Tripartite Model of Depression

1. Tripartite Model of Depression:Tripartite Model of Depression:
PsychopharmacologicalPsychopharmacological
ApplicationsApplications
Dr Khalid MansourDr Khalid Mansour
Locum Consultant PsychiatristLocum Consultant Psychiatrist
St Andrew’s HospitalSt Andrew’s Hospital

3. The Other Face of Depression, Reduced
Positive Affect: The Role of Catecholamines
in Causation and Cure (2006)
David NuttDavid Nutt University of Bristol Psychopharmacology Unit, Bristol, UK.University of Bristol Psychopharmacology Unit, Bristol, UK.
Koen DemyttenaereKoen Demyttenaere UZ Gasthuisberg, Adult and GeriatricUZ Gasthuisberg, Adult and Geriatric
Psychiatry, Belgium.Psychiatry, Belgium.
Zoltan JankaZoltan Janka Department of Psychiatry, University of Szeged,Department of Psychiatry, University of Szeged,
Hungary.Hungary.
Trond AarreTrond Aarre Nordfjord Psychiatric Centre, Sjukehusvegen.Nordfjord Psychiatric Centre, Sjukehusvegen.
Michel BourinMichel Bourin Faculté de Médecine Pharmacologie Clinique, France.Faculté de Médecine Pharmacologie Clinique, France.
Pier Luigi CanonicoPier Luigi Canonico Department Facoltà di Farmacia, UniversitàDepartment Facoltà di Farmacia, Università
del Piemonte Orientale, Italy.del Piemonte Orientale, Italy.
Jose LuisJose Luis CarrascoCarrasco Department of Clinical Psychiatry, U. ComplutenseDepartment of Clinical Psychiatry, U. Complutense
de Madrid, Hospital Universitario Clinico San Carlos de Madrid, Spain.de Madrid, Hospital Universitario Clinico San Carlos de Madrid, Spain.
Steven StahlSteven Stahl Neuroscience Educational Institute, California, USA.Neuroscience Educational Institute, California, USA.

4. Introduction 1
 Tripartite modal was developed mainly in theTripartite modal was developed mainly in the
context of research in clinical psychology tocontext of research in clinical psychology to
create better self assessment questionnaires forcreate better self assessment questionnaires for
both anxiety and depression. In suchboth anxiety and depression. In such
questionnaires differentiating anxiety fromquestionnaires differentiating anxiety from
depression can be difficult.depression can be difficult.
 One of the basic concepts of such researchOne of the basic concepts of such research
models has been that our every day affect ismodels has been that our every day affect is
really the outcome of mixing two differentreally the outcome of mixing two different
affects: Positive Affects (PA) and Negativeaffects: Positive Affects (PA) and Negative
Affects (NA).Affects (NA).

5. Introduction 2
 PA: positive mood states, e.g.PA: positive mood states, e.g. happiness (joy),happiness (joy),
interest, energy, enthusiasm, alertness andinterest, energy, enthusiasm, alertness and
self-confidenceself-confidence..
 NA: distress mood states, e.g.NA: distress mood states, e.g. fear, anxiety,fear, anxiety,
sadness, irritability, loneliness, guilt, disgustsadness, irritability, loneliness, guilt, disgust
and hostilityand hostility..

6. Introduction 3
 Psychiatric studies seems as if it had ignoredPsychiatric studies seems as if it had ignored
such psychological research for a long timesuch psychological research for a long time
(most research done by psychologists).(most research done by psychologists).
 However, recent developments inHowever, recent developments in
psychopharmacology have increased interest inpsychopharmacology have increased interest in
PA and NA as a way to refine treatment ofPA and NA as a way to refine treatment of
depression.depression.
 This new approach has been increasinglyThis new approach has been increasingly
popular among psychiatrists in the USA and UK.popular among psychiatrists in the USA and UK.

