looking at the pathophysiology and comorbidities ...€¦ · context of systemic inflammation in...

ExamineComorbidities.com

Looking at the Pathophysiology and Comorbidities Associated with Bipolar Disorder or Schizophrenia

UNB-002934

Not an actual patient.

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Objectives

• Explore how serious mental illness, including bipolar disorder and schizophrenia, may affect the whole person

• Detail the pathophysiology of both bipolar disorder and schizophrenia and a range of comorbidities that may occur

• Identify opportunities for mental health providers to manage the whole patient

2


Estimated 1-year prevalence ofbipolar I disorder in the US (2011, 2017)2,3

The NIMH defines SMI as a mental, behavioral, or emotional disorder resulting in serious functional impairment that substantially interferes with or limits 1 or more major life activities1

Serious Mental Illness (SMI) Results in Functional Impairment

3

NIMH=National Institute of Mental Health.

1. NIMH. Mental illness. https://www.nimh.nih.gov/health/statistics/mental-illness.shtml#part_154788. Accessed May 8, 2019; 2. Merikangas KR et al. Arch Gen Psychiatry. 2011;68(3):241-251; 3. Blanco C et al. J Psychiatr Res. 2017;84:310-317; 4. NIMH. Schizophrenia. https://www.nimh.nih.gov/health/statistics/schizophrenia.shtml. Accessed January 6, 2019.

≈4.5%≈0.25–0.64%

≈0.6–1.5%

Estimated 1-year prevalence ofschizophrenia in the US (2018)4

Estimated 1-year prevalence of SMI (2017)1


2.08xRisk for

schizophrenia

10-25Years

Higher Mortality Risk Has Been Observed in Patients with Serious Mental Illness

4

*This study was a review of primary care electronic health records in patients in the United Kingdom.†The severe mental disorders to which this information sheet refers are psychosis, bipolar mood disorder and moderate-severe depression.

1. Hayes JF et al. Br J Psychiatry. 2017;211(3):175-181; 2. WHO. Mental Disorders Information Sheet. https://www.who.int/mental_health/management/info_sheet.pdf. Accessed January 1, 2020.

A 2014 fact sheet from the World Health Organization suggested there is a 10-25 year life

expectancy reduction in patients with severe mental disorders2†

1.77xRisk for bipolar

disorder

In a 2017 observational study, patients diagnosed with bipolar disorder or schizophrenia had an

increased risk of mortality compared to the general population (1.77x for bipolar disorder

and 2.08x for schizophrenia)1*


0

200

400

600

800

1000

Respiratory Accidents Suicide Vascular

Ex

ce

ss

de

ath

s

Excess Deaths Have Been Observed in Patients with Bipolar Disorder

5

An analysis of 15,386 patients in Sweden with bipolar disorder suggested respiratory diseases, accidents, suicide and vascular diseases were among the most frequent causes of excess mortality

compared with the general population from 1973–19951,2

1. Osby U et al. Arch Gen Psychiatry. 2001;58(9):844-850; 2. Weiner M et al. Ann Clin Psychiatry. 2011;23(1):40-47.

These were the 4 largest determined causes out of 15 causes of excess mortality, calculated by subtracting the expected number of deaths from the observed number of deaths reported in the in-patient register and the national

cause-of-death register in Sweden; the study was not powered for direct comparison among causes1,2


0

200

400

600

800

1000

Respiratory Accidents Suicide Vascular

Ex

ce

ss

de

ath

s

Excess Deaths Have Been Observed in Patients with Schizophrenia

6

An analysis of 7,784 patients in Sweden with schizophrenia suggested respiratory diseases, accidents, suicide and vascular diseases were among the most frequent causes of excess mortality

compared with the general population from 1973–1995

Osby U et al. Schizophr Res. 2000;45(1-2):21-28.

These were the 4 largest determined causes out of 15 causes of excess mortality, calculated by subtracting the expected number of deaths from the observed number of deaths reported in the in-patient register and the national

cause-of-death register in Sweden; the study was not powered for direct comparison among causes


Patients with SMI May Experience a Range of Common Physical Comorbidities

7

COPD=chronic obstructive pulmonary disease.

