The role of serotonin on major depressive disorder (MDD) and the ethical barriers that

occur under the Mental Health (Compulsory Assessment and Treatment) Act (1992)

(MHA).

To begin, I will explain the synthesis and reuptake of serotonin. I will also investigate the

effectiveness of antidepressants on different forms of depression; there are a range of

different medications that can improve depressive symptoms. The chronic use of many

antidepressants can increase neurogenesis; this process can improve depressive symptoms

related to mental disorders. A diagnosis of a severe mental disorder can result in a patient

being placed under the MHA. There are many rights and restrictions under Section 11 of the

MHA that will affect Katy. Autonomy and non-maleficence are conflicting ethical concepts

that can be applied to Katy’s case. These ethical concepts will assist in the justification of

intervening in a persons right to die.

The role of serotonin and its effects on the symptoms of major depressive disorder

(MDD).

Serotonin (5-hydroxytryptamine) is derived from tryptophan. Tryptophan uptake occurs

across the blood brain barrier and is transported into terminals, which will then be

synthesised into serotonin (5-HT) by the enzymes, tryptophan hydroxylase and aromatic

amino acid decarboxylase. Serotonin is then transported into vesicles by the monoamine

transporter where it can be used for neurotransmission via the axons, which are part of

neuron. Finally serotonin can be released into the synaptic cleft where it is available for use.

Then the reuptake of serotonin into the cytosol occurs via the serotonin transporter, which

terminates the effects of serotonin. Serotonin removal can also occur by the enzyme

1

monoamine oxidase or aldehyde dehydrogenase. These enzymes metabolise serotonin into 5-

hydroxyindoleacetic acid. The reuptake and oxidisation of serotonin can be blocked by using

antidepressants resulting in a therapeutic effect (Best, Nijhout, & Reed, 2010).

Serotonin is a neurotransmitter in the brain that affects our mood, motivation and

energy levels. The 5-HT theory is based on the belief that altered levels of the brain

neurotransmitters noradrenaline and serotonin are the primary cause of depression. (Albert,

Benkelfat, & Descarries, 2012; Cowen & Sherwood, 2013). There are a range of medications

that increase serotonin, these include, selective serotonin reuptake inhibitors (SSRI’s),

serotonin norepinephrine reuptake inhibitors (SNRI’s) and monoamine oxidase inhibitors

(MAOI’s) (Bullock, Manias, & Galbraith, 2007).

SSRI’s function by inhibiting the reuptake of serotonin on the pre synaptic nerve

ending, resulting in an increased level of serotonin in the synaptic cleft. While SSRI’s can

decrease depression they unfortunately have a number of rare adverse effects including

nausea, somnolence and an increased risk of suicide. If this occurs there are other treatment

options including SNRI’s (Yeragani, Ramachandraih, Subramanyam, Bar, & Baker, 2011).

SNRI’s work by inhibiting serotonin and norepinephrine reuptake in the synapse.

SNRI’s antagonise pre synaptic alpha 2 adrenergic receptors increasing norepinephrine and

serotonin. (Yeragani, Ramachandraih, Subramanyam, Bar, & Baker, 2011).

MAOI’s inhibit MAO enzyme. The purpose of the MAO enzyme is to oxidase amines

such as, serotonin therefore rendering these neurotransmitters ineffective. MAOI’s function

by inhibiting monoamine oxidase, which will stop the oxidation of amines and therefore

increase the amount of serotonin in the synapse, which will result in decreasing depressive

symptoms (Yeragani, Ramachandraih, Subramanyam, Bar, & Baker, 2011; Delgado, 2000).

Assuming the cause of Katy’s depression is an imbalance of serotonin we can then conclude

that antidepressants will reduce her presenting symptoms (Albert & Benkelfat, 2013).

2

Neurogenesis has been proven to increase serotonin and therefore alleviate

depression. Neurogenesis is the process of increasing the number of neurone in the

hippocampus (Warner-Schmidt & Duman, 2006) A study by Malberg, Eisch, Nestler, &

Duman revealed that antidepressants increased neurogenesis, decreased stress induced

atrophy of neurons and prevented decreasing levels of hippocampal neurons (Malberg, Eisch,

Nestler, & Duman, 2000). In depressed patients, the long-term use of antidepressants will

increase hippocampal neurogenesis thus improving depressive symptoms (Alenina &

Klempin, 2015). “In the case of depression, chronic manipulation of serotonin by agents that

inhibit serotonin reuptake, leads to clinical improvement associated with a slow, temporal

increase in adult hippocampal neurogenesis” (Alenina & Klempin, 2015, p. 50).

