Reduced plasma Fetuin-A is a promising biomarker of depression in the elderly.

Depression affects 7% of the elderly population, and it often remains misdiagnosed or untreated. Peripheral biomarkers might aid clinicians by allowing more accurate and well-timed recognition of the disease. We sought to determine if plasma protein levels predict the severity of depressive symptomatology or distinguish patients from healthy individuals. The severity of depressive symptoms and global cognitive functioning were assessed by the Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE) in 152 elderly subjects, 76 of which with major depressive disorder (MDD). Plasma levels of 24 proteins were measured by multiplexing and analyzed as continuous predictors or dichotomized using the median value. The association between individual plasma proteins and MDD risk or depressive symptoms severity was investigated using multiple logistic and linear regressions including relevant covariates. Sensitivity analyses were performed excluding cognitively impaired individuals or non-acute patients with MDD. After adjusting for possible confounders and false discovery rate (FDR) correction, we found lower Fetuin-A levels in MDD patients vs. controls (pFDR = 1.95 × 10-6). This result was confirmed by the sensitivity and dichotomized analyses. Lower prolactin (PRL) levels predicted more severe depressive symptoms in acute MDD patients (pFDR = 0.024). Fetuin-A is a promising biomarker of MDD in the elderly as this protein was negatively associated with the disorder in our sample, regardless of the global cognitive functioning. Lower PRL levels may be a peripheral signature of impaired neuroprotective processes and serotoninergic neurotransmission in more severely depressed patients.

How many different symptom combinations fulfil the diagnostic criteria for major depressive disorder? Results from the CRESCEND study.

BACKGROUND: The polythetic nature of major depressive disorder (MDD) in DSM- IV and DSM-5 inevitably leads to diagnostic heterogeneity. AIMS: This study aimed to identify the number of depressive symptom combinations actually fulfilling the DSM-IV diagnostic criteria that can be found in Korean MDD patients and the relative frequencies of each combination. METHODS: Using the data from the Clinical Research Center for Depression (CRESCEND) study in South Korea, we enrolled 853 MDD patients diagnosed using DSM-IV and scored as 8 or more on the Hamilton Depression Rating Scale (HAMD). Descriptive statistical analyses were performed to reveal the degree of diagnostic heterogeneity of the MDD. RESULTS: This study identified 119 different depressive symptom combinations. The most common combination consisted of all nine depressive symptom profiles, and nine different combinations were each present in more than 3% of the patients. CONCLUSION: The findings support the criticism that the diagnosis of MDD is not based on a single mental process, but on a set of 'family resemblances'.

Genes Involved in Neurodevelopment, Neuroplasticity, and Bipolar Disorder: CACNA1C, CHRNA1, and MAPK1.

BACKGROUND: Bipolar disorder (BPD) is a common and severe mental disorder. The involvement of genetic factors in the pathophysiology of BPD is well known. In the present study, we tested the association of several single-nucleotide polymorphisms (SNPs) within 3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1) with BPD. These genes are involved in monoamine-related pathways, as well as in dendrite development, neuronal survival, synaptic plasticity, and memory/learning. METHODS: One hundred and thirty-two subjects diagnosed with BPD and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within CACNA1C, CHRNA17, and MAPK1. Distribution of alleles and block of haplotypes within each gene were compared in cases and controls. Interactions between variants in different loci were also tested. RESULTS: Significant differences in the distribution of alleles between the cases and controls were detected for rs1016388 within CACNA1C, rs1514250, rs2337980, rs6494223, rs3826029 and rs4779565 within CHRNA7, and rs8136867 within MAPK1. Haplotype analyses also confirmed an involvement of variations within these genes in BPD. Finally, exploratory epistatic analyses demonstrated potential interactive effects, especially regarding variations in CACNA1C and CHRNA7. LIMITATIONS: Limited sample size and risk of false-positive findings. DISCUSSION: Our data suggest a possible role of these 3 genes in BPD. Alterations of 1 or more common brain pathways (e.g., neurodevelopment and neuroplasticity, calcium signaling) may explain the obtained results.

Clinical Significance of the Number of Depressive Symptoms in Major Depressive Disorder: Results from the CRESCEND Study.

