There is heterogeneity in the long-term trajectories of depressive symptoms among patients. To date, there has been little effort to inform the long-term trajectory of symptom change and the factors associated with different trajectories. Such knowledge is key to treatment decision-making in primary care, where depression is a common reason for consultation. We aimed to identify distinct long-term trajectories of depressive symptoms and explore pre-treatment characteristics associated with them.

A total of 483 patients from the PsicAP clinical trial were included. Growth mixture modeling was used to identify long-term distinct trajectories of depressive symptoms, and multinomial logistic regression models to explore associations between pre-treatment characteristics and trajectories.

Four trajectories were identified that best explained the observed response patterns: “recovery” (64.18%), “late recovery” (10.15%), “relapse” (13.67%), and “chronicity” (12%). There was a higher likelihood of following the recovery trajectory for patients who had received psychological treatment in addition to the treatment as usual. Chronicity was associated with higher depressive severity, comorbidity (generalized anxiety, panic, and somatic symptoms), taking antidepressants, higher emotional suppression, lower levels on life quality, and being older. Relapse was associated with higher depressive severity, somatic symptoms, and having basic education, and late recovery was associated with higher depressive severity, generalized anxiety symptoms, greater disability, and rumination.

There were different trajectories of depressive course and related prognostic factors among the patients. However, further research is needed before these findings can significantly influence care decisions.

The early prediction of adolescent depression recurrence poses a significant challenge in the field. This study aims to investigate and compare the abilities of the general psychopathology factor (p) and the specific internalizing factor, in predicting depression recurrence over a 2-year course, as well as identifying remitted depressed adolescents from healthy adolescents. Longitudinal changes of these two factors in different trajectory groups were also tracked to examine their sensitivity to sustained remission and relapse.

We included 255 baseline-remitted depressed adolescents and a healthy control group (n = 255) matched in age, sex, and race, sourced from the Adolescent Brain Cognitive Development Study. The linear mixed model was employed for the statistical analysis.

The p factor not only effectively discriminated between remitted depressed adolescents and healthy controls but also robustly predicted the depression recurrence over a subsequent 2-year course. The specific internalizing factor could only differentiate remitted depressed adolescents from healthy controls. Additionally, a noteworthy longitudinal decline of the p factor in the sustained-remission group was observed.

Psychopathology factors serve as the inherent and enduring measurement of long-term mental health aberrations. Longitudinal results indicate that the p factor is more sensitive to respond to sustained remission than the internalizing factor. The ability of the overall p factor to anticipate depression relapse, unlike the specific internalizing factor, suggests the clinical interventions should monitor and mitigate the coincident symptoms across all dimensions to preempt relapse of adolescent depression, rather than an exclusive focus on internalizing symptoms.

The association between obesity and depression may partly depend on the contextual metabolic health. The effect of change in metabolic health status over time on subsequent depression risk remains unclear. We aimed to assess the prospective association between metabolic health and its change over time and the risk of depression across body mass index (BMI) categories.

Based on a nationally representative cohort, we included participants enrolled at the wave 2 (2004–2005) of the English Longitudinal Study of Ageing and with follow-up for depression at wave 8 (2016–2017). Participants were cross-classified by BMI categories and metabolic health (defined by the absence of hypertension, diabetes, and hypercholesterolemia) at baseline or its change over time (during waves 3–6). Logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of depression at follow-up stratified by BMI category and metabolic health status with adjustment for potential confounders.

The risk of depression was increased for participants with metabolically healthy obesity compared with healthy nonobese participants, and the risk was highest for those with metabolically unhealthy obesity (OR 1.62, 95% CI 1.18–2.20). Particularly hypertension and diabetes contribute most to the increased risk. The majority of metabolically healthy participants converted to unhealthy metabolic phenotype (50.1% of those with obesity over 8 years), which was associated with an increased risk of depression. Participants who maintained metabolically healthy obesity were still at higher risk (1.99, 1.33–2.72), with the highest risk observed for those with stable unhealthy metabolic phenotypes.

