Talk:Dopamine hypothesis of schizophrenia

Wiki Education Foundation-supported course assignment

This article was the subject of a Wiki Education Foundation-supported course assignment, between 10 May 2021 and 6 August 2021. Further details are available on the course page. Student editor(s): Jnsellers. Peer reviewers: Jaycar71, Tgil89, Pammul, SomaYukihira21X.

Above undated message substituted from Template:Dashboard.wikiedu.org assignment by PrimeBOT (talk) 19:43, 16 January 2022 (UTC)

Chicken & Egg

Isn't there a possibility that there is a chicken and egg problem. Is the dopamine activity the cause or the effect of the psychosis? Has this been explored?--Jack Upland 06:14, 28 November 2005 (UTC)

Well dopamine antagonism seems to relieve some of the 'positive' symptoms suggesting that the dopamine activity (if you believe in the dopamine hypothesis) underlies the psychosis to some degree. Whether the dopamine dysfunction is secondary to some other disease process or neurological change is difficult to say, since it would require having studied people's brains before they were symptomatic, which is a very large undertaking if you expect only around 1% of people to develop it. --Coroebus 20:48, 26 January 2006 (UTC)

You would have to prove a dopamine difference before giving a "medicine" to a schizophrenic to help them, otherwise any and all brain changes in schizophrenia can be attributed to the drugs given by psychiatry. "Maintenance antipsychotic therapy: is the cure worse than the disease? "http://www.ncbi.nlm.nih.gov/pubmed/2021 --Mark v1.0 (talk) 12:48, 23 October 2015 (UTC)

Article needs re-balancing after addition of Seeman et al refs

This article has been recently edited to include a great deal of research by Philip Seeman. The major changes were here, by Seemanph, so I presume they were done by the author of the research himself.

Consequently, the article needs re-balancing, as it is currently quite one-sided.

- Vaughan 13:47, 11 May 2006 (UTC)

Which side is under-represented? Davis, 213.51.99.242 23:22, 10 December 2006 (UTC)

There's no 'chicken and egg' debate. Anything which increases the amount of dopamine also exacerbates the positive symptoms of schizophrenia. Prolonged use of both cocaine and amphetamine increase dopamine and can cause schizophrenia-like symptoms in people who have no predisposition to the condition. In people predisposed to developing schizophrenia, quite small amounts of these drugs will exacerbate positive symptoms. Dopamine is made from the amino acid, tyrosine. Taking supplemental tyrosine will exacerbate positive symptoms, at least initially. I found the article to be an excellent and concise overview of the subject. William Davidson 25th November 2006

However, it is not clear that every psychotic experience is linked to increased dopamine release (ref the work on NMDA receptor antagonist induced psychosis that is not reverse by antipsychotics) - Vaughan 23:46, 10 December 2006 (UTC)

Second the Motion - Rebalance please!

The chicken-egg question is highly relevant.

I am uncomfortable with the unqualified assertion that schizophrenia is due to a dopamine defect. In order to prove that assertion, one would need to measure dopamine activity in a synapse and prove that it was measurably abnormal as defined by a statistically derived range. Every psychiatrist of course knows that such a test is impossible with current technology so there is no proof to be had. This is why the patient information booklet that comes with every psychotropic prescription drug contains the phrasing 'is believed to'... rather than 'is known to'...

I am uncomfortable with leaving such a large block of criticism unchallenged - I will try and provide my little bit of balance point by point. This is a very simple initial hypothesis. For the electric engineer you seem to be, this is akin to 'A transistor is like a switch'. The scientific world has moved on, from dopamine to dopamine receptors, from dopamine receptors to GABA receptors to glutamate / glycine interactions and brain network hypotheses. Focusing on the dopamine hypothesis as anything more than a first-level abstraction is like teaching schoolkids conventional current. Egmason (talk) 04:11, 29 January 2014 (UTC)

So is the problem in the dopamine synapses, or is it in the bodies of the dopamine nerves themselves, or is it in the organization of the dopamine neurons? Or is it possible that the defect has nothing at all to do with the dopamine system and is actually located in another kind of nerve entirely, or due to some other external stimulus that has not yet been identified? (After all, pain is not an endorphin deficiency disease, nor is it an acetylcholine excess disease!) Or does schizophrenia involve the extended organization of the brain? All of these possibilities are still in play with current technology.

