All studies employed the same widely used and validated screening instrument, the Patient Health Questionnaire-9 , to determine baseline depression diagnosis. However, there was wide variability in the measures used to define study outcomes. To determine depressive symptom improvement, six of nine studies used the PHQ-9, two studies used the Hopkins Symptom Checklist Depression Scale , and one study used the Hamilton Rating Scale for Depression , the Clinical Global Impression Severity Scale , and the Clinical Global Impression Improvement Scale . One study reported that researchers used their own translation of the PHQ-9 to Chinese, which had been validated in a prior study.Other studies did not specify whether they used validated translations or translated their own instruments.All studies adequately described the interventions and the control conditions .Two studies reported post-intervention follow-up and included outcomes a year after the intervention had ended .Not all studies reported how frequently care managers contacted patients in the intervention group during follow-up .The mean age ranged from 34.8 to 57 years across studies, and 1166 of 4859 participants were male. Among the nine studies, 2679 participants had LEP. Most studies focused on Latino immigrants living in the United States , with Spanish as the preferred language3; only two studies included Chinese and Vietnamese immigrants. The majority of LEP participants spoke Spanish. One hundred and ninety-five patients with LEP spoke Mandarin, Cantonese, or Vietnamese . Two studies had poor characterization of participant languages, noting that many spoke BAsian languages,^ and citing only clinic language demographics . In two studies reporting that patients preferred a non-English language,vertical garden indoor the degree of English language proficiency was not described. Three-quarters of participants were recruited from general primary care and had a variety of medical conditions. Other participants were recruited into the studies for specific comorbidities .While intervention details were not always fully described, eight of nine studies employed bilingual care managers for the delivery of care in the collaborative care model.

The ninth study did not explicitly mention how the intervention was delivered to patients with LEP.No studies reported on the use of interpreters. These five studies explicitly tailored their interventions to different cultural groups. The two RCTs and one non-RCT serving Spanish-speaking patients, all conducted by the same research group, culturally tailored the collaborative care model by adapting the intervention materials for literacy and for idiomatic and cultural content. They further included cultural competency training for staff and employed bilingual staff to conduct the intervention.The remaining studies mentioned adding a cultural component to the collaborative care model with the goal of serving Asian immigrants with traditional beliefs about mental illness. One study further adapted the psychiatric assessment for cultural sensitivity.Four of five RCTs reported on change in depressive symptoms; none reported outcomes by preferred language group. Three RCTs reported that the proportion of patients who experienced a ≥ 50% reduction in depressive symptoms score was 13% to 25% greater in the intervention arm than in usual care .The last RCT, Yeung et al., reported no statistically significant difference between treatment groups at 6 months44; however, the investigators noted availability and high uptake of psychiatric services in both study arms . Three of these four RCTs included cultural tailoring of their interventions.Two RCTs reported on receipt of depression treatment and treatment preferences. In one RCT, 84% of patients treated in the collaborative care intervention received depression treatment , compared to only 33% of patients in the enhanced usual care arm, over 12 months of follow-up. Another RCT focused on depression treatment preferences.Using conjoint analysis preference surveys, this study found that patients preferred counseling or counseling plus medication over antidepressants alone, and that patients preferred treatment in primary care rather than in specialty mental health care. Patients in the collaborative care intervention group were much more likely to receive their preferred treatment at 16 weeks than were patients in usual care . However, this study also found that English speakers in both groups were more likely to receive their preferred treatment modality than their Spanish speaking counterparts .

One non-RCT study46 found that 49% and 48% of patients reported improved depressive symptoms at 6 and 12 months, respectively, among study participants treated with collaborative care. The two studies that reported outcomes by preferred language found significant differences between English- and Spanish-speaking patients. Bauer et al. found that Spanish language preference was associated with more rapid and greater overall improvement , when compared to English preference, despite not being associated with receipt of appropriate pharmacotherapy.Similarly, Sanchez et al. found that Spanish-speaking Hispanic patients had significantly greater odds of achieving clinically meaningful improvement in depressive symptoms at 3-month follow-up than did non-Hispanic whites .In contrast, Ratzliff et al. found similar treatment process and depression outcomes at 16 weeks among three groups treated with collaborative care: Asians treated at a culturally sensitive clinic, Asians treated at a general clinic, and whites treated at a general clinic .Furthermore, the study did not have a usual care control group to enable evaluation of the intervention.Despite the existence of effective treatment, depression care for patients with LEP is challenging for both patients and clinicians, and better models of care are needed. In a systematic review of the current literature on outpatient, primary care based collaborative care treatment of depression, we found that collaborative care delivered by bilingual providers was more effective than usual care in treating depressive symptoms among patients with LEP. The systematic review revealed important limitations in the current evidence base. The review was limited by the low number of studies , heterogeneity of study outcomes and definitions, and a lack of data on use of language access services. However, the randomized controlled studies were consistent in treatment effect size, as three of four high-quality RCTs found that 13%–25% more patients reported improved depressive symptoms when treated with collaborative care compared to usual care; the fourth had unusually high rates of treatment in the comparison arm and found no difference between groups.This is consistent with prior systematic reviews of collaborative care treatment.

