"Tom: What happens if you fall in love?
Summer: Well, you don't believe that, do you?
Tom: It's love. It's not Santa Claus."
"Narrator: Most days
of the year are unremarkable. They begin, and they end, with no lasting
memories made in between. Most days have no impact on the course of a life. May
23rd was a Wednesday."
INTRODUCTION:
Standard antidepressant medications that are currently available to patients
takes up to weeks or even months for them to feel the intended effects. Such
prolonged periods are unable to aid a considerable number of patients. So, it
is no surprise that the highest priority in psychiatric research has been
towards the discovery of faster acting alternatives for antidepressant
medications.“Depression affects at least one in six of us at some point in our lifetime, and better treatments are urgently needed,” said senior author Abraham Palmer, PhD, professor of psychiatry and vice chair for basic research at UC San Diego School of Medicine. “A better understanding of the molecular and cellular underpinnings of depression will help us find new ways to inhibit or counteract its onset and severity.” [C]
It was on March 21, 2017, that the Journal of Molecular Psychiatry published a report from a study conducted by researchers at University of California San Diego School of Medicine that has revealed great potential for more effective, fast-acting, and overall better future depression treatments for patients.
They relieved signs of depression in mice by inhibiting the enzyme Glyoxalase 1 [or GLO1 for short]. This enzyme’s functions, GLO1, by inhibiting a byproduct that results from the cell's metabolism. This byproduct inhibits neurons and influences mood and behavior. The tests revealed lower levels of depression in mice within a period of 5 days. Current antidepressants such as Prozac takes up to 2 weeks or 14 days for patients to feel any form of therapeutic effect.
[while Montage of Summer
plays]
Tom: I love her smile. I love her hair. I love
her knees. I love how she licks her lips before she talks. I love her
heart-shaped birthmark on her neck. I love it when she sleeps.
"Tom: I love how she makes me feel, like anything's
possible, or like life is worth it.
Rachel Hansen: Just because she likes the same bizzaro crap you do doesn't mean she's your soul mate. Look, I know you think she was the one, but I don't. Now, I think you're just remembering the good stuff. Next time you look back, I, uh, I really think you should look again."
BACKGROUND INFORMATION:
Individuals may experience anxiety,
apathy, general discontent, guilt, hopelessness, loss of interest, loss of
interest or pleasure in activities, mood swings, or sadness. Sleep patterns may
also become abnormal such as waking up unusually early, sleeping for excessive
periods of time, insomnia, or general restless sleep.
Overall, the physical body may be overwhelmed with fatigue, loss of appetite, or excessive hunger. Symptoms also include social isolation, excessive crying, agitation, or irritability. These effects create a loss or lack of concentration, slowness in activity, or thoughts of suicide.
Overall, the physical body may be overwhelmed with fatigue, loss of appetite, or excessive hunger. Symptoms also include social isolation, excessive crying, agitation, or irritability. These effects create a loss or lack of concentration, slowness in activity, or thoughts of suicide.
“Narrator: If Tom had learned anything... it was that
you can't ascribe great cosmic significance to a simple earthly event.
Coincidence, that's all anything ever is, nothing more than coincidence... Tom
had finally learned, there are no miracles. There's no such thing as fate,
nothing is meant to be. He knew, he was sure of it now.”
"Tom: What happened? Why? Why didn't they work out?
Summer:What always happens. Life."
Treatment consists of antidepressant
medications, talk therapy, or a combination of the two. Increasingly, research
suggests these treatments may normalize brain function associated with
depression. Therapies include Cognitive behavioral therapy, Behavior therapy,
and Psychotherapy.Cognitive behavioral therapy is form of therapy through conversation that is focused on modifying negative thoughts, behaviors, and emotional responses associated with psychological distress. With behavior therapy the focus is on modifying harmful behaviors associated with psychological distress. Then there is psychotherapy where treatment involves the mental or behavioral disorders through talk therapy.
