Evolution of Depressive Symptoms Among Depression Subtypes of Clinical and Functional Variables in Primary Care in Chile

Abstract

Objective:

To compare the evolution of depressive symptoms among depressive subtypes based on clinical and functional variables in a sample of primary care in Chile.

Methods:

A longitudinal study was conducted in the Maule Region of Chile, focusing on 8 primary care from February 2014 to September 2015. Clinical and functional variables, including Mini International Neuro-psychiatric Interview, Outcome Questionnaire interpersonal and social sub-scales, were applied in a latent class analysis. This analysis categorized 210 patients into 3 subtypes: complex depression (N = 100), recurrent depression (n = 96), and unique depression (n = 14). Complex depression, exhibited a higher probability of suicide attempts, interpersonal and social dysfunction, and association with adverse childhood experiences according the Brief Physical and Sexual Abuse Questionnaire. Patients were monitored over 1 year with the Hamilton scale. The Kruskal-Wallis, non-parametric test, followed by paired Mann-Whitney test evaluated difference in the severity of depressive symptoms between the groups. Additionally, data on mental health interventions were collected.

Results:

Out of the 210 patients, 89% were women, with a median age of 50 (range 37-58), and 40.1% with only primary education. Sociodemographic characteristics not differ between groups. Significant differences in depressive symptom severity between the groups were found (X² 90.06, P < .001, Kruskal-Wallis test, η² = 0.084). Post hoc analyses indicated higher depressive symptoms in complex depression compared to recurrent (Z = −9.501, P < .001) and unique (Z = −2.877, P = .004) depression, with no significant difference between recurrent and unique depression (Z = −1.58, P = .113). There were no differences in the number of medical and psychological controls between the groups. The patients with complex depression required greater modifications in the pharmacological prescriptions than those belonging to the other groups.

Conclusion

These results provide additional evidence of a complex depression subtype in primary care in Chile associated with adverse childhood experiences, that had worse resolution of depressive symptoms. Contrary to expectations, patients belonging to this group did not receive further medical and psychological interventions, probably due to a lack of specific clinical recommendations.

Keywords

complex depression depressive symptoms primary care

Background

In Chile, as in the rest of the world, depression presents a significant public health challenge.^1,2 Recent studies reveal that 15.8% of the adult Chilean population reported depressive symptoms, with 6.2% meeting the criteria for major depression.^2,3This condition disproportionately affects women, with a prevalence twice as high as that in men,^2,3 making it the leading cause of disability-adjusted life years in the female population aged 20 to 44.²

Since 2006, depression in Chile has been recognized as a pathology with state-guaranteed care and treatment costs.² Following the tenth version of the International Classification of Diseases (ICD-10), the national depression clinical guide recommends treating this illness based on its severity, determined by the number of depressive symptoms.^4,5 While the majority of depressed patients (90%) receive treatment in primary care,⁶ those with recent suicide attempts, suspected bipolarity, psychosis, and/or therapeutic refractoriness are referred to the specialty care level.⁶

Despite the ICD-10 incorporating a category for unipolar depression, clinical and neurobiological findings suggest that a syndromic perspective is more appropriate for describing this illness, necessitating multidimensional approaches.^7
-9 Unfortunately, these comprehensive views are not consistently integrated into guideline recommendations and clinical practice.¹⁰

Within the context of primary care in Chile, recent studies indicate remission rates near 55%,¹¹ linking poor depression outcomes to high rates of psychiatric comorbidities, a history of previous suicide attempts, and adverse life events.^11
-13 Moreover, a recent latent class analysis identified 3 distinct subtypes based on clinical and functional variables: complex depression, recurrent depression, and unique depression.¹⁴ The complex subtype, representing half of the studied sample, stands out due to its significantly higher likelihood of individuals having a history of suicide attempts, interpersonal difficulties, impaired social functioning, and association with adverse childhood experiences (ACEs).¹⁴ The presence of psychiatric comorbidities distinguishes recurrent depression from unique depression.¹⁴

