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Matcha Sustains Caffeine's Benefits

A study compared matcha, a highly caffeinated green tea, to other sources of caffeine. Which had the greatest cognitive benefits? 

The Cognitive Benefits of Matcha

The Long Shadow of the Towers

Statistical findings from longitudinal studies of mental health among 9/11 witnesses and first responders.


Although cognitive difficulties may not be the primary symptom addressed in patients with schizophrenia, these impairments are a 

 that can contribute to social and functional disability.

 Cognitive dysfunction in schizophrenia affects not only attention, verbal memory, reasoning, and processing speed, but also social 

 Thus, the topic has received increased attention. (For more information, see the 

A growing body of research results indicates viruses may play a role in both schizophrenia and cognitive difficulties. One in particular, Epstein-Barr virus (EBV), has received notable attention in the possible pathophysiology of schizophrenia as well as of associated cognitive dysfunction, although findings have been inconsistent. For instance, in 

y of 229 patients with schizophrenia, the data did not indicate an association between EBV seropositivity and cognitive performance.

 Importantly, previous studies have generally measured exposure by reactivity to a single EBV protein, rather than to a panel of proteins or EBV virions. EBV, also known as human herpesvirus 4, is a lymphotropic virus that can produce acute and latent infections.

Using the MATRICS Consensus Cognitive Battery (MCCB), 

 tested their hypothesis that antibodies to various EBV proteins may be associated with different levels and domains of cognitive functioning in patients with 

 Patients with schizophrenia or schizoaffective disorder were enrolled at the Stanley Research Program at Sheppard Pratt in Baltimore, Maryland, in 1 of 3 trials of adjunctive medications for adults with schizophrenia that were conducted between 2014 and 2019.

Across the 3 trials, inclusion criteria were: receiving outpatient (vs inpatient) treatment; aged > 18 years; diagnosis of schizophrenia/schizoaffective disorder confirmed by structured clinical interview; and current stable antipsychotic treatment. Patients were excluded from the study if they had clinically significant or unstable medical disorders; were pregnant or breastfeeding; had current or recent substance use disorder; or were found to have an intellectual disability or IQ below 70 (

 In addition to the MCCB, the psychopathology of each patient was assessed using the Positive and Negative Syndrome Scale (PANSS). The total sample size was 84 (

Blood was assayed for immunoglobulin G antibodies to EBV antigens derived from intact virions using enzyme immunoassay. Assay values for patients were compared with a standard score based on the reactivity of controls without psychiatric disorders. Reactivity to herpes simplex virus type 1 (HSV-1) was also measured by immunoassay. In all studies, blood samples and cognitive testing were completed before the administration of any study medication. Linear regression models were used to determine whether EBV antibodies (to the whole virion and to specific proteins) were associated with MCCB composite and domain scores (

), controlling for age, sex, race, education, smoking, and HSV-1 serology.

The authors found a significant association between the lower MCCB overall percentile composite score (ie, worse cognition) and higher levels of antibodies to the whole EBV virion, to the EBV nuclear antigen-1 (EBNA-1), and to the EBV viral capsid antigen (VCA). There was also a significant association between lower MCCB social cognition and higher level of EBV virion, EBNA-1, and VCA antibodies. Lower MCCB processing speed was associated with higher EBV virion antibodies at a trend level. Lower MCCB working memory was also associated with higher EBNA-1 antibodies at a trend level.

The authors concluded that worse cognitive functioning in schizophrenia was associated with specific patterns of reactivity to EBV, including global and social cognition. Dickerson and colleagues acknowledged both strengths and limitations of their study. For instance, the present study includes the comprehensive cognitive battery (MCCB) and the measurement of EBV reactivity to specific EBV proteins. The investigators noted that the biological basis for the association between cognitive functioning and immune response to EBV is unknown. However, this study included a relatively small sample size, so the results may not be generalizable to other samples of patients with schizophrenia. Similarly, there may be possible residual confounding effects (eg, diet, genetics).

