Nicholas Fabiano, MD Profile picture
Jun 4, 2024 18 tweets 4 min read Read on X
The neuroplasticity framework of depression has the potential to replace the serotonin deficit hypothesis.

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The serotonin deficit hypothesis explanation for depression has persisted among clinicians and the general public alike despite insufficient supporting evidence. 2/17 nature.com/articles/s4138…
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We must acknowledge that multiple biopsychosocial factors can interact with each other and converge on depression pathophysiology; these myriad of contributing factors converge in ways that are not yet fully understood to cause the symptoms of depression. 3/17 Image
Although heterogeneous and distinct for each patient, these symptoms share features of dysfunction in brain circuits that process emotional and cognitive information and regulate survival functions like energy and motivation. 4/17
These dysfunctional circuits leave individuals “stuck” in a state characterized by negativity bias, depressed mood, anhedonia, and dysfunction in several other behavioural domains, such as motivation, appetite, and sleep. 5/17
In particular, being stuck in a rut of negative information processing can be understood as an impairment in cognitive and emotional flexibility. 6/17
As such, people with depression are slower to adapt to changing rules in cognitive flexibility and remain stuck with a narrow or rigid repertoire of emotions. 7/17
Collectively, these findings result in a tendency to perseverate on negative information and an impaired ability to respond to positive input. 8/17
From a structural level, the behavioural symptoms of depression come from changes in the volume, activity, and connectivity of brain regions and networks involved in emotional salience, reward processing, motivation, and executive functioning. 9/17
Key brain regions involved in depression pathophysiology include the prefrontal cortex (PFC), hippocampus, nucleus accumbens (NAc), and amygdala; broadly speaking, the activity of these brain regions and their connectivity with each other are primarily dampened. 10/17
At the cellular level, there is evidence of dysfunction in synapses: the junctions between neurons where electrical signals and chemical neurotransmitters pass from the axon of a sending (presynaptic) neuron to the dendrites of a receiving (postsynaptic) neuron. 11/17 Image
Synaptic dysfunction is most evident in pyramidal neurons, a prevalent class of neurons that release glutamate, thereby activating target neurons that release other neurotransmitters, such as serotonin, norepinephrine, dopamine, and acetylcholine. 12/17
A growing body of evidence suggests that treatments for depression work by enhancing neuroplasticity, rewiring dysfunctional brain circuits and synapses in adaptive ways that allow patients to become “unstuck” from negative thoughts, emotions, and behaviours. 13/17
Monoamines are still essential for antidepressant effects, but rather than correcting a deficit, the serotoninergic, dopaminergic, and noradrenergic activity of typical antidepressants likely play two major roles in facilitating the therapeutic response. 14/17
(1) triggering downstream molecular cascades that result in neuroplasticity more chronically, and (2) changing emotional processing and behaviour more acutely. 15/17
Similar mechanisms involving neuroplasticity likely underlie the effects of novel “antidepressants” such as ketamine and psychedelics. 16/17
Overall, in this new model, although depression cannot accurately be considered a deficit in serotonin, serotonin still has a role to play through its interactions with mechanisms of neuroplasticity. 17/17
Read more from the full paper in @molpsychiatry here nature.com/articles/s4138…

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More from @NTFabiano

Jul 1
Depression may be contagious through a dysfunctional mirror neuron system.

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This discussion is from a review article in @ElsevierConnect which describes the theory of ‘contagious depression’, whereby depression can be induced or triggered by our social environment. 2/11 sciencedirect.com/science/articl…Image
Emotions can spread like an infectious disease across social networks in a phenomenon called emotional contagion, which can be defined as a tendency to acquire affective states from our social contacts. 3/11
Read 11 tweets
Jun 30
Light can travel through the head, guided by cerebrospinal fluid & tissue geometry.

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These findings are from a study in @spietweets which explored the physical limits of photon transport in the head in the extreme case wherein the source and detector were diametrically opposite. 2/10 spiedigitallibrary.org/journals/neuro…Image
Optical modalities for noninvasive imaging of the human brain hold promise to fill the technology gap between cheap and portable devices such as electroencephalography (EEG) and expensive high-resolution instruments such as functional magnetic resonance imaging (fMRI). 3/10
Read 10 tweets
Jun 29
Quantum entanglement may generate consciousness.

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These findings are from a study in @PhysRevE which employs cavity quantum electrodynamics to explore entangled biphoton generation through cascade emission as a potential source for the synchronized activity of neurons. 2/13 journals.aps.org/pre/abstract/1…Image
Quantum entanglement is the phenomenon of a group of particles being generated, interacting, or sharing spatial proximity in such a way that the quantum state of each particle of the group cannot be described independently of the state of the others. 3/13
Read 13 tweets
Jun 19
Sleep loss is a metabolic disorder.

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These findings are from a paper in @scisignal which describes how sleep deprivation increases resting energy expenditure, leading to the development of a negative energy balance in highly active cells like neurons. 2/8 science.org/doi/10.1126/sc…Image
Sleep loss dysregulates cellular metabolism and energy homeostasis. 3/8 Image
Read 8 tweets
Jun 17
A history of heavy cannabis use is associated with lower brain activation during a working memory task.

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These findings are from a study in @JAMANetworkOpen which examined the association of lifetime history of heavy cannabis use and recent cannabis use with brain activation across a range of brain functions in a large sample of young adults in the US. 2/9 jamanetwork.com/journals/jaman…Image
Given the cognitive effects of cannabis and the disruption of the endogenous cannabinoid system by tetrahydrocannabinol (THC), it may be that brain regions with high cannabinoid 1 (CB1) receptor density might be altered by cannabis. 3/9
Read 9 tweets
Jun 15
Being a father rewires the brain.

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These findings are from a paper in @JAMAPsych which described how the paternal brain is wired by pregnancy. 2/12 jamanetwork.com/journals/jamap…Image
Pregnancy and post partum are accompanied by structural (extensive gray matter volume reductions) and functional brain changes in women that are thought to be important for caregiving. 3/12
Read 13 tweets

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