The clinical characteristics of complex depression align with current knowledge, indicating that ACEs are prevalent in depression and are associated with elevated rates of suicidality, psychiatric comorbidities, chronicity, and resistance to conventional depression treatments.^15,16 This complex clinical profile underscores the enduring neurobiological and psychological impacts of severe stress during vulnerable human developmental periods.^15,16 Authors such as van der Kolk¹⁷ and Teicher et al¹⁸ have highlighted the crucial role of ACEs in diagnosis, treatment, prevention, research, and education throughout life.^17,18 However, there is an important gap in the integration of this knowledge into clinical practice and guideline recommendations.^17
-19

Considering the aforementioned points and underscoring the need for additional research to guide decision-making, particularly in Chile, regarding the validation of a complex clinical subtype of depression associated with ACEs, the principal objective of this study is to compare the progression of depressive symptoms across the different subtypes identified in primary care in Chile (complex, recurrent, and unique depression). Additionally, we aim to evaluate the frequency of medical, psychological, and pharmacological interventions prescribed for each subtype. Our hypothesis posits that complex depression will demonstrate a more adverse outcome compared to the other subtypes, with a correspondingly higher frequency of medical, psychological, and pharmacological interventions.

Methods

Study Design

This longitudinal study followed a cohort of patients who initiated treatment for depression at 8 primary care centers in the Maule Region, Chile, from February 2014 to September 2015. The data are part of the research project “Factors associated with different evolutions presented by patients who enter treatment through explicit health guarantees in depression in primary care, Maule Region, follow-up of a cohort” (FONIS SA13/20135). The study protocol received approval from the Ethics and Research Committees of the University of Talca (3013-08) and the Maule Regional Health Service.

Participants

A total of 404 patients were enrolled and provided informed consent. For patients aged between 15 and 18, assent was also obtained with the approval of guardians. Interviews were conducted by a team of psychiatrists and psychologists, each possessing more than 10 years of clinical experience. Following a predetermined protocol using the MINI Psychiatric Interview,²⁰ the research team evaluated the patients according to the inclusion and exclusion criteria:

Inclusion criteria

Individuals over 15 years of age, enrolled in primary care for the treatment of depression, able to give informed consent (or assent), and meeting the depression criteria described in the Mini International Neuropsychiatric Interview.²⁰

Exclusion criteria

Organic brain damage, sensory impairment, and immediate referral to secondary health services for a current suicide attempt, bipolarity, and/or psychosis.

Of the initial 404 patients, 394 met the inclusion/exclusion criteria. Following the baseline interview, patients underwent follow-up assessments at 3, 6, 9, and 12 months, with 297 of the 394 patients participating in at least 3 follow-up sessions. Moreover, data were collected from the medical records during the observation period for 210 out of the 297 patients, thereby establishing the final sample analyzed in this report.

Procedure

The latent class analysis was reported in a previous study.¹⁴ Briefly, the class groups were obtained from the analysis of the data obtained through the following instruments:

Instruments

Semi-structured clinical interview about sociodemographic information, including age of consultation, marital status, schooling level and current work or activity, and clinical history of depressive illness, including previous depressive episodes and / or treatment for a previous depressive episode.

The Mini International Neuro-Psychiatric Interview (MINI).²⁰ A clinician-administered diagnostic interview with a kappa coefficient of 0.69, a sensitivity of 89%, and a specificity of 92%.^20,21 The Spanish version,²¹ evaluates the main psychiatric disorders of DSM-IV and ICD-10. Each diagnostic category is evaluated in different modules, identified with capital letters, including a suicide module.^20,21

Brief Physical and Sexual Abuse Questionnaire (BPSAQ) by Marshall et al.²² Developed to capture memories of adverse experiences before the age of 15, such as forced separation, substance abuse by a family member, physical harm associated with punishment, and forced sexual contact. External validity showed a Pearson correlation coefficient of 0.88.²³

