Custom Genetic Report for PSSD, PAS and PFS
A growing number of individuals now have direct access to their raw genetic data through consumer services like 23andMe and AncestryDNA. By identifying key variants- especially single-nucleotide polymorphisms (SNPs)- we can gain actionable insights into conditions such as Post-SSRI Sexual Dysfunction (PSSD), Post-Accutane Syndrome (PAS) and Post-Finasteride Syndrome (PFS).
How it works
Using the SecondLife Custom Genetic Report tool is simple
1) Take a DNA Test: The SecondLife Custom Genetic Report is compatible with test from 23andMe, MyHeritage and AncestryDNA.
2) Download your raw DNA data file: This is typically under settings. Make sure to check with your provider for specific instructions.
3) Upload your DNA: Upload the raw DNA file on the Generate Report page and receive a custom DNA report in minutes.
What Are SNPs?
Each SNP represents a single “letter” change in your DNA code. Even a swap from Adenine (A) to Guanine (G) at one position can dramatically alter how your body processes drugs, hormones and neurotransmitters. For example, the rs25531 SNP in the serotonin transporter gene dramatically influences serotonin reuptake. Carriers of the G allele are up to three times more likely to experience gastrointestinal side effects like IBS – an insight that can guide SSRI selection and dosing. [1]
Fig. 1 Rendering of a Single Nucleotide Polymorphism. [2]
How SNPs Impact Risk Developing Post-Accutane Syndrome:
In a large meta-analysis pooling over 8,000 isotretinoin users against 10,000 non-users, isotretinoin treatment was associated with a roughly 30% higher odds of developing depression (pooled OR 1.3, 95% CI 1.1–1.5). Importantly, not every patient on isotretinoin becomes depressed. That discrepancy has led researchers to look for underlying factors – particularly genetic predispositions – that might explain why some individuals are at elevated risk. [3]
Two genes have emerged as candidates in influencing isotretinoin-induced mood changes: RARA (Retinoic Acid Receptor Alpha) and LEP (Leptin Gene). Isotretinoin is a synthetic retinoid that binds retinoic acid receptors (including RARA) in the brain. These receptors regulate gene transcription in neuronal cells, affecting neurotransmitter balance.
Certain single-nucleotide polymorphisms (SNPs) in the RARA gene alter receptor sensitivity or expression levels. In people carrying those variants, isotretinoin may cause exaggerated changes in neurotransmitter pathways (such as serotonin or dopamine signalling), predisposing them to depressive symptoms.
Leptin, produced primarily by fat cells, also modulates brain circuits involved in mood and stress response. LEP polymorphisms can influence leptin levels or receptor interactions in the hypothalamus. When isotretinoin – an agent already known to alter neuroinflammatory signalling – is added, the deficiency of a properly functioning leptin pathway may leave certain patients more vulnerable to depression or low mood.
The review found that patients with high-risk alleles in either Retinoic Acid Receptor Alpha or Leptin had dramatically higher odds of developing depression. In the custom genetic report, we look for these variants (among many others) and offer insights into how your specific genotype may have impacted your response to Isotretinoin treatment.
your own genome, this report equips you and your healthcare provider with a genetic roadmap- helping you make informed choices about treatments, avoid unnecessary side effects, and optimize recovery from post‐medication syndromes.
How SNPs Impact Risk Developing Side Effects from SSRIs:
SSRIs are another class of medication that present the risk of developing debilitating and possibly enduring side effects. Studies have indicated that response to SSRIs are also contingent on individual genetic polymorphisms. In one study, 89 young adults (18–40) with no preexisting sexual difficulties, all starting an SSRI. Researchers looked at a common SNP in the serotonin 2A receptor gene (5HT2A), specifically the promoter variant at position −1438 (G→A).
Patients with the GG genotype at 5HT2A −1438 were 3.6× more likely to develop measurable sexual dysfunction on an SSRI (OR 3.6; 95% CI 1.03–12.6). After adjusting for age, gender, anxiety, and depression severity, the GG group also had significantly lower arousal scores (p = 0.022). By contrast, those carrying at least one A allele (GA or AA) were far less likely to report SSRI‐induced sexual problems.
