Depression phenotypes in spinal cord injury and impact on post-injury healthcare utilization and cost: Analysis using a large claim database.

CONTEXT/OBJECTIVE: Depression is the most common psychological comorbidity associated with spinal cord injury (SCI) and affects healthcare utilization and costs. This study aimed to use an International Classification of Disease (ICD) and prescription drug-based depression phenotypes to classify people with SCI, and to evaluate the prevalence of those phenotypes, associated risk factors, and healthcare utilization. DESIGN: Retrospective Observational Study. SETTING: Marketscan Database (2000-2019). PARTICIPANTS: Individuals with SCI were classified into six ICD-9/10, and prescription drugs defined phenotypes: Major Depressive Disorder (MDD), Other Depression (OthDep), Antidepressants for Other Psychiatric Conditions (PsychRx), Antidepressants for non-psychiatric condition (NoPsychRx), Other Non-depression Psychiatric conditions only (NonDepPsych), and No Depression (NoDep). Except for the latter, all the other groups were referred to as "depressed phenotypes". Data were screened for 24 months pre- and 24 months post-injury depression. INTERVENTIONS: None. OUTCOME MEASURES: Healthcare utilization and payments. RESULTS: There were 9,291 patients with SCI classified as follows: 16% MDD, 11% OthDep, 13% PsychRx, 13% NonPsychRx, 14% NonDepPsych, 33% NoDep. Compared with the NoDep group, the MDD group was younger (54 vs. 57 years old), predominantly female (55% vs. 42%), with Medicaid coverage (42% vs. 12%), had increased comorbidities (69% vs. 54%), had fewer traumatic injuries (51% vs. 54%) and had higher chronic 12-month pre-SCI opioid use (19% vs. 9%) (all P < 0.0001). Classification into a depressed phenotype before SCI was found to be significantly associated with depression phenotype post-SCI, as evidenced by those who experienced a negative change (37%) vs. a positive change (15%, P < 0.0001). Patients in the MDD cohort had higher healthcare utilization and associated payments at 12 and 24 months after SCI. CONCLUSION: Increasing awareness of psychiatric history and MDD risk factors may improve identifying and managing higher-risk patients with SCI, ultimately optimizing their post-injury healthcare utilization and cost. This method of classifying depression phenotypes provides a simple and practical way to obtain this information by screening through pre-injury medical records.

Four maternal characteristics determine the 12-month course of chronic severe postpartum depressive symptoms.

BACKGROUND: Postpartum depression is a heterogeneous disorder in phenotype and etiology. Characterizing the longitudinal course of depressive symptoms over the first year after birth and identifying variables that predict distinct symptom trajectories will expedite efficient mental health treatment planning. The purpose was to determine 12-month trajectories of postpartum depressive symptoms, identify characteristics that predict the trajectories, and provide a computational algorithm that predicts trajectory membership. METHODS: A prospective cohort of women delivering at an academic medical center (2006-2011) was recruited from an urban women's hospital in Pittsburgh, PA. Women with a postpartum depressive disorder (n = 507) participated and completed symptom severity assessments at 4-8 weeks (intake), 3 months, 6 months, and 12 months. Women were predominantly Caucasian (71.8%), married (53.3%), and college educated (38.7%). Clinician interviews of depressive symptom severity, medical and psychiatric history, assessment of function, obstetric experience, and infant status were conducted. RESULTS: Analyses resulted in identification of three distinct trajectories of depressive symptoms: (1) gradual remission (50.4%), (2) partial improvement (41.8%), and (3) chronic severe (7.8%). Key predictive characteristics of the chronic severe versus gradual remission and partial improvement trajectories included parity, education, and baseline global functioning and depression severity. We were able to predict trajectory membership with 72.8% accuracy from these characteristics. CONCLUSIONS: Four maternal characteristics predicted membership in the chronic severe versus gradual remission and partial improvement trajectories with 72.8% accuracy. The trajectory groups comprise clinically relevant subgroups with the potential for tailored treatments to reduce the disease burden of postpartum depression.

