A central theme which ISAN maintains and was championed by Dr. Dan Pavel (1934-2021) is that comorbidity (the presence of two or more diagnoses) is the rule, rather than the exception in psychiatry. Patients with depression have a remarkably high rate of comorbid anxiety (Henderson, 2018; McElroy, 2018). Patients with Post-Traumatic Stress Disorder (PTSD), particularly veterans, often have comorbid Traumatic Brain Injury (TBI) (Henderson, 2016; Hoge, 2008). These comorbid diagnoses cloud the diagnostic process. Current diagnostic methods fail to fully assess the presence and impact of comorbidities.
For an in-depth example, patients with ADHD frequently have comorbid anxiety, oppositional disorders, or learning disorders (Henderson, 2018; Spencer, 1999; Newcorn 2001; Pliszka 2003). The prevalence of anxiety disorders among those with ADHD ranges from 15-35% (Busch; Jensen;). Depressive disorders occur in 12-59% of children with ADHD (Angold; Biederman). The prevalence of conduct disorder and oppositional defiant disorder among those with ADHD ranges from 30-50% (August;Gnanavel). These comorbidities profoundly alter the clinical picture of ADHD and undoubtedly alter the response to medications.
Psychiatry depends heavily on the Diagnostic and Statistical Manual V (DSM-V) a diagnostic guide-turned-bible created by the American Psychiatric Association (APA) for determining a patient’s diagnosis. The DSM-V provides a set of symptoms and signs which must be present to give a patient a certain diagnosis (APA, 2013). Essentially, these diagnostic criteria were determined by a committee and do not stand up to the challenges of diagnosing patients in the real world. In fact, fully 60% of the DSMV diagnoses failed to stand up to validity testing when subjected to field trials (Regier, 2013). Keep in mind that the DSMV was not designed with the brain in mind and the APA has done little to adopt the lessons learned about the neurobiology of psychiatric disorders. It is also a source of millions of dollars in revenue annually for the APA.
A separate important point is that inattention, a cardinal diagnostic symptom of ADHD, is a non-specific symptom. Inattention is found not only in ADHD, mania, anxiety, and depression, but it is also found in TBI, carbon monoxide poisoning, cadmium toxicity, lead toxicity, schizophrenia, PTSD, post-coronary bypass syndrome, multiple sclerosis, substance abuse, space-occupying lesions, CNS infections, dementia, and a litany of other conditions which alter frontal lobe functioning (Henderson, 2020). Lastly, traumatic brain injury (TBI) involving the frontal lobes can result in impulsivity, impaired attention, reduced judgement, and other hallmark symptoms which are indistinguishable from ADHD. By the same token, toxic brain injury can also masquerade as ADHD. Frontal lobe neuronal injury from a host of toxins and other insults can lead to impaired attention and other symptoms of ADHD.It would be foolish to expect an injured brain to respond in the same manner as an intact brain. While, an interview will not help distinguish among these possibilities, neuroimaging can differentiate many of these categories.
A separate important point
A separate important point is that inattention, a cardinal diagnostic symptom of ADHD, is a non-specific symptom. Inattention is found not only in ADHD, mania, anxiety, and depression, but it is also found in TBI, carbon monoxide poisoning, cadmium toxicity, lead toxicity, schizophrenia, PTSD, post-coronary bypass syndrome, multiple sclerosis, substance abuse, space-occupying lesions, CNS infections, dementia, and a litany of other conditions which alter frontal lobe functioning (Henderson, 2020). Lastly, traumatic brain injury (TBI) involving the frontal lobes can result in impulsivity, impaired attention, reduced judgement, and other hallmark symptoms which are indistinguishable from ADHD. By the same token, toxic brain injury can also masquerade as ADHD. Frontal lobe neuronal injury from a host of toxins and other insults can lead to impaired attention and other symptoms of ADHD.It would be foolish to expect an injured brain to respond in the same manner as an intact brain. While, an interview will not help distinguish among these possibilities, neuroimaging can differentiate many of these categories.
