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 suggests that alterations in astrocyte metabolism is a major hallmark of depression. In this Mental Health Minute, Michal Slezak, PhD, explains how he and other researchers used state-of-the-art imaging techniques and genetic approaches to identify molecular processes impaired in depression. The researchers propose that novel, glial-specific drugs could target the molecular mechanics of depression.

 is a group leader at BioMed X Institute studying brain microcircuits in psychiatric diseases.

Does addressing depression at the molecular level sound like a promising treatment to you? 

Share comments with your colleagues by emailing 

. Comments may be shared online pending review and editing for style.

How do defective neuro-glia interactions contribute to depression? 

Studying Depression at a Molecular Level 

Nightmare disorder can produce emotional manifestations of fear, anger, and sadness. Here are 7 reasons parasomnias can challenge even the most astute diagnostician.

7 Things to Know About Parasomnias

March is brain injury awareness month. According to a study by the Centers for Disease Control, nearly 3 million individuals a year suffer a traumatic brain injury (TBI), and psychiatric disturbances are the most-common 

, we speak to David Arciniegas, MD, about how to spot TBI and its psychiatric sequalae—and how to give effective treatment.

is professor and senior research neuropsychiatrist in the Department of Psychiatry and Behavioral Sciences at the University of New Mexico School of Medicine. He is director of research at the Marcus Institute for Brain health and editor of the 

Journal of Neuropsychiatry and Clinical Neurosciences.

Millions of Americans will suffer brain injuries this year, and many of them will need a psychiatrist’s help. 

Recognize and Treat Traumatic Brain Injury

Scott Donofrio, MD, offered the following feedback to my article “

The Psychiatric Pipeline: 10 Agents to Watch

“In the 4th paragraph of the 2nd section (SEP-856: TAAR-1 and 5HT1A Agonist), Dr Miller has written caffeine’s action at heterodimeric adenosine receptor–D2R complexes is that of “a noncompetitive antagonist at the adenosine site.” As further described, the action seems to me to be that of a competitive antagonist with respect to adenosine and a noncompetitive one with respect to dopamine. Is that what Dr Miller means here?”

Dr Donofrio is correct with regards to my mischaracterization of caffeine as a “noncompetitive antagonist at the adenosine site.” Further, Dr Donofrio correctly hypothesizes that caffeine “seems to me to be that of a competitive antagonist w/respect to adenosine.” Caffeine is structurally similar to adenosine. As such, as the caffeine levels in the brain increase, caffeine directly competes with and displaces adenosine’s occupation of the adenosine binding site, reversing adenosine’s effect on dopamine. This, by definition, is the activity of a competitive antagonist.

Unlike adenosine, which decreases dopamine activity as its levels increase, caffeine has no agonistic activity at the adenosine site. Rather, caffeine functions as an antagonist, hence reversing the agonistic effects of adenosine and ultimately increasing brain dopamine levels.

Dr Donofrio’s second question (“caffeine’s action at heterodimeric adenosine receptor–D2R complexes is that of . . . a noncompetitive one w/respect to dopamine. Is that what Dr Miller means here?”) raises an important issue about the definition of a noncompetitive antagonist. In this situation, caffeine is not interacting with the physical D2R receptor in any way, rather its effect is indirect through the adenosine receptor, which together form a heterodimer.

There are 2 accepted definitions of a noncompetitive antagonist, which are mechanistically quite different. The first is that a noncompetitive antagonist is functionally an allosteric antagonist. With this definition, caffeine would putatively bind to a part of the adenosine receptor, which is distinct from and geographically unrelated to the adenosine binding site. However, the caffeine would alter the physical structure of the adenosine receptor to such a degree that it would not function, despite the presence of adenosine.

The second definition of a noncompetitive antagonist would be a drug/molecule that binds irreversibly to the receptor binding site. In this example, caffeine would putatively bind irreversibly to the actual adenosine binding site, so the adenosine receptor is permanently disabled. There can be no competition for binding between caffeine and adenosine because adenosine would not be able to displace the irreversibly bound caffeine.

In conclusion, caffeine is a competitive antagonist at the adenosine binding site, but has no direct activity at the dopamine-2 receptor.

