Is the concept of a neurochemical imbalance a myth? Split from Overdose of Antipsychotics

[tkadm30]

My first doctor told me I had a neuro chemical imbalance

 

 

The neuro chemical imbalance thing is a myth. https://chriskresser.com/the-chemical-imbalance-myth/

There's simply no evidences to support this theory.

 

 

In his book, Valenstein clearly and systematically dismantles the chemical imbalance theory:

1. Reducing levels of norepinephrine, serotonin and dopamine does not actually produce depression in humans, even though it appeared to do so in animals.
2. The theory cannot explain why there are drugs that alleviate depression despite the fact that they have little or no effect on either serotonin or norepinephrine.
3. Drugs that raise serotonin and norepinephrine levels, such as amphetamine and cocaine, do not alleviate depression.
4. No one has explained why it takes a relatively long time before antidepressant drugs produce any elevation of mood. Antidepressants produce their maximum elevation of serotonin and norepinephrine in only a day or two, but it often takes several weeks before any improvement in mood occurs.
5. Although some depressed patients have low levels of serotonin and norepinephrine, the majority do not. Estimates vary, but a reasonable average from several studies indicates that only about 25 percent of depressed patients actually have low levels of these metabolites.
6. Some depressed patients actually have abnormally high levels of serotonin and norepinephrine, and some patients with no history of depression at all have low levels of these amines.
7. Although there have been claims that depression may be caused by excessive levels of monoamine oxydase (the enzyme that breaks down serotonin and norepinephrine), this is only true in some depressed patients and not in others.
8. Antidepressants produce a number of different effects other than increasing norepinephrine and serotonin activity that have not been accounted for when considering their activity on depression.

 

"A theory that is wrong is considered preferable to admitting our ignorance.” – Elliot Vallenstein, Ph.D.

Edited January 7, 2017 by tkadm30

[Phi for All]

 

The neuro chemical imbalance thing is a myth. https://chriskresser.com/the-chemical-imbalance-myth/

There's simply no evidences to support this theory.

 

I disagree that it's a "myth". Like much of science, it's helped a great deal, but our understandings of its limitations are growing. Typically, this means we need to dig deeper and find even better explanations. It doesn't mean it's a myth or a dead-end, it just means we need a broader, more comprehensive understanding than we can achieve by simply thinking of the brain as a chemical soup.

[jbn22]

 

The neuro chemical imbalance thing is a myth. https://chriskresser.com/the-chemical-imbalance-myth/

There's simply no evidences to support this theory.

 

 

"A theory that is wrong is considered preferable to admitting our ignorance.” – Elliot Vallenstein, Ph.D.

 

"No evidence" is misleading. The model of a neurotransmitter dysfunction in the genesis of depression and psychosis is something that has significant clinical relevance. In terms of psychosis, the productive symptoms quickly (i.e. within days) respond to antipsychotic medication. Of course, this isn't to say that there's an underlying cause (especially considering newer genetic findings, brain atrophy caused by neuropil degeneration, etc.). But in the end, the symptoms do also seem to be caused by dopaminergic hyperactivity in the mesolimbic system. And seeing as we have yet to find a potent pharmaceutical to stop synaptic pruning in schizophrenia, we're stuck with resorting to antidopaminergic substances.

 

In terms of major depressive disorder, the mechanism of action of antidepressants seems to be more complex and related to gene expression.

In clincal practice, I find that antidepressant therapy is mainly successful in major melancholic depression. Sadly, many general practitioners seem to perscribe antidepressants whenever a patient says they're sad. Melancholic depression is, in my opinion, not characterized by sadness, but much rather in a lack of emotional response. A

[tkadm30]

 

"No evidence" is misleading. The model of a neurotransmitter dysfunction in the genesis of depression and psychosis is something that has significant clinical relevance. In terms of psychosis, the productive symptoms quickly (i.e. within days) respond to antipsychotic medication. Of course, this isn't to say that there's an underlying cause (especially considering newer genetic findings, brain atrophy caused by neuropil degeneration, etc.). But in the end, the symptoms do also seem to be caused by dopaminergic hyperactivity in the mesolimbic system. And seeing as we have yet to find a potent pharmaceutical to stop synaptic pruning in schizophrenia, we're stuck with resorting to antidopaminergic substances.

 

In terms of major depressive disorder, the mechanism of action of antidepressants seems to be more complex and related to gene expression.

