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.

ZNF804A Gene Variants Have a Cross-diagnostic Influence on Psychosis and Treatment Improvement in Mood Disorders.

OBJECTIVE: Genetic variations in the gene encoding zinc finger protein 804A gene (ZNF804A) have been associated with major depression and bipolar disorder. In this work we focused on the potential influence of ZNF804A variations on the risk of developing specific sub-phenotypes as well as the individual response to available treatments. METHODS: We used two samples of different ethnic origin: a Korean sample, composed by 242 patients diagnosed with major depression and 132 patients diagnosed with bipolar disorder and 326 healthy controls; an Italian sample composed 151 major depression subjects, 189 bipolar disorder subjects and 38 outpatients diagnosed for a primary anxiety disorder. RESULTS: Our analyses reported an association of rs1344706 with psychotic phenotype in the cross-diagnostic pooled sample (geno p = 4.15 × 10-4, allelic p = 1.06 × 10-4). In the cross-diagnosis Italian sample but not in the Korean one, rs7597593 was involved with depressive symptoms improvement after treatment (geno p = 0.025, allelic p = 0.007). CONCLUSION: The present study evidenced the role of ZNF804A alterations in symptoms improvement after treatment. Both manic and depressive symptoms seem to be modulated by ZNF804A, though the latter was observed in the bipolar pooled sample only. The role of this factor is likely related to synaptic development and maintenance; however, further analyses will be needed to better understand the molecular mechanics involved with ZNF804A.

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.

Genes Involved in Neurodevelopment, Neuroplasticity and Major Depression: No Association for CACNA1C, CHRNA7 and MAPK1.

OBJECTIVE: Genetics factors are likely to play a role in the risk, clinical presentation and treatment outcome in major depressive disorder (MDD). In this study, we investigated the role of three candidate genes for MDD; calcium voltage- gated channel subunit alpha1 C ( CACNA1C ), cholinergic receptor nicotinic alpha 7 subunit ( CHRNA7 ), and mitogen- activated protein kinase 1 ( MAPK1 ). METHODS: Two-hundred forty-two MDD patients and 326 healthy controls of Korean ancestry served as samples for the analyses. Thirty-nine single nucleotide polymorphisms (SNPs) within CACNA1C , CHRNA7 , and MAPK1 genes were genotyped and subsequently tested for association with MDD (primary analysis) and other clinical features (symptoms' severity, age of onset, history of suicide attempt, treatment outcome) (secondary analyses). Single SNPs, haplotypes and epistatic analyses were performed. RESULTS: Single SNPs were not associated with disease risk and clinical features. However, a combination of alleles (haplotype) within MAPK1 was found associated with MDD-status. Secondary analyses detected a possible involvement of CACNA1C haplotype in resistance to antidepressant treatment. CONCLUSION: These data suggest a role for MAPK1 and CACNA1C in MDD risk and treatment resistance, respectively. However, since many limitations characterize the analysis, the results must be considered with great caution and verified.

Reduced CXCL1/GRO chemokine plasma levels are a possible biomarker of elderly depression.

BACKGROUND: Depression is the single largest contributor to non-fatal health loss worldwide. A role of inflammation in major depressive disorder (MDD) was suggested, and we sought to determine if cytokine levels predict the severity of depressive symptomatology or distinguish MDD patients from healthy controls (HCs). METHODS: The severity of depressive symptoms and cognitive impairment were assessed by the Korean version of the Geriatric Depression Scale (GDS-K) and Mini-Mental State Examination (MMSE-KC) in 152 elderly subjects (76 with MDD). Plasma levels of 28 cytokines were measured and analysed as continuous predictors or dichotomized using the median value. The association between individual cytokines, MDD risk and depressive symptoms severity was investigated using multiple logistic and linear regressions that included the relevant covariates. A Cytokine Weighted Score (CWS) was calculated by weighting cytokines according to previously reported effect sizes on MDD risk. Sensitivity analyses were performed excluding subjects with significant cognitive impairment. RESULTS: CXCL10/IP-10 levels were higher in subjects with MDD vs. HCs while the opposite was observed for CXCL1/GRO. Only the second association survived after adjusting for possible confounders and excluding subjects with severe cognitive impairment. Using dichotomized cytokine levels, CXCL1/GRO and TNF-α were negatively associated with MDD. The CWS was also negatively associated with MDD. Cytokine levels did not predict the severity of depressive symptoms. LIMITATIONS: Our cross-sectional approach was not able to longitudinally evaluate any temporal fluctuations in the considered cytokine levels. CONCLUSIONS: This study found significantly lower CXCL1/GRO chemokine plasma levels in elderly subjects with MDD compared to HCs.

