The Dark Side of Depression

What effect can Depression have on a person's body? How does a person's Psyche influence or induce inflammation? 

The detailed history and examination findings of the patient can be found here - (Courtesy- Dr. Vaishnavi Adepu ma'am)

Some additional history that was collected from the patient over the phone: 
 

-Her childhood was uneventful. The conditions at home, her relationship with her parents were satisfactory.
- She got married 27 years ago. 
- In the beginning of her marriage, she used to live with her husband, her mother-in-law, father-in-law and brother-in-law. 
- For the first 4-5 years, her in-laws would physically hit and scold her frequently. She said that her husband would hit her when he got drunk, upon being asked to do so by his parents. 
- In 2009, She attempted suicide by drinking poison. She was very upset after having fought with her in-laws (mother-in-law, father-in-law and brother-in-law). 
-Following which she was immediately admitted to Cure Hospital in Khammam. She stayed in the hospital for 2 months while receiving treatment. She was kept on the ventilator for 18 days during her stay. 
- They moved out and separated from her in-laws in 2009. 
- She hasn't had any major health problem since then, until 2017.
- Her eldest son, 25, has been staying away from home since 2002 (2nd class), he has recently completed his MTech. 
- She had a daughter who was born in 1993 and passed away within a 1 month after her birth for unknown reasons.
- The patient used to work as an agricultural labourer 3 years ago, then she quit because of joint pains. 
- Her youngest son, was born in the year 1999 and passed away at the age of 21, 6 months ago. He was blind since birth and was said to have had a genetic condition (as a result of consanguineous marriage between the parents). In 2017, He developed edema all over his body, following which he had multiorgan failure (especially  renal failure and liver failure), followed by his demise in NIMS. 
- His father seldom used to hit him when he was younger. 
- She visited a Psychiatrist on 18/3/2020 with the complaints of multiple body pains, disturbed sleep, reduced appetite, auditory hallucinations (elementary voices - which she still hears). She was diagnosed with severe depression and anxiety without psychosis, the stressor being the death of her son. And possible Schizophrenia?
- She was prescribed the following medications for 1 week :
  • TAB. ESCITALOPRAM 5MG- BD
  • TAB. DULOXETINE 20MG - TID
  • TAB. CLOZAPINE 50MG - TID
  • TAB. RISPERIDONE 1MG - BD
  • TAB. BENOL 50MG - OD


- Following the death of her son 6 months ago, her symptoms aggravated. 
- First, Knee Pains, then headache and depression followed by the recent cerebrovascular accident 2 months ago. 
-She was admitted in the hospital for 1 week and was put on Dual Antiplatelets, Statins. Physiotherapy was done. 
- She was diagnosed with Hypothyroidism during routine investigations when she was admitted for CVA. She takes TAB. THYRONORM 25mg OD. 
- Then, on 17/5/2020, she presented to our hospital with chief complaints of Vertigo, Diplopia, Weakness of the Right Upper and Lower Limbs as already described by Dr. Vaishnavi in her blog. 
- She reported having no financial or socioeconomic problems. 

Some additional investigations which need to be ordered are:
- Lumbar Puncture for CSF analysis including culture and microscopy (to rule out bacterial, fungal or viral infections leading to CNS vasculitis) 
- Fundus Examination (to rule out Papilloedema) 

The major problems that she is currently facing that need our attention are:
1) Depression (Major Depressive Disorder) 
2) Intermittent Headaches (possibly Tension headaches which are linked to Depression) 
3) Hypothyroidism (TSH is elevated) 
4) Large joint pains - knees and elbows
5) Progressive weakness of Right Upper Limb and Lower limb, pyramidal tracts and cerebellum, left UMN type of facial nerve paresis, Right 3rd and 6th cranial nerve paresis (As a result of Stroke and/or a CNS inflammatory disease)

Before we dive deeper into the Anatomical Location, Etiology, Diagnostics and Therapeutics of each of her problems, the following are some important questions and possible hypotheses that enter our mind:

