An electrophysiological model of major depression: Relevance to clinical subtyping and pharmacological management

Cerda, Ivo H.; Fitzgerald, Paul J.

doi:10.1016/j.psychres.2021.114054

Cited by 4 publications

(3 citation statements)

References 97 publications

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“…Acute treatment of healthy male subjects with cortisol resulted in reduced FAA and inhibition of approach motivation, where this effect was maximal at F7/8 [ 25 ]. It has been suggested that cortisol is functionally opposed to norepinephrine in vivo [ 71 ], so one possibility is that this effect of acute cortisol on FAA was in part mediated by inhibition of noradrenergic signaling. In undergraduates exposed to exam stress, EEG measures taken before the exam revealed that reduced FAA was associated with a higher cortisol level after awakening, where this effect was present at F7/8 [ 26 ].…”

Section: Cortisol and Faamentioning

confidence: 99%

“…We suggest here a revised hypothesis: there may be two principal electrophysiological subtypes of MDD, one characterized by reduced FAA and high serotonin (and relatively low norepinephrine), the other by increased FAA and high norepinephrine (as well as relatively low serotonin). In this scenario, the high serotonin type may be a variant of melancholic depression, and the high norepinephrine type a variant of atypical depression [ 71 ]. An overarching principle of this hypothesis is that extreme activation of either the right or left frontal cortex promotes MDD and its symptomatology, consistent with a number of the studies reviewed above [ 39 , 40 ].…”

Section: Proposed Depressive Subtypes and Hemispheric Lateralizationmentioning

confidence: 99%

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Frontal Alpha Asymmetry and Its Modulation by Monoaminergic Neurotransmitters in Depression

Fitzgerald

2024

Clin Psychopharmacol Neurosci

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Frontal alpha asymmetry (FAA) is an electroencephalography (EEG) measure that quantifies trait-like left versus right hemisphere lateralization in alpha power. Increased FAA indicates relatively greater left than right frontal cortex activation and is associated with enhanced reward-related approach behaviors rather than avoidance or withdrawal. Studies dating back several decades have often suggested that having greater FAA supports enhanced positive affect and protection against major depressive disorder (MDD), whereas having greater right frontal activation (i.e., reduced FAA) is associated with negative affect and risk for MDD. While this hypothesis is widely known, a number of other studies instead have found increased FAA in MDD, or evidence that either leftward or rightward bias in FAA is associated with depression. Here we briefly review the literature on leftward or rightward lateralization in FAA in MDD, and find much evidence that MDD is not always characterized by reduced FAA. We also review the limited literature on FAA and monoaminergic neurotransmitter systems, including pharmacologic agents that act on them. Studies of serotonin in particular provide genetic and pharmacologic evidence for modulation of FAA, where some of these data may suggest that serotonin reduces FAA. In a synthesis of the collective literature on FAA and the monoamines, we suggest that serotonin and norepinephrine may differentially affect FAA, with serotonin tending to promote right frontal activation and norepinephrine biased toward left frontal activation. These putative differences in frontal lateralization may influence MDD phenotypes or potential subtypes of the disorder, and suggest pharmacologic treatment strategies.

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Section: Cortisol and Faamentioning

confidence: 99%

Section: Proposed Depressive Subtypes and Hemispheric Lateralizationmentioning

confidence: 99%

Frontal Alpha Asymmetry and Its Modulation by Monoaminergic Neurotransmitters in Depression

Fitzgerald

2024

Clin Psychopharmacol Neurosci

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“…This is more difficult in human subjects, except upon extreme surgical procedures. However, some biomarkers can be used to determine the effects of various antidepressant such as electroencephalography (Cerda et al, 2021;Eckermas et al, 2023;Schwartzmann et al, 2023;Ort et al, 2023;Duerler et al, 2023), diffusivity/brain volume/synaptic density/neuroplasticity (Jorgensen et al, 2016;Lewis et al, 2020;Raval et al, 2021;Vargas et al, 2023), various imaging techniques, such as PET or FDG-PET (Vollenweider et al, 1997a(Vollenweider et al, , 1997b(Vollenweider et al, , 1997cCarhart Harris et al, 2014;Jorgensen et al, 2013Jorgensen et al, , 2017 or near infrared spectroscopy (Scholkmann and Vollenweider, 2023). When it comes to imaging, numerous PET ligands have been developed for SERT and various 5-HT receptors, but most of these radioligands are 5-HT receptor antagonists or SSRIs.…”

Section: Introductionmentioning

confidence: 99%

On serotonin, psychedelics, entactogens and psychoplastogens in depression, anxiety, post-traumatic stress, and related disorders.

Hoyer

2024

Preprint

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There is controversy about a causal role of serotonin (5-HT) in depression, some arguing that there is no proof for impaired brain 5-HT function in depressed patients. Major depressive disorder comes with multiple endophenotypes; not surprisingly classical antidepressants (tricyclics, MAO inhibitors, SSRIs, SNRIs) are not universally effective. Most antidepressants target the 5-HT system, partially if not exclusively, but treatment-resistant depression (TRD) remains a major issue. The most recent and heavily investigated class of potential rapid acting antidepressant, anxiolytic, and/or anti PTSD drugs, namely psychedelics (psilocybin, LSD, DMT, ayahuasca, etc..) or entactogens (MDMA, ibogaine), all target the 5-HT system, at least in part. Phase II / III clinical trials support psychedelics- and/or MDMA-assisted psychotherapy as a new class of rapid acting treatments for GAD, MDD, TRD, PTSD, and other disorders. Psilocybin and MDMA have FDA breakthrough status for TRD/MDD and PTSD, respectively, whereas LSD just received FDA breakthrough status for GAD. All psychedelics act as 5-HT2A receptor agonists, although LSD, DMT, psilocybin may also target other 5-HT and/or dopamine receptors. Psychedelics produce rapid onset and long-lasting antidepressant effects after one or two administrations. They all promote synaptogenesis and synaptic plasticity. Neuroinflammation plays a major role in anxiety, depression, PTSD. Interestingly, psychedelic-induced 5-HT2A receptor agonism has profound anti-(neuro)inflammatory effects. Altogether, the 5-HT system plays an essential, but not unique role in MDD and related disorders. MDD, TRD and PTSD may be considered as biochemical, neurological and immune conditions, given the emerging role of neuroplasticity and neuroinflammation, which until recently, have been overlooked.

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Affective disorders and the loudness dependence of the auditory evoked potential: Serotonin and beyond

Fitzgerald

2024

Neuroscience Letters

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An electrophysiological model of major depression: Relevance to clinical subtyping and pharmacological management

Cited by 4 publications

References 97 publications

Frontal Alpha Asymmetry and Its Modulation by Monoaminergic Neurotransmitters in Depression

Frontal Alpha Asymmetry and Its Modulation by Monoaminergic Neurotransmitters in Depression

On serotonin, psychedelics, entactogens and psychoplastogens in depression, anxiety, post-traumatic stress, and related disorders.

Affective disorders and the loudness dependence of the auditory evoked potential: Serotonin and beyond

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