Age Of Depression Onset Research Articles

Characteristics of early and late onset pediatric depression

IntroductionDepression, anxiety and suicide are serious psychiatric conditions that affect Mexican youth (Institute for Health Metrics and Evaluation, IHME, 2022), with depression showing a prevalence greater than 16%. Suicide ranks as the second most important cause of deathin this age group, (6/100,000 deaths), the first being violent deaths by firearms (15/100,000 deaths;IHME, 2022).ObjectivesTo identify factors related to age of onset of pediatric depression.MethodsA cross-sectional study was carried out during 2018-2020 in two Children’s Psychiatric Hospitals in Mexico City. Data were collected using a survey method. All participants signed an informed consent form. We applied Cox hazard analysis, with the hazard event being the onset of psychiatric symptoms.ResultsData from 400 patients were analyzed, 148 girls (37%) and 252 boys (63%). Mean patient age was 12 years, and mean age of symptom onset was 8 years. The most common diagnoses were hyperkinetic disorder (51%), depression (34%), and anxiety (7.8%). Age of depression onset was significantly reduced in association with male sex (HR=1.46), family history of psychiatric disorder (familial depression HR=2.34; hyperkinetic disorder HR=2.67; psychoactive substance abuse HR=5.09), and certain medical comorbidities (asthma HR=6.41; enuresis HR=3.03). These same covariates were not associated with age of onset of hyperkinetic disorder or anxiety.ConclusionsThese analyses indicate that a subgroup of pediatric depression has an early onset and is associated with familial hyperkinetic disorder and depression, the male sex, and certain medical comorbidities.Disclosure of InterestNone Declared

Clinical Outcomes Following Acute Residential Psychiatric Treatment in Transgender and Gender Diverse Adolescents

Transgender and gender diverse (TGD) individuals, who have a gender identity that differs from their sex assigned at birth, are at increased risk of mental health problems, including depression, anxiety, self-injurious behavior, and suicidality, relative to cisgender peers. To examine mental health outcomes among TGD vs cisgender adolescents in residential treatment. This cohort study's longitudinal design was used to compare groups at treatment entry and discharge, and 1-month postdischarge follow-up. The setting was an adolescent acute residential treatment program for psychiatric disorders. Participants were TGD or cisgender adolescents enrolled in the treatment program. Statistical analysis was performed October 2019 to March 2021. Adolescents participated in a 2-week acute residential treatment program for psychiatric disorders. Primary outcomes were depressive (the Center for Epidemiologic Studies Depression Scale [CES-D]) and anxiety (the Multidimensional Anxiety Scale for Children [MASC]) symptoms, and emotional dysregulation (the Difficulties in Emotion Regulation Scale [DERS]), measured at treatment entry and discharge, and postdischarge follow-up. Age of depression onset, suicidality, self-injury, and childhood trauma also were assessed at treatment entry. Of 200 adolescent participants who completed treatment entry and discharge assessments, the mean (SD) age was 16.2 (1.5) years; 109 reported being assigned female at birth (54.5%), 35 were TGD (17.5%), and 66 (49.3%) completed 1-month follow-up. TGD participants had an earlier mean (SD) age of depression onset (TGD: 10.8 [2.4] years vs cisgender: 11.9 [2.3] years; difference: 1.07 years; 95% CI, 0.14-2.01 years; P = .02), higher mean (SD) suicidality scores (TGD: 44.4 [23.1] vs cisgender: 28.5 [25.4]; difference: 16.0; 95% CI, 6.4-25.5; P = .001), more self-injurious behavior (mean [SD] RBQ-A score for TGD: 3.1 [2.5] vs cisgender: 1.7 [1.9]; difference: 1.42; 95% CI, 0.69-2.21; P = .001) and more childhood trauma (eg, mean [SD] CTQ-SF score for emotional abuse in TGD: 12.7 [5.4] vs cisgender: 9.8 [4.7]; difference: 2.85; 95% CI, 1.06-4.64; P = .002). The TGD group also had higher symptom scores (CES-D mean difference: 7.69; 95% CI, 3.30 to 12.08; P < .001; MASC mean difference: 7.56; 95% CI, 0.46 to 14.66; P = .04; and DERS mean difference: 18.43; 95% CI, 8.39 to 28.47; P < .001). Symptom scores were significantly higher at entry vs discharge (CES-D mean difference, -12.16; 95% CI, -14.50 to -9.80; P < .001; MASC mean difference: -3.79; 95% CI, -6.16 to -1.42; P = .02; and DERS mean difference: -6.37; 95% CI, -10.80 to -1.94; P = .05) and follow-up (CES-D mean difference: -9.69; 95% CI, -13.0 to -6.42; P < .001; MASC mean difference: -6.92; 95% CI, -10.25 to -3.59; P < .001; and DERS mean difference: -12.47; 95% CI, -18.68 to -6.26; P < .001). This cohort study found mental health disparities in TGD youth relative to cisgender youth, with worse scores observed across assessment time points. For all participants, primary clinical outcome measures were significantly lower at treatment discharge than at entry, with no significant differences between discharge and 1-month follow-up. Given the substantial degree of mental health disparities reported in TGD individuals, these findings warrant focused clinical attention to optimize treatment outcomes in gender minority populations.

