The developing brain is not thoroughly studied due to ethical concerns

The prevalence of substance use in the past three months was: 47% for cannabis, 33% for cocaine, 29% for methamphetamine, 26% for hallucinogens, 19% for sedatives, 13% for prescription opioids, 12% for street opioids, 10% for prescription stimulants, 7% for inhalants, and 3% reported the use of other substances, including: “belladonna”, “Hawaiian plant”, “native ritualistic sacraments”, “mushrooms” and “other psychedelics”. A third engaged in poly substance use in the past three months. Over two thirds reported binge drinking in the past year .The median syndemic score was 2 , 18% had no syndemic factors, 22% had one, 38% had two and 21% had three . Three of three possible distinct associations among the syndemic factors were positive and significant, suggesting a high level of clustering among the syndemic factors examined in this analysis . The prevalence of being at risk of clinical depression by the number of syndemic factors was: 27% for zero syndemic factors, 68% for one syndemic factor, 83% for two syndemic factors and 100% for those experiencing three syndemic factors . This is also demonstrated in Fig 1 which shows that the number of syndemic factors increases linearly with depression scores. Results from the bivariate Poisson regression models are presented in Table 4. In adjusted Poisson regression models , those with symptoms of moderate or severe anxiety in the past two weeks were more likely to be at risk of clinical depression compared to those with minimal or mild symptoms of anxiety . TAY experiencing symptoms of PTSD in the past month were significantly more likely to be at risk of clinical depression compared to those without symptoms of PTSD . TAY who engaged in poly substance use,mobile vertical grow rack defined as using three or more distinct drugs in the past three months were also more likely to be at risk of clinical depression compared to those who did not engage in poly substance use , P = 0.012.

This study of the prevalence and correlates of being at risk of clinical depression and the role of syndemic factors among marginally housed and homeless TAY in San Francisco, identified three important findings. First, the prevalence of being at risk of clinical depression was distressingly high among TAY in this study. Second, syndemic-affected TAY were significantly more likely to be at risk of clinical depression compared to those with fewer syndemic factors. Third, there was a high prevalence of the syndemic factors examined including, symptoms of moderate or severe anxiety, symptoms of PTSD and poly substance use. These findings may be informative for social and behavioral health services targeting marginally housed or homeless TAY. Approximately three quarters of TAY in our study were at risk of clinical depression, underlining the need for further psychiatric evaluation in this population. Depression among TAY has been shown to increase the risk of suicidality, attempted suicide and problematic substance use. The literature among TAY and other populations including young adults has also established connections between anxiety, PTSD, drug use and depression, showing how these factors tend to co-occur. Given the high prevalence of being at risk of clinical depression among TAY in this study, behavioral treatments including, cognitive behavioral therapy and interpersonal psychotherapy may help treat those with depression and those at risk of developing depression. There was a high level of clustering among the syndemic factors measured in our study, including symptoms of moderate or severe anxiety, symptoms of PTSD and poly substance use, suggesting that these factors tend to co-occur. Syndemic-affected TAY were more likely to be at risk of clinical depression compared to their counterparts, suggesting that the clustering of these psychosocial problems has an additive effect on the risk of depression among TAY in our study. This is shown in our model examining a nominal syndemic score on the risk of clinical depression, where those with two or three syndemic factors were more likely to be at risk of clinical depression compared to those with zero or one, showing that syndemic-affected TAY may experience worse psychological outcomes compared to their counterparts.

These findings are supported by prior research which shows that depression is associated with anxiety and PTSD, co-occurring more frequently than depression occurs alone. It is important to note that co-occurring depression, anxiety and PTSD are also associated with reduced recovery and increased chronicity of illness, compared to experiencing one of these conditions alone. To address syndemic risk among marginally housed and homeless TAY, structural interventions including, comprehensive medical, social and behavioral health services that have streamlined processes to treat multiple co-occurring conditions may be helpful. This can be achieved by increasing training programs for primary care and mental health clinicians to maximize the potential for treating mental health co-morbidities . In addition, substance use treatment programs for unstably housed youth which incorporate harm reduction principals like “Seeking Safety”, a group based psychotherapy model that simultaneously addresses substance use and PTSD should be considered.Our study has limitations. The baseline assessment did not include diagnostic interviewing for confirmation of depression, anxiety and PTSD. Therefore, data presented on these mental health conditions are based on survey responses and do not represent official diagnoses. Clinical research leveraging diagnostic tools including neuropsychological or cognitive evaluation conducted by psychiatric partitioners is needed to assess the prevalence of diagnosed cases among homeless and marginally housed TAY. The modest sample size, may have increased our chances of committing a type II error . For instance, it is possible that the association between adverse childhood experiences and being at risk of clinical depression would have been detected with a larger sample. However, it should be noted that we used modified Poisson regression with robust error variances to estimate more precise point estimates and smaller confidence intervals.