Can neuroimaging provide a pathognomonic imaging result (a fingerprint, if you will) for each of these conditions? No, but it can eliminate several possibilities and lead you closer to a definitive diagnosis. For example, if a perfusion SPECT scan shows a diffuse pattern of decreased function, ADHD become much less likely and systemic effects such as metal (Geier, 2012), mold (Rea, 2003), or other(Véra, 1999)toxicity, carbon monoxide poisoning (Tsai, 2014), or infection(Shroff, 2018; Henderson, 2020)become more likely. Rather than treating the patient with a stimulant, a clinician would be directed by the scan results to seek a cause for the brain dysfunction.
American Psychiatric Association
It should be noted that the American Psychiatric Association (APA) has taken the position that neuroimaging has no role in Psychiatry. In 2018, the APA published a position paper stating, “neuroimaging has yet to have a significant impact on the diagnosis or treatment of individual patients in clinical settings”(First, 2018). When the APA officially declared that using neuroimaging to look at the brain has no clinical value in psychiatry, it took a step backwards scientifically. As if to codify the aphorism, “The Absence of evidence is evidence of absence”, the APA then conveniently ignores an entire body of SPECT neuroimaging research. It also took a giant leap backward in terms of the evolution of the medical diagnostic process. It is not an overstatement to say that an obvious step in the diagnostic process inherent to all forms of medicine is to actually look at the organ of medical concern. A surgeon would not think of operating – even under the most emergent of conditions – without first obtaining an image of the surgical region. Cardiology uses SPECT neuroimaging as a cornerstone of the diagnostic evaluation of the heart. The APA also took a step backwards morally by denying patients a potentially better way to arrive at the treatment plan. Is it truly better to guess or depend upon intuition versus utilizing all possible forms of diagnostic information at one’s disposal? Are multiple failed trials of antidepressants better for the patient?
The APA’s claim that neuroimaging has not had a significant impact on the diagnosis and treatment of psychiatric illnesses seems to assume that functional brain neuroimaging can only be helpful if it provides a pathognomonic “fingerprint” for a DSM diagnosis. Notwithstanding the absurdity of expecting imaging of the human brain to yield a hallmark of a disorder created by a committee, issues of comorbidity, and the shared final neurophysiological outcome of multiple “diagnoses” make it highly unlikely logically that we will have neuroimaging “fingerprints” for committee-created disorders.
The members of ISAN call upon the APA to re-examine neuroimaging in psychiatry with inclusion of SPECT and FDG-PET research. Rather than set unrealistic expectations for a neuroimaging biomarker, understand the value of incremental steps in a differential diagnosis. Furthermore, ISAN encouraged the APA to explore the use of SPECT and FDG-PET in psychiatry with those who are actually knowledgeable about their practical applications. We acknowledge that interpreting SPECT requires thorough training, just as with interpreting amyloid scans. SPECT scans are technically demanding and poor quality scans can be misleading and dissuasive. On the other hand, high quality SPECT scans with quantitative analysis can provide striking insights into the function of the brain across a diversity of psychiatric conditions. Lastly, neuroimaging is not something to be feared. Neuroimaging does not replace the diagnostician; rather, it can aid the diagnostician in complex cases.
References
1. Henderson, T.A. (2018). Brain SPECT imaging in neuropsychiatric diagnosis and monitoring. EPatient. 1:40-47. http://nmpangea.com/2018/10/09/738/
2. McElroy, E., Fearon, P., Belsky, J., Fonagy, P., Patalay, P. (2018). Networks of Depression and Anxiety Symptoms Across Development. J. Am. Acad. Child. Adolesc. Psychiatry. 57(12):964-973.doi: 10.1016/j.jaac.2018.05.027
3. Hoge, C.W., Castro, C.A., Messer, S.C., McGurk, D., Cotting, D.I., Koffman, R.L. (2008). Combat duty in Iraq and Afghanistan, mental health problems and barriers to care. U.S. Army. Med. Dep. J. Jul-Sep:7-17.
4. Newcorn, J.H., Halperin, J.M., Jensen, P.S., Abikoff, H.B., Arnold, L.E., Cantwell, D.P., et al. (2001). Symptom profiles in children with ADHD: effects of comorbidity and gender. J. Am. Acad. Child. Adolesc. Psychiatry. 40(2):137-46.
