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1 Psychiatric disorders. 2 Disorders of Mind & Brain Mind and brain are two sides of one coin; disorders of the mind are disorders of the brain. Particular.

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Presentation on theme: "1 Psychiatric disorders. 2 Disorders of Mind & Brain Mind and brain are two sides of one coin; disorders of the mind are disorders of the brain. Particular."— Presentation transcript:

1 1 Psychiatric disorders

2 2 Disorders of Mind & Brain Mind and brain are two sides of one coin; disorders of the mind are disorders of the brain. Particular clusters of symptoms (syndromes) tend to occur together in various different mental illnesses The ways in which symptoms cluster together tells us something about the structure of the human mind and brain

3 3 Anatomy of psychiatric disorders Contemporary psychiatry implicates neurotransmitters rather than anatomy. –Schizophrenia :: dopamine –Depression :: serotonin To some degree, this may reflect the popular treatments – neurotransmitters specific to brain regions.

4 4 Major symptom clusters Reality distortion Disorganization Psychomotor poverty Psychomotor excitation Depression Euphoria Anxiety

5 5 Reality distortion Mismatch between representation of reality in individual’s mind and representation supported by objective evidence Hallucinations and delusions –Tend to occur together –Tend to respond similarly to dopamine blocking medication

6 6 Hallucination: perception with quality of a sensory perception but nor derived form stimulation of a sense organ –Individual usually falsely attributes perception’s origin to external world Delusion: fixed belief derived by erroneous inference or unjustified assumption that cannot be accounted for by culture or religion

7 7 Delusions Delusions usually false but the key issue is lack of rational grounds and fixity. Ability to engage in logical deduction about other issues is usually intact; certain ideas seem exempted from the need for logic. Non-psychotic distortions of reality (eg in OCD or in non-psychotic depression) reflect biased thinking but are less resistant to debate

8 8 Psychotic Reality Distortion Can occur in schizophrenia, mania, psychotic depression, brain injury or degeneration Themes: persecution; alien control, religion, grandiosity, guilt Influenced by culture, but some themes are common across cultures

9 9 Reality distortion in schizophrenia Characteristic forms (but not present in every case) –Delusions of alien influence over thought, volition, action, affect, bodily function – characteristic –Third person auditory hallucinations Less specific but common forms: –Persecutory delusions (52%), delusions of reference (50%) –Second person auditory hallucinations

10 10 Affective psychosis Mood disorder with psychotic features is diagnosed if psychotic illness is dominated by mood symptoms unless there is reality distortion without substantial mood symptoms for at least two weeks Delusions and hallucinations are usually mood congruent (eg guilt, worthlessness, critical voices with depressed mood; grandiose delusions and self- reinforcing halluciations in mania) Reality distortion shows similar response to antipsychotic medication irrespective of diagnosis

11 11 Neuropsychological correlates of reality distortion Reality Distortion can occur in absence of general defect in reasoning. Defective internal monitoring of self-generated mental activity (Frith & Done 1989; Mlakar et al, 1994) Jumping to conclusions – the bead test (Huq et al, 1988) Patients with persecutory delusions tend to attribute negative outcomes to external causes (Bentall, 1994)

12 12 Regional cerebral activity and reality distortion Early SPECT studies reported over-activity in medial temporal lobe (eg Musalek et al 1989) More recent PET studies demonstrate overactivity in left parahippocamapl gyrus and hippocampus (Liddle et al 1992; Silbwersweig et al, 1995) Liddle et al, 1992

13 13 Neurochemistry and pharmacology of reality distortion Antipsychotic drugs that block dopamine D2 receptors decrease reality distortion Dopamine agonists (eg amphetamine, cocaine) exacerbate delusions and hallucinations Amphetamine produces greater increase in intra-synaptc dopamine in schizophrenia than in healthy individuals (Laruelle et al 1996)

14 14 Pharmacology of reality distortion Serotonin = 5-hydroxytryptamine, or 5-HT 5HT2 receptor agonists such as LSD (which reduce 5HT signalling via autoreceptors) are hallucinogenic Glutamatergic blockers (eg ketamine) can also produce reality distortion