1. How is Depression (MDD) diagnosed?
  • The DSM-IV criteria for MDD require the presence of five or more of the following symptoms during the same 2-week period accompanied by functional impairment:
  •  (i) insomnia or hypersomnia
  •  (ii) loss of interest or pleasure (anhedonia)
  • (iii) feelings of worthlessness or inappropriate/excessive guilt
  • (iv) fatigue or loss of energy
  • (v) depressed mood
  • (vi) diminished ability to think or concentrate, or indecisiveness
  •  (vii) significant weight loss when not dieting or weight gain, or decrease or increase in appetite
  •  (viii) psychomotor agitation or retardation
  •  (ix) recurrent thoughts of death or suicide. 
  • In order to meet criteria for Major Depression, at least one of the five or more symptoms that are present must either be depressed mood or loss of interest/pleasure.
  •  A frequently used mnemonic can be employed to remember these criteria: SIGEMCAPS (Sleep, Interest, Guilt, Energy, Mood, Concentration, Appetite, Psychomotor agitation or retardation, Suicidal ideation). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181849/
2. Can Depression lead to Stroke? 
Can use of Anti-depressant medication cause Stroke? 
  • In a Cohort Study, "Prevalent depression and antidepressant use were associated with increased mortality hazard, but not the interaction between them. Depression and antidepressants were associated with an increased risk of cardiovascular events, but the interaction term was associated with decreased risk" https://pubmed.ncbi.nlm.nih.gov/31561821/
3. Is this patient at a higher risk for developing Post-Stroke Depression? 
  • "A history of mental illness was the highest ranking modifiable risk factor; other risk factors for PSD were female gender, age (<70 years), neuroticism, family history, severity of stroke, and level of handicap. Social support was a protective factor for PSD." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504146/
4. Are we treating this patient's existing (or current) Depression? If not, don't you think we should? 
5. What are the non-pharmacological treatments for Post-Stroke Depression? 
  • Cognitive Behavioral Therapy (CBT) : The Efficacy of CBT- "CBT has a medium effect size (d = .67) relative to a variety of control conditions ranging from the absence of treatment to non-specific controls." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933381/
  • Ecosystem focused therapy 
  • Life review therapy 
  • Problem Solving Therapy
  • Meridian Acupressure 
  • Repetitive Transcranial Magnetic Stimulation 
  • Music Therapy
  • Exercise 
  • Light Therapy 
  • Motivational interviewing 
  • Robotic-assisted neurohabilitation

6. Is it a CNS Inflammatory condition or vascular disease or Stroke? How can we tell? 
7. Why was her CRP raised? 
  • CRP was found to be elevated in up to 75% of patients with ischemic stroke. "Increase in CRP may reflect a systemic inflammatory response following ischemic stroke, the extent of tissue injury, or concurrent infections." https://pubmed.ncbi.nlm.nih.gov/19609738/
8. Is there a possible link between the headaches and Stroke? 
9. Is there a possible link between large joint pains and Stroke? Or the medication used for large joint pains(NSAIDS) causing Stroke? 
10. What are the drugs that increase the risk for stroke?


HYPOTHESIS 1:
Could her Hypothyroidism have caused her Depression, Headaches, Large Joint Pains and eventually lead to Stroke which may have caused the CNS manifestations? 

HYPOTHESIS 2:
Large joint pains may have occurred first, probably osteoarthritis? (raised CRP?) which may have lead to CNS inflammation or CNS autoimmune vasculitis or Stroke. Depression is a separate entity in this scenario. 

Unless, 

HYPOTHESIS 3:
Is CRP raised in Depression? Can Depression cause a rise in CRP? 
Could the raised CRP caused the inflammation of large joints and eventually lead to CNS inflammation or Stroke? 

This can give us an overall outlook of the patient as a whole, giving us a clue into the etiology / root cause, which will in turn allow us to help her in the longer run, instead of viewing each of her problems as separate 
entities. 

Now, as for her CNS condition: Right sided Hemiparesis with left UMN type of Facial paresis, Right 3rd and 6th cranial nerve paresis and Cerebellar involvement

ANATOMICAL LOCALISATION : Midbrain, Pons and Medulla, Bilateral Middle cerebellar peduncles and hemispheres, Bilateral temporal lobes, thalami, basal ganglia and left optic tract, left lentiform nucleus and central aspect of the cervical cord.

ETIOLOGICAL LOCALISATION : As mentioned in the above possible hypotheses.

PATHOLOGY : Inflammation (Raised CRP)

DIAGNOSIS: Stroke? Inflammatory disease of the CNS? CNS vasculitis?

TREATMENT:
-The patient has improved symptomatically upon administration of IV Methylprednisolone. Her power improved in her right upper limb and lower limb from 2/5 to 4/5 over 2-3 days. 

- Most of the treatments for treating Inflammation are centred around Immunesuppression (Corticosteroids,etc) which is a rather symptomatic approach. But how do we tackle the root cause?

Though medical science is not yet advanced enough, 

- How do we develop new/novel drugs or therapies to prevent or treat the root cause?

- Is genetic engineering/eugenics an option?

CITATIONS:

1. Almeida OP, Ford AH, Hankey GJ, Golledge J, Yeap BB, Flicker L. Depression, antidepressants and the risk of cardiovascular events and death in older men. Maturitas. 2019;128:4‐9. doi:10.1016/j.maturitas.2019.06.009

2. Hadidi NN, Huna Wagner RL, Lindquist R. Nonpharmacological Treatments for Post-Stroke Depression: An Integrative Review of the Literature. Res Gerontol Nurs. 2017;10(4):182‐195. doi:10.3928/19404921-20170524-02

3. Shi Y, Yang D, Zeng Y, Wu W. Risk Factors for Post-stroke Depression: A Meta-analysis. Front Aging Neurosci. 2017;9:218. Published 2017 Jul 11. doi:10.3389/fnagi.2017.00218

4. den Hertog HM, van Rossum JA, van der Worp HB, et al. C-reactive protein in the very early phase of acute ischemic stroke: association with poor outcome and death. J Neurol. 2009;256(12):2003‐2008. doi:10.1007/s00415-009-5228-x


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