Obesity remains a risk factor for depression, independent of whether other metabolic risk factors are present or whether participants convert to unhealthy metabolic phenotypes over time. Long-term maintenance of metabolic health and healthy body weight may be beneficial for the population mental well-being.

Most patients show temporary impairments in clinical orientation after electroconvulsive therapy (ECT)-induced seizures. It is unclear how postictal reorientation relates to electroencephalography (EEG) restoration. This relationship may provide additional measures to quantify postictal recovery and shed light on neurophysiological aspects of reorientation after ECT.

We analyzed prospectively collected clinical and continuous ictal and postictal EEG data from ECT patients. Postictal EEG restoration up to 1 h was estimated by the evolution of the normalized alpha–delta ratio (ADR). Times to reorientation in the cognitive domains of person, place, and time were assessed postictally. In each cognitive domain, a linear mixed model was fitted to investigate the relationships between time to reorientation and postictal EEG restoration.

In total, 272 pairs of ictal-postictal EEG and reorientation times of 32 patients were included. In all domains, longer time to reorientation was associated with slower postictal EEG recovery. Longer seizure duration and postictal administration of midazolam were related to longer time to reorientation in all domains. At 1-hour post-seizure, most patients were clinically reoriented, while their EEG had only partly restored.

We show a relationship between postictal EEG restoration and clinical reorientation after ECT-induced seizures. EEG was more sensitive than reorientation time in all domains to detect postictal recovery beyond 1-hour post-seizure. Our findings indicate that clinical reorientation probably depends on gradual cortical synaptic recovery, with longer seizure duration leading to longer postsynaptic suppression after ECT seizures.

Electroconvulsive therapy (ECT) is an established treatment for depression, but more data on effectiveness and safety in clinical practice is needed. The aim of this register-based study was to investigate short-term effectiveness and cognitive safety after ECT, evaluated by clinicians and patients. Secondary, we investigated predictors for remission and cognitive decline.

The study included 392 patients from the Regional Register for Neurostimulation Treatment in Western Norway. Depressive symptoms and cognitive function were assessed with Montgomery-Åsberg Depression Rating Scale and Mini-Mental State Examination (clinician-rated) and Beck Depression Inventory and Everyday Memory Questionnaire (patient-rated). Assessments were done prior to ECT-series and a mean of 1.7 days after (range 6 days before and 12 days after) end of ECT-series. Paired samples t-tests were extended by detailed, clinically relevant subgroups. Predictors were examined using logistic regression.

Clinician- and patient-rated remission rates were 49.5 and 41.0%, respectively. There was a large reduction in depressive symptoms and a small improvement in cognition after ECT, but we also identified subgroups with non-response of ECT in combination with cognitive decline (4.6% clinician-rated, 15.7% patient-rated). Positive predictors for patient- and clinician-rated remission were increasing age, shorter duration of depressive episode, and psychotic features. Antipsychotic medication at the commencement of treatment and previous ECT-treatment gave higher odds of clinician-rated remission, whereas higher pretreatment subjective depression level was associated with lower odds for patient-rated remission. Clinician-rated cognitive decline was predicted by higher pretreatment MMSE scores, whereas psychotic features, increasing age, and greater pretreatment subjective memory concerns were associated with lower odds for patient-rated cognitive decline.

Our study supports ECT as an effective and safe treatment, although subgroups have a less favorable outcome. ECT should be considered at an early stage for older patients suffering from depression with psychotic features. Providing comprehensive and balanced information from clinicians and patients perspectives on effects and side effects, may assist in a joint consent process.

Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as a mood stabilizer, has shown promising effects on pain.

This naturalistic study included 760 subjects with BD ( FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood-stabilizing blood concentration of lithium.

Subjects with lithium intake were less likely to report pain (odds ratio [OR] = 0.59, 95% confidence interval [CI], 0.35–0.95; p = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5 mmol/l (OR = 0.45, 95% CI, 0.24–0.79; p = 0.008).

This is the first naturalistic study to show lithium’s promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations.

