Most animal working memory paradigms utilize delays while human paradigms manipulate the number of information items , limiting their translational validity. Some rodent span tasks do exist , and models of BD should also be tested in these paradigms as well as tasks that investigate other cognitive domains, e.g., executive functioning in the attentional set-shifting task . Another shortcoming of the presented work is the focus of studies on the manic phase of BD. For instance, the reduced DAT functioning models lack any depression-relevant behaviors, limiting their utility for BD individuals who experience both mania and depression. Future studies should conduct longitudinal and cross-sectional studies of BD patients across the mood state spectrum in translationally relevant paradigms to establish patient behavioral profiles as targets for animal models. For instance, although both depressed and manic patients exhibit impaired IGT performance, depressed subjects seem to be more sensitive to punishment compared to reward hypersensitivity exhibited by manic subjects . Such data could provide clues as to what behavior should be exhibited by the model animal and what mechanisms should be explored for each phase of the disorder. From a biological perspective, there is renewed evidence that suggests that impaired cholinergic mechanisms play a key role during bipolar depression , which may be restored during euthymic phases and switch to aberrant dopaminergic signaling during mania . Thus ideally, future research should focus on the cyclical nature of BD when attempting to model the disease and discover novel treatments. It is possible that the molecular clock machinery in BD is susceptible to internal and external stimuli such as stress or daylight lengths ,indoor agriculture vertical farming which subsequently can change the homeostasis of the DA / acetylcholine systems, resulting in a shift to either mania or depression.

As reviewed elsewhere , it has been reported that: 1) mania onset appears to be linked to long periods of daylight, while depression onset is associated with short daylight durations; 2) concomitant neurotransmitter switching occurs whereby elevated dopamine is apparent during long day light-length and corticotropin releasing factor in short daylight-length; and 3) that increased CRF expression elevates ACh levels in a manner that may predispose to depression. Accordingly, experiments that manipulate the durations of daylight periods in animal models prior to tests using cross-species paradigms relevant to both mania and depression could help to elucidate mechanisms related to the disparate phases of BD and the switching between states that is so characteristic of the disorder. DAT KD/KO mice have also been described as models for ADHD , and indeed hyperactivity, inattention, and impaired decision-making are present in both ADHD and BD populations. Moreover, reduced striatal DAT levels have also been observed in ADHD subjects . However, ADHD subjects tested to-date display a different BPM profile from BD subjects and DAT KD mice . Furthermore, DAT KD mice are also hypersensitive to psychostimulants similar to stimulant-induced mania. In contrast, the hyperactivity of DAT KO mice is attenuated by such stimulants consistent with ADHD treatments. Because ADHD and BD presents with similar clinical symptoms and comorbidity is high , elucidating differences between these disorders in order to avoid potentially harmful treatment of wrongly diagnosed ADHD with stimulants will be important future research. The overlap of affected behaviors in BD and ADHD for which reduced DAT functioning recreates, may also relate more to the cognitive/behavioral domains affected as opposed to a specific disease state. The National Institute of Mental Health has proposed and promoted the Research Domain Criteria initiative, which bypasses diagnostic categories and focuses instead on classifying psychopathology based on dimensions of functioning in patients .

Such an approach may prove to show that reduced DAT activity affects these domains of functioning irrespective of disease state, and that patients with BD simply have lower DAT expression during a manic episode. The reduced DAT models we present here therefore address key aspects of increased dopaminergic transmission. Hence, examining DAT levels and the behavior of patients across diagnostic categories using these translationally relevant paradigms could be a useful RDoC approach. Another avenue of research could include investigating the highly prevalent cannabis usage among BD patients . Although substance abuse in general is high in psychiatric populations, there is evidence that suggests BD patients may be using cannabis as a means to self-medicate . Importantly, interactions exist between the cannabinoid and DA systems, hence future research should investigate their relationship with BD. While the effects of cannabidiol have been investigated on amphetamine-induced oxidative stress , no attempts to measure a behavioral profile were made and, as described above, selective DAT inhibition may better recreate what occurs in BD patients. More research is therefore required in clinical and model behavioral studies. Finally, other neurotransmitter systems relevant to BD besides the catecholamines should be studied, e.g., the involvement of glutamate and NMDA receptors.Advances in scientific discoveries for mental health disorders have been vast in recent years and are increasing in pace. Unfortunately, the research to market success rate for drug development is merely 1 in 1000 compounds. To develop a BD-targeted treatment, it will be important to use a model animal for BD based on etiological and predictive validity. The application of translational approaches will likely reduce the risk of conducting expensive late-phase clinical trials for novel drugs that prove ineffective . A broad range of behaviors across species should be assessed, and the labeling of stimulant-induced hyperactivity as ‘mania-like’ should be reconsidered. Utilizing models with altered mechanisms that potentially underlie BD and exposing them to a set of translational tests used to characterize deficits in patients fills a crucial gap between preclinical and clinical research.