Every electrical engineer knows that the stability of a feedback system (even a simple linear one) is quite sensitive to the loop gain and the phase (frequency-dependent delay). If we attribute the psychosis of schizophrenia to thoughts that feed upon themselves, we can immediately apprehend that schizophrenia is an out-of-control feedback process, which is most likely why it is so frequently associated with the exaggerated oscillating mood excursions of manic-depression and anxiety. We then must acknowledge that the feedback path that is involved in schizophrenia involves broad segments of tissue, manifests as audible or visible hallucination that is essentially the same as the howl of speaker-microphone feedback in a public address system, and traverses dozens of likely suspects in the neuron family as it traverses the cranium.

Neuronal transmission is a complex interaction between receptor-gated and voltage gated ion channels, exocytotic vesicles, excitatory and inhibitory receptors (which can be either presynaptic or post-synaptic) and remote humoral mediators. there are multiple feedback and feedforward connections. Egmason (talk) 04:11, 29 January 2014 (UTC)

Analog electrical engineers make a living by being quite good at compensating the gain and phase of simple linearized feedback loops in order to keep them stable and robust. It is necessary to select the circuit topology with deliberation and care, choose appropriate component types and values, and set the operating point (DC bias condition) in a mid-range where there is adequate headroom to keep the circuit performing in a linear mode without clipping (distorting the waveform). Clipping causes loss of gain as well as increased delay, and it puts the stability of the entire loop in jeopardy. A poorly compensated feedback loop is otherwise known as an oscillator.

Psychiatrists don't have the luxury of being able to retrofit better components. It is more like trying to fix your computer by alternately dipping it in water or oil. In the forties some advocated lobotomy / leucotomy to provide a Programmable read-only memory type modification, but this was ended with the development of the dopamine receptor antagonists. Egmason (talk) 04:11, 29 January 2014 (UTC)

In a discrete time system (digitized signals) all of these same principles apply, with the added complication that the digitized signals include quantization noise, rounding and truncation errors that also impact fidelity as well as stability if not carefully controlled. The brain has within itself a pulsed, firing nerve model that is exactly analogous to digitized electronics. In tweaking neurotransmitter levels, the psychiatrist is essentially skewing the sample rate and the sensitivity threshold of the quantizer simultaneously. Neurons also have some form of complicated processing capability in the nucleus that receives synaptic impulses from many receptor sites on multiple dendrites and converts those into output pulses on the axon(s). The effect of neurotransmitter level on that internal nerve processing engine is never mentioned in the literature (that I know of anyway), it always seems to be assumed that the nucleus operates independently of the rate of firing even though we know this cannot be true.

Any electrical engineer knows that it is possible to affect the stability of a marginally stable electrical system by adjusting bias points and power supply voltages. Sometimes just waving one's hand over the circuitry has a dramatic effect if the wiring has antenna-like characteristics that interact with the impedance of the human hand. The subtle shifts in gain and delay can have destructive effects on circuitry if uncontrolled oscillations lead to excessive power dissipation in vulnerable circuitry. All of these effects are undesirable in electrical circuitry and engineers therefore design these effects out of the system.