Review of two cohort studies that reported outcomes by preferred language found similar-sized improvements as 10% and 27% more Spanish-speaking patients had improved depressive symptoms during 3 months of follow-up when treated with collaborative care, indicating that patients with LEP may benefit as much as, if not more than, English-speaking patients treated with collaborative care.In short, the collaborative care model—with its emphasis on regular screening, standardized metrics, validated instruments, proactive management, and individualized care, and when adapted for care of LEP patients with depression via the use of bilingual providers—appears to improve care for this patient population. Yet while the collaborative care model has performed well in research studies, many questions remain for wider implementation and dissemination in systems caring for patients with LEP. To help guide the dissemination of an effective model of collaborative care for patients with LEP, researchers will need to be more specific in detailing the language skills of participants and any cultural tailoring and adaptations made to the model to serve specific populations, as we found that race and ethnicity are often conflated with language in these studies,vertical garden indoor system and that preferred language and degree of English language proficiency is not always made explicit. Language barriers may increase the possibility of diagnostic assessment bias, diagnostic errors, and decreased engagement and retention in depression care.It is important to note that most studies employed bilingual staff; language concordance may be particularly important when dealing with mental health concerns, as it is associated with increased patient trust in providers, improved adherence to medications, and increased shared decision-making.Furthermore, the collaborative care model may have been addressing cultural barriers to care beyond linguistic barriers. While a few of the studies culturally adapted and modified their collaborative care model and their psychiatric assessments, these adaptations were not addressed in detail and may be difficult to replicate in other settings. Best practices for culturally adapting collaborative care for patients with LEP have yet to be defined. Further research is also needed to more rigorously ascertain the effectiveness of cultural versus linguistic tailoring on the effectiveness of collaborative care in LEP groups. Additionally, given the evidence that depression in racial and ethnic minorities and patients with LEP often goes unrecognized,efforts will be needed to make sure these groups are systematically screened for depressive symptoms and referred for care in culturally sensitive ways. One large implementation study in the state of Minnesota found a marked difference in enrollment into collaborative care by LEP status.Of those eligible for a non-research-oriented collaborative care model, only 18.2% of eligible LEP patients were enrolled over a 3-year period, compared to 47.2% of eligible English-speaking patients . Similarly, Asian patients were underrepresented in studies and likely in collaborative care programs. Yeung et al. reported that the majority of Chinese immigrants with depression were under-recognized and under treated in primary care, as evidenced by the fact that only 7% of patients who screened positive for depression were engaged in treatment in primary care clinics in Massachusetts.Referral processes for collaborative care may also need to be improved for patients with LEP.

The reasons for differences in enrollment by LEP status in collaborative care programs remain poorly elucidated and likely include patient-, provider-, and systems-based factors. However, these results suggest that without targeted efforts to screen, enroll, and engage patients with LEP, collaborative care models may only widen mental health disparities for such patients. Studies that examine implementation and sustainability of the collaborative care model are needed. This review has a number of limitations. We may have missed studies where language and participant origin were not adequately described. Additionally, as has been noted in prior systematic reviews of RCTs of collaborative care, participant and provider blinding would not have been feasible, due to the nature of the interventions.Other limitations include the variability in study duration and outcome assessment, making direct outcome comparison difficult. Finally, of the nine studies included in this review, five were conducted in Los Angeles, CA . This may limit the generalizability of our results.Circadian rhythms arise from genetically encoded molecular clocks that originate at the cellular level and operate with an intrinsic period of about a day . The timekeeping encoded by these self-sustained biological clocks persists in constant darkness but responds acutely to changes in daily environmental cues, like light, to keep internal clocks aligned with the external environment. Therefore, circadian rhythms are used to help organisms predict changes in their environment and temporally program regular changes in their behavior and physiology. The circadian clock in mammals is driven by several interlocked transcription-translation feedback loops. The integration of these interlocked loops is a complicated process that is orchestrated by a core feedback loop in which the heterodimeric transcription factor complex, CLOCK:BMAL1, promotes the transcription of its own repressors, Cryptochrome and Period as well as other clock-controlled genes . Notably, there is some redundancy in this system as paralogs of both PER and CRY proteins participate in the core TTFL. In general, these proteins accumulate in the cytoplasm, interact with one another, and recruit a kinase that is essential for the clock, Casein Kinase 1 δ/ε , eventually making their way into the nucleus as a large complex to repress CLOCK:BMAL1 transcriptional activity. Despite this relatively simple model for the core circadian feedback loop, there is growing evidence that different repressor complexes that exist throughout the evening may regulate CLOCK:BMAL1 in distinct ways. PER proteins are essential for the nucleation of large protein complexes that form early in the repressive phase by acting as stoichiometrically-limiting factors that are temporally regulated through oscillations in expression. As a consequence, circadian rhythms can be disrupted by constitutively over expressing PER proteins or established de novo with tunable periods through inducible regulation of PER oscillations. CK1δ/ε regulate PER abundance by controlling its degradation post-translationally; accordingly, mutations in the kinases or their phosphorylation sites on PER2 can induce large changes in circadian period, firmly establishing this regulatory mechanism as a central regulator of the mammalian circadian clock. CRY proteins bind directly to CLOCK:BMAL1 and mediate the interaction of PER-CK1δ/ε complexes with CLOCK:BMAL1 leading to phosphorylation of the transcription factor and its release from DNA as well as acting as direct repressors of CLOCK:BMAL1 activity by sequestering the transcriptional activation domain of BMAL1 from coactivators like CBP/p300.