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Nanotechnology For Depression: The Futuristic Potential of Nanopsychiatry

Most pharmacological-based treatments for depression aim to increase levels of various neurotransmitters, particularly serotonin (5-HT).  It is thought that approximately 2 out of 3 individuals that seek treatment with standard antidepressants such as SSRIs and SNRIs are able to attain therapeutic relief.  For a certain percentage of these individuals, the benefits of using pharmaceutical interventions significantly outweigh the drawbacks (e.g. side effects).

However, even among those who derive therapeutic relief from current-market treatments, many notice that their antidepressants stop working over time.  This is due to the fact that the brain has become habituated to the surplus of serotonin (and/or other monoamines) being increased via the antidepressant.  At this point the individual is in a tough situation with a few logical choices: increase the dosage (and experience more side effects), discontinue the medication (and experience hellacious withdrawal symptoms), play antidepressant roulette (with a psychiatrist), or test some antidepressant augmentation strategies.

For the other estimated 33.33% of those that seek psychiatric treatment for depression – no drugs actually provide therapeutic benefit.  In fact, sometimes the antidepressants increase depression and suicidality, thus medication-based treatment is perceived as being worse than doing nothing.  With depression predicted to become the number one global disease burden by 2030, it is imperative that new therapeutic interventions are established.

A new branch of medicine called “nanomedicine” is attempting to harness the development of nanotechnology for the treatment of psychiatric disorders.  In fact, many speculate that within the next half-century, the field of nanopsychiatry will emerge along with alternative interventions such as: RNAi for depression and gene therapy for depression.  Those that haven’t found any viable therapeutic treatments for their depression are holding out hope that these new practices will provide complete symptomatic relief from depression and eventually, eradicate this disease from the entire populace of sufferers.

Using Nanotechnology for Depression (Nanomedicine)

Nanomedicine is a specific branch of medicine that involves treating disease with nanotechnology – or materials the size of nanometers (billionths of a meter).  Examples of ways in which nanomedicine could be used for the treatment of depression (and other mental illnesses) include: developing nanoelectronic biosensors (to help diagnose disease), nanocarriers (for superior drug delivery), and nanorobots (to modulate neurophysiological correlates of depression).

Some speculate that the perfection of nanotechnology would dramatically change the entire health-care system due to the fact that nanobots could enter our bodies (and brains) and repair any damage.  They could help correct genetic abnormalities that contribute to feelings of depression (and other conditions).  Moreover, some theorize that nanorobots and other nano-interventions could engineer a state of “super happiness” by shifting our baseline hedonic set points and increase your IQ.

That said, the 33% of people with refractory depression aren’t really concerned with “super happiness,” all they want is to function on a level playing field with the rest of society.  They want to alleviate their depression so that they can do things like hold down a job, stay productive, be good parents, and contribute to society.  Within the next several decades, it is estimated that nanomedicine developments could help give these individuals the relief necessary to function in society.

Nanopsychiatry: Uses of Nanotechnology for Depression

Nanomedicine is in relatively premature (preclinical) stages in regards to being used for the treatment of mental illnesses such as depression.  Within the next couple decades, it is thought that nanotechnology will aid psychiatrists and neurologists as an advanced diagnostic (or neuroimaging) tool, assessing brain activity in greater detail than ever before.  As nanotech is refined and perfected – it holds potential to completely eradicate depression and simultaneously enhance our natural neurocognitive capacity.

  1. Antidepressant Enhancement

The incorporation of specific nanotechnologies could be used as a way to augment the efficacy of antidepressants.  Nanotechnologies would improve delivery of various medications, increase bioavailability, absorption, and metabolization.  Researchers have already been able to load nanoparticles with pharmaceutical compounds to increase their potency (up to several hundred times) in the brains of rats.

