Relationship between Childhood Maltreatment, Suicidality, and Bipolarity: A Retrospective Study

OBJECTIVE: The aims of current study were to determine whether childhood maltreatment contributes to the occurrence of major depressive disorder (MDD) with bipolarity or suicidality. METHODS: In total, 132 outpatients diagnosed with MDD between 2014 and 2015 on the medical records were included. The subjects were divided into two groups according to the presence of childhood maltreatment (CM group) and no childhood maltreatment (NCM group). Depression severity and bipolarity were identified using Beck Depression Inventory (BDI) and the Korean version of Mood Disorder Questionnaire (K-MDQ) respectively on the medical records. In addition, the baseline loud dependence of auditory evoked potentials of 36 patients on medical records were analyzed. RESULTS: The mean total BDI, BDI item 9 (suicide ideation), and total K-MDQ score were significantly higher in the CM group than the NCM group. The number of subjects with bipolarity was significantly higher in the CM than in the NCM group. Furthermore two thirds subjects experienced the significant maltreatment during childhood. The central serotonergic activity of the CM group was also lower than that of the NCM group. CONCLUSION: The findings of this study support that there is a relationship between childhood maltreatment and bipolarity or suicidality in patients with MDD.

How Childhood Maltreatment Is Related to Suicidality, Bipolarity and Central Serotonergic Activity in Patients with Major Depressive Disorder: A Cross-Sectional Pilot Study

OBJECTIVE: The aims of this study were to determine whether childhood maltreatment contributes to the occurrence of major depressive disorder (MDD) with bipolarity, and whether there is a relationship between central serotonergic activity, as assessed using loudness dependence of auditory evoked potentials (LDAEP), and childhood maltreatment. METHODS: Thirty-five MDD patients were stratified according to the presence or absence of childhood trauma into two subgroups, childhood trauma (CT) and no childhood trauma (NCT), using the Korean version of the Childhood Trauma Questionnaire (K-CTQ). The CT group was subjected to further analysis. Several psychometric ratings were also applied. In addition, auditory processing for the loudness dependence of auditory evoked potentials (LDAEP), which was used as a marker of serotonergic activity, was measured before beginning medication. RESULTS: There was a significant difference in total Korean Bipolar Spectrum Disorder Scale score between the CT and NCT groups (t=-2.14, p=0.04). The total K-CTQ score was positively correlated with the total Beck Scale for Suicidal Ideation (BSS) score (r=0.36, p=0.036). In particular, emotional abuse was positively correlated with the total Barratt Impulsiveness Scale (r=0.38, p=0.026), BSS (r=0.38, p=0.025), and Hamilton Depression Rating Scale (HAMD) (r=0.36, p=0.035) scores. There was also a positive correlation between LDAEP and total Hypomania Personality Scale (r=0.49, p=0.02) and HAMD (r=0.58, p=0.004) scores within CT group. CONCLUSION: The findings of this study support that there is a relationship between childhood maltreatment and bipolarity in patients with MDD.

Relationship between Serotonergic Dysfunction Based on Loudness Dependence of Auditory-Evoked Potentials and Suicide in Patients with Major Depressive Disorder

The relationship between suicidality and the loudness dependence of auditory-evoked potentials (LDAEP) remains controversial. This article reviews the literature related to the LDAEP and suicide in patients with major depressive disorder, and suggests future research directions. Serotonergic dysfunction in suicidality seems to be more complicated than was originally thought. Studies of suicide based on the LDAEP have produced controversial results, but it is possible that these are due to differences in study designs and the smallness of samples. For example, some studies have evaluated suicide ideation and the LDAEP, while others have evaluated suicide attempts and the LDAEP. Furthermore, some of the latter studies enrolled acute suicide attempters, while others enrolled those with the history of previous suicide attempts, irrespective of whether these were acute or chronic. Thus, a more robust study design is needed in future studies, for example by evaluating the LDAEP immediately after a suicide attempt rather than in those with a history of suicide attempts and suicide ideation in order to reduce bias. Moreover, genuine suicide attempt, self-injurious behaviors, and faked suicide attempt need to be discriminated in the future.

Chronotype in Relation to Bipolarity, Suicidal Ideation, and Auditory Evoked Potentials in Patients with Major Depressive Disorder : Preliminary Study

OBJECTIVES: The current study investigated the putative relationship between chronotype and suicidality or bipolarity in patients with major depressive disorder (MDD). METHOD: Nineteen outpatients who met the criteria for MDD according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders-text revision were recruited for the current study. The subjects were divided into two subgroups based on their Basic Language Morningness (BALM) scores (dichotomized according to the median BALM score). The Loudness Dependence of Auditory Evoked Potentials (LDAEP) was evaluated by measuring the auditory event-related potentials before beginning medication with serotonergic agents. In addition, K-Mood Disorder Questionaire (K-MDQ), Beck Scale for Suicidal Ideation (BSS), Beck Hopelessness Scale (BHS), Barratt Impulsiveness Scale (BIS) were applied. RESULTS: The K-MDQ, BSS, BHS, BIS score was higher for the eveningness group than for the morningness group. However, the LDAEP, Hamilton Depression Rating Scale, Hamilton Anxiety Scale scores did not differ significantly between them. There were negative correlations between the total BALM score and the total K-MDQ, BSS, and BHS scores (r = -0.64 and p = 0.0033, r = -0.61 and p = 0.0055, and r = -0.72 and p = 0.00056, respectively). CONCLUSIONS: Depressed patients with eveningness are more vulnerable to the suicidality than those with morningness. Eveningness is also associated with bipolarity.

