Neuropsychiatric disorder Flashcards
Neuropsychiatric disorders
Refers to several disorders encompassing a broad range of medical conditions involving both neurology and psychiatry and cognitive deficit disorders
common neuropsychiatric disorders
-ADD
-anxiety
-schizophrenia (SZ)
-Bipolar disorder (BD)
-major depressive disorder (MDD)
ADHD
Anxiety disorder characterisation
Persistent and excessive fear and anxiety and the dysfunctional behavioral changes a patient may use to mitigate these feelings
How do anxiety disorders differ from one another
Based on specific objectives or situations that induce fear, anxiety and associated behavioural changes
Anxiety triggers
Neurobiological responses
-Perpetration of violence
-Self-rewarding lust of violence/gaining power
-Appetitive aggression
-Reactive aggression
-PTSD
_Traumatic experiences
-Violent environment ( stressful life and trauma)
stress response
HPA axis
Stress triggers a freed-forward mechanism of the HPA axis by activating the hypothalamus to release corticotrophin-releasing hormone (CRH), which binds to the anterior pituatary gland and induces secretion of adrenocorticotrophic hormone (ACTH)
ACTH effect
Triggers adrenal cortex to release glucocorticoids like cortisol, which binds to glucocorticoid receptors (GRs) to activate metabolic effects for survival during stressful event
Cortisol role in HPA axis
It balances the freedforward and feedback mechanisms by deactivating both the hypothalamus and the pituatary gland
-Therefore, it is characterised by feeling less alert and having trouble focusing or doing everyday tasks including memory loss
corisol homeostasis
Down regulation of the freed-forward mechanism of the HPA axis is crucial to ensuring the homeostasis of cortisol levels during stress
-disruption can lead to an imbalance between feedforward and feedback mechanisms, with elevated negative feedback thought to result in blunted cortisol due to desensitization, as well as the development of both PTSD and aggression
What causes HPA axis dysfunction?
*Chronic stress can lead to HPA axis
dysfunction and cause consistently increased
cortisol levels in your body
constantly increased cortisol effect
Mental health conditions, like mood
disorders, anxiety disorders,
depression and post-traumatic stress disorder
(PTSD)
*Metabolic diseases, such as
diabetes, obesity and cancer
*Cardiovascular diseases, like high blood
pressure and vascular damage
*HPA axis dysfunction may also play a role
in memory loss and neurodegenerative
conditions like Alzheimer’s disease
HPA axis dysfunction
HPA axis dysfunction is a complex,
biochemical and physiological process
*Research scientists are still investigating and
studying its causes and health impacts
serotonin
-Serotonin is best known as a
neurotransmitter that modulates neural
activity
-a wide range of
neuropsychological processes, and drugs that
target serotonin receptors are used widely in
psychiatry and neurology
serotnin location
*Serotonin is abundantly found outside the
central nervous system
-its
15 receptors are all expressed peripherally
and within the brain
serotonin role
*Serotonin regulates numerous biological
processes, including cardiovascular function,
bowel motility, ejaculatory latency, and
bladder control
serotonin production cell type
Serotonin is almost exclusively produced in
neurons originating in the raphe nuclei
located in the midline of the brainstem
* These serotonin-producing neurons form the
largest and most complex efferent system in
the human brain
location of raphae nuclei
The most caudal raphe innervates the spinal
cord, while the more rostral raphe, the dorsal
raphe nucleus and the medial raphe nucleus
innervate much of the rest of the CNS by
diffuse projections
Trp in physiological conditions
Under physiological conditions, the majority
of Tryptophan (Trp) is degraded along the
kynurenine pathway (KP) and only about 1%
is metabolised into serotonin (5-HT)
serotonin transformation + enzymes
This metabolic route begins with the
transformation of Trp into 5-hydroxytryptophan
and then into serotonin through two consecutive
reactions catalysed by the enzymes tryptophan
hydroxylase (TPH) and 5-hydroxytryptophan is a
decarboxylase (AADC= aromatic l amino acid decarboxylase)
rate limiting enzme + function in serotonin production (melatonin transformation
the rate-limiting enzyme
arylalkylamine N-acetyltransferase (AANAT)
promotes the acetylation of serotonin into Nacetylserotonin (NAS), which, in turn, serves as a substrate for the hydroxy indole-O-methyl
transferase (HIOMT or acetylserotonin Omethyltransferase, ASMT) to generate melatonin
Melatonin functions
Melatonin is an essential player in the
regulation of energy metabolism and glucose
homeostasis
*It is responsible for the daily distribution of
energy metabolism functions (daily phase of
high insulin sensitivity, glycogen synthesis,
and lipogenesis and a sleep phase associated
with the usage of stored energy)
Low melatonin secretion effects
independently been associated with a higher
risk for type 2 diabetes (T2DM)
AFMK
N-acetyl-N-formyl-5-
methoxykynurenamine (AFMK)
AFMK production
-melatonin can be cleaved by indoleamine 2,3-
dioxygenase 1 (IDO1) in a nonspecific reaction
-melatonin can yield AFMK by directly
scavenging hydrogen peroxide or as a substrate of
neutrophils’ myeloperoxidase
NB antioxidant
melatonin and hydogen peroxide reaction
, AFMK can arise from the reaction of
melatonin with hydroxyl radical and the subsequent
interaction of the new-born melatonyl species with
superoxide anion
AFMK research
Research involving cell culture, AFMK
efficiently reduced hippocampal neuronal
death caused by either hydrogen peroxide or
amyloid b25-35 peptide
AFMK significance
*AFMK is a naturally occurring molecule with
potent free radical scavenging capacity
(donating two electrons/molecule)
*It thus may be a valuable new antioxidant for
preventing and treating free radical-related
disorders
genes associated with neuropsychiatric disorders
COMT
encoding for catechol-O-methyl transferase
(COMT), an enzyme that catalyses the
extraneuronal breakdown of catecholamines
epigenetic factors associated with neuropsychiatric disorders
*Additional epigenetic changes found on these
genes, especially at their promoter regions,
influence the disease
*A number of cytosine-guanine methylation have
been found and have been associated with
neuropsychiatric disorders
