Adult ADHD and Depression: What Did the Polygenic Score Show?

Someone who has been diagnosed with ADHD one day hears the sentence "and there is depression too." Then a question comes to mind: is this second thing a continuation of ADHD, or is it something separate? A new study looks at this question from the genetic side. The answer is not definitive, but what the abstract says points in an interesting direction. Below I explain what the abstract says, what it does not say, and what a polygenic score actually measures.

Who the study comes from, and where

The first author of the study is Thorsten M. Kranz and the last author is Georg C. Ziegler. There are sixteen authors in all, among them Rhiannon V. McNeill, Christian P. Jacob, Klaus-Peter Lesch, Andreas Reif and Sarah Kittel-Schneider. The paper was published in the journal Translational Psychiatry in 2026 (volume 16, issue 1). The abstract does not give a detailed publication date.

The design is this: 894 adult patients with ADHD were compared with 1,026 healthy controls. Within the ADHD group, 352 people with a lifetime history of major depression, established by a structured clinical interview (SCID-I), and 349 people with no history of depression at all were looked at separately. The abstract does not state the age range, or which countries or centers the participants came from. The two add up to 701, fewer than 894. The abstract does not say what the situation of the remaining people with ADHD is (this is my own arithmetic reading). The comparison of the patient and control groups, and the comparison within the patient group, is, as far as I can understand from the abstract, an association study. That is, nobody was given a treatment and then followed for the result.

This article is the Turkish summary of the paper published open access in Translational Psychiatry. The paper was published under the Creative Commons Attribution 4.0 (CC BY 4.0) license. The findings belong to the authors of the paper; the account and appraisal here are mine. I rely only on the abstract; I do not know the full text of the paper.

What a polygenic score is and what it is not

The central tool of the study is the polygenic risk score (PRS). The logic is simple: a trait, say ADHD or depression, is not determined by a single gene. Thousands of small genetic differences each contribute with very little effect. Studies that scan the genomes of very large groups of people (the abstract calls them "large-scale genome-wide association studies") estimate which difference carries how much weight. Then, for one person, you look at which of these differences they carry, add them up with their weights, and a single number comes out. This number is called a polygenic score. There are two in the study: PRS-ADHD for ADHD and PRS-MDD for major depression.

This score is not a diagnostic tool. It does not tell a person "you have ADHD" or "you will become depressed." Even when a person's score comes out high, it is only a statistical estimate that reflects a part of genetic predisposition. Of two people with the same score, one may never experience depression. Scores, as in this study, are useful for seeing the average difference between large groups. They are not for predicting the life of a single human being. These sentences are not what the abstract says; they are general knowledge.

What the abstract found

In the first step, the authors compared both scores between the 894 people with ADHD and the 1,026 controls. Both turned out to be associated with ADHD. The odds ratio (OR) was 1.59 for PRS-ADHD and 1.41 for PRS-MDD. The odds ratio is a measure that tells how many times different the odds of a trait occurring are in two groups. Being above 1 means that as the score rises, the likelihood of having ADHD rises too. The abstract does not state for what unit of increase this ratio holds. For both, the p value is below 0.0001. This is a statistic showing that it would be very hard to explain the result by chance.

So the genetic score calculated for depression is also higher, on average, in those with ADHD. This is not unexpected, because the introduction of the abstract already says that there may be a genetic link between the two disorders.

The second step is the really interesting one. Only among people with ADHD, those with a lifetime history of depression were compared with those without. In this comparison, only PRS-MDD turned out to be associated (OR = 1.34, p < 0.001). The ADHD score did not distinguish a history of depression. There is also an additional finding: in those with a history of both depression and an anxiety disorder, PRS-MDD is at its highest value.

What was different in people with ADHD and a history of depression

Alongside the genetic score, the abstract also lists clinical characteristics. In people with ADHD and a history of depression, the likelihood of other internalizing disorders was reportedly higher. Internalizing disorder is the name given to conditions in which the distress is lived inside the person; depression and anxiety are examples (general knowledge). Inattentive symptoms were significantly more pronounced and neuroticism scores higher. Neuroticism is a personality dimension that measures a tendency toward emotional ups and downs and worry (general knowledge). Lower social self-confidence in childhood was reported, and these people had more often received inpatient treatment in a psychiatric ward.

The picture read from this list is that people with ADHD and a history of depression are not simply "people with ADHD who have more symptoms"; they cluster in a particular direction. It is not hyperactivity and impulsivity but inattention and internalizing distress that come to the fore. I described how ADHD looks in adulthood in the article symptoms of ADHD in adults.

The authors' interpretation

The authors sum it up in two sentences. The first: the co-occurrence of ADHD and depression appears to be linked to a genetic predisposition to depression rather than to neurodevelopmental factors inherent to the biology of ADHD itself. The second: the view that comorbid depression in ADHD is connected not to an impulsive and externalizing line but to an inattentive and internalizing line is strengthened by this study.

If I translate this into my own words: when someone with ADHD becomes depressed, the cause may not be mainly ADHD itself. A genetic ground prone to depression may also be present in the same person. It is as if two separate predispositions are stacking up in the same person. This is my reading; the abstract does not write it so explicitly. The abstract also does not say whether the relationship is "causal," and it proposes no mechanism. It offers no neuroscientific explanation.

What this finding means for me

If you have ADHD and have had or are having depression, I think the idea that two things may have become tangled together can be a relief. You do not have to see depression as the "inevitable result" of ADHD, or as "your failure." But do not read it as a verdict either. What the abstract says is an average difference between groups. A single study, and especially a genetic score, cannot tell where your depression comes from.

On the practical side, the abstract contains no treatment recommendation. If inattention and internalizing distress stand out together, I think it makes sense for an assessment to look at both sides, but this is not a conclusion drawn from the abstract; it is my interpretation. Decisions such as medication or therapy are something to discuss with the clinician who knows you. How depression separates from ADHD and how the two intertwine, I explained more broadly in the article ADHD and depression. For the emotional side there is emotional regulation in ADHD, and for anxiety ADHD and anxiety.

What it does not say

A few things need to be separated out clearly. This is a single study and, as far as can be understood from the abstract, an association study. Finding a statistical link between a genetic score and a history of depression does not mean the gene "causes" the depression. The history of depression was taken as "lifetime." That is, people who are depressed right now and those who experienced it in the past are in the same box. The abstract does not give the participants' current state separately.

Although the numbers point to a consistent picture, the effect size is not dramatic. The OR values are between 1.3 and 1.6. That is, there is quite a lot of overlap between the two groups; the difference is in the average. So a high score is not a substitute for depression or for ADHD. Many people with a high score will not experience depression, and some people with a low score will (this sentence is general knowledge). The abstract does not separately address the heritability of ADHD. You can find the place of genetics in ADHD in the article is ADHD hereditary. The possibility of depressive symptoms being confused with bipolar disorder is the subject of the article ADHD or bipolar. This study does not examine that either.

What I am left with

The most useful side of this study, as I see it, is a proposal to make a distinction. When someone with ADHD becomes depressed, it is easy to say "that is just ADHD" and move on. The abstract suggests, at least on the genetic level, that this may not always be true. There may be two separate predispositions, and both may deserve separate attention.

What keeps me cautious is right here: genetic scores are very attractive numbers, because they seem to belong to one person. But they do not. They show an average difference in a group. That is why I would not want you to draw from this article the conclusion "my score is such and such" or "I am prone to depression." Take this instead: ADHD and depression being present in the same person does not show that the two are the same thing. What helps one may not be enough for the other.