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included a Point/Counterpoint feature on electroconvulsive therapy (ECT). You can read the introductory essay, “Electroconvulsive Therapy: Obsolete and Dangerous or Still Just Misunderstood?” by Horacio A. Capote, MD, 

 have agreed to continue their debate online. Ms. Hancock, Cunliffe, and Dr Read argue that ECT is 

. Representing the pro-ECT position, Dr Henry has responded to their article below.

I would also like to thank Sarah Hancock, MS, CRC, Sue Cunliffe, MBchB, RCPCH, John Read, PhD for responding to my article “

Their objections to electroconvulsive therapy (ECT) are primarily focused on the cognitive side effects, which they feel are caused by ECT-induced brain damage, and methodologic issues with studies supporting the efficacy of ECT. The main problem with their critique is that they appear to misinterpret the statistics they are presenting.

For example, when they discussed the findings of Peltzman and colleagues, they reported that the study found that ECT patients in the Veterans Health Administration (VHA) were 1.3 times more likely to die by suicide than 

 They failed to appreciate that when the authors compared the ECT patients to a risk-matched cohort, this finding did not meet statistical significance (

=.095), despite the large sample size of 14,810 ECT patients and 58,369 controls. They also failed to mention the authors’ conclusion that the “use of ECT in the VHA is rare. Patients who receive ECT have a complex and high-risk profile …”

 Similarly, Hancock and colleagues cite statistics from Duma and colleagues regarding 

 In their meta-analysis of the major cardiac events, the authors conservatively excluded 28 of 82 studies because they reported no adverse events. Without inclusion of this group the incidence of cardiac deaths and all-cause mortality were 0.18 and 0.33 per 1000 patients, respectively. When this group of studies was included, the incidence of cardiac deaths and all-cause mortality dropped to 0.04 and 0.13 per 1000 patients. They also did not consider that in the Veterans Health cohort, the risk ratio of all-cause mortality for the ECT group was a statistically non-significant 0.88, less than the non-ECT group.

My previous response to the question of whether ECT causes brain damage has already highlighted the findings and conclusions of Gbyl and Videbech, who reviewed 32 imaging studies of ECT with a total of 467 patients and 285 controls. They reported that none of the studies they reviewed found evidence of 

 Hancock and colleagues point to EEG, PET, SPECT, and fMRI data that show relative decreases in the activity of the frontal and temporal lobes after ECT as evidence that ECT causes brain damage.

 They do not appear to have considered the data that show depression is associated with overactivity in these same brain regions.

In addition to failing to present a balanced interpretation of the safety data for ECT, Hancock and colleagues ignore converging lines of evidence that support the efficacy of ECT. For example, they reject a study such as that published by Helle and colleagues, for lack of a 

 In this study, the authors used a randomized parallel treatment design with blinded raters to compare brief-pulse RUL to algorithm-based pharmacology in 73 subjects with bipolar depression. They found a significantly higher response rate of 73.9% for the ECT group versus 35.0% for the medication group (

 = .01). These results are remarkably similar to those of Perugi and colleagues, who treated 522 consecutive patients with treatment-resistant bipolar disorder with ECT and found response rates of 68.1 for bipolar depression, 72.9% for mixed state, 75% for mania and 80% for catatonia.

 To provide some context for these response rates, one of the pivotal clinical trials for the olanzapine/fluoxetine combination treatment for bipolar depression reported a response rate of 56.1% for the active drug versus 30.4% for the placebo treatment arm.

 Although these latter results are from a separate study, the response rates are consistent with other medication studies in this population.

Most importantly, we should not forget that the treatment options for individuals afflicted with severe depression, many of whom actively contemplate suicide frequently, are limited. Hancock and colleagues should apply balanced, rigorous scientific scrutiny to the available data before they advocate against ECT. Their analysis to date has not met that standard.

is the head of ECT and lecturer on psychiatry at Massachusetts General Hospital. He receives salary support from a National Institutes of Health grant on ECT.

1. Henry ME. ECT: an effective and safe treatment. 

2. Peltzman T, Gottlieb DJ, Shiner B, Riblet N, Watts BV. Electroconvulsive Therapy in Veterans Health Administration Hospitals: Prevalence, Patterns of Use, and Patient Characteristics. 

