Comorbidity

Presentation

Comorbidity

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Comorbidity
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Prevalence of chronic conditions in patients with MDD
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References

In this study, data from the 2007 and 2009 releases of the Medical Expenditure Panel Survey (MEPS) were used.[Bhattacharya et al., 2014] The MEPS is a nationally representative annual survey of households representing the US non-institutionalised civilian population.[Bhattacharya et al., 2014] After inclusion/exclusion criteria were applied, including being aged 22–64, not being underweight, and being alive at the end of the study period, a total sample of >33,000 patients was generated.[Bhattacharya et al., 2014] Diagnosis of the various comorbid conditions of interest used the ICD-9-CM and clinical classification codes, provided in the medical care event files.[Bhattacharya et al., 2014]

 

Bhattacharya et al. BMC Psychiatry 2014;14:10

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Prevalence of MDD in patients with chronic conditions
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References

The analysis discussed here concludes that there exists a bidirectional relationship between depression and chronic illnesses.[Voinov et al., 2013] 

Voinov B, Richie WD, Bailey RK. Depression and chronic diseases: it is time for a synergistic mental health and primary care approach. Prim Care Companion CNS Disord 2013; 15 (2): PCC.12r01468.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5™). © American Psychiatric Association, 2013.

Buckley PF, Miller BJ, Lehrer DS, Castle DJ. Psychiatric comorbidities and schizophrenia. Schizophr Bull 2009; 35 (2): 383–402.

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Depression adds to the burden of chronic conditions
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References

The WHO (World Health Organization) World Health Survey studied >240,000 adults, aged ≥18 years, across 60 countries.[Moussavi et al., 2007] 
An average of 9.3–23.0% of participants with one or more chronic physical disease also had comorbid depression.[Moussavi et al., 2007] Individuals with a chronic condition were significantly more likely to suffer depression than those without a chronic condition (p<0.0001).[Moussavi et al., 2007] Furthermore, depression was associated with lower overall health scores than those observed with other chronic conditions, such as asthma, angina, arthritis and diabetes, and the burden of these chronic conditions was increased when patients had co-morbid depression.[Moussavi et al., 2007]

Moussavi S, Chatterji S, Verdes E, et al. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 2007; 370 (9590): 851–858.

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The effect of comorbidities on patients’ quality of life
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References

The various comorbidities of MDD (psychiatric and physical) adversely affect the quality of life of the patient.[IsHak et al., 2014; IsHak et al., 2018; Zhou et al., 2017] This emphasises the point that attending physicians need to be alive to the potential of the various comorbidities when treating any patient with MDD.[APA, 2010] Timely, and appropriate intervention is needed.[APA, 2010] 
Treatment guidelines for MDD drawn up by the American Psychiatric Association make clear that the psychiatric and physical comorbidities of MDD need to be taken into account when considering treatment options.[APA, 2010] For example, when considering a patient with comorbid hypertension, antidepressant treatments linked to increases in blood pressure should be ruled out; in patients with co-occurring substance-use disorders, treatments known to interact with substances of abuse should be avoided.[APA, 2010]

American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. 3rd edition. 2010.

IsHak WW, Mirocha J, Christensen S, et al. Patient-reported outcomes of quality of life, functioning, and depressive symptom severity in major depressive disorder comorbid with panic disorder before and after SSRI treatment in the STAR*D trial. Depress Anxiety 2014; 31 (8): 707–716.

IsHak WW, Steiner AJ, Klimowicz A, et al. Major depression comorbid with medical conditions: analysis of quality of life, functioning, and depressive symptom severity. Psychopharmacol Bull 2018; 48 (1): 8–25.

Zhou Y, Cao Z, Yang M, et al. Comorbid generalized anxiety disorder and its association with quality of life in patients with major depressive disorder. Sci Rep 2017; 7: 40511.