15 15 Hypothesis for generation of reality distortion Episodic memories rely on context for evaluation and validation; semantic memories (eg Paris is capital of France) do not require contextual validation Neural circuits in hippocampus generate a ‘validation’ signal when a mental event (eg an episodic memory) fits its context promoting consolidation of the memory Aberrant hippocampal firing might reinforce incidental thoughts irrespective of context and allow consolidation without need of contextual validation – delusion formation Internal speech might be processed without context thereby becoming detached from internal source- hallucinations Dopamine hyperactivity might reinforce the effect of hippocampal overactivity via the striato-thalamo-cortical feed back loops which mediates the hippocampal signal (This might be blocked by antipsychotic drugs)

16 16 Disorganization syndrome Disjointed thought, emotion, behaviour Formal thought disorder, inappropriate affect, bizarre behaviour Speech shows ‘looseness of associations’, ‘derailment’, replies can be tangential or incoherent Occurs in schizophrenia (a core feature); mania (less commonly); frontal lobe damage. Severity of disorganization is strong predictor of poor occupational and social function

17 17 Neuropsychological correlates of disorganization Core executive processes, especially the selection between competing mental events. Poor Stroop performance (Liddle & Morris, 1991);Errors of commission in CPT (Frith et al 1992) Abnormal spreading of semantic and phonological associations (Spitzer et al 1994)

18 18 Regional cerebral activity and disorganization Liddle et al, 1992

19 19 Regional cerebral activity and disorganization PET study (Liddle et al 1992): –increased activity in medial frontal cortex/anterior cingulate & thalamus; –decreased activity in ventral prefrontal cortex, insula, temporoparietal junction SPET studies (Ebmeier et al 1993; Yuasa et al, 1995) –replicate finding of increased activity in medial prefrontal cortex/ anterior cingulate (ACC) ACC strongly engaged in response selection, eg in Stroop task

20 20 Psychomotor poverty and excitation Psychomotor poverty: –Poverty of speech –Flat affect, anhedonia –Decreased voluntary activity Psychomotor excitation –Pressure of speech –Excited or irritable mood –Motor hyperactivity Abnormalities of the rate at which the mind generates thoughts, feelings and actions

21 21 Psychomotor poverty & excitation: context Psychomotor poverty –Schizophrenia (negative symptoms) –Retarded depression –Frontal lobe injury or degeneration –Basal ganglia degeneration (eg Parkinson’s disease Psychomotor excitation –Mania –Acute schizophrenia –Basal ganglia degeneration eg Huntingtons’ disease

22 22 Neuropsychological correlates of psychomotor poverty Associated with –impaired memory, –Abstraction –Initiation and planning of activity Decreased verbal fluency (Liddle & Morris, 1992; Norman et al 1997) Increased RT in choice RT tasks (Ngan & Liddle, 2000)

23 23 Regional cerebral activity and psychomotor poverty Liddle et al, 1992

24 24 Psychomotor poverty and brain structure In schizophrenia; some studies report psychomotor poverty is associated with ventricular enlargement (Lewis, 1990)

25 25 Neurochemistry & pharmacology of psychomotor poverty Dopamine metabolism decreased (van Praag & Korf, 1971) Stimulants can reduce apathy (Marin et al 1995) Dopamine blocking antipsychotics can exacerbate psychomotor poverty (van Putten et al, 1990)

26 26 Neurochemistry & pharmacology of psychomotor excitation Drugs that promote dopaminergic neurotransmission (eg amphetamine) produce psychomotor excitation in healthy people (Jaobs and Silverstone, 1986)

27 27 Depression & Elation Depression –Low mood disproportionate to circumstances –Sad facial expression, voice, posture –Anhedonia –Cognitive distortions –negative bias, including low self- esteem, guilt, hopelessness, suicidal thought –Somatic symptoms (loss of sleep, appetite, libido etc) –Sometimes associated with psychomotor poverty Elation –Euphoric mood –Animated expression –Elevated self-esteem and optimism –Decreased need for sleep –often associated with psychomotor agitation