3. Peltzman T, Shiner B, Watts BV. Effects of Electroconvulsive Therapy on Short-Term Suicide Mortality in a Risk-Matched Patient Population. 

4. Duma A, Maleczek M, Panjikaran B, Herkner H, Karrison T, Nagele P. Major Adverse Cardiac Events and Mortality Associated with Electroconvulsive Therapy: A Systematic Review and Meta-analysis. 

5. Gbyl K, Videbech P. Electroconvulsive therapy increases brain volume in major depression: a systematic review and meta-analysis. 

6. Fosse R, Read J. Electroconvulsive treatment: hypotheses about mechanisms of action. 

7. Dale E, Pehrson AL, Jeyarajah T, et al. Effects of serotonin in the hippocampus: how SSRIs and multimodal antidepressants might regulate pyramidal cell function. 

8. Schoeyen HK, Kessler U, Andreassen OA, et al. Treatment-resistant bipolar depression: a randomized controlled trial of electroconvulsive therapy versus algorithm-based pharmacological treatment. 

9. Perugi G, Medda P, Toni C, et al. The role of electroconvulsive therapy (ECT) in bipolar disorder: effectiveness in 522 patients with bipolar depression, mixed-state, mania and catatonic features. 

10. Tohen M, Vieta E, Calabrese J, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. 

11. Bahji A, Ermacora D, Stephenson C, et al. Comparative efficacy and tolerability of adjunctive pharmacotherapies for acute bipolar depression: a systematic review and network meta-analysis. 

12. Pompili M, Verzura C, Trovini G, et al. Lurasidone: efficacy and safety in the treatment of psychotic and mood disorders. 

Research data shows that ECT is often more effective than alternative treatments, and safe too. 

In Defense of ECT

 have agreed to continue their debate online. Below, Ms. Hancock, Ms. Cunliffe, and Dr Read argue that ECT is ineffective and unsafe. Representing the pro-ECT position, Dr Henry has responded to their article 

We thank Michael E. Henry, MD, for responding to our article electroconvulsive therapy (ECT): “

,” Henry challenges the conclusion of a recent review

 that there is no robust evidence to determine whether ECT is better than placebo: “The selection criteria used by Read and colleagues were limited to older studies (1956 to 1985).”

 The selection criteria were not time-limited. There simply have not been any placebo-controlled ECT studies since 1985.

 Furthermore the 11 pre-1986 studies were grossly flawed.

We agree with Henry that modern treatment approval requires rigorous, randomized, placebo-controlled methodology using the universally accepted standards of evidence-based medicine. ECT clearly lacks this sort of evidence-base.

Henry produces 3 traditional defences for this empirical data vacuum. First, he argues that studies without placebo control groups, such as comparing different electrode placements, are sufficient. A review of these non-placebo studies, however, revealed that none “produced robust evidence that ECT is effective for depression, primarily because at least 60% maintained ECT participants on medication, 89% produced no meaningful follow-up data beyond the end of treatment, and none investigated whether ECT prevents suicide.”

Second, Henry refers to “more than 75 years of clinical experience”

 as evidence of efficacy. Unfortunately, history is littered with treatments used for decades until deemed ineffective, harmful, or both.

Third, Henry brings up the “ethical dilemma of treating very ill patients with a placebo treatment.”

 But this assumes ECT is safe and more effective than a placebo, and that is precisely what is in question. Assuming its efficacy would position ECT proponents beyond the parameters of evidence-based medicine. Testing treatments in vulnerable populations is essential to establish efficacy, safety limits, and device regulatory protocols.

Henry portrays ECT-induced brain abnormalities, like hippocampal enlargement, as necessarily beneficial. However, a 2013 review of more than 100 imaging studies concluded “the temporarily improved scores on depression instruments following ECT reflect the combination of frontal and temporal lobe functional impairments and activation of the HPA axis and the mesocorticolimbic dopamine system. These effects as well as other detailed changes observed in structures such as the hippocampus appear consistent with those typically seen after severe stress-exposure and/or brain trauma.”

There is no evidence that ECT prevents suicide. A recent study found that 14,810 ECT patients were 1.3 times more likely to die by suicide than 58,369 ECT controls.

1. ECT provides only short-term symptom relief. There are no studies demonstrating ECT outperforms placebo beyond treatment termination, and none that it prevents suicide.