Outcome Questionnaire (OQ45-2) by Lambert et al.²⁴ Validated in Chile with psychometric properties: sensitivity 0.9 and specificity 0.93.²⁵ For this research, the interpersonal and social subscales were utilized. The interpersonal subscale comprises 12 questions, and scores of 16 points or more indicate interpersonal dysfunction. The social role subscale includes 9 questions, and scores of 14 points or more indicate social role dysfunction.²⁵

Hamilton Depression Rating Scale, 17 items (HDRS-17).²⁶ This scale determines the severity of depression symptoms, validated in Spanish with Cronbach alpha ≥ 0.7, intraclass correlation coefficient (ICC) ≥ .9, inter-rater reliability (ICC) ≥ .9 and sensitivity to change (effect size) ≥ 1.5.²⁶ The National Institute for Health and Care Excellence (NICE) recommends 18 points or less for mild and moderate cases and 19 points or more for severe cases.

Assignment to Depression Subtype

Based on a previous latent class analysis performed on this sample using the 3 latent class model,¹⁴ patients were assigned to the groups as follows:

Complex depression

Patients with a history of attempted suicide, 3 or more than 3 psychiatric comorbidities, more than 16 points on the OQ-45 interpersonal relationships subscale, and more than 14 points on the OQ-45 social role subscale.

Recurrent depression

Patients with no history of suicide attempts, less than 16 points on the OQ-45 interpersonal subscale, less than 14 points on the OQ-45 social role subscale, more of one previous depressive episode.

Unique depression

Patients with no history of suicide attempts, less than 16 points on the OQ-45 interpersonal relationships subscale, less than 14 points on the OQ-45 social role subscale, no previous depressive episodes.

Evolution of Depressive Symptoms

We assessed the evolution of depressive symptoms in the 3 depressive subtypes with the Hamilton Depression Rating Scale. A 17- item questionnaire applied at baseline, 3, 6, 9, and 12 months.²⁶

Data From Clinical Records

We obtained medical records during the study period, including the number of medical check-ups, psychological check-ups, and drug prescriptions. For the prescriptions, we only considered antidepressants, antidepressants plus benzodiazepines, antidepressants plus antipsychotic, and other drug combinations.

Statistical Analysis

The data across the groups was non-normally distributed, as indicated by the Shapiro-Wilk test (P < .05). Consequently, we employed the non-parametric Kruskal-Wallis test to assess statistical differences between the groups. The severity of depressive symptoms between groups was evaluated using the Mann-Whitney test. The impact of time on the severity of depressive symptoms was assessed with the Friedman test, followed by comparisons between different time points using the Wilcoxon test. Pairwise comparisons were adjusted for multiple comparisons using the Bonferroni correction. Categorical data are presented as frequencies while continuous data are presented as mean ± standard deviation and median (range between quartiles 1 and 3). All statistical analyses were conducted using the SPSS software (IBM, Armonk, NY, United States, RRID: SCR_002865) and significance level was set at P < .05.

Results

Out of the 210 patients, 47.6% (n = 100) were categorized as experiencing complex depression, 45.7% (N = 96) recurrent depression, and the unique depression group represented 6.3% (N = 14) of the sample.

Table 1 shows a summary of the sample characteristics. Regarding sociodemographic features, there were no differences among the subtypes. However, complex depression exhibits significantly higher prevalence of posttraumatic stress disorder (X² (2, N = 210) = 12.7, P = .002 Kruskal-Wallis test) and ACEs (X² (2, N = 210) = 12.91, P = .002 Kruskal-Wallis test).

Table 1.

Sociodemographic and Clinical Characteristics in Complex, Recurrent and Unique Depression Subtypes. Primary Care, Maule Region Chile.