Our study aimed to establish the relationship between the number of depressive symptoms and the clinical characteristics of major depressive disorder (MDD). This would enable us to predict the clinical significance of the number of depressive symptoms in MDD patients. Using data from the Clinical Research Center for Depression (CRESCEND) study in Korea, 853 patients with DSM-IV MDD were recruited. The baseline and clinical characteristics of groups with different numbers of depressive symptoms were compared using the χ(2) test for discrete variables and covariance (ANCOVA) for continuous variables. In addition, the scores of these groups on the measurement tools were compared by ANCOVA after adjusting the potential effects of confounding variables. After adjusting the effects of monthly income and history of depression, a larger number of depressive symptoms indicated higher overall severity of depression (F [4, 756] = 21.458, P < 0.001) and higher levels of depressive symptoms (F [4, 767] = 19.145, P < 0.001), anxiety symptoms (F [4, 765] = 12.890, P < 0.001) and suicidal ideation (F [4, 653] = 6.970, P < 0.001). It also indicated lower levels of social function (F [4, 760] = 13.343, P < 0.001), and quality of life (F [4, 656] = 11.975, P < 0.001). However, there were no significant differences in alcohol consumption (F [4, 656] = 11.975, P < 0.001). The number of depressive symptoms can be used as an index of greater illness burden in clinical psychiatry.

Age-related differences in suicidality between young people and older adults with depression: data from a nationwide depression cohort study in Korea (the CRESCEND study).

This study compared young people and older adults with depression to identify differences in suicidality between these groups. A total of 1003 patients with moderate to severe depression (Hamilton Depression Rating Scale [HDRS] score ≥14) were recruited from a national sample of 18 hospitals. Of the patients included in this study, 103 (10.3%) were placed in the younger group (age <25years) and 900 (89.7%) were placed in the older group (age ≥25years). Suicide-related variables and predictive factors associated with significant suicidal ideation were compared between the two groups. Regardless of the severity of depression, subjects in the younger group were more likely than were those in the older group to report significant suicidal ideation (scores ≥6 on the Beck Scale for Suicide Ideation [SSI-B], 79.6 vs. 53.7%, respectively; p<0.001), have had a suicide attempt at the current episode (4.9 vs. 1.6%, respectively; p=0.037), and have a history of suicide attempts (43.7 vs. 19.4%, respectively; p<0.001). Logistic regression models revealed that, in contrast to the predictive factors in the older group, subjects in the younger group were more affected by their history of suicide attempts (OR [95% CI]: 12.4, [1.5-99.1]; p=0.018) and depressive episodes (OR [95% CI]: 13.0, [1.6-104.0]; p=0.016). Also in contrast to the older group, an increase in HDRS score was not identified as a possible precipitating factor of significant suicidal ideation in younger subjects. The present findings demonstrate that suicidality in depressed young people was more severe than in older adults, but that suicidality was not correlated with the severity of depression. These data suggest that close attention should be paid to young people even in mild or moderate depression.

Hazardous drinking-related characteristics of depressive disorders in Korea: the CRESCEND study.

This study aimed to identify clinical correlates of hazardous drinking in a large cohort of Korean patients with depression. We recruited a total of 402 depressed patients aged > 18 yr from the Clinical Research Center for Depression (CRESCEND) study in Korea. Patients' drinking habits were assessed using the Korean Alcohol Use Disorder Identification Test (AUDIT-K). Psychometric scales, including the HAMD, HAMA, BPRS, CGI-S, SSI-Beck, SOFAS, and WHOQOL-BREF, were used to assess depression, anxiety, overall psychiatric symptoms, global severity, suicidal ideation, social functioning, and quality of life, respectively. We compared demographic and clinical features and psychometric scores between patients with and without hazardous drinking behavior after adjusting for the effects of age and sex. We then performed binary logistic regression analysis to identify independent correlates of hazardous drinking in the study population. Our results revealed that hazardous drinking was associated with current smoking status, history of attempted suicide, greater psychomotor retardation, suicidal ideation, weight loss, and lower hypochondriasis than non-hazardous drinking. The regression model also demonstrated that more frequent smoking, higher levels of suicidal ideation, and lower levels of hypochondriasis were independently correlates for hazardous drinking in depressed patients. In conclusion, depressed patients who are hazardous drinkers experience severer symptoms and a greater burden of illness than non-hazardous drinkers. In Korea, screening depressed patients for signs of hazardous drinking could help identify subjects who may benefit from comprehensive therapeutic approaches.