Franz Mesmer and James Braid did the hand-waving thing too. Egmason (talk) 04:11, 29 January 2014 (UTC)

Any electrical engineer also knows that in a nested-loop feedback scenario, every single nested loop must be independently stable in order for the global loop to be stable too. If the human brain contains millions of nested feedback loops, and an instability in any one of those nested loops can cause instability in a wide region of tissue, how can a person then claim definitive proof that all of those loops would otherwise be independently stable under 'normal' neurotransmitter activity, and that the effective mechanism of any psychotropic drug is in 'normalizing' the neurotransmitter levels in a schizophrenic? Obviously it is impossible to make such a claim. Even the simplest and grossest surgical experiments in grand-mal epileptics prove without any doubt that the entire brain can malfunction if a small portion of tissue goes into uncontrolled feedback. Seizures can be induced through brain trauma, and they can be eliminated through surgery. No one is claiming that epilepsy is due exclusively to a defect in neurotransmitter levels even though psychotropic drugs that modulate neurotransmitter levels are commonly used to treat epilepsy. Obsessive-compulsive has also been cured when a patient, driven to suicidality by the severity of his problem, fired a bullet through the roof of his mouth and lobotomized the tissue responsible for his behavior problem.

This comes from your unproven assertion that feedback instability is responsible for schizophrenia. Some seizures produce hallucinations or paranoia, which does actually add to you assertion. Antiepileptic medications are believed to work by focusing on glutamate interactions or regulating neuronal ion channels; not neurotransmitters directly. Egmason (talk) 04:11, 29 January 2014 (UTC)

I could advance a hypothesis that, rather than having excessive loop gain due to a neurotransmitter defect, schizophrenics actually have a delayed phase response due to overly long cross-connected neural feedback paths that arise when spontaneous connections between unrelated nerve cells are formed in an uncontrolled growth process similar to cancer, and no one could prove me wrong. Schizophrenics are known to have pre-existing anomalies in brain structure that present in advance of psychotic symptoms. Besides being impossible to measure the neurotransmitter activity within a synapse, it is also impossible with today's technology to parse all the connections in any brain (even a simple one from a primitive mammal), so it is impossible to gather any statistical data on how long each feedback path is or to even collate an exhaustive list of all the neural feedback paths, never mind compare 'normal' and 'schizophrenic' wiring or analyze stability of multiple nested neural feedback loops with software modeling. The average electrical engineer is lucky if (s)he can simulate a circuit with ten nested feedback loops comprised of a hundred active components (neurons) without causing a convergence failure in the simulation algorithm (even with today's highly advanced computers) or getting a completely erroneous result due to modeling inaccuracies. Yet somehow many of today's psychiatrists are claiming to have ruled out neural organization as a (the?) cause of schizophrenia, as if they had God-like omniscience of all things in the brain.

Those must be the bad psychiatrists, because this is pretty much the hypothesis that I tell my patients that have a tertiary education or a strong interest in science. There is a strong model that says that schizophrenia is a neurodevelopmental disorder (Causes_of_schizophrenia#Prenatal), probably involving changes in growth factors leading to abnormal growth and / or synaptic pruning. Brain biopsy results show abnormal placement of neurons in layers where they do not usually end up. For links on the neuroscience modelling currently being done, look at the Blue Brain Project.Egmason (talk) 04:11, 29 January 2014 (UTC)

A complex, nested, digitized nonlinear feedback processor such as the millions of such nested loops in the brain begs the question of whether the problem lies in the neurotransmitter activity or the organization of the neurons, or both, or neither. Just because one can affect various aspects of neural function by tweaking neurotransmitter activity proves NOTHING about the etiology of a disease.

In addition to the signal path feedback loops, electrical circuitry also has bias feedback loops that maintain a stable operating point even in the presence of external factors such as temperature, power supply voltage, and transistor process characteristics. Brains have a similar bias point. Every psychiatrist knows that when a psychotropic drug is introduced, the neurons compensate by physically modifying their structure, either by changing the number of transmitter/receptor/re-uptake/destructor(?) sites, or by physically altering the wiring itself by pruning neurons here and growing new ones over there (otherwise known as 'chemical lobotomy'). The psychiatrist often has to increase the dosage over time in order to overcome the homeostatic compensation process, and in so doing, is the psychiatrist purely tinkering with the neurotransmitter levels, or is such person also tinkering with the wiring too? Which change is ultimately responsible for the effectiveness of the drug? Usually, the change in the wiring is destructive in the absence of the drug (after withdrawal) and is generally referred to by frightening terms like tardive dis and tardive dat, but in the presence of the drug, is that adaptive change partly responsible for the improvement in overall behavior?