The association of phasic irritability (aggressive outbursts) and tonic irritability (irritable mood) to depression occurrences, symptoms, and subtypes

BackgroundResearch among adults has rarely differentiated between tonic irritability (i.e., irritable mood) and phasic irritability (i.e., aggressive outbursts) with respect to multiple dimensions of depression. The current study explored both tonic and phasic irritability in relation to depression severity, depression chronicity, age of depression onset, individual depressive symptom, and depression subtypes. MethodsThe study included participants (N = 5692) from the National Comorbidity Survey – Replication (NCS-R) part two. The NCS-R used lay-administered, fully standardized diagnostic interviews. The current study implemented linear models, generalized linear models, Cox proportional hazard model, and latent class regression. ResultsBoth types of irritability were significantly associated with greater risk for MDD diagnosis, as well as risk for having at least one depressive symptom, early MDE onset, and MDE chronicity. Both phasic and tonic irritability were associated with greater odds of specific depressive symptoms and were differentially related to distinct depressive symptom constellations. Phasic irritability related only to severe depression. Lastly, both phasic and tonic irritability was associated with suicidal ideation, but only phasic irritability was associated with a suicide plan and attempt, above and beyond depression subtypes. ConclusionsBoth phasic and tonic irritability differentially related to almost all aspects of depression in adults. Specifically, tonic irritability showed overall stronger associations with various depressive features, whereas phasic irritability marked higher depressive severity.

The Rapid Mood Screener (RMS): a novel and pragmatic screener for bipolar I disorder

Objective Depressive episodes and symptoms of bipolar I disorder are commonly misdiagnosed as major depressive disorder (MDD) in primary care. The novel and pragmatic Rapid Mood Screener (RMS) was developed to screen for manic symptoms and bipolar I disorder features (e.g. age of depression onset) to address this unmet clinical need. Methods A targeted literature search was conducted to select concepts thought to differentiate bipolar I from MDD and screener tool items were drafted. Items were tested and refined in cognitive debriefing interviews with individuals with self-reported bipolar I or MDD (n = 12). An observational study was conducted to evaluate predictive validity. Participants with clinical interview-confirmed bipolar I or MDD diagnoses (n = 139) completed a draft 10-item screening tool and other questionnaires. Data were analyzed to identify the smallest possible subset of items with optimized sensitivity and specificity. Results Adults with confirmed bipolar I (n = 67) or MDD (n = 72) participated in the observational study. Ten draft screening tool items were reduced to 6 final RMS items based on the item-level analysis. When 4 or more items of the RMS were endorsed (“yes”), sensitivity was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. These properties were an improvement over the Mood Disorder Questionnaire in the same analysis sample while using 60% fewer items. Conclusion The pragmatic 6-item RMS differentiates bipolar I disorder from MDD in patients with depressive symptoms, providing real-world guidance to primary care practitioners on whether a more comprehensive assessment for bipolar I disorder is warranted.

