Early-onset Major Depression Research Articles

GluCEST Imaging and Structural Alterations of the Bilateral Hippocampus in First-Episode and Early-Onset Major Depression Disorder.

Glutamate dysregulation is one of the key pathogenic mechanisms of major depressive disorder (MDD), and glutamate chemical exchange saturation transfer (GluCEST) has been used for glutamate measurement in some brain diseases but rarely in depression. To investigate the GluCEST changes in hippocampus in MDD and the relationship between glutamate and hippocampal subregional volumes. Cross-sectional. Thirty-two MDD patients (34% males; 22.03 ± 7.21 years) and 47 healthy controls (HCs) (43% males; 22.00 ± 3.28 years). 3.0 T; magnetization prepared rapid gradient echo (MPRAGE) for three-dimensional T1-weighted images, two-dimensional turbo spin echo GluCEST, and multivoxel chemical shift imaging (CSI) for proton magnetic resonance spectroscopy (1 H MRS). GluCEST data were quantified by magnetization transfer ratio asymmetry (MTRasym ) analysis and assessed by the relative concentration of 1 H MRS-measured glutamate. FreeSurfer was used for hippocampus segmentation. The independent sample t test, Mann-Whitney U test, Spearman's correlation, and partial correlation analysis were used. P < 0.05 was considered statistically significant. In the left hippocampus, GluCEST values were significantly decreased in MDD (2.00 ± 1.08 [MDD] vs. 2.62 ± 1.41 [HCs]) and showed a significantly positive correlation with Glx/Cr (r = 0.37). GluCEST values were significantly positively correlated with the volumes of CA1 (r = 0.40), subiculum (r = 0.40) in the left hippocampus and CA1 (r = 0.51), molecular_layer_HP (r = 0.50), GC-ML-DG (r = 0.42), CA3 (r = 0.44), CA4 (r = 0.44), hippocampus-amygdala-transition-area (r = 0.46), and the whole hippocampus (r = 0.47) in the right hippocampus. Hamilton Depression Rating Scale scores showed significantly negative correlations with the volumes of the left presubiculum (r = -0.40), left parasubiculum (r = -0.47), and right presubiculum (r = -0.41). GluCEST can be used to measure glutamate changes and help to understand the mechanism of hippocampal volume loss in MDD. Hippocampal volume changes are associated with disease severity. 2 TECHNICAL EFFICACY: Stage 1.

P714. Pilot Study of Early-Onset Major Depression and Exosomal MicroRNA Cargo Enriched for Neuronal Cell Origin

Major depression (MD) is highly prevalent, ranking second in the global burden of disease, with an overall lifetime risk estimated to be 16.2% in the general population. This pilot study addresses the molecular genetics of early life depression by characterizing the composition of extracellular vesicle (ECV) microRNA cargo in a phenotypically rich, extant twin sample (Parent R01 MH101518; Ntotal=860 twins; ages 15-22; 57% female). We will target both bulk and neuronal-enriched ECVs and analyze the microRNA (miRNA) cargo to investigate potential biomarkers of differential biological pathway regulation based on multiple definitions and markers of MD in young people.

Hippocampal and Hippocampal-Subfield Volumes From Early-Onset Major Depression and Bipolar Disorder to Cognitive Decline.

Background: The hippocampus and its subfields (HippSub) are reported to be diminished in patients with Alzheimer's disease (AD), bipolar disorder (BD), and major depressive disorder (MDD). We examined these groups vs healthy controls (HC) to reveal HippSub alterations between diseases.Methods: We segmented 3T-MRI T2-weighted hippocampal images of 67 HC, 58 BD, and MDD patients from the AFFDIS study and 137 patients from the DELCODE study assessing cognitive decline, including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and AD, via Free Surfer 6.0 to compare volumes across groups.Results: Groups differed significantly in several HippSub volumes, particularly between patients with AD and mood disorders. In comparison to HC, significant lower volumes appear in aMCI and AD groups in specific subfields. Smaller volumes in the left presubiculum are detected in aMCI and AD patients, differing from the BD group. A significant linear regression is seen between left hippocampus volume and duration since the first depressive episode.Conclusions: HippSub volume alterations were observed in AD, but not in early-onset MDD and BD, reinforcing the notion of different neural mechanisms in hippocampal degeneration. Moreover, duration since the first depressive episode was a relevant factor explaining the lower left hippocampal volumes present in groups.

