PS1110 - Biomedical approach

• What is the biological model?

  The biological (or biomedical) model argues that there is no meaningful distinction between mental and physical diseases (even maladaptive behaviour is seen as a disease state)
• What are the assumptions of the biological model?


  Assumptions:

  - Mental disorders are biologically based brain diseases

  - The underlying cause is organic (structural or physical)

  - Mental disorders reflect a disturbance of brain structure and/or function

  - In the model there is an emphasis on medical treatment and the primary aim of research is to uncover the biological cause(s) of mental disorders
• What can be a biological cause of MHD?


  - Neurotransmitters and hormones

  - Genetics

  - Developmental abnormalities

  - Physical deprivation, neglect or stress

  - Toxic or infectious agents
• How do psychotropic drugs influence synaptic transmission?


  - Increased or decreased neurotransmitter synthesis/release

  - Increased or decreased transmitter re-uptake/inactivation

  - Direct stimulation or inhibition of transmitter receptors

  - They can be agonist and antagonist
• Neurotransmitter imbalance in MHD


  - Altered production (or release) of neurotransmitter at synapses, over- or under-stimulating the target neuron

  - Altered re-uptake (or degeneration) of neurotransmitters, increasing or decreasing concentration at synapses

  - Alteration in neurotransmitter receptors, so that they are abnormally sensitive or insensitive
• What does the amine hypothesis of depression state?


  Depression is 'caused by' deficiency of amine neurotransmitters. Anti-depressants work by correcting brain 'amine deficiency'. All modern anti-depressants work by increasing brain amine levels
• What is the evidence for the amine hypothesis?


  In the 1950s the drug resperpine was approved to treat high blood pressure. However, some patients appeared to become depressed or suicidal. it was found to work by depleting nerve cells of amine neurotransmitters (e.g. serotonin, dopamine, noradrenaline)

  
  

  In the late 1950s, a new anti-tuberculosis drug called iproniazid was developed. side effects included euphoria, increased appetite and improved sleep. It was subsequently used to treat depression and was found to work by increasing amine neurotransmitters.
• What is the role of SSRIs?


  - Blocking re-uptake of serotonin increases its concentration at synapses in the brain

  - Zoloft (sertraline) was the most prescribed in the US in 2018
• Criticism of Amine hypothesis


  - Oversimplification - 'correct chemical imbalance' - very small sample sizes, poor control over confiding variables

  - Illustrates the problem with basing a theory of disease causation on the mechanism of a drug used to treat it?
• What genetic vulnerabilities can cause MHD?


  - Chromosomal abnormalities: complete or partial duplications/deletions (e.g. Down syndrome, intellectual disability/dementia)

  - Single gene defects: abnormalities in particular genes (mutations or disease - associated normal variants (polymorphisms)

  - Vulnerabilities to mental disorders usually polygenic (influenced by multiple genes)

  - There is not usually a single 'gene for' a particular mental disorder
• What are epigenetics?


  - A persons genetic code is fixed at birth, but genes can be switched 'on' or 'off' during life (= epigenetics)

  - Genes are 'silenced' by adding molecular tags (methyl groups) to parts of the DNA strand

  - The pattern of gene methylation is influenced by the environment including early life experiences

  - Adverse life experiences (e.g. bullying, neglect) can lead to epigenetic changes that influence risk of mental health disorders in adulthood.
• Gene-environment interaction


  Behaviour is not exclusively determined by the genes you inherit. Psychiatric disease risk depends on both genetic and environmental factors.
• What are hormones?


  Hormones are chemical messengers that control bodily functions (e.g. sex, feeding)
• What is the Hypothalamic-pituitary-adrenal (HPA) axis?

  - Over active in stress states, including chronic psychological stress

  - Leads to persistent elevation of stress hormone cortisol

  
• What is the aim of biological treatments?


  Aim: target the underlying biological function

  
  

  Ultimate goal: discover precise therapeutic agents that target the disease process without causing harm (Moncrieff, 2008)
• Insulin Shock Therapy


  - Manfred Sakel, psychiatrist (1933)

  - Used mainly for sz in the 1940s and 50s

  - Used insulin to induce coma (repeatedly over weeks-months)

  - Risks: obesity, seizures, brain damage or death

  - Replaced by medication by 1960s
• Frontal lobotomy


  - Walter Freeman

  - Performed >3500 lobotomies

  - The 'ice pick' procedure

  - Frontal lobe 'psychosurgery' reduced emotional distress and improved challenging behaviour but felt patients 'flat', passive and unemotional
• Electroconvulsive Therapy (ECT)


  - Controlled induction of convulsive seizures under general anaesthesia (Cerletti & Bini, 1939)

  - Safe, effective in several disorders unlike usual stereotypes

  - Affects numerous neurochemical (neurotransmitter) systems

  - But... high relapse rate (e.g. Kellner et al, 2006)

  - Recommended by NICE only as a 'last resort' for depression
• Pharmacological treatments


  - Psychotropic drugs - any medication capable of affecting the mind, emotions and behaviour

  - By far the most common form of medical treatment for mental disorders:

  ---> Antidepressants (low mood)

  ---> Anxiolytics (anxiety)

  ---> Antipsychotics/neuroleptics (psychosis)

  ---> Mood stabilisers (bipolar disorder)

  
  

  - All influence neurotransmission in the brain