7. General Background: 1
Two Factors Structure of Affect
 Theories like the Tripartite Model ofTheories like the Tripartite Model of
Anxiety and Depression are part of aAnxiety and Depression are part of a
long tradition of psychometric studying oflong tradition of psychometric studying of
emotionsemotions (e.g., Izard, 1972; Tomkins, 1962, 1963,(e.g., Izard, 1972; Tomkins, 1962, 1963,
Davidson, 1992, 1998; Gray, 1994).Davidson, 1992, 1998; Gray, 1994).
 One common feature of these models isOne common feature of these models is
the emphasis on the “Two-Factorthe emphasis on the “Two-Factor
Structure of Affect”Structure of Affect” (Shankman & Klein, 2003).(Shankman & Klein, 2003).

8. General Background: 2
Two Factors Structure of Affect
 Two-Factor theories: emotions fall alongTwo-Factor theories: emotions fall along
two dimensions: Positive Affect (PA) andtwo dimensions: Positive Affect (PA) and
Negative Affect (NA)Negative Affect (NA) (Zevon&Tellegen, 1982)(Zevon&Tellegen, 1982) ..
 Approach-withdrawal ModelApproach-withdrawal Model (Davidson, 1992,(Davidson, 1992,
1998).1998).
Behavioural Activation SystemBehavioural Activation System (Carver & White,(Carver & White,
1994).1994).
Behavioural Facilitation SystemBehavioural Facilitation System (Depue &Iacono,(Depue &Iacono,
1989).1989).

9. General Background: 3
Three-Factor Structure of Affect
 The three-factor theories (e.g.The three-factor theories (e.g.
tripartite model): tend to add to thetripartite model): tend to add to the
PA-NA structure an extra structurePA-NA structure an extra structure
to explain other mood abnormalitiesto explain other mood abnormalities
especially anxiety disorder, phobia,especially anxiety disorder, phobia,
OCD, etcOCD, etc (Shankman & Klein, 2003).(Shankman & Klein, 2003).

10. General Background: 4
Other Three-Factor Theories
Valence-Arousal Model:Valence-Arousal Model: PA, NA andPA, NA and
Arousal/Anxious Apprehension (AA)Arousal/Anxious Apprehension (AA) (Heller et al,(Heller et al,
1995,1997; Heller & Nitchke, 1998).1995,1997; Heller & Nitchke, 1998).
Gray’s Three System ModelGray’s Three System Model (Gray, 1994)(Gray, 1994)::
Behavioural Approach System, BehaviouralBehavioural Approach System, Behavioural
Inhibition System and Fight/Flight System.Inhibition System and Fight/Flight System.

11. Watson & Clark Tripartite Model: 1
Negative Affect (NA)
 NA:NA: general factor of emotional distress: e.g.general factor of emotional distress: e.g.
fear, anxiety, sadness, irritability, loneliness,fear, anxiety, sadness, irritability, loneliness,
guilt, disgust and hostilityguilt, disgust and hostility (Watson & Clark,(Watson & Clark,
1984;Watson &Tellegen, 1985).1984;Watson &Tellegen, 1985).
 A common feature ofA common feature of both anxiety andboth anxiety and
depressiondepression..
 Traditional self-report measures ofTraditional self-report measures of
depression and anxiety are tapping NAdepression and anxiety are tapping NA (Laurent(Laurent
& Ettelson, 2001).& Ettelson, 2001).
 Separating depression from anxiety dependsSeparating depression from anxiety depends
on PAon PA (Laurent & Ettelson, 2001).(Laurent & Ettelson, 2001).

12. Watson & Clark Tripartite Model:
2 Positive Affect (PA)
 PA:PA: ““pleasurable engagement with thepleasurable engagement with the
environment”environment” (Watson, 1988; Watson & Tellegen, 1985)(Watson, 1988; Watson & Tellegen, 1985)
including happiness, interest, energy,including happiness, interest, energy,
enthusiasm, alertness and self-enthusiasm, alertness and self-
confidence:confidence:
Depression is characterized byDepression is characterized by low PAlow PA;;
i.e.i.e. AnhedoniaAnhedonia..
In anxiety, levels of PA are notIn anxiety, levels of PA are not
significantly different than thosesignificantly different than those
expected in the general population.expected in the general population.

