ADHD drug curbs impulsivity in men only, linked to brain wiring differences

A recent study of young adults in Israel found that a 20 mg dose of methylphenidate reduces choice impulsivity in men, but not in women, immediately after taking the drug. In men, the drug’s effects appeared to be related to the structural integrity of neural fibers in the forceps major region of the corpus callosum. The study was published in NeuroImage.

Impulsivity refers to the tendency to act quickly without fully considering the consequences, often leading to risky or inappropriate behavior. It is a common feature of both everyday behavior and clinical conditions such as attention-deficit/hyperactivity disorder, substance use disorders, and certain mood disorders. Impulsivity is a complex trait that can affect decision-making, emotion regulation, and self-control.

There are several types of impulsivity. Motor impulsivity involves acting without thinking, such as blurting out answers or interrupting others. Attentional impulsivity is characterized by difficulty staying focused and being easily distracted. Choice impulsivity refers to a preference for smaller immediate rewards over larger delayed ones, reflecting difficulty with delaying gratification. Cognitive impulsivity involves making decisions quickly without adequately processing available information.

Study author Maryana Daood and her colleagues aimed to assess whether methylphenidate affects choice impulsivity. Methylphenidate is a stimulant medication commonly used to treat attention-deficit/hyperactivity disorder by increasing levels of dopamine and norepinephrine in the brain, which can improve attention and self-control. It is sold under brand names such as Ritalin, Concerta, and Medikinet. Since impulsivity is a central feature of ADHD, verifying that a commonly used treatment reduces this specific behavior has important implications.

The study included 48 young adults recruited through advertisements at the University of Haifa in Israel. The average participant age was between 26 and 27 years, and 28 participants were men.

Each participant took part in two data collection sessions. During each session, they completed structural and functional magnetic resonance imaging (MRI) scans—both at rest and while performing a delay discounting task, a measure of choice impulsivity. In one session, participants received a 20 mg oral dose of methylphenidate. In the other session, they received a placebo capsule identical in appearance but without active ingredients.

Participants were randomly assigned to one of two groups. One group received methylphenidate in the first session and placebo in the second; the other group received the treatments in the opposite order. Neither the participants nor the researchers administering the treatments knew which capsule was taken in each session, making the study double-blind.

In addition to the two experimental sessions, participants completed the delay discounting task on two earlier occasions. This task assesses how much a person devalues a reward based on the time they have to wait for it. It is commonly used to measure choice impulsivity.

Neuroimaging data showed that men had greater white matter integrity in three brain tracts: the anterior thalamic radiation, the cingulum bundle, and the forceps minor of the corpus callosum. Methylphenidate significantly reduced choice impulsivity in men but not in women. In men, the drug’s effectiveness was greater among those with lower neural fiber integrity in the forceps major. In contrast, in women, the drug’s impact was more pronounced among those with higher white matter integrity in the forceps minor.

“Taken together, results uncover sex-specific effects of MPH [methylphenidate] on choice impulsivity, accounted for by inverse associations between choice impulsivity under MPH and the structural integrity of distinct segments of the corpus callosum,” study authors concluded.

The study sheds light on the effects of methylphenidate on choice impulsivity. However, it should be noted that the study was conducted on a small group of healthy young adults, not on individuals with ADHD or with increased impulsivity. Results on larger groups or on individuals with particularly high impulsivity might differ.

The paper, “The impact of methylphenidate on choice impulsivity is inversely associated with corpus callosum fiber integrity across sexes,” was authored by Maryana Daood , Leehe Peled-Avron , Rachel Ben-Hayun , Michael Nevat , Judith Aharon-Peretz , Rachel Tomer , and Roee Admon.


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