Neurons in the brain must establish a balanced network of excitatory and inhibitory synapses during development for the brain to function properly. An imbalance between these synapses underlies various neurological and psychiatric disorders. The formation of excitatory and inhibitory synapses requires precise molecular control. In the hippocampus, the structure crucial for learning and memory, fibroblast growth factor 22 (FGF22) and FGF7 specifically promote excitatory or inhibitory synapse formation, respectively. Knockout of either Fgf gene leads to excitatory-inhibitory imbalance in the mouse hippocampus and manifests in an altered susceptibility to epileptic seizures, underscoring the importance of FGF-dependent synapse formation. However, the receptors and signaling mechanisms by which FGF22 and FGF7 induce excitatory and inhibitory synapse differentiation are unknown. Here, we show that distinct sets of overlapping FGF receptors (FGFRs), FGFR2b and FGFR1b, mediate excitatory or inhibitory presynaptic differentiation in response to FGF22 and FGF7. Excitatory presynaptic differentiation is impaired in Fgfr2b and Fgfr1b mutant mice; however, inhibitory presynaptic defects are only found in Fgfr2b mutants. FGFR2b and FGFR1b are required for an excitatory presynaptic response to FGF22, whereas only FGFR2b is required for an inhibitory presynaptic response to FGF7. We further find that FGFRs are required in the presynaptic neuron to respond to FGF22, and that FRS2 and PI3K, but not PLCγ, mediate FGF22-dependent presynaptic differentiation. Our results reveal the specific receptors and signaling pathways that mediate FGF-dependent presynaptic differentiation, and thereby provide a mechanistic understanding of precise excitatory and inhibitory synapse formation in the mammalian brain.
The causal relationships between problematic internet use and psychological distress remain controversial. The present study investigated the reciprocal relationships between problematic internet use (PIU, i.e., problematic social media use [PSMU], problematic gaming [PG]) and psychological distress (i.e., anxiety, depression). Hong Kong and Taiwan university students (N=645; nmale=266; mean=20.95 years [SD=5.63]) were recruited for a survey study, with follow-ups at three, six, and nine months after baseline assessment. The Bergen Social Media Addiction Scale, Internet Gaming Disorder-Short Form, and the Hospital Anxiety and Depression Scale were used to assess studied variables. Cross-lagged models were constructed to understand the reciprocal relationships between PIU and psychological distress. The level of anxiety significantly impacted the level of PSMU but not in the opposite direction. The level of PSMU significantly impacted the level of depression but not in the opposite direction. In addition, levels of PG and both types of psychological distress had reciprocal impacts on each another. Because PIU can lead to psychological distress, prevention programs on digital health are needed. Moreover, because there is a reciprocity between PG and psychological distress, psychological interventions to break the reciprocal relationship for those with serious PG and psychological distress are warranted.
We found a higher rate of clinically diagnosed depression in our cohort compared to the general population. However, when using the validated PHQ-8 survey, the rate of depression more closely approximated the national incidence. Further, a significant proportion of patients were undiagnosed and/or misdiagnosed by current clinical assessments. Standardizing preoperative depression screening using validated patient-centered tools may prevent the consequences of untreated depression.
OBJECTIVES/SPECIFIC AIMS: Anxiety is prevalent in early childhood and, when left untreated, increases children’s risk for chronic anxiety and depression later in life. Maternal risk factors (e.g. income and marital status) have also been shown to heighten their children’s risk for the development of the aforementioned psychopathology. Sleep plays a critical role in behavior regulation, is affected in depression, and is influenced by a wide range of demographic and psychological variables. The purpose of this study was to examine the relationship between maternal sleep and the presence in their children of reported symptoms relating to anxiety, depression, and behavior regulation. METHODS/STUDY POPULATION: Children (n=59, aged: 4-9 years (M = 6.069, SD = 1.006, 59.3% female) and their mothers were sampled from clinic and community settings and were administered questionnaires. Maternal sleep quality was assessed by the Pittsburgh Sleep Quality Index, which captures both numeric and self-reported categories relating to an individual’s perception of their sleep. Child anxiety and depression were assessed via parent-reported Child Behavioral Checklist (CBCL). Maternal depression symptoms were assessed with the Beck Depression Inventory (BDI). Associations between these measures were analyzed by ANOVA with post-hoc analysis and linear regression as appropriate. RESULTS/ANTICIPATED RESULTS: A statistically significant difference was observed in the mean child CBCL scores when children were sub-set into maternal categories of self-reported days of dysfunction due to sleepiness over the past month. Mean child CBCL T-score domains with statistically significant differences were: attention problems (F = 4.935, p = 0.004), depression problems (F = 3.073, p = 0.035), ADHD (F = 4.422, p = 0.007), oppositional defiant (F = 2.865, p = 0.045), and total t-score (F = 3.073, p = 0.035). Maternal mean DBI scores were also statistically significantly different when grouped by days of maternal dysfunction due to sleepiness (F = 9.791, p < 0.001). There was no relation between these CBCL categories and maternal DBI scores. DISCUSSION/SIGNIFICANCE OF IMPACT: Maternal self-reported days of dysfunction due to sleepiness may potentially increase risk for their children to develop further psychopathology independent of mothers’ depression symptomatology. These findings highlight the need for broader assessment clinically of children’s environments with additional focus on maternal function given the potential impact on their children’s functional outcomes.
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