Attending physician’s mental notes: initial evaluation

Testing of any of these genes may provide information that could be considered in the management of this patient

• – SLC6A4, 5HTTLPR Long(L)/Short(S) promoter insertion/deletion (rs63749047) and L(A)/L(G) (rs25531) polymorphism

  • This patient is homozygous (i.e., has two copies) for L(A)/L(A)

  • May indicate individuals who are more likely to exhibit response to SSRI treatment (compared to those with the S or L(G) allele)

  • They have more normal SERT function

  • They are hypothetically more resilient to stress-induced triggers for depression and suicide

  • L(A)/L(A) alleles are considered good*

• – COMT, 158 Val>Met (472 G>A, rs4680)

  • This patient is homozygous for (158 Val/Val, 472 G/G)

  • May indicate individuals with depression who are more likely to experience associated cognitive symptoms such as slowness of information processing, difficulty with executive functioning, and problem solving

  • They have greater reductions in DA levels in prefrontal cortices

  • VAL/VAL alleles are considered bad

• – MTHFR, 677 C>T

  • This patient is homozygous for T/T

  • May indicate individuals with depression who are also more likely to experience associated cognitive symptoms, especially in those who also express the Val variant of the COMT gene

  • These patients utilize brain L-methylfolate inefficiently, thus lowering their ability to synthesis serotonin, NE, and DA

  • T/T alleles are considered bad

• – CACNA1C, G>A rs1006737

  • This patient is homozygous for (G/G)

  • The A allele (not carried by this patient) may indicate individuals with mood disorders who are more likely to experience frequent relapses and recurrences

  • They may lack neuronal membrane ion channel stability and allow excessive activity perhaps in limbic areas

  • G/G alleles are considered good

• – DRD2, -141C insertion/deletion (rs1799732)

  • This patient is homozygous for (Ins/Ins)

  • May indicate individuals who are more likely to benefit from augmentation with an atypical antipsychotic in the event that they do not respond to an antidepressant (compared to those who carry the Del allele)

  • These patients hypothetically have more normalized function of the D2 receptors in associated neuronal pathways

  • Ins/Ins alleles are considered good

*For simplicity and teaching purposes, the alleles in this case are labeled as good or bad. These are not basic science nor clinical terms. Instead, these terms are used to get the reader accustomed to alleles being protective against psychiatric symptoms and disorders or increasing one’s risk of developing symptoms or disorders. Good means protective in general and bad means that risks increase. Additionally, the reader should be advised that it takes many alleles of many different genes interacting, and all of these interactions must work together with the environment (psychosocial stressors) in order for psychiatric symptoms to occur. For sake of simplicity, it is easier to start with good and bad to learn about the genetic underpinnings of psychiatric symptoms and how to bridge the gap between basic science and clinical application.