There is increasing evidence that childhood Attention-Deficit Hyperactivity Disorder (ADHD) elevates the risk of later Bipolar Spectrum Disorder (BD). However, it remains unclear whether different trajectories of ADHD symptoms confer differential risk for BD.

Data from the Avon Longitudinal Study of Parents and Children were available from 7811 children at age 8 years, 7435 at 10, 6798 at 13, and 1217 at 21–23 years. ADHD symptoms were assessed at 8, 10, and 13 years with the Development and Well-Being Assessment. Clinically significant hypomanic symptoms (CSHS) at 21–23 years were assessed using the Hypomania Symptom Checklist (HCL-32). Group trajectories of ADHD and its subtypes were estimated using latent class growth analysis. The prospective associations between different ADHD trajectories and CSHS were tested using logistic regression analysis.

Persistently high, increasing, remitting, and persistently low ADHD symptom trajectories were identified for the three ADHD-related categories. Individuals with persistently high and increasing levels of ADHD symptoms had increased odds of CSHS compared to persistently low class. Sensitivity analyses validated these results. In separate analyses, persistently high levels of hyperactivity and inattentive, and increasing levels of inattentive symptoms were also independently associated with CSHS.

Young people with a longitudinal pattern of high and increasing ADHD symptoms are at higher risk for developing CSHS in young adulthood compared to individuals with low symptom patterns. These two trajectories in childhood and adolescence may represent distinct phenotypic risk profiles for subsequently developing BD and be clinically significant targets for prevention and treatment of BD.

Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.

We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10–28 years; N = 4,835) and UK Biobank (39–86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8).

Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.

These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

There is a high prevalence of depression among refugee youth in low- and middle-income countries, yet depression trajectories are understudied. This study examined depression trajectories, and factors associated with trajectories, among urban refugee youth in Kampala, Uganda.

We conducted a longitudinal cohort study with refugee youth aged 16–24 in Kampala, Uganda. We assessed depression using the Patient Health Questionnaire-9 and conducted latent class growth analysis (LCGA) to identify depression trajectories. Sociodemographic and socioecological factors were examined as predictors of trajectory clusters using multivariable logistic regression.

Data were collected from n = 164 participants (n = 89 cisgender women, n = 73 cisgender men, n = 2 transgender persons; mean age: 19.9, standard deviation: 2.5 at seven timepoints; n = 1,116 observations). Two distinct trajectory clusters were identified: “sustained low depression level” (n = 803, 71.9%) and “sustained high depression level” (n = 313, 28.1%). Sociodemographic (older age, gender [cisgender women vs. cisgender men], longer time in Uganda), and socioecological (structural: unemployment, food insecurity; interpersonal: parenthood, recent intimate partner violence) factors were significantly associated with the sustained high trajectory of depression.

The chronicity of depression highlights the critical need for early depression screening with urban refugee youth in Kampala. Addressing multilevel depression drivers prompts age and gender-tailored strategies and considering social determinants of health.

The enduring impact of the COVID-19 pandemic on mental health and its implications for COVID-19 vaccine uptake necessitate comprehensive investigation. We aimed to characterize the persistence of moderate to severe anxiety and depression symptoms from July 2020 to July 2023, explore demographic associations with symptom persistence, and assess how these symptoms affected COVID-19 vaccination uptake between May 2021 and July 2023.

Participants from the national community-based CHASING COVID Cohort were enrolled between March and June 2020 and completed quarterly follow-ups until December 2023. Scores ≥10 on the Generalized Anxiety Disorder 7-item and the Patient Health Questionnaire 8-item at 14 follow-up assessments indicated moderate to severe anxiety and depression symptoms, respectively. Missing scores were imputed. Persistent anxiety and depression were defined as experiencing moderate to severe anxiety and depression symptoms ≥7 out of 14 follow-up assessments, respectively.