One final clarification regarding this article: the print issue has a typographical error in the 10th section, 

ALKS 3831: combination of olanzapine and samidorphan

. The print article reads as follows: “Olanzapine needs no introduction, as it was FDA approved as our 3rd atypical antipsychotic in 1966, following clozapine and risperidone.” It wrongly states the FDA approval of olanzapine as “1966,” when it was actually FDA approved in 1996. The online article is correct.

is Medical Director, Brain Health, Exeter, NH; Editor in Chief,

Staff Psychiatrist, Seacoast Mental Health Center, Exeter, NH; Consulting Psychiatrist, Exeter Hospital, Exeter, NH; Consulting Psychiatrist, Insight Meditation Society, Barre, MA.

1. Miller JJ. The psychiatric pipeline: 10 agents to watch. 

https://www.psychiatrictimes.com/view/psychiatric-pipeline-10-agents-watch

2. Ferré S. Caffeine: neurobiological and psychiatric implications. 

Our Editor in Chief addresses a question from our readers about caffeine. 

Caffeine as a Competitive Antagonist

Since the 1980s, shareholder-value ideology (boosting profits above all other considerations) has led to a pattern of corporate behavior with troubling consequences. It has created employment instability, undermined productivity and innovation, exacerbated income inequality, and compromised the environment. The erosion of middle-class jobs has created enormous mental stress and uncertainty. Structural changes in employment help account for this, including the fissuring of the workplace, the end of the norm of a career with one company, and offshoring of employment to low-wage nations (driven by globalization and technological change).

Corporations have implemented these practices purely for financial gain, pursuing strategies to maximize returns to shareholders and high-level executives. This has encouraged an excessive focus on short-term returns and a decline in long-term investment. It has not sufficiently taken into account the human cost of such strategies. As an alternative, there are a number of efforts to advance stakeholder capitalism. Stakeholder capitalism would ensure that the broader interests of workers, local communities, and society are represented on corporate boards. The stakeholder value model thus builds a multi-bottom line approach, which goes beyond shareholder value creation to include a broader array of economic and societal values.

The Economic Burden of Brain Health Disorders

 emotional, behavioral, and cognitive health across the lifespan. In this context, compromised brain health greatly increases the risk of disorders (for example, depression, anxiety, substance misuse, dementias, neurodevelopmental disorders, and neurocognitive disorders).

 In total, brain health disorders cost the global economy more than $3 trillion per year in lost productivity.

In particular, mental health has been a growing concern among workers as the pandemic has worn on. According to data from the Society for Human Resource Management (SHRM), roughly 41% of employees feel burnt out, drained, or exhausted from their work.

 In addition, nearly 1 in 4 employees report frequently feeling down, depressed, or hopeless—yet more than 1 in 3 employees reported having done nothing to cope with these feelings.

 Having a significant proportion of the workforce reporting such symptoms is particularly concerning, as depression is associated with acute changes in cognitive capacity that can persist as residual symptoms after pharmacological treatment.

 These changes in cognitive capacity can have a detrimental impact on problem solving, memory recall, and motivation.

 Given the implications of these effects on workforce productivity and overall well-being, mental health should be among companies most pressing concerns.

Looking beyond mood and psychiatric illness, companies should also consider the implications of dementia and Alzheimer disease. According to a study conducted in Spain, the costs related to loss of labor productivity due to informal caregiving for people with dementia amounted to $5370 per individual per year.

 These informal caregivers experienced partial absenteeism and burdens that disabled them from maximizing productivity. Furthermore, research shows that 23% of individuals who will eventually be diagnosed with Alzheimer disease show accelerated cognitive decline around 5 years before an official diagnosis.

 This accelerated cognitive decline can be clinically referred to as mild cognitive impairment, but it is critical to note that the deterioration in brain health is progressive. Prior to mild cognitive impairment, individuals likely experience a period of undiagnosed mild cognitive decline 6 to 7 years prior, though they may be able to remain in the workforce during this time. 

Notably, issues of mental health and cognitive health are often considered separately, although they are inextricably linked. Brain Capital provides a mechanism to consider these in a more integrated way. 

Brain Capital is a novel form of capital that puts a premium on brain health and brain skills.

 Brain skills are critical in a digitized economy and include self-control, emotional intelligence, creativity, compassion, altruism, systems thinking, collective intelligence, and cognitive flexibility. Brain health must be optimized to support the necessary brain skills to thrive.

We refer to a digitized economy that places a premium on cerebral rather than manual skills as a Brain Economy. Brain Capital is clearly critical in an already digitized economy, especially as automation replaces traditional jobs that relied on manual skill.