Does mirtazapine interfere with naturalistic diabetes treatment?

Mirtazapine is known to induce weight gain and possibly leads to exacerbation of diabetic profiles. However, many cases of diabetic patients, who complained of insomnia and depression, were treated with mirtazapine in the clinical situations. Thus, this study aimed to assess any negative effects that treatment with mirtazapine may incur in diabetic patients.This study included 33 patients enrolled in naturalistic diabetes treatment that had also been diagnosed with depression and prescribed mirtazapine for at least 6 months. Another 33 diabetic patients who had not taken any psychiatric medicines were included as a control group. Body mass index, fasting plasma glucose, HbA1c, total cholesterol, triglyceride levels, high-density lipoprotein, and low-density lipoprotein were assessed at baseline, 3 months, and 6 months.The dose of mirtazapine at baseline was 24.3 ± 14.0 mg/d in the mirtazapine group, and the 2 groups did not differ in any baseline characteristics except for total cholesterol levels. Body mass index increased in both groups, and the change in the mirtazapine group (1.0 ± 0.6 kg/m) was significantly greater than that in the control group (0.3 ± 0.4 kg/m, P < 0.001) at 6 months. Only the control group exhibited a decrease in fasting plasma glucose, whereas both groups showed a decrease in HbA1c, low-density lipoprotein, and total cholesterol, an increase in high-density lipoprotein, and no change in triglyceride levels. None of the differences between the groups were statistically significant.In conclusion, mirtazapine increased the weight gain of diabetic patients; however, other diabetic and lipid markers generally did not worsen during the 6-month treatment period. These results suggest that, at least in the short term, mirtazapine is safe for diabetic patients in a stable state and are undergoing appropriate diabetic treatment.

Personality traits associated with suicidal behaviors in patients with depression: the CRESCEND study.

The aim of the current study was to identify personality traits associated with suicidal behavior in patients with depression. Of the 1183 patients screened for an observational cohort study of depression, 334 (28.2%) who completed the Temperament and Character Inventory (TCI) were included in these analyses. To minimize the effect of current mood state, the TCI was performed 12 weeks after initiation of treatment, and we adjusted for the severity of depression. Of the 344 participants, 59 had a lifetime history of at least one suicide attempt, 37 had a lifetime history of multiple suicide attempts, and 5 attempted suicide during the 12-week study period. At baseline, patients with a lifetime history of at least one suicide attempt, a lifetime history of multiple suicide attempts, and a suicide attempt during the study period expressed more serious current suicidal ideation than did those without such a history, despite the absence of differences among the groups in the severity of depressive and anxiety symptoms. Of the seven personality scales of the TCI, lower scores on the self-directedness scale of the character dimension were associated with a history of at least one suicide attempt (OR [95% CI], 0.91 [0.87-0.96]; p<0.001), a history of multiple suicide attempts (0.91 [0.86-0.97]; p=0.003), and suicide attempts during study period (0.80 [0.69-0.94]; p=0.006). These findings suggest that depressed patients with a history of suicidal behavior differ from non-attempters with regard to personality traits, especially the character dimension of self-directedness. It is noteworthy that this result emerged after controlling for the effect of current mood state.

Impact of childhood adversity on the course and suicidality of depressive disorders: the CRESCEND study.

OBJECTIVE: The impact of childhood adversity persists across the life course. This study aimed to investigate the associations of childhood adversity with the course, suicidality, and treatment outcomes of depressive disorders. METHOD: A total of 919 people with depressive disorders were recruited. Childhood adversities (≤12 years old) were ascertained using a checklist, in sexual abuse, physical abuse by parents, and separation of parents. Various assessment scales were administered at baseline and over 12 weeks of antidepressants treatment. RESULTS: All three forms of childhood adversity were associated with an increased likelihood of experiencing more current stressful events. Scores on the Beck Depression Inventory and Hamilton Anxiety Rating Scale were significantly higher in participants with a history of sexual abuse. Scores on the Beck Depression Inventory, Hamilton Depression Rating Scale, and Perceived Stress Scale were significantly higher, and scores on the WHO Quality of life instrument were significantly lower in participants with a history of physical abuse by parents. They were more likely to receive augmentation and combination treatment after the initial antidepressant treatment, whereas overall response rates to treatment did not differ. Scores on the Beck Scale for suicide ideation were significantly higher after treatment and/or at baseline in patients with sexual or physical abuse. Physical illness was more prevalent in individuals with physical abuse by parents or separation of parents. CONCLUSIONS: Depressive patients with a history of childhood adversities had more severe and chronic forms of depression with high suicidality. More intensive treatment with particular clinical attention is indicated for this special population.

