Individual stress vulnerability is predicted by short-term memory and AMPA receptor subunit ratio in the hippocampus.

Increased vulnerability to aversive experiences is one of the main risk factors for stress-related psychiatric disorders as major depression. However, the molecular bases of vulnerability, on the one hand, and stress resilience, on the other hand, are still not understood. Increasing clinical and preclinical evidence suggests a central involvement of the glutamatergic system in the pathogenesis of major depression. Using a mouse paradigm, modeling increased stress vulnerability and depression-like symptoms in a genetically diverse outbred strain, and we tested the hypothesis that differences in AMPA receptor function may be linked to individual variations in stress vulnerability. Vulnerable and resilient animals differed significantly in their dorsal hippocampal AMPA receptor expression and AMPA receptor binding. Treatment with an AMPA receptor potentiator during the stress exposure prevented the lasting effects of chronic social stress exposure on physiological, neuroendocrine, and behavioral parameters. In addition, spatial short-term memory, an AMPA receptor-dependent behavior, was found to be predictive of individual stress vulnerability and response to AMPA potentiator treatment. Finally, we provide evidence that genetic variations in the AMPA receptor subunit GluR1 are linked to the vulnerable phenotype. Therefore, we propose genetic variations in the AMPA receptor system to shape individual stress vulnerability. Those individual differences can be predicted by the assessment of short-term memory, thereby opening up the possibility for a specific treatment by enhancing AMPA receptor function

A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression

10.1001/archgenpsychiatry.2009.95Archives of General Psychiatry669966-975ARGP

Polymorphisms in the angiotensin-converting enzyme gene are associated wit unipolar depression, ACE activity and hypercortisolism.

Angiotensin-converting enzyme (ACE) is assumed to influence the activity of the hypothalamic-pituitary-adrenocortical (HPA) system, which shows hyperactivity in the majority of patients with major depression. The ACE gene, known to be associated with cardiovascular disorders, which in turn are accompanied with an increased susceptibility for depression, is therefore a promising candidate gene for affective disorders. We investigated the genetic association between 35 single-nucleotide polymorphisms (SNPs) and an insertion/deletion (I/D)-polymorphism in the ACE gene and the susceptibility for unipolar major depression together with the genetic association with ACE serum activity and functional parameters of the HPA system. Two independent case/control samples with a total of 843 unrelated unipolar depressed patients and 1479 healthy controls were investigated. A case/control sample was screened to detect genetic associations with unipolar major depression. In addition, a replication sample was used to confirm the detected associations and to further investigate functional consequences of the genetic variants associated with depression. In the screening sample, two SNPs within the ACE gene were significantly associated with unipolar major depression. The association with unipolar major depression of one SNP (rs4291) located in the promoter region of the ACE gene was confirmed in our replication sample. The T-allele of this SNP was associated with depression and depressed T-allele carriers showed higher ACE serum activity and HPA-axis hyperactivity. Variants of the ACE gene such as SNP rs4291 are suggested susceptibility factors for unipolar major depression. We could show that SNP rs4291 influences ACE activity and HPA-axis hyperactivity and might therefore represent a common pathophysiologic link for unipolar depression and cardiovascular disease

TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies.

The lifetime prevalence of panic disorder (PD) is up to 4% worldwide and there is substantial evidence that genetic factors contribute to the development of PD. Single-nucleotide polymorphisms (SNPs) in TMEM132D, identified in a whole-genome association study (GWAS), were found to be associated with PD in three independent samples, with a two-SNP haplotype associated in each of three samples in the same direction, and with a P-value of 1.2e-7 in the combined sample (909 cases and 915 controls). Independent SNPs in this gene were also associated with the severity of anxiety symptoms in patients affected by PD or panic attacks as well as in patients suffering from unipolar depression. Risk genotypes for PD were associated with higher TMEM132D mRNA expression levels in the frontal cortex. In parallel, using a mouse model of extremes in trait anxiety, we could further show that anxiety-related behavior was positively correlated with Tmem132d mRNA expression in the anterior cingulate cortex, central to the processing of anxiety/fear-related stimuli, and that in this animal model a Tmem132d SNP is associated with anxiety-related behavior in an F2 panel. TMEM132D may thus be an important new candidate gene for PD as well as more generally for anxiety-related behavior

Incorporating different proportions of exotic maize germplasm into two adapted populations

Maize breeders frequently wish to use exotic germplasm in their breeding programs without losing specific characteristics of their adapted material. The objective of this study was to determine the optimal proportions of exotic germplasm to incorporate into adapted populations (F2 = 50% exotic, BC1 = 25% exotic, BC2 = 12.5% exotic and BC3 = 6.25% exotic) to form the initial foundation population and to determine the heterosis between adapted x exotics. We used six exotic populations of different origins and two adapted populations representing a Brazilian heterotic pattern. In 1993-94 and 1994-95, the parents, F1, F2, BC1, BC2, BC3 and four checks were evaluated in six environments in central Brazil using an 8 x 9 simple rectangular lattice design. Higher mean values for yield were obtained as the proportion of exotic germplasm decreased. Some backcrosses produced more than the adapted populations BR 105 (7.59 ton/ha) and BR 106 (8.43 ton/ha). The best results were obtained when incorporating 6.25 or 12.5% of exotic genes. This trend was true for root lodging, stalk lodging and ear diseases but not for plant and ear height. The midparent heterosis for yield varied from -16.1 to 40.3%. Midparent heterosis with positive and negative values were also found for the other traits. The results indicate the potential of exotic germplasm for developing good hybrids. After choosing the best exotic source, some recurrent selection might be appropriate in order to adapt and improve the exotic populations.<br>Os melhoristas de milho que utilizam germoplasmas exóticos nos programas de melhoramento têm a preocupação de não perder as características desejáveis dos materiais adaptados. Buscando atender esta demanda, o presente trabalho teve por objetivo determinar a proporção ideal de germoplasma exótico que deve ser incorporado em populações melhoradas (F2 = 50% exótico; RC1 = 25% exótico; RC2 = 12,5% exótico; RC3 = 6,25% exótico), para formar as populações base para seleção e determinar a heterose entre os germoplasmas exóticos e adaptados. Em 1993/94 e 1994/95, os parentais, F1, F2, RC1, RC2, RC3 e quatro testemunhas foram avaliados em seis ambientes da região central do Brasil, utilizando-se o delineamento em látice simples 8 x 9. De um modo geral, à medida que a proporção de germoplasma exótico decresceu, valores médios mais altos foram obtidos para o caráter peso de espigas. Alguns retrocruzamentos produziram mais que as populações melhoradas BR 105 (7.500 kg/ha) e BR 106 (8.430 kg/ha). Os melhores resultados foram obtidos quando houve a incorporação de 6,25 ou 12,5% de genes exóticos. Esta tendência foi observada para acamamento, quebramento e espigas doentes, mas não para altura de planta e de espiga. A heterose média para peso de espiga variou de -16,1 a 40,3%. Heteroses médias com valores positivos e negativos também foram encontradas para outros caracteres. Os resultados obtidos mostraram o potencial em se utilizar germoplasmas exóticos para a obtenção de híbridos. Sugere-se, após a escolha dos germoplasma, algum esquema de seleção recorrente para adaptar e melhorar as populações exóticas