Neurocognitive deficits in major depression and a new theory of ADHD: A model of impaired antagonism of cholinergic-mediated prepotent behaviours in monoamine depleted individuals

Vakalopoulos, Costa

doi:10.1016/j.mehy.2006.07.018

Cited by 20 publications

(16 citation statements)

References 60 publications

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“…The combined typed also had lower relative in the right hemisphere and more absolute alpha in the temporal-posterior region compared to the inattentive type. This is consistent with the prediction of a selective D2-type signaling deficiency associated with hyperactive-impulsive dimension and D1-type deficit associated with inattention (Vakalopoulos, 2007). …”

Section: The Alpha In Adhd: the Eeg As A Measure Of Imbalance Of Neursupporting

confidence: 90%

“…The MAB hypothesis is modeled on a dual processing theory of cognition and the proposal for an inverse relationship between monoaminergic and cholinergic muscarinic receptor subtypes (Vakalopoulos, 2006, 2007). M1- and M2-type signaling are inversely modulated by 5-HT1A and 5-HT2A signals resulting in segregated couplings of 5-HT2A/C/M2 (conscious) and 5-HT1A/M1 (unconscious) receptor-modulated networks.…”

Section: Eeg Rhythms: Cracking the Codementioning

confidence: 99%

“…A cholinergic theory of affective disorders states that prepotent behaviors associated with emotional dysregulation, such as impulsiveness, rumination, and inflexibility are encoded by implicit cortical traces that form networks with limbic areas (Vakalopoulos, 2007). The formation of unconscious memories that underlie motivation are proposed to be critically dependent on M1-type muscarinic receptor transduction involved in synaptic strength.…”

Section: Eeg Rhythms: Cracking the Codementioning

confidence: 99%

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The EEG as an index of neuromodulator balance in memory and mental illness

Vakalopoulos¹

2014

Front. Neurosci.

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There is a strong correlation between signature EEG frequency patterns and the relative levels of distinct neuromodulators. These associations become particularly evident during the sleep-wake cycle. The monoamine-acetylcholine balance hypothesis is a theory of neurophysiological markers of the EEG and a detailed description of the findings that support this proposal are presented in this paper. According to this model alpha rhythm reflects the relative predominance of cholinergic muscarinic signals and delta rhythm that of monoaminergic receptor effects. Both high voltage synchronized rhythms are likely mediated by inhibitory Gαi/o-mediated transduction of inhibitory interneurons. Cognitively, alpha and delta EEG measures are proposed to indicate automatic and flexible strategies, respectively. Sleep is associated with marked changes in relative neuromodulator levels corresponding to EEG markers of distinct stages. Sleep studies on memory consolidation present some of the strongest evidence yet for the respective roles of monoaminergic and cholinergic projections in declarative and non-declarative memory processes, a key theoretical premise for understanding the data. Affective dysregulation is reflected in altered EEG patterns during sleep.

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Section: The Alpha In Adhd: the Eeg As A Measure Of Imbalance Of Neursupporting

confidence: 90%

Section: Eeg Rhythms: Cracking the Codementioning

confidence: 99%

Section: Eeg Rhythms: Cracking the Codementioning

confidence: 99%

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The EEG as an index of neuromodulator balance in memory and mental illness

Vakalopoulos¹

2014

Front. Neurosci.

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“…The preferential transmission of the CHT Val89 hypomorph to the Combined subtype in the additive model may reflect the importance of cholinergic transmission in modulating fundamental aspects of both motor control and attention [72, 73]. On neuroanatomical grounds, patients with reduced CHT activity should have cholinergic deficits at both cortical and subcortical levels which could produce both inattentive and hyperactivity symptoms.…”

Section: Discussionmentioning

confidence: 99%

Choline transporter gene variation is associated with attention-deficit hyperactivity disorder

