Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort

Spurny-Dworak, Benjamin; Handschuh, Patricia; Spies, Marie; Kaufmann, Ulrike; Seiger, René; Klöbl, Manfred; Konadu, Melisande E.; Reed, Murray Bruce; Ritter, Vera; Baldinger-Melich, Pia; Bogner, Wolfgang; Kranz, Georg S.; Lanzenberger, Rupert

doi:10.1016/j.psyneuen.2022.105683

Cited by 12 publications

(11 citation statements)

References 78 publications

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“…T is also acting at brain levels affecting availability of neurotransmitters and neuropeptides (Spurny-Dworak et al, 2022). This finding further supports the role of T in the regulation of brain processes and behaviours, which could be important to analyse within the pathophysiology of paraphilic disorders.…”

Section: Functions and Mechanisms Of Actionsupporting

confidence: 66%

“…Sex differences in insula neurotransmitters such as higher GABA levels in women may explain why paedophilia is practically exclusively male (Spurny-Dworak et al, 2022). In the dorsal anterior cingulate cortex, pedophilic sex offenders have lower concentrations of GABA than healthy controls (Ristow et al, 2018).…”

Section: Relationship Of Paraphilic Disorders With Sexual Offenses An...mentioning

confidence: 99%

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Androgens, brain and androgen deprivation therapy in paraphilic disorders: A narrative review

2022

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Sexual delinquency is a global problem where those with paraphilic disorders, such as paedophiles, are more likely to commit and reoffend. Androgen deprivation therapy (ADT) has been suggested as a solution. The objective of this narrative review is to present current information on its risks, benefits and limitations as a treatment for paraphilias. The importance of testosterone in sexual function, the effect of its deficiency by age or by pharmacological treatment (anti‐androgens, GnRH agonists and GnRH antagonists) and the effect of testosterone replacement therapy will be reviewed. The relationship between androgens, brain, sexual behaviour and pathophysiology of paraphilic disorders will also be explored. ADT reduces sexual urges, but has adverse effects and, because its reversible nature, it does not ensure less recidivism. Likewise, the research quality of ADT drugs is limited and not enough to support their use. Child sex offenders, and not paraphilic subjects who have not committed assaults, show signs of elevated prenatal exposure to androgens and a higher methylation state of the androgen receptor gene. Sexual behaviour is regulated by subcortical (hypothalamus, brainstem and spinal cord) and cortical structures of the brain, in addition to brain circuits (dopaminergic, serotonergic). Those with paraphilic disorders show abnormalities at these levels that could relate to the risk of sexual offences. In conclusion, androgens represent a significant part of the pathophysiology of paraphilias and therefore, ADT seems promising. Nonetheless, more studies are needed to make definite conclusions about the efficacy of long‐term ADT in paraphilic patients.

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Section: Functions and Mechanisms Of Actionsupporting

confidence: 66%

Section: Relationship Of Paraphilic Disorders With Sexual Offenses An...mentioning

confidence: 99%

Androgens, brain and androgen deprivation therapy in paraphilic disorders: A narrative review

2022

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“…We attempted to determine whether GABA levels were altered in the complex environment of the cerebellum, using staining tests. These data showed that GABA levels were significantly higher in the female offspring groups than the male offspring groups, which this change of GABA-related components are known in humans ( Pandya et al, 2019 ; Spurny-Dworak et al, 2022 ). We identified that the GABA level in the female groups is decreased, and the baseline itself is even higher than in the male control group.…”

Section: Discussionmentioning

confidence: 57%

Maternal lead exposure induces sex-dependent cerebellar glial alterations and repetitive behaviors

Choi

Kim

et al. 2022

Front. Cell. Neurosci.