Continuity of outpatient treatment after discharge of patients with major depressive disorder.

PURPOSE: This study aimed to identify the predictors associated with the continuity of outpatient treatment after discharge for patients with major depression. METHODS: The medical records of patients discharged with diagnosis of major depression were analyzed. The subjects were divided into two groups based on whether they regularly visited the outpatient clinic for more than 4 months after discharge. RESULTS: The 4-month follow-up group was older, had a lower employment rate, and had a lower rate of being divorced or separated. The 4-month follow-up group had a longer duration of illness, a higher rate of recurrent major depressive disorder, older age at onset, and a longer duration of index hospitalization. Longer duration of index hospitalization and combination therapy were significantly related to an increased likelihood of 4-month follow-up visits. CONCLUSIONS: Duration of hospitalization and prescription pattern of psychotropic medication appeared to have an influence on the continuity of outpatient treatment after discharge.

The Change of Suicidal Ideation Over a 12-Week Naturalistic Treatment of Depression: Comparison Between Young People and Older Adults.

OBJECTIVE: We investigated the differences in suicidality between young people and older adults with depression over the course of 12-week naturalistic treatment with antidepressants. METHODS: A total of 565 patients who had moderate to severe depression (Hamilton Depression Rating Scale [HAM-D] score ≥14) and significant suicidal ideation (Beck Scale for Suicide Ideation [SSI-B] score ≥6) were recruited from 18 hospitals. Participants were classified into two groups: the younger group (13-24 years of age, n=82) and the older group (≥25 years of age, n=483). Total scores over time on the SSI-B, HAM-D, and Hamilton Anxiety Rating Scale (HAM-A) were assessed and compared between the two groups. RESULTS: At baseline, the younger group had lower HAM-D scores (21.0 vs. 22.2; p=0.028) but higher SSI-B scores (19.4 vs. 15.6; p<0.001) compared with the older group. The overall 12-week proportion of patients with resolved suicidality was 44.1% in the younger group and 69.2% in the older group. Although the improvement in the HAM-D and HAM-A scores did not differ between the groups, suicidal ideation in the younger group remained more severe than in the older group throughout the treatment. The ratio of the subjects who achieved HAM-D remission or response but did not achieve SSI-B remission was significantly higher in the younger group than in the older group. CONCLUSION: These data suggest that in depressed youths, suicide risk is a serious concern throughout the course of depression even when favorable treatment outcomes are obtained.

Influence of GRIA1, GRIA2 and GRIA4 polymorphisms on diagnosis and response to treatment in patients with major depressive disorder.

The present study is aimed to exploring whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with major depressive disorder (MDD) and whether they could predict clinical outcomes in Korean in-patients, respectively, treated with antidepressants. One hundred forty-five (145) patients with MDD and 170 healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures, including the Montgomery-Asberg Depression Rating Scale (MADRS) for patients with MDD, were recorded. No association was observed between alleles, genotypes and haplotypes under investigation and clinical and demographical variables. As a secondary finding, a marginal association was observed between rs4302506 and rs4403097 alleles within GRIA2 and age of onset in patients with MDD. Our findings provide evidence for a possible association between rs4302506 and rs4403097 SNPs and age of onset in patients with MDD. However, taking into account that the several limitations of our study including the moderately small sample size of our study, our findings should be considered with caution and further research is needed to draw more definitive conclusions.

Factors associated with subjective quality of life in Korean patients with depressive disorders: the CRESCEND study.

