Brain alterations in adolescents with first-episode depression who have experienced adverse events: evidence from resting-state functional magnetic resonance imaging.

Introduction: Adverse life events constitute primary risk factors for major depressive disorder (MDD), influencing brain function and structure. Adolescents, with their brains undergoing continuous development, are particularly susceptible to enduring impacts of adverse events. Methods: We investigated differences and correlations among childhood trauma, negative life events, and alterations of brain function in adolescents with first-episode MDD. The study included 23 patients with MDD and 19 healthy controls, aged 10-19 years. All participants underwent resting-state functional magnetic resonance imaging and were assessed using the beck depression inventory, childhood trauma questionnaire, and adolescent self-rating life events checklist. Results: Compared with healthy controls, participants with first-episode MDD were more likely to have experienced emotional abuse, physical neglect, interpersonal relationship problems, and learning stress (all p' < 0.05). These adverse life events were significantly correlated with alterations in brain functions (all p < 0.05). Discussion: This study contributes novel evidence on the underlying process between adverse life events, brain function, and depression, emphasizing the significant neurophysiological impact of environmental factors.

Interleukin-6 is correlated with amygdala volume and depression severity in adolescents and young adults with first-episode major depressive disorder.

Inflammatory mechanisms may play crucial roles in the pathophysiology of major depressive disorder (MDD), and cytokine concentrations are correlated with brain alterations. Adolescents and young adults with MDD have higher recurrence and suicide rates than adults, but there has been limited research on the underlying mechanisms. In this study, we aimed to investigate the potential correlations among cytokines, depression severity, and the volumes of the amygdala, hippocampus, and nucleus accumbens in Han Chinese adolescents and young adults with first-episode MDD. Nineteen patients with MDD aged 10-21 years were enrolled from the Psychiatry Department of the First Affiliated Hospital of Chongqing Medical University, along with 18 age-matched healthy controls from a local school. We measured the concentrations of interleukin (IL)-4, IL-6, IL-8, and IL-10 in the peripheral blood, along with the volumes of the amygdala, hippocampus, and nucleus accumbens, as determined by magnetic resonance imaging. We observed that patients with MDD had higher concentrations of IL-6 and a trend towards reduced left amygdala and bilateral hippocampus volumes than healthy controls. Additionally, the concentration of IL-6 was correlated with the left amygdala volume and depression severity, while the left hippocampus volume was correlated with depression severity. This study suggests that inflammation is an underlying neurobiological change and implies that IL-6 could serve as a potential biomarker for identifying early stage MDD in adolescents and young adults.

In vivo analyses reveal hippocampal subfield volume reductions in adolescents with schizophrenia, but not with major depressive disorder.

BACKGROUND: Adult studies have reported atypicalities in the hippocampus and subfields in patients with schizophrenia (SCZ) and major depressive disorder (MDD). Both affective and psychotic disorders typically onset in adolescence, when human brain develops rapidly and shows increased susceptibility to adverse environments. However, few in vivo studies have investigated whether hippocampus subfield abnormalities occur in adolescence and whether they differ between SCZ and MDD cases. METHODS: We recruited 150 adolescents (49 SCZ patients, 67 MDD patients, and 34 healthy controls) and obtained their structural images. We used FreeSurfer to automatically segment hippocampus into 12 subfields and analyzed subfield volumetric differences between groups by analysis of covariance, covarying for age, sex, and intracranial volume. Composite measures by summing subfield volumes were further compared across groups and analyzed in relation to clinical characteristic. RESULTS: SCZ adolescents showed significant volume reductions in subfields of CA1, molecular layer, subiculum, parasubiculum, dentate gyrus and CA4 than healthy controls, and almost significant reductions, as compared to the MDD group, in left molecular layer, dentate gyrus, CA2/3 and CA4. Composite analyses showed smaller volumes in SCZ group than in healthy controls in all bilateral composite measures, and reduced volumes in comparison to MDD group in all left composite measures only. CONCLUSIONS: SCZ adolescents exhibited both hippocampal subfield and composite volumes reduction, and also showed greater magnitude of deviance than those diagnosed with MDD, particularly in core CA regions. These results indicate a hippocampal disease process, suggesting a potential intervention marker of early psychotic patients and risk youths.