Erratum: Correction of Acknowledgements Second Generation Antipsychotics in the Treatment of Major Depressive Disorder: An Update.

[This corrects the article on p. 159 in vol. 52, PMID: 27689026.].

Neuroplasticity, Neurotransmission and Brain-Related Genes in Major Depression and Bipolar Disorder: Focus on Treatment Outcomes in an Asiatic Sample.

INTRODUCTION: Mood disorders are common and disabling disorders. Despite the availability of over 100 psychotropic compounds, only one-third of patients benefit from first-line treatments. Over the past 20 years, many studies have focused on the biological factors modulating disease risk and response to treatments, but with still inconclusive data. In order to improve our current knowledge, in this study, we investigated the role of a set of genes involved in different pathways (neurotransmission, neuroplasticity, circadian rhythms, transcription factors, signal transduction and cellular metabolism) in the treatment outcome of major depressive disorder (MDD) and bipolar disorder (BD) after naturalistic pharmacological treatment. METHODS: Totals of 242 MDD, 132 BD patients and 326 healthy controls of Asian ethnicity (Koreans) were genotyped for polymorphisms within 19 genes. Response and remission after 6-8 weeks of treatment with antidepressants and mood stabilizers were evaluated. In secondary analyses, genetic associations with disease risk and some disease-associated features (age of onset, suicide attempt and psychotic BD) were also tested. RESULTS: None of the variants within the investigated genes was significantly associated with treatment outcomes. Some marginal association (uncorrected p < 0.01) was observed for HTR2A, BDNF, CHL1, RORA and HOMER1 SNPs. In secondary analyses, HTR2A (rs643627, p = 0.002) and CHL1 (rs4003413, p = 0.002) were found associated with risk for BD, HOMER1 (rs6872497, p = 0.002) with lifetime history of suicide attempt in patients, and RORA with early onset and presence of psychotic features in BD. Marginal results were also observed for ST8SIA2 and COMT. DISCUSSION: Despite limitations linked to multiple testing on small samples, methodological shortcomings and small significance of the findings, this study may support the involvement of some candidate genes in the outcomes of treatments for mood disorders, as well as in BD risk and other disease features.

Efficacy of antidepressants: bias in randomized clinical trials and related issues.

INTRODUCTION: Countless antidepressant randomized trials were conducted and showed statistically significant benefits of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) over placebo. Meanwhile, critics are increasing regarding the efficacy of antidepressants in the treatment of MDD because at least a proportion of clinical trials could be hampered by various biases. In contrast, number of failed trials is increasing in the recent years which have made developing psychiatric medications progressively more time-consuming and expensive. Areas covered: Biases and related issues in clinical trials for antidepressants can be identified as an important common contributing factor to the two paradoxical phenomenon. This review identifies possible biases that can occur before, during, and after clinical trials of antidepressant. Expert commentary: Recent studies not only may over-estimate efficacy of antidepressants, but also may exaggerate placebo response because of various biases. Sponsorship and publication biases have been one of the targets of the criticism and ethical debate. Thus, initiating new trend of research by re-organizing academic-industry partnership will be the most important task in the next five years.

Hot Genes in Schizophrenia: How Clinical Datasets Could Help to Refine their Role.