Exposure to EBV may contribute to cognitive impairments in patients with schizophrenia, which may have clinical implications. In particular, certain antiviral medications may be relevant to the prevention and treatment of EBV-associated cognitive impairment.

Regardless of these findings, it is important for clinicians to remain vigilant in the identification and assessment of cognitive impairment in schizophrenia, given its impact on social and functional disability. Although there are not any approved medications, clinicians can potentially improve cognitive outcomes by optimizing antipsychotic dosing based on symptoms and adverse effects, treating underlying depression, facilitating treatment of medical comorbidities (eg, hypertension, diabetes), and utilizing other therapies (eg, cognitive remediation) as available and appropriate.

is a professor in the Department of Psychiatry and Health Behavior of Augusta University in Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for 

The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.

1. Dickerson F, Boronow JJ, Ringel N, Parente F. 

Neurocognitive deficits and social functioning in outpatients with schizophrenia

3. Dickerson FB, Boronow JJ, Stallings C, et al. 

Association of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia

. Arch Gen Psychiatry. 2003;60(5):466-472.

4. Dickerson F, Katsafanas E, Origoni A, et al. 

Exposure to Epstein Barr virus and cognitive functioning in individuals with schizophrenia

5. MCCB [MATRICS Consensus Cognitive Battery] Neuropsychological Assessment. MATRICS Assessment Inc. Accessed February 4, 2021. 

A growing body of scientific literature makes the case.

Is Epstein-Barr Virus to Blame for Cognition in Schizophrenia?

The world is in the midst of an unfolding cognition crisis, with devastating personal, societal, and economic implications. The expanding elderly population requires better cognitive care; we are also coming to understand the importance of cognitive interventions and support in early childhood. Furthermore, the COVID-19 pandemic has brought global attention to cognitive issues, with over 50% of individuals recovering from the infection experiencing fatigue and brain fog. Initial studies indicate lasting deficits in executive function, impaired cognitive control, and reduction in global cognition leading to disability or reduced function.

 There are fears that COVID-induced deficits may last for years beyond the infection.

—such as attention, memory, perception, language, and reasoning

—are declining across the whole population. Beyond the effects of COVID-19, there is an alarming increase in the number of individuals around the world with serious cognitive impairments. These impairments co-occur with disorders including depression, anxiety, schizophrenia, autism, posttraumatic stress disorder, dyslexia, obsessive-compulsive disorder, bipolar disorder, attention-deficit/hyperactivity disorder (ADHD), addiction, dementias, and more.

 The severity, type, duration, and course of cognitive dysfunction differ between these disorders. The aging world population will heighten the cognition crisis. By 2060, the 

number of individuals aged 65 and older is projected to double

 is often only assessed when there is a specific, subjective complaint from patients, family members, or caregivers. In this context, there are many factors which suboptimize the value. For example, there are lengthy waiting lists to see neuropsychologists or cognitive neurologists, and various modalities used to assess cognitive dysfunction in later life are inaccessible to most (eg, positron emission tomography and advanced magnetic resonance imaging scans). Furthermore, there is no consistent clinical assessment algorithm for how to use cognitive assessment tools (eg, when to use pencil and paper tests, digital, blood-based, or neuroimaging). When there is no specific, subjective cognitive complaint, cognition is not assessed. This means more subtle and slow-onset forms of cognitive dysfunction may be missed. This can delay treatment and mean more progressive brain changes. If cognition is assessed, it is often not addressed, supported, or followed up in the long-term. Further, in many developing countries, cognition is rarely—if ever—screened, resulting in complications such as high rates of undiagnosed dementia.

 across the lifespan, it is critical that cognition is assessed and monitored across disorders and throughout life. Addressing and building cognition is especially crucial during early childhood, when cognitive difficulties can be caught before they have too much detrimental impact on a child’s developmental trajectory.

Examples of Cognitive Decline in Psychiatric Conditions

Consider depression: More than 264 million individuals around the world suffer from depression, making it the 

 and a major contributor to the overall global burden of disease.

 Depression is commonly associated with a lowering of a patient’s mood and energy for long periods of time. Depression also impairs cognition, including affecting attention, memory, information processing, decision-making skills, cognitive flexibility, and executive functioning.