Transcriptome comparative analysis of amygdala-hippocampus in depression: A rat model induced by chronic unpredictable mild stress (CUMS).

BACKGROUND: Depression is a common and complex mental disease, and its pathogenesis involves several brain regions. Abnormalities in the amygdala-hippocampal neural circuits have been shown to be involved in depression. However, the underlying molecular mechanisms remain unclear. METHODS: A rat model was used to determine the transcriptome changes in the amygdala-hippocampal neural network under chronic unpredictable mild stress (CUMS). Depression-related modules in this neural network were identified using weighted gene co-expression network analysis (WGCNA). Difference and enrichment analyses were used to determine differential gene expression in the two brain regions. RESULTS: The modules in the amygdala and hippocampus associated with depression-like behavior contained 363 and 225 genes, respectively. Forty-two differentially expressed genes were identified in the amygdala candidate module and 37 in the hippocampus. Enrichment analysis showed that candidate genes in the amygdala were associated with neuronal myelination and candidate genes in the hippocampus were associated with synaptic transmission. Finally, based on module hub gene statistics, differential gene expression, and protein-protein interaction networks, 11 central genes were found in the amygdala candidate module, and one central gene was found in the hippocampal module. LIMITATIONS: Our study was based on a rat CUMS model. Further evidence is needed to prove that our results are applicable to patients with depression. CONCLUSION: This study identified critical modules and central genes involved in the amygdala-hippocampal circuit in the context of depression, and may provide further understanding of the pathogenesis of depression and help identify potential targets for antidepressant therapy.

A Bivariate Twin Study of Cortical Surface Area and Verbal and Nonverbal Intellectual Skills in Adolescence.

Understanding the biological basis of cognitive differences between individuals is the goal in human intelligence research. The surface area of the cortex is considered to be a key determinant of human intelligence. Adolescence is a period of development characterized by physiological, emotional, behavioral, and psychosocial changes, which is related to the recombination and optimization of the cerebral cortex, and cognitive ability changes significantly in children and adolescents. This study examined the effects of common genetic and environmental factors between the surface area of the cerebral cortex and intelligence in typical developing adolescents (twins, n = 114, age 12-18 years old). Cortical surface area data were parsed into subregions (i.e., frontal, parietal, occipital, and temporal areas) and intelligence into verbal and nonverbal skills. We found a phenotypic correlation between regional surface areas and verbal intelligence. No correlation was observed between regional surface areas and nonverbal intelligence, except for the occipital lobe and the right hemisphere. In the bivariate twin analyses, the differences in phenotypic correlation between regional surface areas and verbal intelligence were not due to unshared environmental effects or measurement error, but to genetic effects. In summary, the current study has broadened the previous genetic investigations of cognitive ability and cortical surface area.

An autoactive NB-LRR gene causes Rht13 dwarfism in wheat.

Semidwarfing genes have greatly increased wheat yields globally, yet the widely used gibberellin (GA)-insensitive genes Rht-B1b and Rht-D1b have disadvantages for seedling emergence. Use of the GA-sensitive semidwarfing gene Rht13 avoids this pleiotropic effect. Here, we show that Rht13 encodes a nucleotide-binding site/leucine-rich repeat (NB-LRR) gene. A point mutation in the semidwarf Rht-B13b allele autoactivates the NB-LRR gene and causes a height reduction comparable with Rht-B1b and Rht-D1b in diverse genetic backgrounds. The autoactive Rht-B13b allele leads to transcriptional up-regulation of pathogenesis-related genes including class III peroxidases associated with cell wall remodeling. Rht13 represents a new class of reduced height (Rht) gene, unlike other Rht genes, which encode components of the GA signaling or metabolic pathways. This discovery opens avenues to use autoactive NB-LRR genes as semidwarfing genes in a range of crop species, and to apply Rht13 in wheat breeding programs using a perfect genetic marker.

