Lecture 33- Disorders of thought and mood

Question 1

What is the division of depressive disorders?

Answer 1

1. Bipolar affective disorder has two forms: bipolar disorder and cyclothymia (milder manic depression) 2. Major depressive disorder: Major monopolar depression or dysthymia (milder version)

Question 2

What is the DSM definition of a major depressive episode?

Answer 2

A. Five (or more) of the following symptoms have been present during the same 2- week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

1. depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood.
2. markedly diminished interest or pleasure in all, or almost all, activities
3. significant weight loss when not dieting or weight gain (> 5% of body weight in a month), or decrease or increase in appetite nearly every day.
4. insomnia or hypersomnia nearly every day
5. psychomotor agitation or retardation nearly every day
6. fatigue or loss of energy nearly every day
7. feelings of worthlessness or excessive or inappropriate / delusional guilt
8. diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)
9. recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation

Question 3

What feelings are commonly experienced in major depressive episodes?

Answer 3

-In major depressive disorder affective or mood symptoms include depressed mood and feelings of worthlessness or guilt, cognitive and somatic symptoms but also behavioral symptoms including social withdrawal and agitation. -mood symptoms, that affect the way you feel and how other feel about you

Question 4

What feelings are characteristic of manic depression?

Answer 4

-Manic episodes greatly elevated mood, creativity, profusion of thought and pressured speech. May manifest as grandiosity and confidence or anxiety and aggression. Feeling of increased or limitless energy, including reduced need for sleep. Typically highly distractible, irritable, and exhibiting poor judgment. Extreme mania may include disordered (pyschotic) thought. -the depressive phase alternates with mania when they feel extreme pleasure, confidence, also can manifets as anxiety -limitless energy etc. -distractible, delusions about your own potential

Question 5

What is the blood flow in the brain of a depressed person?

Answer 5

• too little blood =chronically underactive
• more blood when in depression episode
• overactivity of the system that makes us feel bad
• Abnormally high blood flow abates with resolution of depression, regardless of the treatment (or lack of) associated with remission

Question 6

What was Robert Schumann’s creativity like during his mania and depression periods?

Answer 6

• in manic depression
• common in people of highly creative people hypomanic= mania, very creative

Question 7

How was the effect of lithium discovered?

Answer 7

-John Cade, a Melbourne Doctor (and UniMelb graduate) was conducting researching in the 1940’s on the effects of uric acid when he accidentally discovered the mood stabilizing effects of lithium on his guinea pigs. -what if urea level too high= can there be an effect on the nervou system -put more urea in dissolved in lithium= after they were much calmer, no extremes of behaviour -lithium is a mood stabilizers= treatment for manic depression

Question 8

How is monopolar depression most often treated?(3)

Answer 8

1. Electroconvulsive therapy= most effective for some people 2. Psychotherapy= the talking cure 3.Antidepressant drugs: Tricyclics, SSRIs NERIs, Monoamine oxidase inhibitors

Question 9

What are the antidepressant drugs used for monopolar depression? (4)

Answer 9

1.Tricyclics= not as common 2. SSRIs ( selective seretonin re uptake inhibitors)= most commonly prescribed 3. NERIs(noradrenalin reuptake inhibitors) =affect neurotransmitter transmission 4. Monoamine oxidase inhibitors

Question 10

Where do drugs interact with neurons?

Answer 10

-Drugs that affect the brain and behaviour (other than those affecting its growth or those having a degenerative or neurogenerative effect) must directly or indirectly affect the excitability of neurons. Interactions with -neurotransmission could occur at numerous places in the biochemical pathways related to neurotransmitter synthesis, storage, release, breakdown, re- uptake and postsynaptic receptor interaction.

Question 11

Where do drugs that affect mood work?

Answer 11

-when drug work on mood= neural transmission effect -lot of scope for subtle changes -blocking release, blocking transport, blocking enzyme that breaks it down, blocking re uptake -modulating the receptor, occupancy…

Question 12

Where do the antidepressive drugs act on?

Answer 12

• act at the noradrenalin and serotonin synapses -affect either reuptake, or enzymatic breakdown of monoamines

Question 13

Where do tricyclics, SSRIs and NERIs act on?

