A Homer 1 gene variant influences brain structure and function, lithium effects on white matter, and antidepressant response in bipolar disorder: A multimodal genetic imaging study

Benedetti, Francesco; Poletti, Sara; Locatelli, Clinio; Mazza, Elena; Lorenzi, Cristina; Vitali, A; Riberto, Martina; Brioschi, S.; Vai, Benedetta; Bollettini, Irene; Melloni, Elisa; Aggio, Veronica; Falini, Andrea; Bartolomeis, Andrea de; Colombo, Cristina

doi:10.1016/j.pnpbp.2017.10.011

Cited by 57 publications

(21 citation statements)

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“…Moreover, the clinical effects of SD are influenced by gene variants affecting the efficiency of catechol‐O‐methyltransferase (COMT) in clearing NA and DA from the synapse (Benedetti, Barbini, et al., ), again with effect sizes comparable to those observed for response to antidepressant drugs (Benedetti, Colombo, Pirovano, Marino, & Smeraldi, ; Benedetti, Dallaspezia, et al., ). (d) Concerning glutamate, the decrease of glutamate/glutamine levels in the ACC after repeated SD is proportional to the antidepressant response (Benedetti, Calabrese, et al., ), and gene variants affecting post‐synaptic scaffolding proteins for glutamate‐mediated synaptic plasticity influence its efficacy (Benedetti et al., ). (e) Concerning clock genes, variants of hPER3 affect efficacy (Dallaspezia et al., ).…”

Section: Where Are We Today?mentioning

confidence: 99%

Perspectives in affective disorders: Clocks and sleep

Wirz‐Justice

Benedetti

2019

Eur J of Neuroscience

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Mood disorders are often characterised by alterations in circadian rhythms, sleep disturbances and seasonal exacerbation. Conversely, chronobiological treatments utilise zeitgebers for circadian rhythms such as light to improve mood and stabilise sleep, and manipulations of sleep timing and duration as rapid antidepressant modalities. Although sleep deprivation (“wake therapy”) can act within hours, and its mood‐elevating effects be maintained by regular morning light administration/medication/earlier sleep, it has not entered the regular guidelines for treating affective disorders as a first‐line treatment. The hindrances to using chronotherapeutics may lie in their lack of patentability, few sponsors to carry out large multi‐centre trials, non‐reimbursement by medical insurance and their perceived difficulty or exotic “alternative” nature. Future use can be promoted by new technology (single‐sample phase measurements, phone apps, movement and sleep trackers) that provides ambulatory documentation over long periods and feedback to therapist and patient. Light combinations with cognitive behavioural therapy and sleep hygiene practice may speed up and also maintain response. The urgent need for new antidepressants should hopefully lead to reconsideration and implementation of these non‐pharmacological methods, as well as further clinical trials. We review the putative neurochemical mechanisms underlying the antidepressant effect of sleep deprivation and light therapy, and current knowledge linking clocks and sleep with affective disorders: neurotransmitter switching, stress and cortico‐limbic reactivity, clock genes, cortical neuroplasticity, connectomics and neuroinflammation. Despite the complexity of multi‐system mechanisms, more insight will lead to fine tuning and better application of circadian and sleep‐related treatments of depression.

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Section: Where Are We Today?mentioning

confidence: 99%

Perspectives in affective disorders: Clocks and sleep

Wirz‐Justice

Benedetti

2019

Eur J of Neuroscience

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“…Recent studies frequently report that volumetric decreases and functional activity of the midline “core” subnetwork predict antidepressant response. Anteriorly, larger baseline rACC/mPFC volume is significantly associated with response to fluoxetine [43], chronotherapeutics [44], and internet-based cognitive therapy [45]. In older adults, rACC volume [46] and white mater integrity is positively correlated with escitalopram response and improvements in negative self-referential rumination [47].…”

Section: Brain Network Biomarkers Of Antidepressant Responsementioning

confidence: 99%

“…However, baseline dACC hyperactivity correctly classified escitalopram response at roughly 70% accuracy [86]. Baseline dACC hyperactivity during emotion processing has also significantly correlated to antidepressant response to chronotherapeutics [44] and venlafaxine [88] with comparable classification accuracy.…”