Depression and the apathy symptom are associated with poorer cognitive functioning in very old men

AbstractBackgroundOlder adults (65+) are among the fastest growing segments of the population, projected to double by 2050. Oldest‐old (85+) manifest the greatest relative increase in population and have the greatest risk of developing Alzheimer’s Disease (AD). Depression is a chronic, debilitating condition in older adults. Depressive symptoms, particularly apathy—and poor concentration—have been associated with poor cognitive functioning and dementia. However, some associations depend upon gender, age of depression onset, and preexisting cognitive impairment; other studies find no association. Associations have been primarily in relatively young samples, and apathy has infrequently been studied in the very old. We investigated the cross‐sectional associations of depressive symptoms and apathy with cognitive functioning in cognitively normal very old men.MethodsParticipants consisted of 74 cognitively intact male veterans (age = 86 ±5.1 [mean ± SD], range = 76‐98; 81.1 % White, 18.9% Black; 15‐item Geriatric Depression Scale [GDS] = 2.6 ±2.7, range = 0‐12; 13.5% depressed [GDS ≥ 6]) enrolled in the Cardiovascular Risk Factors and Successful Cognitive Aging in Very Old Male Veterans study. The predictors were the GDS‐15 and the apathy item “Have you dropped many of your activities and interests?” Cognitive outcomes, from factor analysis of 11 neuropsychological test scores, were three Varimax factor cognitive domains (Episodic Memory, Attention, Executive Function), and the first principal component (global cognition). Linear regression analyses adjusted for age and education.ResultsDepressive symptoms were significantly associated with poorer global cognition (r = ‐.274, p = .020). Apathy was significantly associated with poorer Attention (r = ‐.403, p &lt; .001) and global cognition (r = ‐.377, p = .001). Apathy remained significant after controlling for the sum of other depressive symptoms.ConclusionThese results extend others’ findings by showing that depressive symptoms, and specifically apathy, are associated with poorer cognitive functioning in very old men. This study highlights the relevance of examining depressive symptoms as predictors of cognitive functioning. The small effect sizes (r ≤ .097) for memory, the hallmark cognitive symptom of AD, suggest possible non‐AD biological involvement. Future studies with larger and more demographically and ethnically diverse samples are warranted.

Predictors of Cognitive Improvement Following Treatment for Late-Life Depression.

Cognitive impairment is frequently comorbid with late-life depression (LLD) and often persists despite remission of mood symptoms with antidepressant treatment. Increasing understanding of factors that predict improvement of cognitive symptoms in LLD is useful to inform treatment recommendations. We used data from 2 randomized clinical trials of geriatric depression to examine the relationships between sociodemographic factors (resilience, quality of life) and clinical factors (age of depression onset, severity of depression, apathy) with subsequent cognitive outcomes. One hundred sixty-five older adults with major depression who had completed one of 2 clinical trials were included: (1) methylphenidate plus placebo, citalopram plus placebo, and citalopram plus methylphenidate or (2) citalopram combined with Tai Chi or health education. A comprehensive neuropsychiatric battery was administered; 2 measures of cognitive improvement were examined, one defined as an increase in general cognitive performance score of at least 1 standard deviation and the other 0.5 standard deviation pre-post treatment. At posttreatment, 59% of participants had remitted, but less than a third of those who remitted showed cognitive improvement (29%). Cognitive improvement was observed in 18% of nonremitters. Lower baseline depression severity, greater social functioning, and depression onset prior to 60 years of age were significantly associated with cognitive improvement. None of the other measures, including baseline apathy, resilience, and depression remission status, were significantly associated with cognitive improvement. Lower severity of depression, earlier onset, and greater social functioning may predict improvement in cognitive functioning with treatment for depression in LLD.