	Complex depression	Recurrent depression	Unique depression
	N = 100	N= 96	N = 14
Characteristics	Median (Q1-Q3)	Median (Q1-Q3)	Median (Q1-Q3)	X ²	P
Age	50 (36-57)	48 (49-63)	52 (41-59)	0.69	.71
	N%	N%	N%
Sex	91 (91)	84 (87)	12 (87.5)	0.78	0.68
Education				0.59	0.74
Primary	39 (39)	41 (42.7)	6 (42.9)
Secondary	41 (41)	38 (39.5)	6 (42.9)
Higher	20 (20)	16 (16.7)	2 (14.3)
Live with partners	44 (40)	52 (54.2)	7 (50)	1.46	0.48
Mental comorbidities
General anxiety disorder	30 (30)	31 (32.3)	3 (21.4)	0.69	0.71
Panic disorder	33 (33)	26 (27.1)	1 (7.1)	4.2	0.12
Agoraphobia	29 (29)	18 (18.8)	2 (14.3)	3.08	0.22
Posttraumatic stress	26 (26)	9 (9.4)	0 (0)	12.7	0.02
Social anxiety	22 (22)	13 (13.5)	2 (14.3)	2.52	0.68
Personality disorder	7 (7)	4 (4)	0 (0)	1.61	0.44
Alcohol and drug abuse	7 (7)	4 (4)	1 (7.1)	10.78	0.67
Adverse childhood
Experiences (4 or more)	41 (41)	21 (21.9)	3 (21.4)	12.9	0.02

The Hamilton scores for complex depression showed a decline from a baseline median of 23 (range: 20-27) to 11 (range: 8-18) at 3 months, followed by 10 (range: 3-17) at 6 months, maintaining at 10 (range: 4-17) at 9 months, and finally reaching a median of 11 (range: 5-17) at 12 months. In the case of recurrent depression, scores decreased from a median of 16 (range: 14-17) at baseline to 7 (range: 3-10) at 3 months, further dropping to 6 (range: 3-11) at 6 months, and reaching 4 (range: 2-10) at 9 months, ultimately reaching a median of 4 (range: 1-9) at 12 months. Lastly, for unique depression, scores decreased from a median of 22 (range: 21-24) at baseline to 10 (range: 7-14) at 3 months, reaching a median of 3 (range: 0-5) at 6 months, followed by a median of 5 (range: 2-9) at 9 months, and eventually a median of 4 (range: 1-9) at 12 months (see Figure 1).

Figure 1.

Depressive symptoms over 1 year according complex, recurrent, unique depression subtypes primary care, Maule Region, Chile, 2014.

The Hamilton Scale scores for depressive symptoms exhibited a significant decrease throughout the evaluation period (χ² (4, 210) = 338.46, P < .001, Friedman test). Post hoc analysis, conducted using the Wilcoxon signed-rank test to compare across different time points revealed that depressive symptoms were significantly higher at baseline compared to 3 months (Z = −14.78, P < .001) and at 3 months compared to 6 months (Z = −2.95, P = .003). However, no significant differences were observed between 6 and 9 months (Z = −1.55, P = .12), as well as between 9 and 12 months (Z = −1.03, P = .30) (Figure 1).

The severity of depressive symptoms differed significantly among the groups (X² (2, N = 1050) = 90.06, P < .001, Kruskal-Wallis test) with a moderate effect size of ε² = 0.086. Subsequent post hoc analyses (Mann-Whitney U-test), revealed that depressive symptoms were significantly higher in the complex group compared to both recurrent (Z = −9.501, P < .001) and unique (Z = −2.877, P = .004) groups. However, there was no significant difference in depressive symptoms between the recurrent and unique groups (Z = −1.58, P = .113) (Figure 1).

The number of medical, psychological, and control prescriptions, as well as the type of pharmacological prescriptions, did not differ across the groups, as shown in Table 2. The only significant difference observed was that patients in the complex depression group required more changes in pharmacological prescriptions than the other categories (X² (2, N = 210) = 8.45, P = .014 Kruskal-Wallis test, Mann-Whitney U-test complex versus recurrent (Z = −2.268, P = .023), complex versus unique (Z = −2.241, P = .025) and, recurrent versus unique (Z = −1.231, P = .218) groups.

