SSC2a Flashcards
What is depression and its prevalence
- a recurrent, self-reflective, and uncontrollable fixation on depressed mood.
- Persistent sadness, low mood, anhedonia and/or fatigue. At least one of these, most days, for at least 2 weeks. (ICD-10)
- Other symptoms: disturbed sleep, poor concentration, low self-esteem, appetite disturbances, suicidal ideation and guilt
- The degree of depression depends on the severity and duration of symptoms.
- Depression is the most prevalent psychiatric disorder; affecting approximately 15–17% of the population.
- Main cause of death under 35s is suicide
- Major Depressive Disorder (MDD) patients have 15% suicide risk rate.
the monoamine imbalance hypothesis; explain; what are the functions of following neurotransmitters:
-serotonin
-norepenephrine
- dopamine
- glutamate
- GABA
- The Monoamine Imbalance Hypothesis; depression is caused by an imbalance in neurotransmitters.6 Hypothesis is currently up for debate.
- Serotonin (or 5-HT) is a neurotransmitter responsible for regulating, mood, behaviour and memory.
- Norepinephrine regulates fight-or-flight, attention, memory, the sleep–wake cycle, decision making, and regulates sympathetic states.
- Dopamine responsible for pleasure and reward.1
- Glutamate is an excitatory neurotransmitter responsible for learning and memory
- GABA is an inhibitory neurotransmitter and has a ‘calming effect’ on the CNS
what brain regions are abnormal in patients with depression?
Abnormalities in brain regions; underactive prefrontal cortex, overactive amygdala, smaller hippocampus.
Explain the DMN and ATN; their role in depression
Default Mode Network (DMN) is part of the brain that codes ‘sense of self’. Patients with depression have a hyperactive DMN (particularly medial prefrontal cortex and the posterior cingulate cortex). This increased activity gives rise to excessive negative self-rumination we see in depression.
DMN is made up of= dorsal-medial prefrontal cortex, ventral-medial prefrontal cortex, inferior parietal lobes, temporoparietal junction, posterior cingulate cortex (PCC), hippocampus
- Attention Network (ATN) is part of brain that functions for everyday tasks, focus and planning. ATN is underactive in patients with depression.
ATN made up of intraparietal sulcus (IPS) + frontal eye fields (FEF) + cerebellum
what heritable gene mutation is implicated in depression
Family history; changes in serotonin transporter gene (SLC6A4) = codes for SERT (serotonin transporter)
Patients with depression have deficits in neuroplasticity (adaptive structural and functional changes to the brain based on environment)– why does this cause depression?
These neuroplasticity deficits are consistent with an impaired capacity to engage flexibly with external stimuli and efficiently exert goal-directed cognition in support of task demands, thereby reducing flexible, adaptive behavior in complex environments
Patients with depression often have a hypersensitive hypothalamic-pituitary-adrenal (HPA) axis
individuals with depression often experience HPA axis hyperactivity and high cortisol levels, leading to structural brain changes such as reduced hippocampal volume and impaired neurogenesis.
Explain the difference between neurogenesis and neuroplasticity?
Neurogenesis is the process by which new neurons are formed in the brain i.e. the formation of new neurons. Whereas neuroplasticity refers to the brain’s own ability to reorganize itself by creating new connections.
Neurogenesis is the process of generating new neurons from neural stem cells in the brain.
Neuroplasticity is the brain’s ability to reorganize its structure and function in response to intrinsic or extrinsic stimuli
Adverse effects of psychedelics/ why are they illegal
- Hallucinogen Persisting Perception Disorder (HPPD):
Some individuals report persistent visual disturbances long after the drug’s effects have subsided.
Psychiatric Reactions:
- Acute Anxiety and Panic: Users may experience intense fear, paranoia, or panic during the drug’s active phase.
- Psychosis: There is a risk of triggering psychotic episodes, particularly in individuals predisposed to mental health disorders
How does sodium valproate cause birth defects/ infertility in men?
sodium valproate= used for bipolar + epilepsy
Birth defects:
Valproate inhibits histone deacetylases (HDACs), which affects gene expression during fetal development; causes epigenetic changes
Valproate increases oxidative stress, leading to cell damage in the developing fetus.
Valproate affects early brain development, leading to intellectual disability a
infertility in men:
Valproate increases levels of sex hormone-binding globulin (SHBG), which binds testosterone and reduces free testosterone levels.
What is TRD (classification)
- NICE: “failure to attain significant level of improvement from an accurately diagnosed depressive episode following treatment with an antidepressant given at an adequate dose for a minimum of six weeks.”32
- TRD affects approximately 30% of patients receiving antidepressant treatment33
Explain mechanism of antidepressant SNRIs, SSRIs, NaSSas again ; maybe know about another group you didn’t mention?
Group not mentioned in presentation: Monoamine oxidase inhibitors (MAOIs)
e.g. tranylcypromine
SSRIs= increase serotonin
SNRIs= increase norepenephrine + serotonin
NaSSas= increase norepenephrine, dopamine, serotonin
What part of the brain should ECT be on for depression?
- In depression, ECT mainly targets the prefrontal cortex and temporal lobe.
Structural MRI studies show that post-ECT treatment; increased volumes in the hippocampus and amygdala
What drug can you give someone when taking a psychedelic to block the trip?