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Neuropsychiatric comorbidities
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Psychiatric comorbidities of MDD
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References

The study by Thaipisuttikul and colleagues was a cross-sectional study, conducted between October 2012 and January 2014.[Thaipisuttikul et al., 2014] In total, 190 patients with MDD, as confirmed by the Mini International Neuropsychiatric Interview (MINI), were included.[Thaipisuttikul et al., 2014] The study showed that a variety of psychiatric comorbidities were common in patients with MDD, including anxiety and other mood disorders.[Thaipisuttikul et al., 2014] 
To investigate whether MDD represents a transient increase in risk of psychiatric comorbidity, or a more long-term increase, patients with current MDD (current at the time of the study) were compared with those who had a past diagnosis of MDD.[Thaipisuttikul et al., 2014] Compared with patients with past MDD, patients with current MDD had significantly higher levels of comorbid obsessive–compulsive disorder (OCD), psychotic disorder, and panic disorder.[Thaipisuttikul et al., 2014] The various psychiatric conditions investigated in the analysis present differently, and the authors note the typically more chronic nature of OCD; physicians should therefore always look for OCD in patients with MDD, and not hesitate to treat if found.[Thaipisuttikul et al., 2014]

Thaipisuttikul P, Ittasakul P, Waleeprakhon P, et al. Psychiatric comorbidities in patients with major depressive disorder. Neuropsychiatr Dis Treat 2014; 10: 2097–2103. 

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5™). © American Psychiatric Association, 2013.

Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994; 51 (1): 8–19.

Kessler RC. The prevalence of psychiatric comorbidity. In: Wetzler S, Sanderson WC (eds). An Einstein Psychiatry Publication, No. 14. Treatment Strategies for Patients with Psychiatric Comorbidity. John Wiley & Sons Inc. 1997.

Rush AJ, Zimmerman M, Wisniewski SR, et al. Comorbid psychiatric disorders in depressed outpatients: demographic and clinical features. J Affect Disord 2005; 87 (1): 43–55.

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Anxiety
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References

The Patient Health Questionnaire is a self-administered tool of 2 (PHQ-2) or 9 (PHQ-9) items.[Kroenke et al., 2001; Spitzer et al., 1999] The PHQ-9 establishes the clinical diagnosis of depression and can additionally be used to track the severity of symptoms over time.[Kroenke et al., 2001] The boundaries of the PHQ-9 are as follows:[Kroenke et al., 2001]

PHQ-9 score
Provisional diagnosis

  • 1–4: Minimal symptoms
  • 5–9: Mild depression
  • 10–14: Moderate depression
  • 15–19:Moderate to severe depression
  • >20: Severe depression

Generalised anxiety disorder (GAD) is characterised by excessive anxiety and worry, about numerous events or activities.[APA, 2013] Examples include worrying about household chores, or being late for appointments.[APA, 2013] MDD and GAD are frequently comorbid, individuals with MDD may be concerned about being negatively evaluated by others.[APA, 2013; Fava et al., 2008; Fava et al., 2000; Kessler, 1997] The presence of anxiety symptoms in patients with MDD negatively affects response to antidepressant treatment,[Fava et al., 2008] and negatively affects patient quality of life.[Zhou et al., 2017] Generalised anxiety/worry is a common feature of depressive disorders, but should be diagnosed separately if the excessive worry has occurred outside the course of the depressive illness.[APA, 2013]

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5™). © American Psychiatric Association, 2013.

Fava M, Rankin MA, Wright EC, et al. Anxiety disorders in major depression. Compr Psychiatry 2000; 41 (2): 97–102. 

Fava M, Rush AJ, Alpert JE, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 2008; 165 (3): 342–351.

Kessler RC. The prevalence of psychiatric comorbidity. In: Wetzler S, Sanderson WC (eds). An Einstein Psychiatry Publication, No. 14. Treatment Strategies for Patients with Psychiatric Comorbidity. John Wiley & Sons Inc. 1997.

Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16 (9): 606–613.

Spitzer RL, Kroenke K, Williams JBW. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. JAMA 1999; 282 (18): 1737–1744. 

Zhou Y, Cao Z, Yang M, et al. Comorbid generalized anxiety disorder and its association with quality of life in patients with major depressive disorder. Sci Rep 2017; 7: 40511.