13. Watson & Clark Tripartite Model: 3
Physiological Hyperarousal (PH)
 Clark and Watson (1991) added a factorClark and Watson (1991) added a factor
they believed to be specific to anxiety:they believed to be specific to anxiety:
“Physiological Hyperarousal” (PH).“Physiological Hyperarousal” (PH).
 So, Clark and Watson concluded that dataSo, Clark and Watson concluded that data
about anxiety and depression, were bestabout anxiety and depression, were best
captured by acaptured by a TripartiteTripartite structure.structure.
NA: common to both anxiety and depression.NA: common to both anxiety and depression.
PA: characteristic for depression.PA: characteristic for depression.
PH: characteristic for anxietyPH: characteristic for anxiety

14. Watson & Clark Tripartite Model: 4
Assessment Tools
 Several assessment tools have beenSeveral assessment tools have been
developed based on the tripartite modeldeveloped based on the tripartite model
e.g.e.g.
Positive and Negative Affect SchedulePositive and Negative Affect Schedule
(PANAS)(PANAS) (Watson, Clark, and Tellegen, 1988)(Watson, Clark, and Tellegen, 1988)
Mood and Anxiety SymptomMood and Anxiety Symptom
Questionnaire (MASQ)Questionnaire (MASQ) ((Watson et al, 1995)Watson et al, 1995)..
Depression Anxiety stress Scale (DASS)Depression Anxiety stress Scale (DASS)
(Lovibond & Lovibond, 1995).(Lovibond & Lovibond, 1995).

15. Watson & Clark Tripartite Model: 5
Relationship Between PA & NA
 Some authors believe that PA and NA areSome authors believe that PA and NA are
bipolar or represent opposite ends of abipolar or represent opposite ends of a
continuumcontinuum (e.g., Feldman Barrett & Russell, 1998, 1999; Russell,(e.g., Feldman Barrett & Russell, 1998, 1999; Russell,
1980; Russell & Feldman Barrett, 1999).1980; Russell & Feldman Barrett, 1999).
 Most believe that PA and NA representMost believe that PA and NA represent
independent constructsindependent constructs (e.g., Watson & Clark, 1997;(e.g., Watson & Clark, 1997;
Watson & Tellegen, 1985; Watson, Wiese, Vaidya, & Tellegen, 1999).Watson & Tellegen, 1985; Watson, Wiese, Vaidya, & Tellegen, 1999).
 The second view is the view adopted inThe second view is the view adopted in
psychopharmacology researches.psychopharmacology researches.

16. Psychopharmacological Research
and the Tripartite Model: 1
 Since 1960s with TCA > norepinephrineSince 1960s with TCA > norepinephrine
(NE) and dopamine (DA) play integral part(NE) and dopamine (DA) play integral part
in pathophysiology of depressionin pathophysiology of depression (Willner, 1995;(Willner, 1995;
Delgado, 2000, 2004; Nutt et al, 2006; Stahl, 2009).Delgado, 2000, 2004; Nutt et al, 2006; Stahl, 2009). Many ofMany of
the TCA were causing exactly such effect.the TCA were causing exactly such effect.
 Since the late 1980s, SSRIs started to beSince the late 1980s, SSRIs started to be
the first-line therapy for treatment ofthe first-line therapy for treatment of
depression especially in the primary caredepression especially in the primary care
due to improved safety profile and ease ofdue to improved safety profile and ease of
administrationadministration (Nutt et al, 2006)(Nutt et al, 2006)..