We used cross-sectional data which precludes our ability to draw causal inferences or disentangle temporal associations, thus the present study only reports on associations with being at risk of clinical depression. Other factors that impact the external validity of our study include the use of non-probability sampling methods to recruit the study population. Additionally, because this is an observational study which did not involve randomization to an intervention or control condition, we are not able to rule out potential unmeasured confounders or make any causal inferences from our findings. Finally, we relied on self-reported data of certain sensitive behaviors including drug and alcohol use which may be subject to social desirability bias.The human brain acts as the body’s control center and dictates how our bodies respond to our internal and external environments, however,mobile vertical growing racks the brain is an especially difficult organ to study because brains can usually only be obtained posthumously, or after death.Thus, researchers have been trying to find ways to effectively and ethically study the brain and its development. Current techniques to study human brain development rely on fMRI, or functional MRI, imaging and focus on determining functional connectivity with the fetal brain, which does not completely explain what is happening in the developing brain. Mouse models have also been used to study the developing brain but they have key differences from human brains and therefore may not be the most accurate model for studying human brains. Stem cells can also be used to increase our understanding of the brain as there has been a rise in deriving the cell types found in the brain from stem cells. Stem cell research has provided a means for studying development because the cells in our body are derived and differentiated from base stem cells, such as the embryonic stem cell. Furthermore, more recent advances in stem cell research reveal that stem cell-ness, or the ability to differentiate into different cell types, can be induced4 . Therefore, the creation of the induced pluripotent stem cells has made a major impact on biological research by catalyzing new research into stem cell-based therapies. With IPSCs as a catalyst for further research into stem cells, there has also been an increase in differentiating these cells to create different cell lines. As stem cells have been used to create different cell lines, researchers have also started to create organoids or models for organs in the body derived from stem cells. Organoids are an exciting new field of research in biology because they can be used to provide new insights about tissue and organ development for many of the different organ groups, such as kidneys, brains, and lungs. Organoids are small 3-D models for human organs that contain the different cell types found in the organs they model and can perform many basic functions of the organ they model. It can be difficult to acquire human organs for research purposes, so organoids allow for an alternate means of scientific exploration of these various groups of organs. The organoids also reveal more about the process of cell differentiation in the organs they mimic because distinct and diverse cell types grow from the various stem cells in organoids. Since organoids can host many of the cell types found in the human brain, they may be the key to studying development without having to rely on brains that have been obtained posthumously. Currently, organoid technology is used to create cerebral organoids that develop cell types and structures found in the cerebral cortex. Cerebral organoids are generated using pluripotent stem cells to create a germ layer known as the ectoderm. Once the ectoderm is created, embryoid bodies form as the cells attach to one another. These embryoid bodies remain suspended in media and form neural ectoderm tissue on their surfaces.

These embryoid bodies are then placed in a media with factors and compounds that promote the formation of neural progenitors and the cell types, including a variety of glial cells and neural cells, that differentiate from neural progenitors. The final step of cerebral organoid formation is the addition of Vitamin A to provide retinoic acid to the brain to promote neural differentiation to account for the release of retinoic acid in vivo. After these organoids have been grown for 1 to 2 months brain structures including the cerebral cortex, retinal identities, ventral telencephalon, and choroid plexus are observed. With the creation of these brain structures, cerebral organoids are a model for the human brain. Furthermore, organoids have been shown to be a better model at mimicking fetal brain development than mouse models that were previously used. Mice do not have an inner fiber layer and outer subventricular zone, which are found in human brains. Moreover, mouse models are incapable of modeling microcephaly, a disorder causing abnormally small brain development, because they contain known mutants for some genes known to cause microcephaly. Therefore, these cerebral organoids may potentially provide valuable new insights about how the brain develops or what factors may hinder its development. In fact, the cerebral organoids also have a cell organization that is similar to the human brain, further supporting their validity as a model to study the human brain. Consequently, organoids seem to be an accepted model for studying the human fetal brain. Many groups have also used cerebral organoids to gain new insights on neurodevelopmental, neurodegenerative disorders, and the potential effects of drug treatments on fetal development. For example, organoids were used to model microcephaly by knocking down expression of CDK5RAP2, which was found to be a protein related to microcephaly. Staining of organoids with specific factors and visual growth of the organoids showed key differences in spindle. While visual observations provide an overall view of what is happening in the organoid, exploration of how the neural cell types are behaving in the organoid would provide a deeper understanding of inner mechanisms of development. An exciting approach to organoid research would be to perform single-cell RNA-seq, which is a technique that reveals the individual cell types present in the samples by checking differential expression of cell type specific markers in cells that have been clustered together. When used in conjunction with organoid research, single-cell RNA-seq can allow for a holistic look at the organoid. Only a few studies have used single-cell RNA-seq analysis in conjunction with organoid research.Past studies that involve the use of single-cell RNA-seq analysis and cerebral organoids have been used to study the organoids as models for human development. For example, single-cell analysis of organoids was used to reveal gene signatures that are specific to human development.