 In a Brain Economy, innovation is a tangible and increasingly pivotal measure of employee productivity, and innovation is channeled through employee thoughts, ideas, and creativity.

Innovative Approaches to Promoting Brain Capital in the Workplace

Several approaches can promote Brain Capital in the workplace. These range from multiorganization workplace initiatives (

), to novel accounting frameworks, to social impact investing, to venture capital investing, to novel indices for tracking and measuring issues over time.

One example is emotional flexibility training for private sector knowledge workers. In 1 pilot study conducted to explore the effects of such a program, emotional flexibility advancement was found to be a highly effective treatment in clinical settings for depression, anxiety, and chronic pain.

 This approach—which had not previously been empirically explored with private sector, high-paced, high-demanding, and highly educated knowledge workers—demonstrated broad improvements in self-efficacy for those in the treatment group versus the control group. These results suggest that emotional flexibility boosts both well-being and performance.

Human capital can be a company’s greatest asset; it can make or break the business strategy and is a key differentiator. A company’s intangible assets, including human capital and culture, are now estimated to comprise on average 52% of a company’s market value.

 To date, given the intangible nature of strong corporate culture, stakeholder leadership, and employee well-being, companies have struggled to quantify the contribution of their human capital assets. But the principles of the Human Capital Accounting Framework, recently published by the World Economic Forum and Willis Towers Watson, could help firms measure Brain Capital effectively.

 A Human Capital Accounting Framework couldenable a company to monitor and assess the return on its investments in its employees in the same way that it measures returns on financial and intellectual capital.

The Global Reporting Initiative (GRI), in partnership with the Robert Wood Johnson Foundation, has developed health metrics that include social impact in current sustainability indexes.

 Encouraged by the added measure of certainty and transparency surrounding their activities, investors large and small would allocate more capital to financing positive initiatives, and entrepreneurs would devise business models whose ambition and growth potential match investor and market demand. Continued refinement of these taxation and accounting practices that prioritize Brain Capital may support improved workplace and societal well-being.

Venture capital companies have recently made record-breaking investments in mental health, with $637 million invested in more than 60 different mental health companies, almost 23 times the investment observed in 2013.

 Lyra Health was just valued at more than $1 billion, making it the first unicorn in mental health.

 The company, which provides mental health benefits for large employers, offers an array of in-person and remote behavioral therapy that helps remove access barriers to high-quality mental health care. The demand for teletherapy services is soaring, particularly as employers look to support workers during the 

. The company has added more than 800,000 new members since the start of the pandemic.

Novel Indices for Tracking and Investing in Brain Capital

 The central components of Brain Capital need to be formalized and developed into an investment plan. Since one cannot manage what one does not measure, developing a Brain Capital Index (BCI) to track the progress of this approach is critical.

Such an index could help track the Brain Capital impacts of companies and governments. The index could also track the value of investments in this area. If such an index were investable—as is the case for mutual funds or exchange-traded fund—it would encourage investment in the entire space by opening it to the passive investor. Index-tracking funds have recently passed the $10 trillion mark of assets under management globally, surpassing assets under active management for the first time. Attracting even a small fraction of global passive investment using a BCI would transform the Brain Economy as a whole. Consequently, creating a well-defined and easily computed index is a key part of investing in a Brain Economy.

The BCI could be associated with a range of potential components. Health-related metrics could include incidence and prevalence metrics, access to care, and relapse rates. In particular, access to mental health care for child and youth populations is of paramount importance, so coverage for families and employees should be prioritized. As of September 9, 2020, the National Council for Behavioral Health stated on its website that the demand for mental healthcare is at an all-time high; however, the ratio of professionals to patients is incredibly low, suggesting it should be tracked. To improve access, more efforts toward training and incentivizing providers need to be made. A BCI could also track purpose at work, as it has been shown to have a range of brain health benefits, including reducing the likelihood of dementia and stroke.

 Created in partnership between Thrive Global, SAP SuccessFactors, Qualtrics, and Fortune, the Thrive XM Index aims to assess and quantify individual experiences to gauge how employee well-being is directly connected to business outcomes. According to the Thrive Global website, the Index will combine employee-reported experience information, HR-reported performance insights, and business performance data, allowing companies to receive a comprehensive view of the way experience metrics (X-data™) and HR metrics (O-data™) can collectively serve as leading indicators for business performance.

