Too much serotonin lowers dopamine and its consequences for life and love

I have a worry, and with a wonderful story. The worry is about antidepressants. Over 100 million prescriptions of antidepressants are written every year in the United States. And these drugs are going generic. They are seeping around the world.

I know one girl who’s been on these antidepressants, serotonin enhancing –SSRI serotonin enhancing antidepressants – since she was 13. She’s 23.

I’ve got nothing against people who take them short-term, when they’re going through something perfectly horrible. They want to commit suicide or kill somebody else. I would recommend it.

But more and more people in the United States are taking them long-term. And indeed, what these drugs do is raise levels of serotonin. And by raising levels of serotonin, you suppress the dopamine circuit. Everybody knows that. Dopamine is associated with romantic love.

Not only do they suppress the dopamine circuit, but they kill the sex drive. And when you kill the sex drive, you kill orgasm, and when you kill orgasm, you kill that flood of drugs associated with attachment, the things are connected in the brain. And when you tamper with one brain system, you’re going to tamper with another. I’m just simply saying that a world without love is a deadly place.

Here, on TED, is her whole story, including the video, worth while enjoyng!

http://blog.ted.com/2006/09/06/helen_fisher_on/

And now depression as a gliopathic disorder! Let us listen to Dr Maletic:

Depression is a gliopathic disorder: glia should be the focuss! 

We have unjustly neglected the role of glia cells in neuropsychiatric conditions for a long time. Accumulating evidence suggests that glia cells may be implicated in major depressive disorder (MDD)-related pathology.1-8

The human nervous system has approximately 100 billion neurons and one trillion glia cells, making them an overwhelming majority.Three families of glia cells have very different roles and histological origin. Astroglia are co-partners with neurons in neural transmission and provide structural support. Oligodendroglia are involved with myelination of white matter tracts connecting various components of brain circuitry.Microglia are the main immune cells of the brain; they are of mesodermal origin unlike astroglia and oligodendroglia, which are of ectodermal origin. 1,2,8

Brain architecture appears to be shaped by astrocytes. Each human astrocyte contacts and encapsulates approximately two million synapses! In addition to managing the content of the synaptic cleft, astroglia may have a role in synchronizing the activity of all neurons within their “domains.” Brain connectivity is effectively shaped by astroglia through regulation of synaptic plasticity.Evidence suggests that neurotrophic factors, such as brain-derived and glia-derived neurotrophic factors (BDNF and GDNF), are synthesized within glia cells.Almost all classes of serotonin, norepinephrine, dopamine, cholinergic, gamma-aminobutyric acid (GABA), glutamate, neurotrophin, and cytokine receptors are expressed on glial cell membranes. Additionally, astroglial membranes express monoamine (5-HTT, NAT, DAT) and glutamate transporters. Probably about half of the monoamine uptake sites blocked by conventional antidepressants are located on glia cells! 1,2,8

However, unlike neurons, which release neurotransmitters in response to action potentials, glia cells discharge their transmitters in response to graded increases in cytoplasmic Ca++. “Analog” pattern of glial transmitter release, in contrast to “binary” neuronal transmission, may have contributed to our longstanding neglect of astroglial role in neural signaling. 8

Astroglia also have a role in regulating neuronal energy supply: at times of peak neuronal activity glia cells release lactate in response to increased energy needs. PET imaging studies reflecting glucose metabolism, to a significant degree, reflect glia activity. Cerebral perfusion is also significantly modulated by astroglia: on one end astroglial extensions “sense ” synaptic activity, on the other end their distal processes, or “feet,” modulate vascular tone and capillary permeability. Therefore, fMRI signals are substantially influenced by glial activity. 1,2,8

Glial cell pathology has been reported in the subgenual anterior cingulate cortex (sgACC), dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OPFC), hippocampus, and the amygdala of unmedicated patients with MDD. It appears that both astroglia and oligodendroglia may be affected. Research has noted a prominent 19% reduction in oligodendroglia in the DLPFC of patients with MDD. Having in mind the crucial role that DLPFC plays in executive function and “top-down” limbic regulation, the implications of this finding are striking because it may provide a neurobiological substrate for both the emotional dysregulation and cognitive dysfunction commonly observed in MDD.5-8

A study using immunohistochemistry assessed microglia density in DLPFC, ACC, thalamus, and hippocampus of patients with depression. The authors suggest that significant microgliosis (i.e., increased number of microglia) in patients with depression who committed suicide relative to healthy controls might be a marker of pre-suicidal stress. 9

In contradistinction to widespread glial abnormalities, neuronal changes appear to be subtler and more discrete in MDD. For example, some authors have noted decreased pyramidal somal size in hippocampus, ACC, DLPFC, and OPFC in postmortem studies of patients with MDD. The distribution of this cellular pathology overlaps remarkably with findings from structural and functional imaging studies. Therefore, MDD is more characterized by morphological and functional changes, rather than alterations in neuronal density. 1,5-8

In conclusion, MDD appears to be much more a “gliopathic” rather than “neurodegenerative” disease.

In a recent study in depressed patients, the Trier Social Stress Test (TSST) significanly lowered serum concentrations of palmitoylethanolamide and related endogenous cannabinoids ^[1] Furthermore, one of the targets of palmitoylethanolamide, the nuclear receptors named PPAR, are discussed as new targets for pscyhiatric disorders. ^[2] In animal models ligands of PPAR demonstrated anti-depressant activity. ^[3] 

December 2010, Jan M. Keppel Hesselink, MD, PhD 

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