PURPOSE: A number of studies suggest that depression is associated with the significant disability and the poorer subjective quality of life (QOL). We aimed to assess subjective QOL in Korean patients with depression and explore the factors (sociodemographic characteristics and clinical features) associated with subjective QOL. METHODS: We obtained the data from 808 depressive patients who entered the Clinical Research Center for Depression (CRESCEND) study and evaluated the relationship between subjective QOL and personal sociodemographics, and various clinical features, including depressive severity, and subjective QOL. We assessed subjective QOL using the 26-item abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) instrument. RESULTS: Decrements in patients' physical health, psychological health, social relationships, and environment domains of subjective QOL were all strongly associated with the greater depressive symptom severity. After controlling for age and depressive symptom severity, the lower subjective QOL was independently related to being divorced or separated, the less monthly household income, and having no religious practices. CONCLUSION: Our results suggest the importance of sociodemographic characteristics in addition to symptoms for the understanding of subjective QOL in depressed patients. The prospective studies to compare the different treatments' effects on various subjective QOL domains are needed.

Platelet count alterations associated with escitalopram, venlafaxine and bupropion in depressive patients.

The objective of the present study was to evaluate changes in platelet counts on three different kinds of antidepressant. All subjects (n = 131) in their drug-naïve state had been diagnosed with depression. Escitalopram (n = 42), venlafaxine (n = 50) and bupropion (n = 39) were prescribed, and platelet count was measured before and after 1 month of treatment and compared. Decrease in platelet count on escitalopram was significant, while the others were not. These findings suggest that escitalopram may be associated with decreased platelet count, and bupropion is less likely to exert an influence on platelet count.

Relationship between a history of a suicide attempt and treatment outcomes in patients with depression.

This study aimed to investigate the sociodemographic and clinical correlates of a history of a suicide attempt in people with depression and their relationship with treatment outcomes and subsequent suicidal ideation and deliberate self-harm. Patients with depressive disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were recruited from 18 hospitals across South Korea. Data on sociodemographic and clinical characteristics were obtained, and scales assessing depression, anxiety, and general functioning were administered during the first 12 weeks of antidepressant treatment. Baseline characteristics, responses to treatment, and suicidal ideation/deliberate self-harm during the follow-up period were compared according to a reported history or not of a suicide attempt. In a total of 723 participants, 143 (19.8%) with a history of a suicide attempt had an earlier age of onset, longer duration of illness, and a greater number of depressive episodes. Levels of depression and anxiety were significantly higher at baseline in this group who also experienced significantly lower remission and response rates, as well as longer time to remission. The case group was more likely to experience new suicidal ideation and carry out a deliberate self-harm act during the 12-week treatment period. In conclusion, a history of a suicide attempt in a Korean population with depression was characterized by more severe psychopathology, poorer treatment outcomes, and higher subsequent suicidal ideation and self-harm. Therefore, more intensive and longer-term treatment with particular ongoing clinical attention to risk is indicated in patients with these distinct, chronic, and severe forms of depression and ongoing high suicide risk.

Gender differences in 12-week antidepressant treatment outcomes for a naturalistic secondary care cohort: the CRESCEND study.

This study aimed to determine whether men and women with depression differ in socio-demographic, treatment-related characteristics, and in their responses to treatment with antidepressants, as well as to explore differences in treatment outcomes by menopausal status. From a nationwide sample of 18 hospitals in South Korea, 723 depressive patients were recruited. After baseline evaluation, they received naturalistic clinician-determined antidepressant interventions. Assessment scales for evaluating depression (HAMD), anxiety (HAMA), global severity (CGI-s), and functioning (SOFAS) were administered at baseline and re-evaluated at 1, 2, 4, 8, and 12 weeks later. At baseline, women were older, less educated, less likely to be employed, had lower income, were more likely to be married, and had longer illness duration than men. There were no gender differences in the treatment-regime received. After adjustment for baseline status, women were more likely to achieve HAMD remission (OR=1.51), HAMD response (OR=1.64), and HAMA response (OR=1.61). Women also experienced shorter times to HAMD response, HAMA response, and CGI-s remission. Postmenopausal women showed higher HAMA response with newer dual action antidepressants than premenopausal women. Women were found to have better outcomes following antidepressant treatment than men, and postmenopausal women had a better response on anxiety symptoms with newer dual action antidepressants.

Predictors of 12-week remission in a nationwide cohort of people with depressive disorders: the CRESCEND study.