5. Pliszka, S.R. (2003). Psychiatric comorbidities in children with attention deficit hyperactivity disorder: implications for management. Paediatr. Drugs.5(11):741-50.
6. McElroy, E., Fearon, P., Belsky, J., Fonagy, P., Patalay, P. (2018). Networks of Depression and Anxiety Symptoms Across Development. J. Am. Acad. Child. Adolesc. Psychiatry. 57(12):964-973.doi: 10.1016/j.jaac.2018.05.027
7. Henderson, T.A. (2016). TBI and PTSD symptoms appear similar, but clinical treatments must differ: Some treatment can do more harm than good when proper diagnosis is not made. Behav. Healthc.36(4):34, 36-7.
8. Busch B, Biederman J, Cohen LG, Sayer JM, Monuteaux MC, Mick E, Zallen B, Faraone SV. Correlates of ADHD among children in pediatric and psychiatric clinics. Psychiatr Serv. 2002;53:1103-1111.
9. Jensen PS, Hinshaw SP, Swanson JM, Greenhill LL, Conners CK, Arnold LE, Abikoff HB, Elliott G, Hechtman L, Hoza B, March JS, Newcorn JH, Severe JB, Vitiello B, Wells K, Wigal T. Findings from the NIMH Multimodal Treatment Study of ADHD (MTA): implications and applications for primary care providers. J Dev BehavPediatr. 2001;22:60-73.
10. Angold A, Costello EJ, Erkanli A. Comorbidity. J Child Psychol Psychiatry. 1999;40:57-87.
11. Biederman J, Newcorn J, Sprich S. Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry. 1991;148:564-577.
12. August GJ, Stewart MA, Holmes CS. A four-year follow-up of hyperactive boys with and without conduct disorder. Br J Psychiatry. 1983;143:192-198.
13. Gnanavel S, Sharma P, Kaushal P, Hussain S. Attention deficit hyperactivity disorder and comorbidity: A review of literature. World J Clin Cases 2019; 7(17): 2420-2426.
14. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders, 5th ed. (Arlington VA, American Psychiatric Association).
15. Regier, D.A., Narrow, W.E., Clarke, D.E., Kraemer, H.C., Kuramoto, S.J., Kuhl, E.A., et al. (2013). DSM-5 field trials in the United States and Canada, Part II: test-retest reliability of selected categorical diagnoses. Am. J. Psychiatry. 170(1):59-70.
16. Henderson TA, van Lierop MJ, McLean M, Uszler JM, Thornton JF, Siow YH, Pavel DG, Cardaci J, Cohen P. Functional Neuroimaging in Psychiatry-Aiding in Diagnosis and Guiding Treatment. What the American Psychiatric Association Does Not Know. Front Psychiatry. 2020 Apr 15;11:276.
17. Geier DA, Pretorius HT, Richards NM, Geier MR. A quantitative evaluation of brain dysfunction and body-burden of toxic metals. Med Sci Monit. 2012.18(7):CR425-31.
18. Rea WJ, Didriksen N, Simon TR, Pan Y, et al. Effects of toxic exposure to molds and mycotoxins in building-related illnesses. Arch Environ Health. 2003.58(7):399-405.
19. Véra P, Rohrlich P, Stiévenart JL, Elmaleh M, et al. Contribution of single-photon emission computed tomography in the diagnosis and follow-up of CNS toxicity of a cytarabine-containing regimen in pediatric leukemia. J Clin Oncol. 1999.17(9):2804-10.
20. Tsai CF, Yip PK, Chen SY, Lin JC, et al. The impacts of acute carbon monoxide poisoning on the brain: Longitudinal clinical and 99mTc ethyl cysteinate brain SPECT characterization of patients with persistent and delayed neurological sequelae. Clin Neurol Neurosurg. 2014.119:21-7.
21. Shroff G. Single-photon emission tomography imaging in patients with Lyme disease treated with human embryonic stem cells. Neuroradiol J. 2018.31(2):157-167.
22. First MB, Drevets WC, Carter C, Dickstein DP, et al: Clinical Applications of Neuroimaging in Psychiatric Disorders. Am J Psychiatry 2018.175:915-916.
