The Biological Basis of Psychological Abnormality

Question 1

What are synapses?

Answer 1

• Connection between two neurons
• One cell changes its voltage and passes onto the next cell, happens at the synapse
• The connections and means of communication between nerve cells.
• Each neuron can have thousands of different synapses (connections) with other neurons.
  Communication through axons

Question 2

How do synapses communicate?

Answer 2

• Synaptic communication mediated by the physical movement of chemicals (neurotransmitters). Movement of chemical causes changes in voltage
  Cleft = 0.00002 mm across. Happens on a tiny scale, really small gap

Question 3

What are the 6 stages of synaptic transmission?

Answer 3

1. AP of presynaptic neuron, information (action potential, change in voltage) is coming down from the axon of the presynaptic neuron. Packages of neurotransmitters in the presynaptic neuron
2. Transmitter release into synaptic cleft, after a large voltage change
3. Transmitter binds to receptor
4. Transmitter dissociates from receptor, end of chemical reaction
5. Transmitter reuptake by transporters
6. Transmitter recycling, ready for the next action potential

Question 4

What are the synaptic components?

Answer 4

· Presynaptic receptors, e.g. regulate transmitter release
· Postsynaptic receptors: ionotropic and metabotropic receptors, the two types of receptors
· Transporters, i.e. transmitter reuptake sites
· Enzymes that metabolize transmitters
· Second messenger systems
· All can affect the input-output relationship of neurons

Question 5

What are receptors?

Answer 5

· Work on a ‘lock-and-key’ principle. One neurotransmitter fits a certain kind of receptor.
Each neurotransmitter has its own receptor to bind to

Question 6

Examples of neurotransmitters?

Answer 6

· Monoamines – acetylcholine, serotonin (5-HT)
· Amino acids – GABA, glutamate, and others
· Catecholamines – still monoamines, dopamine, adrenalin/epinephrine, noradrenalin/norepinephrine
· Neuropeptides – Enkephalin – Endorphins – Substance P – Others (50+)
· Also neuromodulators: Mostly peptides
The main groups of neurotransmitters

Question 7

What are multiple receptor subtypes?

Answer 7

· Multiple receptor subtypes… different kinds of receptors
· Ionotropic (receptors) ion channels – voltage change by ions released in the gaps between neurons
· Metabotropic or 2nd messenger gated ion channels, more indirect, binds with the receptor and opens another ion channel

Question 8

What changes can happen at synapses?

Answer 8

· Synapses are capable of changing
· Underlie learning, memory formation and many disorders - Hebbian plasticity, long-term potentiation (LTP), long-term depression (LTD), etc.
· Change in receptor numbers, change in amount of transmitter release, etc.
· Change in structure of synapse
Change in efficacy of second messenger systems

Question 9

How do genes play a role in brain function?

Answer 9

· Play a large role in brain function.
· Code for receptors, enzymes, NTs, etc.
· Role can vary over time. Some influences may be apparent from birth, others may only manifest themselves later.
Environmental factors can determine whether a gene becomes “switched on” or not.

Question 10

How is induction used on animal models?

Answer 10

· Inducing mental health problems
· Genetic studies, e.g. gene “knockouts”
· Pharmacological studies – give them drugs and see how it affects their behaviour
Lesion studies. – removing parts of the brain and see how it changes behaviour

Question 11

How do you measure animal models?

Answer 11

· Behavioural monitoring
· Neural recordings – how single neuron firing patterns change
· Anatomical techniques, e.g. cell counts
Neurochemistry.

Question 12

How are human studies used in investigating brain function?

Answer 12

· Genetics – through twin studies
· Post-mortem studies – after someone has died, looked at the organisation of neurons in their brain
· Structural MRI (large scale abnormalities)
· Functional MRI (brain function)
· PET (changes in NT systems)
Problem: Most people with mental disorders will be taking medications that alter brain function – hard to see if differences are due to medication or mental health issues

Question 13

What are MZ and DZ twins?

Answer 13

· MZ stand for: monozygotic
· Means: identical
· Share 100% of genes
· DZ stands for: dizygotic
· Means: non-identical
Share 50% of genes

Question 14

· For a diagnosis of a major depression:

Answer 14

At least 5 of the following symptoms and at least one of the symptoms should be either (1) depressed mood or (2) loss of interest or pleasure.

Question 15

What are the common symptoms of depression?

Answer 15

· These symptoms must be present during the same 2 week period
· Depressed mood, nearly every day during most of the day
· Marked diminished interest or pleasure in almost all activities
· Significant weight loss (when not dieting), weight gain, or a change in appetite
· Insomnia or hypersomnia (excess sleep)
· Psychomotor agitation or psychomotor retardation – lack of movements
· Fatigue or loss of energy
· Feelings of worthlessness or inappropriate guilt
· Impaired ability to concentrate or indecisiveness
· Recurrent thoughts of death, recurrent suicidal
Depression is common: 1 in 8-10

Question 16

What are the subtypes of depression?