Destructor = Monoamine oxidase Egmason (talk) 04:11, 29 January 2014 (UTC)

What about second- and third-order effects, such as the effect on neurotransmitters that are not specifically targeted by the drug in question? One would expect that the need to find a unique cocktail of four or more drugs for the average schizophrenic (and play with dosage levels on a continual basis, sometimes to even radically alter the entire regimen when it ultimately fails), belies the simplistic explanations that are offered about 'dopamine defect'. Not every side effect is undesirable. If it were simply a matter of dopamine activity, then all the drugs in question should behave in substantially the same fashion, but truth is that even highly selective drugs that primarily affect only a single neurotransmitter can have radically different effects in different individuals. No one ever bothers to explain these differences in terms of dopamine activity, because there essentially is none. So in that case how can one make the claim that dopamine is solely responsible?

(1) The dopamine hypothesis is itself dis-proven by the newer antipsychotic medications which are not primarily dopamine-blocking, but work on many different receptors. (2) Modern Psychiatrists try not to use the term 'schizophrenic' which labels people by just one aspect of their make-up. (3) Getting stuck on 'dopamine is solely responsible' is like demanding we stop the war on Vietnam - now! Egmason (talk) 04:11, 29 January 2014 (UTC)

I often played with electrical circuitry, changing the voltage, tweaking the gain and phase, heating it up, cooling it off, just to see how it behaves. It was my job. I am very familiar with these concepts. I observed how defective circuit designs could be made to work by tweaking the power supply levels up or down, or by controlling the temperature. I also took advantage of tightly controlled parameters such as impedance, voltage, current, temperature, and transistor process matching to reduce the overhead of gain and phase margin requirement while pushing the performance of circuitry to the limits of technology. I played God in my own way, but least I was experimenting with inanimate objects! If I stressed a circuit to the point of permanent damage, it did not have to figure out how to compensate for that damage. It got thrown away, or cross-sectioned. Psychiatric patients should not have to labor under the illusory claim that their drug-induced brain damage was a natural process, yet I have seen just such lies bandied about like gospel by the same people who make extreme claims about neurotransmitter levels.

How much use is 'natural' vs 'unnatural'. Cancer is natural. Schizophrenia is natural. Antibiotics are unnatural. Antiretrovirals are unnatural. Heart and lung transplants are unnatural. Egmason (talk) 04:11, 29 January 2014 (UTC)

As far as the normal brain function is concerned, it is quite obvious that the brain has its own normal feedback paths that continually generate externally observable oscillations, otherwise known as alpha, beta, theta, delta waves. There must be much higher-frequency waves that are only observable inside the brain. It is also quite obvious that some degree of uncontrolled feedback is present in all of us in the form of 'worry' and creative thinking that has a noteworthy survival advantage, namely, the ability to think ahead and hypothesize. Such behavior is known as non-causal output, meaning that it is generated by the feedback loop itself rather than external stimulus. Non-causal systems in electronics are normally undesirable since we typically do not want robotic assembly lines to begin generating their own designs in the spray paint on the hood, but in living beings such behavior is essential to survival.

Deep brain stimulation is successfully being used to treat depression (see below), OCD and Parkinson's disease currently. Egmason (talk) 04:35, 29 January 2014 (UTC)

I can easily imagine any variety of defects in the non-causal brain functions, and since there is no way to measure the pathways that give rise to that non-causal output, my imaginations are just as valid as anyone else's but probably far less interesting than those of the average manic-depressive schizophrenic who might have unique insight into his/her own condition by virtue of subjectively experiencing it first-hand.