28 28 Mood disorders Depression can occur in –Major depressive disorder (15-20% of pop) –Bipolar affective disorder (2% of pop) –Brain injury or degeneration –Drug induced mood disorder –Schizophrenia (depression in >50% of cases)

29 29 Neuropsychological correlates of depression Processing bias, preferential recall or attention to negative material (Gotlib, 1991) Decreased speed of processing (Weingartner et al, 1981) Impaired declarative memory (Zakzanis et al, 1998)

30 30 Brain structure and mood disorders Decreased grey matter in (sub-genual) anterior cingulate cortex in bipolar disorder and in major depression (Drevetts et al 1997) Decreased hippocampal volume associated with duration of illness (Sheline et al, 1996). Possibly due to damage by elevated cortisol during acute episodes

31 31 Regional cerebral activity and depression decreased activity in lateral prefrontal cortex resolves as symptoms resolve (Baxter et al 1989). overactivity in anterior cingulate during acute episodes (Mayberg et al, 1998) evidence underactivity in anterior cingulate and medial prefrontal cortex in those prone to relapse and also in cases that respond poorly to treatment (Bench et al, 1992)

32 32 Regional cerebral activity associated with elation Global increase in regional brain activity during manic episodes (elation + psychomotor excitation) (Baxter et al 1985)

33 33 Regional cerebral metabolism in bipolar disorder (Baxter et al 1985) Depression Mania Depression

34 34 Neurochemistry and pharmacology of mood disorders Depression –Depression is decreased by drugs that enhance monoamine neurotransmission eg SSRIs such as fluoxetine (Prozac) & SNRIs such as venlafaxine – this suggests that serotonin and noradrenaline neurotransmission is under-active in depression, but evidence is inconclusive –Cortisol regulation is disrupted– maybe this is the core biochemical abnormality Elation –Associated with increased dopamine neurotransmission

35 35 Bipolar affective disorder Genetic influence –High concordance of bipolar affective disorder in monozygotic twins between 0.67 and 0.85 (Glahn et al. 2004)-indicate environmental factors must have a role to play. –Occurs around the world at a consistent prevalence, suggests alleles have been present for a long time. Why does this gene survive? Does it pose a benefit. As an analogy, sickle cell trait can lead to illness but is recessive and helps resistantance to malaria. –In low doses the symptoms of hypomania could be advantageous: increase in energy, faster thoughts, less sleep. –Rates of mood disorders elevated among creative individuals (Richards and Kinney, 1989; Jamison, 1989) –Individuals with bipolar traits more likely to be leaders within social groups (Gardner, 1982)

36 36 Anxiety Feeling of unease, dread, fear together with symptoms reflecting over-activity on the sympathetic nervous system –Generalised anxiety disorder –Panic disorder - brief dramatic episodes –Specific phobias eg fear of spiders –Agoraphobia - fear of public places –Post-traumatic stress disorder –Obsessive-compulsive disorder Anxiety disorders frequently coexist, and are often associated with depression

37 37 Regional cerebral activity associated with anxiety Provocation of anxiety produces activation of frontal, limbic and paralimbic cortex in patients and in healthy people

38 38 Pharmacology of anxiety Benzodiazepines (which promote GABA activity) – effective anxiolytics but addictive Antidepressants are also effective anti- anxiety drugs

39 39 Concepts of schizophrenia Characteristic symptoms –Positive – presence of abnormal mental activity Reality distortion Disorganization –Negative – diminution of normal mental activity Psychomotor poverty Many other symptoms: psychomotor excitation; depression Onset tends to occur early in adult life Deterioration in function (variable in degree)

40 40 Reality distortion Delusions –*Thought insertion, withdrawal, broadcast –*Control – made will, made acts, made affect –*Somatic passivity –*Delusional perception –Persecution etc Hallucinations –*Third person auditory (commenting, discussing); Audible thought –Second person auditory –Olfactory, visual, tactile * Schneider’s first rank symptoms

41 41 Age of onset years From Jennen-Steinmetz et al 1997

42 42 Characteristic time course 1 st acute epidsode prodromerelapseresidual phase relapse

