The intensity dependence of the auditory evoked N1 component as a predictor of reponse to Citalopram treatment in patients with major depression

doi:10.1016/j.neulet.2004.06.038

Neuroscience Letters

Volume 367, Issue 3, 9 September 2004, Pages 375-378

https://doi.org/10.1016/j.neulet.2004.06.038 Get rights and content

Abstract

The intensity dependence of the auditory evoked N1 ERP component (IDAP) has been suggested as an indicator of central serotonergic neurotransmission with relevance to pharmacological treatment. We report the results of a study evaluating the IDAP in 16 in-patients fulfilling DSM-IV criteria for major depressive episode in the course of treatment with the SSRI Citalopram. Our data revealed a significant correlation between the intensity slopes of the N1 amplitude prior to Citalopram treatment and treatment response: patients with higher intensity slopes of N1 amplitude showed a significantly stronger decrease of HDRS-Score after Citalopram treatment than patients within the lower intensity slope ranges. Our results indicate an association of N1 amplitude intensity dependence with response to antidepressant treatment with Citalopram.

Section snippets

Acknowledgements

The authors are grateful to Arndt Hesse, R. Windelschmidt, R. Franzke, Nora Löbbecke and Oliver Ligneth-Dahm for help in data collection and to Prof. M. Gastpar for support.