Insomnia in Relation to Suicide and Serotonin in Patients with Major Depressive Disorder / 수면정신생리

OBJECTIVES: The aim of current study is to evaluate the relationship between sleep, suicide and serotonin using some scales and loudness dependence of auditory evoked potentials (LDAEP). METHODS: Total 65 patients who met the criteria for major depressive disorder were enrolled in current study. The patients were divided into two subgroups according to their insomnia and a history of suicide attempts. The auditory event-related potentials were measured to evaluate LDAEP before beginning antidepressants. RESULTS: The scores of total Beck Depression Inventory (BDI) and BDI item 9 (suicide) were higher in insomnia subgroup than non-insomnia subgroup (respectively, p=0.0033 and p=0.03). However, LDAEP did not differ each other. The subgroup with a history of suicide attempts had a higher score of BDI item 9 than the subgroup without a history of suicide attempts (p=0.00012). There was a tendency for the LDAEP to be higher in the subgroup with a history of suicide attempts (1.39+/-0.94 microV) than the subgroup without a history of suicide attempts (1.05+/-0.75 microV), although the difference was not statistically significant (p=0.078). CONCLUSION: Suicidality was related to insomnia. In addition, there was a tendency for serotonin activity to be lower in the subgroup with a history of suicide attempts. In future, more studies are needed.

Can the Loudness Dependence of Auditory Evoked Potentials and Suicidality Be Used to Differentiate between Depressive Patients with and without Bipolarity

OBJECTIVE: This study aimed to test the hypothesis that the loudness dependence of auditory evoked potentials (LDAEP) can be used to predict the presence of bipolarity in patients with major depressive episodes. METHODS: A cohort of 61 patients who met the criteria for major depressive disorder (MDD) following diagnosis using Axis I of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders-text revision, and who had no history of hypomanic or manic episodes was included in this study. The patients were stratified into two subgroups based on whether or not they achieved a positive score for the Korean versions of the Mood Disorder Questionnaire (K-MDQ). The LDAEP was evaluated by measuring the auditory event-related potentials before beginning medication with serotonergic agents. RESULTS: The Barratt Impulsiveness Scale (BIS) score was also higher for the positive screening group (81.24+/-11.87) than for the negative screening group (73.30+/-14.92; p=0.039, independent t-test). However, the LDAEP, Beck Depression Inventory, Hamilton Depression Rating Scale, Beck Hopelessness Scale (BHS), and Hamilton Anxiety Scale scores did not differ significantly between them. When binary logistic regression analysis was carried, the relationship between the positive or negative subgroups for K-MDQ and BIS or Beck Scale for Suicidal Ideation (BSS) score was also significant (respectively, p=0.017, p=0.038). CONCLUSION: We found that LDAEP was not significantly different between depressive patients with and without bipolarity. However, our study has revealed the difference between two subgroups based on whether or not they achieved a positive score for the K-MDQ in BIS or BSS score.

Clinical Usefulness of Loudness Dependence of Auditory Evoked Potentials (LDAEP) in Patients with Bipolar Disorder

While it has been reported previously that the loudness dependence of auditory evoked potentials (LDAEP) is a putative biological marker or a predictor of treatment response, there have been few studies of LDAEP in bipolar disorder. However, a recent study by Park and colleagues raised the possibility that the LDAEP could be useful as a biological marker of bipolar disorder. They found that the LDAEP was significantly higher in normal controls than in patients with either bipolar disorder or schizophrenia. Lee and colleagues also examined the LDAEP in bipolar disorder and normal controls, and found that it differed according to the bipolar phase, being significantly higher in cases of euthymic bipolar disorder, bipolar depression, and bipolar mania. With regard to treatment response, early clinical findings were that a higher LDAEP and a stronger intensity dependence of visual evoked potentials were related to a favorable response to lithium treatment. Juckel and colleagues recently demonstrated that the pretreatment LDAEP could be a predictor of successful prophylactic lithium treatment. The present article reviews the literature in order to determine whether the LDAEP can be used as a biological marker or a predictor of treatment response in patients with bipolar disorder and of manic switch or treatment resistance in patients with major depressive episode(s).