Refining the Return on Investment Analysis

An emphasis on returns on investment (ROI) is critical for tracking and investing in Brain Capital. According to a recent report by Deloitte Canada, a pioneering research initiative determined that positive ROI for workplace mental health initiatives are within reach for Canadian businesses.

 Companies with mental health programs in place for 1 year had a median annual ROI of $1.62 for every dollar invested, and the median annual ROI more than doubled for companies with programs in place for 3 or more years, valued at $2.18 for every dollar spent.

 Components of the research included determining and tracking key performance indicators, assessing the effectiveness of interventions with employees, and regularly calculating ROI. Though often overlooked, these elements are essential to demonstrating the financial and nonfinancial benefits of mental health programs. Robust performance measurement enables organizations to “achieve desired program impact, improve adoption rates, and enhance decision-making.”

 Deloitte’s work helps build a framework for determining the ROI of workplace mental health initiatives. However, for optimal, far-reaching impact, the framework must be expanded to include a wider span of issues that Brain Capital encapsulates, such as brain skill issues and aging brain health conditions.

Recommendations for Building Brain Capital at Work

To propel this field forward in the coming years, clear recommendations are required for all stakeholders. These stakeholders include human resource managers, employee benefit managers, social impact investors, and beyond. Recommendations are outlined in 

Brain and mind issues must play a central role in measuring the sustainability and societal impact of investment in a workforce. A Brain Capital perspective needs to be integrated into existing frameworks, programs, and investment models to prevent or mitigate the profound effects and economic toll brain health disorders have on the workplace and society.

is a pre-medical human biology student at Stanford University.

is an MD candidate at David Geffen School of Medicine at UCLA.

is an associate with the PRODEO Institute and Thiel Fellow at Stanford University.

is head of the OECD New Approaches to Economic Challenges Unit and Senior Advisor to the OECD Secretary General.

is a neuroscientist and senior director at the Milken Institute Center for Strategic Philanthropy.

is the founding director of the Center for Brain Health at UT Dallas.

is a T. Boone Pickens Distinguished Scientist at the Center for BrainHealth, a co- director at Global Brain Health Institute, professor emeritus at Trinity College Dublin, and founding director of its Institute of Neuroscience.

is the global head of Science for Minds at Johnson & Johnson.

is president of the Euro-Mediterranean Economists Association.

is a co-founder of the PRODEO Institute, adjunct associate professor with the Institute for Mental and Physical Health and Clinical Trials (IMPACT) at Deakin University, and an instructor with the Global Brain Health Institute.

1. Ternes K, Iyengar V, Lavretsky H, et al. 

Brain health INnovation diplomacy: a model binding diverse disciplines to manage the promise and perils of technological innovation

2. Patel V, Saxena S, Lund C, et al. The Lancet Commission on global mental health and sustainable development. 

3. Schiavo, A. ‘It’s a fool’s choice’ when employers ignore investments in mental health benefits. 

https://www.benefitnews.com/news/its-a-fools-choice-when-employers-ignore-invest-in-mental-health-benefits

4. Perini G, Ramusino MC, Sinforiani E, et al. Cognitive impairment in depression: recent advances and novel treatments. 

5. Farré M, Kostov B, Haro JM, et al. Costs and burden associated with loss of labor productivity in informal caregivers of people with dementia: results from Spain. 

6. Daley A. Productivity, GDP and Alzheimer’s. 

The American Consumer Institute Center for Citizen Research

https://www.theamericanconsumer.org/2016/05/productivity-gdp-alzheimers/

7. Smith E, Ali D, Wilkerson B, et al. A Brain Capital grand strategy: toward economic reimagination. 

8. Wilson M, Wilkerson B, Price T, et al. BRAIN Health + BRAIN Skills = BRAIN Capital. 2011. Accessed February 15, 2021. 

http://www.mentalhealthroundtable.ca/report/MHR_FinalReport.pdf

9. One Mind at Work. Transforming mental health on a global scale is within reach. Updated 2020. Accessed February 15, 2021. 