Table 2.

Therapeutic Supplies Over 1 Year According to Complex, Recurrent, Unique Depression Subtypes Primary Care, Maule Region, Chile.

	Complex depression	Recurrent depression	Unique depression
	N = 100	N = 96	N = 14
	Mean (SD)	Mean (SD)	Mean (SD)
Therapeutic supplies	Median (Q1-Q3)	Median (Q1-Q3)	Median (Q1-Q3)	X ²	P
Medical check-ups	3.82 (2.59)	3.82 (3.02)	3.92 (3.2)
Medical check-ups	3 (2-5)	3 (2-5)	3 (2-6)	0.14	.93
Psychological check-ups	2.01 (4.59)	2.99 (4.08)	2.67 (4.06)
Psychological check-ups	1 (0-4)	1 (0-4)	1 (0-5)	0.85	.63
	N (%)	N (%)	N (%)
Pharmacological Prescriptions				3.39	.18
Only antidepressants	31 (31)	32 (33.3)	2 (14.3)
Antidepressant plus benzodiazepine	54 (54)	61 (63.5)	10 (71.3)
Antidepressant plus bezodiazepine plus other	14 (14)	3 (3.1)	2 (14.3)
Pharmacological changes	46 (46)	29 (30.2)	2 (14.3)	8.45	.15*

Mann-Whitney U-test complex versus recurrent (Z = −2.268, P = .023), complex versus unique (Z = −2.241, P = .025) and, recurrent versus unique (Z = −1.231, P = .218) groups).

Discussion

The primary aim of our study was to assess the progression of depressive symptoms over time in subgroups defined by complex depression, recurrent depression, and unique depression. As expected, complex depression exhibited a significantly more challenging clinical course than the other groups, as indicated by consistently elevated depressive symptoms over time. This finding supports the notion that complex depression can be identified as a distinct clinical subtype of depression.¹⁴ On the contrary, the absence of a significant difference in clinical progression between recurrent and unique depression suggests that these groups may share common clinical features and could be components of a single relevant clinical subtype.

Our findings align with Teicher and Samson’s²⁷ thesis that ACEs contribute to the differentiation of specific subtypes within each mental condition. These subtypes are characterized by a more complex clinical profile and a less favorable prognosis, necessitating a more specific treatment approach.¹⁹ Trauma-informed care, which acknowledges the intricate interplay between cumulative trauma exposure, socioeconomic disadvantage, depression, and suicidality,^28
-30 becomes crucial in addressing the emotional and relational challenges faced by individuals who have undergone adverse life experiences.^28
-30

From a trauma-informed care standpoint, it is essential for professionals engaged in the care of individuals who have undergone adverse life experiences to cultivate the necessary skills for addressing the emotional and relational challenges.^8,29,30 Considering this perspective, one would logically anticipate that patients classified under complex depression would receive a more extensive array of medical and, notably, psychological interventions. Surprisingly, our observations do not align with this expectation, potentially attributed to the lack of specific recommendations in clinical practice regarding the recognition of ACEs and their consequences.^18,19

Treatment guidelines for depression often derive recommendations from controlled trials involving specific samples, as evidenced by the recurrent and single groups in our study.³¹ Nevertheless, these recommendations may not always prove effective in real-world settings, particularly for patients exhibiting more complex characteristics.³¹ These patients share features reminiscent of refractory depression, a condition for which clinical guidelines predominantly recommend different pharmacological strategies.³² This observation sheds light on the significantly higher frequency of pharmacological changes observed in the complex depression group, underscoring the challenges that primary healthcare teams face in managing these patients.