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Obsessive–compulsive disorder (OCD)
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References

Obsessive–compulsive disorder (OCD) is associated with reduced quality of life, and functional impairments.[APA, 2013, pg. 240] It is defined as:[APA, 2013, pg. 237]
obsession; recurrent and persistent thoughts, urges, or images, that are experienced as unwanted or intrusive and that in most individuals cause anxiety or distress, which the individual attempts to suppress or neutralise with some other thought or action (e.g., a compulsion)
compulsion; repetitive behaviour that the individual feels driven to perform in response to an obsession, and which is aimed at reducing anxiety or distress, but is not connected in a realistic way with what they are designed to neutralise, or are clearly excessive.
The symptoms of OCD can be separated from the rumination experienced in MDD, because thoughts in the latter are usually mood-congruent and not necessarily experienced as intrusive or distressing, and are not linked to compulsions as is the case for OCD.[APA, 2013, pg. 241]

 

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5™). © American Psychiatric Association, 2013.

Dold M, Bartova L, Souery D, et al. Low comorbid obsessive–compulsive disorder in patients with major depressive disorder – findings from a European multicenter study. J Affect Disord 2018; 227: 254–259.

Kessler RC, Berglund P, Demler O, et al.  Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62 (6): 593–602.

Rickelt J, Viechtbauer W, Lieverse R, et al. The relation between depressive and obsessive–compulsive symptoms in obsessive–compulsive disorder: results from a large, naturalistic follow-up study. J Affect Disord 2016; 203: 241–247.

Thaipisuttikul P, Ittasakul P, Waleeprakhon P, et al. Psychiatric comorbidities in patients with major depressive disorder. Neuropsychiatr Dis Treat 2014; 10: 2097–2103.

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Post-traumatic stress disorder (PTSD)
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References

The essential feature of PTSD is the development of a certain set of symptoms after exposure to a traumatic event; the symptoms include fear-based re-experiencing of the traumatic event, but can also include anhedonia, and dysphoric mood states.[APA, 2013, pg. 274] Therefore, separating the diagnosis from one of major depressive disorder is important. A diagnosis of major depressive disorder should be made if the patient’s low mood was not preceded by a traumatic event, and other symptoms of PTSD are not present – specifically intrusive symptoms relating to memories or flashbacks of, or persistent avoidance of stimuli relating to, the traumatic event.[APA, 2013, pg. 279]

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5™). © American Psychiatric Association, 2013.

Fullerton CS, Ursano RJ, Epstein RS, et al. Peritraumatic dissociation following motor vehicle accidents: relationship to prior trauma and prior major depression. J Nerv Ment Dis 2000; 188 (5): 267–272.

Kessler RC. The prevalence of psychiatric comorbidity. In: Wetzler S, Sanderson WC (eds). An Einstein Psychiatry Publication, No. 14. Treatment Strategies for Patients with Psychiatric Comorbidity. John Wiley & Sons Inc. 1997.

Oquendo M, Brent DA, Birmaher B, et al. Posttraumatic stress disorder comorbid with major depression: factors mediating the association with suicidal behavior. Am J Psychiatry 2005; 162 (3): 560–566.

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Attention deficit hyperactivity disorder (ADHD)
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References

The essential feature of ADHD is a persistent pattern of inattention and/or hyperactivity that interferes with functioning or development.[APA, 2013, pg. 61] For example, wandering off task, or difficulty sustaining focus, and excessive motor activity, or fidgeting, or talkativeness.[APA, 2013, pg. 61] The diagnosis must be separated from that of MDD, because some of the clinical features are shared.[APA, 2013, pg. 64] ADHD is a distinct diagnosis from MDD because, in MDD, the difficulty with concentration is a component of the mood disorder, and becomes prominent during a depressive episode.[APA, 2013, pg. 64]

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5™). © American Psychiatric Association, 2013.

Bron TI, Bijlenga D, Verduijn J, et al. Prevalence of ADHD symptoms across clinical stages of major depressive disorder. J Affect Disord 2016; 197: 29–35.

