The Definite Role of Serotonin Excess & Deficiency in Psychiatric Disorders

Serotonin has consistently played a large role in mental illness [1] [2] [3]. However, the role that serotonin plays has been disputed, and research has shown that both excessive levels and deficient levels can contribute to onset of mental illness [4] [5].

The severity of certain disorders such as Generalized Anxiety and Obsessive-Compulsive-Disorder is also directly related to Serotonin status and levels in healthy individuals and Physically ill individuals [6] [7] [8] [9].

Personality traits are also influenced by serotonin levels, and increased serotonin tends to lead to callousness in individuals with Antisocial personality disorder.

CONDITIONS THAT ARE RELATED TO ELEVATED SEROTONIN LEVELS INCLUDE...
Elevated = Moderately High

• Social Anxiety (Social Phobia) [10] [11]
• Obsessive-Compulsive-Disorder [12] [13] [14]
• Schizophrenia [15] [16]
• Pathological Dissociation [17] [18] [19]
• Anorexia-Nervosa and Undereating [20] [21] [22] [23].

DISPUTE  : Why are SSRI's used to treat OCD/Anxiety then?

ANSWER : Simply because, researchers haven't really discovered all of the actions of SSRI's until now, and ''therapeutic response'' often correlates with SSRI-induced downregulation of serotonin receptors and often, to increases in allopregnenolone levels which then enhance endogenous (naturally produced) GABA levels.

Downregulation means that the receptors have decreased in number within one or more regions of the brain.

Therefore, and due to Selective-Serotonin-Reuptake-Inhibitor (SSRI) induced desensitization of other receptors, besides the ones it downregulates, the net (total, summed) effect of SSRI's is actually a long-term anti-serotonin effect on multiple brain regions and an effective 'redirection' or redistribution of the serotonin levels that remain enhanced.

|SOURCES|

Antidepressant Treatment Reduces Serotonin-1A Autoreceptor Binding in Major Depressive Disorder

Effect of chronic administration of selective 5-hydroxytryptamine and noradrenaline uptake inhibitors on a putative index of 5-HT 2C/2B receptor function

Effect of long-term administration of antidepressant treatments on serotonin release in brain regions involved in obsessive-compulsive disorder.

5-HT1B Receptors and More General Insights into Serotonin Role in Mental Disorders

Additionally, 5-HT1B (Serotonin-Receptor 1B) function is increased in obsessive-compulsive disorder and decreased in Cocaine-dependence [24] [25].

This outlines the viability of receptor research in understanding and treating these disorders. 

Being that 5-HT(1)B receptors and their function correlate to Serotonin Transporter (SERT) activity [26] [27] [28], and SERT essentially recycles our brains serotonin [29] [30] and removes it from activity, it would make sense that this key receptor would be heavily involved with the pathophysiology of these various mental disorders [31] [32].

• Updated overview of the putative role of the serotoninergic system in obsessive-compulsive disorder
• Clinically effective OCD treatment prevents 5-HT1B receptor-induced repetitive behavior and striatal activation.
• Association between the 5HT1B receptor gene (HTR1B) and the inattentive subtype of ADHD.
• The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder.
• Brain Serotonin Transporter Binding Potential Measured With Carbon11–Labeled DASB Positron Emission Tomography Effects of Major Depressive Episodes and Severity of Dysfunctional Attitudes

Serotonin Transporters are altered in lovers, as Romantic love has shown to produce dramatic reductions in Serotonin Transporters.

CONDITIONS RELATED TO SEROTONIN DEFICIENCY (Low Levels) INCLUDE...

• Impulsive-Aggressive Behavior [33].
• Compulsive Eating/Poor Control of Appetite [34]
• Depressive Disorders where Despair and Agitation predominate [35].
• Sexual Deviance, Compulsive Sexual Acts [36].
• Sociopathy (as opposed to Psychopathy which can include increased versus decreased serotonin; these types are impulsive rather than calculating, generally) [37] [38].

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Specific research seems to indicate the the low levels of serotonin also correlate with Manic binges in BiPolar disorder patients [!].

Genes related to this phenomenon seem to include the  rs25531 & rs25532 SERT/SLC6A4 variants which are essentially serotonin transporter abnormalities and polymorphisms [!] which cause the Protein to act differently than in normal individuals [!]. Since once again, serotonin transporters (SERT) recycle serotonin from the synapse, any variant (i.e SERT I425V, I425L and G56A) that causes low levels of the Protein may also cause high levels of brain serotonin regardless of blood level of serotonin [!].

TREATMENT OPTIONS FOR THOSE WITH HIGH SEROTONIN LEVELS

DRUGS/PHARMACEUTICALS/MEDICATIONS

• Individuals with elevated serotonin levels in plasma and cerebrospinal fluid tend to benefit from anti-serotonin medications or medications that fall under a ''serotonin-modulator'' class of medications. 
• This includes the novel anti-depressant drugs Mianserin (U.K/Europe/India) and Nefazodone for some countries, as well as Mirtazapine (Remeron) for the USA Residents.
• This may also include the drugs Ritanserin & Metergoline in countries where they are available.

SUPPLEMENTS

• Supplements indicated for elevated Serotonin levels include Shilajit [!], Yohimbine HCL [!] and other natural serotonin antagonist supplements.

TREATMENT OPTIONS FOR THOSE WITH LOW SEROTONIN LEVELS

• Viewing the list of natural SSRI supplements may be helpful.
• Inositol is a good supplement to consider for people with low serotonin levels who have obsessive-compulsive disorder, it may help high serotonin states as well by resensitizing somatodendritic 5-HT1a autoreceptors [!].
• St.John's Wort is considered the only ''true'' serotonin-booster amongst psychoactive herbal substances and amongst those with diagnosed mental illness, is one of the only efficacious treatments.
• Bacopa Monnieri extract is a powerful serotonin synthesis (synthesis = production) enhancer that increases human brain 5-HT synthesis in active/living subjects included [!].
• Vitamin D can increase brain serotonin production if used at 1000-2000 IU's per day [!].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436296/
http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.542.3432&rep=rep1&type=pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418507/

http://s3.amazonaws.com/academia.edu.documents/45595397/539.full.pdf?AWSAccessKeyId=AKIAJ56TQJRTWSMTNPEA&Expires=1480478273&Signature=0f%2F%2Fl76cv958MP97kKROD858NpU%3D&response-content-disposition=inline%3B%20filename%3DFunctional_Interactions_between_5-Hydrox.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576414/