This work would then provide preliminary evidence for targeted mechanistic /cognitive studies in patients during illness states to link preclinical evidence to the clinical state . This translational approach will benefit both the understanding of mechanisms implicated in BD pathology and the opportunity to test novel therapeutics. Importantly, despite having been neglected for BD research in the past, this approach includes assessing neurocognitive deficits in patients. Combining relevant environmental manipulations with genetic susceptibility models that contribute to switching may improve our knowledge about the oscillatory nature of BD. Although few models of the switching between states in BD exist, some have been proposed and would benefit from translational assessment, as has previously been thoroughly reviewed . Ultimately, using translational approaches as described in this review may eventually yield novel therapies that specifically target the biological circuitry of BD, thus improving the lives of patients. Obtaining informed consent for human participation in research is a regulatory obligation; however, it is also an ethical priority. Every effort should be made to ensure all aspects of study participation are clearly presented and easy to understand . Institutional review boards are the administrative bodies that enforce the federal regulations for protection of human research subjects with a goal of evaluating the probability and magnitude of potential risks of harm against potential benefits of knowledge gained, recommending strategies for managing risks and generally promoting rigorous and ethical research. Although IRBs are responsible for reviewing and approving the information presented about a study,indoor vertical farming companies the actual process of obtaining informed consent from a potential research participant can vary both within and across studies. As a result, the informed consent delivery processes can range from simply letting the prospective participants review the informed consent information alone to actively engaging with individuals in a face-to-face discussion to increase the likelihood that study information is understood by the prospective volunteer to make a decision about participation . Whereas informed consent is a cornerstone of behavioral and biomedical research ethics , there are no requirements to assess whether the informed consent process used in a particular study is effective in facilitating authentic informed consent. Research on this topic, however, suggests as many as 50% of participants do not understand some or all components of informed consent across surgical and clinical trials . There are likely several reasons for this: the inclusion of research-oriented language with which many participants may not be familiar ; the inclusion of complex, IRB-required language addressing liability ; and the extensive length of consent documents, which often makes them difficult to navigate and comprehend . Individual IRBs typically require informed consent documents be at or below a certain grade reading level, often ranging from 5th grade to 10th grade reading levels ; however, many informed consent documents have reading levels well above those standards . For example, one study examined readability of 124 HIV clinical trial consent forms and found median readability of 9.2 grade level, with confidentiality sections at a median of 12.6 grade level and overall document length almost 30 pages on average . Ensuring participants are satisfied with the informed consent process is particularly important at research facilities that have long-term relationships with participants , and/or among vulnerable patient populations that may have particularly strong concerns about privacy protections and data confidentiality. For example, HIV is an acquired and potentially transmissible disease that is stigmatized in both social and medical settings .

Although the body of research on people living with HIV is vast, there is only one study that specifically evaluated the thoughts of PWH on the informed consent process . This study, conducted 25 years ago, assessed the informed consent process for an HIV drug trial and found approximately 56% of participants reported understanding all information on informed consent forms and 21% thought too much information was included. Unfortunately, the authors did not evaluate participant thoughts about what information was the most or least helpful, which is necessary for improving the informed consent process. The lack of informed consent research among PWH highlights the need for greater understanding of how PWH perceive the informed consent process. This research on the consent process is essential if we are to improve the likelihood that consent is truly “informed,” and, moreover, ensure individuals have the information needed to provide their voluntary agreement to participate in research. There are validated assessment tools used to evaluate informed consent comprehension , Miller et al. ). These tools have been useful particularly with populations with diminished cognitive capacity . While knowledge assessment tools can provide some indication that relevant information has been conveyed and, potentially understood, more research is needed to identify what influences meaningful and authentic informed consent. The purpose of this study was to evaluate the informed consent process used at a large U.S. HIV research center among participants with and without HIV. An overarching goal was to better understand participant perceptions to inform improvements of the informed consent content and process. Specifically, we assessed aspects of the informed consent content that participants found most and least informative, and explored whether this differed by HIV serostatus. We also examined the efficacy of our informed consent process by assessing whether participants thought the information presented was consistent with what they experienced during the study.Participants enrolled in ongoing studies at the HIV Neurobehavioral Research Program completed a questionnaire regarding their experience with the informed consent process. The questionnaire was administered to participants immediately after enrolling as well as after completing their study visit. All participants were taken through the informed consent process on the same day as their study visit. All participants who came to the HNRP between May 5, 2017 and July 11, 2017 were invited to complete the consent questionnaire. One participant declined due to the paperwork burden of the primary study in which they were enrolled. The participants who chose to enroll in the present study were enrolled in a wide variety of both cross-sectional and longitudinal studies ranging in complexity and length of assessment that involved completion of self-report measures , neuropsychological testing, and participation in clinical trials designed to test the efficacy of new drugs for improving cognition and physical outcomes among PWH.A recruiter from the HNRP was responsible for presenting the informed consent information for this study to our existing HNRP participants. On average, recruitment staff have been with the HNRP for 9.8 years and have an established professional relationship with study participants. Our recruitment staff adhere to a standardized informed consent process as follows.