First off, a quote from Tom Robbins from 'Even Cowgirls Get the Blues' -
"Simplicity is for simpletons"
Can't say I enjoyed the book (though that was some time ago; much has changed) but the phrase "truer words were never spoken" spring to mind.
There are so many forms of 'mental illness'.
There are symptoms that are categorized and classified in such a way as to correspond to a specific diagnoses. I know for me (at least before my two sinus surgeries) that I often didn't know whether I had a cold, the flu, or a sinus infection because the symptoms were so similar. And sure, my pediatrician/PCP (I had the surgeries when I was in elementary school or middle school) could misdiagnose a cold as a sinus infection or the reverse. But not only are there tests to determine whether a diagnosis is accurate, the symptoms are used as tools.
"Mental illness", on the other hand (as I'm sure you know), doesn't work this way. Instead, some set of symptoms are
defined to be the disease, and the focus for decades has been more on inter-rater reliability rather than validity.
clinical depression strongly correlates with hippocampal hypoplasia or atrophy i.e. a smaller than usual hippocampus.
To the extent that the hippocampus is involved in depression, this is largely due to it's role in emotional regulation in general, particularly stress, and thus it is rather hard to say that treatments which promote neurogenesis or hippocampal growth are "curing" anything. And, going back to your point about things not being simple:
"Primarily based on data from experimental studies with rodents, there is strong evidence that hippocampal adult neurogenesis is downregulated by stressful conditions and upregulated by antidepressant drugs and some other, but not all, antidepressant treatments. Some experiments have even suggested that neurogenesis is necessary for the behavioral effects of antidepressants (Santarelli et al. 2003), but this finding was not replicated using a different experimental approach (Meshi et al. 2006). Clinical evidence supporting this hypothesis includes reports of reduced hippocampal volume in MRI and post mortem studies of depressed patients, findings which could also be associated with cognitive deficits observed in these patients. However,
reduced hippocampal volume and cognitive deficits could also be shown in schizophrenic patients as well as in patients with neurodegenerative disorders such as Alzheimer‘s disease.
To date,
studies of post mortem human hippocampal tissue of patients with various types of neuropsychiatric disorders have not been able to find consistent evidence of altered adult neurogenesis in major depression. Three independent studies have set out to test the hypotheses that antidepressant treatment increases NPC number and proliferation rates, and that adult neurogenesis is disturbed in depressed patients compared to controls, but have produced contradictory findings (Reif et al. 2006; Boldrini et al. 2009; Lucassen et al. 2010b). However, decreased NPC proliferation could be linked to schizophrenia (Reif et al. 2006) and increased adult neurogenesis could be shown in patients with Alzheimer‘s disease (Jin et al. 2004)…
Despite much that has been learned from the above-mentioned studies as well as others
, one of the burning questions in the field that has not yet been satisfactorily answered is whether changes in adult neurogenesis associated with depression (or other neuropsychiatric disorders) and its treatment, are causally connected. Indeed,
increasing preclinical and clinical data give researchers reason to doubt the causal nature of changes in adult neurogenesis and the pathophysiology of neuropsychiatric disorders and their treatment. As a consequence one might wonder whether altered adult neurogenesis is merely an epiphenomenon triggered by various external manipulations.”
We find, as usual when it comes to mental health, that the correlations are weak, that there exist the same correlations for other disorders, and that the causal nature is unknown. Not simple.
According to claims associated with NSI-189 -both those made by the company Neuralstem who plan to market the compound, and corroborating anecdotal reports concerning behavioural outcomes - this compound can cause the hippocampus to increase in size by something like 20% in a matter of months
Could you supply more specific links? Because a 20% increase in the size of a major structure in an adult’s brain over a period of a few months or even years sounds fatal. Nor could I find such information on their patents,
The Scientific American magazine article I located, and the only study I found after a bit of searching (“
Is There Anything Really Novel on the Antidepressant Horizon?”) was limited to an entry in Table 1 (Select Compounds in Development for Major Depressive Disorder) where it was the only one to have, in the column “Pharmacodynamic Action”, the words “Unknown/Not Reported”.
The hippocampus is implicated in everything:
“There are several reasons the hippocampus has attracted the interest of scientists in the many disciplines that now characterize modern neuroscience—the hippocampus has something for everyone. Whether you are a psychologist interested in memory, a synaptic physiologist investigating neuronal and synaptic plasticity, or a computational neuroscientist wanting to build a neural network model, the hippocampus and its associated structures are an attractive set of brain structures on which to work. In parallel, clinicians concerned with the basis of neurological conditions such as epilepsy or Alzheimer’s disease had their attention drawn to the hippocampal formation because of the pathological processes observed to occur there and the opportunities that scientific study of this area of the brain offers for novel therapeutics. The hippocampus has been a neural Rosetta Stone.”
