Serotonin and depression

This post is an attempt at summarising and explaining a paper called 5-HT and depression: is the glass half full? Authored by Trevor Sharp and Philip J. Cowen which was published in Current Opinion in Pharmacology, 2011 volume 11 pages 45–51.

The theory that abnormally low levels of the neurotransmitter serotonin (also called 5-hydroxytryptamine, 5-HT) can cause depression is now 50 years old.

The theory arose when it was noticed that depressed patients had low serotonin levels in cerebrospinal fluid, and also that the first effective antidepressant drugs had the effect of increasing the amount of serotonin in the gap between neurons (the synaptic cleft). Since then the old tricyclic antidepressants have been replaced with medications that more accurately target serotonin, the ‘selective serotonin re-uptake inhibitors’ (SSRIs) which have fewer adverse effects and tend to be more effective at relieving depression symptoms.

Despite the progress since 1967, up to half of the patients prescribed antidepressants do not get enough relief from their symptoms, and pharmacologists still don’t clearly understand how changes in serotonin translate to altered mood.

That 5-HT (serotonin) is associated with mood and depression has been shown by pharmacological studies and also positron emission tomography (PET) studies looking at the distribution of 5-HT receptors in the brains of depressed patients. Other studies have shown that artificially restricting dietary intake of the amino L-tryptophan can cause a return of depression symptoms in patients with a history of depression. This is significant because L-tryptophan is the precursor (chemical building block) of 5-HT. Similar L-tryptophan depletion in people who have a high family incidence of depression but themselves have not had depression caused a less severe lowering of mood.

Genetic components

Depression does run in families, with a moderate to high heritability (heritability is a measure of how likely a trait is inherited, low means less likely and high indicates it is more likely to be inherited in a population).

One particular gene, slc6a4, which codes for the 5-HT transporter protein, has been well studied. Levels of the 5-HT transporter can vary by up to sevenfold within the general population. Individuals with low levels of this 5-HT transporter have increased risk of depression when associated with stressful life events. The region of this gene where it is regulated (i.e., ‘the volume control’) is rich in methylation sites which can result in semi-permanent changes to gene expression as a result of environmental influences (such as a stressed or depressed mother during pregnancy, stressful events, childhood trauma).

Neuronal Repair

Current thinking is that increased synaptic 5-HT activates a downstream gene programme that leads to enhanced neuronal plasticity which has failed because of the adverse effects of stress and other environmental and genetic factors.

In effect, some sort of stress derails the ongoing repair and maintenance of brain ‘circuitry’ which can be overcome by bumping up serotonin levels in neurons.

This idea of serotonin enabling improved neuronal plasticity in depressed patients dovetails nicely with ideas of how psychological treatments (such as counselling, CBT, DBT) function to help treat depression. Psychotherapists help a patient to reframe situations and learn more positive ways to view situations. With increased serotonin levels enabling neural repair and realignment of neural pathways, learning is facilitated and so the therapy and drug treatment work together.

I don’t want to know the future


The notebook I’m currently using for writing has some notes in the back of it written in mid-2008 when I was trying to find a way forward from being in a state of burnout. Looking back on the almost ten years since then I’ve come a long way, yet am now glad I could not see much of the path ahead at the time.

In June 2008 I applied for a job as a technical writer for a software company but was unsure if I would get the job so tried to plan how to cope with the next six months in the job I already had. As it turned out I did get the new job, which was a real blessing and gave a reprieve from the stress I had previously been carrying. What I didn’t see but is now obvious to me reading what I wrote back then, is the warning signs of depression.

The change in work enabled me to recover somewhat but two years later the black dog returned and this time there was no denying it. At least his forced me to seek help, beginning a long journey of trying to find a medication combination that worked for me. By this time I’d moved on to what in many ways was a dream job for me, but it came with the downside of a 24/7 roster. In time the shift work messed with my body clock enough to make the next cycle of depression much worse than any before, necessitating a week’s stay in a psychiatric hospital. Recovery that time was long and painful, at least a year before I could consider myself ‘normal’ and not a joyful normal at that.

This is why I’m glad I could not see the future for me in 2008. If I could have seen what was ahead I probably would have given up or run away and hidden from the world. But if I had known what was to come, could I have taken steps to avoid it?