Among 4,851 participants, 15.9% experienced persistent anxiety symptoms and 19.3% persistent depression symptoms from July 2020 to July 2023. Demographic factors associated with symptom persistence included younger age, female or non-binary gender, Hispanic ethnicity, lower education level, household income <$100k, presence of children <18 in the household, greater healthcare barriers and comorbidities. Participants with ongoing moderate to severe anxiety and depression symptoms had 0.95 (95% CI: 0.94, 0.97) and 0.95 (95% CI: 0.93, 0.96) times rates of receiving additional COVID-19 vaccine doses between May 2021 and July 2023, respectively.

Customized support for individuals with mental disorders may mitigate barriers to vaccine uptake. Further investigation is warranted to validate these findings and inform targeted interventions.

Epidemiological studies show that despite the episodic nature, the long-term trajectory of depression can be variable. This study evaluated the heterogeneity of 10-year trajectory of major depressive disorder (MDD) related service utilization and associated clinical characteristics among US Veterans with a first diagnosis after 9/11.

Using a cohort design, electronic health record data for 293,265 Operation Enduring Freedom and Iraqi Freedom (OEF/OIF) Veterans were extracted to identify those with MDD between 2001 and 2021 with a full preceding year of clinical data and 10 years following the diagnosis. Latent class growth analysis compared clinical characteristics associated with four depression trajectories. Across all Veterans Affairs (VA)hospitals, 25,307 Veterans met our inclusion criteria. Demographic and clinical information from medical records was extracted and used as predictors of depression 10-year trajectories.

Among the study cohort (N = 25,307), 27.7% were characterized by brief contact, 41.7% were later re-entry, 17.6% were persistent contact and 12.9% were prolonged initial contact for depression related services. Compared to Veterans with trajectories showing brief contact, those with protracted treatment (persistent or prolonged initial contact) were more likely to be diagnosed with comorbid posttraumatic stress disorder (PTSD) and with MDD that was moderate to severe or recurrent.

Depression is associated with a range of treatment trajectories. The persistent and prolonged initial contact trajectories may have distinct characteristics and uniquely high resource utilization and disability income. We can anticipate that patients with comorbid PTSD may need longer-term care which has implications for brief models of care.

Identifying children and/or adolescents who are at highest risk for developing chronic depression is of utmost importance, so that we can develop more effective and targeted interventions to attenuate the risk trajectory of depression. To address this, the objective of this study was to identify young people with persistent depressive symptoms across adolescence and young adulthood and examine the prospective associations between factors and persistent depressive symptoms in young people.

We used data from 6711 participants in the Avon Longitudinal Study of Parents and Children. Depressive symptoms were assessed at 12.5, 13.5, 16, 17.5, 21 and 22 years with the Short Mood and Feelings Questionnaire, and we further examined the influence of multiple biological, psychological and social factors in explaining chronic depressive symptoms.

Using latent class growth analysis, we identified four trajectories of depressive symptoms: persistent high, persistent low, persistent moderate and increasing high. After applying several logistic regression models, we found that loneliness and feeling less connected at school were the most relevant factors for chronic course of depressive symptoms.

Our findings contribute with the identification of those children who are at highest risk for developing chronic depressive symptoms.

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.

Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. We investigated the association of retinal microvascular function, a proxy for microvascular function in the brain, with incidence and trajectories of clinically relevant depressive symptoms.

Longitudinal data are from The Maastricht Study of 5952 participants (59.9 ± 8.5 years/49.7% women) without clinically relevant depressive symptoms at baseline (2010–2017). Central retinal arteriolar equivalent and central retinal venular equivalent (CRAE and CRVE) and a composite score of flicker light-induced retinal arteriolar and venular dilation were assessed at baseline. We assessed incidence and trajectories of clinically relevant depressive symptoms (9-item Patient Health Questionnaire score ⩾10). Trajectories included continuously low prevalence (low, n = 5225 [87.8%]); early increasing, then chronic high prevalence (early-chronic, n = 157 [2.6%]); low, then increasing prevalence (late-increasing, n = 247 [4.2%]); and remitting prevalence (remitting, n = 323 [5.4%]).