Clinical Implication of Loudness Dependence of Auditory Evoked Potential (LDAEP) in Psychiatic Illness

The loudness dependence of the auditory evoked potential (LDAEP) has been proposed as a valid biomarker of central serotoninergic activity in humans. The specificity and sensitivity of the LDAEP to changes in serotonergic neurotransmission have recently been explored in many studies about pharmacology and genetics. The majority of evidence for an association between the LDAEP and serotonin activity has come from animal studies. Genetic association studies with the LDAEP have provided conflicting reports with additional evidence outlining sensitivity to other neurotransmitter systems including the dopamine and glutamatergic systems. The LDAEP has been revealed to reflect the pathophysiology of various psychiatric illnesses. There is supporting evidence that major psychiatric disorders have differential LDAEP activities. Overall, the LDAEP shows strong evidence as a potential predictor of antidepressant treatment response. It need to be explored whether the LDAEP could be a biological marker of various psychiatric diseases and treatment prediction of antidepressants and serotonin related drugs.

Cognitive Abilities and Auditory Event Related Potentials in Patients with Schizophrenia

OBJECTIVES: Event-related potentials have been suggested as an objective marker for brain functions in psychiatric disorders. This study was aimed to investigate the relationships between P300, the mismatch negativity (MMN), the loudness dependence of the auditory evoked potential (LDAEP), demographic and clinical variables including neurocognitive abilities in patients with schizophrenia. METHODS: P300, the MMN, and the LDAEP were measured and the Korean Stroop color-word test (K-stroop test) and the Wisconsin Card Sorting Test (WCST) were performed in 43 patients with schizophrenia. The relationship of the latency and amplitude of P300 and the MMN as well as regression slope of the LDAEP with demographic and clinical variables were analyzed by t-test and correlation analyses for categorical and continuous variables, respectively. RESULTS: After controlling for age, the latency of central (Cz) and parietal (Pz) P300 posivitively correlated with GAF at admission (Cz ; gamma = 0.385, p = 0.047, Pz ; gamma = 0.421, p = 0.029). The amplitude of parietal P300 correlated with the correction rate of the K-stroop test (gamma = 0.575, p = 0.002). In addition, the frontal (Fz) P300 latency tended to negatively correlated with the correction rate of the WCST (gamma = -0.371, p = 0.057). CONCLUSIONS: Our findings suggest that the values of P300 latency and amplitude might be correlated with GAF at admission and working memory measured by the K-Stroop test and the WCST. Meanwhile, the MMN and the LDAEP did not correlate with demographic and clinical variables. These results support the results of previous studies showing associations with P300 and impaired cognitive ability.

Serotonergic Dysfunction in Patients with Bipolar Disorder Assessed by the Loudness Dependence of the Auditory Evoked Potential

OBJECTIVE: The loudness dependence of the auditory evoked potential (LDAEP) is suggested to be a marker of serotonin system function. This study explored the LDAEP of multiple mood statuses (depression, mania, and euthymia) and its clinical implication in bipolar disorder patients. METHODS: A total of 89 subjects, comprising 35 patients with bipolar disorder, 32 patients with schizophrenia, and 22 healthy controls were evaluated. The bipolar disorder cases comprised 10 depressed patients, 15 patients with mania, and 10 euthymic patients. The N1/P2 peak-to-peak amplitudes were measured at 5 stimulus intensities, and the LDAEP was calculated as the slope of the linear regression. Both cortical and source LDAEP values were calculated. RESULTS: LDAEP varied according to mood statuses, and was significantly stronger in cases of euthymia, depression, and mania. Cortical LDAEP was significantly stronger in patients with bipolar euthymia compared with schizophrenia, stronger in bipolar depression than in schizophrenia, stronger in healthy controls than in schizophrenia patients, and stronger in healthy controls than in patients with bipolar mania. Source LDAEP was significantly stronger in patients with bipolar euthymia, bipolar depression, and bipolar mania compared with schizophrenia, stronger in bipolar euthymia than in bipolar mania. Psychotic features weakened the source LDAEP relative to nonpsychotic features. The severity of the depressive symptom was negatively correlated with source LDAEP. CONCLUSION: These findings suggest that the serotonin activity of patients with bipolar disorder may vary according to mood status. A longitudinal follow-up study should be pursued using drug-naive subjects.

Usefulness of LDAEP to Predict Tolerability to SSRIs in Major Depressive Disorder: A Case Report

We report here a patient with major depressive disorder who experienced severe adverse effects after the administration of SSRIs (serotonin selective reuptake inhibitors) without improvement of his depressive symptoms. These adverse effects disappeared and his depressive symptoms improved after discontinuation of the SSRIs and the administration of tianeptine. The patient exhibited a low value for the loudness dependent of auditory evoked potentials (LDAEP) -0.14 at baseline, which means that his central serotonergic neurotransmission was already highly active. We assumed that it was this high serotonergic activity that rendered him unresponsive to SSRIs, and brought on him the adverse effects, and that the tianeptine was effective due to the lack of serotonin reuptake inhibitory action. Thus, we suggest that LDAEP can be used to predict an individual patient's tolerability and clinical response to SSRIs in major depression.