On this I’m not sure. Certainly I’ve learned signs to watch for  so now seek help sooner than I did in the past. I also know some of the circumstances and situations that can precipitate depression so take steps to avoid or reduce the effects of those situations. However, life always carries a certain amount of stress and my depression has a definite cyclic pattern so I doubt that I could have completely avoided it.

The approach I now take is to have fences to keep the black dog out, a stick handy to push if back if it gets too close, and I try to live as fully as I can when it is not around. Yet I still hear it barking in the distance.

A personal blog

Blogging is dead, why blog? From my perspective, the short answer is, ‘because I want to’. As a longer answer I will give some backstory and explain why I am starting a personal blog.

Over the years since the end of 2009, I’ve had a number of blogs on various platforms (WordPress.com, WordPress.org, Squarespace and Ghost) in combination with half a dozen hosting providers.

My enthusiasm for blogging and frequency of posting has waxed and waned over the years. For a while I published new posts three times a week, more recently it has been less than once in six months. Four months ago I made a deliberate choice to take a complete break from blogging or even thinking about blogging for at least three months, with no expectation of returning to it. The idea behind this was to give myself a break from the blogging mindset in order to assess whether it was truly something I wanted to do or if I was just feeling obligated to maintain the blog I already had.

During that time I also managed to change jobs from one that was exacting a heavy toll on both me and my family to one that is much less stressful and has better working hours. Now that my head has had a chance to reboot I’m finding a rekindled desire to express myself in writing and so the motivation to keep a blog has returned.

Several significant mental shifts have occurred for me during the time I stepped away from blogging. I’ve recovered from a severe and prolonged period of depression, and I’m no longer actively job seeking. Both of these had a large impact on what I thought and what I was willing to publish. Now I’m thinking more positively and am not worried about what a prospective employer might read on my blog so I can feel free to write about any weird oddball topics I want to. One of my ambitions in life is to be an eccentric old man so I need to start practising!

Having had time to consider what I want to write about and whether to simply pick up one of my two existing sites to move forward with, I’ve decided to make a clean start. This will be a blog with no niche, posts will be about whatever I feel like writing or is taking up my brain space at the time. This is a personal blog, the connecting theme is stuff I am personally interested in, no other criteria needs to be met. And because I am entering a new phase of life myself it seems appropriate to start fresh here and let the rest of the story emerge as we go.

Practical biblical advice for despair

When we are hungry, angry, lonely, tired or any combination of the four, our actions, reactions, and choices can be coloured by how we are feeling.

Elijah is one of the outstanding characters of the Old Testament. His epic contest with the false prophets of Baal on Mt Carmel is the high point of his career (see 1 Kings chapter 18). But Jezebel cuts short any celebration of victory, threatening Elijah with death when she catches him. So he runs for his life. I can understand that, I’d skip the country too.

He also becomes quite bummed out by the whole situation, seeing no hope for himself or the nation.

There is plenty of speculation that Elijah was depressed at this time. I’m wary of projecting 21st century psychological ideas onto a person who lived 2,800 years ago. We only have an outline of the highlights of Elijah’s life and that’s not enough information to base a diagnosis on.

Elijah goes from outstanding courage in chapter 18 to despair in chapter 19. Despair is a bad headspace to be in and one current tool used in combating it is summed up with the acronym HALT. This stands for:

  • Hungry
  • Angry (or afraid)
  • Lonely
  • Tired

I can see all of these in Elijah.

He was hungry, so an angel provided food for him. He was afraid to he ran 200km (120 miles) to get away from Jezebel (he was probably also angry at her). He was lonely, telling God he was the only prophet left. And he was tired, sleeping under a broom tree in the desert. He was so fed up that he asked God to take his life.

The idea behind this acronym is that when we are hungry, angry, lonely, tired or any combination of the four, our actions, reactions, and choices can be coloured by how we are feeling. If I am feeling tired, angry or hungry, I am more likely to over react to irritations and inconveniences. By being aware of this I can try to address these things, making it easier to constructively cope with things I don’t have control over.