OBJECTIVE: To estimate the 12-week remission rate of patients with depressive disorders and predictors of this in a naturalistic clinical setting in South Korea. METHODS: For people with DSM-IV depressive disorders about to receive treatment at 18 hospitals, data on sociodemographic and health status were obtained. A free choice of clinical interventions was allowed and naturalistic follow-up took place at 1, 2, 4, 8, and 12 weeks later. Remission was defined as a Hamilton Depression Rating Scale score of ≤7 sustained to 12 weeks or last follow-up, if earlier. RESULTS: For 723 participants, the 12-week remission rate was 31.4%. Remission was more likely in women, and in patients without a prior history of suicide attempt, and those with lower baseline anxiety. CONCLUSIONS: Remission associated with unrestricted clinical interventions was comparable to STAR*D estimates for citalopram alone. Comorbid anxiety and previous suicide attempt were markers of worse outcome.

The acute and long-term effectiveness of amisulpride in patients with schizophrenia: results of a 12-month open-label prospective follow-up study.

OBJECTIVE: To compare the effectiveness of amisulpride in acute (up to 8 weeks) and maintenance (week 8 to 12 months) phases of a 12-month course of treatment in a heterogeneous group of patients with schizophrenia. METHODS: We conducted a 12-month, open-label clinical trial with flexible doses of amisulpride among 129 Korean patients with schizophrenia. The Positive and Negative Symptom Scale (PANSS) and several other scales measuring efficacy and tolerability were analyzed during the acute and maintenance phases. RESULTS: The completion rates were 78.3% by week 8 and 55.8% by month 12. Total PANSS scores and scores on the negative-symptom and general-symptom subscales improved significantly during both acute and maintenance periods, but scores on the positive-symptom subscale improved only during the acute phase. Improvement during both treatment phases was significant in all other scales except for the Drug Attitude Inventory. The negative-symptom and mixed-symptom groups showed significant improvement in the PANSS negative subscale, the Clinical Global Impression scale, and the Global Assessment of Functioning during the maintenance period. Hyperprolactinemia and related events were commonly reported. CONCLUSIONS: This study demonstrated the significant effectiveness and a good safety profile of amisulpride for treating acute and 12-month phases of schizophrenia under natural conditions.

Distinctive clinical characteristics and suicidal tendencies of patients with anxious depression.

This study evaluated clinical characteristics and suicidality of patients with anxious depression in a large cohort of samples. Data were collected from 1003 patients who were depressed. A total of 461 patients were diagnosed with anxious depression and 542 were diagnosed with nonanxious depression. After adjusting for the severity of depression, those in the anxious depression group had significantly younger onset age, had been suffering from depression for a longer period, were more likely to experience a recurrence, and obtained lower scores on a scale assessing quality of life. The anxious depression group was characterized by a significantly higher proportion of individuals reporting significant suicidal ideation and previous suicide attempts, and those in this group tended to obtain higher scores on the Scale for Suicide Ideation. The present findings that were drawn from detailed evaluation of suicidality strongly support previous results assessed only with the help of clinical reports. More attention should be paid to assess suicide risk in these patients.

TAAR6 variations possibly associated with antidepressant response and suicidal behavior.

Trace amines are putative regulatory elements in the brain whose activity may be relevant to the pathophysiology of depressive episodes. TAAR6 is an orphan receptor probably associated with trace amines. Its genetic variations have been associated with bipolar and schizophrenic disorders. In this study we investigated for the first time the possible association between a set of TAAR6 genetic variations (rs7452939; rs4305745; rs6903874; rs6937506; and rs8192625) with clinical features of depression including antidepressant treatment response in a sample of 187 depressive patients all of Korean origins. rs6903874 T/T carriers had a statistically significant better improvement, and rs6937506 C/C genotype was found to be more frequent in patients without a history of suicide attempt (incomplete or unsuccessful suicide). Haplotype analyses confirmed the association with suicide attempt behavior being haplotype G-T at SNPs rs7452939 and rs6937506 at risk of suicide. These results suggest a possible role of TAAR6 in antidepressant response and suicide behavior in patients with depressive disorder. Heterogeneity of treatment, possible stratification bias not controlled by the statistical analyses, and the risk of false-positive finding mandate further analysis in this direction.