Neurogenesis is also affected brain derived neurotropic factor (BDNF), which is

found in the brain and periphery. Treatment with antidepressants that increase serotonin can

increase activity levels of BDNF and neuronal plasticity. This is crucial as suicidal thoughts

and attempts can be due to impaired neuronal plasticity in the brain (Lee & Kim, 2010).

Forms of neuroplasticity that are improved due to BDNF include “neurogenesis,

synaptogenesis and neuronal maturation” (Lee & Kim, 2010, p. 1).

Conflicting evidence shows that an increase in serotonin does not improve symptoms

in certain types of depression. Patients with MDD have been observed to respond more

effectively to SSRI’s compared to patients with mild to moderate depression (Fournier et al.,

2010). MDD is a more severe form of depression and it commonly includes suicidal ideation

(Fils, 2010). Treatment with SSRI’s “may be minimal or nonexistent, on average, in patients

with mild or moderate symptoms. For patients with very severe depression, the benefit over

placebo is substantial” (Fournier et al., 2010, p. 47). Given that Katy has been diagnosed

MDD it is likely that an SSRI would be an adequate form of treatment, that would be

expected to improve her presenting symptoms due to the increased amount of available

3

serotonin. This form of treatment may also benefit Katy by increasing neurogenesis thus

decreasing suicidal ideation (Fournier et al., 2010; Lee & Kim, 2010).

Katy’s weight loss may be due to a multitude of reasons. Katy could be experiencing

symptoms of anorexia, which is a disorder than leads to a preoccupation with calorie intake.

These symptoms are also often seen in patients experiencing minor depression, major

depression and anxiety disorders (Kaye, Gendall, & Strober, 1998). Treatment with SSRI’s

are challenging if the patient is malnourished due to the lack of nutrients required for the

antidepressant to be most effective (Kaye, Gendall, & Strober, 1998). Tryptophan is an

important nutrient that is often lacking in starving people. It is also necessary for the

synthesis of neurotransmitters, without Tryptophan serotonin levels may rapidly decrease

(Andrews, Bharwani, Lee, Fox, & Thomson, 2015). Evidence also shows that “underweight

patients with anorexia have a significant reduction in the basal concentration of the 5-HT

metabolite 5-hydroxyindolecetic acid” (Kaye, Gendall, & Strober, 1998, p.829 ). This

evidence shows that underweight people have lower levels of serotonin compared to the

general population. If we assume that Katy is underweight, this may indicate that her

significant weight loss is aggravating her depressive symptoms (Mahar, Bambico, Mechawar,

& Nobrega, 2014).

Insomnia is another common symptom found in patients with MDD. A lack of sleep

can cause difficulties in functioning and decrease the level of activity during the day, which

will aggravate the already debilitating symptoms of depression. Sleep disturbances can be

treated with antidepressants that act on the 5-HT2 receptor. “Antidepressant drugs with 5-

HT2 blocking properties . . . alleviate insomnia” (Thase, 1999, p.28). Therefore treating Katy

with an antidepressant that inhibits the reuptake of serotonin would again be most effective in

reducing her presenting symptoms (Thase, 1999).

4

Katy’s intrusive thoughts may have caused her to experience general or situational

anxiety. It is likely that these unwanted thoughts were a contributing factor to MDD

(McDougle, Kresch, & Posey, 2000;Allsopp & Williams, 1996). Intrusive thoughts are also a

common symptom of obsessive compulsive disorder, which is a mental illness that is also

often linked to MDD. Treatment with selective serotonin reuptake inhibitors has been found

to diminish obsessive, intrusive thoughts, which therefore will increase mood (McDougle,

Kresch, & Posey, 2000; Prins, Olivier, & Korte, 2011). The “Functions of post-synaptic

5HT2 receptors include long term antidepressant, . . . sleep regulating, anti-obsessive

compulsive disorder (OCD) actions” (Stahl, 1998, p. 217). Decreased levels of serotonin can

also lead to impulsive behaviour, which may have led Katy to attempt suicide (Brigitta,

2002).