Section: Brain Network Biomarkers Of Antidepressant Responsementioning

confidence: 99%

Intrinsic Brain Network Biomarkers of Antidepressant Response: a Review

Dunlop

Talishinsky

Liston

2019

Curr Psychiatry Rep

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Purpose of Review Poor treatment response is a hallmark of major depressive disorder. To tackle this problem, recent neuroimaging studies have sought to characterize antidepressant response in terms of pretreatment differences in intrinsic functional brain networks. Our aim is to review recent studies that predict antidepressant response using intrinsic network connectivity. We discuss current methodological limitations and directions for future antidepressant biomarker studies. Recent Findings Functional connectivity stemming from the subgenual and rostral anterior cingulate has shown particular consistency in predicting antidepressant response. Differences in this connectivity may prove fruitful in differentiating treatment responders to many antidepressant interventions. Future biomarker studies should integrate biological MDD subtypes to address the disorder’s inherent clinical heterogeneity. Summary These clinical and scientific advancements have the potential to address this population marked by limited treatment response. Methodological considerations, including patient selection, response criteria, and model overfitting, will require future investigation to ensure that biomarkers generalize for prospective prediction of treatment response.

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“…A fine-tuned modulation of Homer1a expression has been associated to a number of mechanisms of adaptation to different environmental and pharmacological stressors: for instance, Homer1a overexpression in cortical structures may facilitate the ability to cope with stress (Szumlinski et al, 2006 ). Finally, Homer1 gene variants have been associated with neuropsychiatric disorders such as psychosis in Parkinson disease (De Luca et al, 2009 ), major depression pathophysiology (Serchov et al, 2016 ), and response to lithium treatment (Benedetti et al, 2018 ).…”

Section: Modulation By Antipsychotics Of Iegs Involved In Synaptic Plmentioning

confidence: 99%

Immediate-Early Genes Modulation by Antipsychotics: Translational Implications for a Putative Gateway to Drug-Induced Long-Term Brain Changes

Bartolomeis

Buonaguro

Latte

et al. 2017

Front. Behav. Neurosci.

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An increasing amount of research aims at recognizing the molecular mechanisms involved in long-lasting brain architectural changes induced by antipsychotic treatments. Although both structural and functional modifications have been identified following acute antipsychotic administration in humans, currently there is scarce knowledge on the enduring consequences of these acute changes. New insights in immediate-early genes (IEGs) modulation following acute or chronic antipsychotic administration may help to fill the gap between primary molecular response and putative long-term changes. Moreover, a critical appraisal of the spatial and temporal patterns of IEGs expression may shed light on the functional “signature” of antipsychotics, such as the propensity to induce motor side effects, the potential neurobiological mechanisms underlying the differences between antipsychotics beyond D2 dopamine receptor affinity, as well as the relevant effects of brain region-specificity in their mechanisms of action. The interest for brain IEGs modulation after antipsychotic treatments has been revitalized by breakthrough findings such as the role of early genes in schizophrenia pathophysiology, the involvement of IEGs in epigenetic mechanisms relevant for cognition, and in neuronal mapping by means of IEGs expression profiling. Here we critically review the evidence on the differential modulation of IEGs by antipsychotics, highlighting the association between IEGs expression and neuroplasticity changes in brain regions impacted by antipsychotics, trying to elucidate the molecular mechanisms underpinning the effects of this class of drugs on psychotic, cognitive and behavioral symptoms.

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A Homer 1 gene variant influences brain structure and function, lithium effects on white matter, and antidepressant response in bipolar disorder: A multimodal genetic imaging study

Cited by 57 publications

References 80 publications

Perspectives in affective disorders: Clocks and sleep

Perspectives in affective disorders: Clocks and sleep

Intrinsic Brain Network Biomarkers of Antidepressant Response: a Review

Immediate-Early Genes Modulation by Antipsychotics: Translational Implications for a Putative Gateway to Drug-Induced Long-Term Brain Changes

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