English

Hahn

Gizer

et al. 2009

J Neurodevelop Disord

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The neurotransmitter acetylcholine (ACh) plays a critical role in brain circuits mediating motor control, attention, learning and memory. Cholinergic dysfunction is associated with multiple brain disorders including Alzheimer’s Disease, addiction, schizophrenia and Attention-Deficit Hyperactivity Disorder (ADHD). The presynaptic choline transporter (CHT, SLC5A7) is the major, rate-limiting determinant of ACh production in the brain and periphery and is consequently upregulated during tasks that require sustained attention. Given the contribution of central cholinergic circuits to the control of movement and attention, we hypothesized that functional CHT gene variants might impact risk for ADHD. We performed a case-control study, followed by family-based association tests on a separate cohort, of two purportedly functional CHT polymorphisms (coding variant Ile89Val (rs1013940) and a genomic SNP 3’ of the CHT gene (rs333229), affording both a replication sample and opportunities to reduce potential population stratification biases. Initial genotyping of pediatric ADHD subjects for two purportedly functional CHT alleles revealed a 2–3 fold elevation of the Val89 allele (n = 100; P = 0.02) relative to healthy controls, as well as a significant decrease of the 3’SNP minor allele in Caucasian male subjects (n = 60; P = 0.004). In family based association tests, we found significant overtransmission of the Val89 variant to children with a Combined subtype diagnosis (OR = 3.16; P = 0.01), with an increased Odds Ratio for a haplotype comprising both minor alleles. These studies show evidence of cholinergic deficits in ADHD, particularly for subjects with the Combined subtype, and, if replicated, may encourage further consideration of cholinergic agonist therapy in the disorder.Electronic supplementary materialThe online version of this article (doi:10.1007/s11689-009-9033-8) contains supplementary material, which is available to authorized users.

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“…It has been suggested that dysfunctions of dopaminergic systems in the brain contribute to the pathogenetic basis of ADHD, because the amount of dopamine is reduced in the striatum and prefrontal cortex of ADHD patients [3], and methylphenidate (MPH), a dopamine transporter inhibitor, reverses the down-regulation of dopamine in these areas and improves abnormal behavior in ADHD patients [4]. Moreover, serotonergic and cholinergic dysfunctions also contribute to the development of ADHD [5, 6]. There are genetic and environmental factors for the onset of ADHD; the former includes various genetic variations such as in the dopamine transporter [7–9] and receptors [10, 11], serotonin 5-HT 2A receptor [12], and N-methyl-D-aspartate glutamate receptor subunit [13].…”

Section: Introductionmentioning

confidence: 99%

Daily administration of yokukansan and keishito prevents social isolation-induced behavioral abnormalities and down-regulation of phosphorylation of neuroplasticity-related signaling molecules in mice

Fujiwara

Han

Awale

et al. 2017

BMC Complement Altern Med

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BackgroundOur previous studies demonstrated that post-weaning social isolation (ISO) in mice induces behavior abnormalities such as deficits of sociability- and attention-like behaviors. These deficits can be attenuated by methylphenidate (MPH), a drug used for attention deficit hyperactivity disorder (ADHD), suggesting that ISO mice offer a potential animal model of comorbid developmental disorder with ADHD and autism spectrum disorder symptoms. This study investigated the effects of Kampo formulae, yokukansan (YKS) and keishito (KST), on the neuropsychiatric symptoms of ISO mice to clarify the therapeutic or preventive/delaying potential of these formulae for the treatment of neurodevelopmental disorders.MethodsThree-to-4-week old male ICR mice were socially isolated during an experimental period and YKS and KST (1523.6 and 2031.8 mg/kg, p.o.) was administered starting from week 2 and week 0 after starting ISO for the analysis of their therapeutic and preventive/delaying potentials, respectively. Sociability, attention-related behavior and fear memory were elucidated by a 3 chamber test, a water-finding test and fear conditioning test, respectively. Moreover, the phosphorylation of neuroplasticity-related signaling molecules in mice hippocampus was analyzed using western blotting.ResultsIn a therapeutic procedure, YKS ameliorated ISO-induced impairments of attention-like behavior and context-dependent fear memory, but not of sociability, whereas KST had no beneficial effects in ISO mice. In experiments to analyze the preventive/delaying potentials of these treatments, both YKS and KST improved sociability, attention, and context-dependent fear memory deficits. The improvement of sociability in mice by YKS and KST was not inhibited by a dopamine D1 receptor antagonist, suggesting that YKS and KST improved the ISO-induced sociability deficit by other mechanisms besides activation of the dopaminergic system. On the other hand, the beneficial effects of YKS and KST on attention-like behavior were inhibited by a muscarinic antagonist, suggesting that YKS and KST ameliorated ISO-induced attention-like behavior through a cholinergic mechanism. Moreover, the phosphorylated forms of CaMKII and CREB were down-regulated by ISO stress and restored by YKS and KST administration.ConclusionsThese findings suggest that YKS and KST may be useful for the improvement of neurodevelopmental disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-017-1710-7) contains supplementary material, which is available to authorized users.

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Neurocognitive deficits in major depression and a new theory of ADHD: A model of impaired antagonism of cholinergic-mediated prepotent behaviours in monoamine depleted individuals

Cited by 20 publications

References 60 publications

The EEG as an index of neuromodulator balance in memory and mental illness

The EEG as an index of neuromodulator balance in memory and mental illness

Choline transporter gene variation is associated with attention-deficit hyperactivity disorder

Daily administration of yokukansan and keishito prevents social isolation-induced behavioral abnormalities and down-regulation of phosphorylation of neuroplasticity-related signaling molecules in mice

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