 Indeed, 85 to 94% of individuals with acute depression experience significant cognitive impairments.

 Even when depression has remitted, around 40 to 45% of patients report dysfunction in one cognitive domain.

 Cognitive impairments are not addressed by first-line 

is now proposed as a novel treatment target for depression.

 Cognitive remediation therapy has provided encouraging results for the management of cognitive deficits in major depressive disorder (MDD).

 The incorporation of biobehavioral strategies (eg, exercise) and multimodal treatment approaches (eg, cognitive training, antidepressant therapy, and neuromodulation) is likely to generate therapeutic benefit.

Another example is cancer. It is estimated that at the end of 2020 there were over 70 million cancer survivors worldwide.

 Cognitive impairments—including deficits in visual working memory, sustained attention, new learning, and more—are commonly observed in patients with cancer and those in remission.

 Though cancer- and chemotherapy-related cognitive impairments (eg, confusion, lapses in memory and attention, difficulty concentrating, etc) are often known colloquially as chemo brain or chemo fog, up to 30% of patients with cancer exhibit subtle cognitive impairments prior to treatment, suggesting the body’s physiological response to a tumor (eg, inflammatory processes or vascular changes around the tumor) may be disruptive to cognition.

 Neuroimaging and neuropsychological studies have validated the role of chemotherapy contributing to cognitive issues, with chemotherapy patients having a more difficult time during memory recall than those cancer patients who did not receive the drugs, which suggests that their neural networks had been altered.

 Indeed, 75% of cancer patients have cognitive impairments during treatment, and 35% of survivors have cognitive impairments that continue in the months and years after treatment.

In addition to depression and cancer, there are many other disorders across the lifespan that have been shown to cause cognitive impairments, including ADHD,

 chronic obstructive pulmonary disease (COPD),

 depicts a small subset of disorders with associated cognitive problems.

Innovative measurement-based approaches need to be leveraged to better understand and treat the impacts of cognitive impairments from disorders across the lifespan. Measurement-based care can be defined as the practice of basing clinical care on client data collected throughout treatment. Measurement-based cognitive care, therefore, includes ensuring that cognition is assessed and monitored at all stages of the treatment process across a multitude of disorders—not merely Alzheimer disease (AD) and late-life cognitive decline.

For example, with cancer patients, cognition needs to be assessed before treatment begins and then regularly during and after treatment. Cognitive assessments must also be easy for the patient to access. Since these patients will already be saturated with physical and mental health interventions, it is critical that any cognitive assessments and additional interventions are able to fit into their lives as seamlessly as possible.

Regular assessment and monitoring of cognitive health is also critical across the entire spectrum of health, including those who do not have a present health concern. Innovative delivery systems—such as at-home digital technologies—can ensure accessibility and awareness that these assessments exist. Regularly assessing cognition throughout the lifespan will enable cognition to be used as a new vital sign. Further, it will provide the opportunity to establish an individual’s cognitive baseline; identify changes that may suggest prodromal stages of disease and allow for early intervention. Cognitive care will adopt a more proactive, preventative, and personalized approach to one’s cognitive lifespan. Psychometric quality is clearly critical (ie, robust assessments of performance norms, reliability, validity, sensitivity, and specificity).

 Ensuring cognitive assessments include quality of life and activities of daily living is also important. 

New technologies and tools will help make measurement-based cognitive care a reality. New, predictive tools in cognition include 

 Tracking eye-movement has been found to offer a window into cognitive processes and impairments. Preliminary data indicate that eye-tracking tests may detect early stages of AD

; characterize cognitive impairments in patients with other neurological disorders, including amyotrophic lateral sclerosis, Parkinson disease, multiple sclerosis, autism spectrum disorders,

; and identify and access brain dysfunction in patients—including children—with mental health conditions such as depression.

 When implemented in a digital setting, some novel tools have been found to have a myriad of benefits.

For example, Akili Interactive developed the first and only 

 that has been cleared by the US Food and Drug Administration to treat adolescent ADHD and improves attention impairments.

