March 28, 2023

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Attention deficit disorder is a mental disorder characterized by difficulty paying attention a lack of self-control and excessive activity it is thought to be a developmental disorder since the symptoms usually first appear at the age of 12 given the timeline of atd development and the types of symptoms involved it typically results in poor primary school performance

And if symptoms persist may negatively affect post-secondary schooling and job performance a dd is often treated with counseling and behavioral therapies however the licensing of methylphenidate in the 1960s and subsequent amphetamine based compounds like liz decks amphetamine and dextroamphetamine using medication to treat a dg is now standard practice taking

Medications for long periods at a time however especially as a child raises the questions of whether or not there are any potential long-term effects of these drugs on brain development thro childhood and subsequent behavior in adulthood so in this video i’m going to briefly go over the brain differences between those with and without a dd and how that correlates

With differences in behaviors why and how the drugs would give people with a dd work and then i’ll spend the end of the video detailing what psychological and neuro scientific literature has to say about the potential permanent effects both positive and negative of these stimulant medications on brain development and adult behavior so here’s a short list of some of

The behaviors that characterize a dd and you know just for the sake of simplicity i’m not going to make any distinction in this video between a dd and adhd together these all basically point to three main behaviors inattention hyperactivity and impulsivity covering how the brain difference is observed in children with a dd manifest in these particular behaviors could

Take hours and talking about each one of the individual brain regions involved in those behaviors could be a video in and of itself but because i’m here to talk about the long-term consequences of medication i’ll just give you a brief model the anterior cingulate cortex which we see highlighted here is involved in focusing on tasks and choosing between available

Options presented to you this area of the cortex is usually found to be smaller in size and children with a dd the dorsal lateral prefrontal cortex or dl pfc is also smaller the dl pfc is important for something called working memory this is a specific type of memory which can be defined as the ability to retain information while processing new information so it’s

Quite short only a few seconds in addition to this parts of the basal ganglia like the striatum also appear smaller and we can see the striatum here in deeper parts of the brain the smaller prefrontal cortex and parts of the basal ganglia make up something called the fronto striatal network stratum israel and fronto because of the prefrontal cortex is in the front

And this is one of the more critical circuits underlying attention and inhibition which is why ad d is often referred to as a frontal lobe disorder the cerebellum we can see here in the back is also smaller and this reduction in size thought to contribute to the development of tics and fidgeting and a lack of inhibition of movements as the cerebellum is important

For a coordination and the timing of movements another reported difference is in developmental timelines of the neocortex all these bumps we see along the top layer of the brain take years and years to fully develop it appears that in children with a dd the cortex takes a longer time to develop fully reaching maturity at later ages now individual brain areas

Don’t exist in isolation our highly connected to one another and one way in which brain differences occur in ad and non ad d-branes is in the connectivity across large brain networks examples of these are the default network the brains kind of baseline connective activity when we’re not really doing anything much at all or paying attention as well as the fronto

Straddle network which we talked about connecting the frontal lobes and the striatum detailing these networks these network differences is of course beyond the scope of this brief video the smaller brain areas and changes in connectivity ultimately result in changes in behavior related brain function when you have to focus and pay attention the attention systems

Will become active but a less functional basal ganglia means that you’re less able to inhibit or stop yourself from doing certain things with a dd because these neural systems have reduced functionality the brain makes use of neighboring brain tissue at the cost of efficiency in other words it has to bring in extra resources from other parts of the brain to pick

Up some of the slack namely from the parietal cortex altogether in this brief model we can see how changes in the frontal straddle network lavell ganglia the anterior cingulate cortex and the cerebellum are all related to the symptoms of inattention hyperactivity and impulsivity we’ll be covering two of the most common medications for a dd one is methylphenidate

Which is found in medications like ritalin concerta focalin metadata and date ronna and amphetamine based medications like dextroamphetamine and things like adderall dexedrine and vyvanse stimulant drugs like these that just mentioned increase intra synaptic catecholamines which basically means the levels of dopamine and norepinephrine inside neurons at the point

At which two neurons connect these two neurotransmitters do a lot of things in the brain but one part of the brain that is well known to make use of them is the frontal straggle fronto striatal pathway how this is proposed to work is that if you have a circuit in the brain with reduced function because the brain areas are smaller or the connections are fewer taking

A drug that increases the output of that circuit can make up for its smaller size and reduce connectivity bringing you back up from a deficit to a normal function for example taking a single dose of methylphenidate can increase activity in the cerebellum frontal cortex and basal ganglia as indicated by fmri studies here’s a brief collection of some of the evidence

For stimulant medications positive effects in treating a dd it’s shown with brain imaging taking stimulant medication increases the sizes of many of the affected brain regions over development these medications can increase the size of the thalamus and the cerebellum and reduce the delay of cortical development like we talked to talked about earlier it can also

Correct some of the functional brain activity between areas like the frontal striatal circuit several brain imaging studies have shown that treating a dd with stimulant medication can increase activity in the anterior cingulate cortex and the dl pfc in children with ad d although not not always treating childhood ad d with medication has also been widely studied

For its behavioral effects indicating that these drugs helped with the primary symptoms of impulsivity inattention and hyperactivity when combined with brain imaging it’s presumed that the brain changes observed in those taking medications directly correspond with these changes in behavior however stimulants don’t just affect these brain areas and behaviors that