1. De Hert M et al. World Psychiatry. 2011;10(1):52-77; 2. Bahorik AL et al. J Psychosom Res. 2017;100:35-45; 3. Carney CP et al. J Gen Intern Med. 2006;21(11):1133-1137; 4. Beyer J et al. Neuropsychopharmacology. 2005;30(2):401-404; 5. Carney CP et al. Psychosom Med. 2006;68(5):684-691.

Respiratory

Metabolic

Infectious

Cardiovascular

• COPD

• Asthma

• Diabetes

• Obesity

• Metabolic syndrome

• Hypertension

• Stroke

• HIV

• Hepatitis B/C

Studies have reported increased prevalence of several physical comorbidities in patients with SMI, including bipolar disorder and schizophrenia1-5

These physical illnesses and disease categories were consistently reported to be more common compared with the general population1-5


Schizophrenia: Potential Dysfunction Across Multiple Systems


Schizophrenia May Involve Dysfunction Across Several Systems: Evidence from Antipsychotic-naive Patients

9

GTT=oral gucose tolerance test.

Figure adapted from: Pillinger T et al. Mol Psychiatry. 2018;24(6):776-794.

An analysis of patients with first-episode psychosis, including patients with schizophrenia, suggested schizophrenia may involve dysfunction across cardiometabolic, immune, and endocrine systems; the meta-analysis extracted data from antipsychotic-naive patients from 6 studies (2018)

Endocrine Disturbance

Metabolic Disturbance

↑ Insulin resistance↑ Fasting glucose

↑ Fasting insulin ↑ Glucose post-OGTT↑ Oxidative stress

Immune Disturbance

↑ Cytokines↑ Lymphocyte counts

↑ Prolactin

Cardiac Disturbance

↑ Triglycerides↓ HDL cholesterol

↓ Total cholesterol↓ LDL cholesterol


Reduced Adiponectin Levels Have Been Observed in Patients with Schizophrenia

10

Figure adapted from Menzaghi C et al. Diabetes. 2007;56(5):1198-1209.1. Freyberg Z et al. Front Neurosci. 2017;11:432; 2. Diez JJ et al. Eur J Endocrinol. 2003;148(3):293-300; 3. Di Chiara T et al. J Nutr Metab. 2012;2012:175245; 4. Cohn TA et al. Can J Psychiatry. 2006;51(6):382-386.

• Adiponectin, an adipokine hormone produced primarily by fat cells in adipose tissue, makes tissues more sensitive to insulin, while low levels of adiponectin are associated with insulin resistance, as reported in reviews from 2003, 2012, and 20171-3

• The association between adiponectin and antipsychotic-naive schizophrenia is still unclear. Lower serum adiponectin levels have been detected in this subpopulation compared with healthy controls1,4

• Lower adiponectin levels have been observed in antipsychotic-prescribed patients with schizophrenia1

Adiponectin

↓ Glucose output↓ Fat accumulation↓ Inflammation

↓ Inflammation↓ Endothelial adhesion↓ Foam cell formation

↑ Glucose uptake↓ Fat accumulation↑ Energy expenditure

Protection from:• Insulin resistance• Type 2 diabetes• Coronary artery disease


• Immune activation may occur both peripherally and centrally in patients with schizophrenia1

• Elevated blood cytokine levels, including IL-1β, sIL2R, IL-6 and TNFα, have been observed inantipsychotic-naive patients with schizophrenia2,3

Elevated Blood Cytokines Have Been Observed in Patients with Schizophrenia

11

BMI=body mass index; IL-1β=interleukin one beta; IL-6=interleukin six; TNF-α=tumor necrosis factor alpha; sIL2R=soluble form of interleukin 2 receptor.