 Akili’s digital therapeutic for adolescent ADHD has been found to improve objectively measured inattention as determined by the Test of Variable Attention Attention Performance Index (API) in adolescent patients with ADHD.

 Other digital therapeutics have been found to reduce cognitive impairments in adults living with MDD

 Tools are also being developed to promote the development of cognitive skills during childhood.

 Some smart phone-based technologies may be deployed worldwide including to low- and middle-income countries, allowing greater equity in cognitive care.

The necessity of validated remote evaluations—enabled by many of these new biomarkers—is apparent, underscored by the recent limitations on in-person visits secondary to the COVID-19 pandemic. Digital technologies are well positioned for a role in remote evaluation to be used synchronously or asynchronously and over telemedicine platforms.

We must re-engineer the modern health care team when moving towards measurement-based cognitive care. Just as genetic counselling was established as a new field in 1969 to help individuals navigate genetic risk and testing, a new field needs to be established to help patients navigate cognitive risk and testing. Many new cognition biomarkers provide a risk score or predictive analytic, which like predictive genetics can bring a host of new questions and worries: What does my score mean? How do you interpret a black-box algorithm? What can I do about my risk for cognitive impairment after chemotherapy? Am I developing AD or am I experiencing cognitive problems due to depression? Will these results create issues for my health or life insurance policies?

Cognition counselors are needed as part of the modern care team to 1) ensure that cognition is addressed in disorders where it is commonly overlooked (eg, postsurgery, cancer, diabetes, depression, etc); 2) help patients navigate the new anxieties and questions that arise from new technologies, cognitive assessment, and risk scores; and 3) discuss and coordinate care options and provide referrals to educational services, advocacy and support groups, novel technologies, other health professionals, and community or state services. Cognition counselors will also help overcome the barriers of implementing digital technology in both a clinical and educational setting, increasing acceptance and compliance. Further, existing care team members—such as clinical neuropsychologists—could also be trained or upskilled to fulfill the role of cognition counselors, helping to rethink and 

To optimize the likelihood that measurement-based cognitive care can be instituted, leveraged tools should be brief (≤ 10 minutes), highly scalable, able to be administered by the patient or trained clinical staff, and able to automatically generate an interpretative report with instant electronic medical record integration.

 To further help realize measurement-based cognitive care, health systems must be prepared to move quickly when a new biomarker is seen to add clinical value. We applaud the work of the 

 for proposed frameworks to accelerate such preparedness.

Finally, design thinking principles must be strictly adhered to in the development of novel biomarkers given these tools can be deployed across disorder type and the lifespan.

 For example, elderly individuals may experience changes and challenges that span disability segments, including visual, cognitive, speech, mobility, and neural impairments. From deterioration in vision to difficulty touching screens to everything in between, novel biomarkers and tools must account for these changes and be designed to be accessible to all. The fields of disability studies and assistive technologies will likely be 

 Further, measures must be taken to mitigate practice effects from repeated use of measurement-based cognitive care tools, ensuring that increasing familiarity and exposure to cognitive tests does not become a confounding factor in scores.

Measurement-based cognitive care is the urgently needed to address to the unfolding cognition crisis. Measurement-based cognitive care will bring an era of medicine where cognition is proactively addressed and better understood for disorders across the lifespan; technologies and tools underpin advancements in cognitive assessment and monitoring; and care teams are equipped to help patients navigate the new uncertainties that arise and receive proper care. In doing so, individuals will be able to improve their quality of life and have their capacity to thrive increased. Placing measurement-based cognitive care as a critical component of medicine will bring widespread personal, medical, and societal benefits.

a member of the Steering Committee of the Organization for Economic Co-operation and Development (OECD)-PRODEO Institute Neuroscience-inspired Policy Initiative, and an Atlantic Fellow for Brain Equity at the Global Brain Health Institute at UC San Francisco (UCSF).

Joy Chambers-Grundy Professor of Brain Science and Director of the Chambers-Grundy Center for Transformative Neuroscience, University of Nevada Las Vegas (UNLV).

is a Professor in Cognitive Neuroscience and Director of Research in the Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Australia.