It seems that God did this for Elijah – he slept, then an angel woke him to eat some food, let him sleep some more and provided more food (1 Kings 19:5-7). Then Elijah took a long walk and was reassured that he was safe and would be given someone to take over the burden of being a prophet from him (1 Kings 19:15-17). God showed him that spectacular signs were not what he needed (1 Kings 19:12). The outworking of seemingly ordinary events under God’s control would fulfill God’s plans.

This is a good reminder to me when I am feeling down and just want a way out. The way out of my current situation is by living through it and God will answer my prayers within the bounds of the ‘ordinary’.

Sometimes when life sucks I just need to have some dinner and get an early night. Once I am fed, rested, and have connected with those I love, I’m better able to seek God.


Image: The Prophet Elijah by Daniele da Volterra, courtesy of Wikimedia Commons

Scripture references:

Ref 1 Kings 19:1-14 Ahab told Jezebel all that Elijah had done, and how qhe had killed all the prophets with the sword. Then Jezebel sent a messenger to Elijah, saying, “So may the gods do to me and more also, if I do not make your life as the life of one of them by this time tomorrow.” Then he was afraid, and he arose and ran for his life and came to sBeersheba, which belongs to Judah, and left his servant there. But he himself went a day’s journey into the wilderness and came and sat down under a broom tree. tAnd he asked that he might die, saying, “It is enough; now, O Lord, take away my life, for I am no better than my fathers.” And he lay down and slept under a broom tree. And behold, an angel touched him and said to him, “Arise and eat.” And he looked, and behold, there was at his head a cake baked on hot stones and a jar of water. And he ate and drank and lay down again. And the angel of the Lord came again a second time and touched him and said, “Arise and eat, for the journey is too great for you.” And he arose and ate and drank, and went in the strength of that food uforty days and forty nights to vHoreb, the mount of God. The Lord Speaks to Elijah There he came to a cave and lodged in it. And behold, wthe word of the Lord came to him, and he said to him, “What are you doing here, Elijah?” He said, “I have been very xjealous for the Lord, the God of hosts. For the people of Israel have forsaken your covenant, ythrown down your altars, and killed your prophets with the sword, aand I, even I only, am left, and they seek my life, to take it away.” And he said, “Go out and stand on the mount before the Lord.” And behold, the Lord passed by, and ca great and strong wind tore the mountains and broke in pieces the rocks before the Lord, but the Lord was not in the wind. And after the wind dan earthquake, but the Lord was not in the earthquake. And after the earthquake a fire, but the Lord was not in the fire. And after the fire the sound of a low whisper. And when Elijah heard it, ehe wrapped his face in his cloak and went out and stood at the entrance of the cave. And behold, fthere came a voice to him and said, “What are you doing here, Elijah?” He said, “I have been very jealous for the Lord, the God of hosts. For the people of Israel have forsaken your covenant, ythrown down your altars, and killed your prophets with the sword, and I, even I only, am left, and they seek my life, to take it away.” (ESV)

Repentance

Some choices result in a harder path than others, but the first step along those paths is often no more difficult than the first step down an easy path that leads to destruction.

The last couple of posts I’ve written have looked at some habits I am cultivating to help me live a better life. Self-improvement is fine and I have plenty of room for improvement, but my motivation is not primarily to attain to an improved self.

My motivation to change is based on repentance.

What is repentance?

Oddly, repentance is not commonly discussed on Christian blogs, or even in churches. This is weird because it is the foundation of Jesus’ message to us:

“Repent, for the kingdom of heaven is at hand.” (Matthew 4:17 ESV)

Jesus consistently called everyone to repent, a concept that entails ‘a change of mind’ and both turning away from sin and toward God. Nobody is exempt, all of us sin and so all of us need to turn from that sin and re-orient our lives Godward. It is a deep change of heart which then results in changed behaviour as we live according to new priorities.

This is the demand of Jesus to every soul: Repent. Be changed deep within. Replace all God-dishonoring, Christ-belittling perceptions and dispositions and purposes with God-treasuring, Christ-exalting ones. (Thoughts on Jesus’ Demand to Repent by John Piper)

Is once enough?