2. Between 12% and 55% of ECT recipients live with persistent memory loss,

 which is suffered disproportionately by women and older individuals, ECT’s target demographic groups.

3. Thymatron ECT device manufacturer lists 7 administration technique variables associated with risks of “

permanent brain damage and permanent memory loss

4. One in 50 ECT recipients suffer “major adverse cardiac events and death after ECT.”

5. Despite repeated requests, the US Food and Drug Administration acknowledges never receiving premarket PMA studies assessing safety or Product Development Protocols to establish 

 ECT research has still not produced any safety testing using modern clinical parameters, dosing limits, or universal administration technique protocols to reduce risks and enable replicable results.

6. Medicare reimburses ECT providers who fail to report quality data, without limits in the number of treatments provided or 

 The 34% increase in US hospitals providing ECT since device reclassification may reflect what happens when hospitals identify an unregulated income source.

7. No one knows how many Americans receive ECT each year, or how many treatments each individual receives, or 

8. ECT recipients are not provided legal informed consent regarding all risks.

9. ECT providers are not routinely assessing each patient for all known risks.

10. Repetitive intracranial mild traumatic brain injury has life-long consequence.

11. ECT recipients injured by treatment are rarely referred for comprehensive rehabilitation to improve quality of life.

12. ECT privileging requirements in the US do not include studying its 

 Without such training, psychiatrists cannot provide appropriate long-term follow-up as recommended by Thymatron device manufacturer.

Failure to acknowledge adverse effects of ECT, with life altering consequences in some patients, creates insurmountable barriers to those injured who need appropriate rehabilitation interventions to improve quality of life after treatment. ECT’s immediate and long-term damage to so many far outweigh its temporary benefits for some individuals.

 is a nationally certified rehabilitation counselor and former Clinical Rehabilitation Counseling and Clinical Mental Health faculty member at San Diego State University. More than a decade ago, Sarah received 116 ECT treatments and now lives with long-term neurological sequalae of repeated exposure to high electrical fields.

is professor of clinical psychology at the University of East London. He is chair of the International Institute for Psychiatric Drug Withdrawal and editor of the scientific journal 

. He has authored several books and more than 200 research papers.

was a pediatrician in the UK until she left her job after undergoing ECT. She has become an advocate for other ECT patients. 

. 2021;38(4):4,7. Accessed April 16, 2021.

2. Read J, Hancock S, Cunliffe S, Henry ME. ECT: dangerous on either side of the pond. 

. 2021;38(4):4-6. Accessed April 16, 2021. 

3. Read J, Kirsch I, McGrath L. Electroconvulsive therapy for depression: a review of the quality of ECT versus sham ECT trials and meta-analyses. 

4. Gregory S, Shawcross CR, Gill D. The Nottingham ECT Study. A double-blind comparison of bilateral, unilateral and simulated ECT in depressive illness. 

5. Read J, Arnold C. Is electroconvulsive therapy for depression more effective than placebo? A systematic review of studies since 2009. 

7. Peltzman T, Gottlieb DJ, Shiner B, et al. Electroconvulsive Therapy in Veterans Health Administration Hospitals: Prevalence, Patterns of Use, and Patient Characteristics. 

Regulatory Update to Thymatron System IV Instruction Manual

. Somatics, LLC; 2018. Accessed May 6, 2021. 

9. Duma A, Maleczek M, Panjikaran B, et al. Major adverse cardiac events and mortality associated with Electroconvulsive Therapy: A Systematic Review and Meta-analysis. 

10. Food and Drug Administration. Reclassification of electroconvulsive therapy devices; effective date of requirement for premarket approval for electroconvulsive therapy devices for certain specified intended uses. Published online December 26, 2018. Accessed May 6, 2021. 

11. Centers for Medicare & Medicaid Services. Medicare program: fiscal year 2021 inpatient psychiatric facilities prospective payment system and special requirements for psychiatric hospitals for fiscal year beginning October 1, 2020. 42 CFR Parts 412 and 482. 2020;16990. 

12. Hancock SP. Whose finger is taking the pulse of America’s shock treatment controversy? Mad In America. July 16, 2020. Accessed May 6, 2021. 

13. American Psychiatric Association Committee on Electroconvulsive Therapy. 

The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging: A Task Force Report of the American Psychiatric Association. 2nd ed.

 American Psychiatric Association; 2001. Accessed May 5, 2021. 