I predict that 'neurotransmitter' convention will crumble under the sands of time as knowledge advances, and will eventually be seen to have been inculcated by a profit-driven pharmaceutical industry that so far is the only game in town for desperately ill people who cannot re-organize and stabilize their neural pathways through training alone (i.e. meditation, exercise, study, psychotherapy). I also predict that at some time in the future, most of the so-called 'neurotransmitter defects' we keep hearing about will be proven illusory, and that a systems approach similar to what is used in electronics will eventually take over (when psychiatrists begin teaming up with systems analysts who are facile with the discipline of calculus) that relies primarily on re-organizing the brain through training and control of growth factors but only incidentally relies on psychotropic medication. Until then we will have 'side effects'.

See Biological neuron model for your beloved calculus (yuck, don't get it, can't stand it). See Computational neuroscience and Default mode network for information about medium and large-scale brain networks, and Neural engineering for ideas about using these things for treatment. The interconnecting network hypotheses are really hot in the Neuro-cognitive circles, while the physical science boffins are still plugging away at receptor sub-types and complex gene-expression models. Egmason (talk) 04:11, 29 January 2014 (UTC)

I fully understand the reluctance of psychiatrists to be honest about the limitations of their knowledge. From the healing perspective, it is always a cost-vs-benefit trade-off regardless of whether or not the hypothesis of etiology is valid. Openly acknowledging just how tentative the science behind the explanations is and admitting that they could be inducing defective neurotransmitter levels in an attempt to shut down defective and overactive neural feedback loops might frighten patients away from effective treatments, especially if the patients also comprehend that they are paying a price in terms of permanent brain damage in order to gain a modest degree of drug-dependent functionality back. I know of several people who make that trade-off every day for some inner peace and I see the struggle on their faces. When I look at them I can see immediately that even if their neurotransmitter levels have been pegged at maximum or minimum with heavy doses of drugs, they are still struggling to keep themselves together. Confusing them with elaborate systems analysis is not necessarily going to help them, but somehow I would hope that at least in scientific circles the debate would be honest and there would always be acknowledgment of the near certainty that psychotropic drugs are actually masking the symptoms rather than correcting a probably fictional 'imbalance'.

I am happy to discuss the limitations of my knowledge, but when it accounts for up to 60% of my treatment effect, I also try to project certainty and boundless optimism. Perhaps you are confusing that for belief. Egmason (talk) 04:35, 29 January 2014 (UTC)

If anyone has research data that supports my contentions, it should be included in Wiki. To me, it seems self-evident that the emperor has no clothes, but then I am not a doctor. Just remember, a doctor is not an engineer either so we should stop expecting that degree of precision from doctors. Do psychiatrists really know why their treatments 'work'? No! Neither do I! - CherylJosie

I am a Doctor. (Dammit Jim, I'm a doctor not an engineer!). I am a therapist, a researcher, a teacher, a neuroscientist. I acknowledge there are a lot of grey areas around (and within) what we know, but what we know, we know well. Egmason (talk) 04:11, 29 January 2014 (UTC)

RE: Deep brain stimulation is successfully being used. This is a false claim.

"DBS surgery comes with a host of other potential surgical risks, including: up to an 8% risk of bleeding in the brain that can lead to permanent deficit, or death 1.1% of the time. an 8% chance of stroke or permanent neurological deficits. a risk of infection of up to 15%. 5% risk of hemorrhage. 2% risk of seizure. the potential for air to enter the brain, and leakage of cerebrospinal fluid or brain fluid." source http://www.madinamerica.com/2015/09/adverse-effects-perils-deep-brain-stimulation-depression/ --Mark v1.0 (talk) 16:16, 24 October 2015 (UTC)

100%-8%-1.1%-8%-15%-2%-2%=60.9%; still room for hope. I'm not saying its a good option, nor that it isn't risky. Okay, after further reading, I will withdraw this claim about depression. It is still sitting in 'not proven', and given the effort that has gone into it, that probably means it's a dead duck. Egmason (talk) 04:56, 17 April 2016 (UTC)

Neutrality Tag?