Reading through the Gospels it can seem as if repentance is a single major life event in which a person makes a total break with their old sinful ways and from then on lives fully devoted to God. Life experience and a closer look at the New testament shows this to be an inaccurate idea. The Apostle John writes:

If we say we have no sin, we deceive ourselves, and the truth is not in us. If we confess our sins, he is faithful and just to forgive us our sins and to cleanse us from all unrighteousness. (1 John 1:8–9 ESV)

This clearly indicates that followers of Christ still sin and need to repent and confess their sin. For some church traditions repentance and confession can be a weekly occurrence, my own church does not have a formal confession tradition so this can easily be overlooked. Perhaps closer accountability might have pulled me up sooner, I’m not sure.

A Lenten journey

I suspect that I needed to hit rock bottom to force me to face a multitude of sins in my life. The Bible refers to the Israelites as being stiff-necked (Exodus 32:9), in other words ‘perversely obstinate’ and even resisting the Holy Spirit (see Acts 7:51) – a description which also fits me. While I may never know for sure, it could be that my annus horribilis was necessary to force me to either turn towards God or turn fully away from Him and so seal my fate.

So this Lent I am moving through an unplanned process of repentance and pruning. (I was going to use the word ‘refining’ but there is nothing refined about this process). The hardest parts of last year were due to depression, something I cannot control. The hardest parts now are seeing all the choice points at which I gave in to foolish, selfish and sinful decisions which I justified to myself because I felt too weak to choose better. That is a lie.

Some choices result in a harder path than others, but the first step along those paths is often no more difficult than the first step down an easy path that leads to destruction. Depression does impair decision making, yet I was still able to make the choice of asking my wife to help me get treatment rather than taking the overdose I had in my hands. I’m sure grace played a large part in that also, why did I not allow God’s grace and the strength of the Holy Spirit help me in other decisions?

Joy in repentance

Repentance is hard to walk through, it involves brokenness and humiliation in recalling past sins, but it is not a bad thing. To turn from sinful ways and run to Jesus is actually the best thing. To acknowledge sin is painful, yet it is the pain of having a cancer cut away – it leads to healing. Best of all, it leads to acceptance with God and this is a joyful experience even while wounds may sting.

I tell you, there is joy before the angels of God over one sinner who repents.” (Luke 15:10 ESV)


What others have to say on this topic:

Scripture references:

Exodus 32:9 And the LORD said to Moses, “I have seen this people, and behold, it is a stiff-necked people. (ESV)
Acts 7:51 “You stiff-necked people, uncircumcised in heart and ears, you always resist the Holy Spirit. As your fathers did, so do you. (ESV)

Image: ‘Forgiven Much’ by Keith Johnson (see Luke 7:47: “Therefore I tell you, her sins, which are many, are forgiven—for she loved much. But he who is forgiven little, loves little.”)

Baby steps

Last year my Bible reading went out the window. This was an effect of depression, not the cause, but it did not help. It took huge effort to read even a single chapter, an effort I often could not summon in the midst of depression.

In these early stages of my journey to living a better life, I am setting small goals that I hope will be easily attainable while providing big payoffs over time.

One of these goals is to read 5 chapters of the Bible each day. This is enough to get me through the entire Bible in one year even if I skip the odd day. Also, I’ve done it before so know it is achievable with a little focus.

Last year my Bible reading went out the window. This was an effect of depression, not the cause, but it did not help. It took huge effort to read even a single chapter, an effort I often could not summon in the midst of depression. Now I am able to read more easily it is time to correct the imbalance.

Why read the Bible?

Firstly, because this is how I grow in my understanding of God and how I should live as one of His people.

Secondly, as I read and ponder the Scriptures, the teachings of Jesus and His Apostles take root in my heart. They then have a chance to affect and change my thoughts and attitudes. This is the sort of change that really makes a difference, more so than merely following the latest self-help fad.

Thirdly, reading the Bible washes away my own faulty thinking. By filling my mind with words, thoughts, poetry and stories that are from God I crowd out the mistaken ideas and beliefs I have about myself, others and life that otherwise cause me to make bad choices.

How?

I’ve found two useful ways of reading to enable these three benefits to occur. One is to read slowly, thinking over what each sentence means, what it was written to achieve and how that applies to me. The other way is to read more quickly, covering a lot of ground but persisting until the ‘washing’ effect I mentioned has occurred and my thoughts are aligning themselves with what I’ve been reading.

