This article is a continuation of the first one, it focuses more on the mental health perspective.
- Creatine deficiency
- Major depressive disorder (MDD)
- Bipolar disorder
Considering I’ve delved into the basics of creatine and its uses about cognitive functioning in my last post, I won’t be stating them in this one. For a short overview about creatine, its health benefits, and its risks when it comes to cognitive performance, I suggest reading the first article.
This one focuses on the other side of health. Namely, our mental health. I’ve previously mentioned how people, who were diagnosed with bipolar disorder, reported increased manic symptoms after they started following a regime of creatine supplementation. But this little piece of information represents only a fraction of current research about creatine and mental health.
I’d like to start with two defects, one being an error in creatine synthesis, and the other a creatine transporter defect. In the first one, our body isn’t able to produce creatine itself, and in the second the transporter malfunctioning prevents uptake of creatine into muscle and brain cells. But more importantly, people who have either of these defects are much more susceptible to brain cell death, abnormalities in one of the cellular components, developmental delays, speech and language impairments, autism, and epilepsy. Not something to be taken lightly. [1, 2]
I’m mentioning these effects, because they are a testament to how important proper and optimal creatine production/levels actually are in our bodies.
Interestingly, when people with the creatine synthesis defect receive supplementation between 0.3 – 0.8 g/kg per day, there are visible cognitive and behavioural improvements. Such doses are very high for an average person though, and not really recommended. People with the transporter malfunctioning, however, do not witness such improvements. [3, 4]
Stress is more important than you realize. Psychological stress is associated with impairments in energy metabolism. This increases the susceptibility of our brain cells to oxidative stress, a very dangerous imbalance, where it’s more likely your body won’t be able to combat damage done to cells as effectively as it could otherwise.
There are a few general ideas how creatine supplementation can be beneficial. Mitochondrial dysfunction, one of the possible consequences of stress, might be partly reversible with creatine supplementation. Another possibility is creatine’s safeguarding ability. It prevents oxidative damage through its antioxidant activity. 
However, it’s important to stress (no pun intended) that these things haven’t been studied in humans on a large scale. While there are smaller human studies, the mechanisms have been mostly studied in mice. Therefore, randomized controlled trials will give us more insight into the real potentials of creatine for the treatment of certain mental disorders.
Many of you have probably heard of schizophrenia. It’s most commonly characterized by psychotic episodes. These are events where the person experiences an alteration in their thoughts, they can lose sense of reality, hallucinate, become disorganized, irregular patterns of speech become present, as well as catatonic behaviour and other symptoms.
Some of the neural underpinnings of schizophrenia are impairments in neuronal density, metabolic function, and cellular integrity in different parts of the brain. 
All of these can lead to a lessened ability of one’s brain cells to effectively communicate. And to no surprise, schizophrenic patients seem to have abnormalities in their creatine-phosphocreatinte pathways within the emotional and executive brain regions. In some of them, they have even observed a connection between creatine metabolism and cognitive functioning.
With all that said, in one study where people with schizophrenia were supplemented with creatine, their symptoms did not improve . Possibly due to the heterogeneity of their symptoms and the underlying causes. We must keep in mind that scientists have recently uncovered that schizophrenia is a combination of eight distinct genetic disorders and thus represents a colourful variety of symptoms which can be manifested in someone.
As any other mental disorder, MDD and its clinical symptoms should be taken seriously. At the same time, it’s probably one of the more generally known disorders because many people like to equate feeling “depressed” with being diagnosed with major depressive disorder. Well, it doesn’t work that way. MDD is an illness with attributable symptoms which last over a certain time period, as any other illness. While feeling depressed is (usually) only a temporary state.
In any case, creatine seems to be a promising therapeutic agent for MDD.
Patients with treatment-resistant depression, a type where the conventional approach doesn’t seem to be very effective, were ordered to add a 3-5 g supplementation of creatine for four weeks in one study. They reported an improvement in mood. 
In another study, adolescents were ordered to supplement with 4 g of creatine daily for 8 weeks. Their depressive symptomatics improved, as well as the phosphocreatine concentrations in their brains. 
There are a few clinical trials underway to see whether there would be further improvements in depressive symptoms in people with depression.
Another severe illness is bipolar disorder. It’s characterized by one manic episode, a period when you’d be extremely confident, reckless, euphoric etc., and by a depressive episode. This results in shifts between mood states, ranging from so-called highs (manic states) to lows (depressive states).
So far, there has been one study which assessed whether creatine supplementation would be helpful. Contrasting the findings of depression, it seemed that creatine might have induced a manic episode in two people with bipolar disorder after three weeks of their supplementation regime. Therefore, resulting in a mood shift probably caused by creatine. 
However, it was one study and only two patients from this one study. You can guess by yourselves that these results aren’t highly representative for a grander scale of people.
Interestingly, anxiety disorders are the most common class of mental disorders in the US, they affect around 18% of the population. 
So far, one study assessed the connection between this disorder and creatine. People with treatment-resistant posttraumatic stress disorder (PTSD) saw improvements in their symptoms. The ones, who were depressed at the same time, benefited the most from the supplementation. 
As we can see, research with creatine and different mental illnesses is an ongoing and hot topic to study. Creatine does show promising results in some disorders as a side treatment, while showing less impressive results in others. Further investigation will surely shed more light here and enable us to make claims about it with greater certainty.