The serotonin transporter promoter polymorphism and childhood positive and negative emotionality.

Association studies of the serotonin transporter promoter polymorphism (5-HTTLPR) and negative emotionality (NE) are inconclusive. However, emerging evidence suggests that the association between this polymorphism and NE may be influenced by levels of another temperament trait, positive emotionality (PE). Therefore, this study examined whether the association between the 5-HTTLPR and NE was moderated by PE. A community sample of 413 three-year-old children completed a standardized battery of laboratory tasks designed to tap temperamental emotionality. Children were also genotyped for the 5-HTTLPR. No direct association between 5-HTTLPR genotype and NE was found. However, the interaction of child PE and NE predicted 5-HTTLPR genotype. Furthermore, children with a short allele who were also low in PE had significantly greater NE than children without a short allele or children with high PE. Our findings suggest that the short allele of the 5-HTTLPR is associated with NE only in the context of low PE. Inconsistent links between NE and this gene in previous research may stem from the failure to consider other temperament traits that moderate associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association of the serotonin transporter gene promoter region (5-HTTLPR) polymorphism with biased attention for emotional stimuli.

A deletion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with vulnerability to affective disorders, yet the mechanism by which this gene confers vulnerability remains unclear. Two studies examined associations between the 5-HTTLPR polymorphism and attentional bias for emotional stimuli among nondepressed adults. Biased attention, attention engagement, and difficulty with attention disengagement were assessed with a spatial cuing task using emotional stimuli. Results from Study 1 (N = 38) indicated that short 5-HTTLPR allele carriers experienced greater difficulty disengaging their attention from sad and happy stimuli compared with long allele homozygotes. Study 2 participants (N = 144) were genotyped for the 5-HTTLPR polymorphism, including single nucleotide polymorphism rs25531 in the long allele of the 5-HTTLPR. Consistent with Study 1, individuals homozygous for the low-expressing 5-HTTLPR alleles (i.e., S and LG) experienced greater difficulty disengaging attention from sad, happy, and fear stimuli than high-expressing 5-HTTLPR homozygotes. Because this association exists in healthy adults, it may represent a susceptibility factor for affective disorders that becomes problematic during stressful life experiences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amygdala-dependent fear conditioning in humans is modulated by the BDNFval66met polymorphism.

The brain-derived neurotrophic factor (BDNF) is critically involved in neuroplasticity, as well as the acquisition, consolidation, and retention of hippocampal- and amygdala-dependent learning. A common functional A→G single nucleotide polymorphism (BDNFval66met) in the prodomain of the human BDNF gene is associated with abnormal intracellular trafficking and reduced activity-dependent BDNF release. We studied the effect of BDNFval66met in an aversive differential fear conditioning, and a delayed extinction paradigm in 57 healthy participants. Pictures of male faces were used as stimuli and fear learning was quantified by fear potentiated startle (FPS) and skin conductance responses (SCR). Aware BDNF met-carriers show a deficit in amygdala-dependent fear conditioning as indicated by an absence of FPS responses in the last acquisition block. This deficit was maintained in the first block of extinction. No genotype differences were found in conditioned SCR discrimination. These data provide evidence for the involvement of BDNF signaling in human amygdala-dependent learning. We suggest that the BDNF met-allele may have a protective effect for the development of affective pathologies that may be mediated via reduced synaptic plasticity induced by negative experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The nicotinic acetylcholine receptor gene CHRNA4 is associated with negative emotionality.

Knock-out studies in mice suggest a role of the CHRNA4 gene in anxiety. In the present study we extend this finding to humans by means of a genetic association study. In a sample of N = 574 healthy White participants, the CHRNA4 rs1044396 polymorphism is related to the common variance of several conceptualizations of negative emotionality. Compared to carriers of at least one T-allele, carriers of the homozygous C/C genotype described themselves as more anxious and emotionally unstable on various psychometric personality questionnaires. The scope of the genetic effect is remarkable because other prominent genetic markers for anxiety show specificity for the diagnostic tool used. The present study is the first study that demonstrates the relevance of the CHRNA4 gene for negative emotionality in humans and sets a starting point for further investigations that could inform on the treatment of various affective psychiatric disorders. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

An association between the DAT1 polymorphism and smoking behavior in young adults from the national longitudinal study of adolescent health.

Associations between smoking behavior and polymorphisms in the dopaminergic genes (DAT1 and DRD2) were tested by using within- and between-family measures of allelic transmission in 2,448 young adults from the National Longitudinal Study of Adolescent Health. The 9-repeat allele of the dopamine transporter gene polymorphism (DAT1) was inversely associated with smoking in samples that included all subjects and only those who had initiated smoking, accounting for approximately 1% of the variance. Never smokers and current nonsmokers had an excess transmission of the 9-repeat allele compared with regular smokers, suggesting a protective effect of the 9-repeat allele, which is hypothesized to alter synaptic dopamine levels. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term potentiation and spatial learning are associated with increased phosphorylation of TrkB and extracellular signal-regulated kinase (ERK) in the dentate gyrus: Evidence for a role for brain-derived neurotrophic factor.

