The amygdala is an important structure contributing to socio-emotional behavior. However, the role of the amygdala in autism remains inconclusive. In this study, we used the 28–35 days valproate (VPA)-induced rat model of autism to observe the autistic phenotypes and evaluate their synaptic characteristics in the lateral nucleus (LA) of the amygdala. The VPA-treated offspring demonstrated less social interaction, increased anxiety, enhanced fear learning and impaired fear memory extinction. Slice preparation and electrophysiological recordings of the amygdala showed significantly enhanced long-term potentiation (LTP) while stimulating the thalamic-amygdala pathway of the LA. In addition, the pair pulse facilitation (PPF) at 30- and 60-ms intervals decreased significantly. Whole-cell recordings of the LA pyramidal neurons showed an increased miniature excitatory postsynaptic current (EPSC) frequency and amplitude. The relative contributions of the AMPA receptor and NMDA receptor to the EPSCs did not differ significantly between groups. These results suggested that the enhancement of the presynaptic efficiency of excitatory synaptic transmission might be associated with hyperexcitibility and enhanced LTP in LA pyramidal neurons. Disruption of the synaptic excitatory/inhibitory (E/I) balance in the LA of VPA-treated rats might play certain roles in the development of behaviors in the rat that may be relevant to autism. Further experiments to demonstrate the direct link are warranted.

Comorbidity exists between metabolic disorders and depressive syndrome with unclear mechanisms. To characterize the causal relationship, we adopted a 12-week high-fat diet (HFD) to induce metabolic disorder and depressive phenotypes in mice. Initially, we identified an enhanced glutamatergic input in the nucleus accumbens of HFD mice. Retrograde tracing and chemogenetic inhibition showed that the hyperactive ventral hippocampal glutamatergic afferents to the nucleus accumbens determined the exhibition of depression-like behavior in HFD mice. Using lentiviral knockdown and overexpression approaches, we proved that HFD-induced downregulation of glial glutamate transporters, GLAST and GLT-1, contributed to the observed circuit maladaptations and subsequent depression-like behaviors. Finally, we identified a potential therapeutic agent, riluzole, which could mitigate the HFD-induced behavioral deficits by normalizing the expressions of GLAST and GLT-1 and ventral hippocampal glutamatergic afferents to the nucleus accumbens. Overall, astrocyte-mediated disturbance in glutamatergic transmission underlies the metabolic disorder-related depressive syndrome and represents a therapeutic target for this subtype of depressive mood disorders.

Accumulating evidence suggests that dysfunction of the amygdala is related to abnormal fear processing, anxiety, and social behaviors noted in autistic spectrum disorders (ASDs). In addition, studies have shown that disrupted brain serotonin homeostasis is linked to ASD. With a valproate (VPA)-induced rat ASD model, we investigated the possible role of amygdala serotonin homeostasis in autistic phenotypes and further explored the underlying mechanism. We first discovered that the distribution of tryptophan hydroxylase immunoreactivity in the caudal raphe system was modulated on postnatal day (PD) 28 of the VPA-exposed offspring. Then, we found a significantly higher serotonin transporter availability in the amygdala of the VPA-exposed offspring on PD 56 by using single photon emission computed tomography and computed tomography co-registration following injection of 123I-labeled 2-((2-(dimethylamino)methyl)phenyl)thio)-5-iodophenylamine(123I[ADAM]). Furthermore, treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, increased social interaction and improved fear memory extinction in the VPA-exposed offspring. 8-OH-DPAT treatment also reversed the characteristics of miniature excitatory post-synaptic currents as well as paired pulse facilitation observed in lateral amygdala slices. These results provided further evidence to support the role of the amygdala in characteristic behavioral changes in the rat ASD model. The serotonergic projections that modulate the amygdala function might play a certain role in the development and treatment of behavioral symptoms exhibited in individuals with ASD.

Abstract  The aims of this study were: (i) to assess the impact of caring for patients with schizophrenia on the mental health status of the caregivers; and (ii) to examine the direct and buffer effects of social support on the mental health status of these caregivers. A total of 61 key caregivers of patients with schizophrenia were administered the Chinese Health Questionnaire (CHQ) and the Measure of Support Function (MSF) self‐report questionnaire to assess their mental health and social support status. The MSF questionnaire constitutes four subscales, including: (i) the perceived crisis support (PCS); (ii) the perceived routine support (PRS); (iii) the received crisis support (RCS); and (iv) the received routine support (RRS) subscale. The Positive and Negative Syndrome Scale (PANSS) was used to assess the psychopathology severity of the patients they cared for. Then the authors used the hierarchical multiple regression model to analyze the relationship between these variables. The psychopathology severity of the patients reflected by the PANSS scores correlated inversely with the caregivers’ CHQ scores. Besides, the PCS subscale scores correlated positively with the caregivers’ CHQ scores. Moreover, the interaction between the RCS subscale scores and the PANSS scores was significant. Significant positive correlation between the RCS and CHQ exists only in the higher PANSS subgroup, but not in the lower PANSS subgroup. The psychopathological severity of the patients has a negative impact on their caregivers’ mental health. PCS has a direct effect, and RCS has a buffer effect on the mental health status of these caregivers.