Figure adapted from Nakamizo S et al. Trends in Immunotherapy. 2017;1(2):67-74.1. Leonard BE et al. J Psychopharmacol. 2012;26(5 Suppl):33-41; 2. Pillinger T et al. Mol Psychiatry. 2019;24(6):776-794; 3. Fernandez-Egea E et al. Br J Psychiatry. 2009;194(5):434-438; 4. Fernandes BS et al. Mol Psychiatry. 2016;21(4):554-564.

↓ Adiponectin

IL-6(TNF)-α

LeptinResistin

LL-37

Elevated pro-inflammatory cytokines have been differentially associated with regional brain volume

alterations, although correlations are inconsistent and further studies are required to clarify these alterations in the context of systemic inflammation in first-episode psychosis2

Adipose tissue also releases pro-inflammatory cytokines (IL-6 and TNFα), which may contribute to insulin resistance,1 and antipsychotic-naive patients with

schizophrenia with higher BMI have been observed to have increased levels of c-reactive protein, a biomarker of

inflammation directly modulated by IL-64


• Prolactin is a polypeptide hormone secreted from the anterior pituitary gland, and it is believed that prolonged elevations in prolactin may be associated with certain health effects, including sexual dysfunction and osteoporosis, as reported in a 2016 study1

• A 2016 meta-analysis of 208 antipsychotic-naive patients, including patients with schizophrenia, reported elevated prolactin levels in male and female patients compared with matched controls1

• Prolactin release may be increased in response to stress and be associated with HPA activity1,2

Elevated Prolactin Levels Have Been Observed in Patients with Schizophrenia

12

HPA=hypothalamic-pituitary-adrenal

1. Gonzalez-Blanco L et al. Schizophr Res. 2016;174(1-3):156-160; 2. Pillinger T et al. Mol Psychiatry. 2018;24(6):776-794.

Hyperprolactinemia is associated with1:• Amenorrhea• Galactorrhea• Osteoporosis• Low libido• Erectile dysfunction• Breast cancer

Prolactin


Schizophrenia: Pathophysiology


The Pathophysiology of Schizophrenia May Involve Dysfunction Across Several Neurotransmitter Systems

GABA=γ-amino-butyric acid.

1. Brisch R et al. Front Psychiatry. 2014;5:47; 2. Toda M et al. Curr Psychiatry Rep. 2007;9(4):329-336; 3. Yang AC et al. Int J Mol Sci. 2017;18(8); 4. Balu DT. Adv Pharmacol. 2016;76:351-382.

Dopamine

Serotonin

Acetylcholine

GABA

Glutamate

Dopamine hyperactivityin the mesolimbicregions of the brain

14

Dopamine hypoactivity in the prefrontal cortex

Dopamine hypothesis of schizophrenia1,2:

Dysregulated glutamatergic neurotransmission

Negative symptoms & cognitive impairment

N-methyl-d-aspartate (NMDA) hypothesis of schizophrenia3,4:

Symptoms of schizophrenia


Dopaminergic Brain Circuits May Be Associated with Many Functions

15

Brisch R et al. Front Psychiatry. 2014;5:47; Toda M et al. Curr Psychiatry Rep. 2007;9(4):329-336; Stahl SM. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge University Press; 2013.

Ventral Tegmental Area Substantia Nigra

Prefrontal Cortex

Dorsal Striatum

Ventral Striatum

Mesocortical Pathway

Nigrostriatal Pathway

Brainstem Dopaminergic Neurons

Striatum

“reward circuitry”

“Regulation of emotion/affect”“Cognition and executive function”

“motor control”

Mesolimbic Pathway


Positive Symptoms That Define Schizophrenia May Be Associated with Mesolimbic Dopaminergic Dysregulation

16

1. Brisch R et al. Front Psychiatry. 2014;5:47; 2. Toda M et al. Curr Psychiatry Rep. 2007;9(4):329-336; 3. Stahl SM. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge University Press; 2013.