Fischer AG, Bau CH, Grevet EH, et al. The role of comorbid major depressive disorder in the clinical presentation of adult ADHD. J Psychiatr Res 2007; 41 (12): 991–996.

Katzman MA, Bilkey TS, Chokka PR, et al. Adult ADHD and comorbid disorders: clinical implications of a dimensional approach. BMC Psychiatry 2017; 17: 302.

Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006; 163 (4): 716–723.

McGorry PD, Hickie IB, Yung AR, et al. Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Aust N Z J Psychiatry 2006; 40 (8): 616–622.

Torgersen T, Gjervan B, Rasmussen K. ADHD in adults: a study of clinical characteristics, impairment and comorbidity. Nord J Psychiatry 2006; 60 (1): 38–43.
 

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Schizophrenia
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The essential feature of schizophrenia is the presence of hallucinations, delusions, disorganised speech or behaviour, or of negative symptoms.[APA, 2013, pg. 100]  As noted on the slide, some of the diagnostic criteria for schizophrenia overlap with those for MDD, particularly MDD with psychotic or catatonic features.[APA, 2013]  To distinguish the two, the temporal relationship between the mood disturbance and the psychosis should be considered; if the delusions or hallucinations occur exclusively during a depressive episode, then the diagnosis is MDD with psychotic features (or bipolar with psychotic features, if that diagnosis more accurately reflects the symptoms).[APA, 2013, pg. 104

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5™). © American Psychiatric Association, 2013.

Castle D, Bosanac P. Depression and schizophrenia. Adv Psychiatr Treat 2012; 18: 280–288.

Chiappelli J, Kochunov P, DeRiso K, et al. Testing trait depression as a potential clinical domain in schizophrenia. Schizophr Res 2014; 159 (1): 243–248.

Kessler RC. The prevalence of psychiatric comorbidity. In: Wetzler S, Sanderson WC (eds). An Einstein Psychiatry Publication, No. 14. Treatment Strategies for Patients with Psychiatric Comorbidity. John Wiley & Sons Inc. 1997.

Upthegrove R. Depression in schizophrenia and early psychosis: implications for assessment and treatment. Adv Psychiatr Treat 2009; 15: 372–379.
 

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Substance-use disorder
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References

Substance-use disorders are a group of cognitive, behavioural, and physiological symptoms indicating that the individual continues to use a substance despite problems related to the use of that substance.[APA, 2013, pg. 483] Substances can include alcohol, cannabis, hallucinogens, opioids, sedatives, and tobacco.[APA, 2013, pg. 482] Substance-use disorders are typified by craving for a substance, tolerance, withdrawal symptoms, and continued use of a substance despite negative consequences, amongst other criteria.[APA, 2013, pg. 509]

Depressive disorder can be as a result of another medical condition, or as the result of substance or medication use.[APA, 2013, pg. 180] MDD, however, frequently co-occurs with substance-related disorders.[APA, 2013, pg. 175] A differential diagnosis is made based on whether a substance is aetiologically related to the mood disturbance.[APA, 2013, pg. 171]

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5™). © American Psychiatric Association, 2013.

Davis LL, Frazier E, Husain MM. Substance use disorder comorbidity in major depressive disorder: a confirmatory analysis of the STAR*D cohort. Am J Addict 2006; 15 (4): 278–285. 

Kessler RC. The prevalence of psychiatric comorbidity. In: Wetzler S, Sanderson WC (eds). An Einstein Psychiatry Publication, No. 14. Treatment Strategies for Patients with Psychiatric Comorbidity. John Wiley & Sons Inc. 1997.

Rappeneau V, Bérod A. Reconsidering depression as a risk factor for substance use disorder: insights from rodent models. Neurosci Biobehav Rev 2017; 77: 303–316.

Tolliver BK, Anton RF. Assessment and treatment of mood disorders in the context of substance abuse. Dialogues Clin Neurosci 2015; 17 (2): 181–190.