ECT has been in use for decades, but does that mean it is safe or effective? 

Raising Doubts About ECT

Elysa Marco, MD, talks about positive play—how using digital media can enhance specific abilities for kids, especially those with attention-deficit/hyperactivity disorder. 

is a board-certified cognitive and behavioral pediatric neurologist, neuroscience researcher, and author. She specializes in the evaluation and treatment of children with sensory processing disorder, autism, and other neurodevelopmental conditions at Cortica in San Rafael, California.

Kids will find the screens. Health care providers should join them in order to supply the most helpful digital treatments. 

You Can't Beat the Screens

Psychodynamic psychotherapy has receded into the background in many residency programs. But according to Richard D. Lane, MD, PhD, psychotherapy is not only foundational to the history of psychiatry—it still has a lot to offer.

In this Mental Health Minute, Lane uses a brain-based perspective to reimagine how psychotherapy works. In his latest book, 

Neuroscience of Enduring Change: Implications for Psychotherapy

, he collects the latest neuroscientific research on how psychotherapy works and translates the scientific findings into ideas for effective clinical practice.

is Professor of Psychiatry, Psychology, and Neuroscience at the University of Arizona.

How should neuroscience inform psychiatric practice? 

Share comments with your colleagues by emailing 

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

Key neural mechanisms are responsible for emotion, memory consolidation, and lasting personal change. 

What Are the Neuroscientific Secrets to Successful Psychotherapy?

 has partially clarified the role of microglia cells in the progression of Alzheimer disease (AD), which in turn may lead to new targets for 

Normally, microglia cells are responsible for clearing out amyloid plaques and other kinds of cellular debris, but in cases of AD progression 

 Investigators at Duke-National University of Singapore (NUS) Medical School and Monash University set out to discover why. “We sought to understand the molecular mechanisms and differences between microglia that were actively engulfing amyloid plaques in Alzheimer’s disease and those that weren’t,” Enrico Petretto, PhD, associate professor at Duke-NUS Medical School, said in a statement to the press.

When comparing microglia that were and were not eliminating amyloid plaque, Petretto and his co-investigators found that they had different gene expression patterns induced by the 

 gene. The researchers found that microglia cells with reduced 

 expression also had a decreased ability to take up and eliminate an abnormal protein like amyloid. Conversely, high expressions of 

 were associated with more active and effective microglia cells.

“Understanding this mechanism is important because now we have several new targets to go after, and in the future, these targets may open a new front against this devastating disease,” added Jose M. Polo, PhD, an ARC Future Fellow at Monash University.

 This research is built on a larger Duke-NUS initiative to create a comprehensive map of gene expression changes that are associated with AD 

 and AD remains incompletely understood, “future work could focus on using gene editing tool CRISPR to test the impact of manipulating Hif1a on symptom severity and disease progression,” Gabriel Chow, MD-PhD candidate at Duke-NUS Medical School, further explained.

1. Grubman A, Choo XY, Chew G, et al. Transcriptional signature in microglia associated with Aβ plaque phagocytosis. 

Scientists discover gene signature for plaque-eating microglia in Alzheimer’s disease

Duke-NUS study reveals how individual cell types in the brain contribute to Alzheimer’s disease

. Duke-NUS Medical School. November 28, 2019. Accessed May 27, 2021. 

Gene expressions in microglia cells may explain why some of them are ineffective and allow dementia to progress. 

A New Target for Intervention in Alzheimer Disease? 

Too often, the medical issues associated with traumatic brain injury are mistaken as psychiatric disorders, and patients are referred to psychiatrists for treatment, Gregory J. O’Shanick, MD, DLFAPA, told attendees of the 2021 

American Psychiatric Association Virtual Annual Meeting

O’Shanick, who is the medical director of the 

in Richmond, Virginia, urged psychiatrists to leverage their medical knowledge when assessing patients to determine when the diagnosis is a psychiatric disorder and when patients are presenting with medical mimics associated with traumatic brain injury (TBI). He shared his frustration with psychiatry’s loss of medical identity, especially as it related to brain injury medicine. In his 40-year career, he found “all too often, physicians, both MDs and DOs, psychiatrists, [were] missing basic neurologic issues that we as physicians should catch. If we are to be vocal regarding the necessity of having a MD and DO to ultimately provide oversight of care for those with behavioral disorders and writing prescriptions for psychotropic medications, we must not relinquish the use of those tools and skills that were taught to us in medical school.”