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

a Senior Clinical Advisor for Cohen Veterans Bioscience’s Trauma Research Programs. She serves as Strategic Advisor co-leading CVB’s Suicide Strategy Initiative.

Turner Institute for Brain and Mental Health, Neurodevelopment Program School of Psychological Sciences, Monash University.

is the professor of psychiatry, Director, Late-life Mood, Stress and Wellness, and Integrative Psychiatry research programs UCLA Semel Institute for Neuroscience and Human Behavior.

cofounder of the PRODEO Institute, co-lead of the OECD-PRODEO Institute Neuroscience-inspired Policy Initiative,

instructor in brain health diplomacy at the Global Brain Health Institute. He holds adjunct positions with IMPACT at Deakin University and Baylor College of Medicine.

1. Ortelli P, Ferrazzoli D, Sebastianelli L, et al. Neuropsychological and neurophysiological correlates of fatigue in post-acute patients with neurological manifestations of COVID-19: Insights into a challenging symptom

2. Agadjanyan MG, Petrovsky N, Ghochikyan A. A fresh perspective from immunologists and vaccine researchers: active vaccination strategies to prevent and reverse Alzheimer's disease. Alzheimers Dement. 2015;11(10):1246-1259.

3. Gazzaley A. The Cognition Crisis: The Perils and Promise of Technology and the Brain. Digital Media and Developing Minds National Conference. October 17, 2018. Accessed July 14, 2017. 

https://www.childrenandscreens.com/2018-conference/talks-and-panels/the-cognition-crisis-the-perils-and-promise-of-technology-and-the-brain/

Textbook of Clinical Neurology, Volume 355

The Distracted Mind: Ancient Brains in a High-Tech World

6. ACL Administration for Community Living. 

 April 30, 2018. Accessed July 14, 2021. 

https://acl.gov/news-and-events/announcements/announcing-2017-profile-older-americans

7. Jitapunkul S, Chansirikanjana S, Thamarpirat J. Undiagnosed dementia and value of serial cognitive impairment screening in developing countries: a population‐based study. 

 Depression. January 30, 2020. July 14, 2021. 

https://www.who.int/news-room/fact-sheets/detail/depression

9. McIntyre RS, Xiao HX, Syeda K, et al. The prevalence, measurement, and treatment of the cognitive dimension/domain in major depressive disorder

10. Millan MJ, Agid Y, Brüne M, et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. 

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

12. Conradi HJ, Ormel J, de Jonge P. Presence of individual (residual) symptoms during depressive episodes and periods of remission: a 3-year prospective study. 

13. Advances in Understanding Neurobiological Underpinnings and Treatment Interfaces of Cognition in Depression.

14. Shilyansky C, Williams LM, Gyurak A, et al. Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study

15. Cartreine J. More than sad: depression affects your ability to think. Harvard Health Blog. May 6, 2016. Accessed July 14, 2021. 

https://www.health.harvard.edu/blog/sad-depression-affects-ability-think-201605069551

16. Richardson L, Adams S. Cognitive deficits in patients with depression

17. Carvalho AF, Alves GS, Köhler CA, McIntyre RS. Cognitive enhancement in major depressive disorder

 In Keefe RS, Reichenberg A, Cummings J, eds. 

Cognitive Enhancement in CNS Disorders and Beyond

18. Weiss B. Chemobrain: a translational challenge for neurotoxicology. 

19. Hodgson KD, Hutchinson AD, Wilson CJ, Nettelbeck T. A meta-analysis of the effects of chemotherapy on cognition in patients with cancer. 

20. Janelsins MC, Heckler CE, Peppone LJ, et al. Longitudinal trajectory and characterization of cancer-related cognitive impairment in a nationwide cohort study. 

21. Pendergrass JC, Targum SD, Harrison JE. Cognitive impairment associated with cancer: a brief review

22. Olson B, Marks DL. Pretreatment cancer-related cognitive impairment—mechanisms and outlook. 

23. Palmer C. Cognition and cancer treatment. American Psychological Association. 2020;51(2):42.

24. Kesler SR, Bennett FC, Mahaffey ML, Spiegel D. Regional brain activation during verbal declarative memory in metastatic breast cancer. 