An epigenome-wide association study of early-onset major depression in monozygotic twins

Major depression (MD) is a debilitating mental health condition with peak prevalence occurring early in life. Genome-wide examination of DNA methylation (DNAm) offers an attractive complement to studies of allelic risk given it can reflect the combined influence of genes and environment. The current study used monozygotic twins to identify differentially and variably methylated regions of the genome that distinguish twins with and without a lifetime history of early-onset MD. The sample included 150 Caucasian monozygotic twins between the ages of 15 and 20 (73% female; Mage = 17.52 SD = 1.28) who were assessed during a developmental stage characterized by relatively distinct neurophysiological changes. All twins were generally healthy and currently free of medications with psychotropic effects. DNAm was measured in peripheral blood cells using the Infinium Human BeadChip 450 K Array. MD associations with early-onset MD were detected at 760 differentially and variably methylated probes/regions that mapped to 428 genes. Genes and genomic regions involved neural circuitry formation, projection, functioning, and plasticity. Gene enrichment analyses implicated genes related to neuron structures and neurodevelopmental processes including cell–cell adhesion genes (e.g., PCDHA genes). Genes previously implicated in mood and psychiatric disorders as well as chronic stress (e.g., NRG3) also were identified. DNAm regions associated with early-onset MD were found to overlap genetic loci identified in the latest Psychiatric Genomics Consortium meta-analysis of depression. Understanding the time course of epigenetic influences during emerging adulthood may clarify developmental phases where changes in the DNA methylome may modulate individual differences in MD risk.

Similarities of Aspects of Biological Rhythms between Major Depression and Bipolar II Disorder Compared to Bipolar I Disorder: A Finding from the Early-Onset Mood Disorder Cohort.

ObjectiveThe biological rhythm is closely related to mood symptoms. The purpose of this study was to assess the differences in biological rhythms among subjects with mood disorder [bipolar I disorder (BD I), bipolar II disorder (BD II), major depressive disorder (MDD)] and healthy control subjects. MethodsA total of 462 early-onset mood disorder subjects were recruited from nine hospitals. The controls subjects were recruited from the general population of South Korea. Subject groups and control subject were evaluated for the Korean language version of Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN) at the initial evaluation. ResultsThe mean K-BRIAN scores were 35.59 [standard deviation (SD)=13.37] for BD I, 43.05 (SD=11.85) for BD II, 43.55 (SD=12.22) for MDD, and 29.1 (SD=8.15) for the control group. In the case of mood disorders, biological rhythm disturbances were greater than that in the control group (p<0.05). A significant difference existed between BD I and BD II (BD I <BD II, p<0.001) and between BD I and MDD (BD I<MDD, p< 0.001) but no difference was observed between BD II and MDD. ConclusionBD II and MDD are similar to each other but different from BD I in biological rhythm patterns in early-onset mood disorder cases. Biological rhythm disturbances are similar for early-onset major depression and BD II.

De novo variant of TRRAP in a patient with very early onset psychosis in the context of non-verbal learning disability and obsessive-compulsive disorder: a case report

BackgroundTRRAP encodes a multidomain protein kinase that works as a genetic cofactor to influence DNA methylation patterns, DNA damage repair, and chromatin remodeling. TRRAP protein is vital to early neural developmental processes, and variants in this gene have been associated with schizophrenia and childhood disintegrative disorder.Case presentationHere, we report on a patient with a de novo nonsynonymous TRRAP single-nucleotide variant (EST00000355540.3:c.5957G > A, p.Arg1986Gln) and early onset major depression accompanied by a psychotic episode (before age 10) that occurred in the context of longer standing nonverbal learning disability and a past history of obsessions and compulsions.ConclusionsThe de novo variant and presentation of very early onset psychosis indicate a rare Mendelian disorder inheritance model. The genotype and behavioral abnormalities of this patient are reviewed.

Young adult cognitive ability and subsequent major depression in a cohort of 666,804 Danish men

