I can add that dopaminergic agonists (treatment for Parkinson disease) or other psychostimulants (amphetamines, cocaine) increasing the NA/DA activity of meso.cortical pathways, may also produce the symtoms of psychosis, mania or pathological gambling. In that case we call that adverse drug reaction and not illness. But not all patients have these reactions, so there must be a kind of vulneraibilty, where?

Dear Rachel,

There is no simple single CAUSE to mental illness. Genetics and environmental factors contribute to ill health. Negative life events such as deaths, losses and other traumas as well as positive life events such as marriage and celebrating christmas correlate with stress responses that vary in strength (loss of spouse gives 100 stress points and christmas 10 on Holmes-Rahe's stress scale). The stress responses affect complex physiological mechanisms such as ANS and neurotransmittors, BDNF- levels, circuits in the brain, and so forth. The work "On Emotions: A Psycho-Physiological Study" was published in 1885 and started the discussion wether feelings come first and physiological arousal follows or vise versa. The monoamine hypothesis and the dopamine hypothesis are no longer "IN". Is the "chemical imbalance" the hen or the egg? As researchers use to write: further research is needed. Links:

http://en.wikipedia.org/wiki/Chemical_imbalance

http://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor

Beatrice, thanks for your informative answer. I am interested in the relative merits of drug treatments for serious mental illness, so your comment on the current status of the monoamine and dopamine hypotheses is very interesting.

" Is there any scientific evidence that changes in synaptic neurotransmitter concentrations actually cause mental illness"

There is plenty of good evidence that many drugs that interfere with transmitters cause or closely mimic mental illnesses, including psychosis, so it is not impossible that transmitter changes can generate psychosis.  With respect to auditory hallucinations, I think these arise from a hypersensitive state of the inner ear, which then becomes susceptible to a very wide range of drugs or toxins which generate the hallucinations.

There is robust evident that prove that alteration in synaptic neurotransmitter concentrations actually cause or may complicate mental illness. Although, most likely, it may not be the sole contributing factor because environmental, genetic, or the use of drugs of abuse may lead to mental illness. In terms of drug of abuse, some of them cause changes in neurotransmitter release, neuroplasticity, and may alter the way the neurons fire to increase the vulnerability to mental illness. Even genetic factors, such as single nucleotide polymorphisms (SNPs) may lead to alterations in the expression of neurotransmitters. So really, changes in neurotransmitter concentration seem to be at the center of it all.

Key point to transformatin of mental representation is enkephalins and endorphins. There are  bigest brain-managers of all sensory related signals

Dear Rachel,

Recommended reading:

HASLER,G. PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS? World Psychiatry. Oct 2010; 9(3): 155–161.

Current neurobiological theories with the most valid empirical foundation and the highest clinical relevance are reviewed with respect to their strengths and weaknesses.

Also you should read:

Stahl’s essential Psychopharmacology (also online):

 https://stahlonline.cambridge.org/common_home.jsf

Kind regards, Matheus Arts

Stahl is very good but what came first the life event or the chemical imbalance?

Dopaminergic hyperactivity IS involved in several mental illness like:

 psychosis, mania, pathological gambling. And the symptomatology is imrpoved with D2 receptors antagonists (antipsychotics). It is well know that the higher is the affinity to the D2 rec, the lower is the efficient clinical dose of these psychotropes.

But there is always a life event inducing the dopaminergic hyperactivity (e.x. loss of somebody important, falling in love) and just some people react will symptoms.

"Dopaminergic hyperactivity IS involved in several mental illness " we know that as well as the genetic predisposition for schizophrenia based on twin studies. However this is no simple relationship.

An important question, nicely expressed. I never cease to be surprised by the subjective and oblique interpretations that people give in their answers (such as some of those above) to such apparently clear questions, however. Having said that, I realise this may well apply to my answer too, but I'll try to be objective!

If by "cause" you mean "the primary event or phenomenon that results in...", then the causes of mental illness, as mentioned above, lie in genetic and environmental risk factors. These result in a pathophysiology of the brain - in some cases, perhaps, mediated by BDNF dysfunction (mentioned above). Since brain function is, in essence, neurotransmitter function, any dysfunction of the brain will be expressed by disturbances of neurotransmission. In psychosis/schizophrenia, this primarily involves a pathology of GABA and/or glutamate neurons; in some people with schizophrenia there is, probably secondary to these neurotransmitter disturbances, a hyperfunction of dopamine neurotransmission which relates to some of the symptoms of the disorder. Such increased dopamine activity and the consequent positive symptoms can be reversed by antipsychotic dopamine D2 receptor antagonists.

There are more examples we could work through for other disorders, although there is still much we don't know. So, back to your question - neurotransmitter changes are not causal, but nor are they purely epiphenomena, they may provide the link between pathology and symptoms and thus provide a target for psychiatric drugs.

I can add that dopaminergic agonists (treatment for Parkinson disease) or other psychostimulants (amphetamines, cocaine) increasing the NA/DA activity of meso.cortical pathways, may also produce the symtoms of psychosis, mania or pathological gambling. In that case we call that adverse drug reaction and not illness. But not all patients have these reactions, so there must be a kind of vulneraibilty, where?

this is a great question. I am a Psychiatry Registrar working in a tertiary service in Newcastle, Australia.

From my understanding the concept of "chemical imbalance" was proposed as a simplistic attempt to describe treatment. In other words, because the medication had an effect by modulating neurochemicals (or their receptors) than it was derived that there is an imbalance.

Sadly, this is both too simple, and not appropriate as a description of what is actually happening. Just because a medication works on a symptom, this is not the same as the lack of the chemical CAUSING the symptom.

For example, if you hurt your knee, and I give you paracetamol, and the pain goes away. I cannot say that your knee has a paracetamol deficiency, that is deriving too much from the treatment and assuming too much about aetiology.

Thanks for all these interesting answers to my question. I had wondered whether anyone had reviewed SPECT analyses of neurotransmitter changes in disease, drug therapy and subsequent recovery. There would appear to be just too many neurotransmitters involved to come to any definitive answer.