25. Rubia K. Cognitive neuroscience of attention deficit hyperactivity disorder (ADHD) and its clinical translation. 

26. Munshi MN. Cognitive dysfunction in older adults with diabetes: what a clinician needs to know. 

27. Robinson OJ, Vytal K, Cornwell BR, Grillon C. The impact of anxiety upon cognition: perspectives from human threat of shock studies. 

28. Torres-Sánchez I, Rodríguez-Alzueta E, Cabrera-Martos I, et al. Cognitive impairment in COPD: a systematic review.

29. Andrianopoulos V, Gloeckl R, Vogiatzis I, Kenn K. Cognitive impairment in COPD: should cognitive evaluation be part of respiratory assessment? 

31. Sumowski JF, Benedict R, Enzinger C, et al. Cognition in multiple sclerosis: state of the field and priorities for the future. 

32. Benedict RH, Amato MP, DeLuca J, Geurts JJG. Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. 

33. Aging2.0 OPTIMIZE Conference: Savonix Presentation. 2018.

34. Charalambous AP, Pye A, Yeung WK, et al. Tools for app-and web-based self-testing of cognitive impairment: systematic search and evaluation. 

35. Williamson JR, Quatieri TF, Helfer BS, et al. Vocal and facial biomarkers of depression based on motor incoordination and timing. 

Proceedings of the 4th International Workshop on Audio/Visual Emotion Challenge

36. Ali MR, Myers T, Wagner E, et al. Facial expressions can detect Parkinson's disease: preliminary evidence from videos collected online. arXiv. December 9, 2020. Accessed July 14, 2021. 

37. Cummins N, Scherer S, Krajewski J, et al. A review of depression and suicide risk assessment using speech analysis.

38. Dagum P. Digital biomarkers of cognitive function. 

39. Hart J, Kraut MA, Womack KB, et al. Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study. 

40. Liotti M, Mayberg HS. The role of functional neuroimaging in the neuropsychology of depression. 

41. Zetterberg H, Blennow K. Blood biomarkers: democratizing Alzheimer’s diagnostics. 

42. Bull CN, Asfiandy D, Gledson A, et al. Combining data mining and text mining for detection of early stage dementia: the SAMS framework

https://eprints.lancs.ac.uk/id/eprint/79004/1/combining_data_mining.pdf

43. Mengoudi K, Ravi D, Yong KX, et al. Augmenting cognitive assessment with instruction‐less Eye‐tracking tests: a machine learning approach for detecting abnormal oculomotor biomarkers. 

44. Crutcher MD, Calhoun-Haney R, Manzanares CM, et al. Eye tracking during a visual paired comparison task as a predictor of early dementia. 

45. Falck-Ytter T, Carlström C, Johansson M. Eye contact modulates cognitive processing differently in children with autism. 

46. Tao L, Wang Q, Liu D, et al. Eye tracking metrics to screen and assess cognitive impairment in patients with neurological disorders. 

47. Harrison AJ, Gibb BE. Attentional biases in currently depressed children: an eye-tracking study of biases in sustained attention to emotional stimuli. 

48. Sanchez A, Vazquez C, Marker C, et al. Attentional disengagement predicts stress recovery in depression: an eye-tracking study. 

49. Gotlib IH, Joormann J. Cognition and depression: current status and future directions. 

50. Itti L. New eye-tracking techniques may revolutionize mental health screening. 

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52. Kollins SH, DeLoss DJ, Cañadas E, et al. A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial. 

The world is facing a cognition crisis. Here’s how to face it with measurement-based cognitive care.

Addressing the Cognition Crisis in Our COVID-19 World

“Sleep problems are understudied,” Ellen Lee, MD, told attendees at the 2021 American Psychiatric Association (APA) Annual Meeting. “They’re underdiagnosed and undertreated in people with mental illness.” Thus, Lee encouraged clinicians to screen for sleep problems, because sleep “is a modifiable and important target for intervention.” Lee, along with other colleagues, shared insights and preliminary research results on how sleep may impact mental health and psychiatric disorders.

