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How many people are affected by mental and neurological disorders?

- more than 450 million people around the world


How does WHO classify the most significant mental and neurological disorders?

Four categories:
- mental diseases
- neurological disorders
- learning and developmental disabilities
- substance abuse disorders

- difference between mental and neurological diseases/disorders has come about through historical ideas about how the brain works


What is the distinction between mental and neurological?

- the classification relates to an antiquated notion that some disorders were organic (the subject of neurology) while others might be purely functional (the subject of psychiatry) – a malfunction in the mental operations of the brain without an organic cause
- while there is no reason to postulate properties or actions of the mind that are not directly associated with the action of the brain, the classification of "mental" illness – disorders that manifest as abnormal operation of the mind – is still used

software vs hardware

but the two are inexorably related


What are learning and developmental disabilities?

- include functional limitations that manifest in infancy or childhood as a result of disorders of or injuries to the developing nervous system


What are the major types of developmental disability?

- genetic
-- chromosomal (e.g. Down syndrome)
-- seg. autosomal syndromes (Prader-willi, Angelman)
-- sex linked, single gene (fragile X, Rett)
-- autosomal recessibe (Phenylketonuria, Tay Sachs)
-- autosomal dominant (neurocutaneous syndromes e.g. neurofibromatosis)

- multifactorial
-- genetic and nutritional (neural tube)

- nutritional
-- prenatal and childhood (maternal iodine deficiency leads to Developmental iodine deficiency disorder)

- infections
-- prenatal or perinatal (toxoplasmosis, rubella, cytomegalovirus, STD e.g. HIV)
-- postnatal or childhood (encephalitis, meningitis, cerebral malaria, polio, trachoma, otitis media)

- toxic exposures
-- prenatal (alcohol, lead, mercury, antimicrobials, other drugs e.g. thalidomide)

- perinatal complications
-- brain injuries associated with premature birth, birth asphyxia (cerebral palsy, cognitive disabilities, seizure disorders)

- injury
-- trauatic brain injuries, vehicle crashes, child abuse and neglect, warfare etc (cognitive, motor, speech, vision, hearing, seizure, and behavioural disabilities)

- poverty, economic disadvantage
-- mild mental retardation


What are mental disorders?

- mental disorders are diseases that affect cognition, emotion and behavioural control and substantially interfere both with the ability of children to learn and with the ability of adults to function in their families, at work and in the broader society
- mental disorders tend to begin early in life and often run a chronic recurrent course


What is aetiology of mental disorder?

- mental disorders have complex aetiologies that involve interactions among multiple genetic and non-genetic risk factors


How is gender related to risk of mental disorders?

- males have higher rates of attention deficit hyperactivity disorder, autism, and substance use disorders
- females have higher rates of major depressive disorder, most anxiety disorders, and eating disorders


What are the most significant mental disorders?

- schizophrenia (enlarged ventricles?)
- bipolar affective disorder (manic depression)
- major depressive disorder
- panic disorder


Are there organic biases in mental disorders?

- development of pharmacological therapies beginning in the early 1950s
- treated the symptoms of schizophrenia, depression, anxiety disorders, and others
- suggests possible underlying pathophysiology
- anti-psychotics


What are anxiety disorders?

- abnormal experiencing of anxiety can occur in a variety of ways
- commonly classified as follows:

- generalised anxiety disorder (GAD)
- panic attack
- panic disorder
- phobias
- obsessive compulsive disorder
- post-traumatic stress disorder


What drugs are effective in treating anxiety disorders?

- benzodiazepine
- anzyolytic drugs
- break down anxiety
- ethanol also effective: used almost invariably in social situations where there might be anxiety/desire to reduce social anxiety
- single molecule can change a very complex phenotype
- GABA receptor
- normally gating a chloride channel (depolarises the membrane)
- tells neurons to settle down
- subtly modulating this will alter tone/firing of systems with this particular receptor

- not completely cured/treated but there is something important about the gaba-ergic system and anxiety


What is the efficacy of D2 receptor antagonists in the treatment of schizophrenia?