Ventral Tegmental Area

Ventral Striatum

Hyperactivity of dopamine transmission at D2 receptors is hypothesized to contribute to the positive symptoms of schizophrenia1,2

Positive Symptoms

• Delusions

• Hallucinations

Hyperactivation

D2 Receptors


Cognitive Symptoms of Schizophrenia May Be Associated with Mesocortical Dopaminergic Dysregulation

17

1. Toda M et al. Curr Psychiatry Rep. 2007;9(4):329-336; 2. Stahl SM. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge University Press; 2013.

Cognitive symptoms associated with schizophrenia may be due to the hypofunction of dopamine D1 receptor neurotransmission in the prefrontal cortex

Cognitive Symptoms

• Declarative memory

• Verbal & working memory

• Executive functions

• Deficits in attention


Prefrontal Cortex

Hypoactivation

D1 Receptors


Negative Symptoms of Schizophrenia May Be Associated with Mesocortical Dopaminergic Dysregulation

18

1. Brisch R et al. Front Psychiatry. 2014;5:47; 2. Toda M et al. Curr Psychiatry Rep. 2007;9(4):329-336; 3. Stahl SM. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge University Press; 2013.

The negative symptoms of schizophrenia include anhedonia and lack of motivation, and may be associated with reduced dopaminergic signaling in the prefrontal cortex1,2

Negative Symptoms

• Alogia

• Avolition, apathy

• Anhedonia

• Flat affect


Prefrontal Cortex

Hypoactivation

D1 Receptors


Mesolimbic Reward System Dysconnectivity May Relate to Reward Deficits in Patients with Schizophrenia

19

*This is a graphic figure adapted from Sharma A et al. Am J Psychiatry. 2017;174(7):657-666.BAS=behavioral activation scale; DMN=default mode network; NAc=nucleus accumbens.

1. Sharma A et al. Am J Psychiatry. 2017;174(7):657-666.

In a connectome-wide analysis involving 225 patients, including 51 patients with schizophrenia, reward deficits were associated with dysconnectivity between the ventral striatum and major functional areas1

Greater anhedonia

BAS Reward

Between NAc-DMN

Ventral Striatum Connectivity

9 12 15 18

1.0

0.5

0.0

-0.5

-1.0

Co

nn

ec

tivit

y (

z[r]

)

Weaker connectivity*

Default Mode Network

Ventral Striatum


Schizophrenia: Behavioral Risk Factors and Common Physical Comorbidities in Patients


Dopamine Reward Circuit Dysregulation is Hypothesized to Be Associated with Comorbid Substance Use in Patients with Schizophrenia

21

Khokhar JY et al. Schizophr Res. 2018;194:78-85.

Genetic risk or an early environmental insult may lead to a dysfunctional mesocorticolimbic brain reward circuit

Mesocorticolimbic dopamine reward circuit dysregulation is hypothesized to contribute to vulnerability to both the initiation and continued use of substances in patients with schizophrenia; this content is theoretical and more research

is needed before the co-occurrence of schizophrenia and substance use disorder can be understood

Initiation/continued substance useOnset of schizophrenia

Greater risk of substance use in pre-psychotic individuals


In a 2006 review of records from the Veterans Integrated Service Network, patients with

schizophrenia and co-occurring substance use disorder had ≈8x greater odds of hepatitis C infection compared with controls1

Studies Have Reported Greater Odds or Risk of Infectious Diseases in Patients with Schizophrenia with Co-Occurring Substance Use

22

1. Huckans MS et al. Psychiatr Serv. 2006;57(3):403-406; 2. Helleberg M et al. Lancet HIV. 2015;2(8):e344-350.

In a 2015 review of nationwide records in Denmark, patients with schizophrenia and co-

occurring substance use disorder had ≈1.8x greater risk of HIV infection compared

with the general population2


There are many hypotheses for the higher prevalence of smoking in patients with schizophrenia, including theories of increased negative symptomatology, deficits in reward

processing, and alterations in reward-related brain circuitry3

6xOdds

Tobacco Use Is More Common in Patients with Schizophrenia

23

In a 2014 study, smokers with schizophrenia had greater cigarette cravings in anticipation of relief of negative affect during abstinence than controls2*

The estimated odds for tobacco use among patients with first-episode schizophrenia compared to age-

and gender-matched controls1 Time after abstinence

Cra

vin

g i

n a

nti

cip

ati

on

of

relie

f o

f n

eg

ati

ve

aff

ec

t

*Cigarette cravings were assessed using the 10-item Questionnaire on Smoking Urges-brief form (QSU); this is an illustrative graphic adapted from the QSU F2.

