Adult Psychiatry 1 Flashcards
Point prevalence estimate of depression?
7%
Which age group is at highest risk for depression?
> 30
Mean age of onset of depression?
30
When does first depressive episode occur for 50% of patients?
<40
Mean number of episodes of depression in patients with lifetime depression?
5
Longest duration of depression?
24 weeks per episode
How many depressed patients receive antidepressants in a year?
21%
How many patients have consulted their GP in a year about their depression?
One third
How many patients with depression have seen a psychiatrist in one year?
21%
How many patients with depression remain untreated despite seeking help?
21%
Mean age of treatment onset for depression?
33.5 years - lag 3 years
Most common comorbidity with depression?
Alcohol use (>40%)
Anxiety (>40%)
PD (30%)
Which PD has a strong association with lifetime depression?
Cluster C except for anankastic
How many people with depression attempt suicide?
9%
How many patients with depression fail to seek treatment?
43%
How many times do patients with depression see their GP compared to non-sufferers?
Three times as many
How many patients with depression who seek help are given antidepressants?
31%
25% of these are antidepressants
In how many patients does the initial diagnosis of depression change?
56%
What does the initial diagnosis of depression change to in patients?
Schizophrenic spectrum - 16%
PD - 9%
Neurotic, stress-related and somatoform disorders - 8%
Bipolar - 8%
Who did studies into the changes in diagnosis of patients initially diagnosed with depression?
Kessing, 2005
In the community, how many patients with a depressive episode go on to develop mania?
One in ten patients within ten years
How many severely depressed patients in hospital go on to develop an episode of mania?
50%
Which types of patients with bipolar typically begin with a depressive episode?
Females
What factors are associated with a change from depression to mania?
Young age
FH of bipolar
Antidepressant-induced hypomania
Hypersomnia
Retarded phenomenology
Psychotic depression
Postpartum episode
Mean age of onset of mania following depressive episode
32 years
Risk of suicide in patients with mood disorders compared to the general population
14 times greater
How long does an untreated depressive episode last for?
6-13 months
How long does a treated episode of depression last for?
3 months
What happens to depressive episodes as the course of the disorder progresses?
More frequent episodes that last longer
Median episode length of depression?
12 weeks
How many patients with depression only had one episode and no future episodes
50%
How many patients with depression will experience a recurrence in 5 years?
50%
What is the risk of a patient with 2 major depressive episodes having a third?
70%
What did Paykel et al show re relapses of depression?
Risk of relapse recurrence is higher in patients with residual symptoms (75% in 15 months) compared with those in full remission (25% in 15 months)
Over a lifetime, how many episodes do bipolar patients have compared to patients with depression?
Twice as many
What is defined as a partial response to treatment for depression?
26-49% decrease in symptom severity
What is remission for depression?
When no scale can detect meaningful measure of depression (e.g. HAMD<7) and continue to do so after the natural period of a treated depressive episode (>3m)
What is recovery in depression?
No scale can detect meaningful measure of depression after natural period of untreated depressive episode (>6m)
What is a relapse of depression?
Any repeat of a depressive episode before recovery
What is a recurrence of depression?
Repeat of a depressive episode after recovery
Good prognostic indicators for depression
Mild episodes
Absence of psychotic sx
Short hospital stay
Hx of sold friendships during adolescence
Stable family functioning
Sound social functioning for 5 years prior to illness
Absence of comorbid psychiatric disorder
No more than one previous hospitalization for depression
Relapse indicators for depression
Persistent dysthmia
Comorbid conditions - both psychiatric and medical
Female
Longer episodes of illness before seeking treatment
3 or more episodes of depression prior to treatment
Never marrying
Remission status at 3 months - partial remission predicts recurrence
Previous episode in past year
Severity of episode
Long previous episodes
What is necessary re depression in primary care?
Screening high risk groups
What do you treat first if someone presents with both anxiety and depression?
Depression
What needs to be done before depression can first be treated?
Severity must be classified
When is watchful waiting an agreeable strategy for depression?
For mild depression; must be reviewed in 2 weeks
Antidepressants for mild depression?
Poor risk-benefit ratio
Best advice for mild depression?
CBT-based guided self-help
Best advice for mild/moderate depression?
