Aberrant Hippocampal Development in Early-onset Mental Disorders and Promising Interventions: Evidence from a Translational Study.
Jingyu YangHuiling GuoAoling CaiJunjie ZhengJuan LiuYao XiaoSihua RenDandan SunJia DuanTongtong ZhaoJingwei TangXizhe ZhangRongxin ZhuJie WangFei WangPublished in: Neuroscience bulletin (2023)
Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence. The methylazoxymethanol acetate (MAM) animal model, in which disruption in neurodevelopmental processes is induced, mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective. We conducted longitudinal structural magnetic resonance imaging (MRI) scans during childhood, adolescence, and adulthood in MAM rats to identify specific brain regions and critical windows for intervention. Then, the effect of repetitive transcranial magnetic stimulation (rTMS) intervention on the target brain region during the critical window was investigated. In addition, the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders (diagnosed with major depressive disorder or bipolar disorder) to evaluate its clinical translational potential. The results demonstrated that, compared to the control group, the MAM rats exhibited significantly lower striatal volume from childhood to adulthood (all P <0.001). In contrast, the volume of the hippocampus did not show significant differences during childhood (P >0.05) but was significantly lower than the control group from adolescence to adulthood (both P <0.001). Subsequently, rTMS was applied to the occipital cortex, which is anatomically connected to the hippocampus, in the MAM models during adolescence. The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group (P <0.01), while the volume of the striatum remained unchanged (P >0.05). In the clinical trial, adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline (P <0.01), and these volumetric changes were associated with improvement in depressive symptoms (r = - 0.524, P = 0.018). These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for early-onset mental disorders with neurodevelopmental etiology as well as the promise of rTMS as a therapeutic approach for mitigating aberrant neurodevelopmental processes and alleviating clinical symptoms.
Keyphrases
- early onset
- transcranial magnetic stimulation
- depressive symptoms
- high frequency
- bipolar disorder
- major depressive disorder
- cerebral ischemia
- late onset
- randomized controlled trial
- magnetic resonance imaging
- social support
- early life
- sleep quality
- resting state
- functional connectivity
- clinical trial
- contrast enhanced
- subarachnoid hemorrhage
- young adults
- computed tomography
- cognitive impairment
- big data
- white matter
- diffusion weighted imaging
- study protocol
- mental health
- risk assessment
- congenital heart disease
- open label
- multiple sclerosis
- temporal lobe epilepsy
- oxidative stress
- cancer therapy
- stress induced
- endothelial cells