- thought disorder - fragmentation of thought
- very complex
- affects those attributes of meaning and significance and the way we interact with the environment
- and yet a single receptor seems to be at the heart or near the heart of this disorder

- many different anti-psychotic medications

- need far less of a drug that has tighter binding for D2 receptor
- spiperone is tightest need less than 1.0 mg/day

- promazine is lowest affinity - need ~1000mg/day

- some people with this disease don't respond at all to these kinds of drugs

- complex phenomenology, relatively simple pharmacology


What are the most significant neurological diseases?

- alzheimer's disease and other dementias
- epilepsy
- parkinson's disease
- stroke

AD and dementia (and others) biggest risk factor = age
- as society gets older bigger burden of disease


What is dementia?

- dementia is a deterioration of intellectual function and other cognitive skills that is of sufficient severity to interfere with social or occupational functioning


What is Alzheimer's disease?

- most common form of dementia
- first described by Alois Alzheimer, a neuropathologist, in 1907
- it is characterised by deposition of amyloid protein and the disruption of the neuronal cytoskeleton

- disorder associated with getting old not just a consequence of getting old

- extracellular plaques caused by a build up of abnormal configuration of a protein amyloid - this causes neurons to produce abnormal configuration of a protein amyloid
- this causes neurons to produce abnormal intracellular aggregations of tau protein
- tau protein is normally present in neurons where it stabilises microtubules
- in brains producing amyloid, an intracellular tau forms aggregates (neurofibularly tangles)
- this may be the cause of neuronal death

- tends to be rather localised: fits with some functions being preserved and others being lost
- neurons in mediotemporal areas particularly vulnerable (not understood why)
- and parietal and temporal cortex as well


What is epilepsy?

- epilepsy is a common brain disorder characterised by two or more unprovoked seizures
- although around 7 - 10% of the population may experience a seizure during their lifetime, epilepsy is a condition of a recurrence of seizures
- this affects about 1% of the population (50 - 70 million worldwide)
- anywhere from mildly disruptive to completely disruptive

- the recording of the small electrical fields generated by "orthogonally oriented" cortical neurons
- abnormal coherent behaviour of the brain
- not compatible with normal, concious brain activity

epilepsy is more a symptom of a disease than a disease itself


What are seizures?

- discrete events caused by transient, hyper-synchronous, abnormal neuronal activity
- seizures may occur in close temporal association with acute stroke, sepsis, or alcohol withdrawal
- however, the vast majority of seizures have no immediate identifiable cause
- huge high amplitude low frequency oscillations


What are possible causes of epilepsy?

- can be a quite obvious temporal association with an event e.g. dramatic/traumatic event such as infection, substance abuse,
- most people who experience this it comes out of no where


How can epilepsy be categorised?

broadly divided into three categories:
1. idiopathic epilepsy (such as childhood-onset absence epilepsy), which is thought to have a genetic basis (10%)
2. secondary or symptomatic epilepsy, which is caused by a known central nervous system injury or disorder, such as infection, stroke or traumatic injury (20%)
3. cryptogenic epilepsy, for which there is no clear evidence of an etiological factor (60%)


What are inherited epilepsies?

- the genetic mutations underlying several inherited (familial) epilepsies have been identified
- they are genes encoding proteins directly associated with neuronal excitability, such as ion channels, neurotransmitter receptors
- slightly more excitable
- subtle mutations in sodium channels that don't change it from being a sodium channel but subtly change the dynamics of it

- an imbalance of excitation and inhibition, beginning at a site of brain damage, or as a result of mutation in an ion channel gene, may initiate spreading sinchronous firing
- small shift could lead to a cascading global shift


What is multiple sclerosis?

- Jacqueline du Pré, O.B.E (january 26 1945 - october 19, 1987)
- british cellist, today acknowledge as one of the greatest exponents of the instrument
- particularly associated with the elgar cello concerto in E minor
- her interpretation of this work has been described as "definitive" and "legendary"
- in 1971, aged 26, her playing began an irreversible decline when she bgan to lose sensitivity in her fingers, as well as other parts of her body

- doesn't follow a clear inheritence pattern
- MS is a chronic, autoimmune disease characterised by destruction of myelin in the CNS
- MS can cause a variety of symptoms
- changes in sensation, visual problems, muscle weakness, depression, difficulties with coordination and speech, severe fatigue, cognitive impairment, problems with balance, overheating and pain
- relapsing and remitting condition


What are three risk factors associated with MS?

- young adult
- female
- middle class