The prevalence of TBI has increased over the last 10 or so years, O’Shanick explained, although he acknowledged that the increase may be partially due to increased awareness. According to 

 from the Centers for Disease Control and Prevention, there was a 53% increase from 2006 to 2014 in TBI-related emergency department visits, hospitalizations, and deaths. In older adults and the very young, falls account for the number 1 cause of TBI.

 A combination of motor vehicle accidents, sports, falls, and other activities were the cause for the “very active” and maybe not as cautious young adult population (aged 15 years to 24 years).

Meanwhile, research has found a link between psychiatric disorders and TBI, O’Shanick noted, with an increase of disorders following TBI.

 Jennie Ponsford, PhD, and colleagues explored this phenomenon and found that only about 23% and 21% of individuals had a pre-TBI history of a mood disorder or anxiety disorder, respectively. They found an increase in psychiatric symptomology within the first year after TBI, with a stabilization at the 5-year point. Mood and anxiety symptoms were most common in patients with TBI, with 17.2% to 62% presenting with mood symptoms and 10.3% to 34.2% with anxiety symptoms. Interestingly, he noted depression is 4 to 6 times more common in patients with TBI than the general population, and is the most common cause of depression in men (as opposed to women, for whom menopause is the number one cause).

It is possible, he explained, that some of these mood disturbances and anxiety symptoms may be better explained as a medical consequence of TBI—or a signal of homeostatic disruption. In such cases, providing psychopharmacological treatment might help the patient with the symptoms, but will not address the underlying cause.

O’Shanick provided an example of a phobia being misattributed. He pointed to an individual who is afraid of a jumping off a diving board. They go up the stairs, walk to the edge, realize they are frightened, and go back down. They have conditioned themselves to be afraid—there is a learned component.

Next, he presented the case of an individual who has unrecognized balance and visual issues as a result of TBI. The person goes into a crowd and feels a sense of anxiety, because they have trouble feeling and remaining stable, and the learned component may be inappropriately linked to an anxiety disorder.

“As a physician, we need to figure that out,” O’Shanick emphasized.

Fortunately, a toolkit to help decipher these TBI-related medical mimics is relatively inexpensive, O’Shanick shared. All you need is a pen, index card, blindfold (or ask your patient to close their eyes), a sofa cushion, a tuning fork (which can be procured online for about $6), and a few questions. For example, to determine if the issue is 

 or a vestibular in nature, ask your patient if they need to touch the wall when closing their eyes in the shower to prevent falling. Or, if they feel anxious in a crowded area like a store or mall, does pushing a cart or stroller or holding on to someone make them feel better? If so, there are a few simple follow-up tests (eg, the Balance Error Scoring System and Fukuda Stepping Test) to help confirm the medical mimic. A referral for vestibular physical therapy and a neuro-ENT may prove useful for such patients.

Similarly, to determine if there is social phobia or vergence, ask your patient if they are having trouble seeing/reading books at a normal distance. Then, check near point convergence and conduct a cover test. A referral to a neuro-optometrist should be considered.

Sometimes a central auditory processing disorder may be confused with 

. It is especially important to decipher the difference, O’Shanick explained, because stimulants will worsen the central auditory processing disorder. Ask your patient if they have better sustained attention for visual vs verbal interactions, or if they have trouble understanding what people say if they cannot see their faces or mouths. Weber and Rinne tests can also prove useful, and a referral to an audiologist is indicated.

, posttraumatic neuroendocrine (PTNE) disorders may be relatively common in patients with TBI,

 and mood symptoms are associated with PTNE, O’Shanick explained. Psychiatrists should inquire about changes in menses, sex drive, cold intolerance, and skin and hair dryness to elucidate if PTNE is a potential cause of the mood symptoms. Lab studies should be considered, including 

, TSH, FSH, LH, IG-1, estradiol/testosterone, and am/pm cortisol. In considering TBI in these cases, O’Shanick reminded attendees that they should not overlook 

Finally, O’Shanick illuminated inherent biases in the Minnesota Multiphasic Personality Inventory-2, which might lead to an incorrect diagnosis. For instance, stomach trouble and headaches score positively on the hypochondriasis scale, but both may be related to TBI and TBI treatments. Similarly, positive scores on the hysteria scale result from noting they are unable to work, feel sad, and have trouble sleeping, all of which are associated with TBI.