Subthreshold hypomania during a major depressive episode challenges the bipolar-unipolar dichotomy. In our study we employed a cross-diagnostic cluster analysis - to identify distinct subgroups within a cohort of depressed patients.

A k-means cluster analysis— based on the domain scores of the Mood Spectrum Self-Report (MOODS-SR) questionnaire—was performed on a data set of 300 adults with either bipolar or unipolar depression. After identifying groups, between-clusters comparisons were conducted on MOODS-SR domains and factors and on a set of sociodemographic, clinical and psychometric variables.

Three clusters were identified: one with intermediate depressive and poor manic symptomatology (Mild), one with severe depressive and poor manic symptomatology (Moderate), and a third one with severe depressive and intermediate manic symptomatology (Mixed). Across the clusters, bipolar patients were significantly less represented in the Mild one, while the DSM-5 “Mixed features” specifier did not differentiate the groups. When compared to the other patients, those of Mixed cluster exhibited a stronger association with most of the illness-severity, quality of life, and outcomes measures considered. After performing pairwise comparisons significant differences between “Mixed” and “Moderate” clusters were restricted to: current and disease-onset age, psychotic ideation, suicidal attempts, hospitalization numbers, impulsivity levels and comorbidity for Cluster B personality disorder.

In the present study, a clustering approach based on a spectrum exploration of mood symptomatology led to the identification of three transdiagnostic groups of patients. Consistent with our hypothesis, the magnitude of subthreshold (hypo)manic symptoms was related to a greater clinical severity, regardless of the main categorical diagnosis.

Suicidal ideation (SI) is an important risk factor of death by suicide. Recent data suggest that suicidal depression (i.e., moderate to severe depression with SI) could be a specific depression subtype with worse clinical outcomes than nonsuicidal depression (i.e., without SI).

Among 898 French adult inpatients (67% women, mean age: 41.23 [SD: 14.33]) with unipolar depression, 71.94% had moderate to severe depression (defined using the cut-offs of validated scales: beck depression inventory, clinician-rated 30-item inventory depression symptomatology, and quick inventory of depressive symptomatology) and among them, 63.6% had SI according to the suicidal item (score ≥ 2) of the depression scale they filled in. Clinical features (anxiety, psychological pain, and hopelessness) were assessed at baseline. The occurrence of a suicide attempt (SA) or a suicide event (SE) (i.e., actual, aborted or interrupted SA, or hospitalization for SI) was recorded during the 1-year follow-up. The risk of actual SA and SE was compared between groups with adjusted Cox regression models.

The risk of actual SA and SE during the follow-up was 2- and 1.8-fold higher, respectively, in patients with suicidal depression, independently of potential cofounders such as history of lifetime SA, age, sex, and baseline depression severity.

Suicidal depression is associated with poorer prognosis in terms of actual SA/SE, despite optimal care (i.e., care in a hospital department specialized in the management of suicidal crisis). Specific therapeutic strategies might be needed for these patients.

Psychopathological network model has received attention recently in the traditional debate about the continuity of depression. However, there is little evidence for comparing the network structure of depressive symptoms in several depressive states at different clinical stages. Through this study of a broad sample of patients with nonclinical to clinical depression, we examined differences in the network structure of depressive symptoms.

Four groups of participants, including cohorts of clinical depression (current depression, n = 294; remitted depression, n = 118) and nonclinical depression (subthreshold depression, N = 184; healthy control, n = 257), responded to Beck Depression Inventory-II (BDI-II). After adjusting for age and sex, the residual scores of the 21 BDI-II items were input into a regularized partial correlation network for each group. Then, the estimated edge strengths/densities and node characteristics were compared.

Current depression has a discontinuous structure with a stronger and denser network of symptoms compared with nonclinical groups. Interestingly, remitted depression had improved to the level in healthy controls; however, it retained the same network structure as current depression, which indicates a trace of depression.

We found the traces of depression that remained even after the symptoms disappeared. This study might provide a novel framework for elucidating the development and formation of depression.