In this study, the authors investigate changes in the presynaptic terminal of the dentate gyrus that accompany 2 types of hippocampal-dependent plasticity: spatial leanting and long-term potentiation (LTP). Parallel changes occurred in the dentate gyrus of rats that had undergone training in the Morris water maze and had sustained LTP. In both cases, KCl-induced brain-derived neurotrophic factor release was increased, and this was accompanied by increased phosphorylation of TrkB and the mitogen-activated protein kinase, ERK. Glutamate release was also enhanced, and the data suggest thak this may be a consequence of increased activation of TrkB and ERK. Because the data indicate that similar cellular modifications are shared by these 2 forms of plasticity, they provide circumstantial evidence that LTP satisfies some of the requirements of a memory-inducing cellular substrate. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exercise is associated with reduction in the anxiogenic effect of mCPP on acoustic startle.

Voluntary exercise has been associated with reduced anxiety across several animal models. Manipulation of central 5-HT can alter anxiety-like behaviors and administration of the 5-HT agonist metachlorophenylpiperazine (mCPP) increases anxiety in rodents and humans. To examine whether the anxiolytic effect of exercise is associated with an alteration in 5-HT systems, we examined the anxiogenic effect of mCPP in exercising and nonexercising mice. C57BL/6J mice were given 2 weeks of free access to either a functioning or nonfunctioning running wheel. Mice were then tested for acoustic startle following systemic injection of either 0, 0.1, 0.3, or 1 mg/kg of mCPP. Consistent with its anxiogenic properties, mCPP produced a dose-dependent increase in acoustic startle in nonexercising mice. However, this anxiogenic effect was blunted in exercising mice. These findings suggest that exercise may help to reduce anxiety by altering 5-HT systems, perhaps by down-regulating postsynaptic 5HT 2B/2C receptors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The TNF-α-238G > A single-nucleotide polymorphism protects against memory decline in older adults with Type 2 diabetes.

Inflammatory markers predict memory dysfunction in elderly patients, but their contribution to memory deficits in adults with Type 2 diabetes mellitus (T2DM) is less well understood. The present study determined whether specific single-nucleotide polymorphisms in the promoter region of tumor necrosis factor-alpha (TNF-α) predict verbal memory in older patients with T2DM. Immediate and delayed verbal memory were assessed using word list and paragraph recall tests in a cohort of subjects with T2DM during 2 sessions, separated by 48 weeks. The presence of the TNF-α-238A allele, which has been shown to decrease gene expression, consistently predicted better baseline performance and protected against memory decline over a period of 48 weeks. Therefore, inflammatory mediators may be important modulators of memory function in individuals with T2DM. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of 5-HT1A receptors in the behavioral responses associated with innate fear.

Fear is a response induced by threatening stimuli and represents an important adaptive system. The serotonin (5-HT) system has been shown to be involved in the modulation of fear responses and anxiety disorders. In preclinical studies, it has been demonstrated that R (+)-8-hydroxy-dipropylaminotetralin (8-OHDPAT), a 5-HT1A agonist, has anxiolytic properties. However, 8-OHDPATs potential role in unconditioned fear has yet to be elucidated. The current study was designed to investigate the effects of 8-OHDPAT on behavioral and HPA axis function in response to an innate fear-inducing stimulus. Pretreatment with 8-OHDPAT resulted in a significant decrease in freezing grooming, and climbing and caused a significant increase in approach after exposure to an extract from fox feces, 2,5-dihyrdo-2,4,5-trimethylthiazoline (TMT), an unconditioned fear-inducing stimulus. Furthermore, 8-OHDPAT pretreatment also resulted in a significant decrease in blood corticosterone levels, a marker of HPA activation. Taken together, these results suggest an additional anxyolitic-like effect of 8-OHDPAT in innate fear paradigms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The negativity bias is eliminated in older adults: Age-related reduction in event-related brain potentials associated with evaluative categorization.

Studies of younger adults have found that negative information has a stronger influence than positive information across a wide range of domains. T. A. Ito, J. T. Larsen, N. K. Smith, and J. T. Cacioppo (1998) reported that during evaluative categorization, extreme negative images produced greater brain activity than did equally extreme positive images in younger adults. Older adults have been reported to optimize affect and attend less to negative information. In this article, the negativity bias was examined in 20 older versus 20 younger adults during evaluative categorization, with a focus on brain activity occurring roughly 500 ms after presentation of visual stimuli. Results demonstrated a significant decrease in brain activity to both positive and negative stimuli (p