The 5HT2A receptor is a key target in the brain’s serotonin pathway. An SSRI already boosts synaptic serotonin – if your 5HT2A promoter is the “GG” variant, your neurons may express more or differently regulated 5HT2A receptors that amplify SSRI’s impact on sexual circuitry – leading to greater arousal deficits. [4]
Another study of 201 Japanese patients, 36 of whom developed clinically significant sexual dysfunction on paroxetine, fluvoxamine, or milnacipran) – a genome wide association screen of 186,320 SNPs was performed to pinpoint genetic hotspots linked to SSRI/SNRI‐induced sexual side effects. Eleven SNPs identified a strong association with the MDGA2 (a gene implicated in neural development and synaptic adhesion). The strongest signal came from rs1160351, where each risk allele nearly tripled the odds of SSRI/SNRI‐induced sexual dysfunction (risk ratio 2.92). [5]
How SNPs Impact Response to Finasteride:
Finasteride is a medication that offers the possibility of preserving a youthful hairline by inhibiting the synthesis of a key metabolite of testosterone called DHT. However, in recent years it’s become apparent that depleting this key androgen carries the risk of serious cognitive, mood and sexual side effects – a condition that can even persist beyond discontinuation, called ‘Post-Finasteride Syndrome’.
Genetic variants in the two 5α-reductase genes, SRD5A1 and SRD5A2, can significantly alter how much testosterone (T) is converted into dihydrotestosterone (DHT) and downstream metabolites – both in the prostate and circulation. Since finasteride works by inhibiting 5α-reductase, knowing your personal SRD5A genotype helps predict not only how well the drug will lower DHT but also who might be especially prone to side effects like sexual dysfunction or mood changes.
Studies have found men carrying the rs2208532 risk allele show a 32% increase in prostate-tissue testosterone levels (because the polymorphism reduces local 5α-reductase activity, so less T is converted into DHT). At baseline, these individuals have relatively lower intraprostatic DHT and downstream neurosteroid metabolites (e.g., 3α-diol-17G, androsterone-glucuronide). Conversely the rs12470143 allele associates with higher blood levels of 3α-androstane-17β‐diol-17-glucuronide (3α-diol-17G) – an inactive DHT metabolite.
High-risk rs2208532 carriers already have reduced 5α-reductase, so they start with lower DHT and higher residual T. When they take finasteride, the incremental drop in DHT may be less dramatic – possibly requiring a lower dose to achieve therapeutic effect but also putting them at greater risk for sexual side effects, since their neurosteroid pool (e.g. 3α-diol-17G) is already low. [6]
What Your Comprehensive Report Includes:
By harnessing the power of your own genome, this report equips you and your healthcare provider with a genetic roadmap- helping you make informed choices about treatments, reduce risk of side effects, and optimize recovery from post‐medication syndromes.
- Personalized SNP Summary: A curated list of personalised risk-related variants- complete with genotype and associated studies.
- Condition-Specific Insights: How your genetics may influence susceptibility to or recovery from PSSD, PAS and PFS, including predicted drug efficacy and adverse-effect risk.
- Research References: Direct links to the studies underpinning each genetic association, so you can delve deeper if you wish.
- Rapid Insights: You will receive your custom genetic report in the form of a downloadable PDF within minutes of uploading your raw DNA data.
- Secure Handling of Data: All your data is encrypted and handled securely. All data including your report in deleted within 24 hours by default (so make sure to download your report when you get it). For added peace of mind you can still delete your data before then at any time.
Here is a sample of one of the pages of the DNA report based on real data, relating to polymorphisms affecting Retinoic Acid signalling and response to Isotretinoin treatment.
You can purchase the Custom Genetic Report from the Shop:
References
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC4048923/
[2] SNP model by David Eccles (gringer), CC BY 4.0 https://creativecommons.org/licenses/by/4.0, via Wikimedia Commons
[3] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4984257
[4] https://www.nature.com/articles/1301090
[5] https://www.sciencedirect.com/science/article/abs/pii/S0165178112000534