17. Psychopharmacological ResearchPsychopharmacological Research
and the Tripartite Model: 2and the Tripartite Model: 2
 However, 28-55% of patients fail to respondHowever, 28-55% of patients fail to respond
to SSRI therapyto SSRI therapy (Nierenberg(Nierenberg et al.et al., 1999, Nierenberg and, 1999, Nierenberg and
DeCocco, 2001; PetersonDeCocco, 2001; Peterson et al.et al., 2005; Trivedi, 2005; Trivedi et alet al., 2006)., 2006)..
 30%-50% of the responding patients continue30%-50% of the responding patients continue
> residual symptoms> residual symptoms (Fawcett, 1994; Bothwell & Scott,(Fawcett, 1994; Bothwell & Scott,
1997; Nierenberg et al, 1999)1997; Nierenberg et al, 1999) e.g. sleep disturbances,e.g. sleep disturbances,
diminished pleasure, loss of interest, fatiguediminished pleasure, loss of interest, fatigue
or loss of energy and decreased motivationor loss of energy and decreased motivation
(i.e. low PA) (Kopta(Kopta et alet al., 1994; Barkham., 1994; Barkham et alet al., 1996;., 1996;
OpdykeOpdyke et alet al., 1996–1997; Nierenberg., 1996–1997; Nierenberg et alet al., 1999; Shelton and., 1999; Shelton and
Tomarken, 2001).Tomarken, 2001).

18. Psychopharmacological ResearchPsychopharmacological Research
and the Tripartite Model: 3and the Tripartite Model: 3
 In the mean time, preliminary evidence >In the mean time, preliminary evidence >
antidepressants that enhanceantidepressants that enhance
noradrenaline and dopamine (e.g. SNRIs)noradrenaline and dopamine (e.g. SNRIs)
may > therapeutic advantage over SSRI inmay > therapeutic advantage over SSRI in
treatment of low PA e.g. loss of interest,treatment of low PA e.g. loss of interest,
loss of energy and loss of motivation”,loss of energy and loss of motivation”,
(Bremner(Bremner et alet al., 1984; Rampello., 1984; Rampello et alet al., 1991; Dalery., 1991; Dalery et al.et al., 1997;, 1997;
JouventJouvent et al.et al., 1998; Jamerson, 1998; Jamerson et al.et al., 2003; Papakostas, 2006;, 2003; Papakostas, 2006;
JeffersonJefferson et alet al., in press).., in press).

19. Psychopharmacological ResearchPsychopharmacological Research
and the Tripartite Model: 4and the Tripartite Model: 4
 Professor Nutt and Professor Stahl startedProfessor Nutt and Professor Stahl started
to suggest the usage of PA and NAto suggest the usage of PA and NA
concepts for prescribing antidepressantsconcepts for prescribing antidepressants
(Nutt et al, 2006 & Stahl 2009):(Nutt et al, 2006 & Stahl 2009):
Depressed patients with dominant “lowDepressed patients with dominant “low
PA” > to be treated with drugs whichPA” > to be treated with drugs which
enhance DA and NA e.g. SNRIenhance DA and NA e.g. SNRI
Depressed patients with dominant “highDepressed patients with dominant “high
NA” > to be treated with drugs whichNA” > to be treated with drugs which
enhance 5HT e.g. SSRI.enhance 5HT e.g. SSRI.

20. Neurobiological Model of
Depression (Nutt et al, 2006)

21. Neurobiological Model of Depression
(Nutt et al, 2006): Criticism 1
Many psychological studies dispute theMany psychological studies dispute the
sufficiency and/or validity of the Tripartitesufficiency and/or validity of the Tripartite
model and found it not able to explainmodel and found it not able to explain
many aspects of depression and anxietymany aspects of depression and anxiety
(Lonigan et al, 1994; Clark et al, 1994; Burn & Edison, 1998;(Lonigan et al, 1994; Clark et al, 1994; Burn & Edison, 1998;
Buckby et al, 2008).Buckby et al, 2008).
Including: guilt, sadness, irritability, fear,Including: guilt, sadness, irritability, fear,
anxiety, etc,anxiety, etc, in one category, NA, does notin one category, NA, does not
make much sense from clinical point ofmake much sense from clinical point of
view.view.