Adult plant stem rust resistance in durum wheat Glossy Huguenot: mapping, marker development and validation.

KEY MESSAGE: Adult plant stem rust resistance locus, QSrGH.cs-2AL, was identified in durum wheat Glossy Huguenot and mendelised as Sr63. Markers closely linked with Sr63 were developed. An F3 population from a Glossy Huguenot (GH)/Bansi cross used in a previous Australian study was advanced to F6 for molecular mapping of adult plant stem rust resistance. Maturity differences among F6 lines confounded assessments of stem rust response. GH was crossed with a stem rust susceptible F6 recombinant inbred line (RIL), GHB14 (M14), with similar maturity and an F6:7 population was developed through single seed descent method. F7 and F8 RILs were tested along with the parents at different locations. The F6 individual plants and both parents were genotyped using the 90 K single nucleotide polymorphism (SNP) wheat array. Stem rust resistance QTL on the long arms of chromosomes 1B (QSrGH.cs-1BL) and 2A (QSrGH.cs-2AL) were detected. QSrGH.cs-1BL and QSrGH.cs-2AL were both contributed by GH and explained 22% and 18% adult plant stem rust response variation, respectively, among GH/M14 RIL population. RILs carrying combinations of these QTL reduced more than 14% stem rust severity compared to those that possessed QSrGH.cs-1BL and QSrGH.cs-2AL individually. QSrGH.cs1BL was demonstrated to be the same as Sr58/Lr46/Yr29/Pm39 through marker genotyping. Lines lacking QSrGH.cs-1BL were used to Mendelise QSrGH.cs-2AL. Based on genomic locations of previously catalogued stem rust resistance genes and the QSrGH.cs-2AL map, it appeared to represent a new APR locus and was permanently named Sr63. SNP markers associated with Sr63 were converted to kompetetive allele-specific PCR (KASP) assays and were validated on a set of durum cultivars.

The wheat Sr22, Sr33, Sr35 and Sr45 genes confer resistance against stem rust in barley.

In the last 20 years, stem rust caused by the fungus Puccinia graminis f. sp. tritici (Pgt), has re-emerged as a major threat to wheat and barley production in Africa and Europe. In contrast to wheat with 60 designated stem rust (Sr) resistance genes, barley's genetic variation for stem rust resistance is very narrow with only ten resistance genes genetically identified. Of these, only one complex locus consisting of three genes is effective against TTKSK, a widely virulent Pgt race of the Ug99 tribe which emerged in Uganda in 1999 and has since spread to much of East Africa and parts of the Middle East. The objective of this study was to assess the functionality, in barley, of cloned wheat Sr genes effective against race TTKSK. Sr22, Sr33, Sr35 and Sr45 were transformed into barley cv. Golden Promise using Agrobacterium-mediated transformation. All four genes were found to confer effective stem rust resistance. The barley transgenics remained susceptible to the barley leaf rust pathogen Puccinia hordei, indicating that the resistance conferred by these wheat Sr genes was specific for Pgt. Furthermore, these transgenic plants did not display significant adverse agronomic effects in the absence of disease. Cloned Sr genes from wheat are therefore a potential source of resistance against wheat stem rust in barley.

Transfer of stem rust resistance gene SrB from Thinopyrum ponticum into wheat and development of a closely linked PCR-based marker.