In clincal practice, I find that antidepressant therapy is mainly successful in major melancholic depression. Sadly, many general practitioners seem to perscribe antidepressants whenever a patient says they're sad. Melancholic depression is, in my opinion, not characterized by sadness, but much rather in a lack of emotional response. A

 

Well then, can you show us a paper which defines clearly the mecanism of this "chemical imbalance" ? Also, why no measurements of the brain neurotransmitters levels are made before prescribing neuroleptics ?

 

 

I disagree that it's a "myth". Like much of science, it's helped a great deal, but our understandings of its limitations are growing. Typically, this means we need to dig deeper and find even better explanations. It doesn't mean it's a myth or a dead-end, it just means we need a broader, more comprehensive understanding than we can achieve by simply thinking of the brain as a chemical soup.

 

That won't help. Psychiatrists generally do not examine any neuroimaging data in order to make a diagnosis. A psychiatric evaluation is based on the perceptions of the symptoms discussed by the patient. Claiming the cause of the disorder is a "chemical imbalance" without evidences of neurotransmitter dysfunction in order to pharmacologicaly regulate dopamine/serotonin levels with atypical antipsychotics is a risky business for the patient.

[hypervalent_iodine]

!

Moderator Note

The above posts in this thread have been removed from http://www.scienceforums.net/topic/66925-overdose-of-antipsychotics/page-0

While this topic remains as a discussion of the science of neurochemical imbalances and what we currently know or don't know about them, this thread shall remain where it is. However, tkadm30, if your plan is to use this thread to champion your own hypotheses, staff will have move the thread to a more appropriate sub forum. If this is your intention, please inform me via PM or by reporting this post and staff will move it.

[jbn22]

 

Well then, can you show us a paper which defines clearly the mecanism of this "chemical imbalance" ? Also, why no measurements of the brain neurotransmitters levels are made before prescribing neuroleptics ?

 

 

That won't help. Psychiatrists generally do not examine any neuroimaging data in order to make a diagnosis. A psychiatric evaluation is based on the perceptions of the symptoms discussed by the patient. Claiming the cause of the disorder is a "chemical imbalance" without evidences of neurotransmitter dysfunction in order to pharmacologicaly regulate dopamine/serotonin levels with atypical antipsychotics is a risky business for the patient.

 

 

The exact mechanisms are still not understood. Fact is that psychopharmaceuticals that counteract this imbalance lead to a significant recovery in patients suffering from schizophrenia. This is well documented (and the basis for every FDA approval of antipsychotic medication).

As for studies, you will find plenty of reviews that summarize the evidence for aberrations in neurotransmitters between control groups and schizophrenia groups.

 

As for neuroimaging data - I believe it's a matter of economics and evidence based medicine. As a practicitioner in a country with a socialized medical welfare system, it is impossible for me to justify gathering neuroimaging data of every single of my patients before perscribing them antipsychotic medications. I really wish it were easier - not so much in the area of schizophrenia (in my opinion, clinical diagnosis of schizophrenia is, in the vast majority of cases, very simple) but especially in the area of diagnosis of depression. After all, it's not rare for me to have the impression that a patient may be aggravating his symptoms in order to be diagnosed with a major depressive disorder in order to gain some welfare benefits when in fact the problem lies elsewhere.

Psychiatric diagnostics is mostly clinical. The only way that I can justify further diagnostics (every first manifestation of a schizophrenic episode or major depression gets an cMRI for example) is by saying I need further diagnostics to ensure that no organic component (inflammation, tumor) is causing the symptoms. That is limited to a cMRI and, in some cases, the collection and analysis of spinal fluid.

 

Have you ever been in a psychiatric ward that treats acutely mentally ill patients?

I think there might be a misconception as to how ill someone with an acute psychotic episode actually is. It's not a matter of "believing" delusions or not - I'm no investigator. It is, much rather, a question of formal thought disorders that provide the basis for all accessory symptoms (hearing voices, delusions, ego-disorders).

Edited January 14, 2017 by jbn22

[StringJunky]

 

 

The exact mechanisms are still not understood. Fact is that psychopharmaceuticals that counteract this imbalance lead to a significant recovery in patients suffering from schizophrenia. This is well documented (and the basis for every FDA approval of antipsychotic medication).

As for studies, you will find plenty of reviews that summarize the evidence for aberrations in neurotransmitters between control groups and schizophrenia groups.

 

As for neuroimaging data - I believe it's a matter of economics and evidence based medicine. As a practicitioner in a country with a socialized medical welfare system, it is impossible for me to justify gathering neuroimaging data of every single of my patients before perscribing them antipsychotic medications. I really wish it were easier - not so much in the area of schizophrenia (in my opinion, clinical diagnosis of schizophrenia is, in the vast majority of cases, very simple) but especially in the area of diagnosis of depression. After all, it's not rare for me to have the impression that a patient may be aggravating his symptoms in order to be diagnosed with a major depressive disorder in order to gain some welfare benefits when in fact the problem lies elsewhere.