BackgroundEarly life cognitive ability (CA) might influence the risk of developing major depression (MD). The aim was to investigate the association between young adult CA and subsequent MD in relation to different MD disease characteristics. MethodsInformation on CA was assessed at conscription board examinations 1957–1984 (mean age 19 years) and information on MD was based on hospital diagnosis retrieved from Danish Patient registers 1969–2015. Associations between CA and MD were examined using Cox regression analyses. ResultsA total of 666,804 men (born 1939–1959) were followed and 25,841 (3.9%) developed MD during a mean follow-up of 40.8 years. Lower CA was associated with an increased risk of incident MD. The association was stronger for early-onset (<60 years) (HRper1SDdecrease = 1.23; 95%CI:1.21,1.24) compared to late-onset (≥60 years) MD (HRper1SDdecrease = 1.14; 95%CI:1.11,1.16), but CA was not related to number of depressive episodes. The association was stronger for single depressive episodes (HRper1SDdecrease = 1.21; 95%CI:1.19,1.23) compared to recurrent depression (HRper1SDdecrease = 1.13; 95%CI:1.09,1.16), while the strength of the association did not differ according to MD disease severity (ICD10: mild, moderate, and severe depression). LimitationsThe study sample only included men and only MD cases diagnosed at hospital were included which limits the generalizability. ConclusionLow CA could be a risk factor for especially early onset MD in men, whereas the influence of CA on re-occurrence seems less strong. Lower pre-morbid CA increases the risk of MD and should therefore be part of the depression risk assessment in clinical practice.

A Genetic Susceptibility Mechanism for Major Depression: Combinations of polymorphisms Defined the Risk of Major Depression and Subpopulations.

Major Depression (MD) is a highly inherited psychiatric disorder. The norepinephrine transporter (NET) gene plays important role in pathophysiology of MD. This study attempted to examine the relationship between polymorphisms of NET gene and MD.Patients with MD and healthy controls were recruited and subgrouped. The T-182C and G1287A polymorphisms of NET gene were genotyped by direct sequencing. The genotypic and allelic frequencies were compared using the Pearson χ2 analysis. The linkage disequilibrium was analyzed using the UNPHASED program.Significant differences in genotypic and allelic frequencies of T-182C polymorphism were observed between MD subgroups and controls. When referenced by TT genotype, the OR value increased gradient from TC to CC genotype; when referenced by T allele, the odds ratio value of C allele also increased. Compared with those having both −182 T/T and 1287 G/G genotypes, in patients with MD, early-onset MD, and MD with suicide concept group, the −182 C/C and 1287 G/A combinatorial genotype has significant risk; yet in patients with MD family history, the −182 C/C and 1287 A/A combinatorial genotype has significant risk.Different combinations of T-182C and the G1287A polymorphisms of NET gene might increase morbidity risk of MD subpopulations.

Metamoodics: meta-analysis and bioinformatics resource for mood disorders

Mood disorders, including Major Depression (MD) and Bipolar Disorder (BP), are among the most common psychiatric disorders1. Although genetic factors play an important role in their etiology2, 3, the heritability of these disorders remains largely unexplained. Due to advances in high-throughput genomic technologies, it is becoming increasingly feasible to investigate the genetic architecture of these disorders at an unprecedented resolution. The challenge is how to make sense of the enormous flood of data generated by the diverse genomic studies that use these new technologies. It is essential to integrate the findings from such studies in order to develop a more comprehensive understanding of the genetic contribution to these disorders that can be readily translated into new and more rational therapeutic interventions. Towards this end, we have developed a bioinformatics resource called Metamoodics (www.metamoodics.org), which integrate results from various genomic studies of mood disorders and enhance their interpretation by placing them within an enriched genomic context. Metamoodics was created as a resource for the research community to explore what is currently known about the genetic contribution to mood disorders. Metamoodics synthesizes data from existing genome-wide linkage, expression and association studies for both MD and BP. It brings together results from up-to-date meta- or mega-analyses of these studies, and presents them in both tabular and graphical modes. The genome-wide linkage data comes from among the largest and most comprehensive of such studies with MD and BP. Data for BP comes from a mega-analysis carried out with 972 informative pedigrees of European ancestry pooled from eight research groups in North America and the United Kingdom3. Linkage statistics for twelve different phenotype-by-genotype models were calculated for a genome-wide panel of 6090 SNPs. For MD, data from the Genetics of Recurrent Early-Onset Major Depression (GenRED) collaborative are provided4. This included data on 418 microsatellite markers genotyped in 656 families consisting of 1,494 all possible informative affective relative pairs. Data for genome-wide association studies (GWAS) were obtained from the psychiatric GWAS consortium (PGC). For BP, the sample included 7,481 cases and 9,250 controls, all of European ancestry, with data on ~2.5M genotyped and/or imputed SNPs5. Data on MD consisted of more than 1.2 million SNPs in 9,240 cases and 9,519 controls of recent European ancestry6. Gene expression data was obtained through a systematic review of studies on BP (n=13) and MD (n=7) using post-mortem brain tissue. Mega-analyses of the most comprehensive and rigorous of these studies were carried out using samples from all regions of the brain, the pre-frontal cortex, and the hippocampus, where sufficient data was available7. Finally, Metamoodics includes a comprehensive meta-analysis of published candidate gene association studies of BP. Data on 33 polymorphisms in 18 genes reported on by three or more case-control studies were included in the meta-analysis8. A similar meta-analysis for MD is forthcoming. Metamoodics includes a variety of online applications and tools for visualization and further analysis of the genomics data. Data visualization makes use of NCBI SeqView API and a local mirror of the UCSC genome browser. The results can be queried by gene or chromosomal position to obtain either a gene level view via chromosomal or regional plots, or a more global view via the genome browser to investigate the genomic context of the findings. User-defined data can be uploaded to the genome browser using the custom track option to visualize alongside the Metamoodics tracks. Analysis tools include SVAw9 for surrogate variable analysis, METAw for meta-analysis and a gene expression package for individual and mega analysis of expression data. Metamoodics presents the latest results from genomic studies of mood disorders in a user-friendly web interface that enables users to rapidly compare findings from different experimental platforms across the genome, as well as drill down to specific findings to visualize how these relate to underlying genomic structure and function. Metamoodics provides the entire set of results of a given study rather than just significant ones, thus providing a complete and unbiased report of the findings. We will continue to update Metamoodics with findings from the latest genomic experiments of mood disorders, such as whole exome or genome sequencing and epigenetic studies. Metamoodics is a vital bioinformatics tool for investigating the genetic etiology of mood disorders that will only grow more powerful as new data are added.