After a median follow-up of 7.0 years (range 1.0–11.0), 806 (13.5%) individuals had incident clinically relevant depressive symptoms. After full adjustment, a larger CRAE and CRVE were each associated with a lower risk of clinically relevant depressive symptoms (hazard ratios [HRs] per standard deviation [s.d.]: 0.89 [95% confidence interval (CI) 0.83–0.96] and 0.93 [0.86–0.99], respectively), while a lower flicker light-induced retinal dilation was associated with a higher risk of clinically relevant depressive symptoms (HR per s.d.: 1.10 [1.01–1.20]). Compared to the low trajectory, a larger CRAE was associated with lower odds of belonging to the early-chronic trajectory (OR: 0.83 [0.69–0.99]) and a lower flicker light-induced retinal dilation was associated with higher odds of belonging to the remitting trajectory (OR: 1.23 [1.07–1.43]).

These findings support the hypothesis that cerebral microvascular dysfunction contributes to the development of depressive symptoms.

The aim of the study was to investigate longitudinal trajectories of change in anxiety and depression symptoms in Polish adolescents during the second year of the COVID-19 pandemic and after the outbreak of the war in Ukraine. Additionally, we aimed to identify risk/protective factors and outcomes associated with these trajectories.

We collected data in three waves between November 2021 and May 2022. Adolescents (N = 281 in the first wave) completed the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Filial Responsibility Scale for Youth, and questions related to the COVID-19 pandemic and war in Ukraine.

We identified three trajectories of depressive symptoms: resilient with low, stable symptoms (71% of participants), chronically elevated symptoms (11%), and acute symptoms followed by recovery (18%). We distinguished two trajectories of anxiety symptoms: resilient (75%) and chronic (25%). Non-resilient trajectories were predicted by higher levels of familial unfairness (perceived lack of equality and reciprocity in the family), relationship difficulties at school and at home, older age, and poor socioeconomic status. Chronic depressive and anxiety symptoms were associated with higher war-related concerns.

These findings can inform preventive and therapeutic interventions for at-risk adolescents to reduce negative long-term outcomes of social crises.

Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory.

One hundred and twenty-six persons aged 18–85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics.

Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model.

Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.

Mental health problems are elevated in autistic individuals but there is limited evidence on the developmental course of problems across childhood. We compare the level and growth of anxious-depressed, behavioral and attention problems in an autistic and typically developing (TD) cohort.

Latent growth curve models were applied to repeated parent-report Child Behavior Checklist data from age 2–10 years in an inception cohort of autistic children (Pathways, N = 397; 84% boys) and a general population TD cohort (Wirral Child Health and Development Study; WCHADS; N = 884, 49% boys). Percentile plots were generated to quantify the differences between autistic and TD children.

Autistic children showed elevated levels of mental health problems, but this was substantially reduced by accounting for IQ and sex differences between the autistic and TD samples. There was small differences in growth patterns; anxious-depressed problems were particularly elevated at preschool and attention problems at late childhood. Higher family income predicted lower base-level on all three dimensions, but steeper increase of anxious-depressed problems. Higher IQ predicted lower level of attention problems and faster decline over childhood. Female sex predicted higher level of anxious-depressed and faster decline in behavioral problems. Social-affect autism symptom severity predicted elevated level of attention problems. Autistic girls' problems were particularly elevated relative to their same-sex non-autistic peers.

Autistic children, and especially girls, show elevated mental health problems compared to TD children and there are some differences in predictors. Assessment of mental health should be integrated into clinical practice for autistic children.

Our study aimed to (1) identify trajectories on different mental health components during a two-year follow-up of the COVID-19 pandemic and contextualise them according to pandemic periods; (2) investigate the associations between mental health trajectories and several exposures, and determine whether there were differences among the different mental health outcomes regarding these associations.

We included 5535 healthy individuals, aged 40–65 years old, from the Barcelona Brain Health Initiative (BBHI). Growth mixture models (GMM) were fitted to classify individuals into different trajectories for three mental health-related outcomes (psychological distress, personal growth and loneliness). Moreover, we fitted a multinomial regression model for each outcome considering class membership as the independent variable to assess the association with the predictors.