We investigated the effect of a set of SNPs within 5 genes identified by GWASs as possible risk genes for schizophrenia (SCZ) in two independent samples, comprising 176 SCZ patients and 326 controls of Korean origin and 83 SCZ patients and 194 controls of Italian origin. The PANSS was used to assess psychopathology severity and antipsychotic response (AR). Several clinical features were assessed at recruitment. In the Korean sample, the SP4 gene haplotype rs2282888-rs2237304-rs10272006-rs12673091 (p = 0.02) was associated with SCZ. In the Italian sample, PPP3CC rs11780915 (genotypic: p = 0.006; allelic: p = 0.001) and rs2249098 (genotypic: p = 0.0004; allelic: p = 0.00006) were associated with SCZ, as well as the PPP3CC rs11780915-rs10108011-rs2249098 and the ZNF804A rs7603001-rs1344706 haplotypes (p = 0.03 and p = 0.02). Several RORA variants were associated with AR in both the samples, although only the haplotype rs1020729-rs1871858 in the Korean sample survived to the statistical correction (p = 0.01). Exploratory analyses suggested that: (1) PPP3CC, ST8SIA2, and SP4 genes may modulate psychotic symptoms, and (2) RORA and ZNF804A genes may influence AR. Our results partially support a role for these genes in SCZ and AR. Analyses in well phenotyped samples may help to refine the role of the genes identified by GWASs.

Clinical Validation of the Psychotic Depression Assessment Scale, Hamilton Depression Rating Scale-6, and Brief Psychiatric Rating Scale-5: Results from the Clinical Research Center for Depression Study.

OBJECTIVE: The aim of this study was to validate the psychotic depression assessment scale (PDAS), which includes the six-item melancholia subscale from the Hamilton depression rating scale (HAMD-6) and the five-item psychosis subscale from the brief psychiatric rating scale (BPRS-5). Data from the Clinical Research Center for Depression (CRESCEND) study, which is a 52-week naturalistic trial, were analyzed. METHODS: Fifty-two patients with psychotic depression from the CRESCEND study met our inclusion criteria. The patients underwent the following psychometric assessments: the PDAS, including HAMD-6 and BPRS-5, the clinical global impression scales, the HAMD, the positive symptom subscale, and the negative symptom subscale. Assessments were performed at the baseline and then at weeks 1, 2, 4, 8, 12, 24, and 52. Spearman correlation analyses were used to assess the clinical validity and responsiveness of the PDAS. RESULTS: The clinical validity and responsiveness of the PDAS, including HAMD-6 and BPRS-5, were acceptable, with the exception of the clinical responsiveness of the PDAS for positive symptoms and the clinical responsiveness of BPRS-5 for negative symptoms. CONCLUSION: The clinical relevance of the PDAS has been confirmed and this clinical validation will enhance its clinical utility and availability.

Paroxetine versus Venlafaxine and Escitalopram in Korean Patients with Major Depressive Disorder: A Randomized, Rater-blinded, Six-week Study.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of escitalopram, paroxetine and venlafaxine in Korean patients with major depressive disorder (MDD). METHODS: A total of 449 Korean MDD patients were recruited in a six-week, randomized, rater-blinded, active-controlled trial and were evenly randomized to paroxetine, venlafaxine, or escitalopram treatment. RESULTS: When comparing the mean difference for the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HDRS) total scores during six weeks, paroxetine (-6.4±0.4, and -5.4±0.4, respectively) was found to be significantly superior to escitalopram (-3.7±0.5 and -3.1±0.4, respectively). Venlafaxine had a significantly lower MADRS total score (-5.4±0.4) than escitalopram. When adjusting baseline variables, the response, according to the MADRS and HDRS scores, in the paroxetine group was greater than that for the escitalopram group (odds ratio [OR]=2.43, 95% confidence interval [CI]=1.42-4.16 for MADRS; and OR=2.32, 95% CI=1.35-3.97 for HDRS) and the venlafaxine group (OR=1.94, 95% CI=1.17-3.21 for MADRS; and OR=1.71, 95% CI=1.03-2.83 for HDRS). Despite that the overall tolerability was high and similar among the three groups, a total of 268 subjects (59.7%) prematurely discontinued treatment, representing the main limitation of the present study. CONCLUSION: Although a low study completion rate limits generalizability, our findings suggest that paroxetine might be superior to escitalopram in Korean MDD patients. Further studies should be conducted to draw a definite conclusion.

Genetic Variants Within Key Nodes of the Cascade of Antipsychotic Mechanisms: Effects on Antipsychotic Response and Schizophrenia Psychopathology in a Naturalistic Treatment Setting in Two Independent Korean and Italian Samples.

