Depression and PET

Major depressive disorder (MDD) is a mental disorder with high prevalence, often early age of onset, low recovery rates, and high rates of co-morbidity. MDD is strongly linked to anxiety disorders and cognitive impairment. Depression is moderately heritable, and numerous environmental risk factors have been identified. Epigenetic mechanisms play a role in susceptibility to depression.

Structural MRI studies have identified morphological changes in several brain regions. Brain PET imaging has been used to study regional changes in metabolism and neurotransmitter systems in depression and the effects of treatment.

Most MDD patients benefit from treatment with antidepressants that modulate the monoamine system (serotonergic system, dopaminergic system, noradrenaline). Psychotherapy and brain stimulation are effective in treatment of depression but with limited availability. Serotonin reuptake inhibitors (SSRIs) are currently the most used antidepressants, followed by noradrenaline reuptake inhibitors (NRIs), or their combination (SNRIs); these drug inhibit serotonin transporter (SERT) or/and noradrenaline transporter (NAT).

Psychedelics bind to BDNF receptor TrkB to induce neuroplasticity and antidepressant effects (Moliner et al., 2023).

Ketamine, targeting glutamatergic system and TrkB, can be useful in treatment of depression. Ketamine transiently increases glutamate transmission, which can be assessed with PET as decreased mGluR5 availability (DeLorenzo et al., 2015; Esterlis et al., 2018; Holmes et al., 2020). Ketamine is thought to restore lost synaptic connections. Lower SV2A density, marking synaptic loss, is associated with depression severity across individuals with MDD and PTSD (Holmes et al., 2019). Ketamine administration did not produce measurable effect on SV2A density on group level, but in subgroup with lower baseline SV2A an increase was seen and it was associated with reduction in depression severity (Holmes et al., 2022).

The opioid system and melatonin/orexin systems are involved in the pathophysiology of MDD. Anti-inflammatory medication may have role as part of treatment.

Inflammation (both neuroinflammation and systemic inflammation) has a cause and effect relationship with MDD and several other psychiatric and neurological disorders. Neuroinflammation in MDD has been studied using TSPO radioligands in humans (Richards et al., 2018) and in animal models (Kopschina Feltes et al., 2019). Meta-analysis of TSPO PET studies indicates widespread increase of TSPO expression in MDD (Eggerstorfer et al., 2022).

See also:


Vazquez-Matias DA, de Vries EFJ, Dierckx RAJO, Doorduin J. PET imaging of animal models with depressive-like phenotypes. Eur J Nucl Med Mol Imaging 2023 (in press). doi: 10.1007/s00259-022-06073-4.

McIntyre RS, Rong C, Subramaniapillai M, Lee Y (eds): Major Depressive Disorder. Elsevier, 2019. doi: 10.1016/C2017-0-01421-0.

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Updated at: 2023-10-30
Created at: 2021-04-23
Written by: Vesa Oikonen