  • Bioavailability: It is thought that nanotechnology would augment psychiatric drugs (e.g. antidepressants) by maximizing the amount of the drugs that elicit an effect. The greater the bioavailability of a certain drug, the greater the effect at lower doses.  This allows for a smoother overall absorption and a possible reduction of side effects.
  • Delivery: In the future, antidepressant formulations may be attached to nanocarriers that make their way into the brain, fully penetrating the blood-brain barrier. Researchers have already used silica-based nanocarriers loaded with piracetam, a popular “racetam” nootropic.  The nanocarriers were able to transfer a greater amount of piracetam across the blood-brain barrier than when taken orally. The absorption and adsorption were reportedly nearly 200 times greater than standard administration of piracetam.
  • Efficacy: Nanotechnology has been suggested as a way to significantly ramp up the efficacy of antidepressants. Nanotech could provide superior delivery modalities of antidepressants and increase potency of smaller doses.  Furthermore, nanobots could guide doses of a drug to isolated regions of the brain, without affecting other (potentially non-problematic) regions.  Some pharmaceutical companies may devise nanopharmaceuticals to treat mental illnesses.
  • Metabolism: Many people metabolize antidepressants differently as a result of genetics and neurophysiology. Those that rapidly metabolize certain drugs may require higher doses than those who are slower metabolizers.  Nanotech could be used to ensure that all drugs are optimally metabolized and processed by the body.
  • Side effects: Most people hate antidepressant side effects such as sexual dysfunction, weight gain, and dry mouth. Nanotech may be used to ensure that drugs are delivered at the minimal effective dose to the proper areas of the brain so that side effects can be minimized.  It should be thought that people in the future may derive therapeutic relief from antidepressants without any noticeable side effects.
  • Tolerance prevention: Imagine if you found an antidepressant that was working brilliantly, but over time it stopped working. The “poop out” effect is common among current-market drugs and occurs due to physiological tolerance (this is common sense).  Assuming you never developed tolerance as a result of highly complex nanobots, you’d get lifelong relief from your depression with the first medication you found effective.
  • Withdrawal symptoms: Some nanotech may be used to track biomarkers pre-treatment, during treatment, and post-treatment. The recordings collected by nanorobots may provide scientific data regarding how a person’s neurophysiology has changed throughout the course of treatment.  Then medical professionals can use this information to help the individual quickly target problematic biomarkers – reversing them to homeostasis and expediting withdrawal.  In advanced stages, nanotech may repair the nervous system so quickly, that no withdrawal is apparent to the user.

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449887/
Source: http://www.springer.com/us/book/9780387776675
Source: http://www.ncbi.nlm.nih.gov/pubmed/21451188
Source: http://www.ncbi.nlm.nih.gov/pubmed/23354916

  1. Diagnoses & Mood Tracking

In addition to enhancing the efficacy of antidepressants for the treatment of depression (and other psychiatric drugs), nanotechnology can be used to improve diagnostic accuracy and track neurophysiological changes over a period of time.  Nanorobots may provide data regarding your current mood and an array of neurophysiological variables associated with depression.  Nanotech may help determine whether you’re responding favorably to a medication or whether treatment should be discontinued.

Diagnostic biomarkers: The diagnostic criteria for depression these days is based off of interaction between a patient and psychiatrist.  The psychiatrist will generally administer a depression rating scale to assess severity of symptoms.  However, much of the interpreted severity is based off of subjective self-assessments by the patients, in conjunction with subjective interpretations made by the psychiatrist.

To ameliorate the diagnostic pitfalls of depression, researchers are currently developing blood tests for depression to measure symptomatic severity based on objective biomarkers.  Unfortunately, these blood-based biomarkers may not account for every biomarker necessary to diagnose depression and/or distinguish severity (or subtype).  Nanotechnology could be used to probe a multitude of biomarkers, allowing professionals to make more accurate diagnoses.

Nanosensors to determine efficacy: Researchers have already been experimenting with nanosensors designed to interpret efficacy of certain drugs.  It is thought that these nanosensors would be able to give researchers feedback in regards to the drug’s efficacy, potency, and effects.  Nanosensors may provide in-depth details regarding antidepressant (and psychotropic) mechanisms of action and provide complete patient-specific data.

A theorized benefit of using nanosensors is that they can be cheaply manufactured, allowing for quick universal adoption as soon as they are deemed safe and effective.  Impressively, these nanosensors may be able to determine whether individuals are benefiting from a “cocktail” of psychiatric drugs, which drugs are most effective, and which should be discarded from the regimen.  Feedback may be sent to a practitioner as to whether a dosage of a medication needs to be tweaked.