For the outcomes studied we identified three latent trajectories, differentiating two major trends, a large proportion of participants was classified into ‘resilient’ trajectories, and a smaller proportion into ‘chronic-worsening’ trajectories. For the former, we observed a lower susceptibility to the changes, whereas, for the latter, we noticed greater heterogeneity and susceptibility to different periods of the pandemic. From the multinomial regression models, we found global and cognitive health, and coping strategies as common protective factors among the studied mental health components. Nevertheless, some differences were found regarding the risk factors. Living alone was only significant for those classified into ‘chronic’ trajectories of loneliness, but not for the other outcomes. Similarly, secondary or higher education was only a risk factor for the ‘worsening’ trajectory of personal growth. Finally, smoking and sleeping problems were risk factors which were associated with the ‘chronic’ trajectory of psychological distress.

Our results support heterogeneity in reactions to the pandemic and the need to study different mental health-related components over a longer follow-up period, as each one evolves differently depending on the pandemic period. In addition, the understanding of modifiable protective and risk factors associated with these trajectories would allow the characterisation of these segments of the population to create targeted interventions.

This paper examined whether distinct life-course trajectories of psychological distress from adolescence to midlife were associated with poorer mental health outcomes during the pandemic.

We present a secondary analysis of two nationally representative British birth cohorts, the 1958 National Child Development Study (NCDS) and 1970 British Cohort Study (BCS70). We used latent variable mixture models to identify pre-pandemic longitudinal trajectories of psychological distress and a modified Poisson model with robust standard errors to estimate associations with psychological distress, life satisfaction and loneliness at different points during the pandemic.

Our analysis identified five distinct pre-pandemic trajectories of psychological distress in both cohorts. All trajectories with prior symptoms of psychological distress irrespective of age of onset, severity and chronicity were associated with a greater relative risk of poorer mental health outcomes during the pandemic and the probability of poorer mental health associated with psychological distress trajectories remained fairly constant. The relationship was not fully attenuated when most recent pre-pandemic psychological distress and other midlife factors were controlled for.

Whilst life-course trajectories with any prior symptoms of psychological distress put individuals at greater risk of poor mental health outcomes during the pandemic, those with chronic and more recent occurrences were at highest risk. In addition, prior poor mental health during the adult life-course may mean individuals are less resilient to shocks, such as pandemics. Our findings show the importance of considering heterogeneous mental health trajectories across the life-course in the general population in addition to population average trends.

The course of Bipolar Disorder (BD) is highly variable, with marked inter and intra-individual differences in symptoms and functioning. In this study, we identified illness trajectories across major clinical domains that could have etiological, prognostic, and therapeutic relevance.

Using the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we performed univariate and multivariate trajectory modeling of depressive symptoms, manic symptoms, and psychosocial functioning. Multinomial regression was performed to identify baseline variables associated with poor outcome trajectories.

Depressive symptoms predominated, with most subjects being found in trajectories characterized by various degrees of depressive symptoms and 13% of subjects being classified in a poor outcome ‘persistently depressed’ trajectory. Most subjects experienced few manic symptoms, although approximately 10% of subjects followed a trajectory of persistently manic symptoms. Trajectory analysis of psychosocial functioning showed impairment in most of the sample, with little improvement during follow up. Multi-trajectory analyses highlighted significant impairment in subjects with persistently mixed and persistently depressed trajectories of illness. In general, poor outcome trajectories were marked by lower educational attainment, higher unemployment and disability, and a greater likelihood of adverse clinical features (rapid cycling and suicide attempts) and comorbid diagnoses (anxiety disorders, PTSD, and substance abuse/dependence disorders).

Subjects with BD can be classified into several trajectories of clinically relevant domains that are prognostically relevant and show differing degrees of associations with a broad range of negative clinical risk factors. The highest level of psychosocial disability was found in subjects with chronic mixed and depressive symptoms, who show limited improvement despite guideline-based treatment.