An internationally recognized expert consensus suggests that refractory depression is most accurately conceptualized as difficult-to-treat depression.³³ This perspective aligns with the evolving approach to depression management, transitioning from a medical model to a patient-cantered, multidimensional, biopsychological model, in harmony with the principles of trauma-informed care.^28,29 Importantly, studies have showed that integrating psychotherapy with standard care significantly enhances depression symptoms in treatment-resistant depression.³⁴

Nevertheless, it is noteworthy that Latin American consensus guidelines for treatment-resistant depression predominantly emphasize biomedical interventions, side-lining psychotherapy in their treatment algorithm.³⁵ Furthermore, there appears to be a notable oversight in recognizing ACEs in patients with refractory depression within these guidelines.^35,36 Our study underscores a substantial gap in recommendations for managing depression in primary care, particularly for cases with more intricate presentations.³⁷

While our study yields robust results, it is imperative to recognize the inherent limitations. One such limitation is tied to our deliberate sampling strategy, which predominantly focused on women. Consequently, prudence is advised when generalizing our findings to wider populations or different outpatient settings. However, it is reassuring that the analysis test did not reveal significant sociodemographic differences among the 3 groups, validating the robustness of our results and mitigating concerns about potential confounding variables related to sociodemographic. Importantly, the observed differences between the groups were discerned to be linked to clinical and functional factors.

Additional limitations include the exclusion of variables such as emotion regulation.³⁸ Our analysis focused exclusively on the number of interventions documented in medical records during the observation year. The use of nonparametric analyses limited our ability to demonstrate differences between groups and interactions over time, in contrast to ANOVA. Lastly, future research should delve into differences among various measures within each group, uncovering specific intervention needs at different stages of the depressive trajectory for each group.

In conclusion, this study represents a pioneering effort in primary care research, systematically tracking a sample of depression, categorizing depressive subtypes identified through latent class analysis, and evaluating their trajectories. Utilizing validated instruments in Spanish, we captured crucial clinical and functional variables—elements often overlooked in routine clinical practice.^39,40 Our results unveiled a complex clinical depression subtype linked to ACEs and a more unfavorable progression, which, regrettably, did not receive distinctive clinical attention.

Looking forward, it is crucial to continue the efforts in producing evidence that guides decision-making concerning the identification and handling of clinical characteristics linked to more complex depression, with a specific emphasis on recognizing ACEs. These elements, often overlooked in routine clinical care,^3,18,19,40 require heightened focus and inclusion in forthcoming clinical depression guidelines to enhance the effectiveness and comprehensiveness of patient care.

Footnotes

Data Availability Statement

The data used to support the findings of this study are available from the corresponding author upon request.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors received financial support from ANID-FONIS Proyect SA13/20135.

ORCID iD

Verónica Vitriol

References

World Health Organization (WHO). Depressive disorder (Depression). 2023. Accessed March, 2024. https://www.who.int/news-room/fact-sheets/detail/depression/

Ministerio de Salud de Chile (MINSAL). National Health Survey, Ens, 2016-2017. 2018.

Nazar

Gatica-Saavedra

Provoste

, et al. Factores Asociados a depresión en Población Chilena. Resultados Encuesta Nacional De Salud 2016-2017. Rev Med Chile. 2021;149(10):1430-1439.

Ministerio de Salud de Chile (MINSAL). Guía Clínica Depresión En Personas De 15 Años Y Más, 2013. https://wwwbiblioteca.minsal.cl/wp/wp/content/uploads/2016/04GUIA-CLINICA-DEPRESION-15-Y-MASpdf

Organización Panamericana de la Salud (OPS). CIE-10, Clasificación Estadística Internacional De Enfermedades Y Problemas De La Salud 10. Edición Organización Panamericana de la Salud. 1992.

Araya

Alvarado

Sepúlveda

Rojas

Lessons from scaling up a depression treatment program in primary care in Chile. Rev Panam Salud Publica. 2012;32(3):234-240. doi:10.1590/s1020-49892012000900009

Cole

McGuffin

Farmer

AE.

The classification of depression: are we still confused?

Br J Psychiatry. 2008;192(2):83-85. doi:10.1192/bjp.bp.107.039826

Kendler

KS.

