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ORIGINAL ARTICLE
Year : 2022  |  Volume : 31  |  Issue : 2  |  Page : 243-247  Table of Contents     

Comparative change in P300 indices following antidepressant treatment in patients with major depressive disorder


1 Department of Physiology, AIIMS, Bhopal, Madhya Pradesh, India
2 Department of Psychiatry, AIIMS, Bhopal, Madhya Pradesh, India

Date of Submission13-Oct-2021
Date of Acceptance17-Jan-2022
Date of Web Publication08-Aug-2022

Correspondence Address:
Dr. Sandip Meghnad Hulke
Department of Physiology, AIIMS, Bhopal, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ipj.ipj_214_21

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   Abstract 


Context: Cognitive disturbance is seen in patients with major depressive disorder (MDD). Event-related potential can assist in measuring the neurocognition, and P300 is the most commonly used noninvasive electrophysiological parameter for measuring cognition. Aims: The aim of this study is to assess the baseline P300 parameters, Hamilton Rating Scale for Depression (HAM-D), and Montgomery–Asberg Depression Rating Scale (MADRS) scores and compare them with their levels after 3 months of antidepressant therapy. Settings and Design: a longitudinal study was done on total 24 diagnosed cases of major depression who underwent P300, HAM-D, and MADRS assessment in the gap of 3 months before and after starting antidepressant therapy. Subjects and Methods: Newly diagnosed cases of MDD patients were assessed using HAM-D and MADRS for severity rating. P300 assessment was also carried out with auditory oddball paradigm using Nihon Kohden NCV-SMG-EP system. The assessments were repeated after 3 months of antidepressant treatment. Statistical Analysis Used: The Wilcoxon test was used to compare mean values of P300 parameters, HAM-D, and MADRS score. Spearman correlation analysis was done to study the association between various parameters of P300 and HAM-D and MADRS score before and after treatment of 3 months of antidepressant therapy. Results: Significant difference is shown in various parameters P300 except for A11-P300 amplitude and A31-P300 amplitude. A significant difference was shown in HAM-D and MADRS scores. No significant correlation was seen between other P300 parameters and HAM-D and MADRS scale before as well as after antidepressant therapy. Conclusions: P300 may be used as an index to evaluate the response to antidepressant treatment in patients with MDD.

Keywords: Hamilton Rating Scale for Depression, major depressive disorder, Montgomery–Asberg Depression Rating Scale


How to cite this article:
Wakode SL, Hulke SM, Sutar R, Thakare AE. Comparative change in P300 indices following antidepressant treatment in patients with major depressive disorder. Ind Psychiatry J 2022;31:243-7

How to cite this URL:
Wakode SL, Hulke SM, Sutar R, Thakare AE. Comparative change in P300 indices following antidepressant treatment in patients with major depressive disorder. Ind Psychiatry J [serial online] 2022 [cited 2022 Dec 2];31:243-7. Available from: https://www.industrialpsychiatry.org/text.asp?2022/31/2/243/353554



P300 is a long latency evoked potential and is also referred to as cognitive evoked potential or event-related potential (ERP). It is a positive wave located chiefly centrally around the parietocentral region of the scalp, elicited by the subject's active involvement in task processing, appearing at around 250–600 ms (average 300 ms). It is regarded as the marker of the cognitive abilities of the subjects.[1] P300 is an electrophysiological test that can be recorded in a noninvasive way. P300 is the objective test where we get latency and amplitude of the ERP.

Depression may be associated with cognitive disturbances. It is considered to be a core symptom of depression.[2],[3] Pseudodementia is often labeled to the cognitive disturbances in depressed patients.[4] Antidepressant medications, psychotherapy, and neuromodulation which are used as a form of treatment in depression have shown improved cognition.[5]

Cognitive assessment may be done objectively by P300. In various cross-sectional studies, P300 was found to be prolonged in patients with major depression.[6],[7],[8] However, there are very few longitudinal studies in this regard and also limited studies are available in the Indian population. There has been no uniform agreement in the findings of P300 and further studies have been recommended.[9],[10]

Major depressive disorder (MDD) patients are assessed clinically as well as by rating scales. Hamilton Rating Scale for Depression (HAM-D) and Montgomery–Asberg Depression Rating Scale (MADRS) have been most commonly used for rating the severity of depression and have demonstrated adequate reliability and validity for assessing depressive symptoms.[11] HAM-D score was converted to MADRS score and vice versa in the patients of MDDs. Percent reduction in one scale was corresponding to another scale.[12] In the present study, both scales were used so as to increase accuracy for grading the severity of depression. Two or more scales were used assesses response to treatment and grading of severity of depression.[13],[14]

With this study, we had attempted to see whether P300 can be used as an index to evaluate the response to treatment in patients with major depression. A longitudinal study was planned to see the effect of 3 months of antidepressant therapy on P300, HAM-D, and MADRS scales were to grade the severity of depression.