Andersen, P., Morris, R. Amaral, D., Bliss, T. & O’Keefe, J. (2007). The Hippocampal Formation. In Anderson et al. (eds.)
The Hippocampus Book. Oxford University Press.
Diseases are characterized by their underlying pathology (whether this an infectious agent or hypertension). The current approach to mental diseases is a bit like identifying that someone has trouble breathing and suspecting that this probably involves either the longs or the airways and then, when there is evidence it does, asserting that this is evidence for X diagnoses vs. Y despite the fact that the physiological basis for each is basically the same and both were determined to exist in the first place (via the equating of particular symptoms with a specific disease).
Why don't all SSRIs feel the same ?
Partially because of the extent to which the placebo effect is necessarily involved (people who tend to believe the meds won’t work tend to feel they don’t work, and vice versa). Partially because we really don’t know a lot about how they work, and partly because every brain is unique.
there are two basic ways of raising the levels of neurotransmitters in general
As usual, it’s a bit more complicated (even put simply!). First, the increase/decrease of serotonin is mediated by serotonergic pathways (more specifically, soma in the raphe nuclei). Increasing activity in this area increases serotonin production and vice versa. Second, to a certain extent the neurotransmitter view within psychiatry is antiquated. Even serotonin itself is called a “classical neurotransmitter” both because it has long been known of and because it is described as functioning in a way we know it often/usually doesn’t. From co-released neurotransmitters & modulatory transmitters to an increased understanding of firing itself (which is what neurons do and the transmission of chemical signals is important only in their contribution modulating firing rates and timing) all tells against the “simple” interpretation of some key role played by a neurotransmitter. The reason these views remain is because the “classical neurotransmitters” (a handful out of hundreds identified) are the ones so vastly important to neuronal function and thus in any and all mental, emotional, & cognitive processes. Third, and relatedly, increasing neuronal activity in specific brain areas can “bypass” serotonergic pathways by creating the structural changes in networks that serotonin might.
Lots of foods (including "drugs" - which are often very simple foods in my book) affect serotonin levels. Lots of foods affect dopamine levels. There are foods and medicines/drugs/compounds/alkaloids - the 'preferred' term is chosen for specific political reasons, a.k.a." the spin " - which raise or lower both, and various other brain chemicals.
Well-spoken.
For the record, ecstacy (MDMA) is a form of amphetamine, and raises serotonin, dopamine and oxytocin levels (at least).
I don’t know about “at least”, though probably that’s true; I’d tend towards “we think.” Here’s the most concise summary from the literature I could find quickly and I’ve removed a portion on evidence from studies of rat brains:
“The drug MDMA is a potent indirect monoaminergic agonist, which is thought
to act by both increasing the release and inhibiting the reuptake of serotonin and, to a lesser extent, dopamine. Serotonin is involved in the regulation of a variety of behavioral functions, including mood, anxiety, aggression, appetite, and sleep. Dopamine is the primary neuro-transmitter of the “reward pathway” and is involved in motivational processes such as reward and reinforcement…
In addition to causing the release of serotonin and inhibiting its reuptake, MDMA may have direct agonist effects on serotonin and dopamine receptors. It has affinities for a broad range of neurotransmitter recognition sites and may act at both serotonin subreceptors, 5-HT2A and 5-HT2C. Selective serotonin reuptake inhibitors (SSRI) such as fluoxetine and citalopram block the release of serotonin induced by MDMA, both in vitro and in vivo.
Consequently, the release of serotonin by MDMA may be dependent on the serotonin transporter SERT. MDMA shows different potencies for the neurotransmitter systems than either amphetamines or hallucinogens.” (emphasis added)
Freye, E. (2009).
Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs: A Comprehensive Review on their Mode of Action, Treatment of Abuse and Intoxication. Springer.
]We know two thirds of sweet FA about the glial brain, and how it interacts with the neuronal brain.
I don’t know the acronym but if you are saying “we don’t know much about the neuronal-glial interaction” then I absolutely agree. However, given that a single neuron modulates the rate/time of its spike trains based upon input from upwards of a hundred thousand neurons, even understanding how a
part of the neuron contributes to neuronal activity (I include the roles of other cells, such as glial, as part of neuronal activity) is not simple. We’ve probably moved beyond the rate vs. temporal “neural code” debate to a consensus that whatever the neural code is, it probably involves both but we don’t know much about when, why, or how.
About as far from it as is possible.
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