Nanowire assessments: It is possible to implant nanowires within the brain to read individualized signals of a person’s depression.  Swedish researchers in 2013 were already able to develop a device only 200 nanometers in diameter and implant it within the brain of a rat.  These nanowires may be able to provide neuroscientists with valuable data they need to understand depression as well as how to develop new treatments.

These nanowires appear to be extremely thin and flexible, yet don’t seem to disrupt any brain tissue.  They were created with materials that wouldn’t interrupt active neurons, yet are able to collect data of neurotransmission and nerve signals within the brain.  As Moore’s law and other technological advances continues, we should expect the abilities of these nanowires to increase.

Additionally, some researchers believe that electrodes could be nanostructured for specific purposes within the brain.  The structuring would allow the nanowires to be a perfect fit based on the specific part of the brain in which they are inserted.  One person could have a nanoimplant recording data about activity within a specific part of the prefrontal cortex, while another may have an implant documenting neurotransmission speed or levels of neurotransmitters.

Source: http://www.ncbi.nlm.nih.gov/pubmed/20222866
Source: http://www.ncbi.nlm.nih.gov/pubmed/23545476

  1. Standalone Treatment

It is hoped that by 2060, nanotechnology can be used as a standalone option for the treatment (and cure) of mental illnesses like depression and other neurological disorders.  Our understanding of the brain and its functions are progressing with each consecutive year, and nanotechnology will continue to improve with time.  Nanobots may be inserted into the brain for the repairing of damaged tissue and neurons, but may also be used to artificially stimulate certain regions of the brain to offset depression and anxiety.

Nano-neurostimulation: We already know that stimulation of specific regions of the brain alleviates depressive symptoms.  This is evidenced by rTMS (repetitive transcranial magnetic stimulation).  Repetitive TMS (rTMS) in the left-prefrontal cortex is known to reduce depression.  Furthermore, implanted electrodes or neural implants within the brain that stimulate the pleasure centers may also offset depressive symptoms.

The regional stimulation via the aforementioned modalities may provide temporary relief, but it isn’t typically sustained.  DARPA is already using advanced technology to develop bionic brain implants for PTSD that function by correcting abnormal brain signaling and circuitry dysfunction. What if nanobots could be implanted within the brain that were strategically preprogrammed to stimulate certain regions of the brain and modulate neurotransmission?

Many with depression may opt for nanostimulation, nano-wireheading, (or “nanoheading”) as this may provide a functional cure for a variety of mental illnesses.  This shouldn’t produce any tolerance like pharmaceuticals, and would provide long-lasting (possibly lifelong) relief.  In fact, a person may be able to use nanotechnology to gain full control over their brain activity at whim.

Should they want to feel a certain way, just implant specific nanowires that allow them to flexibly modulate their neural activation that’s optimal for a given task. Unlike standard “wireheading” which aims to maximize bliss by targeting the pleasure centers, nano-neurostimulation could be used to improve mood without hampering creativity, motivation, and intelligence.  In fact, it could be used to enhance all aspects of brain function simultaneously.

Neural nano-repairs: Many people with depression have endured abnormal brain development and/or experienced some sort of brain damage.  Consider ex-NFL players, often ending up severely depressed and suicidal as a result of neurological damage from cumulative concussions.  Those with depression as a result of cumulative brain damage could be effectively repaired by pre-programmed nanobots inserted into brains.

These nanobots could make repairs naturally, but they could also use artificial nano-replacements, or carry stem-cells to replace damaged tissue.  Inevitably there will be some ethical concerns with this nano-neurological enhancement and correction.  Cost will continue to bring this technology down, resulting in everyone having access to great nano-repair services (hopefully sooner than later).