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Neurological disorders and MDD
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References

See Slide deck #3 of this series – ‘Neurobiology and aetiology’ to read more about the potential shared pathways underlying MDD and other neurological disorders.
Disentangling the various comorbidities of MDD is a herculean challenge, because many conditions are interrelated.[Cha et al., 2014; APA, 2013] For example, depression appears to enhance the risk of developing Alzheimer’s disease, but also of type-2 diabetes.[Cha et al., 2014] However, type-2 diabetes is itself a risk factor for Alzheimer’s disease.[Cha et al., 2014] Investigating the role of depression as a risk factor for Alzheimer’s disease therefore involves attempting to control for the potentially confounding influence of type-2 diabetes. 
It appears that patients with depression are at an increased risk of developing various dementias and Parkinson’s disease.[Gustafsson et al., 2015; Rodrigues et al., 2014; Wilson et al., 2014] In one study of >1,700 older individuals, the presence of depressive symptoms was associated with the rate of cognitive decline observed.[Wilson et al., 2014] However, it is not clear how the presence of depression contributes to cognitive decline.[Wilson et al., 2014]

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5™). © American Psychiatric Association, 2013.

Cha DS, Carvalho AF, Rosenblat JD, et al. Major depressive disorder and type II diabetes mellitus: mechanisms underlying risk for Alzheimer’s disease. CNS Neurol Disord Drug Targets 2014; 13 (10): 1740–1749.

Gustafsson H, Nordström A, Nordström P. Depression and subsequent risk of Parkinson disease: a nationwide cohort study. Neurology 2015; 84 (24): 2422–2429.

Rodrigues R, Petersen RB, Perry G. Parallels between major depressive disorder and Alzheimer’s disease: role of oxidative stress and genetic vulnerability. Cell Mol Neurobiol 2014; 34 (7): 925–949.

Wilson RS, Capuano AW, Boyle PA, et al. Clinical–pathologic study of depressive symptoms and cognitive decline in old age. Neurology 2014; 83 (8): 702–709.

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Alzheimer’s disease (AD) and MDD
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References

Whether or not, and to what extent, depression is a risk factor for, or a constituent part of the prodrome of, dementia, is still a contentious issue.[Cha et al., 2014; Mirza et al., 2014] One study followed >4,300 non-demented individuals for 13.7 years, and tracked the development of dementia and depressive symptoms.[Mirza et al., 2014] Of the total sample, 582 patients developed dementia within the timeframe of the study.[Mirza et al., 2014] Compared to those without depressive symptoms, those with depressive symptoms had an 8% increased risk of developing dementia.[Mirza et al., 2014] However, in order to further interrogate the data, the authors analysed the effect of the time interval between depressive symptoms and dementia onset in their results.[Mirza et al., 2014] The risk of dementia was highest in the short-term following depression, and reduced, according to the length of the time interval, to zero risk beyond ten years.[Mirza et al., 2014] These observations suggest that depression is part of the dementia prodrome, rather than being an independent risk factor.[Mirza et al., 2014] But, as ever, more research is needed to fully elucidate the relationship.

Cha DS, Carvalho AF, Rosenblat JD, et al. Major depressive disorder and type II diabetes mellitus: mechanisms underlying risk for Alzheimer’s disease. CNS Neurol Disord Drug Targets 2014; 13 (10): 1740–1749.

Mirza SS, de Bruijn RFAG, Direk N, et al. Depressive symptoms predict incident dementia during short- but not long-term follow-up period. Alzheimers Dement 2014; 10 (5 Suppl): S323–S329.

Chen R, Hu Z, Wei L, et al.  Severity of depression and risk for subsequent dementia: cohort studies in China and the UK. Br J Psychiatry 2008; 193 (5): 373–377. 

Dal Forno G, Palermo MT, Donohue JE, et al. Depressive symptoms, sex, and risk for Alzheimer’s disease. Ann Neurol 2005; 57 (3): 381–387.

Gibson J, Russ TC, Adams MJ, et al. Assessing the presence of shared genetic architecture between Alzheimer’s disease and major depressive disorder using genome-wide association data. Transl Psychiatry 2017; 7 (4): e1094.