The dopamine transporter gene possibly affects personality traits in patients with early-onset major depressive disorder.

Comorbid personality pathologies may affect the outcome of patients with major depression (MD). The dopamine transporter gene DAT1 (SLC6A3) has been suggested to play a role in both depression and specific personality traits. The aim of this study was to assess five polymorphisms of the DAT1 gene (rs2550948, rs2975226, rs6347, rs27072, and 3'-VNTR) to determine whether this gene influences personality traits in patients with MD or its subgroups. The DAT1 polymorphisms were analysed in 463 unrelated Han Chinese MD patients. The personality traits, novelty seeking (NS), and harm avoidance (HA), were examined using the Tridimensional Personality Questionnaire. The patients were also divided into four clinical subgroups on the basis of differences in their sex (male or female) and age at disease onset (early or late). There was no association between the DAT1 gene and either NS or HA in the total MD sample or in the sex-based subgroups. However, early-onset MD patients with the G/G genotype of rs2550948 and the T/T genotype of rs2975226 had lower NS scores than did patients with the other genotypes (p corrected = 0.05 for rs2550948 and p corrected = 0.005 for rs2975226). Our study suggests that DAT1 promoter variants possibly influence specific personality traits in the early-onset subgroup of depressed patients in the Han Chinese population. Further prospective cohort studies are required to verify our preliminary finding and to confirm the effects of personality susceptibility on long-term disease outcomes.

Predictors of Alcohol Dependence Relapse During Recurrence of Major Depression

This study sought to determine clinical predictors of alcohol relapse during recurrence of major depression. The total sample included 2,820 adults with a history of alcohol dependence who had a comorbid current episode of major depression. Twenty-six percent had a relapse of alcohol dependence. Relapsers were more likely to be male, single, less educated, and younger than non-relapsers. Early onset alcohol dependence and past year drug use disorder significantly increased the likelihood of relapse. Early onset substance use dependence is a more powerful predictor of alcohol relapse than early onset major depression.

La cimentation complète ou partielle de l’embase tibiale d’une PTG n’influe pas sur la survie

Our study aims at replicating our previous finding of an association between COMT rs4680 G/A polymorphism and early onset major depression (MD). We included 462 MD, 147 bipolar disorders (BD) subjects and 295 healthy controls. We could partially replicate previous findings. In particular, rs4680 GG + AG genotypes were more represented in the subgroup of early onset MD patients (p = 0.04). Additionally, we observed an association between rs737865 alleles and early onset MD (p = 0.04). Rs4680 genotype was associated with early onset BD as well (p = 0.01). In conclusion, we partially replicated our previous findings confirming a possible influence of COMT variants in MD and BD, particularly in early onset subjects, though not with the same risk genotypes.

Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression

Early-onset major depressive disorder (MDD) is a serious and prevalent psychiatric illness in adolescents and young adults. Current treatments are not optimally effective. Biological markers of early-onset MDD could increase diagnostic specificity, but no such biomarker exists. Our innovative approach to biomarker discovery for early-onset MDD combined results from genome-wide transcriptomic profiles in the blood of two animal models of depression, representing the genetic and the environmental, stress-related, etiology of MDD. We carried out unbiased analyses of this combined set of 26 candidate blood transcriptomic markers in a sample of 15–19-year-old subjects with MDD (N=14) and subjects with no disorder (ND, N=14). A panel of 11 blood markers differentiated participants with early-onset MDD from the ND group. Additionally, a separate but partially overlapping panel of 18 transcripts distinguished subjects with MDD with or without comorbid anxiety. Four transcripts, discovered from the chronic stress animal model, correlated with maltreatment scores in youths. These pilot data suggest that our approach can lead to clinically valid diagnostic panels of blood transcripts for early-onset MDD, which could reduce diagnostic heterogeneity in this population and has the potential to advance individualized treatment strategies.

COMT and age at onset in mood disorders: A replication and extension study

Our study aims at replicating our previous finding of an association between COMT rs4680 G/A polymorphism and early onset major depression (MD). We included 462 MD, 147 bipolar disorders (BD) subjects and 295 healthy controls. We could partially replicate previous findings. In particular, rs4680 GG + AG genotypes were more represented in the subgroup of early onset MD patients ( p = 0.04). Additionally, we observed an association between rs737865 alleles and early onset MD ( p = 0.04). Rs4680 genotype was associated with early onset BD as well ( p = 0.01). In conclusion, we partially replicated our previous findings confirming a possible influence of COMT variants in MD and BD, particularly in early onset subjects, though not with the same risk genotypes.

Mood Disorder Susceptibility Gene CACNA1C Modifies Mood-Related Behaviors in Mice and Interacts with Sex to Influence Behavior in Mice and Diagnosis in Humans

Recent genome-wide association studies have associated polymorphisms in the gene CACNA1C, which codes for Ca(v)1.2, with a bipolar disorder and depression diagnosis. The behaviors of wild-type and Cacna1c heterozygous mice of both sexes were evaluated in a number of tests. Based upon sex differences in our mouse data, we assessed a gene × sex interaction for diagnosis of mood disorders in human subjects. Data from the National Institute of Mental Health Genetics Initiative Bipolar Disorder Consortium and the Genetics of Recurrent Early-Onset Major Depression Consortium were examined using a combined dataset that included 2021 mood disorder cases (1223 female cases) and 1840 control subjects (837 female subjects). In both male and female mice, Cacna1c haploinsufficiency was associated with lower exploratory behavior, decreased response to amphetamine, and antidepressant-like behavior in the forced swim and tail suspension tests. Female, but not male, heterozygous mice displayed decreased risk-taking behavior or increased anxiety in multiple tests, greater attenuation of amphetamine-induced hyperlocomotion, decreased development of learned helplessness, and a decreased acoustic startle response, indicating a sex-specific role of Cacna1c. In humans, sex-specific genetic association was seen for two intronic single nucleotide polymorphisms, rs2370419 and rs2470411, in CACNA1C, with effects in female subjects (odds ratio = 1.64, 1.32) but not in male subjects (odds ratio = .82, .86). The interactions by sex were significant after correction for testing 190 single nucleotide polymorphisms (p = 1.4 × 10⁻⁴, 2.1 × 10⁻⁴; p(corrected) = .03, .04) and were consistent across two large datasets. Our preclinical results support a role for CACNA1C in mood disorder pathophysiology, and the combination of human genetic and preclinical data support an interaction between sex and genotype.

P03-278 - Gene-environment interactions of corticotropin-releasing hormone receptor 1 (CRHR1) and stressful life events in suicide attempts

ObjectivesSuicide is a leading cause of death in young people worldwide. Risk factors for suicidal behaviors and endophenotypes are partly heritable, and include variants in genes that drive stress diathesis in addition to, or by interaction with, certain adverse environments. Hypothalamic-Pituitary-Adrenal (HPA) axis genes are candidates for association with the dysregulated cortisol response to psychosocial stress that is observed in suicidal individuals. The role of HPA axis genetic variation will be explored in the context of varying “susceptibility” to suicidality after exposure to certain stressful life events.MethodsA family-based association test was used on a case offspring-parent “trio” sample of 672 suicide attempt cases and their parents. Single nucleotide polymorphisms (SNP's) and/or haplotypes in CRHR1 were studied for interaction with age of exposure to physical and/or sexual assault, gender, and/or lifetime exposure to other types of stressful events.ResultsPreliminary findings show interactions of certain CRHR1 SNP's with sexual and/or physical assault that are associated with suicide attempt, possibly using a violent method. Possible associations with candidate endophenotypes such as Cluster B personalities and early-onset major depression are under investigation.ConclusionsInteractions of HPA axis genetic variants and stressful life events are consistent with a stress diathesis model of suicidal behavior, and may additionally influence the method and medical damage outcomes of suicide attempts, which may explain part of the diversity within this phenotype.

