Dr Quentin Huys is an Honorary Consultant Psychiatrist with C&I’s Complex Depression, Anxiety and Trauma service, and a Senior Clinical Lecturer at the Max Planck UCL Centre for Computational Psychiatry and Ageing Research. His interests are in mood disorders and addictions, particularly alcohol addiction.
At C&I’s latest “Mental Health Matters” event for Trust members, entitled the “Unhealthy mix between alcohol and mental health” he gave an overview of the impact of alcohol on the brain and its inter-relationship with mental health issues.
Here he explains in more detail the neurobiology of alcohol, and why it is so dangerous in the context of mental health.
The impact of alcohol on the brain
Alcohol affects the very basics of how our brain works. The brain consists of billions of neurones that talk to each other via synapses. These are magnificent structures where electrical information – technically the excitation of a neuron - is converted into a chemical signal that can in turn produce electrical activity in the next neuron down the line.
The way this happens is that electrical signals lead to the release of molecules called neurotransmitters or neuromodulators. These attach themselves to receptors on the next neuron. When they do so, a new electrical signal is generated in the next neuron. Alcohol affects both neurotransmitters and neuromodulators.
How it affects neurotransmitters and neuromodulators
Neurotransmitters are the workhorse of brain cell communication. They are used throughout the brain, and don't represent any particular information, but are a bit like letters that can be combined into words to mean something. One such neurotransmitter is called GABA (Gamma-Aminobutyric Acid). Alcohol influences the receptors for GABA. Neuromodulators on the other hand are a bit more special. They are chemical signals generated only by a few small clusters of cells deep in the middle of the brain, but broadcast widely across the brain. One such neuromodulator is called dopamine.
To understand alcohol, both the impact on GABA and on dopamine is important. GABA is the main inhibitory neurotransmitter in the brain. Because lots of neurons talk to each other and excite each other, the brain is in a bit of a dangerous place. All the positive feedback can generate explosive activity resulting in epilepsy.
To avoid this, there has to be inhibition in the system, and GABA is the key player in this. Alcohol stimulates GABA receptors, and thereby dampens activity in the brain. It is thought that this is why it produces an immediate reduction of anxiety, and overdoses can lead to coma.
The dangers of alcohol and its impact on GABA receptors
If there is a constant supply of alcohol, however, the brain receptors adapt by reducing GABA receptors. All is good as long as there is alcohol in the system driving the few remaining GABA receptors hard. But if a regular drinker stops very suddenly, say from one day to the other, then suddenly there is insufficient inhibition in the system and epileptic fits can result. This is why a heavy drinker should never stop drinking without medical support. It's dangerous. Less severe versions of this result in the morning withdrawal symptoms well-known to heavy drinkers - anxiety, sweating, tremor, nervousness, agitation, anger, dysphoria.
In fact, this is the new "normal" when drinking heavily - the GABA adaptation puts the brain into a constant state of anxiety, irritation and agitation.
How alcohol can cause depression and anxiety
To understand why we continue drinking despite these negative effects, we have to turn to two other aspects of alcohol. First, like other drugs, it mischievously seems to sort out the mess it creates: The first morning dose of alcohol appears as a helpful friend - miraculously resolving all tremors, anxiety and nausea it caused itself in the first place, subtly sending the signal that alcohol helps with emotional upset. This is of course a lie. By constantly driving the brain into an aversive state, alcohol alone can cause depression and anxiety.
In addition, it turns out to be neurotoxic, killing brain cells and thereby undermining our ability to recover. It also has a long list of other negative effects on the body, ranging from liver to the heart, our arteries, the pancreas and virtually every cell in the body, all of which conspire to make us feel ill.
Alcohol’s impact on dopamine
To really understand why alcohol keeps us drinking it in these situations, we have to turn to its effect on dopamine. Dopamine signals when things are better than expected. This error in prediction can be used to learn by a variety of different brain areas. Hey - something happened that was better than we thought. Let's make sure we remember that and see if we can repeat it. Alcohol affects dopamine signalling such that this kind of learning becomes more prominent. It turns out that this type of learning is what underlies habits, and so alcohol directly alters our brain's mechanism for acquiring habits by affecting the learning signals.
Alcohol and mental health
Now that we have some understanding of how alcohol affects our brain, let's think about how it relates to other mental illnesses. First, its impact on dopamine can lead to the most obvious illness, namely addiction. When addicted, only drug-related cues and activities are relevant to us. Our day shrinks to finding drugs and ingesting them. We neglect our work, our friends, our family.
Because nothing else is rewarding again, our enjoyment of life more generally takes a hit and we start the descent into depression. That is the consequence of alcohol's impact on dopamine. Indeed, stopping drinking, or smoking, or any other drug of abuse for that matter, is an excellent anti-depressant. In fact, kicking the habit is often the best anti-depressant and anti-anxiety intervention around.
Second, the impact on the GABA receptor puts us into a constant state of tension. First, this tension resembles anxiety, and indeed while one drink relaxes us by stimulating GABA, the nth drink gets rid of GABA and so causes a state of constant anxiety.
Hence, alcohol can cause disorders of anxiety, and promoting everything from obsessions to panic attacks. Because of how hard this is on us, it further promotes depression. More generally, mental illness is always an interaction between the environment and our predisposition. Some people have serious mental illnesses, but are in a very supportive environment and are essentially fine. Others have a very lucky predisposition, but are in such rough environments that they suffer mental illness. Alcohol addiction, by putting us into a constant state of anxiety, and tension, functions as a harsh environment, and worsens all known mental illnesses, from schizophrenia to bipolar disorder, from borderline personality disorder to autism.
So why then, if it makes all these mental illnesses worse, do people with common and serious mental illnesses have a predilection for alcohol? The answer, of course, lies in the lovely short-term effects, which are the exact opposite of the long-term effects. While the short-term effects are easy to ascribe to alcohol, the stealthy long-term effects are not, and so the drug that causes the problems can long feel like a crutch without which life is impossible.
Treatment of alcohol addiction
So how is alcohol addiction treated? First, because alcohol, like other substances, pretends to be such a good relief to our emotional havoc, treatment involves building motivation for change. Not only do we have to learn to deal with emotions we regulated with alcohol again, but often one's life has to be rebuilt from the ground up. A new job found, friendships terminated and re-established, debts paid, medical consequences of drinking lived with etc.
Facing all this is hard, particularly if alcohol has long allowed us to avoid all these problems for so long. Once motivation has built up, the work starts with detoxification. This involves either a slow gradual reduction in drinking to allow the GABA receptors to recover, or treatment with a drug that temporarily stimulates GABA receptors and is gradually withdrawn, again allowing the GABA receptors to recover without an epileptic fit. Third, the hard work begins. Learning to deal with emotions and rebuilding a life without alcohol.
This last stage is the hardest, and this is why relapses are common and simply part and parcel of the progress out of addiction.