10. SHRM. SHRM Foundation, One Mind, Psych Hub launch mental health and wellness in the workplace initiative for employers. News release. July 15, 2020. 

https://www.shrm.org/about-shrm/press-room/press-releases/pages/shrm-foundation-one-mind-psych-hub-launch-mental-health-and-wellness-in-the-workplace-initiative-for-employers.aspx

11. PsychHub. Mental health & wellness in the workplace. Accessed February 15, 2021. 

https://psychhub.com/initiatives/mental-health-wellness-in-the-workplace/

12. American Psychiatric Assocation. Center for workplace mental health. Accessed February 15, 2021. 

"R U OK?": A meaningful question to foster a culture of caring at EY

http://workplacementalhealth.org/News-Events/News-Listing/R-U-OK-A-Meaningful-Question

14. UsAgainstAlzheimer's. The Global CEO Initiative on Alzheimer Disease (CEOi). Accessed February 15, 2021. 

https://www.usagainstalzheimers.org/our-enterprise/CEOi

15. Brassey J, van Witteloostuijn A, Huszka C, et al. Emotional flexibility and general self-efficacy: A pilot training intervention study with knowledge workers. 

16. Klemash S, Neill BM, Smith JC, et al. How and why human capital disclosures are evolving. 

Harvard Law School Forum on Coporate Governance

. November 15, 2019. Accessed February 15, 2021. 

https://corpgov.law.harvard.edu/2019/11/15/how-and-why-human-capital-disclosures-are-evolving/

17. World Economic Forum. Human capital as an asset: an accounting framework to reset the value of talent in the new world of work. August 19, 2020. Accessed February 15, 2021. 

https://www.weforum.org/reports/human-capital-as-an-asset-an-accounting-framework-to-reset-the-value-of-talent-in-the-new-world-of-work

18. Global Reporting Initiative. Catalyst for a sustainable world. Accessed February 15, 2021. 

https://www.globalreporting.org/about-gri/

19. Shah RN, Berry OO. The Rise of venture capital investing in mental health. 

https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2770792

20. Landi H. Lyra Health gains unicorn status as demand for teletherapy soars. 

https://www.fiercehealthcare.com/tech/lyra-health-lands-110m-funding-round-as-demand-for-teletherapy-soars

21. Dhingra N, Emmett J, Samo A, et al. Igniting individual purpose in times of crisis. 

https://www.mckinsey.com/business-functions/organization/our-insights/igniting-individual-purpose-in-times-of-crisis

22. Deloitte. Realizing the positive ROI of supporting employees’ mental health. 

https://www2.deloitte.com/ca/en/pages/about-deloitte/articles/mental-health-roi.html

23. Big Society Capital. Exploring the role for social impact investing in preventing and tackling mental ill health. November 6, 2019. Accessed February 15, 2021. 

https://bigsocietycapital.com/latest/exploring-role-social-impact-investing-preventing-and-tackling-mental-ill-health/

24. Karsh M, Kishan S, Marsh A, et al. From mental health to credit risk, here are next big ESG topics. 

. October 23, 2020. Accessed February 15, 2021. 

https://www.bloomberg.com/news/articles/2020-10-23/from-mental-health-to-credit-risk-here-are-next-big-esg-topics

25. Chapman J. Investors and entrepreneurs need to address the mental health crisis in startups. 

. December 30, 2018. Accessed February 15, 2021. 

https://techcrunch.com/2018/12/30/investors-and-entrepreneurs-need-to-address-the-mental-health-crisis-in-startup-culture/

Brain health disorders cost the global economy more than $3 trillion per year in lost productivity. What can we do about it?

Smart Growth: the Case for Measuring Brain Capital

Food is an ideal drug delivery system, and an intriguing trio of studies suggest antidepressant potential for 1 food in particular: the blueberry.

All 3 studies hail from a single group lead by Claire Williams at the University of Reading, England.

 the effect of a powdered blueberry drink—equivalent to 1 cup of fresh blueberries—on mood in 144 children, adolescents, and young adults through 3 randomized, placebo-controlled trials. The placebo drink had the same sugar and vitamin C content as the 

 juice, and both drinks were made to look the same by mixing them with concentrated orange juice. The 

 outlines the key points from these studies.

The first 2 studies (which were published in a single paper) examined mood 2 hours after a single drink, and the third looked at longer term effects of a daily drink over 4 weeks.

 All 3 studies were positive, with effect sizes that ranged from small (0.27) to medium (0.65).

The main limitation is the fact that the studies were small and came from a single research group. Also, they all enrolled healthy participants, so we don’t know if blueberries actually treat clinical depression. No risks were identified, though one might wonder if blueberries can trigger mania. Reassuringly, 3 animal studies found anti-manic effects with blueberries, 1 of which compared them with lithium.