Psychiatric Comorbidity
A central theme which ISAN maintains
A central theme which ISAN maintains and was championed by Dr. Dan Pavel (1934-2021) is that comorbidity (the presence of two or more diagnoses) is the rule, rather than the exception in psychiatry. Patients with depression have a remarkably high rate of comorbid anxiety (Henderson, 2018; McElroy, 2018). Patients with Post-Traumatic Stress Disorder (PTSD), particularly veterans, often have comorbid Traumatic Brain Injury (TBI) (Henderson, 2016; Hoge, 2008). These comorbid diagnoses cloud the diagnostic process. Current diagnostic methods fail to fully assess the presence and impact of comorbidities.
For an in-depth example, patients with ADHD frequently have comorbid anxiety, oppositional disorders, or learning disorders (Henderson, 2018; Spencer, 1999; Newcorn 2001; Pliszka 2003). The prevalence of anxiety disorders among those with ADHD ranges from 15-35% (Busch; Jensen;). Depressive disorders occur in 12-59% of children with ADHD (Angold; Biederman). The prevalence of conduct disorder and oppositional defiant disorder among those with ADHD ranges from 30-50% (August;Gnanavel). These comorbidities profoundly alter the clinical picture of ADHD and undoubtedly alter the response to medications.
Psychiatry depends heavily on the Diagnostic and Statistical Manual V (DSM-V) a diagnostic guide-turned-bible created by the American Psychiatric Association (APA) for determining a patient’s diagnosis. The DSM-V provides a set of symptoms and signs which must be present to give a patient a certain diagnosis (APA, 2013). Essentially, these diagnostic criteria were determined by a committee and do not stand up to the challenges of diagnosing patients in the real world. In fact, fully 60% of the DSMV diagnoses failed to stand up to validity testing when subjected to field trials (Regier, 2013). Keep in mind that the DSMV was not designed with the brain in mind and the APA has done little to adopt the lessons learned about the neurobiology of psychiatric disorders. It is also a source of millions of dollars in revenue annually for the APA.
A separate important point is that inattention, a cardinal diagnostic symptom of ADHD, is a non-specific symptom. Inattention is found not only in ADHD, mania, anxiety, and depression, but it is also found in TBI, carbon monoxide poisoning, cadmium toxicity, lead toxicity, schizophrenia, PTSD, post-coronary bypass syndrome, multiple sclerosis, substance abuse, space-occupying lesions, CNS infections, dementia, and a litany of other conditions which alter frontal lobe functioning (Henderson, 2020). Lastly, traumatic brain injury (TBI) involving the frontal lobes can result in impulsivity, impaired attention, reduced judgement, and other hallmark symptoms which are indistinguishable from ADHD. By the same token, toxic brain injury can also masquerade as ADHD. Frontal lobe neuronal injury from a host of toxins and other insults can lead to impaired attention and other symptoms of ADHD.It would be foolish to expect an injured brain to respond in the same manner as an intact brain. While, an interview will not help distinguish among these possibilities, neuroimaging can differentiate many of these categories.
A separate important point
A separate important point is that inattention, a cardinal diagnostic symptom of ADHD, is a non-specific symptom. Inattention is found not only in ADHD, mania, anxiety, and depression, but it is also found in TBI, carbon monoxide poisoning, cadmium toxicity, lead toxicity, schizophrenia, PTSD, post-coronary bypass syndrome, multiple sclerosis, substance abuse, space-occupying lesions, CNS infections, dementia, and a litany of other conditions which alter frontal lobe functioning (Henderson, 2020). Lastly, traumatic brain injury (TBI) involving the frontal lobes can result in impulsivity, impaired attention, reduced judgement, and other hallmark symptoms which are indistinguishable from ADHD. By the same token, toxic brain injury can also masquerade as ADHD. Frontal lobe neuronal injury from a host of toxins and other insults can lead to impaired attention and other symptoms of ADHD.It would be foolish to expect an injured brain to respond in the same manner as an intact brain. While, an interview will not help distinguish among these possibilities, neuroimaging can differentiate many of these categories.