Answer 16

· Unipolar depression: Depression that alternates with “normal” emotional states. (10% of men, 20% of women suffer.)
Bipolar depression: Fluctuation between depressive periods and episodes of euphoric, positive mood/mania. (Equal numbers of men and women – less common than unipolar.)

Question 17

What do twin studies show about depression?

Answer 17

· Chance that if one twin has it, what’s the chance the other twin will have it
· Unipolar concordance: MZ = 40%, DZ = 15%
· Bipolar concordance: MZ = 70%, DZ = 15%
· Adoption studies show higher rates of depression in biological than adoptive parents.
Linkage studies have failed to identify a single gene for depression. Many genes contribute to a susceptibility, and environmental factors can trigger depression.

Question 18

What are Monoamine Oxidase Inhibitors?

Answer 18

· 1950s: Iproniazid (first MAOI) – first used
· 1960s: Reserpine (catecholamine depletion) - has an effect on catecholamines
· Normally serotonin is broken down by MAOI – stop the enzyme from breaking them down
· MAOI have side effects – control muscle, digestion (bad)
Led to Catecholamine theory of Depression (Schildkraut, 1965)

Question 19

What are Tricyclic Antidepressants?

Answer 19

· 1950s: Tofranil
· Tricyclic Antidepressants
Similar effect to MAOIs (catecholamine agonist) but different action.

Question 20

What are Catecholamines?

Answer 20

· Catecholamines: NA and Dopamine
· Reduced levels in the brains/bodies of depressed patients? No.
· Ignores another important NT – 5-HT (serotonin)
Therefore – more broadly – Monoamine theory of depression

Question 21

What are Selective Serotonin Reuptake Inhibitors?

Answer 21

· SSRIs are most modern drug treatment for depression: Prozac, sertraline, citalopram
· Works by stopping the reuptake of serotonin
Little effect on NA

Question 22

What are the main anti-depressants and how do they work?

Answer 22

· MAOIs – Affect mononamines. Highly effective. Nasty side effects. Only used in most resistant cases.
· TADs – Affect monoamines. Also highly effective. Some side effects. Suicide risk.
· SSRIs – Affect 5-HT (not NA or DA). Safe, and relatively few side effects.
· So, NA/DA or 5-HT important? Both?
· Low 5-HT disrupts functioning of NA/DA system = Depression
Correction of 5-HT system = correction of NA/DA system = symptom alleviation

Question 23

How is depression imaged?

Answer 23

· Increased activity in neural systems supporting emotion processing, e.g. amygdala and medial prefrontal cortex
Decreased activity in neural systems supporting regulation of emotion, e.g. dorsolateral prefrontal cortex

Question 24

How is bipolar treated?

Answer 24

· Standard antidepressants have little effect.
· 1940s: Discovery of Lithium’s effect in Bipolar. – an element
· Without Lithium – cycle every 14 months on average, with Lithium – every nine years. Extends your cycle rather than stopping it
Detailed mechanism unknown – neurotrophic and neurotransmitter systems affected.

Question 25

What is the definition of schizophrenia?

Answer 25

DSM-V definition: Two or more of the following for at least a one-month (or longer) period of time, and at least one of them must be 1, 2, or 3:

Question 26

What are the common symptoms of schziophrenia?

Answer 26

· Delusions – false beliefs · Hallucinations · Disorganized speech – can’t talk clearly · Grossly disorganized or catatonic behaviour – not moving your limbs correctly, or not moving at all · Negative symptoms, such as diminished emotional expression · Some signs of the disorder must last for a continuous period of at least 6 months. This six-month period must include at least one month of symptoms (or less if treated). At least one of the symptoms needs to be a positive symptom (i.e., delusions, hallucinations, disorganized speech). Not split personality of multiple personality

Question 27

What are positive symptoms of schziophrenia

Answer 27

``` · Behaviour you didn’t have · Hallucinations (auditory) · Delusions of grandeur, persecution etc. · Disordered thought processes Bizarre behaviours ```

Question 28

What are negative symptoms of schizophrenia

Answer 28

``` · Behaviour that you used to have · Social withdrawal · Flat affect (blunted emotional response) · Anhedonia Reduced motivation · Poor focus on tasks Catatonia ```

Question 29

Do genes play a role in schizophrenia?

Answer 29

Family studies · The closer the biological relatedness, the greater chance that the relative will also be schizophrenic (Gottesman 1991) A number of genes implicated in schizophrenia: · Neuregluin 1: participates in glutamate, GABA and ACh receptor regulation · COMT: catecholamines G72: glutamatergic activity

Question 30

Twin studies and schzioprenia

Answer 30

· Concordance: MZ = 50%, DZ = 17% · The symptomatic twin (identical twins, the one who has schizophrenia) frequently weighs less at birth (differential development in the womb) · More physiological distress (affected twin has experienced different environmental factors) The twins act differently, receiving different parental responses (e.g. affected twin is often more sensitive and tearful)

Question 31

Brain abnormalities in schzioprehnia?

