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Addiction

Very Different Psychiatric Diagnoses Share Common Genes

Substance use disorders cluster together supporting unified addiction-liability.

Key points

  • A 2026 Nature cross-disorder genomics study demonstrated different psychiatric disorders cluster together.
  • The study showed 14 common psychiatric disorders shared substantial genetic liability within five clusters.
  • Alcohol, cannabis, opioid, and nicotine use disorders cluster together genetically into one brain disorder.

By integrating genome-wide data from a million-plus people with 14 psychiatric disorders, a 2026 Nature study marks a turning point in psychiatric science, showing many common psychiatric diagnoses are not genetically separate diseases. Instead, they share genetic liability (five genomic factors) across major psychiatric diagnoses, shaped by neurodevelopmental biology and life experiences. These findings challenge the disease model in psychiatric diagnoses and the Diagnostic and Statistical Manual of Mental Disorders (DSM).

Psychiatric manual categories still help with communication and treatment planning, but are imperfect proxies for personalized medicine or treatment predictions. The study confirmed what some clinicians already knew: How patients respond to treatment matters more than the disorder’s name. Also, comorbidity is common, and patients often move between diagnoses in the same cluster.

Depression, anxiety, and posttraumatic stress disorder (PTSD) often present together because of overlapping tendencies like negative emotions and stress sensitivity. However, when a patient has both major depressive disorder and generalized anxiety disorder, DSM psychiatry considers them two separate illnesses. The new genetic data suggest that these disorders cluster together due to shared neurodevelopmental risks. Cross-disorder psychiatric genomics shows high comorbidity and genetic overlap. Patients often move within diagnostic clusters over time, such as anxiety preceding depression, and psychotic symptoms preceding a bipolar diagnosis. These are not random transitions but expressions of a latent liability interacting with environment, maturation, trauma, and life experiences. Genomic phenotypes may help psychiatry move away from the trend of stacking one diagnosis on another in a single person.

Substance Use Disorders May Be One Disorder

Cross-disorder genomics strongly reinforces substance addiction as a single disease category: Alcohol, cannabis, opioid, and nicotine use disorders cluster together genetically. Substance use disorder (SUD) diagnoses support a shared addiction-liability dimension across major substances. Reflecting differences in reward sensitivity, impulsivity, stress reactivity, and executive control, some individuals are more susceptible to developing SUDs, regardless of which drug they encounter first.

Highly stereotyped behavioral patterns present with these addictions, and compulsive use, escalation, relapse, drug-seeking, and use despite harm are all hallmarks of addictive conditions, regardless of the drugs involved. Drug testing and laboratory data are commonly utilized to confirm a diagnosis. With alcohol use disorder (AUD), for example, the carbohydrate-deficient transferrin (CDT) test indicates chronic heavy drinking, unlike immediate blood alcohol tests. Directly observable intoxication, physical exam findings, and withdrawal syndromes reinforce the diagnosis.

Cannabis, opioids, cocaine, benzodiazepines, amphetamines, and fentanyl can be detected through routine toxicology screens and forensic testing. In contrast, there are no laboratory tests or measurable markers for most psychiatric diagnoses. Directly observable intoxication, physical exam findings, and withdrawal syndromes reinforce the diagnosis. Clear diagnosis, medical-psychosocial-psychiatric interventions, long-term outcomes, and research evidence have helped personalize treatment. Experts know polysubstance use is the rule rather than the exception. Because of this, an SUD diagnosis more consistently predicts the course of the illness, treatment choices, and responses than other diagnoses.

In practical terms, this new research supports integrated treatment approaches across substances and undermines stigmatizing interpretations of compulsive use. SUDs are not caused by poor judgment or inadequate willpower; they are brain diseases caused by a substance use-related neuroadaptation of reward, motivation, stress, and executive control brain circuits. These changes persist long after detoxification; thus, relapse risks remain high, even after prolonged abstinence. Abstinence without ongoing support is associated with persistent vulnerability and relapse risk, especially under cue- or stress-exposures. Addiction is best viewed as a chronic, relapsing brain disease rather than a behavioral problem.

These large-scale genomic studies show substance use disorders cluster together genetically, supporting a unified addiction-liability dimension and addictive disease rather than drug-specific diseases. Comorbidity between SUDs and other psychiatric disorders should be anticipated because shared liability increases risks across domains. Treatment must be integrated: Treating mood or psychotic symptoms without addressing existing addictions is rarely successful, and treating addiction without addressing underlying psychiatric vulnerability increases relapse risk. Addiction represents a unitary brain disorder with shared susceptibility rather than being a collection of drug-specific illnesses; polysubstance use is logical and should be considered the rule rather than the exception.

Conclusion

This new, large-scale genomic study demonstrates that 14 common psychiatric disorders share substantial genetic liability, helping explain their high comorbidity and frequent diagnostic transitions across the lifespan. The new study’s finding that alcohol, cannabis, opioid, and nicotine use disorders cluster within a single genetic liability dimension provides powerful biological confirmation of addiction as a brain disease with multiple phenotypic expressions. SUDs have predictable clinical courses, established chronic disease management models, and psychosocial and other treatments clearly related to disease mechanism and course.

