Neurogenesis within the hippocampus after chronic methylphenidate exposure

Oakes, Hannah; DeVee, Carley; Farmer, Brandon C.; Allen, Serena; Hall, Alexis; Ensley, Tucker; Medlock, Kristen; Hanley, Angela; Pond, Brooks B.

doi:10.1007/s00702-018-1949-2

Cited by 14 publications

(12 citation statements)

References 40 publications

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“…In vivo, alterations in the expression of mRNAs involved in neuronal, synaptic, and axonal processes, in differentiation and in the Wnt-signaling were observed in MPH-treated rodents 64 , 65 . In addition, Oakes and collaborators 81 found that β-catenin (as well as a vascular endothelial growth factor—VEGF —and tropomyosin receptor kinase B—TrkB) levels in juvenile male mice were elevated after a low dose of chronic MPH treatment (1 mg/kg) and reduced after high dose chronic treatment (10 mg/kg) administrated by intraperitoneal injections. The initial increase in the concentration of these factors by lower doses was followed by increased proliferation and survival of hippocampal cells, indicating that they might act as mediators of these cellular processes 81 (Fig.…”

Section: Introductionmentioning

confidence: 99%

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

et al. 2020

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Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric neurodevelopmental disorders in children and adolescents. Although ADHD has been studied for nearly a century, the cause and pathophysiology of ADHD is yet largely unknown. However, findings from previous studies have resulted in the formation of a new hypothesis: Apart from the well-known multifactorial etiology of ADHD, recent evidence suggests that the interaction between genetic and environmental factors and especially Wnt- and mTOR-signaling pathways might have an important role in the pathophysiology of ADHD. The Wnt-signaling pathway is known to orchestrate cellular proliferation, polarity, and differentiation, and the mTOR pathway is involved in several significant processes of neurodevelopment and synaptic plasticity. As a result, dysregulations of these pathways in a time-dependent manner could lead to neurodevelopmental delays, resulting in ADHD phenotype. This review presents further evidence supporting our hypothesis by combining results from studies on ADHD and Wnt- or mTOR-signaling and the influence of genetics, methylphenidate treatment, Omega-3 supplementation, and stress.

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Section: Introductionmentioning

confidence: 99%

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

et al. 2020

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“…The hippocampal volume in the ADHD group was not different from that in the control group, but the right hippocampal volume was positively correlated with inattentiveness. Chronic low doses of stimulant medications increase hippocampal neurogenesis and cell survival [ 31 ]. In a study with more than half of ADHD patients undergoing stimulant treatment, their hippocampal volumes were greater than that of the control group and associated with fewer symptoms [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Disrupted Association between Empathy and Brain Structure in Attention-Deficit/Hyperactivity Disorder

Lee

Son

Kim

et al. 2021

J Korean Acad Child Adolesc Psychiatry

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Objectives To investigate the relationship between brain structure and empathy in early adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods Nineteen early adolescents with ADHD and 20 healthy controls underwent 3T MRI. All the participants were assessed for different aspects of empathy using measures including the Interpersonal Reactivity Index and Empathy Quotient. Cortical thickness and subcortical structural volume based on T1-weighted scans were analyzed using FreeSurfer. Results Cognitive empathy (t=-2.52, p=0.016) and perspective taking (t=-2.10, p=0.043) were impaired in the ADHD group compared with the control group. The cluster encompassing the left posterior insular, supramarginal, and transverse temporal cortices [cluster-wise p-value (CWP)=0.001], which are associated with emotional empathy, was significantly smaller in the ADHD group, and the volume of the left nucleus accumbens was greater than that of the control group (F=10.12, p=0.003, effect size=0.22). In the control group, the left superior temporal (CWP=0.002) and lingual cortical (CWP=0.035) thicknesses were positively associated with cognitive empathy, while the right amygdala volume was positively associated with empathic concern (Coef=14.26, t=3.92, p=0.001). However, there was no significant correlation between empathy and brain structure in the ADHD group. Conclusion The ADHD group had a smaller volume of the cortical area associated with emotional empathy than the control group, and there was no brain region showing significant correlation with empathy, unlike in the control group.

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“…However, the maintenance and integration of newly-formed neurons were only observed in the low-dose group. Authors concluded that chronic exposure to MPH at high doses initially increased neurogenesis but that hippocampus atrophy ensued as newly-formed neurons failed to survive long-term ( Oakes et al, 2018 ). A review on the neurotoxic effects of psychostimulants reported similar findings, where young rats repeatedly administered MPH displayed significant decreases in the number of neurons and astrocytes in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…However, human studies have primarily investigated the acute effects of ADHD medication between treatment-naïve and treatment-exposed children with ADHD. Consequently, the effects of long-term medication use on brain structure, remain to be clearly determined ( Oakes et al, 2018 , Schmitz et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Cumulative exposure to ADHD medication is inversely related to hippocampus subregional volume in children

Fotopoulos

Devenyi

Guay

et al. 2021

NeuroImage: Clinical

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Highlights Cumulative exposure to ADHD medication characterized as the product of lifetime duration and dose. Medication effects investigated on 51 subregional volumes. Smaller hippocampus CA1 volumes associated with higher medication exposure. Effects remained when correcting for age and ADHD symptom severity. No global effects of medication on cortical thickness or surface area detected.

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Neurogenesis within the hippocampus after chronic methylphenidate exposure

Cited by 14 publications

References 40 publications

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

Disrupted Association between Empathy and Brain Structure in Attention-Deficit/Hyperactivity Disorder

Cumulative exposure to ADHD medication is inversely related to hippocampus subregional volume in children

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