Answer 31

· Ventricular abnormalities – e.g. larger ventricles (larger gaps in the centre of the brain filled with fluid) · Enlargement not related to length of illness or duration of hospitalization · Grey Matter loss: Thompson et al. (2001) Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Schizophrenia manifests in adolescence. Early onset, small amount of grey matter then spreads to other areas of the brain as time goes on Cellular disarray of the hippocampus in chronic schizophrenia. The most impaired individuals show the greatest disorganization (Conrad 1991)

Question 32

Functional abnormalities in schizophrenia

Answer 32

· The hypofrontality hypothesis: Less activity in frontal lobes in schizophrenics. · Decreased activity in right middle frontal gyrus (BA 9) during a context processing task in patients with schizophrenia. Holmes et al. (2005) Schizophrenia research 76: 199-206

Question 33

The dopamine hypothesis

Answer 33

· Large doses of amphetamine (a strong DA agonist) can cause psychosis, with similar symptoms to schizophrenia. · Treatment of Parkinson’s disease (associated with reduced dopamine) with L-dopa (a precursor to dopamine) may induce psychotic symptoms. · Dopamine receptor antagonists such as chlorpromazine are effective anti-schizophrenic drugs. E.g. these “neuroleptic” drugs bind to dopamine D2 receptors, some of which are associated with projections from the mesolimbic dopamine system. Some studies have found an increase in dopamine receptors (especially D2) in schizophrenic persons, including those no longer taking neuroleptic drugs.

Question 34

Is the dopamine hypothesis too simplistic?

Answer 34

· Some patients show no improvement when treated with DA antagonists. · Atypical neuroleptics (i.e. clozapine) affect many receptor types, e.g. serotonin as well as D2 receptors. More effective at relieving negative symptoms than typical neuroleptics. · Clozapine can also increase dopamine activity in the frontal cortex. Studies on D2 receptor levels in schizophrenics are inconsistent.

Question 35

Glutamate hypothesis

Answer 35

· NMDA receptor - postsynaptic glutamate receptor. · NMDA receptor antagonists, e.g. phencyclidine, ketamine, produce phenomena resembling both -ve and +ve symptoms. · Glutamate receptor agonist LY2140023 reported to · improve +ve and -ve symptoms in schizophrenia Patil et al. (2007) Probably not just one NT system involved.

Question 36

Synthesis of schizophrenia

Answer 36

· Genetic influences lead to “brain abnormalities” · Developmental influences/birth complications may exaggerate such abnormalities · The emergence of schizophrenia is dependent on whether the “damaged” brain is exposed to environmental stressors Rosso et al. 2000

Question 37

What are the 7 main groups of anxiety?

Answer 37

``` · DSM-V has seven major groups of anxiety disorders: · Panic Disorder · Social Phobia/Anxiety · Agorophobia · Specifc phobias · Generalised Anxiety Disorder · Separation anxiety disorder Selective mutism ```

Question 38

Is anxiety good?

Answer 38

· Fear is an important emotion as it protects us from dangerous situations. · Anxiety is less focussed on an immediate external threat – more anticipatory. · Promotes caution, and apprehension, while curbing excessive or careless behaviour. Becomes a clinical problem when it occurs for no particular reason, or is excessively intense or long- lasting.

Question 39

What is panic disorder?

Answer 39

· Overwhelming anxiety, feeling of being about to die, general SNS activation – fight or flight response · Causes: · Psychological factors (general stress, life · transitions etc.) · Stimulants (caffeine, SSRIs) · Metabolic hypothesis of panic – triggers for panic are lactate (acid formed in the muscles), carbon dioxide (not getting enough air) Amygdala abnormalities

Question 40

Panic and the amygdala

Answer 40

· Amygdala is a crucially important link in the brain’s fear system. – appeared in our early evolution · Ziemann et al (2009): Amygdala is a chemosensor that reacts to changes in the body’s pH produced by high levels of CO2 · Inhaling CO2 produces fear responses in mice, same responses produced by reducing pH of the amygdala with microinjections. Hayano et al. (2009): Volume of amygdala is related to anxiety in PD

Question 41

How is anxiety treated?

Answer 41

· Benzodiazepines – potent class of anxiolytics. · Includes diazepam (Valium) – one of the most prescribed drugs ever. · They act selectively on GABA receptors, which mediate inhibitory synaptic transmission, potentiating the effect of GABA – i.e. increasing inhibitory effects. However, anti-depressants such as SSRIs can also be effective.