CBT
Counselling
Problem-solving therapy
Which antidepressants are first line for depression?
SSRIs
Best treatment for severe depression?
Combination of antidepressants and CBT - more cost-effective
How long should antidepressants be continued in those with moderate or severe depression?
For at least 6 months after remission
Which patients must continue antidepressants for 2 years?
Patients with >2 episodes in recent past or residual impairment
Treatment for atypical depression?
SSRI first line
Referral to specialist second line
What may specialists consider for women presenting with atypical depression?
Phenelzine if no response to SSRIs
How long should patients remain on Lithium augmentation of antidepressant if helpful?
At least 6 months
When should ECT be considered in depression?
If adequate trial of other treatments is ineffective and/or when condition is potentially life-threatening in severe depression
Is ECT maintenance recommended in depression
No
How long should treatment be continued for a single episode of depression?
At least 6-9 months after resolution of sx
What does the MHRA say about SSRIs?
Use lowest possible dose
Monitor closely in early stages for restlessness, agitation and suicidality - particularly in those <30 y/o
Doses should be tapered gradually on stopping
What is NNT for antidepressant response?
4-5
What is NNT for antidepressants for remission?
6-7
What is NNT for elderly with depression on TCAs?
4
What is NNT for elderly with depression on SSRIs?
8
What is NNT for elderly with depression on MAOIs?
3
NNT benefit and harm for Paroxetine in children?
NNT benefit 12
NNT harm 20
NNT benefit of Sertraline in depression in kids?
10
NNT benefit of Fluoxetine in Depression in kids?
5
Who conducted a meta-analysis of 47 trials including 4-8 weeks RCT of antidepressants?
Kirsch
What did Kirsch’s meta-analysis include
47 trials including 4-8 weeks RCTs of Nefazadone, Venlafaxine, Fluoxetine and Paroxetine.
Weighted mean improvement in Kirsch’s meta-analysis between treatment and placebo?
- 6 points on Hamilton in drug group
7. 8 in placebo
Did Kirsch’s meta-analysis show significance in findings for antidepressant treatment?
Statistical significance but not the three-point Hamilton criterion for NICE for clinical significance.
Magnitude of difference was a function of baseline of severity of depression.
What did Kirsch’s meta-analysis show re placebo effect?
It declined as severity increased
What type of approach does NICE recommend for treating depression?
Stepped care model advocated by WHO in managing chronic illness
Who created the phases of depression treatment after one episode?
Hirschfeld 2001
How long does acute phase of depression last?
3 months
How long does continuation phase of depression last?
If relapse free, 6-12 months.
How long does maintenance phase of depression last?
Aims to prevent recurrences - depends on risk factors and probability of recurrence.
What was Geddes research?
Pooled analysis of data from 31 randomised trials of 4,410 patients taking antidepressants
What did Geddes research show?
Continued treatment with all classes of antidepressants reduced risk of relapse by 70% compared with treatment discontinuation after acute episode
Average rate of relapse on placebo in Geddes research?
41%
Average rate of relapse on antidepressant in Geddes research?
18%
Treatment effect duration of antidepressants in Geddes research?
36 months
What is STAR*D?
Sequenced treatment alternative for depression was a pragmatic RCT - 2/3 had comorbid physical disorder, 2/3 had co-morbird psychiatric diagnosis and 40% had onset of depression at <18 years of age - similar to the real world.
How many patients in the STAR*D study?
4041 patients at 25 sites in the USA
How did STAR*D study work?
4 steps of treatment.
Any patient who failed to meet remission criteria at each step was moved up to the next level.
What was Level 1 in the STAR*D study?
Citalopram for up to 12 weeks
What was Level 2 in the STAR*D study?
If after 12 weeks patient failed remission, they were randomized as per their preference to switch to either Bupropion, Sertraline or Venlafaxine, to cognitive therapy or to augment citalopram with Bupropion or Buspirone or to combine citalopram with cognitive therapy.
What was level 3 in the STAR*D study?
Participants who did not achieve remission after 12 weeks in level 2 were randomised to switch to mirtazapine, nortriptyline or augment level 2 treatment with lithium or thyroid medication.
What was level 4 in the STAR*D study?
Patients who did not achieve remission after 12 weeks in level 3 were switched to an MAOI, tranylcypromine or switch to a combination of venlafaxine XR and mirtazapine.