Rodrigues R, Petersen RB, Perry G. Parallels between major depressive disorder and Alzheimer’s disease: role of oxidative stress and genetic vulnerability. Cell Mol Neurobiol 2014; 34 (7): 925–949.
 

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Physical comorbidities
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Physical comorbidities of MDD
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References

This analysis was a naturalistic 12-year follow-up of general hospital admissions, comparing patients with MDD and age-matched controls visiting one of three hospitals in Manchester, UK, between January 2000 and June 2012.[Schoepf et al., 2014] The sample comprised the >360,000 patients admitted in that period, from which the >9,600 patients with depression, and >96,000 age-matched controls were taken.[Schoepf et al., 2014]
A wide range of comorbidities were identified as being more prevalent in patients with MDD compared with the age-matched controls.[Schoepf et al., 2014] Interestingly, incidences of ‘cataract’ and ‘angina’ were shown to have decreased prevalence in the MDD population.[Schoepf et al., 2014] The authors are clear about possible limitations to their study, which include lacking any data about medication usage.[Schoepf et al., 2014] It is possible that some of the associations identified in the study are linked to adverse effects of medications, rather than the depression itself.[Schoepf et al., 2014]

Schoepf D, Uppal H, Potluri R, et al. Comorbidity and its relevance on general hospital based mortality in major depressive disorder: a naturalistic 12-year follow-up in general hospital admissions. J Psychiatr Res 2014; 52: 28–35.

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Diabetes
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References

Whilst the association between depression and diabetes is clearly complex, several meta-analyses have shown an increased risk in patients with MDD compared with the general population.[Vancampfort et al., 2016; Mezuk et al., 2008] It is not clear what pathology underlies this association.[Vancampfort et al., 2016; Mezuk et al., 2008; Kreider, 2017] It has been hypothesised that the dysregulation of the hypothalamic–pituitary–adrenal axis, commonly seen in patients with MDD, could be partly responsible for symptoms of insulin resistance.[Kreider, 2017] More research is needed to clarify the relationship. In the meantime, attending physicians should be aware of the potential comorbidity of type 2 diabetes with depression, and be prepared to diagnose and manage the conditions in tandem.[Kreider, 2017]

Kreider KE. Diabetes distress or major depressive disorder? A practical approach to diagnosing and treating psychological comorbidities of diabetes. Diabetes Ther 2017; 8 (1): 1–7.

Mezuk B, Eaton WW, Albrecht S, Golden SH. Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care 2008; 31 (12): 2383–2390.

Vancampfort D, Correll CU, Galling B, et al. Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta-analysis. World Psychiatry 2016; 15 (2): 166–174.

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Hypertension
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References

Hypertension is a commonly under-diagnosed condition, but it is a serious one; high blood pressure can increase the risk of having a heart attack or a stroke.[BHF] Several analyses have concluded that depression is a risk factor for the development of hypertension.[Patten et al., 2009; Meng et al., 2012; Wu et al., 2012]

British Heart Foundation website. High blood pressure. https://www.bhf.org.uk/heart-health/risk-factors/high-blood-pressure. Accessed April 2018.

Patten SB, Williams JVA, Lavorato DH, et al. Major depression as a risk factor for high blood pressure: epidemiologic evidence from a national longitudinal study. Psychosom Med 2009; 71 (3): 273–279. 

Meng L, Chen D, Yang Y, et al. Depression increases the risk of hypertension incidence: a meta-analysis of prospective cohort studies. J Hypertens 2012; 30 (5): 842–851. 

Wu EL, Chien IC, Lin CH, et al. Increased risk of hypertension in patients with major depressive disorder: a population-based study. J Psychosom Res 2012; 73 (3): 169–174.

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Cardiovascular disease
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References

Cardiovascular disease is an umbrella term that includes coronary heart disease, angina, congenital heart disease, hypertension, stroke, and vascular dementia.[BHF] Multiple analyses have demonstrated an increased risk of cardiovascular disease in patients with depression.[Dhar & Barton, 2016; Gan et al., 2014; Meijer et al., 2011]
 

British Heart Foundation website. Cardiovascular disease. https://www.bhf.org.uk/heart-health/conditions/cardiovascular-disease. Accessed April 2018.