Psychiatric diagnostics is mostly clinical. The only way that I can justify further diagnostics (every first manifestation of a schizophrenic episode or major depression gets an cMRI for example) is by saying I need further diagnostics to ensure that no organic component (inflammation, tumor) is causing the symptoms. That is limited to a cMRI and, in some cases, the collection and analysis of spinal fluid.

 

Have you ever been in a psychiatric ward that treats acutely mentally ill patients?

I think there might be a misconception as to how ill someone with an acute psychotic episode actually is. It's not a matter of "believing" delusions or not - I'm no investigator. It is, much rather, a question of formal thought disorders that provide the basis for all accessory symptoms (hearing voices, delusions, ego-disorders).

Interesting. Can you give some examples of formal thought disorders and explain what it is meant by that?

[jbn22]

Interesting. Can you give some examples of formal thought disorders and explain what it is meant by that?

 

Formal thought disorders are disorganized thinking. Since we can't "see" or "hear" thoughts, formal thought disorders are characterized by disorganized speech.

Somewhat simplified, thought disorders can be an abberation in speed, initiation and coherency - or a combination of any three.

 

A less severe thought disorder may be, for example, associative derailment (the professional term may be different, English is not my mother tongue). This would be characterized by the patient jumping from topic to topic without a sense of coherency. An example: I was brought here by the police. Police wear green uniforms. I always loved the color green. The Green Party really steps up for the environment. The environment is in big danger, due to global warming. I myself feel warm today. My coffee was very hot. I nearly burnt my tongue.

=> In other words, the formal thinking is constantly derailed by topics that have some relation to the sentence beforehand but the patient is not able to coherently explain why he was brought here by the police.

A more severe thought disorder may be absentmindedness (again, I don't know if this is the professional English term). In this, sentences are correct in syntax but are completely incoherent. Example: I was brought here by police. Oh Jesus, oh Jesus! Trump is a great president. I have four fingers and two toes.

The most severe thought disorder (in terms of coherency) is schizophasia, in which the entire language structure including is completely lost. Questions may elecit a response that seem to fit the topic, but are absolutely not understandable. For example: answering to the question "who brought you here": Trump fingers toes Jesus walking green green evil man Abu Dhabi come here you tabletop chair.

 

Thought disorders can also be a matter of speed, where accelerated thinking/speech is witnessed in manic episodes. Patients may speak very quickly (but coherently), to the point where the examiner may be unable to follow their train of thought because they are simply "too fast". Conversely, organic dysfunctions (intoxications, for example with benzodiazepines or alcohol) may cause decelerated thinking, in which the coherency remains but the time necessary to report is significantly slower.

 

And, last but not least, formal thought disorders can also be a matter of initiation/termination. Schizophrenics often suddenly stop during the middle of the sentence and don't realize that they had a thought that was suddenly terminated. Some even report that they are under the impression that someone else is "stealing" their thoughts from the outside as a way to explain why their train of thought is suddenly disrupted.

Conversely, in major depressive disorder, patients may need a long pause before being able to answer a question. Upon asking the patients why they responded to the question only with such a delay, they often say that it's as if they "try to think but there's a blockade they need to overcome", or that they lack the drive to think.

Additionally, aside from formal thought disorders, schizophrenics oftentimes also exhibit disorders in higher cognitive functions.

This means, for example, they have troubles in abstraction.

 

When asked for the meaning of a common proverb, for example, they may have troubles explaining.

Or, when asked for (for example) the difference between a child and a dwarf, they may also have troubles explaining.

Understanding sarcasm or irony may also be periodically disturbed during phases of increased disease activity.

 

Also, mentalization may be disrupted.

This refers to the ability to switch one's perspective into the mind of one else. That is, understanding that someone may have a different opinion or viewpoint, or that someone else may have different information.

For example, someone with an acute psychosis may refer to family members and friends by their names, assuming the examiner already knows all of them.

[StringJunky]

 

Formal thought disorders are disorganized thinking. Since we can't "see" or "hear" thoughts, formal thought disorders are characterized by disorganized speech.

Somewhat simplified, thought disorders can be an abberation in speed, initiation and coherency - or a combination of any three.

 

A less severe thought disorder may be, for example, associative derailment (the professional term may be different, English is not my mother tongue). This would be characterized by the patient jumping from topic to topic without a sense of coherency. An example: I was brought here by the police. Police wear green uniforms. I always loved the color green. The Green Party really steps up for the environment. The environment is in big danger, due to global warming. I myself feel warm today. My coffee was very hot. I nearly burnt my tongue.