Psychiatric comorbidities and suicide attempts are highly prevalent in Bipolar Disorders (BD). We examined the associations between childhood maltreatment, psychiatric comorbidities, and suicide attempts, in terms of lifetime prevalence, sequence of onset, and current symptoms.

We assessed 3,047 individuals with BD for suicide attempts, anxiety disorders, substance use disorders, and eating disorders. Participants completed a self-report for the assessment of childhood maltreatment. Associations between childhood maltreatment and characteristics of comorbidities (lifetime prevalence, current symptoms, and age at onset) were examined using logistic regressions and network analyses.

Psychiatric comorbidities were frequent with a mean number per individual of 1.23 (SD = 1.4). Most comorbidities occurred prior to the onset of BD. Participants who reported higher levels of childhood maltreatment had more frequent and multiple comorbidities, which were also more currently active at inclusion. Childhood maltreatment did not decrease the age of onset of comorbidities, but was associated with a faster accumulation of comorbidities prior to the onset of BD. Logistic regression and network analyses showed that emotional abuse and sexual abuse might play a prominent role in the lifetime prevalence of psychiatric comorbidities and suicide attempts.

Childhood maltreatment was associated with suicide attempts, and with frequent, multiple, and persistent psychiatric comorbidities that accumulated more rapidly prior to the onset of BD. Hence, childhood maltreatment should be systematically assessed in individuals with BD, in particular when the course of the disorder is characterized by a high comorbid profile or by a high suicidality.

Bipolar disorder (BD) is recognized to be at high risk for developing negative psychopathological sequelae to potentially traumatic events. Nevertheless, scant data are still available about the effects of the COVID-19 emergency on the clinical course of BD. The present study examined prospectively the development and trajectories of post-traumatic stress, depressive, and anxiety symptoms among subjects with BD that were followed in an outpatient psychiatric clinic at the time of pandemic onset.

A cohort of 89 subjects with BD was enrolled during the first wave of the COVID-19 pandemic, and assessed at baseline (T0), 2-months (T1), and 6-months (T2) follow-up. A K-means cluster analysis was used to identify distinct trajectories of depressive, anxiety, and post-traumatic stress symptoms during the three time points.

We identified three trajectories: the Acute reaction (13.5%); the Increasing severity (23.6%); and the Low symptoms (62.9%) groups, respectively. In the Acute reaction group a significant prevalence of female gender was reported with respect to the Low symptoms one. Subjects in the Increasing severity group reported significantly lower employment rate, and higher rate of relatives at risk for COVID-19 medical complications. Subjects in the Increasing Severity group reported higher rates of previous hospitalization and manic symptoms at baseline than those included in the Low symptoms one.

Our results describe three distinct symptom trajectories during the COVID-19 emergency in a cohort of subjects suffering from BD, suggesting the need of a long-term follow-up for detecting the impact of the COVID-19 pandemic in this vulnerable population.

Metacognitive knowledge (MK; general awareness of cognitive functioning) and metacognitive experience (ME; awareness of cognitive performance on a specific cognitive task) represent two facets of metacognition that are critical for daily functioning, but are understudied in bipolar disorder. This study was conducted to evaluate MK and ME across multiple cognitive domains in individuals diagnosed with bipolar disorder and unaffected volunteers, and to investigate the association between metacognition and quality of life (QoL).

Fifty-seven euthymic participants with bipolar disorder and 55 demographically similar unaffected volunteers provided prediction and postdiction ratings of cognitive task performance across multiple cognitive domains. Self-ratings were compared to objective task performance, and indices of MK and ME accuracy were generated and compared between groups. Participants rated QoL on the Quality of Life in Bipolar Disorder Scale (QoL.BD).

Metacognitive inaccuracies in both MK and ME were observed in participants with bipolar disorder, but only in select cognitive domains. Furthermore, most metacognitive inaccuracies involved underestimation of cognitive ability. Metacognitive indices were minimally associated with medication variables and mood symptoms, but several indices were related to QoL.

