Background: Animal and clinical studies have demonstrated that the loudness dependence of auditory evoked potentials (LDAEP) is inversely related to central serotonergic activity, with a high LDAEP reflecting weak serotonergic neurotransmission and vice versa, though the findings in humans have been less consistent. In addition, a high pretreatment LDAEP appears to predict a favorable response to antidepressant treatments that augment the actions of serotonin. The aim of this study was to test whether the baseline LDAEP is correlated with response to long-term maintenance treatment in patients with major depressive disorder (MDD). Methods: Scalp N1, P2 and N1/P2 LDAEP and standardized low resolution brain electromagnetic tomography-localized N1, P2, and N1/P2 LDAEP were evaluated in 41 MDD patients before and after they received antidepressant treatment (escitalopram (n = 32, 10.0 ± 4.0 mg/day), sertraline (n = 7, 78.6 ± 26.7 mg/day), and paroxetine controlled-release formulation (n = 2, 18.8 ± 8.8 mg/day)) for more than 12 weeks. A treatment response was defined as a reduction in the Beck Depression Inventory (BDI) score of >50% between baseline and follow-up. Results: The responders had higher baseline scalp P2 and N1/P2 LDAEP than nonresponders (p = 0.017; p = 0.036). In addition, changes in total BDI score between baseline and follow-up were larger in subjects with a high baseline N1/P2 LDAEP than those with a low baseline N1/P2 LDAEP (p = 0.009). There were significantly more responders in the high-LDAEP group than in the low-LDAEP group (p = 0.041). Conclusions: The findings of this study reveal that a high baseline LDAEP is associated with a clinical response to long-term antidepressant treatment.

The interaction between genes and environment often occurs when they depend on one another. We hypothesized that adverse childhood experiences (ACEs) would interact with genetic predispositions to bipolar disorder (BD), demonstrating earlier age at onset (AAO) and worse clinical outcomes. We aimed to clarify the effects of the interaction between ACEs and genetic susceptibility using polygenic risk score (PRS) on AAO and clinical outcomes. Single nucleotide polymorphisms and clinical data, including ACEs, were obtained from the Bipolar Genomic Study, which contains a large sample of BD participants. A total of 1615 subjects with BD I were obtained and divided into two groups according to the presence or absence of ACEs and an additional four groups based on the number of ACEs (none versus one versus two versus ≥ three types). ACEs was evaluated using the childhood life events scale (CLES). BD–PRS was obtained from the Psychiatric Genomics Consortium, which compared BD patients and healthy controls. The BD–PRS was higher in the group with ACEs than without ACEs at most p-value thresholds. In multivariate linear regression analyses, both groups with more ACEs and higher BD–PRS were independently and interactively associated with an earlier AAO of BD; however, only greater ACEs were associated with worsened clinical outcome. These findings highlight the clinical importance of evaluating ACEs and polygenic risk in research of the etiology of BD.

Studies have reported an association between adverse childhood experiences (ACEs) and the clinical outcomes of bipolar disorder (BD). However, these studies have several limitations; therefore, we aimed to clarify the effect of the type and number of ACEs and the timing of adverse experiences on clinical outcomes in patients with BD. We analyzed the data of patients with BD (N = 2675) obtained from the National Institute of Mental Health: Bipolar Disorder Genetic Association Information Network, Translational Genomic Institute-I, and Translational Genomic Institute-II. All patients had been diagnosed using the Diagnostic Interview for Genetic Studies. ACEs were evaluated using the Childhood Life Events Scale (CLES). We analyzed the relationship between childhood trauma and clinical outcome in patients with and without exposure to ACEs. We found that ACEs had a robust negative effect on clinical outcomes, including earlier age at onset, presence of psychotic episodes, suicide attempts, mixed symptoms or episodes, substance misuse comorbidity, and worse life functioning. Specifically, the number of ACEs had the most significant effect on clinical outcomes; however, specific ACEs, such as physical abuse, had a considerable influence. Moreover, post-childhood adverse experiences had a weaker effect on clinical outcomes than ACEs did. There was an association of ACEs with negative clinical outcomes in patients with BD. This indicates the importance of basic and clinical research on ACEs in patients with BD.

The aim of this study was to test the hypothesis that serum levels of brain-derived neurotrophic factor (BDNF) are correlated with the loudness dependence of auditory evoked potentials (LDAEP). The question of whether there is a difference in BDNF levels between depressive patients according to their illness severity, history of suicide attempts, and central serotonin activity was also addressed. A sample of 51 patients who met the criteria for major depressive disorder following diagnosis using axis I of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders – text revision comprised the study subjects. The patients were stratified into two subgroups based on their illness severity, history of suicide attempts, and their LDAEP values. The LDAEP was evaluated by measuring the auditory event-related potentials, and serum BDNF was measured using blood sampling before beginning medication with serotonergic agents. There was no difference in serum BDNF levels between the two patient subgroups. The subgroup with moderate-to-severe depression (n = 16) was reanalyzed after stratifying it into two subgroups according to LDAEP and BDNF values (dichotomized at the medians into low and high). The high-LDAEP subgroup had higher serum BDNF levels and total Barratt Impulsiveness Scale score than the low-LDAEP subgroup (p = 0.03 and 0.036, respectively). Serum BDNF levels were positively correlated with LDAEP and total Beck Hopelessness Scale (BHS) score (r = 0.56, p = 0.025, and r = 0.59, p = 0.016, respectively). The high-BDNF subgroup had a higher LDAEP and total BHS score than the low-BDNF subgroup (p = 0.046 and p = 0.011, respectively). This is the first study to demonstrate a relationship between the BDNF level and LDAEP in Asian depressive patients. Intriguingly, the high-BDNF subgroup (divided according to illness severity) exhibited a more severe psychopathology on some psychometric rating scales, a finding that conflicts with previous results.

Park YM, et al. Psychiatry Investig. 2012 Mar;9(1):80-82. http://dx.doi.org/10.4306/pi.2012.9.1.80