SSRIs, Autism, & Low Level Laser Therapy

Examining the Reversibility of Long-Term Behavioral Disruptions in Progeny of Maternal SSRI Exposure

Serotonin is understood to play a large role in the development of numerous regions of the brain. This mouse study set out to determine whether the previously observed associations between SSRI antidepressant use during pregnancy and autism spectrum disorder in children is related to SSRIs or some other factor. The study used fluoxetine/ Prozac. The study analysed ultrasonic vocalizations made by mice (among other things).

“As opposed to sonic vocalizations, ultrasonic vocalizations cannot be detected by the human ear. USVs serve as social signals, and are categorized according to their frequency. Different categories of USVs are elicited in response to different situations and varying affective states. The behavioral functions of USVs vary as a rat or mouse pup reaches the juvenile/adult stage of their development.”[*]

Ultrasonic vocalizations and social behaviors were reduced in response to SSRI drugs use in utero. The offspring also exhibited behaviours indicating an increased sensitivity to touch (tactile hypersensitivity). This is evidence that SSRI exposure in utero could cause alterations relevant to autism spectrum disorder. Some of the changes were reversed when the offspring were exposed to SSRIs. SSRIs can increase brain allopregnanolone and their effect on serotonin in the synapse is (probably) time-dependent. Fluoxetine tends to increase synaptic serotonin for a few weeks before it is likely decreased. (Claims that SSRIs improve some of the deficits caused by SSRI use in utero by fixing a “serotonin deficiency” seem unlikely.)

“Serotonin plays widespread trophic roles during neurodevelopment; thus perturbations to this system during development may increase risk for neurodevelopmental disorders. Epidemiological studies have examined association between selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy and increased autism spectrum disorder (ASD) risk in offspring…..

We exposed mouse dams to fluoxetine during different periods of gestation and lactation, and characterized offspring on tasks assessing social communicative interaction and repetitive behavior patterns including sensory sensitivities. We demonstrate robust reductions in pup ultrasonic vocalizations and alterations in social hierarchy behaviors, as well as perseverative behaviors and tactile hypersensitivity.

These findings indicate maternal fluoxetine treatment, independent of maternal stress, can induce behavioral disruptions in mammalian offspring, thus contributing to our understanding of the developmental role of the serotonin system and the possible risks to offspring of SSRI treatment during pregnancy.

Our mouse studies show that, in the absence of other maternal manipulations or stressors, maternal selective serotonin reuptake inhibitor (SSRI) exposure alone can alter the behavioral circuits for sensory, social and repetitive behaviors, relevant to ASD, in a mammalian brain, and that some of these changes are reversible by SSRI re-exposure.”

Further reading on serotonin, SSRIs, autism etc.:

Origin of the blood hyperserotonemia of autism [*]

Hyperserotonemia and amine metabolites in autistic and retarded children. [*]

The hyperserotonemia of autism. [*]

Hyperserotonemia in adults with autistic disorder. [*]

Elevated Serotonin Levels in Autism: Association with the Major Histocompatibility Complex [*]

Maternal serotonin transporter genotype affects risk for ASD with exposure to prenatal stress. [*]

A transient placental source of serotonin for the fetal forebrain [*]

Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain. [*]

Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain. [*]

Newborn Brain Function Is Affected by Fetal Exposure to Maternal Serotonin Reuptake Inhibitors. [*]

Prenatal SSRI exposure: Effects on later child development. [*]

Effects of prenatal maternal stress on serotonin and fetal development [*]

5-HT2cR antagonist reverses social deficits in mice [*]

Cyproheptadine in treatment of autism [*]

Cyproheptadine in the treatment of autistic disorder: a double-blind placebo-controlled trial. [*]

Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. [*]

Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits. [*]

Decrease in endogenous brain allopregnanolone induces autism spectrum disorder (ASD)-like behavior in mice: A novel animal model of ASD. [*]

 

Effects of Low-Level Laser Therapy in Autism Spectrum Disorder

 

This study looked at the effect of the Erchonia EAL Laser on parameters related to autism spectrum disorder. The study reportedly used a pulsed 15 mW (average power), 635 nm, red laser for the active treatment. (The trial record actually lists 2X 7.5mw, 640nm lasers [*].) I cannot find full parameters for the EAL Laser.

The study enrolled 40 participants with a diagnosis of autism spectrum disorder between the ages of five and 17 years old. Participants were split almost 50-50 between the treatment group and a sham, placebo group. The sham group received similar treatment with a (presumably lower peak power) red LED of identical wavelength.

Treatment lasted five minutes per session. Treatment was twice a week for an eight week period. The active treatment group saw improvements over a number of measures by the end of eight weeks. There was a particularly impressive improvement in test scores relating to irritability, lethargy and social withdrawal, hyperactivity, and inappropriate speech. Improvements were seen in most measures at all test intervals – 2, 4, and 8 weeks. At 8 weeks all patients were reported as improved and 18/21 were much improved or very much improved according to Clinical Global Impressions ratings.

“The study examined the efficacy of low-level laser therapy, a form of photobiomodulation, for the treatment of irritability associated with autistic spectrum disorder in children and adolescents aged 5–17 years…

 The evaluation took place at baseline, week 2 (interim), week 4 (endpoint), and week 8 (post-procedure) of the study. The adjusted mean difference in the baseline to study endpoint change in the ABC irritability subscale score between test and placebo participants was −15.17 in favor of the test procedure group…

ANCOVA analysis found this difference to be statistically significant (F = 99.34, p < 0.0001) compared to the baseline ABC irritability subscale score. The study found that low-level laser therapy could be an effective tool for reducing irritability and other symptoms and behaviors associated with the autistic spectrum disorder in children and adolescents, with positive changes maintained and augmented over time.”