  • Artificial neurons: Synthetic, artificial nanoneurons could be manufactured and inserted into someone’s brain for improved performance. Nanobots in clinical trials have already been tested as red blood cells with nearly 100-fold the power of a standard endogenous red blood cell.  Individuals that have lost a significant amount of brain cells may not need to be concerned with hippocampal neurogenesis because nanoneurons may provide substantially greater benefit than standard neurons.
  • Artificial circuits: Brain circuits are highly important for neuronal communication – neurons don’t function alone, they work together with other neurons to send messages across various regions. The circuitry within the brain is necessary for regional communication and optimal mental health.  Individuals with abnormal circuitry and/or circuit activation may experience depression.  Fortunately, artificial nanobots could repair faulty circuitry, modulate existing circuit activity, and/or form an artificial circuit.
  • Artificial neurotransmitters and receptors: It is thought that neurotransmitters and receptor densities play a major role in the pathology of depression. Someone with low serotonin may be more prone to sadness than an individual with normalized serotonin levels.  In addition, someone with a low density of certain neurotransmitter receptors in a particular region may be more prone to depression.  Artificial nano-neurotransmitters and nano-receptors could serve to replace endogenous ones – assuming they’re safe.
  • Artificial tissue: While brain tissue (matter) loss often occurs among individuals with neurodegenerative diseases, it could be the cause of a person’s depression. Nanobots may be able to repair certain tissue damage, but probably won’t be able to stimulate growth of new tissue unless coupled with stem cell therapy.  That said, nano-tissue could serve as a viable replacement for endogenous tissue and may even offer superior functioning by comparison.
  • Silencing or “knocking out” functions: Individuals with depression may have too many neurotransmitters and/or receptors. Production of these neurotransmitters and/or receptors tend to have specific genetic correlates.  Nanotechnology will eventually be able to alter genes, but insertion of nanobots may be able to reduce receptor densities and/or neurotransmitter levels in specific regions.

Nano-scaled implants: Japanese researchers are using nanotechnology to deliberately alter neural pathways within the brain.  They believe that by developing nano-scaled implants to mimic receptor proteins, neural pathways can be directly altered.  The research noted that these implants would be able to increase the release of neurotransmitters responsible for both excitatory and inhibitory activity.

These implants could help those with depression, but are currently thought to be most practical for stroke victims.  The implants are designed to replenish lost connections that were damaged by a stroke.  Moreover, other researchers are considering nanoscale polymers for the coating of brain implants.  These nanoscale polymers hold potential to affect single neurons, ultimately upregulating endogenous production of specific neurotransmitters.

Source: http://www.ncbi.nlm.nih.gov/pubmed/19955285
Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474440/

Nanopsychiatry: A Future Field of Nanomedicine?

An article published in 2013 discussed the future of nanomedicine in psychiatry in which the combined practice would be dubbed “nanopsychiatry.”  Researchers conducted a systematic review of all studies up to 2012 involving nanotechnology and psychiatry.  They analyzed studies that contained the terms: “nanotechnology,” “nanoparticles,” or “nanomedicine” along with “central nervous system.”

A total of 76 papers were uncovered and incorporated into a review.  The review indicated three postulated uses of nanotechnology in psychiatry including:

  1. Pharmacology

As was mentioned above, the initial usage of nanotechnology in psychiatry will likely be to enhance the efficacy of various medications.  Nanotechnology could maximize the amount of the drug that crosses the blood-brain barrier, and deliver the drugs directly to targeted areas of the brain (or specific neurons).  Strategic usage of nanoparticles may significantly increase the bioavailability of drugs.

Moreover, the entire pharmacokinetic profile of medications could be improved; safety and efficacy of medications would be enhanced.  Enhanced medication delivery may include the usage of: liposomes, nanobubbles, nanoparticle polymers, or nanosomes.  It was also noted that nanoshells and dendrimers may provide additional therapeutic effects via enhanced potency and increased synergy (of combined treatments).

The research suggested that nanoparticle size should be between 10 nm and 100 nm.  Specific rigidity and shapes of these nanoparticles is important to ensure that the contact angle between particle and cell membrane is less than 45 degrees.  Below is a list of various investigative delivery options for antidepressants and other drugs.

