Preclinical studies have shown that brain-derived neurotrophic factor (BDNF) may be involved in both antidepressant action and the pathophysiology of major depressive disorder (MDD). The present study tested the hypothesis that the BDNF-gene Val66Met polymorphism is associated with MDD, its clinical manifestations, and antidepressant response. To elucidate a genetic predisposition of MDD, we studied BDNF-gene Val66Met polymorphism in 152 MDD patients in 255 normal controls. We also examined the association of this polymorphism and fluoxetine therapeutic response in 110 MDD patients who received a 4-week fluoxetine treatment. No significant differences were demonstrated for the genotype or allele frequency of the BDNF polymorphism comparing the MDD and control groups. Further, no significant differences were noted comparing the three-genotype groups for depressive-cluster symptoms. However, a trend (P = 0.086) to improved 4-week-fluoxetine antidepressant response was demonstrated for heterozygous patients in comparison to homozygous analogs. This finding suggests the BDNF polymorphism investigated plays no major role in the pathogenesis of MDD.

Neurotrophins have been implicated in the pathophysiology of many neuropsychiatric diseases. Brain-derived neurotrophic factor (BDNF) is the most abundant and widely distributed neurotrophin in the brain. Its Val66Met polymorphism (refSNP Cluster Report: rs6265) is a common and functional single-nucleotide polymorphism (SNP) affecting the activity-dependent release of BDNF. BDNF Val66Met transgenic mice have been generated, which may provide further insight into the functional impact of this polymorphism in the brain. Considering the important role of BDNF in brain function, more than 1,100 genetic studies have investigated this polymorphism in the past 15 years. Although these studies have reported some encouraging positive findings initially, most of the findings cannot be replicated in following studies. These inconsistencies in BDNF Val66Met genetic studies may be attributed to many factors such as age, sex, environmental factors, ethnicity, genetic model used for analysis, and gene–gene interaction, which are discussed in this review. We also discuss the results of recent studies that have reported the novel functions of this polymorphism. Because many BDNF polymorphisms and non-genetic factors have been implicated in the complex traits of neuropsychiatric diseases, the conventional genetic association-based method is limited to address these complex interactions. Future studies should apply data mining and machine learning techniques to determine the genetic role of BDNF in neuropsychiatric diseases.

Proinflammatory cytokines, including interleukin (IL)-1beta, are suggested to have a role in the pathogenesis of major depressive disorder (MDD) and be related to the therapeutic effects of antidepressants. To elucidate a genetic predisposition of MDD, we studied biallelic polymorphism in the promoter region (position -511) of the IL-1beta gene in 157 patients with MDD and in 112 controls. We also examined the association of this polymorphism and fluoxetine therapeutic response in 119 MDD patients who received a 4-week fluoxetine treatment. No significant difference was found in the genetic polymorphism between MDD patients and controls. However, MDD patients who were homozygous for the -511T allele of the IL-1beta gene had a trend of less severity of depressive symptoms and more favorable fluoxetine therapeutic response than -511C carriers. Further study with a larger sample is needed to clarify the role of the IL-1beta genetic polymorphisms in the symptoms and treatment effects in MDD.

Crystallographic characterization and the ferroelectric properties of 50 nm-thick sputter-deposited Al0.78Sc0.22N films deposited at room temperature (RT) and 400 °C are investigated. c-axis oriented growths were confirmed by x-ray diffraction patterns with rocking curve measurements for both samples. Al0.78Sc0.22N films were found to grow in the c-axis direction and showed poling-free ferroelectric properties, which are advantageous for practical memory and piezoelectric applications. Although the metal-ferroelectric-metal (MFM) capacitors represent low switching cycle endurance, MFM capacitors revealed remnant polarization (Pr) of 70 μC/cm2 and 113 μC/cm2 for RT- and 400 °C-deposited samples, respectively. Ferroelectric films with low-temperature process capability can open a wide range of applications.

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