3.9.7 Major depressive disorders
Major Depressive Disorders
Major depressive disorders (MDD) are managed and treated inadequately for a large proportion due to a lack of clear neurobiological research. Depression has a significant neurobiological consequence involving both structural, functional and molecular level alterations to multiple areas of the brain (Nestler, 2002).
Milder cases of ‘depression’ are classified as “dysthymia,” although there is no clear distinction between the two.
One in six people will experience MDD at some point in their lifetime, with women experiencing it nearly twice as frequently as men. MDD has a complex aetiology with a heritability of about 35%, according to estimates. Environmental variables such as childhood sexual, physical, or emotional abuse are very closely linked to the likelihood of having MDD. All facets of the disease cannot be explained by any known single mechanism.
DSM vs ICD
The criteria for the diagnosis of Major Depressive Disorder (MDD) in the DSM-5 and ICD-11 are similar but have some differences.
The DSM-5 criteria for MDD require the presence of at least five symptoms of depression, including at least one of the following two core symptoms: depressed mood or loss of interest or pleasure. The additional symptoms can include changes in appetite and weight, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or excessive guilt, diminished ability to think or concentrate, or recurrent thoughts of death or suicide. The symptoms must be persistent (nearly every day) for at least two weeks and cause significant distress or impairment in functioning to be considered MDD (American Psychiatric Association, 2013).
The ICD-11 criteria for MDD require the presence of at least two core symptoms of depression, including either low mood or loss of interest or pleasure, and at least two additional symptoms, including changes in appetite or weight, sleep disturbance, psychomotor agitation or retardation, fatigue or loss of energy, feelings of guilt or worthlessness, diminished ability to think or concentrate, or recurrent thoughts of death or suicide. The symptoms must persist for at least two weeks and cause significant distress or functional impairment to be considered MDD (World Health Organization, 2019).
The main difference between the DSM-5 and ICD-11 criteria is the number of symptoms required for diagnosis. The DSM-5 requires the presence of at least five symptoms, while the ICD-11 requires the presence of at least two core symptoms and two additional symptoms.
A comparison of the DSM-5 and ICD-11 criteria for Major Depressive Disorder is presented in the table below:
| DSM-5 Criteria for Major Depressive Disorder: | ICD-11 Criteria for Major Depressive Disorder: |
|---|---|
| At least five symptoms of depression | At least two core symptoms of depression and two additional symptoms |
| At least one of the two core symptoms: depressed mood or loss of interest or pleasure | Either low mood or loss of interest or pleasure as a core symptom |
| Changes in appetite and weight | Changes in appetite or weight |
| Insomnia or hypersomnia | Sleep disturbance |
| Psychomotor agitation or retardation | Psychomotor agitation or retardation |
| Fatigue or loss of energy | Fatigue or loss of energy |
| Feelings of worthlessness or excessive guilt | Feelings of guilt or worthlessness |
| Diminished ability to think or concentrate | Diminished ability to think or concentrate |
| Recurrent thoughts of death or suicide | Recurrent thoughts of death or suicide |
| Symptoms must be persistent (nearly every day) for at least two weeks | Symptoms must persist for at least two weeks |
| Significant distress or impairment in functioning | Significant distress or functional impairment |
White Matter Hyperintensities
There is a strong association between mood disorders and the number/severity of focal signal hyperintensities on MRI T2-weighted images. White matter hyperintensities occur in the deep subcortical white matter, basal ganglia and periventricular tissue. They are seen in both bipolar and unipolar mood disorders. White matter hyperintensities confer a poor prognosis in both MDD and bipolar disorder.
Pathophysiology of Depression
A unified theory of depression conceptualises MDD as a complex matrix of genetic, epigenetic, and environmental factors that are interwoven with personality vulnerabilities that predispose an individual to process biases, belief formation, and stress reactivity that precipitates pathophysiological mechanisms across multiple levels of our biology: molecular, cellular, and behavioural levels (Beck and Bredemeier, 2016).
However, MDD is related to functional abnormalities in certain brain circuits, including the affective-salience network and the cognitive control network, as well as changes in regional brain sizes, particularly the hippocampus. Additionally, MDD is characterised by abnormalities in the primary neurobiological stress-responsive systems, such as the immune system and the hypothalamic-pituitary-adrenal axis. Psychotherapy and drug therapy make up the majority of management. The treatment having the strongest empirical support for patients who are treatment-resistant and who have not improved after multiple augmentations or combination treatment efforts is electroconvulsive therapy.
Monoamine hypothesis:
The monoamine hypothesis of depression has guided the pharmaceutical industry to the development of multiple antidepressants. Given the suboptimal efficacy of SSRIs and their delayed onset of efficacy, a reasonable conclusion to make is that serotonin deficiency alone is too simplistic (Racagni, 2008).
Stahl’s Essential Psychopharmacology states “there is no clear and convincing evidence that monoamine deficiency accounts for depression (Stahl, 2013).
Dysregulation of the hippocampus and the hypothalamic-pituitary-adrenal axis:
The brain reacts to acute/chronic stress by activation of the hypothalamic-pituitary-adrenal (HPA) axis:
(Maletic, 2007)
Neurotransmitters in MDD recovery:
Selective serotonin reuptake inhibitors and norepinephrine reuptake inhibitors increased their respective monoamine levels supposedly in the brain. These monoamine reuptake inhibitors indirectly lead to an increase in brain-derived neurotrophic factor synthesis, enhanced growth hormone sensitivity and reduced cytokine signalling. This is thought to be one mechanism that produces the therapeutic response seen in these antidepressants (Duman, 1997).
References:
(1) (APA) American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.
(2) Beck, A.T. and Bredemeier, K. (2016). A Unified Model of Depression. Clinical Psychological Science, 4(4), pp.596–619. doi:10.1177/2167702616628523.
(3) Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry. 1997;54:597–606.
(4) Maletic, V., Robinson, M., Oakes, T., Iyengar, S., Ball, S.G. and Russell, J. (2007). Neurobiology of depression: an integrated view of key findings. International Journal of Clinical Practice, [online] 61(12), pp.2030–2040. doi:10.1111/j.1742-1241.2007.01602.x.
(5) Nestler, E.J., Barrot, M., DiLeone, R.J., Eisch, A.J., Gold, S.J. and Monteggia, L.M. (2002). Neurobiology of Depression. Neuron, [online] 34(1), pp.13–25. doi:10.1016/s0896-6273(02)00653-0.
(6) Stahl, S.M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical application. 4th ed. Cambridge ; New York: Cambridge University Press.
(7) Racagni, G. and Popoli, M. (2008). Cellular and molecular mechanisms in the long-term action of antidepressants. Dialogues in Clinical Neuroscience, [online] 10(4), pp.385–400. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181899/.
(8) World Health Organization. (2019). International Classification of Diseases, 11th Revision (ICD-11). Geneva, Switzerland: World Health Organization.