   Subjects and Methods Top


This was an intervention study with pre- and postdesign conducted by the department of physiology in collaboration with the department of psychiatry in a medical college in Central India. The study was conducted giving due consideration to guidelines for reporting observational studies.[15] Study involved 24 number of patients diagnosed with major depression. Initially, 49 patients were recruited for the study, however, 25 patients were lost during follow-up. The study was carried out by recruiting consecutive new patients with a diagnosis of unipolar major depression of any severity requiring outpatient clinical management from the psychiatry outpatient clinic. The diagnosis was made using clinical interviews, mental status examination, and Structured Clinical Interviews for Diagnostic and Statistical Manual of Mental Disorders 4th-Text Revision diagnoses.

Consecutive patients treated with antidepressants were referred by the psychiatrist for cognitive assessment after written informed consent. Patients with a history of prior exposure to antidepressants, comorbid seizure disorder, substance use (except nicotine), and patients with hearing impairment were excluded. To maintain the homogeneity of the treatment effect, the patients receiving add-on cognitive-behavior therapy, complementary and alternative medicine, and other treatment for improving depression were excluded from the study.

After written informed consent, they were further assessed on HAM-D and MADRS by psychiatrist and assessment of P300 using Nihon Kohden NCV-SMG-EP system in the department of physiology.

All the patients were reassessed 3 months after starting the treatment, and comparisons between the mean scores of P300, HAM-D, and MADRS score at baseline and after 3 months were carried out.

P300 assessment would be done using the Nihon Kohden NCV-SMG-EP system. P300 was recorded using standard procedure, and auditory oddball paradigm was used. Fpz was used as a grounding electrode. Reference electrodes were placed on both mastoids. Active electrodes were positioned at Fz, Cz, and Pz for A11, A21, and A31, respectively.[16]

The study was conducted after the approval Research Review Board and Institutional Ethics Committee (IHEC-LOP/2018/IM0188, dated July 11th, 2018).

Statistical analysis

Statistical analysis was done using statistical software Systac version 13 Starcom Information Technology Limited, Banglore, India. The Wilcoxon test was used to compare mean values of P300 parameters, HAM-D, and MADRS score. Spearman correlation analysis was done to study the association between various parameters of P300 and HAM-D and MADRS score before and after treatment of 3 months of antidepressant therapy.


   Results Top


Twenty-four patients completed both the assessments at baseline and after 3 months. The mean age of the participants was 28.1 years (standard deviation ± 7.15). Fourteen were male and ten were female participants. [Table 1] shows the change in latency and amplitude measure of P300 at three sites and HAM-D and MADRS scores at baseline and after 3 months of antidepressant treatment. The significant difference is shown in various parameters P300 except for A11-P300 amplitude and A31-P300 amplitude. A significant difference was also seen in HAM-D and MADRS scores [Table 1]. The distribution of the patients as per the severity of the depression by HAM-D and MADRS score is shown in [Figure 1] and [Figure 2]. The change in P300 latency is depicted in [Figure 3].
Table 1: P300 latencies, amplitude fz (A11), cz (A21), and pz level (A31), (Hamilton Rating Scale for Depression) and. (Montgomery-Asberg Depression Rating Scale) before and after 3 months of antidepressant therapy (n=24)

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Figure 1: Patient distribution as grading Hamilton Rating Scale for Depression score - pretreatment and posttreatment

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Figure 2: Patient distribution as grading MADRS score - pretreatment and posttreatment

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Figure 3: P300 latency before and after treatment. Arrow corresponds y-axis line 4, before treatment P300 is coming after y-axis line 4 while after treatment, it is coming before y-axis line 4

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HAM-D scores dropped from 13.7 to 7.4 indicating moderate depression to remission whereas MADRS scores dropped from 13.7 to 7.7 which indicates continuing mild depression as per the cutoff values. A positive association was observed with Spearman correlation between the difference in HAM-D score with the difference in P300 latencies, and amplitude but it was statistically not significant [Table 2]. Similarly, a positive association was observed with Spearman correlation between the difference in MADRS score with the difference in P300 latencies and amplitude and it was statistically not significant [Table 3].
Table 2: Correlation between the difference in Hamilton Rating Scale for Depression score with the difference in P300 latencies, and amplitude (n=24)

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Table 3: Correlation between the difference in Montgomery-Asberg Depression Rating Scale score with the difference in P300 latencies, and amplitude (n=24)

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   Discussion Top


In the present study, we found a significant reduction in depression scores across two scales as well as a significant difference in neurocognition measured with latencies and amplitudes of P300 before and after starting antidepressant treatment.