This article strikes me as pretty balanced - evidence for and against is presented. Would anyone have an issue with removing the neutrality tag? Or could we get a list of issues that need to be addressed? StripeyBadger 11:04, 5 March 2007 (UTC)

I am replying a little late but I just wanted to chime in and say , wasn't there an article on the adrenolutin hypothesis on here (wikipedia)? Very recently? If it did actually get removed that is a tragic show of ignorance. The dopamine hypothesis and the andrenolutin hypothesis and the serotonin hypothesis should all be given equally room, or at least included in a single article.

Serotonin?

The sentence

The blockade of serotonin (5-HT2) receptors does not contribute to either the antipsychotic action or to alleviating the Parkinsonism that can occur at high doses of antipsychotic medication.[7]

is very anachronistic. Can its writer either elaborate or explain its function? Insomnis 04:38, 20 July 2007 (UTC)

Comorbidity with Parkinson's Disease

One of the cogent pieces of evidence against the dopamine hypothesis is that Parkinson's disease and schizophrenia may co-exist in the same person. The only reference this article currently makes to Parkinson's disease is that people treated with dopamine lowering medicine for this illness may show psychotic symptoms. More needs to be said on evidence against the dopamine hypothesis in this article. ACEOREVIVED 21:08, 9 November 2007 (UTC)

Dopamine medication to treat Parkinson's (e.g. L-DOPA) increases not lowers dopamine function and can indeed can cause psychosis. - Vaughan 11:40, 10 November 2007 (UTC)

"Theory has been discredited"?

The theory has been discredited and proven as far too simplistic.

I am not expert on the subject, but as far as I am aware, this is an exaggeration. Is there any evidence to back up this claim?

As far as I know (do correct me if I am mistaken), yes the original hypothesis was overly simplistic. However, in recent years a revised dopamine hypothesis is emerging, which focuses on hypofunction and relates to the negative symptoms in schizophrenia too. Moreover, it is not a deterministic hypothesis; so to state that it is discredited because other factors can influence the onset of schizophrenia would be incorrect.Ihatechoosingnames (talk) 02:24, 11 April 2008 (UTC)

Sounds good to me. I worked on the chemical imbalance theory article and pretty well came to the same conclusion. Feel free to make the edits here, you have my blessings. --scuro (talk) 02:34, 11 April 2008 (UTC)

What about Nicotine?

If cocaine and amphetamines may be associated with schizophrenia, why not nicotine, which also messes with dopamine in a major way? Maybe smoking makes you crazy, in addition to killing you. —Preceding unsigned comment added by 75.72.202.72 (talk) 00:49, 6 July 2010 (UTC)

Removal of entry in "Evidence against..." section

"The excitatory neurotransmitter glutamate is now also thought to be associated with schizophrenia. Phencyclidine (also known as PCP or "Angel Dust") and ketamine, both of which block glutamate (NMDA) receptors, are known to cause psychosis closely resembling schizophrenia, further suggesting that psychosis and schizophrenia cannot fully be explained in terms of dopamine function, but may also involve other neurotransmitters.[12]"

Unfortunately, 'psychosis closely resembling schizophrenia' is vague and subjective, and can be produced via a multitude of drugs, disorders, and illnesses. removed the entry because it cannot be considered to be unbiased. 64.186.120.109 (talk) 20:07, 12 December 2011 (UTC)

I think you make a very good point about not conflating everything that superficially looks like a psychosis. At the same time, the glutamate hypothesis of schizophrenia is supported by sufficiently many sources that I'd rather not remove the material entirely. I restored it, but I also reworded it, to make it clearer that PCP/ketamine symptoms do not actually equal schizophrenia. --Tryptofish (talk) 22:35, 12 December 2011 (UTC)

Original research in introduction? "Early medical intervention is crucial in..."

I took a look at the cited sources of the introduction regarding its basis for early intervention, but it appears that the statement in the "Introduction" section regarding the effects/importance of early intervention isn't mentioned in its sources.

"...Patients on neuroleptic or antipsychotic medication have significantly less atrophy within these crucial areas. As such, early medical intervention is crucial in preventing the advancement of these profound deficits in bilateral communication at the root of all psychotic disorders. Advanced, chronic schizophrenia can not respond even to clozapine, regarded as the most potent antipsychotic, as such, a cure for highly advanced schizophrenia is likely impossible, so the value of early intervention cannot be stressed enough."