INTRODUCTION: Schizophrenia (SCZ) is one of the most disabling psychiatric disorders. Genetic factors play an important role in both SCZ liability and its treatment outcome. In the present paper, we investigated the effects of several single nucleotide polymorphisms (SNPs) within ten strong candidate genes involved with antipsychotics (APs) mechanisms of action. METHODS: Two independent samples were investigated in the present study. Totals of 176 SCZ subjects and 326 controls of Korean ancestry, and 83 SCZ subjects and 194 controls of Italian ancestry were recruited and genotyped. SCZ risk and other parameters were also investigated. RESULTS: Concerning APs response, only a nominal association with HOMER1 rs3822568 in the Korean sample was found. In the haplotype analysis, rs9801117 C-rs12668837 C-rs4621754 A haplotype within ESYT2 and NCAPG2 genes was associated with APs response in the same sample. As for secondary outcomes, rs7439 within PKDCC and rs12668837 within NCAPG2 were associated with SCZ risk in the Italian sample. In the haplotype analysis, rs2788478 G-rs2657375 T-rs1039621 A within the region between WDR60 and ESYT genes and rs2013 C (ESYT2)-rs6459896 A (NCAPG2) haplotypes were associated with SCZ in the same sample. No association was found in the Korean sample. Finally, our exploratory data suggest a possible modulation of HOMER1, ARC, BDNF, TXNRD2, WDR60, and ESYT2 genes in the APs response to specific symptom clusters. CONCLUSION: Our results did not support a primary role for the genes investigated in the APs response. On the other hand, our secondary results suggest a possible involvement of NACPG2 and PKDCC in SCZ liability. Finally, our exploratory findings may deserve further investigations in specific studies.

Investigational dopamine antagonists for the treatment of schizophrenia.

INTRODUCTION: Schizophrenia is a debilitating illness with a chronic impact on social function and daily living. Although various antipsychotics are available, there are still many challenges and unmet needs. Thus, many compounds with diverse mechanisms have been investigated, but all approved antipsychotics still require interactions with dopamine D2 receptors. Areas covered: We searched for investigational drugs using the key words 'dopamine' and 'schizophrenia' in American and European clinical trial registers (clinicaltrials.gov; clinicaltrialsregister.eu). Published articles were searched in PubMed, Embase, Medline, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Web of Science and the Cochrane Central Register of Controlled Trials Library. Expert opinion: The prospect of developing a dopamine antagonist is hopeful. Brexpiprazole and cariprazine, which were agents listed as 'investigational dopamine antagonists,' just received FDA approval. Novel agents such as BL 1020, ITI-007, and JNJ-37822681 have solid published data available, and agents such as L-THP, Lu AF35700, S33138, and SB-773812 are under vigorous investigation. However, the expected benefits of the newly developed antagonists may not be great because they offer little enhanced efficacy for negative symptoms, cognition and functional outcomes.

Modafinil for the treatment of attention-deficit/hyperactivity disorder: A meta-analysis.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common and a debilitating neuro-behavior disorder in the pediatric population. Although numerous effective psychostimulants are available, more than 30% of patients still do not show adequate treatment response rendering diverse pharmacological options. We aimed at assessing the efficacy and safety of modafinil in the treatment of children and adolescents with ADHD by conducting a meta-analysis. An extensive search of databases and clinical trial registries resulted in five published short-term randomized, double-blind, placebo-controlled trials. Primary efficacy measures were mean change in ADHD Rating Scale-IV Home (ADHD-RS-IV Home) and School Version (ADHD-RS-IV School) from baseline to study end point. The results showed that modafinil more significantly improved ADHD-RS-IV Home (SMD, -0.77 [95%CI, -1.11 to -0.44]) and School (SMD, -0.71 [95%CI, -0.96 to -0.47]) than placebo. Dropout rate due to adverse event did not significantly differ between two groups. In terms of commonly observed side effects, modafinil showed significantly higher incidence of decreased appetite (RR = 5.02, 95% CIs, 2.55 to 9.89, P < 0.00001) and insomnia (RR = 6.16, 95% CIs, 3.40 to 11.17, P < 0.00001). Modafinil did not cause a clinically significant increase of heart rate, systolic blood pressure, and diastolic blood pressure. Although we found that modafinil may be another treatment option in children and adolescents with ADHD, the results should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of clinical trials.

