Minority Stress and the Effects on Emotion Processing in Transgender Men and Cisgender People: A Study Combining fMRI and Proton Magnetic Resonance Spectroscopy ( 1H-MRS)

Background Minority stress via discrimination, stigmatization, and exposure to violence can lead to development of mood and anxiety disorders and underlying neurobiochemical changes. To date, the neural and neurochemical correlates of emotion processing in transgender people (and their interaction) are unknown. Methods This study combined functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy ( 1H-MRS) to uncover the effects of anxiety and perceived stress on the neural and neurochemical substrates, specifically Choline, on emotion processing in transgender men. Thirty transgender men (TM), 30 cisgender men (CM), and 35 cisgender women (CW) passively viewed angry, neutral, happy, and surprise faces in the fMRI scanner, underwent a 1H-MRS scan and filled out mood and anxiety related questionnaires. Results As predicted, Choline levels modulated the relationship between anxiety and stress symptoms and the neural response to angry and surprise (but not happy faces) in the amygdala. This was only the case for TM but not cisgender comparisons. More generally, neural responses in the left amygdala, left middle frontal gyrus, and medial frontal gyrus to emotional faces in TM resembled that of CW. Conclusions These results provide first evidence of a critical interaction between levels of analysis and that Choline may influence neural processing of emotion in individuals prone to minority stress.

Relating Neurochemical Changes Associated with THC Use to Learning and Memory in Adolescent Rats

<p>Cannabis is the most widely used illicit drug. Adolescents may be especially vulnerable to the effects of cannabis, and alarmingly, adolescence is also a period of heavy cannabis use. However, few studies have investigated the cognitive effects of cannabis use in adolescents specifically. Furthermore, the neurochemical correlates of cognitive impairment associated with cannabis use at any age have received very little experimental attention. This research project sought to address these shortcomings in the literature using THC, the major psychoactive component of cannabis, and a rat model of adolescence. The rate of learning was slower in THC-treated animals, and this was attributable to deficits in the cognitive function of 'chunking', a process by which the information capacity of short-term memory is enlarged. Impairment of chunking by cannabinoids has not been previously reported. Behavioural impairment by THC was associated with impaired hippocampal plasticity, including changes in synaptic activity and architecture, as well as changes in neurogenesis. The attenuation of structural and functional plasticity in the hippocampus in response to training in a learning task was more pronounced than the subtle effects of THC-treatment on the survival and early development of newborn neurons. Importantly, no effects of THC were seen in animals not trained in the maze. Thus, plasticity is more sensitive to the effects of THC during times of learning, and this greater sensitivity likely accounts for the behavioural impairment associated with cannabis use. The data presented in this thesis add significantly to the existing literature by identifying novel behavioural and neurochemical processes by which cannabis use may impair learning and memory. Whether these impairments represent a greater sensitivity of adolescents to THC remains to be determined.</p>

Relating Neurochemical Changes Associated with THC Use to Learning and Memory in Adolescent Rats

<p>Cannabis is the most widely used illicit drug. Adolescents may be especially vulnerable to the effects of cannabis, and alarmingly, adolescence is also a period of heavy cannabis use. However, few studies have investigated the cognitive effects of cannabis use in adolescents specifically. Furthermore, the neurochemical correlates of cognitive impairment associated with cannabis use at any age have received very little experimental attention. This research project sought to address these shortcomings in the literature using THC, the major psychoactive component of cannabis, and a rat model of adolescence. The rate of learning was slower in THC-treated animals, and this was attributable to deficits in the cognitive function of 'chunking', a process by which the information capacity of short-term memory is enlarged. Impairment of chunking by cannabinoids has not been previously reported. Behavioural impairment by THC was associated with impaired hippocampal plasticity, including changes in synaptic activity and architecture, as well as changes in neurogenesis. The attenuation of structural and functional plasticity in the hippocampus in response to training in a learning task was more pronounced than the subtle effects of THC-treatment on the survival and early development of newborn neurons. Importantly, no effects of THC were seen in animals not trained in the maze. Thus, plasticity is more sensitive to the effects of THC during times of learning, and this greater sensitivity likely accounts for the behavioural impairment associated with cannabis use. The data presented in this thesis add significantly to the existing literature by identifying novel behavioural and neurochemical processes by which cannabis use may impair learning and memory. Whether these impairments represent a greater sensitivity of adolescents to THC remains to be determined.</p>

M146. NEUROCHEMICAL MODULATION OF AUDITORY CORTEX FUNCTIONAL CONNECTIVITY IN PATIENTS WITH AUDITORY VERBAL HALLUCINATIONS

Background Auditory hallucinations have been linked to aberrant functioning of the left superior temporal gyrus (STG) and are associated with impaired cognitive control regulated by areas in the prefrontal cortex. However, the mechanisms behind these dysfunctions are still unclear. Methods The current study combined resting state connectivity fMRI with MR spectroscopy (MRS) in a sample of 81 psychosis patients to explore how neurochemical correlates of auditory hallucinations modulate left STG functioning. The analyses were focused on glutamate (Glu) and gamma-aminobutyric acid (GABA), two neurotransmitters with excitatory and inhibitory functions, respectively, since these have previously been implicated in psychosis. Results Glu and GABA showed differential relationships with left STG connectivity in patients with and without hallucinations. Specifically, Glu concentration in the anterior cingulate cortex (ACC) was positively related to functional connectivity between the left and right temporal lobe in hallucinating patients only. In contrast, GABA concentration in the ACC was negatively related to connectivity between the left and right temporal lobe in non-hallucinating patients only. Discussion These findings support a recently proposed model of interhemispheric temporal lobe miscommunication in auditory hallucinations and indicate prefrontal neurochemical modulation as a potential underlying mechanism. The results can further be integrated with previously suggested excitatory/inhibitory imbalances as neurochemical modulators in AVH.