The origin of our modern concept of depression-the history of Melancholia from 1780-1880: a review. JAMA Psychiatr. 2020;77(8):863-868. doi:10.1001/jamapsychiatry.2019.4709

Velásquez

Gómez-Maquet

Ferro

, et al. Multidimensional analysis of major depression: association between BDNF methylation, psychosocial and cognitive domains. Front Psychiatry. 2021;12:768680. doi:10.3389/fpsyt.2021.768680

10.

van Loo

Cai

Gruber

, et al. Major depressive disorder subtypes to predict long-term course. Depress Anxiety. 2014;31(9):765-777. doi:10.1002/da.22233

11.

Vitriol

Cancino

Serrano

Ballesteros

Potthoff

Remission in depression and associated factors at different assessment times in primary care in Chile. Clin Pract Epidemol Ment Health. 2018;14:78-88. doi:10.2174/1745017901814010078

12.

Vitriol

Cancino

Leiva-Bianchi

, et al. [Association between adverse childhood experiences with depression in adults consulting in primary care]. Rev Med Chil. 2017;145(9):1145-1153. doi:10.4067/s0034-98872017000901145

13.

Cancino

Leiva-Bianchi

Serrano

, et al. Factors associated with psychiatric comorbidity in depression patients in primary health care in Chile. Depress Res Treat. 2018;2018:9. doi:10.1155/2018/1701978

14.

Vitriol

Cancino

Serrano

, et al. Latent class analysis in depression, including clinical and functional variables: evidence of a complex depressive subtype in primary care in Chile. Depress Res Treat. 2021;2021:6629403. doi:10.1155/2021/6629403

15.

Nemeroff

CB.

Paradise Lost: the Neurobiological and clinical consequences of child abuse and Neglect. Neuron. 2016;89(5):892-909. doi:10.1016/j.neuron.2016.01.019

16.

Lippard

ETC

Nemeroff

CB.

The devastating clinical consequences of child abuse and neglect: increased disease vulnerability and poor treatment response in mood disorders. Am J Psychiatr. 2023;180(8):548-564. doi:10.1176/appi.ajp.19010020

17.

van der Kolk

. Commentary: the devastating effects of ignoring child maltreatment in psychiatry–a commentary on Teicher and Samson 2016. J Child Psychol Psychiatry. 2016;57(3):267-270. doi:10.1111/jcpp.12540

18.

Teicher

Gordon

Nemeroff

CB.

Recognizing the importance of childhood maltreatment as a critical factor in psychiatric diagnoses, treatment, research, prevention, and education. Mol Psychiatry. 2022;27(3):1331-1338. doi:10.1038/s41380-021-01367-9

19.

Martínez

Gloger

Diez de Medina

, et al. [Systematic review of treatment alternatives for depressed adults with early adverse stress]. Rev Med Chile. 2021;149(10):1473-1484. doi:10.4067/s0034-98872021001001473

20.

Lecrubier

Sheehan

Weiller

, et al. The mini international neuropsychiatric interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI. Eur Psychiatr. 1997;12(5):224-231.

21.

Bobes

Gilbert

Soto

MINI Mini International Neuropsychiatric Interview, Versión En Español 5.0.0. DSM IV. Instituto IAP; 1998.

22.

Marshall

Schneier

Lin

, et al. Childhood trauma and dissociative symptoms in panic disorder. Am J Psychiatr. 2000;157(3):451-453. doi:https://doi.org/10.1176/appi.ajp.157.3.451

23.

Cuneo

González

Jara

, et al. External validation of the Trauma Scale Marshall. In: Florenzano

Weil

Carvajal

Cruz

, eds. Trauma infanto-juvenil y psicopatología adulta. Universidad de los Andes; 2004: 146. doi:10.13140/RG.2.1.3358.4086

24.

Lambert

Smart

Campbell

, et al. Psychotherapy outcome, as measured by the oq-45, in African American, Asian/Pacific Islander, Latino/a, and Native American clients compared with matched Caucasian clients. J College Stud Psychother. 2006;20:17-29. doi:10.1300/j035v20n04_03

25.

von Bergen

de la Parra

. OQ-45.2, an outcome questionnaire for monitoring change in psychotherapy: adaptation, validation and indications for its application and Interpretation. Terapia Psicológica. 2002;20(2):161-176.