These findings are supported in part by a 

 where blueberry juice prevented postpartum blues (ie, the brief lability seen after delivery known as the “baby blues”) in healthy pregnant women, but the juice in that small controlled trial also contained tryptophan (2 g) and tyrosine (10 g).

 In contrast, 2 other independent groups that 

 blueberries in healthy older patients did not find any mood benefits.

This does not mean blueberries are only helpful in the young. Although the berries did not improve mood in the geriatric studies, they did improve cognition, which was the primary outcome. There are 13 controlled trials of the cognitive effects of blueberries and their extracts all age groups, and 85% of those 

What is the medication inside this efficient drug delivery system? Blueberries have several positive effects on the brain. They are neuroprotective, increasing brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1); anti-inflammatory; and raise production of 

 Most of these effects are because of anthocyanins, a group of 

 that give the fruit its purplish-blue hue.

Anthocyanins are found in other purple-tinted foods, like blackberries, blackcurrants, acai, black “forbidden” rice, eggplant, and the exotic purple varieties of cauliflower, asparagus, and sweet potatoes. Anthocyanins are also featured in red produce like cranberries, cherries, pomegranate, and red cabbage.

, but super-foods are not what nutritional psychiatry is all about. When working with medications, we shy away from polypharmacy, and aim instead to bring about the miracle of remission with a single pill. In nutritional psychiatry, polypharmacy is the ideal. The brain and body do best with a healthy mix of nutrients, and while 1 cup a day of blueberries is unlikely to cause harm, too much of a good thing is not the intent of this research.

is the Mood Disorders Section Editor for 

 He has written several books on mood disorders, most recently 

 with his co-host Kellie Newsome, PMH-NP. The author does not accept honoraria from pharmaceutical companies but receives royalties from PESI for 

. Effects of acute blueberry flavonoids on mood in children and young adults.

2. Fisk J, Khalid S, Reynolds SA, Williams CM. 

Effect of 4 weeks daily wild blueberry supplementation on symptoms of depression in adolescents.

3. Spohr L, Soares MSP, Oliveira PS, et al. 

Combined actions of blueberry extract and lithium on neurochemical changes observed in an experimental model of mania: exploiting possible synergistic effects.

4. Dowlati Y, Ravindran AV, Segal ZV, et al. 

Selective dietary supplementation in early postpartum is associated with high resilience against depressed mood.

5. Boespflug EL, Eliassen JC, Dudley JA, et al. 

Enhanced neural activation with blueberry supplementation in mild cognitive impairment.

6. Miller MG, Hamilton DA, Joseph JA, Shukitt-Hale B. 

Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial.

7. Travica N, D'Cunha NM, Naumovski N, et al. 

The effect of blueberry interventions on cognitive performance and mood: A systematic review of randomized controlled trials.

8. Rutledge GA, Sandhu AK, Miller MG, et al. 

Blueberry phenolics are associated with cognitive enhancement in supplemented healthy older adults.

Improved metabolic function and cognitive performance in middle-aged adults following a single dose of wild blueberry

10. Bensalem J, Dudonné S, Etchamendy N, et al. 

Polyphenols from grape and blueberry improve episodic memory in healthy elderly with lower level of memory performance: a bicentric double-blind, randomized, placebo-controlled clinical study.

Three new trials suggest a novel antidepressant hides inside the blue-skinned fruit.

Blueberries Treat Depression, With a Catch

“George” is a 15-year-old male in the 10th grade who is being evaluated by his school psychologist for declining academic performance. Last year, he earned grades of all As and Bs, but this year he has mostly Bs and Cs, with one D in an advanced math class. George has a 4-year history of generalized anxiety disorder, for which he takes a low-dose selective serotonin reuptake inhibitor. He has no active medical problems. He does not currently use tobacco, alcohol, or illicit drugs but admits to trying marijuana once at a party in the past year. There is no history of physical, sexual, or verbal abuse. He has a maternal aunt with chronic schizophrenia. His mother had gestational diabetes mellitus during her pregnancy with him, which was otherwise without complications. She states that he had frequent infections as a child and seemed to “get sick easily.” He has been slightly more irritable recently. George reports having a few close friends.