Both approaches take time, but to read 5 chapters at a sedate pace only takes around 15 minutes which can easily fit into most daily schedules. The real battle is often the willpower to block out competing distractions and simply start.

To keep track of my progress I have a printed list of the books of the Bible and the chapters in each book. I simply cross off each chapter once I’ve read it. This allows me to read in whatever order I like while keeping track of progress. There are smart phone apps but I’ve found they don’t give the flexibility of pen on paper.

Here are some suitable checklists:

(I am only recommending the checklists from these websites, I cannot vouch for the other content of the sites)

For a good discussion of the benefits of reading the Bible see:


Image: Shutterstock

Rock bottom

What I am aiming for is to be a better person. Not perfect, not even ‘the best’, just better than I am now.

The inside of an old industrial chimney shaft photographed from the bottom - circular stone wall with tree growing from it and blue sky with white clouds in the opening in the centre, verticalIn 2014 I hit rock bottom.

In just one year I dug myself into a huge credit card debt, gained 10 kg of excess weight, was admitted to a psychiatric hospital in a suicidal state, and almost ruined my marriage. Not my best effort.

Fortunately my depression has improved and my wife is graciously giving me a chance to make things better. I urgently need to change how I “do life”. This year my blog will trace my journey to ‘a better me’.

This is not about ‘radical’ or extreme changes, there is no room for such things when I am in debt, have health problems and have to work full time to support my family. It is also not a quest for perfection, all of us let ourselves and others down every day. What I am aiming for is to be a better person. Not perfect, not even ‘the best’, just better than I am now.

Because I have made such a mess of things and failed in a multitude of ways, this self-improvement project will range over many areas. Of particular interest to me is how to make changes stick and finding what will have the biggest payoff for even small improvements.

Do not be afraid

I can worship God, pray to Him, cry out to Him and be heard and helped by Him no matter what my physical, mental or emotional state.


2014 was a dark year for me, by God’s grace and with a lot of support from my wife and kids I lived through an awful valley of depression. Thankfully, I am now doing OK, but the experience has caused me to reconsider some of what I read in the Bible in a new light. One such thing is the exhortation to not fear:

Be strong and courageous. Do not fear or be in dread of them, for it is the LORD your God who goes with you. He will not leave you or forsake you. (Deuteronomy 31:6 ESV)

Do not fear or be in dread, the Lord your God goes with you. He will not leave or forsake you. For those of us who live in the ambiguity of faith and depression these are astonishing words.

An impossible command

Firstly, to be depressed and told not to fear or dread is an impossible thing. Fear, dread, anxiety are hallmark traits of this mental illness and those who are unwell cannot prevent these emotions and associated thoughts from occurring. Yet the Bible consistently commands us to do the impossible, for example:

Count it all joy, my brothers, when you meet trials of various kinds, (James 1:2 ESV)

Normal people do not consider it joy when things are going badly, they get upset, annoyed, grumpy and sad. Joy in such situations springs either from some sort of delusion or from a hope or goal that is unaffected by the current circumstances. The command to have joy or to rejoice is rife in the New Testament (e.g., Matthew 5:12, Romans 5:3, Philippians 4:4).

What is the point in commanding something that is humanly impossible to fulfill?

Moses, the prophets, the apostles and God Himself are well aware of our weaknesses and that while we might be willing in spirit to live a life of purity, holiness and discipleship, in the messiness of real life it is usually only a short time before we stumble and fail to live up to our high aspirations (see Mark 14:38). This is true for each of us as individuals and even on a national scale for historical Israel.

Failure in obedience to God is inevitable. But sometimes we are like Peter and cannot be told, so have to experience failure first hand. Then once we are faced with the shattering truth of our failure, inability and sin, we say to God, “don’t come near me, I am too sinful” (see Luke 5:8). At this point we are given the promise of God’s presence:

The LORD your God who goes with you.

The unshakeable promise

Like the kid facing a bully whose Dad says, “Don’t worry, I will come with you”, God promises to cross over the Jordan river with the Israelites to face their enemies in the land of Canaan.

This is the God who parted the Red Sea and destroyed the Egyptian army, who opened the earth to swallow those who challenged His authorised spokesman, and provided food for the horde of Israelites in a desert for 40 years. God is powerful, well worth having beside you in a fight.

