The short answer is that it doesn't matter what I think, what matters is what evidence is out there.

This is a place where literature searching is important. You have both case reports and potential biological models to search for.

I recommend JANE (http://jane.biosemantics.org) for searches where you are not quite sure where to start looking. JANE is a semantic search engine, so it can pick up literature that doesn't turn up on other engines. It also sorts the results by semantic similarity to your query.

Once you find one article of relevance, you can then begin chasing the thread by putting the abstract back into JANE, locating the article and checking references and citing papers.

Then you can return here and give us your informed summary!

Thanks Ronan Michael Conroy.

Actually, I have done my literature review but results were and are still controversial, and thus I intend to see opinions of different researchers on what possible mechanism are underlying this effect other than a conceivable hypothesis of the induction of serotonin syndrome.

Moreover, it has not yet been clearly indicated that SSRIs (that inhibit serotonin reuptake) act mostly through inhibiting which mechanisms of sertonin disposal from synaptic clefts of say PFC neurons.

This will get even more engaging and also perplexing when studies show that chronic SSRI administration significantly increase suicidal thoughts and the chance of suicide attempts in schizophrenics.

I'd be very interested to see if anyone here knows more about it than you clearly do, Bahman Sadeghi !

Certainly, there's a lot of literature on SSRIs and suicidality, something that the drug companies suppressed for as long as they could. But what's the story with the MAOIs??

You cannot combine SSRI and MAOI without enduring a high risk of inducing the serotonin syndrome. Normally MAOI needs a wash out period of two weeks. There are very many combinations of psychopharmacological substances that increase the risk for serotonin syndrome. Check e.g. serotonin syndrome on Wikipedia if you do not have more professional literature.

Cause

"A large number of medications and street drugs can cause serotonin syndrome when taken alone at high doses or in combination with other serotonergic drugs. The table below lists some of these drugs.

Antidepressants Monoamine oxidase inhibitors (MAOIs),[4] TCAs,[4] SSRIs,[4] SNRIs,[4] nefazodone,[9] trazodone[9] and mirtazapine.[4]

Opioids Dextropropoxyphene,[10] tramadol,[4] tapentadol, pethidine (meperidine),[4] fentanyl,[4] pentazocine,[4] buprenorphine[11] oxycodone,[12] hydrocodone[12]

CNS stimulants MDMA,[4] MDA,[4] methamphetamine,[13] lisdexamfetamine,[14] amphetamine,[15] phentermine,[10] amfepramone (diethylpropion),[10] serotonin releasing agents[7] like hallucinogenic substituted amphetamines,[10] sibutramine,[4] methylphenidate,[10] cocaine[10] 5-HT1 agonists Triptans[4][10]

Psychedelics 5-Methoxy-diisopropyltryptamine,[4] LSD[16] Herbs St John's Wort,[4] Syrian rue,[4] Panax ginseng,[4] Nutmeg,[17] Yohimbe[18]

Others tryptophan,[4] L-Dopa,[19] valproate,[4] buspirone,[4] lithium,[4] linezolid,[4][20] dextromethorphan,[4] 5-hydroxytryptophan,[9] chlorpheniramine,[10] risperidone,[21] olanzapine,[22] ondansetron,[4] granisetron,[4] metoclopramide,[4] ritonavir,[4] metaxalone[4]"

Quote from Wikipedia

Thanks Beatrice.

Well of course the SSRIs in particular will cause inhibition of serotonin reuptake from synaptic cleft of certain neurons as I myself had actually mentioned it in the description, and thus increase the chance of serotonin syndrome occurrence. It seems that this is the only reasonable explanation for those who take SSRIs only to treat depression and are not schizophrenic or do not have co-morbid psychiatric disorders.

We already know about the disparate classes of those drugs. But my point was the unknown neurochemical mechanisms of such adverse effects of these treatments when it comes to co-morbidity of depression and schizophrenia per se.

The fact that I based my question on is that I am seeking more opinions on biochemical path or molecular mechanisms that can shed light on the controversy of antidepressant-induced positive symptoms.

Those schizoaffective patients with postpsychotic depression that are typically prescribed with SSRIs and are normally assumed to experience less positive symptoms, but show gradually exacerbated symptoms that in many cases have led them to commit suicide. This is what still remains disputatious and I would like to see more opinions and comments about.

Dear Dr Bahman Sadeghi,

Sorry for misunderstanding you. I found a paper that may be helpful and the resaerchers may be here on RG:

Long-Term Antidepressant Treatment for Negative Symptoms in Schizophrenia: The ACTIONS Study

Thomas Barnes et al.

Verity Leeson

Schizophrenia Bulletin, Volume 43, Issue suppl_1, 1 March 2017, Pages S214–S215, https://doi.org/10.1093/schbul/sbx022.010

Published:

20 March 2017

Conclusion: The study findings suggest that citalopram can have a positive effect, at least in the short-term, on the avolition-amotivation negative symptom domain, which is recognized as a critical barrier to psychosocial rehabilitation and better social and community functional outcomes. Comprehensive assessment of side-effect burden did not identify any serious safety or tolerability issues for citalopram. Further investigation of the viability and risk-benefit of long-term, adjunctive antidepressant treatment for the treatment of negative symptoms in schizophrenia may be warranted.

Thanks.

Although this paper scrutinized "persistent negative symptoms" of SCZ and my focus here is "antidepressant-induced positive symptoms", it is also thought-provoking and insightful in terms of the findings about yet another antidepressant (citalopram) effects.

Another issue with such researches is that they often fail to provide rationale for treatment efficiency in schizophrenics who do have a co-morbid illness such as acute major depressive disorder. Thus, I would not be surprised if further research indicate rather adverse effects with long-term administration of citalopram for instance.

Co-morbidity as I mentioned before, makes efficiency of such treatments tricky and convoluted, no matter what would be their pharmacokinetics and EC50 or IC50. And this can also be discussed further.

Yes.