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.

A midbrain GABAergic circuit constrains wakefulness in a mouse model of stress.

Enhancement of wakefulness is a prerequisite for adaptive behaviors to cope with acute stress, but hyperarousal is associated with impaired behavioral performance. Although the neural circuitries promoting wakefulness in acute stress conditions have been extensively identified, less is known about the circuit mechanisms constraining wakefulness to prevent hyperarousal. Here, we found that chemogenetic or optogenetic activation of GAD2-positive GABAergic neurons in the midbrain dorsal raphe nucleus (DRNGAD2) decreased wakefulness, while inhibition or ablation of these neurons produced an increase in wakefulness along with hyperactivity. Surprisingly, DRNGAD2 neurons were paradoxically wakefulness-active and were further activated by acute stress. Bidirectional manipulations revealed that DRNGAD2 neurons constrained the increase of wakefulness and arousal level in a mouse model of stress. Circuit-specific investigations demonstrated that DRNGAD2 neurons constrained wakefulness via inhibition of the wakefulness-promoting paraventricular thalamus. Therefore, the present study identified a wakefulness-constraining role DRNGAD2 neurons in acute stress conditions.

Ethylene and jasmonate signaling converge on gibberellin catabolism during thigmomorphogenesis in Arabidopsis.

Touch induces marked morphological changes in plants, including reduced rosette diameters and delayed flowering, a process called thigmomorphogenesis. Previous studies have revealed that thigmomorphogenesis in Arabidopsis (Arabidopsis thaliana) results from touch-induced accumulation of jasmonic acid (JA) and GIBBERELLIN 2-OXIDASE7 (GA2ox7) transcripts, which encode a gibberellin (GA) catabolism enzyme, leading to reduced levels of active GAs. However, the mechanisms underlying thigmomorphogenesis remain uncharacterized. Here, we showed that touch induces ethylene (ET) production in Arabidopsis. After touch treatment, ET biosynthesis and signaling mutants exhibited even greater thigmomorphogenic changes and more decreased GA4 contents than did wild-type (WT) plants. Biochemical analysis indicated that the transcription factor ETHYLENE INSENSITIVE3 (EIN3) of the ET pathway binds to the promoter of GA2ox8 (encoding another GA 2-oxidase performing the same GA modification as GA2ox7) and represses GA2ox8 transcription. Moreover, MYC2, the master regulator of JA signaling, directly promoted GA2ox7 expression by binding the G-box motif on GA2ox7 promoter. Further genetic analysis suggested that the ET and JA pathways independently control the expression of GA2ox8 and GA2ox7, respectively. This study reveals that the ET pathway is a novel repressor of touch-induced thigmomorphogenesis and highlights that the ET and JA pathways converge on GA catabolism but play opposite roles to fine-tune GA4 content during thigmomorphogenesis.

Elevating herbivore-induced JA-Ile enhances potato resistance to the polyphagous beet armyworm but not to the oligophagous potato tuber moth.

BACKGROUND: The oligophagous potato tuber moth (PTM), Phthorimaea operculella, and the polyphagous beet armyworm (BAW), Spodoptera exigua, are two destructive pests of potato, and infestations can lead to serious reduction in potato yield. However, potato plant responses to the two herbivories are only poorly understood. Endogenous jasmonoyl-isoleucine (JA-Ile) is a signal responsible for the induction of plant anti-herbivore defenses. Elevation of JA-Ile by blocking its catabolism is considered to be an effective and sustainable approach to enhance plant resistance to insect pests. However, it is not clear whether this approach can enhance potato resistance to PTM and BAW. RESULTS: We demonstrated that the transcriptional changes induced by simulated PTM and BAW feeding overlap to a large extent, and that 81.5% of the PTM- and 90.5% of the BAW-responsive genes were commonly regulated. We also generated potato transgenic lines, irStCYP94B3s, in which the three JA-Ile hydroxylases were all simultaneously silenced. These lines exhibited enhanced resistance only to BAW, but not to PTM, although levels of JA-Ile and its downstream induced defensive chemicals, including caffeoylputrescine, dicaffeoylspermidine, lyciumoside II, and the nicotianosides I, II, and VII, were all present at higher levels in PTM-infested than in BAW-infested irStCYP94B3s lines. CONCLUSION: Our results provide support for the hypothesis that StCYP94B3 genes are able to act as potential targets for the control of polyphagous insect pests in potato, and reveal that the oligophagous PTM has evolved an effective mechanism to cope with JA-Ile-induced anti-herbivore defenses. © 2022 Society of Chemical Industry.

A paraventricular thalamus to central amygdala neural circuit modulates acute stress-induced heightened wakefulness.