Answer 13

-noradrenaline and serotonin are broken down but also they are up taken by the cell inhibition of its re uptake= prolong its action= it is like you released more

Question 14

Where do monoamine oxidase inhibitors act on?

Answer 14

-this breaks down the enzyme that breaks them down= so increase in serotonin and noradrenaline

Question 15

What do MAO inhibitors do?

Answer 15

-MAO is the enzyme responsible for the destruction of all monoamines (Noradrenalin, adrenaline, dopamine and serotonin).

Question 16

What do MA reuptake inhibitors do? (SSRI, NERI)

Answer 16

-Monoamine reuptake (the other mechanism for limiting the action of monamines at synapses) further supports the idea of impaired monoamine transmission underlying depression.

Question 17

What does lithium do?

Answer 17

Lithium salts are the third category of drugs used to treat depression, particularly manic depression; their mode of action is not understood but may modulate phosphoinositol second messengers.

Question 18

What are the diffuse modulatory systems?

Answer 18

-the dopamine, serotonine, acetylcholine, noradrenaline systems -always from one or a few nuclei and project to most of the brain -their action is subtle change, modulate overall state of the brain -so the entire brain can be affected by these systems (except dopamine that is more targeted)

Question 19

What are the 4 characteristics of diffuse modulatory systems?

Answer 19

1. A nucleus or cluster of nuclei with relatively few neurons (thousands rather than millions) 2. Most of the nuclei are in the “central core” of the brain: the brainstem (most here) and basal forebrain 3. Each neuron can influence many (maybe hundreds of thousands) of neurons elsewhere in the brain – this is called a highly divergent projection 4. The synapses made by these cells are typically “en passant”

Question 20

What is the serotonin system like?

Answer 20

• cell bodies are in the reticular core of the brainstem,
• raphe= on the midline,
• some project to the spinal cord= spinal pattern generator, some to cerebellum and huge projection to most of cerebrum

Question 21

What is the norepinephrine system like?

Answer 21

• main locus-locus coeruleus
• projects almost everywhere

Question 22

What is the acetylcholine system like?

Answer 22

• one nucleus in basal forebrain
• other in brainstem
• massive projections to everywhere

Question 23

What is the dopamine system like?

Answer 23

• distinct as it doesn’t project to spinal cord and cerebellum
• only VTA to nucleus accumbens is the main projection

Question 24

What is an ionotropic neurotransmitter channel?

Answer 24

• rapid changes in neuronal excitability -what do they do- subtle changes -ionotrpoic receptor, for a particular neurostranmitter - monoamines do not affect these -there is a recpetor, binding site, opens a channel (ionotropic) allows ions to come in usually plus -acetocholyne -rapid changes in excitability -

Question 25

What do metabotropic neurotransmitter receptors do?

Answer 25

• more subtle modulation of excitability
  1. either they affect metabotropic- bind and activate biochemical process, usually an enzymatic process -the enzyme can do sth to the channel, so dynamics are different, stays open longer or shorter etc.
  2. activate an enzyme that makes a second messenger, can change expression of the ion channel genes makes the response of cell subtly different
• change the overall state of large portions of the brain, subtle change of excitability (the systems like serotonin etc)

Question 26

What are the signs people with schizophrenia have prior to psychotic episodes?

Answer 26

-prodromal signs:

• social withdrawal
• neglect of personal hygiene
• odd ideas and behaviour
• flattened affect and paucity of speech
• These signs are an absence of normal actions and are thus called negative symptoms.
• non-psychotic symptoms may include:
• certain tendencies to become overloaded with information
• difficulty in crowded rooms or when lots of people are talking

easily distracted

• periods of great mental activity and creativity and excitement
• suspiciousness

Question 27

What are the two categories of DSM criteria for schizophrenia?

Answer 27

A. Characteristics symptoms B. Social/occupational dysfunction

Question 28

What are the A.Characteristic symptoms in DSM for Schizophrenia? (5)

Answer 28

• two or more of the following each present for a significant portion of time during a 1 month period
  1. delusions
  2. hallucinations
  3. disorganized speech (frequent derailment or incoherence)
  4. grossly disorganized or cataconic behaviour
  5. negative symptoms (affective flattening, alogia, avolition)
• only one criterion A is required if delusions are bizarre or hallucinations consist of a voice keeping up a running commentary on the behaviour or thoughts

Question 29

What are the B. Social/ occupational dysfunction of DSM for schizophrenia?