Earlier studies have reported the effect of depression on amplitude as well as the latency of ERPs.[6],[7],[17] One study has reported a significant reduction in latency parameter of P300,[8] whereas few studies have reported no change in amplitude of P300 after antidepressant treatment.[7],[18] Few studies have found only significant change in amplitude of P300 but not in latency,[9],[17] whereas others found no significant change in amplitude as well as latency.[10] In the present study, the significant difference in P300 latency fz (A11), cz (A21), pz level (A31), and amplitude cz (A21), whereas no difference was observed across P300 amplitude at (fz-A11) and (pz-A31).

In terms of the relationship between P300 and treatment response, delayed P300 latency was considered to be related to a nonresponse to sertraline treatment of 12 weeks,[18] and no relation between P300 amplitude and treatment response was noticed which is similar to our observation except that fact that we included antidepressants from three different classes that is selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressant. Greater increase in P300 amplitude was associated with positive antidepressant response. In this study, HAM-D and MADRS scores were used to assess the severity of depression and correlation was studied similar to ours. In males, P300 latency correlated positively with baseline HAM-D but P300 amplitude correlated negatively with HAM-D score. No significant correlation was seen in females.[9] In our study, we got the significant change in amplitude as well as latency; however, no significant correlation was seen between the difference in HAM-D score, MADRS score, and P300 parameters. The gender difference was not studied in the present study.

The latency denotes the speed of stimulus classification resulting from the discrimination of one event from another. Shorter latencies suggest superior mental performance. In the superior mental ability, information processing speed is considered to be faster. Latency has been assumed to be a reliable index of the time needed to evaluate and categorize the given stimulus.[19] Amplitude is related to attention; greater attention produces a larger amplitude. A decrease in task involvement may produce a smaller amplitude.[1] Amplitude is considered to represent attention-related inhibition of ongoing brain activity to facilitate the consolidation of the target's mental representation in working memory.[20]

Cognitive deficits are common in patients with MDD in the form of difficulty in focused attention, sustained attention, concentration, complex decision-making, reasoning, processing speed, judgment, and immediate and short-term memory. Few authors have recommended using P300 latency as a measure of severity of depression; however, it was noticed in a study that depressed patients performed the experimental task significantly less accurately than healthy controls while observing no difference in any of the P300 parameters.[21] All these domains of cognitions are difficult to measure individually and P300 latencies and amplitude may not be specific to any of these domains as seen in the present study.[22] Thus, cognition impairment may not be reflected in P300, also there are various simple tests to measure cognition these tests should be done along with P300.[23] Further, P300 recording would be possible at only tertiary care set up, also adding P300 to check cognitive impairment may not be cost-effective. Objective assessment of cognition can be done by P300; however, further studies should be planned where relation of P300 would be correlated with various simple tests of cognition.

HAM-D and MADRS do measure depressive cognitions, suicidal cognitions, and psychomotor cognitions but these domains are not specific to neuropsychological cognitions, therefore correlating domains on these scales with P300 parameters may not accurately reflect the change in the measure of cognitive domains. This may be reason for nonsignificant correlation in the present study. However, this is the first study to observe such a correlation where difference in the scale score was correlated with difference in P300 parameters (before and after treatment).


   Conclusions Top


Thus, to conclude, the author found a significant decrease in depressive and cognitive parameters; however, whether improvement in depressive symptoms after 3 months of antidepressant treatment, improves neurocognition, or there is independent improvement among depressive and cognitive symptoms is difficult to conclude as detailed neuropsychological assessments were not conducted in the current study. Therefore, P300 should also be coupled with the detailed cognitive assessment to look for an independent measure of cognitive improvement in patients with MDD.

We can recommend with caution that P300 may be used as an index to evaluate the response to treatment in patients with major depression. Caution is due small sample size and cost-effectiveness of P300. It is recommended that further longitudinal studies with a larger sample size should be planned, and P300 test must be supplemented with various cognition tests.

Limitations of the study

Small sample size with almost 50% of patients were lost during follow-up. P300 test should be supplemented with detailed cognitive and neurophysiological assessment. Pharmacotherapy was not uniform to all patients in the study. P300 is electrophysiological test which depends on patient cooperation and proper recording techniques. Although we had ensured all these, it may be recommended to do these tests at least two times so as to avoid chances of erroneous results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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