Neurocognitive profile of outpatients with unipolar depressive disorders

ABSTRACTIntroduction: It is widely accepted that major depressive disorder (MDD) is associated with impairments in several cognitive domains in inpatients, but cognitive functioning has barely been systematically investigated in depressed outpatients. The aims of the present study were to examine cognitive functioning in depressed outpatients in comparison with healthy controls and to determine whether cognitive deficits vary as a function of different disorder characteristics and demographic variables.Method: We compared 103 outpatients with recurrent MDD in an acute phase of the illness with 103 healthy controls matched on age, gender, and education level using a neuropsychological battery covering the domains of processing speed, attention, memory, working memory, and executive functions.Results: Depressed outpatients were found to be impaired in all five assessed cognitive domains. These impairments varied as a function of the disorder characteristics, particularly severity of depression, intake of medication, age of depression onset, duration of current episode, and rumination as a psychological variable as well as age, premorbid intelligence, and education level as demographic variables.Conclusions: In the present study we tried to systematically investigate the impact of different disorder characteristics and demographic variables on the cognitive dysfunction of outpatients with MDD. The results indicate a moderate to severe cognitive impairment of outpatients with MDD and reveal an influence of different disease characteristics as well as demographics. These cognitive impairments may affect the course of the disease and should be considered in outpatient therapy.

Latent Classes of Cognitive Functioning Among Depressed Older Adults Without Dementia.

Use latent class analysis (LCA) to identify patterns of cognitive functioning in a sample of older adults with clinical depression and without dementia and assess demographic, psychiatric, and neurobiological predictors of class membership. Neuropsychological assessment data from 121 participants in the Alzheimer's Disease Neuroimaging Initiative-Depression project (ADNI-D) were analyzed, including measures of executive functioning, verbal and visual memory, visuospatial and language functioning, and processing speed. These data were analyzed using LCA, with predictors of class membership such as depression severity, depression and treatment history, amyloid burden, and APOE e4 allele also assessed. A two-class model of cognitive functioning best fit the data, with the Lower Cognitive Class (46.1% of the sample) performing approximately one standard deviation below the Higher Cognitive Class (53.9%) on most tests. When predictors of class membership were assessed, carrying an APOE e4 allele was significantly associated with membership in the Lower Cognitive Class. Demographic characteristics, age of depression onset, depression severity, history of psychopharmacological treatment for depression, and amyloid positivity did not predict class membership. LCA allows for identification of subgroups of cognitive functioning in a mostly cognitively intact late life depression (LLD) population. One subgroup, the Lower Cognitive Class, more likely to carry an APOE e4 allele, may be at a greater risk for subsequent cognitive decline, even though current performance on neuropsychological testing is within normal limits. These findings have implications for early identification of those at greatest risk, risk factors, and avenues for preventive intervention.