Rights and restrictions under section 11 of the Mental Health (Compulsory Assessment

and Treatment) Act (1992).

A mental disorder is defined as an abnormal state of mind, which may cause the patient to

harm themselves or others. The main sign that led Katy to the diagnosis of MDD was a

suicide attempt, possibly caused by recurring intrusive thoughts. The reason Katy has been

placed under the MHA is due to the fact that she is a danger to herself and does not have the

ability to make beneficial medical decisions.

Katy has been placed under section 11, which requires her to undergo compulsory

assessment and treatment for 5 days. Under Section 8a a concerned person that suspects that

someone is suffering from a mental disorder may then apply to have them assessed. Under

Section 9 the assessment will be arranged and conducted by a medical practitioner, preferably

a psychiatrist, if available. In Katy’s case the medical practitioner decided that Katy is

5

mentally disordered and therefore she was placed under Section 11 (New-Zealand

Legislation, 1992).

Katy is restricted, as she has lost the ability to take her own life. She is also unable to

refuse treatment and assessment under the MHA therefore she loses her autonomy, although

it could be said she is not capable of making an important decision regarding her health due

to the severity of her mental health disorder which, renders her un autonomous. This

restriction also dictates that she must stay in a particular place of residence during the first

period for assessment and treatment purposes. This will restrict her freedom and she may feel

as though she lacks independence, choice and autonomy (New-Zealand Legislation, 1992).

If Katy disputes the Medical Practitioners findings, she has the legal right to have her

condition reviewed under Section 16. During the review the judge will need to consult with

the responsible clinician and another appropriate health professional. If the judge is satisfied

with the patient’s mental state, they will then have the ability to be released from their current

status (New-Zealand Legislation, 1992).

Katy also has rights under the Code of Health and Disability Services Consumers

Rights. An Important right under section 2 includes, the right to be treated with respect.

Under Section 2, if Katy feels that her rights have been breached she may apply to make a

complaint to the Health and Disability Commissioner. The case may then be further

investigated.

Under Section 2(5) when Katy has recovered and is mentally stable she may develop

an advanced directive, meaning she may allocate someone the responsibility to make

decisions regarding her healthcare (New-Zealand Legislation, 1996). Even though Katy has

the right to develop an advanced directive, she may still feel that she lacks autonomy because

she does not have the ability to refuse treatment outright.

6

The purpose of these rights is to ensure that the healthcare model does not include any

aspects of institutionalization (Salem, 1999). The diagnosis of a mental disorder can make

one feel stigmatized, prejudiced and unfairly judged by society, therefore it can be difficult

for recovering patients to be integrated back into the community. Minority groups or solo

parents may also find reintegration challenging due to housing availability and affordability

(Kearns & Joseph, 2000). Katy may experience these difficulties and therefore it is important

that she has adequate support.

Ethical principles justifying the intervention of a persons right to die.

Katy’s individual autonomy has been removed because she is unable to make safe decisions

regarding her health. Non-maleficence also relates to this case due to the importance of

Katy’s wellbeing. Conflicting opinions arise due to the fact that autonomy and non-

maleficence can be seen as equally important (Gillon, 2014).

Non-maleficence is one of the most important ethical principals to uphold as it

reiterates the importance of the Hippocratic oath in health care, which states that it is

imperative that health professionals shall do no harm to others. Page believes that “On

average, individuals have a significant preference for non-maleficence over the other

principles” (Page, 2012 p.10). Ensuring Katy does not harm herself is the most important

factor in this case.

Autonomy relates to the idea that patients should have the right to make their own

medical decisions (Gordon, Rauprich, & Vollmann, 2009). In this case the patient is choosing

to commit suicide therefore, it is imperative that non-maleficence is upheld by the health

practitioners in this scenario. MDD denies the patient the ability to think rationally and into

the future so they may lose hope (Yeragani, Ramachandraih, Subramanyam, Bar, & Baker,

7

2011). Another relevant factor is that Katy does not have the mental capability to make an

autonomous choice or give informed consent because of her mental illness (Gillon, 2014).