Sleep problems affect between 30 and 80% of individuals with schizophrenia and are associated with lower quality of life and poorer cognitive and frontal lobe functioning, explained Lee, assistant professor in residence in the Department of Psychiatry at the University of California at 

 In as-yet unpublished research, Lee found that sleep apnea is associated with increased inflammation, while higher subjective reports of sleep quality are associated with lower levels of inflammation. Since inflammation is also associated with 

 treating sleep problems could also improve the symptoms of mental illnesses.

Beyond schizophrenia, sleep issues also appear in mood disorders like depression. Stephen Smagula, PhD, presented research on possible links between morning activation deficits and depression among family members caring for patients with dementia.

Older individuals with depression often report difficulty getting up and active in the 

 Morning activation deficits are sometimes thought to be immutable (some individuals are just not morning people), but in functional magnetic resonance imaging readings, dementia caregivers with depression showed higher resting-state amygdala-PCC connectivity, which is associated with stress, fear, and 

 “Although this is speculative,” Smagula cautioned, “it seems plausible that the non-morning type caregivers are doing behaviorally disengaged, emotion-focused coping. So put another way, some caregivers might wake up, feel overwhelmed, say ‘Expletive! I’m going back to bed.’”

This raises the possibility, according to Smagula, who is assistant professor of psychiatry and epidemiology at the University of Pittsburg, that “instead of treating the depression and hoping the morning activation deficit goes away, we could be targeting the morning activation deficit to treat the depression.” Clinicians could consider treatments such as activity scheduling, which would get the caregivers up and moving, increase their light exposure, decrease fragmented sleep, and limit the time they spend ruminating—all of which could improve their depressive symptoms.

Sleep also affects cognition, especially in older adults. Ruth O’Hara, PhD, presented initial data on the impacts of delta activity at sleep onset (DASO). Study participants with DASO demonstrated better affective function overall and over time, which led O’Hara to conclude that testing DASO or other variables may help clinicians predict patients’ cognitive futures. “We think that characterizing sleep dysregulation in older adults may in fact identify valuable biomarkers,” explained O’Hara, who is the Josephine Q. Berry Professor of Psychiatry and Behavioral Sciences at Stanford University. They could “help us predict cognitive decline and onset of dementia, as well as predicting affective dysfunction.”

1. Cohrs S. Sleep disturbances in patients with schizophrenia: impact and effect of antipsychotics. 

2. Keshavan MS, Montrose DM, Miewald JM, Jindal RD. Sleep correlates of cognition in early course psychotic disorders. 

3. Bromundt V, Köster M, Georgiev-Kill A, et al. Sleep-wake cycles and cognitive functioning in schizophrenia. 

4. Lee EE, Ancoli-Israel S, Eyler LT, et al. Sleep disturbances and inflammatory biomarkers in schizophrenia: focus on sex differences. 

5. Smagula SF, Capps CS, Krafty RT. Evaluating the timing of differences in activity related to depression symptoms across adulthood in the United States. 

6. Smagula SF, Karim HT, Ibrahim TS, et al. Resting-state function connectivity associated with being a "morning-type" dementia caregiver and having lower depression symptom severity. 

Sleep problems are understudied, underdiagnosed, and undertreated. 

Dreaming of New Treatments

When do cognitive impairments emerge in patients with schizophrenia?

PsychQuiz: Cognition in Schizophrenia

 for significant procognitive effects for antipsychotics and other pharmacologic approaches.

 Therefore, treatment of cognitive impairment in schizophrenia represents a tremendous area of unmet need.

 on the effects of exercise on brain structure and functional performance.

 found that aerobic exercise exerted a positive effect on global cognition and some, but not all, cognitive domains in patients with schizophrenia. Unfortunately, findings are limited by small samples, as well as variable types and intensity of exercise and study designs.

