This thesis examines physiological aspects of two psychiatric brain stimulation treatments: electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS).

ECT’s therapeutic effect depends on epileptic seizures that activate subcortical regions, and involves increased gamma-aminobutyric acid (GABA) inhibition. Clinical ECT seizure evaluation parameters show varying correlation to clinical outcome and uncertain correlation to subcortical activation. Serum prolactin and cortisol increase postictally, and postictal prolactin reflects subcortical seizure activation. The GABA-agonistic hormone allopregnanolone affects psychiatric illness and increases postictally in epilepsy, but is unexplored after ECT seizures.

RTMS’s therapeutic effect depends on altering cortical excitability which affects synapse plasticity, subsequently modulating functional neural network activity. Motor cortex excitability measured with TMS paired with electromyography (TMS-EMG), which includes GABA modulated indices, may be altered in psychiatric illness. Prefrontal rTMS affects motor cortex excitability, and TMS-EMG may predict rTMS treatment outcome, but the rTMS protocol intermittent theta burst stimulation (iTBS) is less explored. 

Study I analysed correlations between clinical ECT seizure evaluation parameters and prolactin and cortisol serum levels. Ictal tachycardia correlated with postictal prolactin, but not cortisol, suggesting that ictal tachycardia reflects subcortical seizure engagement. 

Study II investigated progesterone and allopregnanolone serum levels after an ECT seizure, finding no postictal increase or correlation to seizure evaluation parameters. Postictal progesterone increased in men in a subgroup analysis.

Study III examined GABA_A receptor availability measured with positron emission tomography and TMS-EMG indices in participants with depression before and after iTBS. Baseline comparisons showed no difference from healthy. After iTBS, changes in GABA_A receptor availability and TMS-EMG motor threshold correlated negatively, indicating GABA_A mediated regulation of motor cortex signalling. 

Study IV investigated whether iTBS affects TMS-EMG and whether baseline TMS-EMG predicts iTBS outcome on negative symptoms in schizophrenia and depression, with negative results. Compared to participants with depression and healthy, participants with schizophrenia had more GABA_B receptor dependent inhibition, which also correlated with antipsychotic medication dose.

These results contribute to the understanding of ECT and rTMS physiology, facilitating future developments for improved efficacy and reduced side effects. 

This thesis investigates the function of inhibitory neurotransmission in depression. Gamma-aminobutyric acid (GABA) serves as the primary inhibitory neurotransmitter in the brain and is implicated in the pathophysiology of depression. Furthermore, GABA is thought to play a role in the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). GABA levels in depression measured with magnetic resonance spectroscopy seem to be reduced, while changes following rTMS appear more inconsistent. Additionally, the availability of GABA_A-receptors in depression and following rTMS remains largely unexplored. Cortical excitability also seems to be altered during depression, though results are heterogeneous, while research on excitability changes following prefrontal rTMS is limited.

Depression can present with a wide range of symptoms, leading to the identification of clinical subtypes, which may have distinct neurobiological mechanisms. GABA dysfunction might hold particular relevance in specific symptom profiles of depression, such as melancholic features. 

Study I found that the rTMS protocol intermittent theta-burst stimulation (iTBS) did not affect average GABA and glutamate levels in the dorsal anterior cingulate cortex (dACC) or GABA_A-receptor availability as measured by positron emission tomography. However, a decrease in GABA levels was associated with symptom improvement, and lower baseline GABA_A-receptor availability in the nucleus accumbens was related to the antidepressant effect following iTBS.

Study II found no changes in motor cortical excitability in depression or schizophrenia following iTBS, as measured using transcranial magnetic stimulation paired with electromyography (TMS-EMG). Furthermore, baseline TMS-EMG could not predict the effect of iTBS on negative symptoms in depression. Participants with schizophrenia exhibited higher GABA_B-receptor-mediated activity than depressed and healthy controls, with this activity also correlating with the dose of antipsychotic medication. 

Study III examined the relationship between GABA_A-receptor availability and TMS-EMG indices. In participants with depression, changes in GABA_A-receptor availability in the hand motor cortex were inversely related to changes in the resting motor threshold.

Study IV could not establish that melancholic features, specifically psychomotor retardation and vegetative symptoms, are related to GABA levels in the dACC or GABA_A-receptor availability in the dACC, basal ganglia, and hypothalamus. 

These findings contribute to the understanding of the pathophysiology of depression and the mechanisms of iTBS.