Can neuroimaging provide a pathognomonic imaging result (a fingerprint, if you will) for each of these conditions? No, but it can eliminate several possibilities and lead you closer to a definitive diagnosis. For example, if a perfusion SPECT scan shows a diffuse pattern of decreased function, ADHD become much less likely and systemic effects such as metal (Geier, 2012), mold (Rea, 2003), or other(Véra, 1999)toxicity, carbon monoxide poisoning (Tsai, 2014), or infection(Shroff, 2018; Henderson, 2020)become more likely. Rather than treating the patient with a stimulant, a clinician would be directed by the scan results to seek a cause for the brain dysfunction.
American Psychiatric Association
It should be noted that the American Psychiatric Association (APA) has taken the position that neuroimaging has no role in Psychiatry. In 2018, the APA published a position paper stating, “neuroimaging has yet to have a significant impact on the diagnosis or treatment of individual patients in clinical settings”(First, 2018). When the APA officially declared that using neuroimaging to look at the brain has no clinical value in psychiatry, it took a step backwards scientifically. As if to codify the aphorism, “The Absence of evidence is evidence of absence”, the APA then conveniently ignores an entire body of SPECT neuroimaging research. It also took a giant leap backward in terms of the evolution of the medical diagnostic process. It is not an overstatement to say that an obvious step in the diagnostic process inherent to all forms of medicine is to actually look at the organ of medical concern. A surgeon would not think of operating – even under the most emergent of conditions – without first obtaining an image of the surgical region. Cardiology uses SPECT neuroimaging as a cornerstone of the diagnostic evaluation of the heart. The APA also took a step backwards morally by denying patients a potentially better way to arrive at the treatment plan. Is it truly better to guess or depend upon intuition versus utilizing all possible forms of diagnostic information at one’s disposal? Are multiple failed trials of antidepressants better for the patient?
The APA’s claim that neuroimaging has not had a significant impact on the diagnosis and treatment of psychiatric illnesses seems to assume that functional brain neuroimaging can only be helpful if it provides a pathognomonic “fingerprint” for a DSM diagnosis. Notwithstanding the absurdity of expecting imaging of the human brain to yield a hallmark of a disorder created by a committee, issues of comorbidity, and the shared final neurophysiological outcome of multiple “diagnoses” make it highly unlikely logically that we will have neuroimaging “fingerprints” for committee-created disorders.
The members of ISAN call upon the APA to re-examine neuroimaging in psychiatry with inclusion of SPECT and FDG-PET research. Rather than set unrealistic expectations for a neuroimaging biomarker, understand the value of incremental steps in a differential diagnosis. Furthermore, ISAN encouraged the APA to explore the use of SPECT and FDG-PET in psychiatry with those who are actually knowledgeable about their practical applications. We acknowledge that interpreting SPECT requires thorough training, just as with interpreting amyloid scans. SPECT scans are technically demanding and poor quality scans can be misleading and dissuasive. On the other hand, high quality SPECT scans with quantitative analysis can provide striking insights into the function of the brain across a diversity of psychiatric conditions. Lastly, neuroimaging is not something to be feared. Neuroimaging does not replace the diagnostician; rather, it can aid the diagnostician in complex cases.
References
1. Henderson, T.A. (2018). Brain SPECT imaging in neuropsychiatric diagnosis and monitoring. EPatient. 1:40-47. http://nmpangea.com/2018/10/09/738/
2. McElroy, E., Fearon, P., Belsky, J., Fonagy, P., Patalay, P. (2018). Networks of Depression and Anxiety Symptoms Across Development. J. Am. Acad. Child. Adolesc. Psychiatry. 57(12):964-973.doi: 10.1016/j.jaac.2018.05.027
3. Hoge, C.W., Castro, C.A., Messer, S.C., McGurk, D., Cotting, D.I., Koffman, R.L. (2008). Combat duty in Iraq and Afghanistan, mental health problems and barriers to care. U.S. Army. Med. Dep. J. Jul-Sep:7-17.
4. Newcorn, J.H., Halperin, J.M., Jensen, P.S., Abikoff, H.B., Arnold, L.E., Cantwell, D.P., et al. (2001). Symptom profiles in children with ADHD: effects of comorbidity and gender. J. Am. Acad. Child. Adolesc. Psychiatry. 40(2):137-46.