22. Neurobiological Model of Depression
(Nutt et al, 2006): Criticism 2
Many patients are still having limitedMany patients are still having limited
response to both SSRI and SNRI.response to both SSRI and SNRI.
SNRI advantage over SSRI is modestSNRI advantage over SSRI is modest
(NNT = 24)(NNT = 24) ((Papakostas et al, 2006)Papakostas et al, 2006)
Including Nor-adrenaline in both PA andIncluding Nor-adrenaline in both PA and
NA in Nutt’s model, does not make sense,NA in Nutt’s model, does not make sense,
chemically, as Nor-adrenaline system haschemically, as Nor-adrenaline system has
many differences from 5HT and Dopaminemany differences from 5HT and Dopamine..

23. Neurobiological Model of Depression
(Nutt et al, 2006): Criticism 3
Nutt’s model needs further development.Nutt’s model needs further development.
Nutt’s model does not involveNutt’s model does not involve
environmental factors in eitherenvironmental factors in either
causing or treating depression.causing or treating depression.
This model does not explain otherThis model does not explain other
major chemical transmitters in themajor chemical transmitters in the
brain e.g. glutamte, glycine orbrain e.g. glutamte, glycine or
acetylcholine.acetylcholine.

24. Neurobiological Model of Depression
(Nutt et al, 2006): Prescribing
 It has many clinical applications e.g.It has many clinical applications e.g.
 Patients with ↓ PA; better avoid anti-dopaminergicPatients with ↓ PA; better avoid anti-dopaminergic
drugs as augmentation therapy for treatment ofdrugs as augmentation therapy for treatment of
depression.depression.
 Fluoxetine can be considered superior SSRI as it alsoFluoxetine can be considered superior SSRI as it also
enhances Dopamine and Nor-adrenaline. Sertralineenhances Dopamine and Nor-adrenaline. Sertraline
and Paroxetine also enhance dopamine to lessand Paroxetine also enhance dopamine to less
extent.extent.
 This model might rekindle usage of drugs likeThis model might rekindle usage of drugs like
Bupropion, MAOI or even Amphetamines in low-PA-Bupropion, MAOI or even Amphetamines in low-PA-
depression.depression.

25. Neurobiological Model of Depression
(Nutt et al, 2006): non-chemical therapies
 Concepts of PA or NA can also be used inConcepts of PA or NA can also be used in
behavioural therapy and psychotherapybehavioural therapy and psychotherapy
perhaps in both neurosis and well asperhaps in both neurosis and well as
psychosis:psychosis:
Low PA (-ve): ? Mainly motivational and selfLow PA (-ve): ? Mainly motivational and self
esteem activities e.g. DBT, drug rehab, etc.esteem activities e.g. DBT, drug rehab, etc.
High NA (ve+): ? Mainly correctional and re-High NA (ve+): ? Mainly correctional and re-
training activities e.g. CBT for phobia or OCD.training activities e.g. CBT for phobia or OCD.

26. Neurobiological Model of Depression
(Nutt et al, 2006): Future Research
Add one extra dimension for betterAdd one extra dimension for better
assessment and treatment ofassessment and treatment of
depression for the first time in aboutdepression for the first time in about
60 years.60 years.
It brings psychiatrists one step furtherIt brings psychiatrists one step further
to more efficient neurobiologicalto more efficient neurobiological
models, though not sufficient yetmodels, though not sufficient yet
(Bullmore et al, 2009; Craddock et al, 2008; St John-Smith et al,(Bullmore et al, 2009; Craddock et al, 2008; St John-Smith et al,
2009)2009)

27. Neurobiological Model of Depression
(Nutt et al, 2006): “10 dimensions Depression”
 Other components of depression could be considered inOther components of depression could be considered in
future classifications of depression e.g.:future classifications of depression e.g.:
 Poor interestPoor interest
 Grief (life losses)Grief (life losses)
 Low MotivationLow Motivation
 Negative / Dysfunctional CognitionNegative / Dysfunctional Cognition
 Doubts / anxietyDoubts / anxiety
 Homeostasis (discomfort / pain)Homeostasis (discomfort / pain)
 Low Energy (e.g. asthenia, chronic fatigue syndrome)Low Energy (e.g. asthenia, chronic fatigue syndrome)
 Stress (environmental & biological)Stress (environmental & biological)

28. Thank you
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