Brain on Fire Series – Part 1:

Theories of Neurological Disorders including Anxiety, Depression, Parkinson’s etc.

Naturopathic Living | Unionville Markham Naturopath | Dr. Debbie Smrz

by Dr. Debbie Smrz, BSc, ND
Naturopathic Doctor

Serotonin Deficiency Theory of Depression

Psychology 101 has drilled into us that when it came to neurological conditions like anxiety and depression the cause is a neurotransmitter deficiency.  Every text book has a picture such as the one below, showing how nerves bring neurotransmitters such as serotonin (our happy hormone) to the synaptic junction where the neurotransmitter are released and then bind to a receptor causing an action – in this case happiness. So, the theory tells us, depression is a serotonin deficiency.

Picture Credit:

In fact, this theory has spawned a sixteen billion dollar industry.  The first anti-depressant to hit the market were the tricyclic antidepressant and mono-amine oxidase inhibitors (MAOI).  MAOIs were initially a created for fighting tuberculosis, and scientists found a side effect of the medication was improved mood, hence our first anti-depressant were born.  Unfortunately, they came with a slew of side effects causing low compliance. The 1980’s rang in the 2nd generation of anti-depressants, selective serotonin reuptake inhibitors (SSRIs) and the 90’s rang in the 3rd generation; serotonin and norepinephrine reuptake inhibitors – all working on the serotonin receptor, or are they.  As we will learn later in the series, there may be an additional mode of action creating the mood-altering affect of these drugs.

Psychodynamic and Cognitive Theories of Depression

Beck Theory of Depression

During the 1960’s psychodynamic theories dominated psychology and psychiatry. Depression was understood in terms of inwardly directed anger (Freud, 1917), introjection of love object loss, severe super-ego demands (Freud, 1917), excessive narcissistic, oral and/or anal personality need (Chodoff, 1972), loss of self-esteem (Bibring, 1953; Fenichel, 1968), and deprivation in the mother child relationship during the first year (Kleine, 1934).

In 1967 Aaron Beck introduced the Beck Theory of depression, in which he identified 3 mechanism which he believed to be responsible for depression :

1. The cognitive triad (of negative automatic thinking),

2. Negative self schemas and

3. Errors in Logic (i.e. faulty information processing).

He proposed that perpetual negative thoughts eventually become automatic and lead to depression.

Learned Helplessness Theory of Depression

The leaned helplessness theory claims that depression occurs when a person learns that their attempts to escape negative situations make no difference.

Macrophage Theory of Depression (1991)

The Macrophage theory of depression states that activation of macrophages (the immune system) produces cytokines which cause depression symptoms.

When macrophages are activated, they release a number of cytokines, including IL-1, which has been shown to cause depressive symptoms, and when given to volunteers produced the symptoms necessary for diagnosis of Major Depressive disorder.

The marcrophage theory of depression is beginning to get more attention, as we see the growingcorrelation between immune stimulation and mood. Our next article in the series will focus on Sickness Syndrome, explaining mechanically what is happening in your body to cause mood abnormality during sickness and how this may correlate with anxiety and depression.


  1. Curr Pharm Des.2009;15(14):1563-86. monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today.
  2. McLeod, S. A. (2015). Psychological theories of depression. Retrieved from
  3.  The macrophage theory of depression, Smith, R.S.  1991, October.  Medical Hypotheses , Volume 36 , Issue 2 , 178