Impaired implicit learning and reduced pre-supplementary motor cortex size in early-onset major depression with melancholic features

Background:Major depression is a heterogeneous disorder. Biological markers and cognitive tasks have been employed to distinguish clinical subtypes but results have been inconclusive. Methods:The current study assessed implicit learning with the Serial Reaction Time Task (SRTT) known to be sensitive to frontostriatal dysfunctions and regional brain volumes of the anterior supplementary motor area (pre-SMA) in participants with early-onset major depression (MD) of either melancholic (n=26) or non-melancholic (n=9) subtype, and 26 matched controls. Results:Depressive subjects with melancholic features but not those with non-melancholic depression showed implicit learning deficits. This deficit could not be explained in terms of more severe depression or psychomotor retardation. Regional volumes of the right pre-SMA were reduced in depressive subjects with melancholic features. Limitations:Medication effects in depressive subjects and the small size of the non-melancholic sample should be taken into consideration when reviewing the implications of these results. Conclusions:Deficits in implicit motor sequence learning seem to be an additional characteristic of the melancholic subtype of depression. It might be linked to dysfunction within structural or functionally altered frontostriatal circuits. Use of implicit sequence learning tasks could offer useful diagnostic and aetiological cues for future research.

Premenstrual mood symptoms: study of familiality and personality correlates in mood disorder pedigrees

We sought to determine whether premenstrual mood symptoms exhibit familial aggregation in bipolar disorder or major depression pedigrees. Two thousand eight hundred seventy-six women were interviewed with the Diagnostic Interview for Genetic Studies as part of either the NIMH Genetics Initiative Bipolar Disorder Collaborative study or the Genetics of Early Onset Major Depression (GenRED) study and asked whether they had experienced severe mood symptoms premenstrually. In families with two or more female siblings with bipolar disorder (BP) or major depressive disorder (MDD), we examined the odds of having premenstrual mood symptoms given one or more siblings with these symptoms. For the GenRED MDD sample we also assessed the impact of personality as measured by the NEO-FFI. Premenstrual mood symptoms did not exhibit familial aggregation in families with BP or MDD. We unexpectedly found an association between high NEO openness scores and premenstrual mood symptoms, but neither this factor, nor NEO neuroticism influenced evidence for familial aggregation of symptoms. Limitations include the retrospective interview, the lack of data on premenstrual dysphoric disorder, and the inability to control for factors such as medication use.

Association Between Age of Onset and Symptom Profiles of Late-Life Depression

Objective:The recognition of later late-onset (LLO) major depression (MD) is a matter of concern.Method:Cross-sectional study assessed MD with the MINI structured interview and the MADRS in a referred sample of 13 377 non-demented adult out-patients visiting their physicians. Among 6850 patients with a first episode of MD, 370 LLO (75 years of age and older) MD were compared with 814 late-onset (LO) (60-74 years old) MD and 5666 early-onset (EO) (18-59 years old) MD.Results:There are many similarities between the symptom patterns of EO, LO and LLO MDs. However, the symptom pattern of LLO MD includes more retardation/agitation, lassitude, reduced appetite and apparent sadness, and less sleep disturbances, guilt feelings, pessimism and inner tension than LO and EO MD.Conclusion:The differences in symptom profiles are very modest and between-group differences may not be meaningful on an individual level.

Association between age of onset and symptom profiles of late‐life depression

The recognition of later late-onset (LLO) major depression (MD) is a matter of concern. Cross-sectional study assessed MD with the MINI structured interview and the MADRS in a referred sample of 13 377 non-demented adult out-patients visiting their physicians. Among 6850 patients with a first episode of MD, 370 LLO (75 years of age and older) MD were compared with 814 late-onset (LO) (60-74 years old) MD and 5666 early-onset (EO) (18-59 years old) MD. There are many similarities between the symptom patterns of EO, LO and LLO MDs. However, the symptom pattern of LLO MD includes more retardation/agitation, lassitude, reduced appetite and apparent sadness, and less sleep disturbances, guilt feelings, pessimism and inner tension than LO and EO MD. The differences in symptom profiles are very modest and between-group differences may not be meaningful on an individual level.