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Lead (Pb) is one of the most prevalent heavy metals we encounter daily. Although there are many reports regarding their toxic effects on humans, the effects of exposure to low lead concentrations throughout the pregnancy period on the offspring are not fully elucidated yet. This study aimed to investigate the cellular mechanisms that occur in response to lead exposure. To this end, we administered lead-containing water to pregnant mice from the day of conception till delivery or till day 28 postnatally. Furthermore, we performed neurodevelopmental disorder-related behavior tests and RNA-sequencing analysis. We used both genders for all experiments because neurodevelopmental disorders usually show several sex-dependent differences. The results revealed increased levels of gliosis in the cerebella of lead-exposed pups compared to those in littermates belonging to the control group. Additionally, we observed altered behaviors of male mice in the autism spectrum disorder-related tests. RNA-sequencing results revealed changes in gamma-aminobutyric acid (GABA) signaling in the lead-exposed mouse model. Specifically, the lead-exposed male mice showed decreased monoamine oxidase B and increased levels of diamine oxidase enzyme, which is related to the synthesis of GABA in astrocytes. These findings demonstrate sex-dependent basal developmental changes in glial cells and an increased prevalence of autistic-like behaviors in the young pups of mothers exposed to lead during pregnancy.

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“…In the course of this analyses, we aimed to investigate seasonal patterns in neurotransmitter ratios of healthy individuals, derived from MRSI. To this end, baseline measurements of four different studies (Silberbauer et al, 2020 ; Spurny et al, 2021 ; Spurny‐Dworak et al, 2022 ) using the same MRSI sequence and parameters, were pooled. All studies were approved by the ethics committee of the Medical University of Vienna (EK 1739/2012, 1104/2015, 2169/2016, 2170/2016, 1410/2020) and were performed in accordance with the Declaration of Helsinki 1964.…”

Section: Methodsmentioning

confidence: 99%

The influence of season on glutamate and GABA levels in the healthy human brain investigated by magnetic resonance spectroscopy imaging

Spurny-Dworak

Reed

Handschuh

et al. 2023

Human Brain Mapping

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Seasonal changes in neurotransmitter systems have been demonstrated in imaging studies and are especially noticeable in diseased states such as seasonal affective disorder (SAD). These modulatory neurotransmitters, such as serotonin, are influencing glutamatergic and GABAergic neurotransmission. Furthermore, central components of the circadian pacemaker are regulated by GABA (the suprachiasmatic nucleus) or glutamate (e.g., the retinohypothalamic tract). Therefore, we explored seasonal differences in the GABAergic and glutamatergic system in 159 healthy individuals using magnetic resonance spectroscopy imaging with a GABA‐edited 3D‐MEGA‐LASER sequence at 3T. We quantified GABA+/tCr, GABA+/Glx, and Glx/tCr ratios (GABA+, GABA+ macromolecules; Glx, glutamate + glutamine; tCr, total creatine) in five different subcortical brain regions. Differences between time periods throughout the year, seasonal patterns, and stationarity were tested using ANCOVA models, curve fitting approaches, and unit root and stationarity tests, respectively. Finally, Spearman correlation analyses between neurotransmitter ratios within each brain region and cumulated daylight and global radiation were performed. No seasonal or monthly differences, seasonal patterns, nor significant correlations could be shown in any region or ratio. Unit root and stationarity tests showed stable patterns of GABA+/tCr, GABA+/Glx, and Glx/tCr levels throughout the year, except for hippocampal Glx/tCr. Our results indicate that neurotransmitter levels of glutamate and GABA in healthy individuals are stable throughout the year. Hence, despite the important correction for age and gender in the analyses of MRS derived GABA and glutamate, a correction for seasonality in future studies does not seem necessary. Future investigations in SAD and other psychiatric patients will be of high interest.

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Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort

Cited by 12 publications

References 78 publications

Androgens, brain and androgen deprivation therapy in paraphilic disorders: A narrative review

Androgens, brain and androgen deprivation therapy in paraphilic disorders: A narrative review

Maternal lead exposure induces sex-dependent cerebellar glial alterations and repetitive behaviors

The influence of season on glutamate and GABA levels in the healthy human brain investigated by magnetic resonance spectroscopy imaging

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