How about when the ‘enemy’ is from within? When my fear is fueled by my own heart and mind? God’s power and strength are great, but I am anxious that such strength could crush me.

In Jesus we see more of God than power alone, He is also gentle and carries us in our despair:

Surely he has borne our griefs
and carried our sorrows;

(Isaiah 53:4)

Jesus also promised, “I will never leave you or forsake you” (Hebrews 13:5) and “I am with you always, to the end of the age” (Matthew 28:20). Even in the depths of despair when it feels as if God has deserted me, I can trust that He determined long ago not to do so.

An unseeable promise

But I still do not see or sense God near me. This is not surprising when God is described in the Bible as “the invisible God” (Colossians 1:15), and “eternal, immortal, invisible” (1 Timothy 1:17) with Jesus telling us that, “No one has ever seen God” (John 1:18).

What did Jesus mean when He said, “I will never leave you or forsake you” then about a month later ascended into heaven?

God is spirit, and Jesus had previously told His disciples, Nevertheless I tell you the truth: It is expedient for you that I go away; for if I go not away, the Comforter will not come unto you; but if I go, I will send him unto you. (John 16:7 ASV). The Comforter, (also translated as ‘Helper’, ‘Counselor’, ‘Advocate’) is the Holy Spirit and this is the One who is promised to never leave us or forsake us.

As Spirit we cannot interact or sense God through our physical senses. However, we are not only physical beings, we have a spirit too and God gives life to our spirit through rebirth by faith in Jesus as the Son of God. This means that my spirit can commune with the Holy Spirit who is always present.

I may not be able to feel it through my senses, but I can worship God, pray to Him, cry out to Him and be heard and helped by Him all in the realm of the spiritual no matter what my physical, mental or emotional state. He will not leave, He will not abandon me, and He can strengthen me by His Spirit. Fear and despair may come, but in my despair God’s power is undiminished and His resolve to be with me and strengthen me step by step, breath by breath through the darkness is backed by repeated promises through the Bible.


Image: iStock

When I am weak

when-i-am-weak

As we stare down the rapidly looming freight train of Christmas, it drags with it the realisation that 2014 is almost at an end. Frankly, I will be happy to see the last of this year, or at least the difficulties it has contained. To quote Queen Elizabeth II, for me 2014 has been an ‘annus horribilis’. This year brought weakness and brokenness in my mind and soul of an intensity that nearly did me in.

Recovering from such a place has taken most of the year, and while I’m now much better it has left a sharp awareness of vulnerability along with some fear of ending up in such a mess again. It has been hard work to implement changes of lifestyle to improve chances of recovery, but much of the improvement is due to other people helping me, especially my wife. I suspect that it is by God’s grace that I did not fall so low while I was single and had nobody close to spot when I needed help.

There are many such graces which I now notice looking back over the valley we are emerging from. These attest to God having been with me despite my inability to perceive Him while passing through the darkness and gloom. This also reminds me of some parts of the New Testament where our human weakness is highlighted as having been taken into consideration in God’s plan for our salvation:

For while we were still weak, at the right time Christ died for the ungodly (Romans 5:6 ESV).

There are times when we do not have the ability to even cry out to God for what we most desperately need, yet He has already preempted such times of desperation by taking our weakness and sin upon Himself so that even the barrier of being weak is no longer a barrier between us and Him. I consider this one of the most hopeful truths of the Gospel; that being weak, foolish, sinful, or despised need not keep us from God. And that nobody in the Church has the right to boast as if they get God’s favour by their own merit because in truth none of us do, or ever will:

But God chose what is foolish in the world to shame the wise; God chose what is weak in the world to shame the strong; God chose what is low and despised in the world, even things that are not, to bring to nothing things that are, so that no human being might boast in the presence of God (1 Corinthians 1:27–29 ESV).

The great thing about this is that within the body of Christ (the Church) we all have various times of relative weakness and strength so when one member is weak those who are in a place of strength at that time can walk alongside and lift the weaker one up for a while. We all have ups and downs and I am convinced that it honours God more to ask for help when we need it than to feign strength and walk in falseness and pride, refusing assistance despite it being obvious to others that we need help.