Dhar AK, Barton DA. Depression and the link with cardiovascular disease. Front Psychiatry 2016; 7: 33.

Gan Y, Gong Y, Tong Y, et al. Depression and the risk of coronary heart disease: a meta-analysis of prospective cohort studies. BMC Psychiatry 2014; 14: 371.

Meijer A, Conradi HJ, Bos EH, et al. Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis of 25 years of research. Gen Hosp Psychiatry 2011; 33 (3): 203–216.

Wu EL, Chien IC, Lin CH, et al. Increased risk of hypertension in patients with major depressive disorder: a population-based study. J Psychosom Res 2012; 73 (3): 169–174.

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Cancer
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References

Research into the association between depression and cancer has generated conflicting results, but several lines of evidence point to a small positive association.[Jia et al., 2017; Pinquart & Duberstein, 2010; Satin et al., 2009] One of the difficulties of researching this area is the complication caused by there being many different types of cancer. Research in this field must also be mindful of potentially confounding factors, such as cigarette smoking and alcohol use/abuse, that can contribute to an elevated cancer risk.[Jia et al., 2017]

Jia Y, Li F, Liu YF, et al. Depression and cancer risk: a systematic review and meta-analysis. Public Health 2017; 149: 138–148. 

Pinquart M, Duberstein PR. Depression and cancer mortality: a meta-analysis. Psychol Med 2010; 40 (11): 1797–1810.

Satin JR, Linden W, Phillips MJ. Depression as a predictor of disease progression and mortality in cancer patients: a meta-analysis. Cancer 2009; 115 (22): 5349–5361.

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Summary of the increased risk of comorbidities in patients with MDD
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References

This slide summarises the increased risk that the presence of depressive symptoms confers on an individual for developing a variety of comorbid conditions.

Bron TI, Bijlenga D, Verduijn J, et al. Prevalence of ADHD symptoms across clinical stages of major depressive disorder. J Affect Disord 2016; 197: 29–35.

Cha DS, Carvalho AF, Rosenblat JD, et al. Major depressive disorder and type II diabetes mellitus: mechanisms underlying risk for Alzheimer’s disease. CNS Neurol Disord Drug Targets 2014; 13 (10): 1740–1749.

Chen R, Hu Z, Wei L, et al.  Severity of depression and risk for subsequent dementia: cohort studies in China and the UK. Br J Psychiatry 2008; 193 (5): 373–377. 

Gan Y, Gong Y, Tong Y, et al. Depression and the risk of coronary heart disease: a meta-analysis of prospective cohort studies. BMC Psychiatry 2014; 14: 371.

Jia Y, Li F, Liu YF, et al. Depression and cancer risk: a systematic review and meta-analysis. Public Health 2017; 149: 138–148. 

Kessler RC. The prevalence of psychiatric comorbidity. In: Wetzler S, Sanderson WC (eds). An Einstein Psychiatry Publication, No. 14. Treatment Strategies for Patients with Psychiatric Comorbidity. John Wiley & Sons Inc. 1997.

Mezuk B, Eaton WW, Albrecht S, Golden SH. Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care 2008; 31 (12): 2383–2390.

Rickelt J, Viechtbauer W, Lieverse R, et al. The relation between depressive and obsessive–compulsive symptoms in obsessive–compulsive disorder: results from a large, naturalistic follow-up study. J Affect Disord 2016; 203: 241–247.

Thaipisuttikul P, Ittasakul P, Waleeprakhon P, et al. Psychiatric comorbidities in patients with major depressive disorder. Neuropsychiatr Dis Treat 2014; 10: 2097–2103. 

Wu EL, Chien IC, Lin CH, et al. Increased risk of hypertension in patients with major depressive disorder: a population-based study. J Psychosom Res 2012; 73 (3): 169–174.

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