Serotonin-1A receptor imaging in recurrent depression: replication and literature review

An earlier study (Borg et al., Am J Psychiatry 2003) found an inverse correlation between [carbonyl-11 C]WAY-100635 ligand binding to 5-HT 1A receptors and scores for self-transcendence, but no other of the six dimensions of the Temperament and Character Inventory, in a group of healthy males. The aim of this study was to investigate if the finding of an inverse correlation between spirituality and 5-HT 1A could be seen in patients suffering from major depressive disorder or replicated among healthy volunteers. A total of 23 patients with major depressive disorder and 20 healthy volunteers were examined with PET using [carbonyl-11 C]-WAY-100635 as the radioligand. The personality traits were measured using the Finnish version of the Temperament and Character Inventory and correlated with ligand binding (BP). No significant correlations were found between the different Temperament and Character Inventory subscales and BP in any of the studied brain regions (amygdala, anterior cingulate cortex, dorsal raphe nuclei, dorsolateral prefrontal cortex, angular gyrus, inferior, middle, and superior temporal gyri, medial prefrontal cortex orbitofrontal cortex, hippocampus, insular cortex, subgenual anterior cingulate cortex, supramarginal gyrus, ventrolateral prefrontal cortex, and posterior cingulate cortex). These results do not support the idea that the serotonin system forms the biological basis of spiritual experiences among patients suffering from major depressive disorder or among healthy volunteers.

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“…4,5 At the same time, there seems to be no correlation between the severity of depressive symptoms and BP ND.…”

Section: Introductionmentioning

confidence: 97%

No association between serotonin 5-HT1A receptors and spirituality among patients with major depressive disorders or healthy volunteers

et al. 2009

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“…Importantly, a partial maternal 5-HT 1A R deficit is sufficient to elicit the maternal effect [in WT(H) mice]. Reduced (up to 40-50%) 5-HT 1A R binding has been found in individuals with anxiety-and depression-related personality traits and in patients with anxiety and depressive disorders (3,5,6,31), raising the possibility that maternal receptor deficit may increase the offspring's risk for anxiety and stress disorders via a nongenetic mechanism.…”

Section: Discussionmentioning

confidence: 99%

The serotonin _1A receptor gene as a genetic and prenatal maternal environmental factor in anxiety

Gleason

Liu²,

Bruening³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Low serotonin 1A receptor (5-HT 1A R) binding is a risk factor for anxiety and depression, and deletion of the 5-HT 1A R results in anxiety-like behavior in mice. Here we show that anxiety-like behavior in mice also can be caused, independently of the offspring's own 5-HT 1A R genotype, by a receptor deficit in the mother: a nongenetic transmission of a genetic defect. Some of the nongenetically transmitted anxiety manifestations were acquired prenatally and linked to a delay in dentate gyrus maturation in the ventral hippocampus of the offspring. Both the developmental delay and the anxiety-like phenotype were phenocopied by the genetic inactivation of p16 ink4a encoding a cyclin-dependent kinase inhibitor implicated in neuronal precursor differentiation. No maternal 5-HT 1A R genotype-dependent anxiety developed when the strain background was switched from Swiss Webster to C57BL/6, consistent with the increased resilience of this strain to early adverse environment. Instead, all anxiety manifestations were caused by the offspring's own receptor deficiency, indicating that the genetic and nongenetic effects converge to common anxiety manifestations. We propose that 5-HT 1A R deficit represents a dual risk for anxiety and that vulnerability to anxiety associated with genetic 5-HT 1A R deficiency can be transmitted by both genetic and nongenetic mechanisms in a population. Thus, the overall effect of risk alleles can be higher than estimated by traditional genetic assays and may contribute to the relatively high heritability of anxiety and psychiatric disorders in general.genetic risk | heritability | cross-fostering S tudies have identified mutant/polymorphic variants of genes, each with a relatively small contribution to the risk of depression, anxiety, schizophrenia, and other psychiatric diseases. However, demonstrable genetic influences explain only a small fraction of estimated heritability in psychiatric conditions. This "missing heritability" could be caused by a large number of undiscovered alleles or by mechanisms that amplify the effect of risk alleles but are not genetic in nature. We tested the hypothesis that mutant/polymorphic variants can have a larger effect if, besides their purely genetic effect, they have an additional "environmental" effect. For example, gene variants could influence maternal physiology, affecting the developmental program of the offspring, and consequently also increasing the risk for psychopathology. Indeed, adverse prenatal maternal and/or postnatal environment increases vulnerability to various diseases, including psychiatric disorders, in adulthood (1, 2), and one may extrapolate these findings to an abnormal maternal/parental environment related to disease-associated genes/gene variants.One of the few candidate genes whose function has been associated with anxiety and depression encodes the serotonin 1A receptor (5-HT 1A R) (3). Reduced binding or binding potential in the 5-HT 1A R has been linked to posttraumatic stress and panic disorders (3) and depression (4), and a...