Heightened wakefulness in response to stressors is essential for survival but can also lead to sleep disorders like insomnia. The paraventricular thalamus (PVT) is both a critical thalamic area for wakefulness and a stress-sensitive brain region. However, whether the PVT and its neural circuitries are involved in controlling wakefulness in stress conditions remains unknown. Here, we find that PVT neurons projecting to the central amygdala (CeA) are activated by different stressors. These neurons are wakefulness-active and increase their activities upon sleep to wakefulness transitions. Optogenetic activation of the PVT-CeA circuit evokes transitions from sleep to wakefulness, whereas selectively silencing the activity of this circuit decreases time spent in wakefulness. Specifically, chemogenetic inhibition of CeA-projecting PVT neurons not only alleviates stress responses but also attenuates the acute stress-induced increase of wakefulness. Thus, our results demonstrate that the PVT-CeA circuit controls physiological wakefulness and modulates acute stress-induced heightened wakefulness.

Cortical thickness distinguishes between major depression and schizophrenia in adolescents.

BACKGROUND: Early diagnosis of adolescent psychiatric disorder is crucial for early intervention. However, there is extensive comorbidity between affective and psychotic disorders, which increases the difficulty of precise diagnoses among adolescents. METHODS: We obtained structural magnetic resonance imaging scans from 150 adolescents, including 67 and 47 patients with major depressive disorder (MDD) and schizophrenia (SCZ), as well as 34 healthy controls (HC) to explore whether psychiatric disorders could be identified using a machine learning technique. Specifically, we used the support vector machine and the leave-one-out cross-validation method to distinguish among adolescents with MDD and SCZ and healthy controls. RESULTS: We found that cortical thickness was a classification feature of a) MDD and HC with 79.21% accuracy where the temporal pole had the highest weight; b) SCZ and HC with 69.88% accuracy where the left superior temporal sulcus had the highest weight. Notably, adolescents with MDD and SCZ could be classified with 62.93% accuracy where the right pars triangularis had the highest weight. CONCLUSIONS: Our findings suggest that cortical thickness may be a critical biological feature in the diagnosis of adolescent psychiatric disorders. These findings might be helpful to establish an early prediction model for adolescents to better diagnose psychiatric disorders.

Jasmonoyl-l-isoleucine and allene oxide cyclase-derived jasmonates differently regulate gibberellin metabolism in herbivory-induced inhibition of plant growth.

The trade-off between plant growth and resistance to herbivory is thought to be at least partly mediated by the interactions between jasmonates and gibberellins (GAs). Insect herbivory activates jasmonate biosynthesis and signaling, and plant growth is concomitantly inhibited. Whether or not the herbivory-induced jasmonates suppress the accumulation of GAs and thus reduce plant growth, and which jasmonates are functional in this process, remain unclear. In this study, we show that herbivory-induced stunted growth of Nicotiana attenuata was completely dependent on allene oxide cyclase (AOC) and coronatine insensitive1 (COI1), which encode a JA biosynthetic enzyme and the receptor, respectively, but only partially dependent on jasmonic acid-isoleucine conjugate (JA-Ile), the bioactive jasmonate. Quantification of GAs and exogenous treatments indicated that herbivory-induced growth inhibition was caused by GA4 deficiency, and that the reduction in GA4 accumulation was strongly associated with both decreased concentrations of GA biosynthetic gene transcripts and transcriptional activation of GA catabolic genes. We further show that JA-Ile only positively regulated the levels of GA catabolic genes, while the accumulation of GA biosynthetic gene transcripts was controlled by certain AOC-derived jasmonate(s) rather than by JA-Ile. This work sheds light on the mechanisms by which plants adapt to herbivory by using intricate phytohormone signaling and transcriptional regulatory networks.

Silencing JA hydroxylases in Nicotiana attenuata enhances jasmonic acid-isoleucine-mediated defenses against Spodoptera litura.

Jasmonic acid (JA) plays important roles in plant resistance to insect herbivores. One important derivative of JA is 12-OH-JA, which is produced by two independent pathways: direct hydroxylation of JA by jasmonate-induced oxygenases (JOXs) or hydrolyzation of 12-OH-JA-Ile.Yet the function of 12-OH-JA in plant-herbivore interactions remains largely unknown. In this study, we silenced four JOX homologs independently in the wild tobacco Nicotiana attenuata by virus-induced gene silencing (VIGS), and found that all four JOX homologs are involved in JA hydroxylation. Simultaneously silencing the four JA hydroxylases in VIGS-NaJOXs plants decreased herbivory-induced 12-OH-JA by 33%, but JA and JA-Ile levels increased by 45% and 30%, respectively, compared to those in control plants. Compared to direct hydroxylation from JA, hydrolyzation from 12-OH-JA-Ile is equally important for herbivory-induced 12-OH-JA accumulation: in the 12-OH-JA-Ile deficient irJAR4/6 plants, 12-OH-JA decreased 34%. Moreover, VIGS-NaJOXs plants exhibited enhanced resistance to the generalist herbivore Spodoptera litura. The poor larval performance was strongly correlated with high levels of several JA-Ile-dependent direct defense metabolites in the VIGS-NaJOXs plants. When we simultaneously silenced all four JA hydroxylases in the JA-Ile-deficient irJAR4/6 background, the enhanced herbivore resistance diminished, demonstrating that enhanced herbivore resistance resulted from elevated JA-Ile levels. Given that silencing these NaJOX-like genes did not detectably alter plant growth but highly increased plant defense levels, we propose that JOX genes are potential targets for genetic improvement of herbivore-resistant crops.