Biological explanations

• Conditions


  • Low tryptophan levels
  • Low stress levels
• Figure 6.17 shows molecules of serotonin contained in vesicles on the presynaptic cells before they have been released. You can also see a 5HT reuptake pump transporter molecule in the presynaptic membrane.
• Monoamine hypothesis


  Early biochemical explanations of mood disorders focused on noradrenaline and serotonin as neurotransmitters central to the communication of neurons in the brain's emotion centres
• Reserpine, a drug used to treat high blood pressure, causes depression as a side effect by reducing noradrenaline levels
• Serotonin was found to control noradrenaline levels, so an imbalance of serotonin could allow noradrenaline levels to drop, leading to a depressive episode, or become too high, leading to manic episodes
• Serotonin imbalances


  Serotonin levels can rise and fall for numerous reasons, such as changes in diet affecting tryptophan levels, or inhibition by cortisol associated with chronic stress
• Problems with receptor sites on the postsynaptic cell could interfere with communication between neurons, such as receptors becoming over-sensitive when serotonin levels are low
• The postsynaptic cell may attempt to compensate for low serotonin levels by creating more receptors (upregulation), but this can create more problems than it solves
• Problems with transporter molecules in the presynaptic cell membrane that absorb serotonin back into the cell can mean serotonin is not cleared properly from the synaptic cleft
• Serotonin


  Not cleared out of the synapse effectively, takes longer to be taken back into the presynaptic cell, can reduce the sensitivity of serotonin molecules for binding on the postsynaptic cell, levels may also fall if there is too much monoamine oxidase (an enzyme that breaks down serotonin)
• Genetic factors in depression

  Biopsychologists believe thoughts, feelings and behaviours are determined by signals passed between neurons, and genes provide the instructions for how these networks develop
• Twin studies


  • Kendler et al. (2006) found higher concordance rates for depression in monozygotic twins compared to dizygotic twins, suggesting a genetic component, especially in females
  • Bipolar disorder appears more heritable than unipolar depression
• Candidate genes


  • Genetic research has focused on genes coding for serotonin receptors (e.g. 5-HT2C) and transporter molecules (e.g. 5-HTT), which have polymorphisms resulting in different alleles
• Short and long alleles

  Individuals who inherit two short alleles have an increased risk of depression following a stressful life event than those who inherit either two long alleles or a combination of both
• Caspi et al. (2003) found that people carrying two copies of the short allele were more likely to become depressed following a stressful life event than people carrying one short allele, or two long alleles
• The more negative life events the person had faced, the stronger the effect
• Large genome wide association studies (GWAS) have failed to identify a consistent pattern of genes associated with depression (Hek et al., 2013)
• Genetics of depression


  Highly complex and may involve countless genes, each of which increase our vulnerability by a tiny degree
• Gene expression


  Shaped by environmental factors and genes may be switched 'on' and 'off' according to our changing life circumstances
• It is this level of complexity that makes it difficult to predict phenotype from a knowledge of genotype alone
• Differences in concordance rates between MZ and DZ twin studies

  May result from differences in how MZ and DZ twin pairs are treated by others, not just differences in shared DNA
• Adoption studies


  Support the role of nurture in the development of mood disorders, as increased risk for depression in adoptive children where the adoptive parent had depression suggests transmission is not always due to genetic inheritance
• Adoption studies on bipolar disorder

  Support the genetic explanation, as 31% of biological parents of adopted children with bipolar disorder had also been diagnosed with a mood disorder, compared to only 12% of adoptive parents
• Progress has been made in identifying specific genes linked to some subtypes of depression, such as recurrent and early onset depression
• A study involving over 10,000 Chinese women revealed significant associations between recurrent depression and two genes called SIRT1 and LHPP, but this finding did not replicate in women of European heritage
• Stress increases cortisol production


  Inhibits serotonin production in regions such as the hippocampus
• Mindfulness training


  Can lead to epigenetic effects specific to the 5-HTT gene and improve psychological wellbeing by reducing stress and cortisol production
• Lilijana Oruč


  Professor of Neuropsychiatry and Clinical Psychiatry at the Sarajevo School of Science and Technology Medical School, in Bosnia and Herzegovina, in south-eastern Europe. She has more than 35 years of experience and has published approximately 170 papers and authored and co-authored numerous books about biological and clinical psychiatry. She guest lectures at many universities and regularly participates in conferences, workshops and seminars. In addition, she supervises masters and doctorate students and serves on the editorial board of many professional journals.
• Selecting candidate genes


  • Biochemical research had already underlined the importance of serotonin in mood disorders and suicidal behaviour, so genetic research began to focus on candidate genes known to code for proteins involved in serotonergic transmission in the central nervous system.
  • The serotonin antagonist clozapine has great affinity for 5-HT2c receptors on the postsynaptic cell and Oruč et al. note that these receptors are also linked with appetite control. As appetite is frequently disrupted in major depressive episodes, Oruc et al. suggest that bipolar disorder may also be linked to irregularities of these receptors. Research into antidepressant drugs had also revealed that problems with the serotonin transporter protein 5-HTT may increase vulnerability to mood disorders
• Correlation study


  Analyses the association between diagnosis of bipolar and specific alleles of two candidates genes
• Genotype and free will/determinism


  Life is like a game of cards - the hand that is dealt you represents determinism, the way you play it is free will