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Management of Major Depressive Disorder (MDD) might be improved by a biomarker to predict whether a selected medication is likely to lead to remission. We previously reported on a quantitative electroencephalogram-based biomarker, the Antidepressant Treatment Response (ATR) index, that integrated recordings at baseline and after one week of treatment. The present study prospectively tested whether treatment directed by the biomarker increased the likelihood of remission; we hypothesized that continued treatment with a drug predicted to lead to remission (i.e., high ATR values) would be associated with better outcomes than if the drug was predicted not to lead to remission (i.e., low ATR values). We enrolled 180 adult outpatients with unipolar MDD from the community. After one week of escitalopram treatment to determine the biomarker, stratified randomization (high vs. low ATR) was used to assign subjects to either continued escitalopram or a switch to bupropion as a blinded control condition, for seven additional weeks. For the 73 evaluable subjects assigned to continued escitalopram treatment, the remission rate was significantly higher for those in whom ATR had predicted remission versus non-remission (60.4% vs. 30.0%, respectively, p = 0.01). Accuracy was enhanced by combining 1-week depressive symptom change with ATR (68.6% vs 28.9%). This prospective validation study supports further development of the ATR biomarker, alone or together with early symptom change, to improve care by identifying individuals unlikely to remit with their current treatment, and support the decision to change treatment after one week rather than after failing a full, prolonged course of medication.
The loudness dependence of auditory evoked potentials as an electrophysiological marker of central serotonergic neurotransmission: implications for clinical psychiatry and psychopharmacotherapy
2020, Handbook of Behavioral Neuroscience
The serotonergic system plays a crucial role in the pathophysiology of various psychiatric disorders, including major depression, obsessive-compulsive disorder, anxiety disorders, and schizophrenia (Lucki, 1998). Therefore, reliable indicators of central serotonergic neurotransmission, particularly of synaptically released serotonin, are of high clinical relevance for diagnostic and therapeutic purposes (Hegerl, Gallinat, & Juckel, 2001). Such an indicator could help to identify individual patients with a serotonergic dysfunction and to select more specific pharmacological interventions that are associated with better treatment outcome. Peripheral functional measures such as monoamine or monoamine metabolite levels in serum and cerebrospinal fluid have been shown to be nonspecific as they only partially reflect central serotonergic activity (Murphy, 1990; Potter & Manji, 1993). In the following years, research efforts focused on neurophysiological measures to assess central serotonergic function. In particular, preclinical and clinical studies in animals and humans indicated that the loudness dependence of auditory evoked potentials is related to the serotonergic neurotransmission in the primary auditory cortex and might therefore be a promising in vivo biomarker of central serotonergic activity.
Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): Rationale and design
2016, Journal of Psychiatric Research
Remission rates for Major Depressive Disorder (MDD) are low and unpredictable for any given antidepressant. No biological or clinical marker has demonstrated sufficient ability to match individuals to efficacious treatment. Biosignatures developed from the systematic exploration of multiple biological markers, which optimize treatment selection for individuals (moderators) and provide early indication of ultimate treatment response (mediators) are needed. The rationale and design of a multi-site, placebo-controlled randomized clinical trial of sertraline examining moderators and mediators of treatment response is described. The target sample is 300 participants with early onset (≤30 years) recurrent MDD. Non-responders to an 8-week trial are switched double blind to either bupropion (for sertraline non-responders) or sertraline (for placebo non-responders) for an additional 8 weeks. Clinical moderators include anxious depression, early trauma, gender, melancholic and atypical depression, anger attacks, Axis II disorder, hypersomnia/fatigue, and chronicity of depression. Biological moderator and mediators include cerebral cortical thickness, task-based fMRI (reward and emotion conflict), resting connectivity, diffusion tensor imaging (DTI), arterial spin labeling (ASL), electroencephalograpy (EEG), cortical evoked potentials, and behavioral/cognitive tasks evaluated at baseline and week 1, except DTI, assessed only at baseline. The study is designed to standardize assessment of biomarkers across multiple sites as well as institute replicable quality control methods, and to use advanced data analytic methods to integrate these markers. A Differential Depression Treatment Response Index (DTRI) will be developed. The data, including biological samples (DNA, RNA, and plasma collected before and during treatment), will become available in a public scientific repository.
Clinical Trial Registration: Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC).
Identifier: NCT01407094.
URL: http://clinicaltrials.gov/show/NCT01407094.
The Loudness Dependence of Auditory Evoked Potentials (LDAEP) in individuals at risk for developing bipolar disorders and schizophrenia
2016, Clinical Neurophysiology
The Loudness Dependence of Auditory Evoked Potentials (LDAEP) is considered as an indicator of central serotonergic activity. Alteration of serotonergic neurotransmission was reported in bipolar disorders and schizophrenia. In line with previous reports on clinically manifest disorders, we expected a weaker LDAEP in subjects at risk for bipolar disorders and schizophrenia compared to healthy controls.
We analyzed LDAEP of individuals at risk for developing bipolar disorders (n = 27), with high-risk status (n = 74) and ultra-high-risk status for schizophrenia (n = 86) and healthy controls (n = 47).
The LDAEP did not differ between subjects at risk for schizophrenia or bipolar disorders and controls. Among subjects without medication (n = 122), the at-risk-bipolar group showed a trend towards a weaker LDAEP than both the high-risk and the ultra-high-risk groups for schizophrenia.
The LDAEP did not appear as a vulnerability marker for schizophrenia or bipolar disorders. This suggests that an altered LDAEP may not be measurable until the onset of clinically manifest disorder. However, the hypothesis that pathogenic mechanisms leading to bipolar disorders may differ from those leading to schizophrenia is supported.
This is the first study investigating LDAEP in a population at risk for bipolar disorders.
Spatiotemporal properties of auditory intensity processing in multisensor MEG
2014, NeuroImage
Citation Excerpt :
While studies about treatment response prediction are promising in LDAEP research, the optimal used analysis method is still debated (Jaworska et al., 2013; Mulert et al., 2002; Park et al., 2011). However, scalp measured potentials, for instance at Cz, might reflect serotonergic modulated responses from both the PAC and the PCC (e.g. Linka et al., 2004). To our knowledge, there exists no study investigating a modulatory effect of the 5-HT system on the PMC.
Loudness dependence of auditory evoked potentials (LDAEP) evaluates loudness processing in the human auditory system and is often altered in patients with psychiatric disorders. Previous research has suggested that this measure may be used as an indicator of the central serotonergic system through the highly serotonergic innervation of the auditory cortex.
However, differences among the commonly used analysis approaches (such as source analysis and single electrode estimation) may lead to different results. Putatively due to discrepancies of the underlying structures being measured. Therefore, it is important to learn more about how and where in the brain loudness variation is processed.
We conducted a detailed investigation of the LDAEP generators and their temporal dynamics by means of multichannel magnetoencephalography (MEG). Evoked responses to brief tones of five different intensities were recorded from 19 healthy participants. We used magnetic field tomography in order to appropriately localize superficial as well as deep source generators of which we conducted a time series analysis.
The results showed that apart from the auditory cortex other cortical sources exhibited activation during the N1/P2 time window. Analysis of time courses in the regions of interest revealed a sequential cortical activation from primary sensory areas, particularly the auditory and somatosensory cortex to posterior cingulate cortex (PCC) and to premotor cortex (PMC). The additional activation within the PCC and PMC has implications on the analysis approaches used in LDAEP research.
Clinical implications of loudness dependence of auditory evoked potentials in patients with atypical depression
2014, Progress in Neuro-Psychopharmacology and Biological Psychiatry
The loudness dependence of auditory evoked potentials (LDAEP) has been proposed as a useful biomarker of serotonin activity, and the LDAEP value is low in patients with melancholic depression. In this study, we evaluated LDAEP levels in patients with atypical depression.
We recruited 53 patients with atypical depression and 68 patients with non-atypical depression. Subjects were evaluated by the Atypical Depression Diagnostic Scale (ADDS), Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety (HAMA), Beck Scale for Suicidal Ideation (BSI), Behavioral Inhibition System and Behavioral Activation System (BIS/BAS) scales, and Hypomanic Personality Scale (HPS). To determine LDAEP, the peak-to-peak N1/P2 was measured at five stimulus intensities and the LDAEP was calculated as the linear-regression slope.
Patients with atypical depression had stronger LDAEP values and higher BAS and HPS scores than those with non-atypical depression. LDAEP showed a pattern of gradual decrease according to ADDS score hierarchy in patients with major depressive disorder. In the atypical depression group, LDAEP showed significant negative correlation with the BSI score and significant positive correlation with BAS score. In the non-atypical depression group, LDAEP did not show any significant correlations with the scores of psychological scales.
Our results suggest that there is a relatively deficient serotonergic activity in patients with atypical depression and that LDAEP reflects mood reactivity. The transient drop of serotonergic activity induced by mood vulnerability might contribute to suicidal tendencies in patients with atypical depression.

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The intensity dependence of the auditory evoked N1 component as a predictor of reponse to Citalopram treatment in patients with major depression

Abstract

Section snippets

Acknowledgements

Neuropsychopharmacology

Neuropsychopharmacology

Neuropsychopharmacology

An inventory for measuring depression

Arch. Gen. Psychiatry

Sensation seeking and affective disorders: characteristics in the intensity dependence of acoustic evoked potentials

Neuropsychobiology

Stimulus intensity control and the cortical evoked response

Psychosom. Med.

Electrophysiological evidence of serotonergic impairment in long-term MDMA (“ecstasy”) users

Am. J. Psychiatry

The loudness dependency of the auditory evoked N1/P2-component as a predictor of the acute SSRI response in depression

Psychopharmacology (Berl.)

Development of a rating scale for primary depressive illness

Br. J. Soc. Clin. Psychol.

The serotonin syndrome scale: first results on validity

Eur. Arch. Psychiatry Clin. Neurosci.

The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans

Pharmacopsychiatry