43 43 ICD 10 diagnostic criteria At least one strongly characteristic symptom –Schneiderian first rank symptom (eg 3 rd person hallucination; delusion of control.) –Persistent bizarre delusion OR two less characteristic symptoms –Other hallucinations –Formal thought disorder –Catatonia –Negative symptoms Duration: at least one month Exclusion of affective psychosis; exclusion of overt brain disease, or drug toxicity

44 44 Aetiology : predisposing factors Genes – twin concordance: MZ 45%, DZ 12-15% – adoption: risk is determined by biological parent Intra-uterine insult –Maternal viral infection –Maternal starvation –Maternal stress Birth complications

45 45 Aetiology: precipitating factors Stress Drug abuse- –amphetamine, cocaine, –marihuana etc

46 46 Brain structure in schizophrenia Ventricular enlargement (but effect size is only 0.6 – therefore most cases in nromal range) Loss of grey matter in many brain regions, most marked in medial temporal lobe and thalamus

47 47 Executive function, attention, memory (e.g. Green, 1998) Variation over time and between patients is complex, symptoms tend to be worse during acute episodes, but also present during remission Cognitive deficits in schizophrenia

48 48 Pharmacology Typical antipsychotics: eg chlorpromazine; haloperidol: block dopamine - alleviate reality distortion, disorganization and excitation Atypical antipsychotics: block dopamine + other transmitters (eg serotonin). Slightly greater efficacy against positive symptoms; moderate effect on negative symptoms, small improvment in cognition

49 49 Bipolar mood disorder Depressive episode –Depressive syndrome Sad mood, anhedonia Negative thoughts, hopelessness, suicidality Guilt (can be delusional) Somatic symptoms often accompanied by: –Psychomotor poverty (retarded depression) or –Psychomotor excitation (agitated depression) Manic episode –Psychomotor excitation Elation or irritability Pressure of speech Overactivity, reduced need for sleep often accompanied by: –Grandiose reality distortion Grandiose delusions Mood congruent hallucinations

50 50 Genetics Concordance for affective disorders is 67% in monozygotic twins and in 20% in dizygotic twins (Bertelson et al., 1977), genetic factors for unipolar depression related by partially distinguishable Aetiology of bipolar disorder

51 51 Ventricular enlargement (e.g. Pearlson & Veroff, 1981) usually less marked than in schizophrenia Decreased grey matter in anterior cingulate (Drevets et al., 1997) Anatomy of bipolar disorder

52 52 Pharmacology of bipolar disorder Antipsychotics (which block dopamine): effective in treating psychomotor excitation and reality distortion during acute episodes of mania Mood stabilizers (eg Lithium, and various anticonvulsants) Antidepressants have a limited role as they promote mania

53 53 Psychopathy A personality disorder (enduring throughout adult life) with two main groups of features: –Callous disregard for others (Lack of empathy; lying; manipulative; glib; shallow affect; lack of remorse or guilt) –Impaired regulation of behaviour (impulsivity, irresponsibility; need for stimulation)

54 54 Aetiology of psychopathy Genes – Concordance for antisocial personality disorder is 51% in monzygotic twins and 22% in dizygotic twins Brain injury: –damage to frontal lobes in infancy can lead to psychopathy –Frontal damage in adulthood can produce pseudopsychpathy – impaired behavioural regulation without callousness (Phineas Gage) Adverse social circumstances ?

55 55 Cognition and information processing in psychopathy Psychopaths do not show widespread cognitive impairments (Hart et al., 1990), but there is evidence of orbital frontal cortex dysfunction (Lapierre et al., 1995) Reaction time to affect-laden words reduced in healthy people but not psychopaths in lexical decision task (Williamson et al, 1991); less limbic activation while processing affect laden words (Kiehl et al 2001) Abnormal ERPs for response inhibition (Kiehl et al., 2000) and target detection (Kiehl et al 1999)

56 56 Psychopaths exhibit a large fronto-central negativity during stimulus detection tasks that is also present in patients with anterior temporal lobe lesions (Kiehl et al., 1999) Kiehl et al. Yamaguchi & Knight (1993) Johnson (1989) ms ms Nonpsychopaths Controls Psychopaths Temporal lobe damaged patients Temporal lobectomy Parietal lobe damaged patients


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