What is measurement-based care which was used in the STAR*D study?
Routine measurement of symptoms and side effects at each treatment visit with the use of a treatment manual-guided when and how to modify doses tailored to each individual.
What happened has patients went up the levels in the STAR*D study?
Remission rates dropped
Relapse rates increased
Cumulative remission rate after all 4 steps in STAR*D study?
67%
Cumulative non-response rate in STAR*D study?
33%
How many patients became symptom free after 2 levels in the STAR*D study?
Half of participants
What was the difference between switching to a class outside of an SSRI and to an SSRI in the STAR*D study?
No statistical difference
What were the findings at level 3 of the STAR*D study?
No statistical difference between the different antidepressants or augmentation with Lithium or T3.
What were the results at level 4 in the STAR*D study?
No difference between MAOI and Mirtazapine/Venlafaxine XR combination although degree of symptom relief was better with the latter.
Factors leading to immediate attrition in STAR*D study?
Younger age
Less education
Higher perceived MH functioning
Factors leading to late attrition (within 12 weeks) in the STAR*D study?
Younger age
Less Education
African American
Evidence of dose escalation for depression?
Dose escalation before 4 weeks of treatment appears to be ineffective.
What did STAR*D study show re difference between men and women?
Men have more suicidal ideation and are 2-4 times more likely to complete suicide. They have more psychomotor agitation and substance use.
Women report more suicidal attempts, have more sx of anxiety and atypical depression, earlier age of onset and longer episodes.
Who is at risk of suicidal behaviours when started on antidepressants?
<25 years of age
What did Hawton et al study in 2010?
Toxicity of antidepressants in OD
What did Hawton el al (2010)’s study show?
TCAs have greater toxicity in OD than Venlafaxine & Mirtazapine, both of which have greater toxicity than SSRIs.
Which TCAs are more toxic in an OD?
Dosulepin
Doxepin
Which SSRIs are most toxic in an OD?
Citalopram
What are the 5As which can result in apparent resistance to antidepressant treatment?
Alcoholism Lack of adequate dosage Lack of adherence Axis 2 disorders (PD) Alternative diagnosis
Which combination of antidepressants can lead to a risk of serotonin syndrome?
SSRI-MAOIs
What is ‘Californian rocket fuel’?
Venlafaxine & Mirtazapine combination
How does the SSRI and TCA combination work?
SSRIs inhibit TCA metabolism
Which combination of antidepressants is found to be most effective?
No single combination is found to be superior to others
How does Agomelatine work?
5HT2C antagonist, Metaltonergic agonist.
GABA interneurons tonically inhibit noradrenergic circuits for locus coeruleus and dopaminergic circuits from ventral tegmentum projecting to prefrontal cortex.
5HT2C receptor stimulation drives these GABA interneurons. Thus, norepinephrine and dopamine circuits are inhibited by the normal tonic release of serotonin.
What medication has been found which when combined with antidepressants can speed response and reduce drop-out?
Benzos - manages early anxiety/agitation and insomnia
How to reduce sexual SEs of antidepressants?
Switching antidepressant
Adding Sildenagil or Tadafinil for erectile dysfunction or Bupropion 150mg BD for sexual dysfunction in men
Adding bupropion or sildenafil in women
How can fatigue be reduced as a SE of antideoressants?
Modafinil may improve fatigue
Evidence for St Johns Wort in depression?
No conclusively positive findings.
Folate has a significant effect only when combined with an antidepressant.
St Johns Wort can increase effects of SSRIs.
How does Ketamine act as an antidepressant?
Blockage of glutamatergic NMDA receptors and relative upregulation of AMPA receptors.
May also act on mammalian target of rampamycin (mTOR) and BDNF to affect intracellular signalling.
Clinical evidence of Ketamine as an antidepressant?
Rapid improvements in mood and suicidal thinking in 70% of participants, although effects are temporary when single infusion is administered.
What other disorders can Ketamine be used for (in research)?
Bipolar - positive results
Prevalence of Bipolar?
1.5%
What is NCS-replication?
Part of the World Mental Health survey initiative
Lifetime prevalence of bipolar in NCS-replication?