Ultimately, the psychiatrist is the ideal position to leverage their medical and behavioral knowledge to support these patients.

“Hopefully this will allow you to think a little bit differently when patients come into your office,” O’Shannick concluded. “Maybe ask some increased questions when it comes to injury related issues, concussion related issues… and to see if there is some other types of medical issues behind some of the anxieties that your patients have. At the end, you may just find that you’re practicing … much more successfully and ultimately helping your patients.”

1. CDC. Surveillance report of traumatic brain injury-related emergency department visits, hospitalizations, and deaths. 2014. Accessed May 2, 2021. 

https://www.cdc.gov/traumaticbraininjury/pdf/TBI-Surveillance-Report-FINAL_508.pdf

2. Ponsford J, Always Y, Gould KR. Epidemiology and natural history of psychiatric disorders after TBI. 

3. Beyer C, Zaytsev J, Donegan D, et al. 

The effects of traumatic brain injury on pituitary function: a systematic review and meta-analysis

Too often, the medical issues associated with traumatic brain injury are mistakenly diagnosed as psychiatric disorders. A few simple questions and tests can elucidate the real culprit and lead to appropriate treatment.

Is It a Psychiatric Disorder or TBI Medical Mimic?

In the 1930s and 1940s, researchers identified childhood autism as a unique condition. At the same time, many believed that children became autistic because they had cold, intellectual, emotionally withholding mothers.

But Clara Park, a woman whose daughter had autism, set out to understand autism differently and, along with other families and dedicated researchers, she upended the medical establishment’s view of her daughter’s condition.

In this Mental Health Minute, Marga Vicedo, PhD, discusses her recent book, 

Intelligent Love: The Story of Clara Park, Her Autistic Daughter, and the Myth of the Refrigerator Mother

. Along with telling Park’s story, the book shows how medical research can both reflect social attitudes and change them.

is professor of the history of science and medicine in the Institute for the History of Philosophy of Science and Technology at the University of Toronto. She is the author of 

Has the history of psychiatry informed your practice? 

A mother’s quest to understand her child revolutionized our understanding of autism. 

What Causes Autism?

John J. Miller, MD, gives an overview of functioning across neuronal systems. 

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.

A message flowing through the brain, across neuronal systems... where is it headed?

The Bigger Picture: Across Neuronal Systems

A classification system to identify communication between brain regions brings us closer to predicting and diagnosing attention deficit hyperactivity disorder (ADHD) with better precision than ever before, according to a 

In this Q&A, we speak with lead author of the study, Chris McNorgan, PhD. Dr McNorgan is assistant professor, Department of Psychology at the University at Buffalo, State University of New York, and director of Computational Cognitive Neuroscience Laboratory, in the Department of Psychology at the University at Buffalo — SUNY.

Psychiatric Times (PT): You talk about task-based functional connectivity as a biomarker of ADHD. Can you tell us more about that?

 The challenge with using behavior to diagnose cognitive disorders is that behavior is extremely variable, even within individual patients. Behavioral indicators commonly used to identify ADHD might meet a subjective threshold on one day, but not during a follow-up test, leading to diagnostic instability.

 detects or confirms the presence of a condition of interest by virtue of covarying with the condition: If the biomarker is present, then so is the condition. ADHD is associated with atypical activity patterns, and because the brain does not rewire itself every day, we expected to find persistent differences between ADHD and controls in the connectivity that governs those activity patterns. 

Although a computer is required to represent the complex connectivity patterns that distinguished between controls and ADHD, the high classification accuracy for these machine-learning models establishes that these connectivity patterns provide sufficient evidence to reliably identify ADHD.

PT: What new information does the study provide?

 Ours was not the first study that assumed ADHD can be identified by characteristic functional connectivity. However, the substantial improvement in prediction accuracy over previous studies tells us a few things. First, that task-based functional connectivity within a brain network involved in a task that taxes inhibitory control appears to be more predictive of ADHD than resting state connectivity collected while individuals let their minds wander.

The second finding is more of an analytic innovation, explicitly tying diagnostic accuracy to performance on a relevant behavioral task. The 

 (IGT) was developed under a particular theory about the role of inhibitory processing in ADHD. However, just because it is theoretically tied to ADHD does not make it so. 