=> In other words, the formal thinking is constantly derailed by topics that have some relation to the sentence beforehand but the patient is not able to coherently explain why he was brought here by the police.

A more severe thought disorder may be absentmindedness (again, I don't know if this is the professional English term). In this, sentences are correct in syntax but are completely incoherent. Example: I was brought here by police. Oh Jesus, oh Jesus! Trump is a great president. I have four fingers and two toes.

The most severe thought disorder (in terms of coherency) is schizophasia, in which the entire language structure including is completely lost. Questions may elecit a response that seem to fit the topic, but are absolutely not understandable. For example: answering to the question "who brought you here": Trump fingers toes Jesus walking green green evil man Abu Dhabi come here you tabletop chair.

 

Thought disorders can also be a matter of speed, where accelerated thinking/speech is witnessed in manic episodes. Patients may speak very quickly (but coherently), to the point where the examiner may be unable to follow their train of thought because they are simply "too fast". Conversely, organic dysfunctions (intoxications, for example with benzodiazepines or alcohol) may cause decelerated thinking, in which the coherency remains but the time necessary to report is significantly slower.

 

And, last but not least, formal thought disorders can also be a matter of initiation/termination. Schizophrenics often suddenly stop during the middle of the sentence and don't realize that they had a thought that was suddenly terminated. Some even report that they are under the impression that someone else is "stealing" their thoughts from the outside as a way to explain why their train of thought is suddenly disrupted.

Conversely, in major depressive disorder, patients may need a long pause before being able to answer a question. Upon asking the patients why they responded to the question only with such a delay, they often say that it's as if they "try to think but there's a blockade they need to overcome", or that they lack the drive to think.

Additionally, aside from formal thought disorders, schizophrenics oftentimes also exhibit disorders in higher cognitive functions.

This means, for example, they have troubles in abstraction.

 

When asked for the meaning of a common proverb, for example, they may have troubles explaining.

Or, when asked for (for example) the difference between a child and a dwarf, they may also have troubles explaining.

Understanding sarcasm or irony may also be periodically disturbed during phases of increased disease activity.

 

Also, mentalization may be disrupted.

This refers to the ability to switch one's perspective into the mind of one else. That is, understanding that someone may have a different opinion or viewpoint, or that someone else may have different information.

For example, someone with an acute psychosis may refer to family members and friends by their names, assuming the examiner already knows all of them.

Thanks for the explanation. Is it possible for a person having a schizophrenic episode to rationalise - with professional help - that their accessory symptoms are endogenous manifestations or is total denial a defining feature of this condition that can't be turned around or stabilised by talking therapies?

 

Note: I use the word 'denial' loosely because I appreciate the sufferer has no choice in what they experience and, from their perspective, it's all real.

Edited January 15, 2017 by StringJunky

[jbn22]

Thanks for the explanation. Is it possible for a person having a schizophrenic episode to rationalise that their accessory symptoms are endogenous manifestations or is total denial a defining feature of this condition that cant be turned around or stabilised by talking therapies?

 

All the studies I know that have been conducted on the subject show that during acute phases, talking therapies have no effect on delusions or other productive symptoms.

Nonetheless, I would say that - after a partial remission has been induced by neuroleptics - guiding a patient and encouraging them to reevaluate their psychotic beliefs may benefit them in terms of discerning symptoms from reality (in addition to a continuous use of neuroleptics). But that's just my opinion, I don't have studies to back that up.

 

As for talking therapies in the intervals between active exacerbations, psychoeducation is the way to go. It's important for patients to recognize warning signs, to be informed about medication benefits and side effects and about measures to cope with stress. This has been shown to have a beneficial effect. Also I find it important for patients and caregivers to build a trusted relationship since many symptoms (and side effects of medication, e.g. sexual dysfunction) may be embarassing to speak about.

I'm not sure as to how negative symptoms (apathy, alogy, lack of incentive, anhedonia, etc.) may be influenced by talking therapies.

[Strange]

Thanks for the explanation. Is it possible for a person having a schizophrenic episode to rationalise - with professional help - that their accessory symptoms are endogenous manifestations or is total denial a defining feature of this condition that can't be turned around or stabilised by talking therapies?

 

 

I have heard some very powerful and moving interviews with people who are fully aware that they have schizophrenia and are suffering from hallucinations (which doesn't make them any less real). One of these was a practising psychiatrist!

 

As jbn22 says, I don't know if they are always this self aware.