From checking the source, concludes possible hypertrophy of certain brain regions (found to be "higher caudate, putamen, and thalamus volumes" compared to nontreated and healthy subjects) due to antipsychotic medication, while discusses the relationship of certain brain regions (even apparently different from those in - ie. "Corpus Callosum [abnormalities were] related to the severity of their psychotic symptoms") to symptoms. However, to say the least, neither source considered the antipsychotics to thus prevent deterioration or deficits, or consider it as a basis for early intervention; it seems to me that the studies were nowhere near saying that.

This is also conflicting with the Psychosis and Early intervention in psychosis articles, which on the other hand cite sources directly regarding early intervention, finding early intervention to only be controversial or questionable in its long-term benefit, with little gains sustained after 5 years.

This suggests to me that this is original research. However, I'm not an expert on the subject myself, and a good amount of the introduction seemed to be too technical for me to really evaluate. I'm also not that familiar with Wikipedia procedure :\ so I'd like to check with you guys - would it be appropriate to, say, tag the section as original research? What should we do about this? 96.48.197.114 (talk) 10:45, 22 August 2013 (UTC)

This is not 'original research'; as a search or the links you point to will show, there is a large body of published work around Early Intervention. As you also point out, the early hope of the field has not been proven with time, but the hope is still there that while biological progression of schizophrenia might not be slowed by medication, people might still do better psycho-socially with more initial input. The statement might be introduced better to show its balanced context in the history of psychiatry. Egmason (talk) 00:56, 3 February 2014 (UTC)

References

evidence against section

"The antipsychotic aripiprazole occupies over 90% of D2 receptors, but this drug is both an agonist and an antagonist at D2 receptors." is there a source for this statement? it's contrary to my understanding (and anything i can find) of dopaminergic effects of aripiprazole is that it's a dopamine receptor partial agonist at D2-D4 receptors. Indeed, aripiprazole also has partial agonism at the 5ht2a receptor. — Preceding unsigned comment added by 198.49.6.225 (talk) 10:56, 6 September 2015 (UTC)

ugh, partial agonists are inherently competitive antagonists. it just seems redundant- sorry. — Preceding unsigned comment added by 198.49.6.225 (talk) 10:29, 7 September 2015 (UTC)

evidence for section

"People with Schizophrenia appear to have a high rate of self-medication with nicotine; the therapeutic effect likely occurs through dopamine modulation by nicotinic acetylcholine receptors." is there a source on this? it seems to be highly speculative to say "the therapeutic effect likely occurs..." perhaps a little more equivocation is in order, like saying "possibly" or "potentially". — Preceding unsigned comment added by 198.49.6.225 (talk) 11:02, 6 September 2015 (UTC)

Introduction: Broca's area and Wernicke's area (clarification needed)

This sentence near the beginning of the introduction "A relative excess of these receptors within the limbic system means Broca's area, which can produce illogical language, has an abnormal connection to Wernicke's area, which comprehends language but does not create it.[citation needed]" I believe requires clarification in addition to a citation. In healthy individuals these two areas are connected by the arcuate fasciculus, so the presence of a connection between these two areas is not atypical as the sentence seems to suggest. Even knowing this, the reinterpretation of the sentence is that there is something atypical about the connection, but without saying what that something is. Anditres (talk) 00:05, 31 October 2020 (UTC)

Criticisms

I was trying to add more references to the paragraph on criticisms but an other editor was too fast for me. "cite web" is accepted by Wikipedia on other pages and has a webpage on it https://wiki.riteme.site/wiki/Template:Cite_web. The additional web page reference I was about to place was https://www.medscape.com/viewarticle/823368_2 . I don't want to get into an edit war so I am leaving it for now. ( Who did the third WRONG edit? I don't know)--Mark v1.0 (talk) 17:23, 27 October 2021 (UTC)