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'.

Second Generation Antipsychotics in the Treatment of Major Depressive Disorder: An Update.

Less than one third of patients who suffer from major depressive disorder (MDD) report remission following antidepressant treatments requiring more diverse treatment approaches. Augmentation of second generation antipsychotics (SGAs) has been increasingly recognized as an important treatment option. The authors have previously provided a comprehensive review of SGAs for the treatment of MDD in 2013. Since then, numerous additional clinical trials have been conducted to investigate diverse issues regarding the utility of SGAs in MDD. Moreover, a new SGA, brexpiprazole, was recently approved by the Food and Drug Administration in July 2015 for the treatment of MDD as an augmentation agent to antidepressants. Thus, the aim of this study was to provide a concise update of all the available SGAs for the treatment of MDD, in particular on the additional clinical trials which have been published since 2013.

Association of treatment response with obesity and other metabolic risk factors in adults with depressive disorders: Results from a National Depression Cohort study in Korea (the CRESCEND study).

BACKGROUND: Available studies indicate that obesity may exert a moderational effect on antidepressant treatment response. The aim of this study was to investigate the relationship between treatment response and metabolic abnormalities amongst patients with depressive disorders in a large naturalistic clinical setting. METHODS: A nationwide prospective study was conducted in 18 hospitals in South Korea; 541 depressive patients meeting DSM-IV criteria were recruited. After baseline evaluation, subjects received naturalistic clinician-determined antidepressant interventions. Assessment was performed at baseline and weeks 1, 2, 4, 8, 12, 24 and 52. Treatment response was defined as a ≥50% reduction from baseline on at least one evaluation point. RESULTS: In univariate comparison, the patients who showed insufficient response to antidepressant therapy were more likely to be male, unmarried, unemployed, and obese. After adjusting for baseline variables, male sex (OR=1.82) and obesity (OR=1.55) remained as were significant variables. Stratification of the subjects into one of three groups, i.e. male, pre-menopausal female and post-menopausal female, revealed that males with concurrent metabolic problems, (i.e. the presence of one or more of hypertension, hyperglycemia, or hypercholesterolemia) had significantly higher risk for insufficient response (OR=2.32) and, after adjusting for baseline variables, obesity predicted insufficient response in post-menopausal female (OR=2.41). CONCLUSIONS: The presence of metabolic abnormalities in patients with depressive disorders was associated with decreased treatment response to antidepressants. These results underscore the neurobiological relationship between obesity and the central nervous system, and provide empiric evidence supporting stratification of treatment response in depression.

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.

Potential Relationship between Season of Birth and Clinical Characteristics in Major Depressive Disorder in Koreans: Results from the CRESCEND Study.

We aimed to examine the potential relationship between season of birth (SOB) and clinical characteristics in Korean patients with unipolar non-psychotic major depressive disorder (MDD). Using data from the Clinical Research Center for Depression (CRESCEND) study in South Korea, 891 MDD patients were divided into two groups, those born in spring/summer (n=457) and those born in autumn/winter (n=434). Measurement tools comprising the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Brief Psychiatric Rating Scale, Scale for Suicidal Ideation, Clinical Global Impression of severity, Social and Occupation Functional Assessment Scale, WHO Quality of Life assessment instrument-abbreviated version, Alcohol Use Disorder Identification Test, and Temperament and Character Inventory were used to evaluate depression, anxiety, overall symptoms, suicidal ideation, global severity, social function, quality of life, drinking, and temperament and character, respectively. Using independent t-tests for continuous variables and χ² tests for discrete variables, the clinical characteristics of the two groups were compared. MDD patients born in spring/summer were on average younger at onset of first depressive episode (t=2.084, p=0.038), had greater loss of concentration (χ²=4.589, p=0.032), and were more self-directed (t=2.256, p=0.025) than those born in autumn/winter. Clinically, there was a trend for the MDD patients born in spring/summer to display the contradictory characteristics of more severe clinical course and less illness burden; this may have been partly due to a paradoxical effect of the 5-HT system.