Effects of genetic deletion versus pharmacological blockade of the LPA1 receptor on depression-like behaviour and related brain functional activity.

Animal models of psychopathology are particularly useful for studying the neurobiology of depression and characterising the subtypes. Recently, our group was the first to identify a possible relationship between the LPA1 receptor and a mixed anxiety-depression phenotype. Specifically, maLPA1-null mice exhibited a phenotype characterised by depressive and anxious features. However, the constitutive lack of the gene encoding the LPA1 receptor (Lpar1) can induce compensatory mechanisms that might have resulted in the observed deficits. Therefore, in the present study, we have compared the impact of permanent loss and acute pharmacological inhibition of the LPA1 receptor on despair-like behaviours and on the functional brain map associated with these behaviours, as well as on the degree of functional connectivity among structures. Although the antagonist (intracerebroventricularly administered Ki16425) mimicked some, but not all, effects of genetic deletion of the LPA1 receptor on the results of behavioural tests and engaged different brain circuits, both treatments induced depression-like behaviours with an agitation component that was linked to functional changes in key brain regions involved in the stress response and emotional regulation. In addition, both Ki16425 treatment and LPA1 receptor deletion modified the functional brain maps in a way similar to the changes observed in depressed patients. In summary, the pharmacological and genetic approaches could ultimately assist in dissecting the function of the LPA1 receptor in emotional regulation and brain responses, and a combination of those approaches might provide researchers with an opportunity to develop useful drugs that target the LPA1 receptor as treatments for depression, mainly the anxious subtype.This article has an associated First Person interview with the first author of the paper.

The dysregulation of hippocampal serotonin receptor 4 and let-7a were associated with dual stress-induced depression in rats / 中华行为医学与脑科学杂志

Objective To study the effect of dual stress on the behaviors and the expression of hippocampal let-7a and serotonin receptor 4(HTR4) in rats.Methods Newborn SD rats were randomly divided into dual stress group (DS,n=6) and control group (C,n=6).The DS rats were deprived of the mother care 6 hours per day from postnatal day 1 to 14 and then were exposed to chronic mild stress for 21 days from 10 weeks old,while the rats from C group received no experimental handle but husbandry care.Open field test,forced swimmiug test and sucrose consumption test were conducted to evaluate rats' depression-like behaviors at the age of thirteen weeks.The let-7a level in hippocampus was detected by real-time Polymerase Chain Reaction and the HTR4 protein level was measured by Western Blotting.Results In the open filed test,the rearing times of DS rats was shorter than that of C group((7.50±2.35) vs (19.00±5.73),P＜0.05).In the forced swimming test,the floating time of DS rats was longer than that of C group ((110.17 ± 1.72)s vs (70.33± 1.16)s,P＜ 0.05).In the sucrose c onsumption test,DS rats consumed less sucrose than rats from C group did((0.80±0.73) vs (0.52±0.26),P＜ 0.05).The protein level of hippocampal HTR-4 in DS group was lower than that of C group((1.44±0.38) vs (0.46±0.29),P＜0.01).The let-7a level in DS group was higher than that of C group((0.04±0.01) vs (1.58±0.27),P＜0.01).The Pearson correlation analysis revealed that the sucrose preference rate of rats were negatively and positively correlated with hippocampal let-7a and HTR4 level respectively(r=-0.653,P＜0.05; r=0.774,P＜0.01),and hippocampal let-7a level showed negative association with HTR4 protein level (r=-0.803,P＜0.01).Conclusion Dual stress can induce the depressive behaviors of rats and affect the expression of let-7a and HTR4 in hippocampus.Hippocampal HTR4 and let-7a might be involved in determining individual ability to experience pleasure in rats;and hippocampal let-7a may be involved in the regulation of HTR4 gene expression in rats.