On interview, his affect is slightly restricted, but it brightens when he talks about his hobby (origami). He reported hearing whispering voices on a few occasions at night, which he attributed to noises outside his bedroom window. He reports this academic year it is harder for him to concentrate at school. 

 was notable for impairment in processing speed (about half standard deviation) and borderline impairment in visual learning compared with age- and sex-matched peers. His mother is concerned about his risk of schizophrenia.

Cognitive deficits are a well-replicated 

 across the course of illness, including the psychosis prodrome, in schizophrenia.

 There is evidence for cognitive decline in patients at clinical high risk (CHR) for psychosis compared with controls, with 

 in patients who transition to a psychotic disorder.

 There is also meta-analytic evidence for broad cognitive impairments in memory, attention, verbal and visuospatial abilities, social cognition, and executive function in CHR patients.

 Furthermore, cognitive deficits in CHR are independent predictors of conversion to psychosis and other outcomes, including role and social functioning.

 Although it is not yet possible to definitively predict patients at CHR who will subsequently develop a psychotic disorder, this area of research offers visions of secondary and even primary prevention of psychosis. Is it possible to use cognitive testing, which is brief, easily performed, reliable, and noninvasive, to identify individuals at risk for psychosis? Similarly, among those at CHR, can cognitive testing predict who will convert to psychosis? What role does cognitive testing play in the clinical care of patients like George?

 aimed to relate baseline cognitive performance to a broad range of clinical outcomes at 1-year follow-up in patients at CHR of psychosis and controls from the ShangHai-At-Risk-for-Psychosis (SHARP) study, which launched in China in 2010. They hypothesized that patients with CHR who converted to psychosis (CHR-C) would have greater cognitive impairments than those who did not convert (CHR-NC), and both CHR groups would have greater cognitive impairments than healthy controls. They also analyzed outcomes in patients at CHR based on clinical status (trichotomized as remission, symptomatic, or poor outcome).

A total of 217 participants at CHR and 133 healthy controls from the SHARP study completed the MATRICS Consensus Cognitive Battery (MCCB) at baseline and provided complete clinical data. These patients represented more than 90% of the patients who provided 1-year assessment data. The mean age of participants was aged 18.6 years; 47% were male; and all were lifetime psychotropic naïve at study entry. Subsequently, 80% of patients at CHR received antipsychotic medications. Inclusion criteria for all participants were aged 13 to 45 years, at least 6 years of education, and an available legal guardian for patients 18 years or younger. Participants with an 

, severe somatic disease, and lifetime substance dependence were excluded. Psychotic disorder or prodromal symptoms in healthy controls were ruled out by structured clinical interview.

Raw scores on the MCCB were converted to Z-scores based on healthy control scores. The CHR group was divided into CHR-NC (n = 155) and CHR-C (n = 41) based on the 1-year follow-up assessment. In other analyses, the CHR group was trichotomized to 3 clinical outcomes at 1-year: CHR-remission (n = 102), CHR-symptomatic (n = 37), and CHR-poor outcome (n = 57). The CHR-remission group included patients with spontaneous remission or improvement with antipsychotic medication to mildly impaired ranges or better (Structured Interview for Prodromal Syndromes [SIPS] positive symptom scores ≤ 2) and global function at least 60 at follow-up. The CHR-symptomatic group included medicated participants with SIPS positive 

 of 3 to 5 and global function of at least 60 at follow-up. The CHR-poor outcome group included those who converted to psychosis (n = 41) and medicated patients with unremitting positive symptoms (SIPS positive symptom scores of 3 to 5) and poor global function (less than 60) at follow-up (n = 16). Data were analyzed using multivariate analysis of variance with Bonferroni-adjusted post hoc pair-wise comparisons between groups for MCCB scores. Effect sizes were calculated using Cohen’s d.

Is it possible to use cognitive testing, which is brief, easily performed, reliable, and noninvasive, to identify individuals at risk for psychosis?









Neuropsychiatry

Studying Depression at a Molecular Level

7 Things to Know About Parasomnias

Recognize and Treat Traumatic Brain Injury

Caffeine as a Competitive Antagonist

Smart Growth: the Case for Measuring Brain Capital

Blueberries Treat Depression, With a Catch

The Troublesome Tale of Cognitive Deficits in Patients at CHR for Psychosis

The Battle of the Sexes in First-Episode Psychosis

Talking to Patients and Rediscovering Disordered Selfhood in Schizophrenia

Remodeling the Brain