5. Pliszka, S.R. (2003). Psychiatric comorbidities in children with attention deficit hyperactivity disorder: implications for management. Paediatr. Drugs.5(11):741-50.
6. McElroy, E., Fearon, P., Belsky, J., Fonagy, P., Patalay, P. (2018). Networks of Depression and Anxiety Symptoms Across Development. J. Am. Acad. Child. Adolesc. Psychiatry. 57(12):964-973.doi: 10.1016/j.jaac.2018.05.027
7. Henderson, T.A. (2016). TBI and PTSD symptoms appear similar, but clinical treatments must differ: Some treatment can do more harm than good when proper diagnosis is not made. Behav. Healthc.36(4):34, 36-7.
8. Busch B, Biederman J, Cohen LG, Sayer JM, Monuteaux MC, Mick E, Zallen B, Faraone SV. Correlates of ADHD among children in pediatric and psychiatric clinics. Psychiatr Serv. 2002;53:1103-1111.
9. Jensen PS, Hinshaw SP, Swanson JM, Greenhill LL, Conners CK, Arnold LE, Abikoff HB, Elliott G, Hechtman L, Hoza B, March JS, Newcorn JH, Severe JB, Vitiello B, Wells K, Wigal T. Findings from the NIMH Multimodal Treatment Study of ADHD (MTA): implications and applications for primary care providers. J Dev BehavPediatr. 2001;22:60-73.
10. Angold A, Costello EJ, Erkanli A. Comorbidity. J Child Psychol Psychiatry. 1999;40:57-87.
11. Biederman J, Newcorn J, Sprich S. Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry. 1991;148:564-577.
12. August GJ, Stewart MA, Holmes CS. A four-year follow-up of hyperactive boys with and without conduct disorder. Br J Psychiatry. 1983;143:192-198.
13. Gnanavel S, Sharma P, Kaushal P, Hussain S. Attention deficit hyperactivity disorder and comorbidity: A review of literature. World J Clin Cases 2019; 7(17): 2420-2426.
14. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders, 5th ed. (Arlington VA, American Psychiatric Association).
15. Regier, D.A., Narrow, W.E., Clarke, D.E., Kraemer, H.C., Kuramoto, S.J., Kuhl, E.A., et al. (2013). DSM-5 field trials in the United States and Canada, Part II: test-retest reliability of selected categorical diagnoses. Am. J. Psychiatry. 170(1):59-70.
16. Henderson TA, van Lierop MJ, McLean M, Uszler JM, Thornton JF, Siow YH, Pavel DG, Cardaci J, Cohen P. Functional Neuroimaging in Psychiatry-Aiding in Diagnosis and Guiding Treatment. What the American Psychiatric Association Does Not Know. Front Psychiatry. 2020 Apr 15;11:276.
17. Geier DA, Pretorius HT, Richards NM, Geier MR. A quantitative evaluation of brain dysfunction and body-burden of toxic metals. Med Sci Monit. 2012.18(7):CR425-31.
18. Rea WJ, Didriksen N, Simon TR, Pan Y, et al. Effects of toxic exposure to molds and mycotoxins in building-related illnesses. Arch Environ Health. 2003.58(7):399-405.
19. Véra P, Rohrlich P, Stiévenart JL, Elmaleh M, et al. Contribution of single-photon emission computed tomography in the diagnosis and follow-up of CNS toxicity of a cytarabine-containing regimen in pediatric leukemia. J Clin Oncol. 1999.17(9):2804-10.
20. Tsai CF, Yip PK, Chen SY, Lin JC, et al. The impacts of acute carbon monoxide poisoning on the brain: Longitudinal clinical and 99mTc ethyl cysteinate brain SPECT characterization of patients with persistent and delayed neurological sequelae. Clin Neurol Neurosurg. 2014.119:21-7.
21. Shroff G. Single-photon emission tomography imaging in patients with Lyme disease treated with human embryonic stem cells. Neuroradiol J. 2018.31(2):157-167.
22. First MB, Drevets WC, Carter C, Dickstein DP, et al: Clinical Applications of Neuroimaging in Psychiatric Disorders. Am J Psychiatry 2018.175:915-916.