PHENOTYPING PROSPECTIVE COGNITIVE OUTCOMES OF LATE-LIFE DEPRESSION

Introduction It has long been known that major depressive disorder during later life (LDD) is associated with cognitive decline and development of Alzheimer's disease and other dementias. Less is known about the characteristics of LLD that contribute to individual cognitive outcomes, but identifying phenotypes of these outcomes could make important contributions to early detection and treatment. The current study explored clinical and neuroimaging phenotypes associated with normal and non-normal cognitive diagnostic outcomes in LLD. Methods The data were from a prospective study of individuals (N = 240) with acute depression at baseline and followed under treatment for a minimum of five years. Baseline assessment included clinical measures of mood, neuropsychological assessment, and neuroimaging. Mood was assessed during regular treatment over the course of each year, and neuropsychological assessment was obtained annually. A consensus review was held annually to assign clinical diagnoses based on cognitive status, which included categories of normal cognition; cognitive impairment, no dementia (CIND); dementia, with subtypes including Alzheimer's disease (AD). The current study analyzed diagnostic outcomes at five years from study entry, and the clinical characteristics that predict these outcomes. Results We found that 90% of cognitive diagnostic outcomes over five-years of follow-up were in three diagnostic categories: 1) cognitively normal, 2) persistent CIND, and 3) AD. The remaining 10% were non-AD dementias and various medical and neuropsychiatric diagnoses. Individuals with normal cognition were 50% of the sample, and this endpoint was associated with first depression onset before age 60 and indicators of heightened sensitivity to stress. Individuals with persistent CIND (22%) were not associated with age of depression onset, but were associated with clinical characteristics of frailty and indicators of cerebrovascular pathology on neuroimaging. Individuals with AD (18%) were associated with age of depression onset after age 60, depressive symptoms of appetite/weight loss, reduced hippocampal volume, and worse memory performance at study entry. Conclusions The current study found distinct clinical and neuroimaging profiles associated with the three major cognitive endpoints of LLD. Approximately half of individuals with LLD maintained normal cognition over five years, which appeared to be associated with a lifetime predisposition to depression and heightened sensitivity to stress. In contrast, nearly 20% of individuals with LLD converted to AD within five years of follow up, and results suggest a clinically detectable phenotype of prodromal AD based on appetitive disturbance, reduced hippocampal volume, and memory deficits. Individuals with persistent CIND demonstrated a profile consistent with physical decline and cerebrovascular pathology, which did not manifest as dementia over 5 years, but may represent a slower progress toward vascular dementia relative to those with AD. These clinical phenotypes reflect a starting point for mechanistic discovery while also improving current treatment of LLD by identifying individuals on distinct cognitive trajectories who many benefit from differentiated approaches to the treatment of mood and cognition. The current cohort is part of a collaborative project to further detect and characterize linkages between cognitive outcomes of LLD and their clinical and neuroimaging phenotypes. This research was funded by This research was supported by funding from the National Institute of Mental Health (R01MH108560), and the Leo and Anne Albert Charitable Trust. The authors have no industry or other conflicts to report.

Increased measles seronegativity in adults with major depressive disorder

Current and/or recent psychological stress or depression can impair vaccine efficacy. Nevertheless, the relationship between the efficacy of vaccinations received during childhood and depression in adulthood is unclear. Here, we tested for the presence of IgG antibodies against measles in volunteers meeting DSM-IV-TR criteria for current major depressive disorder (dMDD, n = 85, 81% females, age = 34.6 ± 9.4 years, 62.3% unmedicated), remitted MDD (rMDD, n = 82, 80% females, age = 32.0 ± 10.2 years, 81% unmedicated) as well as healthy controls (HC, n = 136, 68% females, age = 30.6 ± 9.3 years), all born after the introduction of the measles vaccine in 1963. Logistic regression analyses controlling for age and sex showed that both the dMDD group (OR = 2.07, p = 0.026) and the rMDD group (OR = 1.98, p = 0.040) had reduced seropositivity to measles compared to HC. There were no significant relationships between age of depression onset or self-reported number of depressive episodes and measles seropositivity. All dMDD and rMDD subjects reported onset of depression subsequent to the recommended ages for MMR vaccination in the USA (12–15 months with second dose at 4–6 years). This study suggests that adults with a depressive disorder may not be fully protected from measles, and more generally raises the possibility that adolescent or adult-onset depression may reduce the ability of the immune system to maintain the long-term antibody protection normally conveyed by vaccination in childhood.