U can give someone psych and get antidepressant effects without trip if u block receptors with risperidone (atypical antipsychotic)
N.b. risperidone= atypical antipsychotic antagonizes serotonin 5-HT2A and dopamine D2 receptors, which are implicated in the effects of many psychedelics
what does it mean when a drug antagonises vs agonises
antagonist= reduces activity of receptor
agonist= increases activity of receptor
Agonist: A substance that binds to a receptor and activates it, producing a physiological response.
Mechanism: Agonists have both affinity (the ability to bind to a receptor) and intrinsic efficacy (the ability to activate the receptor upon binding).
Antagonist: A substance that binds to a receptor but does not activate it, thereby blocking or dampening the action of agonists.
Mechanism: Antagonists possess affinity for receptors but lack intrinsic efficacy, meaning they occupy the receptor without triggering a response, effectively preventing agonists from exerting their effects.
where do ssris specifically increase serotonin?
SSRIs increase serotonin specifically in the synapse, also known as the synaptic cleft.
Explain why steven johnson syndrome can be fatal?
Adverse effect of combining mood stabilisers is Stevens-Johnsons Syndrome; starts with flu-like symptoms then rash develops; life-threatening emergency
Stevens–Johnson syndrome (SJS) is a severe and potentially life-threatening condition characterized by widespread detachment of the skin and mucous membranes. This extensive epithelial damage can lead to several fatal complications:
- sepsis
-multiple organ failure
-
where are the alpha2-adrenergic receptors that NaSSAs work on?
α2A adrenergic receptor is localised in the following central nervous system (CNS) structures:
Brainstem (especially the locus coeruleus as presynaptic & somatodendritic autoreceptor)
Midbrain.
Hypothalamus.
Olfactory system.
Hippocampus.
Spinal cord.
Cerebral cortex.
TMS vs ECT? Why ECT used if TMS better tolerated (TMS uses magnets, ECT uses electricity)
In the NHS (UK), both Electroconvulsive Therapy (ECT) and Transcranial Magnetic Stimulation (TMS) are available for treating depression, but they are used in different situations.
Which One is More Common in the NHS?
ECT is more commonly used in the NHS for severe depression, as it has been an established treatment for many years.
TMS is newer and less widely available, but it is offered in some NHS services and private clinics for depression that has not responded to standard treatments.
What is CBT + give examples of CBT techniques
structured, goal-oriented psychotherapy techniques
GABAergic compounds
GABAergic deficit hypothesis: patients with depression have reductions in GABA, altered expression of GABAA receptors and low levels of neuroactive steroids (NASs)
NASs increase GABAergic activity
Currently, NASs are being investigated for their potential to modulate GABA receptors and support neuroplasticity in patients with depression
Medications that enhance GABAA receptor activity, such as Benzodiazepines (not typically used as addictive) provide temporary relief from depression by increasing GABA in the brain.
Brexanolone
* an IV NAS which increases inhibitory effect of GABA
* available in US for use in postpartum depression
Drugs currently on trial:
Zuranolone an oral medication that increases inhibitory effect of GABA
PH10 a intranasal spray acts on nasal chemosensory receptors and reduces depression– mechanism not understood55
How do the following mood stabilisers work:
- Lithium
- Sodium Valproate
-Lamotrigine
-Carbamazepine
Lithium; inhibits sodium channels, increases serotonin + GABA, decreases dopamine.
Risks: toxic and can cause significant kidney damage; requires careful monitoring
Sodium Valproate= inhibits sodium channels, increases GABA + decreases glutamate.
Risks: teratogenic, male infertility, liver damage
what is difference between phasic and tonic inhibition? How is this relevant when comparing GABAergic compounds zuranolone + brexanolone to benzodiazepines
Phasic Inhibition (Short & Quick)
Think of phasic inhibition like a light switch—it turns on and off quickly.
It happens when GABA is released in short bursts from one neuron to another.
The GABA binds to GABA-A receptors, causing a brief but strong inhibitory effect.
This keeps brain signals controlled and prevents over-excitation.
Example: It helps fine-tune brain activity, like adjusting focus or preventing seizures.
Tonic Inhibition (Constant & Steady)
Think of tonic inhibition like a dimmer switch—it’s always on at some level.
It happens when GABA is constantly present, not just in bursts.
Instead of short bursts, the GABA lingers around neurons and keeps them more inhibited over a longer time.
It acts more like a background control system, maintaining a general calmness in brain activity.
Example: It helps prevent anxiety, maintain stability in brain networks, and regulate sleep.
How Phasic vs. Tonic Inhibition Relates to Antidepressants
Benzodiazepines (e.g., Diazepam, Lorazepam) – Affect Phasic Inhibition
How they work: These drugs enhance phasic inhibition by increasing the effect of GABA at GABA-A receptors.
Impact: They provide quick relief from anxiety and agitation, which often co-exists with depression.
Downside: Since they boost short bursts of inhibition, they can lead to dependence and tolerance, meaning the brain adapts and needs higher doses over time.
Neurosteroids (e.g., Brexanolone for Postpartum Depression) – Affect Tonic Inhibition
How they work: Some new treatments (like Brexanolone) enhance tonic inhibition, meaning they create a more sustained calming effect.
Impact: Helps stabilize mood without sedation or addiction risks like benzodiazepines.
Example: Brexanolone (a GABA-based drug) is approved for postpartum depression and works by enhancing tonic GABA signaling in brain areas linked to mood regulation
how do GABAergic compounds work?