Because the classifiers had to identify both IGT performance and ADHD diagnosis from the same set of functional connections, it had to find which connections, if any, were predictive of both. Successfully solving the problem established that performance on the IGT is relevant to ADHD by virtue of the fact that the same functional connections predict both. The study provides a template for similarly linking other diagnostic measures to outcomes.

PT: What can you tell us about the future of machine learning in predicting ADHD with diagnostic accuracy?

 Although task-based connectivity was more diagnostic than resting-state, running an experimental task in an MRI scanner will not be a practical diagnostic tool anytime soon. However, by explicitly linking neuroimaging results to easily administered behavioral tasks, models like this might be used in the future. They may translate a particular behavioral performance profile into a likely connectivity profile confirmed by MRI if need be. These results might inform the choice of intervention. 

ADHD diagnoses have been described as unstable: The same individual may fall above or below threshold at different times. So the fact that childhood ADHD diagnoses were 

 in fMRI scans taken from young adults is remarkable, and I think points to the disorder as something that is deeply ingrained at the neurological level, although it may appear much more transitory at the behavioral level. We do not have information about severity in the participants at the time of the scan, but even if we assumed all of them were symptom-free, their brains are clearly doing something identifiably different.

Finally, these models are remarkably accurate because they make use of many different data points. The optimal precision was calculated based on 4 individual fMRI scans per participant. There may be different subtypes that could be identified by an extension of this paradigm using new tasks. All this points to the general idea that having more information on-hand leads to better evaluations, though the information required to achieve very high accuracy may take a computer to process it.

PT: Did you find anything in your research that was unexpected?

 In hindsight, finding subgroups seems obvious, but we were not looking for different connectivity profiles for high- and low-scorers on the IGT. This was purely for a proof-of-concept, and to make it easier to argue that the classifier had identified activity that was related to inhibitory control. This got us thinking about how this sort of approach might be useful for identifying subpopulations.

PT: Can you tell us about future directions in this research?

 There are a few interesting directions that immediately suggest themselves. Clinical endpoints may be based on subjective self-report. As a surrogate, the 

 must not only be correlated with the condition, but evidence of a causal link must be established between the condition and the biomarker. Research that examines whether and/or which interventions lead to related changes in functional connectivity and in clinical endpoints might establish functional connectivity as a surrogate endpoint. This would allow connectivity to provide additional context for interpreting subjective patient reports.

A second direction would be to link diagnostically predictive connectivity patterns to other commonly used behavioral indicators. We found different connectivity profiles for those with ADHD that scored uncharacteristically high on the IGT, which is commonly used in an experimental setting. This indicates that individuals with ADHD may be differentiated by different patterns of hyper- or hypo-connectivity, and these differences may inform choice of intervention, eg, a drug that targets the hypo-connected circuit. 

 to performance on other tasks more commonly used in a clinical setting may lead to more effective treatment of ADHD in patients who show atypical performance on 1 or more clinically relevant measures.

1. McNorgan C, Judson C, Handzlik, Holden JG. Linking ADHD and Behavioral Assessment Through Identification of Shared Diagnostic Task-Based Functional Connections. 

 2020;11:583005. Accessed April 13, 2021. 

https://www.frontiersin.org/articles/10.3389/fphys.2020.583005/full

New research brings us closer to linking diagnostically predictive connectivity patterns in patients with ADHD.

Advances in Predicting and Diagnosing ADHD

An international group of experts analyzed findings from a large pool of select studies and developed an updated consensus statement with declarations about attention deficit hyperactivity disorder (ADHD). They curated a collection of validated statements, addressing questions on topics ranging from nutrition, neuropsychiatry, and nonpharmacologic treatments. The 

Lead author Stephen V. Faraone, PhD, joins us in this Q&A to talk about the study. Dr Faraone is Distinguished Professor in the Departments of Psychiatry and Neuroscience and Physiology, Psychiatry Research Division, SUNY Upstate Medical University, Syracuse, New York. He is President of the 

Psychiatric Times (PT): What prompted the consensus guidelines and why are they important now?

Despite a large scientific literature about ADHD, much misinformation about ADHD is spread by the internet and other media. This creates 

A collection of validated statements addresses overarching topics ranging from nutrition, neuropsychiatry, and nonpharmacologic treatments.

Neuropsychiatry