Bipolar 1 - 1%
Bipolar 2 - 1.1%
Mean age of onset of BP 1 and 2?
1 - 18.2
2 - 20
Which Bipolar disorder has greater severity and impairment?
2
What did Angst et al (2003)’s study show re Bipolar?
20 year long prospective study showed patients with depression and clinically undiagnosed subsyndromal hypomania have similar risk factors, course and outcome compared to Bipolar 2
Suicide rate of Bipolar?
15-18x higher than the general population.
How many people with bipolar experience another MH disorder?
2/3
What are the two dimensions of mood disorders?
Proportionality - from predominant depression to predominant mania
Severity - from normal emotional states to psychotic mood states
Who described an extension to bipolar 1 & 2 classification?
Akiskal and Pinto in 1999
What was Akiskal and Pinto (1999)’s extension to Bipolar 1 and 2 classification?
1: manic-depressive illness
1 1/2: depression with protracted hypomania
2: depression with spontaneous hypomanic episodes
2 1/2: depression superimposed on cyclothymic temperament
3: recurrent depression plus hypomania occurring solely in association with antidepressant or other somatotherapy
3 1/2: mood swings that persist beyond stimulant and/or alcohol abuse
4: depression superimposed on a hyperthymic temperament
What does DSM V now include re bipolar?
Emphasis on changes in activity and energy as well as mood when making diagnosis of manic of hypomanic episodes
In how many patients with bipolar is a prodrome seen?
Half
How long is the prodrome for bipolar?
> 1 year
Which sx were more common in patients with bipolar who had a prodrome period?
Attenuated positive sx
Increased energy/goal-directed activity
All in patients with later psychotic mania
Who confirmed that there was a correlation between stressful life events and first manic admission?
Ambelas
In which patients is there a correlation between stressful life events and first manic episode?
Younger patients
thought that sleep reduction may be final common pathway to mania
How many patients with bipolar get misdiagnosed with depression?
40%
Which diagnosis of bipolar is more stable?
1
Median time to recover from mania with treatment?
4-5 weeks
Course specifiers for bipolar in DSM?
Chronicity
Seasonality
Rapid cycling
How many patients with bipolar display specific pattern of predominant polarity?
56%
How many patients with bipolar may be classified as predominantly depressed?
60%
How many patients with bipolar are classified as predominantly manic or hypomanic?
40%
Which type of bipolar is predominantly of depressive polarity?
2
Which polarity of bipolar is seen in younger age group?
Mania
Which polarity of bipolar shows more seasonality?
Depressive
Which polarity of bipolar has more suicide attempts?
Depressive
Which polarity of bipolar responds better to antipsychotics?
Manic
Suicide rate in bipolar?
10-19%
15x greater than the general population
How many people with bipolar will attempt suicide?
1/4
Risk of recurrence in people with bipolar?
50% in one year
>70% at 4 years
compared with other psychiatric disorders
How often do people with Bipolar 2 suffer from mood sx?
54%
How often do people with Bipolar 1 suffer from mood sx?
47%
How many people with Bipolar 2 experience depressive sx?
93%
How many people with Bipolar 1 suffer from depressive sx?
67%
What did Perlis et al. find re bipolar?
Biggest predictor of relapse was residual sx
Majority of relapse were into depression
Which type of patients with bipolar spent the highest proportion of time being ill?
Patients with a depressive index spent 65% of the time unwel
What % of time did people with a manic index phase unwell?
30%
What is the ‘final common pathway’ triggering mania and depression?
Sleep disruption
What comorbidities are linked to relapse of Bipolar?
Substance use increases risk of manic relapse
Anxiety increases risk of depressive relapse
What is ‘switch’ in bipolar?
Antidepressant-induced mania
When does switch occur?
Soon after starting antidepressants
Definition of switch
Anti-depressant induced mania within 2 months of treatment - Ghaemia
What is mood destabilisation?
Antidepressants result in increased frequency of mood episodes over time that would have occurred in the national course
Which antidepressants have low rates of acute manic switch?
New generation
Which antidepressants can produce long-term mood destabilisation?
New generation
Which study found that new generation antidepressants can cause long-term mood destabilisation?
STEP-BD trial - Ghaemia, 2008
What % of bipolar patients have had anti-depressant induced mania/hypomania?