Network basis of suicidal ideation in depressed adolescents

BackgroundSuicidal ideation rates rise precipitously in adolescence, contributing to risk for attempts. Although researchers are beginning to explore the brain basis of attempts in depressed adolescents, none have focused on the basis of ideation, which has implications for prevention. This study examined the association between intrinsic neural network coherence and the severity of suicidal ideation in depressed adolescents. MethodsForty adolescents diagnosed with Major Depressive Disorder were administered the Columbia-Suicide Severity Rating Scale and underwent resting-state fMRI. We quantified within-network coherence in the executive control (ECN), default mode (DMN), and salience (SN) networks, and in a non-relevant network consisting of noise signal. We associated coherence in each of these networks with the greatest lifetime severity of suicidal ideation experienced, covarying for motion, age of depression onset, and severity of current depressive and anxious symptoms. ResultsLower coherence in the left ECN, anterior DMN, and SN were independently associated with greater lifetime severity of suicidal ideation. When including all three significant networks and covariates in a single model, only the left ECN significantly predicted suicidal ideation. LimitationStudies with a larger sample size are needed to verify our findings. ConclusionsOur finding of hypoconnectivity in multiple networks extends emerging evidence for hypoconnectivity in adolescent suicidality and is consistent with theoretical conceptualizations of suicidal ideation as a complex set of cognitions associated with cognitive control, self-referential thinking, and processing salient information. While multiple networks could be targets for effective early interventions, those targeting ECN functionality (cognitive control) may be particularly beneficial.

Identification of commonly altered genes between in major depressive disorder and a mouse model of depression

The heterogeneity of depression (due to factors such as varying age of onset) may explain why biological markers of major depressive disorder (MDD) remain uncertain. We aimed to identify gene expression markers of MDD in leukocytes using microarray analysis. We analyzed gene expression profiles of patients with MDD (age ≥50, age of depression onset <50) (N = 10, depressed state; N = 13, remitted state). Seven-hundred and ninety-seven genes (558 upregulated, 239 downregulated when compared to those of 30 healthy subjects) were identified as potential markers for MDD. These genes were then cross-matched to microarray data obtained from a mouse model of depression (676 genes, 148 upregulated, 528 downregulated). Of the six common genes identified between patients and mice, five genes (SLC35A3, HIST1H2AL, YEATS4, ERLIN2, and PLPP5) were confirmed to be downregulated in patients with MDD by quantitative real-time polymerase chain reaction. Of these genes, HIST1H2AL was significantly decreased in a second set of independent subjects (age ≥20, age of onset <50) (N = 18, subjects with MDD in a depressed state; N = 19, healthy control participants). Taken together, our findings suggest that HIST1H2AL may be a biological marker of MDD.

Neuroticism in Remitted Major Depression: Elevated with Early Onset but Not Late Onset of Depression

Background: The personality trait of neuroticism is strongly related to depression, but depression is etiologically heterogeneous. Late-onset depression (LOD) may be more closely related to vascular factors, and previous studies of neuroticism in LOD versus early-onset depression (EOD) have not been consistent. Method: We examined neuroticism, extraversion and perceived stress in 88 fully remitted depressed patients with a mean age of 60 years and with a history of hospitalization for major depressive disorder. Patients were divided into those with onset after and those with onset before 50 years of age (LOD and EOD, respectively), and the two groups were compared both with each other and with matched control groups of healthy subjects. Results: EOD patients showed increased levels of neuroticism in comparison with both LOD and matched controls, who did not differ. The association between age of onset and neuroticism was confirmed in analyses based on age of depression onset as a continuous variable. Conclusion: Neuroticism may be an etiological factor in EOD but not or less so in LOD. This finding contributes to the growing evidence for etiological differences between early- and late-onset late-life depression.

The association between depressive disorder and cardiac autonomic control in adults 60 years and older.