It is common for treatment of
depression to be paired with therapy alongside medication. Although medication
is available for treating clinical depression, some of these drugs take a long
time to work or may pose health risks because of their side effects. Some of
the medications include those known as Selective
Serotonin Reuptake Inhibitor (SSRI). SSRI’s ease symptoms of depressed mood and
anxiety. A common SSRI medication is known as Sertraline [treats depression,
obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD),
premenstrual dysphoric disorder (PMDD), social anxiety disorder, and panic
disorder].
Between 2009-2010, 8 million individuals in United States and 60 million
worldwide were medically diagnosed with major depressive disorder. The Centers
for Disease Control and Prevention (CDC) reports show that depression is common
and affects the quality of life and well-being of many people. However, current
studies conducted on mice with depression are paving the way for faster acting
and more effective treatment of depression in humans. [D]
RESEARCH:
Many current pharmacological treatments for neuropsychiatric
disorders, such as anxiety and depression, are limited by a delayed onset of
therapeutic effect, adverse side effects, abuse potential or lack of efficacy
in many patients. These off-target effects highlight the need to identify novel
mechanisms and targets for treatment. [B]
Abraham A. Palmer, PHD and his colleagues had previously discovered a molecular process which influenced mice with depression through inhibition of GLO1 enzyme. This reduced symptoms of anxiety in mice. Cells generate
energy and when this happens, a byproduct is also produced. This byproduct
inhibits neurons, subsequently influencing behavior. In normal situations, the
enzyme GLO1 functions to remove this byproduct. It was quickly discovered that
by inhibiting GLO1, this results in an increase of activity in specific neurons
favorably.
However, when GLO1 levels were over active-concluded from several previous studies- this might also contribute to depression. These observations led to the team investigating the effects of inhibiting the enzyme for more effective ways to treat major depression.
However, when GLO1 levels were over active-concluded from several previous studies- this might also contribute to depression. These observations led to the team investigating the effects of inhibiting the enzyme for more effective ways to treat major depression.
"Tom:"Go for it" "You can do
it"? That's not inspirational, that's suicidal. If pickles goes for it
right there, that's a dead cat. These are lies. We're liars. Think about it.
Why do people buy these things? It's not 'cause they wanna say how they feel.
People buy cards 'cause they can't say how they feel or they're afraid too. We
provide the service that lets them off the hook. You know what? I say to hell
with it. Let's level with America. At least let them speak for themselves!
Right? I mean, look! What-What is this? What does it say? "Congratulations
on your new baby." Right? How 'bout, "Congratulations on your new
baby. Guess that's it for hanging out. Nice knowing you."
Vance: Sit down, Hansen.
Tom: How bout this one, with all the pretty
hearts on the front? I think I know where this ones going. Yep! "Happy
Valentines Day, sweetheart. I love you." That sweet? Ain't love grand?
This is exactly what I'm talking about. What does that even mean,
"love"? Do you know? Do you? Anybody?
McKenzie: Tom...
Tom: If somebody gave me this card, Mr. Vance,
I would eat it. It's these cards, and the movies and the pop songs, they're to
blame for all the lies and the heartache, everything. We're responsible. *I'm
responsible.* I think we do a bad thing here. People should be able to say how
they feel, how they really feel, not you know, some words that some stranger
put in their mouths. Words like "love"... that don't mean anything.
Sorry, I'm sorry. I, uh... I quit. I'm... There's enough bullshit in the world
without my help.”
Since the greater amount GLO1 activity that Palmer’s mice displayed the more anxious the animals were, the team decided to reduce this activity by genetic manipulation or by administering two different GLO1-inhibiting chemicals. By modifying Glo1 (glyoxalase I) activity, researchers have been able to show regularity in the behavior of mice that were not only prone to anxiety but also seizures. These observations subsequently led Palmer and his team to question whether they could reduce signs of depression by inhibiting this GLO1 enzyme.
The researchers used several different antidepressant tests. They compared
responses in three groups of mice: 1) untreated, 2) treated by inhibiting GLO1,
either genetically or with an experimental compound, and 3) treated with Prozac,
a selective serotonin re-uptake inhibitor commonly used to treat depression.
"Summer: We've been like Sid and Nancy for months
now.