Individuals with bipolar disorder demonstrate inaccuracies in rating their cognitive functioning and in rating their online cognitive task performance, but only on select cognitive functions. The tendency to underestimate performance may reflect a negative information processing bias characteristic of mood disorders. Metacognitive variables were also predictive of QoL, indicating that further understanding of cognitive self-appraisals in persons with bipolar disorder has significant clinical relevance.

Increasing age as well as borderline personality pathology are associated with a lower level of health-related quality of life (HR-QoL). Our objective was to investigate whether the presence of borderline personality traits modifies the association between age and HR-QoL in the general population.

Cross-sectional data from 5,303 respondents (aged 21–72 years) of the Netherlands Mental Health Survey and Incidence Study-2 were analyzed. Borderline personality traits were assessed with the International Personality Disorder Examination questionnaire. Mental and physical HR-QoL were measured with the Medical Outcomes Study Short Form Health Survey. Multiple linear regression analysis was used to examine the association of borderline personality traits, age and their interaction on mental as well as physical HR-QoL, adjusted for demographic variables as well as somatic and mental disorders.

A total of 1,520 (28.7%) respondents reported one or more borderline personality traits of which 58 (1.1%) reported five or more indicative of a borderline personality disorder. A higher age was associated with lower physical HR-QoL. This negative association became significantly stronger in the presence of borderline personality traits. The association between increasing age and mental HR-QoL was positive in the absence of borderline personality traits and negative in the presence of borderline personality traits.

Borderline personality traits negatively interfere with the association between age and HR-QoL irrespective of somatic and mental disorders. Attention of clinicians and researchers for subthreshold borderline personality pathology is needed in middle-aged and older persons.

Depressive symptoms are highly prevalent among partnered dementia caregivers, but the mechanisms are unclear. This study examined the mediating role of loneliness in the association between dementia and other types of care on subsequent depressive symptoms.

Prospective data from partnered caregivers were drawn from the English Longitudinal Study of Aging. The sample consisted of 4,672 partnered adults aged 50–70 living in England and Wales, followed up between 2006–2007 and 2014–2015. Caregiving was assessed across waves 3 (2006–2007), 4 (2008–2009), and 5 (2010–2011), loneliness at wave 6 (2012–2013), and subsequent depressive symptoms at wave 7 (2014–15). Multivariable logistic regression models were used to assess the association between caregiving for dementia and depressive symptoms compared to caregiving for other illnesses (e.g., diabetes, coronary heart disease (CHD), cancer, and stroke). Binary mediation analysis was used to estimate the indirect effects of caregiving on depressive symptoms via loneliness.

Care for a partner with dementia was associated with higher odds of depressive symptoms at follow-up compared to those not caring for a partner at all (odds ratio [OR] = 2.6, 95% confidence intervals [CI]: 1.4, 5.1). This association was partially mediated by loneliness (34%). Care for a partner with other conditions was also associated with higher odds of depressive symptoms compared to non-caregiving partners (OR = 1.7, 95% CI: 1.2, 2.5), but there was no evidence of an indirect pathway via loneliness.

Loneliness represents an important contributor to the relationship between dementia caregiving and subsequent depressive symptoms; therefore, interventions to reduce loneliness among partnered dementia caregivers should be considered.

Changes in inflammatory and metabolic markers are implicated in the pathogenesis in both the development and progression of bipolar disorder (BD). Notwithstanding, these markers have not been investigated in newly diagnosed BD.

We compared high-sensitive C-reactive protein (hs-CRP) and homocysteine (Hcy) levels in 372 patients with newly diagnosed BD, 106 unaffected first-degree relatives (URs), and 201 healthy control persons (HCs). Within the patient group, we also investigated possible associations between hs-CRP and Hcy, respectively, with illness-related characteristics and psychotropic medication.

No statistically significant differences in Hcy and hs-CRP levels were found when comparing BD and URs with HCs. Similarly, there were no differences when comparing only patients in remission or patients with affective symptoms, respectively, with HCs. Hcy levels were found to be 11.9% (95% CI: 1.030–1.219) higher in patients with BD when compared with their URs (p = 0.008), when adjusting for folate and cobalamin status, age, sex, and self-reported activity levels. Hcy levels were significantly associated with folate, cobalamin, gender, and age in all models (p < 0.05).