“Mrs Morris” is a 48-year-old Black woman with a history of chronic schizophrenia. During hospitalization for an episode of illness exacerbation, her antipsychotic medication was modified. Over the next 4 months, she gained approximately 50 lb. Mrs Morris declined to lower the dose of her antipsychotic or change medications because of her clinical improvement. She worried about risk of another illness relapse. However, she was receptive to the recommendation for increased physical activity for weight loss.

Mrs Morris started walking with a neighbor for about 30 minutes at a moderate pace at least 3 times per week. Over the next year, she lost 36 lb. Although there were no clinically appreciable changes in her cognitive function, she reported feeling better as a result of her exercise regimen.

 performed a 12-week randomized controlled trial of the effects of aerobic walking on cognitive function in patients with schizophrenia.

 The goal was to determine if the intensity of aerobic walking is associated with changes in cognition. Patients were randomized 1:1 based on age and sex to usual treatment with antipsychotics with or without aerobic walking. Inclusion criteria were 20 to 60 years, DSM-5 diagnosis of schizophrenia, stable antipsychotic dose for at least 1 month, Positive and Negative Syndrome Scale (PANSS) total score < 95, no history of major physical illness, and no physical disability that caused difficulty walking.

The program comprised 150 minutes/week of outdoor walking, typically divided over 3 to 5 sessions and each with a 5-minute warm-up, followed by a 5-minute cool-down. Transportation was provided to the exercise sessions as needed. Participants wore a Fitbit to monitor heart rate and exercise intensity and were supervised by research staff who provided guidance based on heart rate. The patients could rest if needed. Participants were stratified into high- and low-intensity groups based on the average in-session heart rate reserve. Cognition was evaluated with the Brief Assessment of Cognition in Schizophrenia (BACS).

Data were analyzed using intention-to-treat and per-protocol analyses. Multivariate general linear model repeated measures were used to investigate the effects of time, group, and the time x group interaction on cognition, controlling for illness duration. The authors randomized 67 patients to treatment as usual (TAU, n = 34) or aerobic walking (n = 33) who completed the baseline assessment. Thirty-three patients in the TAU and 31 in the aerobic walking group completed the 12-week trial (

). At baseline, participants in the aerobic walking group scored approximately 0.5 standard deviations lower on 

 than the TAU group. The mean duration of aerobic walking was 129 minutes/week. Eleven patients achieved high-intensity walking and 22 maintained low-intensity. In the entire intent-to-treat sample, the authors found a trend for a group effect for greater improvement in verbal fluency in the aerobic walking group. They also found a significant group effect on attention and processing speed in high- versus low-intensity aerobic walking.

This was the first trial of the effects of aerobic walking and exercise intensity on 

in schizophrenia, according to the study authors. Most (> 90%) patients completed the trial with a mean of 3 days of exercise per week. The findings suggest that this intervention is feasible and acceptable to patients, and that supervision and transportation are associated with retention. Study limitations included the modest sample size (especially in the high-intensity group) and a relatively short study duration, as well as the inability for blinding to the intervention.

A supervised aerobic walking program involving moderate-intensity exercise is feasible and acceptable in patients with schizophrenia. Higher intensity aerobic exercise may have modest procognitive effects in these patients. Considering the other health benefits of aerobic walking, these programs can be useful for patients with schizophrenia.

is a professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for 

. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain & Behavior Research Foundation, and the Stanley Medical Research Institute.

Pharmacological cognitive enhancement in schizophrenia

Aerobic exercise has been found to exert a positive effect on global cognition and some, but not all, cognitive domains in patients with schizophrenia.

Cognitive Disorders

The Cognitive Benefits of Matcha

The Long Shadow of the Towers

Is Epstein-Barr Virus to Blame for Cognition in Schizophrenia?

Addressing the Cognition Crisis in Our COVID-19 World

Dreaming of New Treatments

PsychQuiz: Cognition in Schizophrenia

Is There a Link Between Exercise, Cognition, and Schizophrenia

Early Warnings: Neuropsychiatric Manifestations of Huntington Disease

Smart Growth: the Case for Measuring Brain Capital

Mini Quiz: Evaluating Dementia