Tom: Summer, Sid stabbed Nancy, seven times
with a kitchen knife, I mean we have some disagreements but I hardly think I'm
Sid Vicious.
Summer: No, I'm Sid.
Tom: Oh, so I'm Nancy...
[Pancakes arrive]
Summer: Let's just eat and we'll talk about it
later. Mmm, that is good, I'm really glad we did this. I love these pancakes...
What?
[Tom gets up and walks away
from the table]
Summer: Tom, don't go! You're still my best
friend!"
The first tests they used were the tail suspension test and
the forced swim tests, which are often used to determine if a compound is an
antidepressant. They then evaluated
the animals’ behavior. They used several established tests to measure
depression-like behavior in the animals, such as observing how hard they tried
to escape difficult situations and how they coped with chronic mild stress. The
same tests were performed with mice that were not treated and again with mice
that had Prozac [aka: fluoxetine] in their system – the most popular/common
antidepressant medication prescribed to patients.
RESULTS:
Animal studies
suggest switching off an enzyme called GLO1 may rapidly relieve symptoms of
depression. When the enzyme GLO1 was inhibited in mice, depression-like behaviors
declined within five days.
Depression-like
behaviors declined within five days of treatment for the animals in which GLO1
had been inhibited. Depression-like behaviors also declined in animals that
were given Prozac, but for this group, it took two weeks for the antidepressant
to take effect.
The scientists say
inhibiting GLO1 likely increases the level of a brain chemical called
methylglyoxal, which influences neural signaling.
CONCLUSION:
Although this new treatment has shown promise in treating
depression in mice, more time is needed before GLO1 inhibitor can be safely tested in
humans. This is an exciting time in research for treating depression after
studies such as this one has given hope that there are new and unexplored
approaches to treating depression exist.
Currently, research in this area is still ongoing as medicinal chemists persist on better developing compounds that inhibit the enzyme, GLO1. Results from these studies will potentially aid in providing quick-acting and ultimately more efficient treatments for depression. Additional research will help specialists to refine these treatments for individuals who struggle with depression.
Currently, research in this area is still ongoing as medicinal chemists persist on better developing compounds that inhibit the enzyme, GLO1. Results from these studies will potentially aid in providing quick-acting and ultimately more efficient treatments for depression. Additional research will help specialists to refine these treatments for individuals who struggle with depression.
Palmer and team have applied for a patent related to this work. They are already working with medicinal chemists at UC San Diego to develop drugs that target GLO1. Meanwhile, Dulawa also published their own article critiquing the ways in which specific behaviroal and molecular approaches are being applied in addition to the goal of aiding other researchers in discovering new antidepressants. [C]
"Summer: I just... I just woke up one day and I
knew.
Tom: Knew what?
Summer:Well, you know, I guess it's 'cause I was
sitting in a deli and reading Dorian Gray and a guy comes up to me and asks me
about it and... now he's my husband.
Tom: Yeah. And... So?
Summer: So, what if I'd gone to the movies? What
if I had gone somewhere else for lunch? What if I'd gotten there 10 minutes
later? It was, it was meant to be. And... I just kept thinking... Tom was
right.
Summer: Yeah, I did.
[laughs]
Summer: I did. It just wasn't me that you were
right about."
Links:
https://www.bbrfoundation.org/content/animal-studies-suggest-new-path-fast-acting-antidepressant [A]
http://www.medicalnewstoday.com/articles/316486.php [D]
*Please note! These images are not mine. They were found on various tumblr, pinterest, google image sites! If any are yours please let me know so that I can give you credit for them! Also the people in the images have no relation to the diseases, illnesses, or cancers I write about. Thanks so much & enjoy~
Quotes found on: imdb.com/500daysofsummer
Images found on: filmscreencaps.com/ 500daysofsummer
*Please note! These images are not mine. They were found on various tumblr, pinterest, google image sites! If any are yours please let me know so that I can give you credit for them! Also the people in the images have no relation to the diseases, illnesses, or cancers I write about. Thanks so much & enjoy~
Quotes found on: imdb.com/500daysofsummer
Images found on: filmscreencaps.com/ 500daysofsummer
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