  • Liposomes: These are nanoparticles in the shape of spheres that consist of a “lipid bilayer membrane.” Liposomes are able to target a specific cell with drug delivery via ligand coupling.
  • Nanosomes: These are considered uniform liposomes that are manufactured with supercritical fluid technology.
  • Nanotubes: These are tube-like structures consisting of graphite. They are regarded as being soluble and effective for transportation of some drugs.
  • Polymeric nanoparticles: These are tiny particles that carry molecules to locations within specific cells. Polymeric nanoparticles could preserve the drug and increase the likelihood of a drug reaching a specific location within the brain.  Additionally, these can open the blood-brain barrier and maximize duration of drug release.
  • Nanobubbles: These are considered tiny (nano) bubbles that contain gas within a cavity submerged in a liquid solution.
  1. Neurophysiological Assessments

Nanotechnology could be used to enhance brain imaging (e.g. MRIs) and analysis of the metabolome.  These assessments would help improve diagnoses of mental illnesses, predict responses to various treatments, and help clinicians personalize treatments to best suit their patient.  In other words, implementation of nanotechnology has potential to significantly improve psychiatric treatment outcomes.

  • In-vivo imaging: It has already been established that nanoparticles can enhance resolution of fMRI neuroimaging.  This enhancement would allow clinicians to get a better understanding of their patient’s brain activity.  Nanoparticles can be used as neural biomarkers to determine how a person’s brain may differ with depression compared to another condition.  These nanoparticle biomarkers could also be used to predict responses to antidepressants (and other psychiatric drugs).
  • Metabolome biomarker data: The metabolome refers to the entire contents of small-molecule chemicals within a biological sample.  The metabolome has been researched among those with cancer, diabetes, cardiovascular problems, and neurodegenerative diseases.  Nanotechnology could be used to assess an individual’s metabolome and understand the severity of their depression (or other mental illness).
  1. CNS modeling

Enhancing the efficacy of pharmaceutical drugs and providing more advanced biomarker data are two possible applications of nanotechnology.  Another plausible use of nanotech would be to model the human CNS (central nervous system).  It is already known that the brain is extremely complex to the extent that we currently understand space better than the interworkings of our own neural networks.

Nanotechnology could unveil how the brain is organized, the functions of various neural circuits, and offer replicable models for the testing of certain drugs prior to their usage in humans.

Neural networks: Nanotechnology is being used to develop artificial neural networks, or learning models based on biological networks.  With the advance of nanotechnology, it is hypothesized that the artificial networks will be capable of modeling a human brain, helping us determine pathological neural activity among those with depression. Nanodevices consisting of metal oxides and other materials have been used in the development of neural network models.

Specifically, nanowires represent axons and dendrites, nanocircuits represent neurons, and other molecular switches have been combined to form “CrossNets.”  These CrossNets are being engineered to contain over 1000 neurons and 1000 synapses with a silicon-based surface.  This artificial construct may provide insight as to how CNS abnormalities contribute to depression and/or other mental illnesses.

Inorganic synapses: Researchers noted that nanotechnology has already achieved success in modeling inorganic synapses.  This model was created with Ag2S nanoparticles and was reported in 2011.  It incorporated short-term potentiation and long-term potentiation.  The modeling of inorganic synapses is considered a major advancement.

  • Source: http://www.nature.com/nmat/journal/v10/n8/full/nmat3054.html
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23545476

Potential Risks of Using Nanotechnology for Depression

Despite the fact that futuristic applications of nanotechnology for depression (and other neurological disorders) are seemingly limitless, there remain an array of substantial risks.  Engineers will need to optimize nanotechnology to make it safe for human application and mitigate risks before it can be used for the treatment of depression.

Drug clearance: It is thought that various types of nanocarriers could aid in the delivery of pharmaceutical drugs to the brain.  However, one risk associated with using this technology to deliver drugs is that they may not get properly cleared from the brain.  Improper clearance as a result of nanocarrier administration may trigger inflammation and have other deleterious long-term consequences.

Environmental dilemma: The usage of nanotechnology for the treatment of depression or other mental illnesses could be disastrous for the environment.  Nanoscale materials (billionths of a meter) manufactured to help treat depression could make their way into the environment and destroy the ecosystem.  While it is already known that antidepressants are harming Starling birds (via seeping into the environment), nanoscale materials could have a similar (potentially more problematic) effect.