Our results do not support hs-CRP or Hcy as markers in newly diagnosed BD.

Increasing educational attainment (EA) could decrease the occurrence of depression. We investigated the relationship between EA and depressive symptoms in older individuals across four European regions.

We studied 108,315 Europeans (54% women, median age 63 years old) from the Survey on Health, Ageing and Retirement in Europe assessing EA (seven educational levels based on International Standard Classification of Education [ISCED] classification) and depressive symptoms (≥4 points on EURO-D scale). Logistic regression estimated the association between EA and depressive symptoms, adjusting for sociodemographic and health-related factors, testing for sex/age/region and education interactions.

Higher EA was associated with lower odds of depressive symptoms, independent of sociodemographic and health-related factors. A threshold of the lowest odds of depressive symptoms was detected at the first stage of tertiary education (OR 0.60; 95% confidence interval [CI] 0.55–0.65; p < 0.001; relative to no education). Central and Eastern Europe showed the strongest association (OR for high vs. low education 0.37; 95% CI 0.33–0.40; p < 0.001) and Scandinavia the weakest (OR for high vs. low education 0.69; 95% CI 0.60–0.80; p < 0.001). The association was strongest among younger individuals. There was a sex and education interaction only within Central and Eastern Europe.

Level of EA is reflected in later-life depressive symptoms, suggesting that supporting individuals in achieving EA, and considering those with lower EA at increased risk for depression, could lead to decreased burden of depression across the life course. Further educational support in Central and Eastern Europe may decrease the higher burden of depressive symptoms in women.

Standard depression rating scales like the Hamilton Depression Rating Scale and the Montgomery–Åsberg Depression Rating Scale were developed more than 40 years ago. They are mandatory in clinical trials but are for a variety of reasons seldom used in clinical practice. Moreover, most clinicians are less familiar with more recent trends or with some dilemmas in assessment tools for major depression.

Narrative review.

Asssessment tools can be observer-rating or self-rating scales, disease-specific or non–disease-specific scales, subjective scales or objective lab assessments, standard questionnaires or experience sampling methods. An overarching question is to what degree current assessment methods really address the individual patient’s needs and treatment expectations.

The present paper aims to offer a framework for understanding the current trends in assessment tools that can orientate and guide the clinician.

Birth weight influences not only brain development, but also mental health outcomes, including depression, but the underlying mechanism is unclear.

The phenotypic data of 12,872–91,009 participants (59.18–63.38% women) from UK Biobank were included to test the associations between the birth weight, depression, and brain volumes through the linear and logistic regression models. As birth weight is highly heritable, the polygenic risk scores (PRSs) of birth weight were calculated from the UK Biobank cohort (154,539 participants, 56.90% women) to estimate the effect of birth weight-related genetic variation on the development of depression and brain volumes. Finally, the mediation analyses of step approach and mediation analysis were used to estimate the role of brain volumes in the association between birth weight and depression. All analyses were conducted sex stratified to assess sex-specific role in the associations.

We observed associations between birth weight and depression (odds ratio [OR] = 0.968, 95% confidence interval [CI] = 0.957–0.979, p = 2.29 × 10−6). Positive associations were observed between birth weight and brain volumes, such as gray matter (B = 0.131, p = 3.51 × 10−74) and white matter (B = 0.129, p = 1.67 × 10−74). Depression was also associated with brain volume, such as left thalamus (OR = 0.891, 95% CI = 0.850–0.933, p = 4.46 × 10−5) and right thalamus (OR = 0.884, 95% CI = 0.841–0.928, p = 2.67 × 10−5). Additionally, significant mediation effects of brain volume were found for the associations between birth weight and depression through steps approach and mediation analysis, such as gray matter (B = –0.220, p = 0.020) and right thalamus (B = –0.207, p = 0.014).

Our results showed the associations among birth weight, depression, and brain volumes, and the mediation effect of brain volumes also provide evidence for the sex-specific of associations.