[MonDie]

Remember that serotonin isn't just important to mood disorders, but also to anxiety disorders, OCD, and borderline personality disorder. I'm trying to find a free-to-read pubmed publicatin that I read previously. They identified a neuroanatomical difference that mediated the relationship of Neuroticism to depression (or, longitudinally, the onset of depression?), and I think it was reduced hippocampal volume (the brain region started with H), but alas I cannot find the publication. It seems that Neuroticism comes first, ultimately contributing to the eventual onset of depression.

 

Many disorders associated with heightened Neuroticism are improved or have a better prognosis with SSRIs. For example, schizophrenia and other psychotic disorders are treated with dopamine antagonists, and these drugs temporarily resolve psychosis, but there is no direct, experimental-longitudinal evidence that they actually slow the progression of schizophrenia. On the other hand, there is evidence that the anti-depressant lithium may have a protective effect in Ultra High Risk (UHR) individuals, but alas I don't know much about this line of research, and the finding is probably complicated by the fact that many UHR individuals go on to develop psychotic depression (psychotic symptoms during depression), whereas psychosis in the absence of mood symptoms is requisite for a diagnosis of schizophrenia or shizoaffective disorder.

 

This is probably further complicated by the fact that depression may be a heterogenous disorder that requires a different treatment depending on the case. There is depression, atypical depression, psychotic depression (serotonin + cortisol). Some research has found that many cases of depression are due to low omega-3 fatty acids, and in these cases omega-3 is an effective treatment.

Edited January 15, 2017 by MonDie

[MonDie]

By the way I have no expertise in any science, and I've had no formal study in psychiatry. But my brain contains relevant information:

 

Regarding the effectiveness of delaying psychosis in UHR individuals, it occurred to me that psychosis frequently has its onset in response to "psychosocial stressors". Perhaps low serotonin, which is to related to Neuroticism traits described by excessive worrying, makes people more susceptible to the effects of stress, and the stress in turn induces problems such as depression or psychosis onset. Another problem related to stress, PTSD, has a strong relationship to depression, so depression does appear to occur in response to stress. Furthermore, there does appear to be heritable variation in susceptibility to stress.

 

Even borderline personality and dissociative disorders are related to childhood trauma. And yet, much like the other personality disorders, borderline personality is highly heritable: your genetics play a large role in your susceptibility to its development. In psychopathic personality, the "primary psychopath" is a psychopathic subtype with lower rates of depression, anxiety, and suicide (i.e. less Neuroticism), and this subtype mainly differs in the Factor 1, Fearless Dominance/Affective-Interpersonal traits. The psychopathy Fearless Dominance (FD) subscale describes lower vulnerability to stress, and this subscale is specifically correlated with holding high risk professions. That is, the primary psychopath exposes himself to more stress while experiencing fewer stress-related effects. Thus it seems that there are heritable variations in the vulnerability to the effects of stress.

 

The question then becomes: are serotonergic abnormalities and Neuroticism simply the outcomes of stress exposure to which some of us are more susceptible, or could some of these differences actually be heritable differences that exist prior to the stress and influence our susceptibility to it? The research on lithium in UHR individuals appears to be evidence for the latter. The conclusion would then be that it isn't serotonin per se, but the protective effect of serotonin against stress that may be important to preventing depression, depression being an outcome that is predicted by and preceded by Neuroticism.

 

For occupational findings:

Correlates of psychopathic personality in every day life: results from a large community study

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106400/

 

For differences between primary and secondary:

Psychopathic Personality Traits and Environmental Contexts: Differential Correlates, Gender Differences, and Genetic Mediation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387315/

 

 

 

PCL-R F1 and FD show selective relations with interpersonal dominance and narcissism, and negative associations with measures of anxiety, fear, internalizing psychopathology, and suicidal behavior (Benning et al., 2003, 2005; Blonigen et al., 2005, 2010; Hall et al., 2004; Harpur et al., 1989; Hicks & Patrick, 2006; Kennealy et al., 2007; Poythress et al., 2010b; Verona et al., 2001, 2005). Conversely, PCL-R F2 and IA show selective positive relations with impulsivity, measures of negative emotionality (distress, fear, and anger), alcohol and drug abuse, externalizing psychopathology, reactive aggression, and suicidal behavior (Benning et al., 2003, 2005; Blonigen et al., 2005, 2010; Hall et al., 2004; Harpur et al., 1989; Kennealy et al., 2007; Patrick et al., 1997, 2006; Poythress et al., 2010b; Verona et al., 2001, 2005).

Edited January 18, 2017 by MonDie