1. Myles N et al. J Clin Psychiatry. 2012;73(4):468-475; 2. Tidey JW et al. Nicotine Tob Res. 2014;16(3):326-334; 3. Lucatch AM et al. Front Psychiatry. 2018;9:672.

0 6 24 30 48 54 72

4.0

3.0

2.0

1.0

P<0.0001

Control SmokersSchizophrenia Smokers


Higher Odds of Respiratory Diseases Have Been Observed in Patients With Schizophrenia

24

Sokal J et al. J Nerv Ment Dis. 2004;192(6):421-427.

A 2004 survey study reported greater odds of respiratory diseases in patients with schizophrenia compared with the general population

Emphysema Asthma Chronic Bronchitis

≈3.7x

The odds for asthma, chronic bronchitis, and emphysema were approximately 2.2, 3.1, and 7.2 times greater, respectively, when controlling for tobacco smoking

≈2.4x ≈9.1x


Dopamine Signaling is Hypothesized to Be Related to Altered Reward Anticipation and Dysregulated Energy Allocation in Patients with Schizophrenia

25

Grimm O et al. Neurosci Biobehav Rev. 2017;75:91-103.

• Decreased striatal dopamine signaling may be associated with reduced sensitivity to natural rewards and lead to compensatory, compulsive eating in both obesity and schizophrenia

• Striatal dopaminergic dysregulation may be related to weight gain and obesity in schizophrenia, but our understanding is limited

• Low dopamine levels associated with schizophrenia may also result in dysregulated energy allocation

This content is theoretical and more research is needed to confirm this hypothesis


There May Be Several Factors Related to Increased Cardiovascular Disease in Patients with Schizophrenia

Cardiovascular Disease

26

Unhealthy lifestyle• Poor diet• Sedentary behavior• SmokingLess access to healthcare and cardiovascular risk screening

Increased likelihood of risk factors, including:• Diabetes• Hypertension• Dyslipidemia• Obesity

Metabolic Risk Factors Lifestyle and EnvironmentLifestyle and Environment

De Hert M et al. Eur Psychiatry. 2009;24(6):412-424; Ringen PA et al. Front Psychiatry. 2014;5:137.


Bipolar Disorder: Potential Dysfunction Across Multiple Systems


Bipolar Disorder May Involve Dysfunction Across Several Systems

28

CRP=C-reactive proteinFigure adapted from: Pillinger T et al. Mol Psychiatry. 2018;24(6):776-794.

1. Muneer A. Chonnam Med J. 2016;52(1):18-37; 2. Regenold WT et al. J Affect Disord. 2002;70(1):19-26; 3. Girshkin L et al. Psychoneuroendocrinology. 2014;49:187-206; 4. Uyanik V et al. Psychiatry Res. 2015;228(3):386-392.

Immune Disturbance1,4

↑ Pro-inflammatory cytokines↑ CRP

Endocrine Disturbance1,3

↑ Cortisol

Metabolic Disturbance1,2

• Insulin dysregulation


Increased Prevalence of Type 2 Diabetes and Greater BMI Have Been Observed in Patients with Bipolar Disorder

29

1. Regenold WT et al. J Affect Disord. 2002;70(1):19-26; 2. Maina G et al. J Affect Disord. 2008;110(1-2):149-155.

In a 2002 study, increased prevalence of type 2 diabetes was observed in patients

with bipolar I disorder compared with national norms, independent of

psychotropic medication1

In a 2008 study, greater weight and BMI were

observed in drug-naive patients with bipolar disorder

compared with controls2

There is a need for prospective observational studies to further evaluate these observations


Elevated Pro-Inflammatory Cytokines Have Been Observed in Patients with Bipolar Disorder

30

IL-6=interleukin 6; IL-4=interleukin 4; IFN-γ=interferon gamma; IL-10=interleukin 10.