KEY MESSAGE: We report transfer of a rust resistance gene named SrB, on the 6Ae#3 chromosome, to wheat by recombination with the 6Ae#1 segment carrying Sr26 and development of a linked marker. A stem rust resistance gene from a South African wheat W3757, temporarily named SrB, has been transferred onto chromosome 6A. Line W3757 is a 6Ae#3 (6D) substitution line in which the Thinopyrum ponticum chromosomes carry SrB. Crosses were made between W3757 and a T6AS·6AL-6Ae#1 recombinant line named WA-5 carrying the stem rust resistance gene Sr26 on a chromosome segment from another accession of Th. ponticum. The 6Ae#1 and 6Ae#3 chromosomes had previously been shown to pair at meiosis and were polymorphic for the distally located RFLP probes BCD001 and MWG798. A recombinant plant (Type A) was identified carrying a distal chromosome segment from the 6Ae#3 chromosome and a sub-terminal segment from the 6Ae#1 chromosome. Rust tests on the recombinant Type A showed the infection type for SrB. Segregation and linkage data combined with genomic in situ hybridization studies demonstrated that SrB had been transferred to wheat chromosome arm 6AL by recombination between the Thinopyrum chromosome segments. A recombinant positive for the 6Ae#1-6Ae#3 chromosome showed enhanced stem rust resistance compared to the 6Ae#3 addition line in repeated rust tests. A diagnostic PCR-based marker was developed for the 6Ae#3 chromosome segment on the Type A recombinant carrying SrB that distinguishes it from the Sr26-containing segment. A stem rust resistant line which combines SrB with Sr26 would be a great addition to the pool of resistant germplasm for wheat breeders to achieve more durable and effective control of stem rust because virulence has not been found for either of these two genes.

Loss of AvrSr50 by somatic exchange in stem rust leads to virulence for Sr50 resistance in wheat.

Race-specific resistance genes protect the global wheat crop from stem rust disease caused by Puccinia graminis f. sp. tritici (Pgt) but are often overcome owing to evolution of new virulent races of the pathogen. To understand virulence evolution in Pgt, we identified the protein ligand (AvrSr50) recognized by the Sr50 resistance protein. A spontaneous mutant of Pgt virulent to Sr50 contained a 2.5 mega-base pair loss-of-heterozygosity event. A haustorial secreted protein from this region triggers Sr50-dependent defense responses in planta and interacts directly with the Sr50 protein. Virulence alleles of AvrSr50 have arisen through DNA insertion and sequence divergence, and our data provide molecular evidence that in addition to sexual recombination, somatic exchange can play a role in the emergence of new virulence traits in Pgt.

Ultrasonic treatment stimulates multiple shoot regeneration and explant enlargement in recalcitrant squash cotyledon explants in vitro.

Ultrasonic treatment (0.5-2 min) stimulated multiple shoot regeneration to high levels in vitro from recalcitrant cotyledon explants of commercial squash (Cucurbita pepo L.) cultivars Ma'yan and Bareqet, on Murashige and Skoog [Physiol Plant 15:473-497, 1962] (regeneration) medium augmented with 4.4 microM benzyladenine. At this stage, unsonicated control explants regenerated only a few very small shoots or bud-like structures. Ultrasound also stimulated massive explant growth. Ultrasound treatment resulted in further multiple shoot production (five times greater than control) after explant transfer to elongation medium (Murashige and Skoog [Physiol Plant 15:473-497, 1962] medium with 0.44 microM benzyladenine and 2.9 microM gibberellic acid). Longer ultrasonic treatments (5 or 10 min) promoted multiple shoot regeneration and explant growth accompanied by hyperhydration. Scanning electron microscope observations showed that 2 min ultrasound changed the joint area between epidermal cells and removed some of the surface from the cotyledon epidermal cells, without gross surface injury to the explants. Longer periods of ultrasound (5-10 min) caused further surface erosion. Rubbing the explant contact surface with chloroform or sandpaper emulated the effect of sonication on shoot regeneration and explant growth, demonstrating that ultrasound exerts its morphogenic influence by surface removal. Sonication of explants from other batches of squash seeds (of cultivars Ma'yan and True French), that regenerated without such treatment, reduced regeneration and caused hyperhydration. This is the first report of stimulation of in vitro regeneration by ultrasound treatment.