One could argue that autonomy is a significant ethical belief that must be upheld over

other principles due to the importance of individual rights. Gillon also suggested that

“autonomy . . . is morally very precious and ought not merely to be respected, but its

development encouraged and . . . extolled as virtues” (Gillon, 2003, p. 310). Although

autonomy is an important, due to the circumstances of Katy’s case I believe that full

autonomy cannot be applied and non-maleficence must be upheld, as it would clearly be a

disturbing proposition to allow full autonomy.

Conclusion

Antidepressants have been shown to decrease the severity of the presenting symptoms

Katy is experiencing. They can work through a multitude of ways including, increasing

neurogenesis and the availability of serotonin and other relevant amines. These are adequate

forms of treatment for major depressive disorder that adhere to important ethical concepts.

Hadley Grace Robinson-Lewis

8

References

Albert, P. R., Benkelfat, C., & Descarries, L. (2012). The neurobiology of depression-

Revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms.

Philosophical Transactions of the Royal Society B: Biological Sciences,

367(1601), 2378-2381. doi:10.1098/rstb.2012.0190

Albert, P. R., & Benkelfat, C. (2013). The neurobiology of depression-Revisiting the

serotonin hypothesis. II. Genetic, epigenetic and clinical studies. Philosophical

Transactions of the Royal Society B: Biological Sciences, 368(1615), 20120535-

20120535. doi:10.1098/rstb.2012.0535

Alenina, N., & Klempin, F. (2015). The role of serotonin in adult hippocampal

neurogenesis. Behavioural Brain Research, 277, 49-57.

doi:10.1016/j.bbr.2014.07.038

Allsopp, M., & Williams, T. (1996). Intrusive thoughts in a non-clinical adolescent

population. European Child and Adolescent Psychiatry, 5(1), 25-32. Retrieved

from http://www.ncbi.nlm.nih.gov/pubmed/9117536

Andrews, P. W., Bharwani, A., Lee, K. R., Fox, M., & Thomson, J. A. (2015). Is serotonin

an upper or a downer? The evolution of the serotonergic system and its role in

depression and the antidepressant response. Neuroscience & Biobehavioral

Reviews, 51, 164-188. doi:10.1016/j.neubiorev.2015.01.018

Best, J., Nijhout, H. F., & Reed, M. (2010). Serotonin synthesis, release and reuptake in

terminals: a mathematical model. Theor Biol Med Model, 7(1), 34.

doi:10.1186/1742-4682-7-34

Brigitta, B. (2002). Pathophysiology of depression and mechanisms of treatment. Dialogues

in Clinical Neuroscience, 4(1), 7-20. Retrieved from

9

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181668/

Bullock, S., Manias, E., & Galbraith, A. (2007). Antidepressants and mood stabilisers. In

Fundamentals of pharmacology (7th ed., pp. 381-397). Frenchs Forest, NSW:

Pearson Education Australia.

Cowen, P., & Sherwood, A. C. (2013). The role of serotonin in cognitive function: Evidence

from recent studies and implications for understanding depression. Journal of

Psychopharmacology, 27(7), 575-583. doi:10.1177/0269881113482531

Delgado, P. L. (2000). Depression: The case for a monoamine deficiency. Journal of

Clinical Psychiatry, 61(6), 7-11. Retrieved from

http://www.pubfacts.com/detail/10775018/Depression:-the-case-for-a-

monoamine-deficiency

Fils, J. M., Penick, E. C., Nickel, E. J., Othmer, E., DeSouza, C., Gabrielli, W. F., &

Hunter, E. E. (2010). Minor versus major depression: A comparative clinical

study. The Primary Care Companion The Journal of Clinical Psychiatry, 12(1), 1-

7. Retrieved from dx.doi.org/10.4088%2FPCC.08m00752blu

Fournier, J. C., DeRubeis, R. J., Hollon, S. D., Dimidjian, S., Amsterdam, J. D.,

Shelton, R. C., & Fawcett, J. (2010). Antidepressant drug effects and depression

severity. The Journal of the American Medical Association, 303(1), 1-15.

doi:10.1001/jama.2009.1943

Gillon, R. (2003). Ethics needs principles-four can encompass the rest and respect for

autonomy should be "first among equals". Journal of Medical Ethics, 29(5), 307-

312. doi:10.1136/jme.29.5.307

Gillon, R. (2014). Defending the four principles approach as a good basis for good medical

practice and therefore for good medical ethics. Journal of Medical Ethics, 41(1),

111-116. doi:10.1136/medethics-2014-102282

10

Gordon, J., Rauprich, O., & Vollmann, J. (2009). Applying the four principle approach.