Uyanik V et al. Psychiatry Res. 2015;228(3):386-392.

In a 2015 study of 30 patients with bipolar disorder before and after treatment with an antipsychotic and mood stabilizer, inflammatory cytokine ratios were elevated compared with healthy controls

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

IL-6/IL-4 TNF-α/IL-4 IFN-γ/IL-4 IFN-γ/IL-10

Cyto

kin

e r

ati

os

Control Group (n=28)Patients with Bipolar Disorder (Before Treatment; n=30)Patients with Bipolar Disorder (After Treatment; n=30)

P<0.0001

P<0.0001

P<0.0001 P=0.013

P=0.001

P<0.0001 P=0.0007

P<0.0001

P<0.0001

P=0.0007


• Cortisol, a glucocorticoid product of the HPA axis, may be elevated following increased adrenocorticotropic hormone (ACTH) secretion in patients with bipolar disorder, as reported in a 2014 review1

• Although the role of abnormal HPA axis activity in bipolar disorder pathophysiology is unclear, associations between HPA axis activity and neural-structural alterations have been observed in drug-free patients2

• Elevated cortisol was reported in meta-analyses of drug-free and medicated patients with bipolar disorder2,3

Elevated Activity in the HPA Axis Has Been Observed in Patients with Bipolar Disorder

31

1. Maletic V et al. Front Psychiatry. 2014;5:98; 2. Belvederi M et al. Psychoneuroendocrinology. 2016;63:327-342; 3. Girshkin L et al. Psychoneuroendocrinology. 2014;49:187-206.

ACTH Cortisol


Bipolar Disorder: Pathophysiology, Behavioral Risk Factors, and Common Physical Comorbidities


Dopamine and Glutamate May Be Disrupted in Bipolar Disorder

33

1. Whitton AE et al. Curr Opin Psychiatry. 2015;28(1):7-12; 2. Ashok AH et al. Mol Psychiatry. 2017;22(5):666-679; 3. Gigante AD et al. Bipolar Disord. 2012;14(5):478-487.

Abnormalities in dopamine and glutamate signaling have been found across states of bipolar disorder1,2

Mania/Depression

Dopamine

The effects of dopamine may be mediated by glutamatergic signals in the prefrontal cortex1,3

This content is theoretical and more research is needed to confirm this hypothesis for bipolar disorder

The dopamine hypothesis of bipolar disorder suggests

hyperdopaminergia/ hypodopaminergia during mania versus depression,

respectively2

Glutamate


Dopamine Dysregulation May Be Associated with the Manic Features of Bipolar Disorder

34

1. Whitton AE et al. Curr Opin Psychiatry. 2015;28(1):7-12; 2. Ashok AH et al. Mol Psychiatry. 2017;22(5):666-679.

Substantia Nigra

Prefrontal Cortex

Dorsal Striatum

Mesocortical Pathway

Nigrostriatal Pathway

Evidence from pharmacologic and imaging studies suggest a hyperactive dopaminergic network underlies mania in bipolar disorder1,2

Ventral Striatum

Mesolimbic Pathway


This content is theoretical and more research is needed to confirm this hypothesis


Increased Odds of Hepatitis C Were Observed in Patients With Both Bipolar Disorder and Substance Use Disorder

35

Matthews AM et al. Bipolar Disord. 2008;10(2):266-270.

greater risk

≈1.3x

greater risk

A 2008 study suggested patients with bipolar disorder, substance use disorder, or co-occurring disorders had greater rates of hepatitis C infection compared with controls

Dual Diagnosis of Bipolar Disorder and Substance Use Disorder

N=4724

Substance Use Disorder OnlyN=37,970

Bipolar Disorder OnlyN=5026

greater risk

≈5.5x ≈4.9x

ControlsN=277,690


Higher Odds of Respiratory Diseases Have Been Observed in Patients With Bipolar Disorder

36

Sokal J et al. J Nerv Ment Dis. 2004;192(6):421-427.