20-40%
What % of patients on Lithium had mood switches and what % did not?
15% lithium
44% not on lithium
Risk factors for anti-depressant induced switch?
Previous antidepressant-induced mania
FHx of bipolar
Exposure to multiple antidepressants
Initial illness beginning in adolescence or young adulthood
Which medications can cause a switch from mania to depression?
Antipsychotics
What does Bipolar have that depression does not?
Lesser anxiety Fewer physical complaints More withdrawal More retardation Hypersomnia More atypical sx
What type of depression is suggestive of bipolar?
Psychotic depression in early adulthood
What is rapid cycling?
4 or more episodes in a year - both mania and depression
What is ultra-rapid cycling?
4 or more episodes in a month
What is ultra-ultra rapid or ultraradian cycling?
4 or more episodes in a week
What % of rapid cyclers are women?
80%
Age of onset of illness of rapid cyclers?
Earlier than non-rapid cyclers
Features of patients with rapid cycling
More severe depression and mania Lower global functioning Earlier age of onset Current hypothyroidism Poor response to lithium
What is secondary mania?
Due to organic brain damage - usually right hemisphere
More common in elderly
Which medications are associated with mania?
L-Dopa
Steroids
DSM criteria for hypomania
4 days
Duration criteria for mania
7 days
Treatment of new onset mania
Antipsychotics - rapid anti-manic effect
Which medication should not be used first line for new onset mania?
Lamotrigine
Recommendations if patient presents with new onset mania and is on an antidepressant?
Consider stopping antidepressant
Offer antipsychotic regardless of whether antidepressant is stopped
Recommendation of benzos for mania?
Clonazepam/Lorazepam can be used for agitation and insomnia
Research re benzos for bipolar
For bipolar 1 experiencing a manic episode, clonazepam may be as effective as lithium in improving manic sx at 1-4 weeks.
First option for acute manic relapse in a known bipolar patient?
Increasing dose of mood stabiliser
Treatment option for manic relapse in bipolar patient on lithium
Check serum lithium levels and consider establishing higher serum level if good compliance.
2nd line treatment for manic relapse in bipolar patient on lithium
Consider adding haloperidol, olanzapine, quetiapine or risperidone
In which patients with bipolar can antipsychotic augmentation be done?
Those on valproate
When is ECT considered in mania?
Severely ill manic patients
Treatment-resistant mania
Those who prefer ECT
Severe mania during pregnancy
Which psychiatric drug has a high association with low Na?
Carbamazapine
Oxcarbazepine
First line treatment for depression in bipolar
Psychological intervention specific for bipolar depression or high-intensity psychological intervention
Pharmacological treatment guidelines for depression in bipolar
If not on medication, fluoxetine combined with olanzapine or quetiapine on its own
Second step for pharmacological treatment of depression in bipolar
Lamotrigine
When does NICE recommend using long-term maintenance treatment for bipolar?
After manic episode involving significant risk and adverse consequences
Bipolar 1 with 2 or more acute episodes
Bipolar 2 with significant functional impairment or risk
First line maintenance treatment for bipolar?
Lithium
Which drug is associated with reduced risk of suicide in bipolar?
Lithium
Lithium maintenance responders profile?
Euphoric mania No rapid cycling Full interepisode remission No comorbidity No psychotic features Fewer lifetime episodes
Other treatment options for maintenance of bipolar
Valproate Olanzapine Quetiapine Carbamazapine Lamotrigine
Which medications prevent depressive relapses more than manic?
Lamotrigine
Which medications prevent manic relapses more than depressive?
Valproate
Olanzapine
How to manage mixed episodes of bipolar?
Treat as manic episodes
Avoid antidepressants
Best evidence is for valproate and atypical antipsychotics
What to consider when treating rapid cycling?
Treat any hypothyroidism or substance misuse
Stop antidepressants
Consider suboptimal medication regime, lithium withdrawal and non-compliance
Treatment of rapid cycling?
Lithium, valproate or Lamotrigine
How long should maintenance treatment be continued for in bipolar?
2 years after episode
5 years if high-risk factors for relapse
First line treatment for paediatric bipolar?
Atypical antipsychotic
Research for adjunctive antidepressant use in bipolar?