Altered cardiac autonomic control has often been reported in depressed persons and might play an important role in the increased risk for cardiovascular disease (CVD). A negative association between cardiac autonomic control and depression might become specifically clinically relevant in persons 60 years or older as CVD risk increases with age. This study included data of 321 persons with a depressive disorder and 115 controls participating in the Netherlands Study of Depression in Older Persons (mean age = 70.3 years, 65.7% female). Respiratory sinus arrhythmia (RSA), heart rate (HR), and preejection period (PEP) were measured and compared between depressed persons and controls. In addition, the role of antidepressants and clinical characteristics (e.g., age of depression onset and comorbid anxiety) was examined. Compared with controls, depressed persons had lower RSA (mean [standard error of the mean] = 23.5 [1.2] milliseconds versus 18.6 [0.7] milliseconds, p = .001, d = 0.373) and marginally higher HR (73.1 [1.1] beats/min versus 75.6 [0.6] beats/min, p = .065, d = 0.212), but comparable PEP (113.9 [2.1] milliseconds versus 112.0 [1.2] milliseconds, p = .45, d = 0.087), fully adjusted. Antidepressants strongly attenuated the associations between depression and HR and RSA. Antidepressant-naïve depressed persons had similar HR and RSA to controls, whereas users of antidepressants showed significantly lower RSA. In addition, tricyclic antidepressant users had higher HR (p < .001, d = 0.768) and shorter PEP (p = .014, d = 0.395) than did controls. Depression was not associated with cardiac autonomic control, but antidepressants were in this sample. All antidepressants were associated with low cardiac parasympathetic control and specifically tricyclic antidepressants with high cardiac sympathetic control.

Mild Cognitive Impairment Subtypes in Older People With Depressive Symptoms: Relationship With Clinical Variables and Hippocampal Change.

To examine the rates and clinical characteristics of mild cognitive impairment (MCI) in older people with depressive symptoms and to determine the relative contribution of hippocampal volume and MCI to memory change. One hundred and fifty-two participants with lifetime Major Depression and remitted or mild symptoms and 28 healthy controls underwent psychiatric and neuropsychological assessments. Magnetic resonance imaging was also conducted in a subset of the patients (n = 81) and healthy controls (n = 18). MCI was diagnosed in 75.7% of the patients and was associated with increasing age, medical burden, vascular risk factors, later age of depression onset and smaller hippocampi. Multiple regression showed that both hippocampal volume and MCI diagnosis mediate memory performance in depression. MCI occurs in older adults with a history of depression and is not simply due to symptom severity. Memory change is linked to underlying hippocampal atrophy in this patient group.

Clinical characteristics and temperament influences on ‘happy’ euphoric and ‘snappy’ irritable bipolar hypo/manic mood states

BackgroundWhile mood elevation and euphoria are the most commonly described phenotypic descriptors of hypo/mania, irritability and anger may dominate. This study was designed to pursue possible determinants of such differing states. MethodsPatients with bipolar I or II disorder were assigned to an ‘irritable/snappy’ or ‘euphoric/happy’ sub-set on the basis of their dominant hypo/manic symptoms. Group differences were examined across clinical, personality, lifestyle and illness impact measures. ResultsThe two sub-sets did not differ on age of depression onset, family history of mood disorders, or depression severity and impairment. The snappy sub-set reported higher levels of irritability in depressed phases and were more likely to have a comorbid anxiety disorder. Their hypo/manic episodes were shorter and they were more likely to be hospitalized at such times. On a temperament measure they scored as more irritable and self-focussed and as less cooperative and effective – indicative of higher levels of disordered personality functioning. LimitationsSome comparison analyses were undertaken on a reduced sample size, giving rise to power issues. Our bipolar I and II diagnoses deviated to some extent from DSM-5 criteria in not imposing duration criteria for hypo/manic episodes. ConclusionsFindings support a spectrum model for the bipolar disorders linking temperament to bipolar symptomatic state and which may have treatment implications.

Appetite loss and neurocognitive deficits in late-life depression.