We’ve just talked about but all the brain areas that make use of dopamine and norepinephrine also the brain areas mentioned don’t just do the behaviors we talked about but a whole host of other things because they’re connected to a whole bunch of other brain areas and so they’re involved in a whole wide variety of different brain circuits this is why several

Side effects are reported when taking stimulant medication like reduced appetite insomnia edginess and gastrointestinal upset now i’m gonna spend the remainder of the video focusing on the potentially permanent effects that using these medications for long periods of time might have so we know that stimulant medications can be effective at treating the symptoms

Of a dd and their neurological correlates and as we’ve already discussed when taking four periods during development have been shown to balance out some of the anatomical and functional brain differences between those with and without a dd and this is presumed to be a good a good thing however one concern is that other more damaging changes might take place in

The brain that are unrelated to the disorder so in this part of the video i’ll cover some of the research that has been done on the potential effects of long term stimulant medication use in laboratory animals and then in children so first the rodent literature the pre the preclinical animal literature is quite varied in its result but a number of studies have

Attempted to analyze cognitive emotional and neurological effects of long term stimulant use during development how this would work is that you would take some rats as they’re growing up from infancy to adulthood you give them daily doses of stimulant medications relative to their body weight and then test them at a later time when they’re adults and some of

These effects will start off with our increased decreased or sometimes no change at all as seen in spatial learning there have been no effects found for object memory deficits and there have also been quite varied results on things like anxiety and depression there have been some substantial brain related changes however some of the potential long-term effects

Are a reduction in dopamine in the striatum reduced bdnf which is brain derived neurotrophic factor this is a protein that helps grow new neurons reduced cortical thickness and permanent changes to the prefrontal cortex it’s important to note that the trend in rodent studies is that very high doses tend to produce impairments and damages but when these doses are

Limited down to therapeutically relevant doses or the types of doses that you would expect human children to take whatever that corresponds to in a rat that these impairments to don’t ever show up it’s also important to note that it’s very hard to give a rat adhd and that most of the studies of methylphenidate and stimulants involve normal healthy rats with normal

Healthy brains and so the results should of course be taken with a bit of a grain of salt however if you’re interested here’s a paper you can check out on rann models of a d d with all that being said some of the rat evidence indicates changes in brain structure and function particularly with regards to the front o straddle circuit given that the prefrontal cortex

Is still developing in young children this has become a major concern when giving children drugs that affect that part of the brain to contrast this a few monkey studies have been done in a similar vein of giving long-term clinically relevant doses of methylphenidate to adolescent monkeys and no findings of permanent damage to the brain have been found no rats and

Monkeys are great but they’re not people so what does the work on humans have to say well one of the first things we can say is that stimulant medications appear to be reliable long-term medications for the treatment of symptoms that is to say that taking stimulants will treat your ad d symptoms right now and for several years to come without complications and of

Course that’s that’s a good thing we now know that one of the primary neurological mechanisms behind a d d is dopamine particularly in the frontal straddle circuit while the circuit and its use of dopamine is also heavily implicated in addiction and so it shouldn’t come as a surprise that those with a d d experience higher rates of substance use and substance use

Disorders when they’re adults compared to the rest of the population and so it begs the question whether we should be giving those with a dd stimulants a type of drug with a very high addiction profile in one long-term study it was found that childhood ad d use was positively associated with adult substance use but that the earlier the child was when they started

Their medication the lower the risk indicating a beneficial effect of the medication in preventing future addiction indeed much of the literature supports this claim showing that there is either no effect or a protective effect much work has shown that many of the brain changes we talked about earlier regarding acute effects of the drug maintain themselves over

Time and result in the permanent normalization of those brain areas so i mean meaning long term stimulant use in a dd will result in a more normal basal ganglia thalamus and corpus callosum however in one study of adults with a dd who had never taken medication before they were given methylphenidate for 12 months they found that when the participants were no longer

On the medication they had lasting up regulation of dopamine transporters suggesting that being on medication for long periods of time might make symptoms worse when you get off the medication however another study looked at brain activity during a test of compulsiveness in children with a dd comparing ovis with a long history of medication to those without and

They found no differences in how their brains dealt with that task one thing in particular that i was interested in looking at or finding out when i started this video with something called neuronal imprinting a process where by taking a drug can alter the trajectory of your brain development if you’re a normal healthy child and all things go according to plan

Then you’ll end up a normal healthy adult but under the influence of some drug you might end up somewhere completely different it looks unfortunately as though the literature on long-term stimulant and use on child brain development is sparse with many people expressing a need for this exact type of research to be done in conclusion chronic stimulant treatment

May normalize brain development over time leading to brain structure and function more closely resembling those without the disorder the only evidence for abnormal effects is in dopamine transporters and of course this is just one study that i found the animal literature is less optimistic but it has dosing problems associated with it leading to less translatable

Results and that doesn’t appear to be much of a concern for the later development of addictive disorders either so here’s a small infographic that i’ll end with which summarizes everything that i on this topic i hope you found it informative and interesting so please like share subscribe and as always have a great day

Transcribed from video
Long term effects of ADHD medication in children By This is your brain on science