Bioethics, 25(6), 293-300. doi:10.1111/j.1467-8519.2009.01757.x

Kaye, W., Gendall, K., & Strober, M. (1998). Serotonin neuronal function and selective

serotonin reuptake inhibitor treatment in anorexia and bulimia nervosa. Biological

Psychiatry, 44(9), 825-838. doi:10.1016/s0006-3223(98)00195-4

Kearns, R. A., & Joseph, A. E. (2000). Contracting opportunities: Interpreting post-asylum

geographies of mental health care in Auckland, New Zealand. Health and Place,

6(3), 159-169. doi:10.1016/s1353-8292(00)00020-4

Lee, B., & Kim, Y. (2010). The roles of bdnf in the pathophysiology of major depression

and in antidepressant treatment. Psychiatry Investigation, 7(4), 231.

doi:10.4306/pi.2010.7.4.231

Mahar, I., Bambico, F. R., Mechawar, N., & Nobrega, J. N. (2014). Stress, serotonin, and

hippocampal neurogenesis in relation to depression and antidepressant effects.

Neuroscience & Biobehavioral Reviews, 38, 173-192.

doi:10.1016/j.neubiorev.2013.11.009

Malberg, J. E., Eisch, A. J., Nestler, E. J., & Duman, R. S. (2000). Chronic antidepressant

treatment increases neurogenesis in adult rat hippocampus. The Journal of

Neuroscience, 20(24), 9104-9110. Retrieved from

http://www.jneurosci.org/content/20/24/9104.full#abstract-1

McDougle, C. J., Kresch, L. E., & Posey, D. J. (2000). Repetitive thoughts and behaviour in

pervasive developmental disorders: Treatment with serotonin reuptake inhibitors.

Journal of Autism and Developmental Disorders, 30(5), 427-435. Retrieved from

http://www.ncbi.nlm.nih.gov/pubmed/11098879

New-Zealand Legislation. (1992). Mental Health (Compulsory Assessment and Treatment)

Act 1992 No 46. Retrieved from

11

http://www.legislation.govt.nz/act/public/1992/0046/latest/whole.html#whole

New-Zealand Legislation. (1996). Health and Disability Commissioner (Code of Health and

Disability Services Consumers' Rights) Regulations 1996. Retrieved from

http://www.legislation.govt.nz/regulation/public/1996/0078/latest/

whole.html#whole

Page, K. (2012). The four principles: Can they be measured and do they predict ethical

decision making? BMC Medical Ethics, 13(1), 10. doi:10.1186/1472-6939-13-10

Prins, J., Olivier, B., & Korte, S. M. (2011). Triple reuptake inhibitors for treating subtypes

of major depressive disorder: The monoamine hypothesis revisited. Expert

Opinion on Investigational Drugs, 20(8), 1107-1130.

doi:10.1517/13543784.2011.594039

Salem, T. (1999). Physician-assisted suicide: Promoting autonomy or medicalizing suicide?

The Hastings Center Report, 29(3), 30. doi:10.2307/3528193

Stahl, S. M. (1998). Mechanism of action of serotonin selective reuptake inhibitors.

Serotonin receptors and pathways mediate therapeutic effects and side effects.

Journal of Affective Disorders, 51(3), 215-235. Retrieved from

https://www.researchgate.net/profile/Stephen_Stahl2/publication/12964711_Mech

anism_of_action_of_serotonin_selective_reuptake_inhibitors/links/

55259c490cf25d66dc945e75.pdf

Thase, M. E. (1999). Antidepressant treatment of the depressed patient with insomnia.

Journal of Clinical Psychiatry, 60(17), 28-31. doi:1555-2101

Warner-Schmidt, J. L., & Duman, R. S. (2006). Hippocampal neurogenesis: Opposing

effects of stress and antidepressant treatment. Hippocampus, 16(3), 239-249.

doi:10.1002/hipo.20156

Yeragani, V., Ramachandraih, C., Subramanyam, N., Bar, K., & Baker, G. (2011).

12

Antidepressants: From maois to ssris and more. Indian Journal of Psychiatry, 53(2),

180. doi:10.4103/0019-5545.82567

Hadley Grace Robinson-Lewis

13