Long-term management is also essential. Alcoholics Anonymous and Narcotics Anonymous (AA/NA) describe addiction as a unified "malady," considering alcoholism and other addictions a single disorder rather than separate diseases. AA's abstinence and 12-step approach are built on understanding addiction as a profound, overwhelming disorder. This view is in sync with the modern view of addiction as an acquired chronic brain disease. Like diabetes or hypertension, addiction requires ongoing monitoring, medication when indicated, behavioral intervention, and relapse prevention. The convergence of genetics, neurodevelopment, circuitry, and a predictable course reframes addiction as a medical condition, not a moral lapse.

In a field often criticized for diagnostic ambiguity, SUDs stand out as a model of what biologically anchored psychiatric diagnosis could look like—and as psychiatry moves toward personalized medicine, mechanism-based classification, and prediction, addiction medicine is unusually well-positioned to lead rather than follow.

References

Grotzinger AD, Werme J, Peyrot WJ, Frei O, de Leeuw C, Bicks LK, Guo Q, Margolis MP, Coombes BJ, Batzler A, Pazdernik V, Biernacka JM, Andreassen OA, Anttila V, Børglum AD, Breen G, Cai N, Demontis D, Edenberg HJ, Faraone SV, Franke B, Gandal MJ, Gelernter J, Hatoum AS, Hettema JM, Johnson EC, Jonas KG, Knowles JA, Koenen KC, Maihofer AX, Mallard TT, Mattheisen M, Mitchell KS, Neale BM, Nievergelt CM, Nurnberger JI, O'Connell KS, Peterson RE, Robinson EB, Sanchez-Roige SS, Santangelo SL, Scharf JM, Stefansson H, Stefansson K, Stein MB, Strom NI, Thornton LM, Tucker-Drob EM, Verhulst B, Waldman ID, Walters GB, Wray NR, Yu D; Anxiety Disorders Working Group of the Psychiatric Genomics Consortium; Attention-Deficit/Hyperactivity Disorder (ADHD) Working Group of the Psychiatric Genomics Consortium; Autism Spectrum Disorders Working Group of the Psychiatric Genomics Consortium; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Eating Disorders Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Nicotine Dependence GenOmics (iNDiGO) Consortium; Obsessive-Compulsive Disorder and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium; Post-Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Substance Use Disorders Working Group of the Psychiatric Genomics Consortium; Lee PH, Kendler KS, Smoller JW. Mapping the genetic landscape across 14 psychiatric disorders. Nature. 2026 Jan;649(8096):406–415. doi: 10.1038/s41586-025-09820-3. Epub 2025 Dec 10. PMID: 41372416; PMCID: PMC12779569.

Pathak GA, Pietrzak RH, Lacobelle A, Overstreet C, Wendt FR, Deak JD, Friligkou E, Nunez YZ, Montalvo-Ortiz JL, Levey DF, Kranzler HR, Gelernter J, Polimanti R. Epigenetic and genetic profiling of comorbidity patterns among substance dependence diagnoses. Mol Psychiatry. 2025 Sep;30(9):4435–4443. doi: 10.1038/s41380-025-03031-y. Epub 2025 Apr 17. PMID: 40247127; PMCID: PMC12343199.

Grotzinger AD, Werme J, Peyrot WJ, Frei O, de Leeuw C, Bicks LK, Guo Q, Margolis MP, Coombes BJ, Batzler A, Pazdernik V, Biernacka JM, Andreassen OA, Anttila V, Børglum AD, Cai N, Demontis D, Edenberg HJ, Faraone SV, Franke B, Gandal MJ, Gelernter J, Hettema JM, Jonas KG, Knowles JA, Koenen KC, Maihofer AX, Mallard TT, Mattheisen M, Mitchell KS, Neale BM, Nievergelt CM, Nurnberger JI, O'Connell KS, Robinson EB, Sanchez-Roige SS, Santangelo SL, Stefansson H, Stefansson K, Stein MB, Strom NI, Thornton LM, Tucker-Drob EM, Verhulst B, Waldman ID, Walters GB, Wray NR; Anxiety Disorders Working Group; Attention-Deficit/Hyperactivity Disorder (ADHD) Working Group; Autism Spectrum Disorders Working Group; Bipolar Disorder Working Group; Eating Disorders Working Group; Major Depressive Disorder Working Group; Nicotine Dependence GenOmics (iNDiGO) Consortium; Obsessive-Compulsive Disorder Working Group; Post-Traumatic Stress Disorder Working Group; Schizophrenia Working Group; Substance Use Disorders Working Group; Tourette Syndrome Working Group; Lee PH, Kendler KS, Smoller JW. The Landscape of Shared and Divergent Genetic Influences across 14 Psychiatric Disorders. medRxiv [Preprint]. 2025 Jan 15:2025.01.14.25320574. doi: 10.1101/2025.01.14.25320574. PMID: 40568675; PMCID: PMC12191084.

Tesfaye M, Jaholkowski P, Shadrin AA, van der Meer D, Hindley GFL, Holen B, Parker N, Parekh P, Birkenæs V, Rahman Z, Bahrami S, Kutrolli G, Frei O, Djurovic S, Dale AM, Smeland OB, O'Connell KS, Andreassen OA. Identification of Novel Genomic Loci for Anxiety and Extensive Genetic Overlap with Psychiatric Disorders. medRxiv [Preprint]. 2024 Apr 8:2023.09.01.23294920. doi: 10.1101/2023.09.01.23294920. Update in: Psychiatry Clin Neurosci. 2024 Dec;78(12):783–791. doi: 10.1111/pcn.13742. PMID: 37693403; PMCID: PMC10491354.

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