24% of antidepressant achieved primary outcome
27% of placebo group achieved primary outcome
Which study did research in adjunctive antidepressant use in bipolar?
STEP_BD
Which antidepressant as a higher risk of precipitating a switch to mania?
TCAs
What happens in antidepressant-associated chronic irritable dysphoria?
Occurs in bipolar patients who have received antidepressants for a long period of time.
Sx of antidepressant–associated chronic irritable dysphoria?
Irritability
Mixed insomnia
Dysphoria
Which anti-epileptic can cause psychosis?
Vigabatrin
Bauer et al.’s definition of a mood stabiliser?
Efficacy in: treatment of acute manic sx treatment of acute depressive sx prevention of manic sx prevention of depressive sx
According to Bauer et al., which medications can be classified as mood stabilisers?
Lithium
Suicide risk of bipolar patients admitted to hospital long-term?
10%
Components of CBT for bipolar?
Psych-education
Self-monitoring
Self-regulation: action plans and modification of behaviours
Increased compliance
Difference in criteria for bipolar in children as per NICE?
Mania must be present
Euphoria must be present most days, most of the time (7 days)
Irritability is not a core diagnostic criterion.
Incidence of schizophrenia
16-42 per 100,000
What did McGrath et al. show?
Five-fold difference in incidence rates of schizophrenia across various sites
Risk of schizophrenia in urban sites vs rural?
Two-fold in urban
Incidence of schizophrenia in migrants?
3-5 times more common than the native population
Which births increase risk of schizophrenia?
Winter/spring birth
Male:female ratio of schizophrenia?
1.4:1
Median prevalence of schizophrenia?
4.6/1000 - point prevalence
Period prevalence of schizophrenia
3.3/1000
Lifetime prevalence for schizophrenia
4/1000
Lifetime morbid risk of schizophrenia
7.2/1000
Which groups have higher rates of schizophrenia?
Migrants
Homeless
Which countries have a lower prevalence of schizophrenia?
Developing countries
Catatonia in developing vs developed countries
10% in developing
1% in developed
Hebephrenia in developing vs developed countries
13% in developed
4% in developed
Which study looked at schizophrenia in BME communites?
AESOP study
What did the AESOP study find?
All psychoses are more common in BME groups compared to white population in Bristol, SE london and Nottingham
What did ONS 2000 Psychiatric comorbidity survey of households find?
- 5% endorsed at least one psychosis item
- 2% endorsed hallucination item: of this, 4.2% said they heard/saw something others could’nt, 0.7% reported hearing voices
What is the genetic assumption re schizophrenia?
Individuals at enhanced genetic risk of schizophrenia i.e. FHx of schizophrenia inherit a state of vulnerability characterised by transient and partial psychosis-like sx
Who did a study into genetic risk of schizophrenia?
Johnstone et al. 2005
What did Johnstone et al. 2005’s study find re schizophrenia?
10% risk present in those with high risk FHx increases to nearly 50% in subgroup of those who have a high score on schizotypal cognition and social withdrawal.
What did Johnstone et al. 2005’s study show re discriminating factors for high risk development of schizophrenia?
Measures of episodic memory may be significantly discriminating between those with high risk who develop schizophrenia frm those who do not; suggestive of temporal lobe dysfunction.
What did the Australian PACE clinic sample show?
20 of 49 high-risk subjects (40.8%) developed a psychotic disorder within 12 months.
What did Australian PACE clinic sample show were risk factors of developing psychosis?
Long duration of prodrome Poor functioning at intake Low-grade psychotic sx Depression Disorganization
What did a German study show re schizophrenia?
Using Bonn Basic Sx criteria, high conversion rate was seen in help-seeking individuals in long follow-up period of 10 years.
They found 5 of the sx clusters of the Bonn scale were a significant predictive discriminator.
Which 5 sx clusters of the Bonn scale have been found to be significant discriminators of psychosis in the future?
Presence of thought, language, perception and motor distrubances
What did the North American Prodrome Longitudinal study (NAPLS) find?
High risk UHR criteria predict early transition to psychosis.
Incidence of delusional disorders
0.7-1.3 per 100,000
Prevalence of delusional disorders
24-30 per 100,000
Proportion of people with delusional disorder admitted to hospital
1-3%
Mean age of onset of delusional disorder
39 y/o
Sex ratio of delusional disorder
1.18:1 - M:F
What was the structure of the Iowa study show re outcomes for schizophrenia?
