but not among male offspring. Female offspring of mothers who smoked during pregnancy were more likely to smoke at 16 years than were their male counterparts. Moreover, in this same subgroup, female offspring smoking at 16 years was associated with an increased likelihood of smoking at 30/33 years. Further investigation in larger studies with greater detail of factors shaping smoking in childhood and adulthood and biochemically verified outcome measures would be desirable to clarify the relationship.

Are the cognitive effects of atypical antipsychotics influenced by their affinity to 5HT-2A receptors?

It is well documented that atypical antipsychotics have an influence on cognitive function in patients with schizophrenia, although the neurochemical basis for this effect is not well understood. One suggestion is that the effects are exerted through action on 5HT-2A receptors, which leads to changes in the level of dopamine in the prefrontal cortex. The following study explored this hypothesis by comparing the cognitive effects of the atypical antipsychotics which have a high affinity for 5HT-2A receptors, with those that have little or no affinity to these receptors. Forty-four patients with a DSM-IV diagnosis of schizophrenia were recruited within 6 weeks of starting one of the atypical antipsychotics: clozapine, olanzapine, risperidone, quetiapine, or amisulpride. The patients were divided into two groups according to the 5HT-2A affinity of the individual medications (high 5HT-2A affinity--clozapine, olanzapine, risperidone vs. low 5HT-2A affinity--quetiapine, amisulpride). Patients were tested on a broad range of neuropsychological measures after 9 months and 18 months of treatment. The high 5HT-2A affinity group showed a decrement in performance on tests of visual recognition memory and planning ability. In contrast, the low-5HT-2A affinity group showed improvements on these measures in addition to others. The 5HT-2A affinity of the atypical antipsychotics is an important determinant of their cognitive effects.

Assessment of insight in psychosis: a re-standardization of a new scale.

Over the last decade, a number of tools have been developed to evaluate, in a systematic way, patients' insight into their psychotic illness. Such tools, however, capture different clinical phenomena of insight. So far, there is no indication as to which phenomenon of insight might be the most useful or predictive (e.g. clinically or therapeutically) to assess. This article reports the re-standardization of a revised self-administered insight scale in patients with psychosis, first published in 1992. It is meant to capture views held by individuals suffering from psychosis about changes occurring within themselves and in their environment. The scale was administered to 64 patients with a diagnosis of schizophrenia but with a range of symptoms and in different stages of their illnesses. This new version is simpler to use and score than the original instrument and shows good reliability, internal consistency and concurrent validity. This study forms the preliminary basis for future work examining the phenomenon of insight, its relationship to clinical variables and its predictive validity in terms of patients' behaviours and prognoses.