26.

Bobes

Bulbena

Luque

, et al. A comparative psychometric study of the Spanish versions with 6, 17, and 21 items of the hamilton depression rating scale. Med Clin. 2003;120(18):693-700. doi:https://doi.org/10.1016/s0025-7753(03)73814-7

27.

Teicher

Samson

JA.

Childhood maltreatment and psychopathology: a case for ecophenotypic variants as clinically and neurobiologically distinct subtypes. Am J Psychiatr. 2013;170(10):1114-1133. doi:10.1176/appi.ajp.2013.12070957

28.

Vitriol

Sciolla

Cancino

, et al. Cuidado informado en trauma: un Modelo Emergente para el Abordaje del Subtipo depresivo con historia De Adversdad Infantil. Rev Chil Neuropsiquiatr. 2020;58:348-362.

29.

Raja

Hasnain

Hoersch

Gove-Yin

Rajagopalan

Trauma informed care in medicine: current knowledge and future research directions. Fam Community Health. 2015;38(3):216-226. doi:10.1097/fch.0000000000000071

30.

Peckham

Introducing the neuroplastic narrative: a non-pathologizing biological foundation for trauma-informed and adverse childhood experience aware approaches. Front Psychiatry. 2023;14:1103718. doi:10.3389/fpsyt.2023.1103718

31.

Wisniewski

Rush

Nierenberg

, et al. Can phase III trial results of antidepressant medications be generalized to clinical practice? A STAR*D report. Am J Psychiatr. 2009;166(5):599-607. doi:10.1176/appi.ajp.2008.08071027

32.

Gaynes

Lux

Gartlehner

, et al. Defining treatment-resistant depression. Depress Anxiety. 2020;37(2):134-145. doi:10.1002/da.22968

33.

McAllister-Williams

Arango

Blier

, et al. The identification, assessment and management of difficult-to-treat depression: an international consensus statement. J Affect Disord. 2020;267:264-282. doi:10.1016/j.jad.2020.02.023

34.

Ijaz

Davies

Williams

, et al. Psychological therapies for treatment-resistant depression in adults. Cochrane Database Syst Rev. 2018;5(5):CD010558. doi:10.1002/14651858.CD010558.pub2

35.

Corral

Bojórquez

Cetkovich-Bakmas

, et al. Latin American consensus recommendations for the management and treatment of patients with treatment-resistant depression (TRD). Span J Psychiatry Ment Heal. 2023. doi:10.1016/j.sjpmh.2023.06.001

36.

Mladen

Williams

Griffin

Perrin

Rybarczyk

BD.

Models of trauma exposure, depression, and suicidality in safety-net primary care. J Trauma Stress. 2021;34(6):1139-1148. doi:10.1002/jts.22658

37.

de la Parra

Zúñiga

Dagnino

Gómez-Barris

. Complex depression in high-pressure care settings: Strategies and therapeutic competences. In: de la Parra

Dagnino

Behn

, eds. Depression and Personality Dysfunction: An Integrative Functional Domains Perspective. Springer International Publishing; 2021: 213-244.

38.

Martínez

Gloger

Dagnino

de Medina

. Early adverse stress and depression severity:A pilot exploration of mediating mechanisms. Dev Psychopathol. 2023. doi:10.1017/S0954579423000688

39.

Weinreb

Savageau

Candib

, et al. Screening for childhood trauma in adult primary care patients: a cross-sectional survey. Prim Care Companion J Clin Psychiatry. 2010;12(6): PCC.10m00950. doi:10.4088/pcc.10m00950blu

40.

Tink

Turin

Kelly

Adverse childhood experiences: survey of resident practice, knowledge, and attitude. Fam Med. 2017;49(1):7-13.