186 people with schizophrenia were followed-up for 35 years.
What did the Iowa study show re outcomes for schizophrenia?
46% of people improved or recovered.
What was the structure of the Bonn Hospital Study in Germany?
502 people with schizophrenia were followed up for 22.4 years.
Results of Bonn Hospital Study in Germany?
22% had complete remission of sx
43% had non-characteristic types of remission (non-psychotic)
35% experienced characteristic schizophrenia residual sx.
Structure of Chestnut Lodge study
446 patients with schizophrenia were followed-up for 15 years
What did the Chestnut Lodge study show re schizophrenia?
36% recovered or functioned adequately.
What did the Vermont longitudinal study show re outcomes of schizophrenia?
68% of patients who underwent a rehab programme had good functioning as per the GAF scale.
What was the International study of Schizophrenia (ISoS 1997)
Follow-up analysis of two major WHO incidence cohorts from 9 countries.
Results from ISoS 1997 study
52% of patients in developing countries were assessed to be in the ‘best’ outcome category (single episode followed by partial or full recovery) compared with 39% in developed countries
What did ISoS 1997 study show re follow-up of patients with schizophrenia?
At 5 years, 73% of those from developing countries were in the best outcome group compared with 52% in developed countries.
What did the DOSMeD study show re schizophrenia?
Highest rates of recover occurred in the developing world.
What should we divide risk factors into?
Risk indicators
Risk modifiers
What are risk indicators?
Increased risk but not causative
What are risk modifiers?
Associated with causation
Risk of schizophrenia if both parents have schizophrenia
40-50%
Single nucleotide polymorphisms (SNPs) linked to schizophrenia
12p13.33
12q24.11
1q42.2
11q23.2
2q33-34
5q33.2
16p13
7q21
1p21
8p12
17p13
18q21
2q32
Copy Number Variations (CNVs) linked to schizophrenia
2p16.3 deletion
7q36.3 duplication
Hemi deletion of 22q11
Gene of 12p13.33
CACNA1C (L-type calcium channel)
What is CACNA1C important for?
Neuronal function
What do mutations of CACNA1C cause?
Timothy Syndrome
Brugada Syndrom
Gene of 12q24.11?
D-amino acid oxidase
What is D-amino acid oxidase important for?
Degrades d-serine (NMDA co-agonist)
Gene of 1q42.2?
DISC-1
What is DISC-1 seen in?
Scottish family with 1:11 translocation
Disrupted in schizophrenia
Gene of 11q23.2?
Dopamine D2 receptor
Importance of 11q23.2?
Target for antipsychotic action
Gene for 2q33-34?
Receptor tyrosine kinase erbB4
Importance of 2q33-34?
Neuregulin 1 receptor
Gene for 5q22.3?
AMPA receptor subunit 1
Importance of 5q33.2?
Affects synaptic plasticity
Gene for 16p13?
NMDA receptor subunit 2A
Importance of 16p13?
Influences channel conductance and synaptic localisation
Gene of 7q21?
Metabotropic glutamate receptor 3
Importance of 7q21?
Inhibitory autoreceptor
Gene of 1p21?
Micro RNA 137
Importance of 1p21?
Regulates transcription
Gene of 8p12?
Neuregulin 1
Importance of 8p12
Growth factor
Gene of 17p13?
Serine racemase
Importance of serine racemase?
Synthesizes d-serine from l-serine
Gene of 18q21?
Transcription factor 4
Importance of transcription factor 4?
Deletion causes Pitt-Hopkins syndrome
Gene of 2q32?
Zinc finger 804A
Importance of zinc finger 804A?
Affects gene regulation especially in cortical pyramidal neurons
Gene of 2p16.3 deletion?
Neurexin 1
Importance of Neurexin 1?
Involved in synaptic structure
Gene at 7q36.3 duplication?
Vasoactive intestinal peptide receptor 2
Importance of VIP receptor 2?
Regulates synaptic transmission in hippocampus and development of neural progenitor cells in dentate gyrus
Gene at 22q11
COMT coding genes
What does hemi deletion of 22q11 cause?
Velocardiofacial syndrome