One hypothesized scenario is that nanoparticles could make their way into wastewater streams, ultimately killing bacteria that are necessary for ecosystems.  Destroying this bacteria may have significant unwanted consequences for nature as well as humanity.  Therefore stringent regulations of nanomaterials are warranted before they can be used on a mainstream scale.

Ethical considerations: Assuming nanotechnology can be used to treat mental illness, who’s to say that it can’t also be used to augment a person’s natural capacity?  What if a person doesn’t have a mental illness, but wants to feel even happier?  What if the usage of nanotechnology alters a person’s core personality or has long-lasting unwanted consequences?  It is important to consider ethical restraints that may be imposed upon nanotech being used to target the brain.

Immune reactions: Since nanoparticles aren’t endogenously produced by the body, they may be viewed as enemies by the immune system.  Introduction of these nanoparticles may set off a cascade of unwanted immune reactions, possibly leading to sickness and/or death.  Therefore, it is important to ensure that nanoparticles are biologically safe prior to their testing in humans.

Toxicity: There remains concern that nanomaterials could be toxic to an individual’s CNS, ultimately damaging neurophysiology.  Assuming the nanomaterials are toxic, they may end up inflicting significant damage to a person’s brain rather than improving it.  For example, these nanoparticles may accumulate upon inhalation, leading to brain damage similar to air pollution.

Laboratory mice have already experienced increased rates of cancer, heart disease, neurological dysfunction, and expedited aging as a result of nano-titanium exposure.  It is thought that the nanoparticles damaged the DNA of the mice, and increased oxidative stress.  Some experts speculate that inhalation of nanotubes may be as harmful as asbestos, ultimately causing mesothelioma.

When will nanotechnology be used to treat depression?

Authors of the 2013 review of “Nanopsychiatry” concluded that using nanomedicine for the treatment of psychiatric disorders is unlikely to happen anytime soon.  That said, they noted that psychiatrists should be aware of this emerging technology and its potential to enhance the treatment of mental illnesses like depression.  It is clear that the field of nanomedicine will continue to progress, possibly at an accelerated (or even exponential) rate with each passing year.

It’s really just a matter of time before neuroscientists are able to unveil therapeutic applications of nanomedicine for the treatment of neurological disorders.  As nanotechnology and nanomedicine continue to gain mainstream attention and demonstrate efficacy for the treatment of depression, implications of usage will need to be considered.  Should everyone be allowed to use nanotechnology and nanomedicine to enhance their homeostatic well-being?

Before you get too excited about nanomedicine for the treatment of depression, it appears as though we’re several decades away from feasible application in humans.  Some sources estimate that nanotechnology will be used in drug delivery within the next decade, but I have my doubts.  While not a professional futurist, I’d estimate that nanotechnology becomes a viable option for the treatment of depression between 2040 and 2050.

I hope my predictions are irrationally conservative and off by a longshot, but want to avoid getting sucked into the futurism hyperbole.  Some of the predictions seem so irrational, that I’m not even sure why I’m citing a (non-scientific) source.  An article from 2010 predicted that by 2025, “Nanorobots perform cellular repairs that could cure almost any disease.” (I remain skeptically optimistic).

  • Source: http://www.dummies.com/how-to/content/nanotechnology-timeline-and-predictions.html

Do you think it will be used in your lifetime to treat depression?

If you are familiar with nanotechnology, mention (realistically) what year you think nanomedicine will be used for the treatment of depression (and other mental illnesses).  Understand that many people still remain skeptical as to whether nanomedicine will ever be a practical option for usage in humans.  I think it’s inevitable that nanotechnology will intertwine with various aspects of healthcare, including psychiatry, but it may take longer than expected.  Assuming nanotechnology was safe and effective for the treatment of depression, would you let little nanobots modulate your brain?

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  • Jane Knoch October 23, 2015, 2:38 am

    This article was super well written and informative and I really appreciate this being available. I am a student trying to find out about this information and this article has been so helpful in minimalizing the hours of research I need to do for a paper. Thank you for writing this!!!!

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