The effects of the CACNA1C rs1006737 A/G on affective startle modulation in healthy males.

BACKGROUND: The CACNA1C rs1006737 risk A allele has been associated with affective psychoses and functional studies indicate that it is associated with increased hippocampal/amygdala activity during emotional face-processing. Here we studied the impact of the risk A allele on affective startle modulation. METHODS: Hundred and ninety-four healthy males stratified for their CACNA1C rs1006737 genotype (GG:111, GA:67, AA:16) were presented with 18 pleasant, 18 unpleasant and 18 neutral pictures with acoustic probes (104 dB) occurring during 12 pictures in each affective category. Baseline startle was assessed during blank screens. State mood was self-rated on arrival, pre- and post-test and the emotional valence and arousal of affective pictures at post-test. RESULTS: Relative to the other genotypes, risk A allele homozygotes presented with higher anxiety/negative affect at pre-test, reduced and exaggerated physiological responses to the pleasant and negative pictures respectively, negative affect with reduced arousal at post-test and rated the affective pictures as less arousing and inconsistently to their physiological responses (all P<0.05). Sustained contextual negative mood predicted reduced baseline and affective startle reactivity in the AA group. CONCLUSIONS: Healthy homozygous males for the risk A allele appear to have marked contextual sensitivity, affective reactivity akin to anxiety and depression and inefficient emotional appraisal. Our findings provide phenotypic detail of the CACNA1C AA genotype in non-symptomatic individuals, which suggest primary effects in emotional circuitry, consistent with previously documented alterations in hippocampal/amygdala processing.

Sub-optimal parenting is associated with schizotypic and anxiety personality traits in adulthood.

Part of the variation in personality characteristics has been attributed to the child-parent interaction and sub-optimal parenting has been associated with psychiatric morbidity. In the present study, an extensive battery of personality scales (Trait Anxiety Inventory, Behavioural Inhibition/Activation System questionnaire, Eysenck Personality Questionnaire-Revised, Temperament and Character Inventory, Schizotypal Traits Questionnaire, Toronto Alexithymia Scale) and the Parental Bonding Instrument (PBI) were administered in 324 adult healthy males to elucidate the effects of parenting on personality configuration. Personality variables were analysed using Principal Component Analysis (PCA) and the factors "Schizotypy", "Anxiety", "Behavioural activation", "Novelty seeking" and "Reward dependence" were extracted. Associations between personality factors with PBI "care" and "overprotection" scores were examined with regression analyses. Subjects were divided into "parental style" groups and personality factors were subjected to categorical analyses. "Schizotypy" and "Anxiety" were significantly predicted by high maternal overprotection and low paternal care. In addition, the Affectionless control group (low care/high overprotection) had higher "Schizotypy" and "Anxiety" compared with the Optimal Parenting group (high care/low overprotection). These results further validate sub-optimal parenting as an important environmental exposure and extend our understanding on the mechanisms by which it increases risk for psychiatric morbidity.

The adverse skeletal effects of selective serotonin reuptake inhibitors.

Selective serotonin reuptake inhibitors (SSRIs) are a widely used group of antidepressants (ADs) with reported potential detrimental effects on bone mineral density (BMD) and increased fracture risk. Here, a comprehensive review of the in vitro, in vivo and clinical studies to date was carried out using the medical search engines MEDLINE (1950 to September 2010) and EMBASE (1980 to September 2010). Serotonin (5-HT) receptors have been identified on osteoclast, osteoblast and osteocyte cell lines. The effect of SSRIs on bone formation and resorption appears to be governed by the activation of a number of 5-HT receptors on osteoblasts and osteoclasts via endocrine, autocrine/paracrine and neuronal pathways. In vitro, in vivo and clinical collective data appears to indicate that SSRIs have a negative effect on bone at the therapeutic dose levels widely used for the treatment of depression in current clinical practice. Caution may therefore have to be employed with the use of SSRIs in patients at an increased risk of falls and osteoporosis. Further studies are needed in order to fully elicit the role of SSRIs in bone formation and their effects in the low oestrogen state.

Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population.

Despite the common use of MDMA (ecstasy) in the UK, the mechanism underlying associated potentially fatal cerebral oedema is unclear. We used a new experimental approach working directly with clubbers to perform a study on 30 (17 male) experienced clubbers (mean 6.6 years of clubbing). Pre- and post-clubbing measurements were performed to compare plasma levels of pituitary hormones (vasopressin, oxytocin), plasma and urine osmolality, urinary pH, and plasma sodium and urea. Ecstasy consumption was confirmed by using urinary drug screening pre- and post-clubbing. MDMA was detected in the urine samples of 17 subjects, three of which tested positive during pre-clubbing tests. Mean plasma vasopressin concentration increased in the MDMA group (1.28 +/- 0.29 to 1.43 +/- 0.41 pmol/l), but fell in other participants (1.23 +/- 0.42 to 1.16 +/- 0.0.34 pmol/l). Similarly, mean plasma oxytocin concentrations increased after ingestion of MDMA (2.02 +/- 0.29 to 2.43 +/- 0.24 pmol/l), but fell in the group that did not use MDMA (2.17 +/- 0.36 pmol/l to 1.89 +/- 0.37 pmol/l). There was a significant group by time interaction for plasma osmolality and plasma sodium (p = 0.001 and p = 0.003, respectively) and between change in urinary osmolality (p < 0.001) and MDMA use, with the pattern of change being consistent with the induction of inappropriate vasopressin secretion (also known as SIADH) by MDMA. This report demonstrates SIADH in ecstasy-using "clubbers", which has important clinical implications.