Answer 29

-For a significant portion of the time since the onset of the disturbance, one or more areas of functioning such as work, interpersonal relationships, self-care are markedly below the level achieved before =this looks like prefrontal function= social cognition

Question 30

What are acute psychotic episodes characterized by (schizophrenia)?

Answer 30

-delusions of paranoia, grandiosity, spiritual or supernatural experiences, auditory hallucinations, the feeling that they are being controlled by external forces and the misattribution of significance

Question 31

What is misattribution of significance?

Answer 31

= loss of insight into behaviour

Question 32

What is paranoia?

Answer 32

thinking about other people’s motives and getting them wrong

Question 33

What is common in people diagnosed with the disorganized subtype of schizophrenia?

Answer 33

-strange emotional responses, inappropriate to the situation -strange facial responses, silly, inappropriate laughter -complete lack of expressed emotion is seen sometimes -apparent indifference -anhedonia (lack of pleasure) -and avolition (lack of motivation)

Question 34

What is paranoia often associated with?

Answer 34

-psychotic illnesses, sometimes schizophrenia

Question 35

What are the cognitive problems associated with schizophrenia? (4) the most important ones for us!

Answer 35

1. Directionless- lack goals or the ability to set and achieve goals 2. Trouble with social cues- not being able to interpret body language, eye contact, voice tone, and gestures appropriately 3.Often not responding appropriately and thus coming off as cold, distant and detached 4. Difficulty focusing attention and engaging in goal directed behaviour =all are prefrontal function

Question 36

What are some other examples of the cognitive problems associated with schizophrenia? (8)

Answer 36

1. Ruminating thoughts 2. Racing thoughts 3. Making up new words (neologism) 4. Becoming incoherent or stringing unrelated words together (word salad) 5. Frequent loose association of thoughts and speech 6. Poor concentration/ memory 7. Nonsensical logic 8. Thought, behaviour and actions are not integrated

Question 37

Is there a genetic component to schizophrenia?

Answer 37

• yes
• if identical twin has it 50% chance the other one will
• more closely related= higher chance

Question 38

What is frequent anatomical correlate of schizophrenia?

Answer 38

• enlarged ventricles
• some patients don’t exhibit this however

Question 39

What are chemically the drugs used to treat schizophrenia?

Answer 39

D2 receptor antagonists -the efficacy of the drugs is dependent on the affinity to D2 receptor, how well they bind to that receptor -the antagonist is effective= so suggesting that the cause is overstimulation by dopamine

Question 40

What is the efficacy of drugs for schizophrenia determined by? =dopamine hypothesis

Answer 40

-the efficacy of the drugs is dependent on the affinity to D2 receptor, how well they bind to that receptor -the antagonist is effective= so suggesting that the cause if schizophrenia and other mental illness is overstimulation by dopamine

Question 41

What is the problem with the dopamine hypothesis?

Answer 41

-dopamine is too simple as an explanation -the drug effect should be within minutes to hours -yet the benefits of the drugs take weeks to feel better 1) Dopamine antagonists can be shown to bind to receptors a short time after administration, but relieve of symptoms takes several weeks (as with antidepressants). 2) PCP (angel dust) is a drug that causes psychotic states with similarities to schizophrenia (such as paranoid delusions and auditory hallucinations that control the person) but it acts on a subclass of glutamate receptors not dopamine receptors. 3) Some people with schizophrenia don’t respond to D2 blockers, but to drugs that show broad monoamine antagonism.

Question 42

What is the connection between glutamate and schizophrenic symptoms?

Answer 42

• PCP (angle dust), a NMDA (glutamate receptor) antagonist, can case florid psychotic behaviour in people= these are glutamate antagonist yet produce schizophrenic symptoms, so the dopamine hypothesis is not the whole picture

Question 43

What was the experiment with mice and glutamate withdrawal?

Answer 43

• Experimental reduction in glutamate receptors, causes social withdrawal in mice -reduction in glutamate= mice less social -oversimplified the approach, neurotransmitter is really complex, the serotonin and dopamine receptors= interact etc.