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“…By knocking down the endogenous receptor, we improved on gain-of-function strategies, which are plagued by ectopic expression (Gross et al, 2002). Finally, autoreceptor levels were reduced by only 40%, which is representative of the range of 5-HT1A expression variation observed in the human population (Drevets et al, 2007). As a result, we have been able to hone in on the behavioral importance of this specific 5-HT1A receptor sub-population during a relatively small window of time.…”

Section: -Ht1a-mediated Anxiety Phenotypes Are Developmental In Originmentioning

confidence: 99%

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

Donaldson

Piel

Santos

et al. 2013

Neuropsychopharmacol

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The serotonin 1A receptor (5-HT1A) has a major role in modulating the effects of serotonin on mood and behavior. Previous studies have shown that knockout of 5-HT1A selectively in the raphe leads to higher levels of anxiety during adulthood. However, it remains unclear whether this phenotype is due to variation in receptor levels specifically during development or throughout life. To test the hypothesis that developmental sensitivity may underlie the effects of 5-HT1A on anxiety, we used an inducible transgenic system to selectively suppress 5-HT1A levels in serotonergic raphe neurons from post-natal days (P) 14 to P30, with a maximal reduction of 40% at P21 and return to regular levels by P30. This developmental decrease in receptor levels has long-lasting consequences, increasing anxiety and decreasing social investigation in adulthood. In addition, post-natal knockdown of autoreceptors leads to long-term increases in the excitability of serotonergic neurons, which may represent a mechanism underlying the effects of post-natal receptor variation on behavior later in life. Finally, we also examined the interplay between receptor variation and juvenile exposure to stress (applied from P14 to P21). Similar to receptor knockdown, juvenile exposure to stress led to increased anxiety phenotypes but did not exacerbate 5-HT1A knockdown-mediated anxiety levels. This work indicates that the effects of 5-HT1A autoreceptors on anxiety and social behaviors are developmentally mediated and suggests that natural variations in the expression of 5-HT1A may act during development to influence individual anxiety levels and contribute to susceptibility to anxiety disorders.

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Serotonin-1A receptor imaging in recurrent depression: replication and literature review

Cited by 350 publications

References 94 publications

No association between serotonin 5-HT1A receptors and spirituality among patients with major depressive disorders or healthy volunteers

No association between serotonin 5-HT1A receptors and spirituality among patients with major depressive disorders or healthy volunteers

The serotonin _1A receptor gene as a genetic and prenatal maternal environmental factor in anxiety

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

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Serotonin-1A receptor imaging in recurrent depression: replication and literature review

Cited by 350 publications

References 94 publications

No association between serotonin 5-HT1A receptors and spirituality among patients with major depressive disorders or healthy volunteers

No association between serotonin 5-HT1A receptors and spirituality among patients with major depressive disorders or healthy volunteers

The serotonin 1A receptor gene as a genetic and prenatal maternal environmental factor in anxiety

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

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Resources

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The serotonin _1A receptor gene as a genetic and prenatal maternal environmental factor in anxiety