A 2004 survey study reported greater odds of respiratory diseases in patients with bipolar disorder compared to the general population

Emphysema Asthma Chronic Bronchitis

≈4.6x

≈2.6x ≈4.2x

The odds for asthma, chronic bronchitis, and emphysema were approximately 2.5, 4.2, and 3.6 times greater, respectively, when controlling for tobacco smoking


≈2.5x

Greater odds of stroke compared with controls

Greater odds of hypertension compared with controls

≈1.5x

Patients with Bipolar Disorder Experienced Increased Odds for Cardiovascular Comorbidities

37

Bahorik AL et al. J Psychosom Res. 2017;100:35-45.

A 2017 electronic health records data analysis identified patients with bipolar disorder had >1.5 times the odds for cardiovascular comorbidities compared with controls


Opportunities for Mental Health Providers to Manage the Whole Patient


There Are Several Strategies for Improving Care for Patients with SMI

39

1. Mangurian C et al. J Gen Intern Med. 2016;31(9):1083-1091; 2. American Diabetes Association (ADA); American Psychiatric Association (APA), American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Diabetes Care. 2004;27:596-601.

Promoting integration of care1

Sharing electronic health records between physical and

mental health care systems1

Regular monitoring2

Referral to specialized services2

Enhancing tobacco smokingcessation efforts1


The APA practice guideline for schizophrenia suggests patients with SMI, and schizophrenia in particular, may more frequently experience a variety of health conditions and should discuss

relevant physical and laboratory assessments that may be needed with their physician as part of initial evaluation and follow up assessment

These health conditions include, but are not limited to:

The 2020 APA Guidelines Recommend Evaluation for and Ongoing Monitoring of Physical Conditions

40

American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia (Dec 2019). https://www.psychiatry.org/File%20Library/Psychiatrists/Practice/Clinical%20Practice%20Guidelines/APA-Draft-Schizophrenia-Treatment-Guideline-Dec2019.pdf. Accessed January 14, 2020.

Dental Chart

Cardiovascular Disease

Poor Oral Health

Sleep ApneaHepatitis C HIV infection

Obesity Metabolic Syndrome

Diabetes Mellitus

Cancer

The APA published these guidelines with a statement that they are undergoing copyediting and that the final version is expected to be released summer 2020


Summary• The pathophysiology of bipolar disorder or schizophrenia may include dysfunction

across several neurotransmitter systems1-5

• Dysfunction and comorbidities across several non-CNS systems have also been observed6-10

• There is an opportunity to improve whole patient care through comprehensive management of comorbidities and behavioral risk factors that may be present in patients living with bipolar disorder or schizophrenia11,12

41

1. Brisch R et al. Front Psychiatry. 2014;5:47; 2. Toda M et al. Curr Psychiatry Rep. 2007;9(4):329-336; 3. Yang AC et al. Int J Mol Sci. 2017;18(8); 4. Whitton AE et al. Curr Opin Psychiatry. 2015;28(1):7-12; 5. Ashok AH et al. Mol Psychiatry. 2017;22(5):666-679; 6. Pillinger T et al. Mol Psychiatry. 2018;24(6):776-794; 7. Muneer A. Chonnam Med J. 2016;52(1):18-37; 8. Girshkin L et al. Psychoneuroendocrinology. 2014;49:187-206; 9. Uyanik V et al. Psychiatry Res. 2015;228(3):386-392; 10. Bahorik AL et al. J Psychosom Res. 2017;100:35-45; 11. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia (Dec 2019). https://www.psychiatry.org/File%20Library/Psychiatrists/Practice/Clinical%20Practice%20Guidelines/APA-Draft-Schizophrenia-Treatment-Guideline-Dec2019.pdf. Accessed January 14, 2020; 12. ADA, APA, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Diabetes Care. 2004;27:596-601.

ExamineComorbidities.com 42

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looking at the pathophysiology and comorbidities ...€¦ · context of systemic inflammation in...

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