This study aimed to examine the association of appetite loss symptoms to neurocognitive performance in late-life depression (LLD). This study used cross-sectional data from individuals aged 60+ years with major depressive disorder (N = 322). Participants received clinical assessment of depression and neuropsychological testing. Factor analysis was used to characterize depression symptom factors, and composite scales were developed for episodic memory, psychomotor-executive functions, verbal fluency, and working memory span. Factor analysis produced a five-factor solution: (1) anhedonia/sadness; (2) suicidality/guilt; (3) appetite/weight loss; (4) sleep disturbance; and (5) anxiety/tension. In separate multivariate models for each neurocognitive domain and including all five depression factors, higher appetite-loss-related symptoms were associated with lower performance in episodic memory, psychomotor-executive functions, and verbal fluency; results were significant with covariates of age, education, race, sex, age of depression onset, and illness burden. No other depression factors were associated with neurocognitive performance in these models. In an additional set of models, the appetite factor mediated the association between global depression severity and neurocognitive performance. A factor of appetite and weight loss symptoms in LLD was uniquely associated with neurocognitive performance, in contrast to lack of association among other depression symptom factors. Cognitive deficits are a major adverse outcome of LLD, and prominent appetite loss during acute depression may be a marker for these deficits, independent of overall depression severity. Research is needed to understand the mechanisms that may explain this association, and how it is related to the cognitive and symptomatic course of LLD.

Age of major depression onset, depressive symptoms, and risk for subsequent dementia: results of the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe)

Whether late-onset depression is a risk factor for or a prodrome of dementia remains unclear. We investigated the impact of depressive symptoms and early- v. late-onset depression on subsequent dementia in a cohort of elderly general-practitioner patients (n = 2663, mean age = 81.2 years). Risk for subsequent dementia was estimated over three follow-ups (each 18 months apart) depending on history of depression, particularly age of depression onset, and current depressive symptoms using proportional hazard models. We also examined the additive prediction of incident dementia by depression beyond cognitive impairment. An increase of dementia risk for higher age cut-offs of late-onset depression was found. In analyses controlling for age, sex, education, and apolipoprotein E4 genotype, we found that very late-onset depression (aged ≥ 70 years) and current depressive symptoms separately predicted all-cause dementia. Combined very late-onset depression with current depressive symptoms was specifically predictive for later Alzheimer's disease (AD; adjusted hazard ratio 5.48, 95% confidence interval 2.41-12.46, p < 0.001). This association was still significant after controlling for cognitive measures, but further analyses suggested that it was mediated by subjective memory impairment with worries. Depression might be a prodrome of AD but not of dementia of other aetiology as very late-onset depression in combination with current depressive symptoms, possibly emerging as a consequence of subjectively perceived worrisome cognitive deterioration, was most predictive. As depression parameters and subjective memory impairment predicted AD independently of objective cognition, clinicians should take this into account.

From pathophysiological aspects towards unravelling the neurobiological background of cognitive deficits

From pathophysiological aspects towards unravelling the neurobiological background of cognitive deficits

Temperament and personality in bipolar II disorder

There is limited research examining temperament and personality in bipolar II disorder. We sought to determine any over-represented temperament and personality features in bipolar II disorder compared to other affective groups. Scores on a self-report measure of temperament and personality were examined in a sample of 443 participants diagnosed with unipolar, bipolar I and bipolar II disorder. After controlling for age, gender, age of depression onset and current depression severity, those with bipolar II disorder were characterized by higher irritability, anxious worrying, self-criticism and interpersonal sensitivity scores, and with lower social avoidance scores compared to unipolar participants. No differences were found between bipolar sub-types on any temperament and personality sub-scales. Limitations included the lack of a control group, a relatively small sample of bipolar I participants, and with the cross-sectional design disallowing conclusions regarding premorbid personality traits as opposed to illness 'scarring' effects. Further research should seek to clarify whether certain temperament and personality styles are over-represented in bipolar II disorder. Any over-represented characteristics may assist with diagnostic differentiation from phenomenologically similar conditions and lead to more appropriate clinical management.