Chapter 9: Persistent Depressive Disorder (PPD)

Daniel N. Klein

Sarah R. Black

Background

Depressive disorders traditionally conceptualized as episodic, remitting conditions

Shift to viewing depression as recurrent and chronic

Reality is variability in course (e.g., single episode, recurrent episodes with full remission in between, chronic depression)

Chronic depressions ~30% of cases in community and ~50% in outpatient settings

Evidence that chronicity is a key aspect of the clinical and etiological heterogeneity of depression that should be considered in both clinical practice and research

Description and Diagnostic Criteria

DSM-5 Criteria: Dysthymic Disorder

Chronic course, persistent symptoms, insidious onset

At least two of six depressive symptoms required: Low energy or fatigue, insomnia or hypersomnia, poor appetite or

overeating, low self-esteem, poor concentration or difficulty making decisions, and feelings of hopelessness

Cognitive, affective, social-motivational symptoms more common than vegetative symptoms

At some point, most individuals experience superimposed MDEs (“double depression”)With DSM-IV, given given both MDD and dysthymia diagnoses

if experience double depression

Persistent Depressive Disorder (PDD)

Chronic course: most of day, more days than not, for at least two years

Persistent symptoms: no symptom-free periods of more than 2 months

Insidious onset typical: but ok if MDD present during first 2 years

At least 2 of 6 depressive symptoms required: Low energy or fatigue, insomnia or hypersomnia, poor appetite or overeating,

low self-esteem, poor concentration or difficulty making decisions, and feelings of hopelessness

Cognitive, affective, social-motivational symptoms more common in PDD than are vegetative symptoms

At some point, most individuals experience superimposed MDEs ( called “double depression” in the past)

In DSM-5, those who would meet for DSM-IV chronic MDD will now receive PDD diagnosis

Summary of DSM-5 Changes for Depressive Disorders

Persistent Depressive Disorder – consolidation of DSM-IV criteria for chronic MDD & dysthymic disorder

Same as criteria for dysthymia in DSM-IV, except D criteria DSM-IV: No MDE has been present during first 2 years of the

disturbance DSM-5: Criteria for a MDD may be continuously present for first 2

years

DSM-5 Persistent Depressive Disorder: Specifiers

Partial remission versus full remissionEarly Onset (before 21) versus LateWith pure dysthymic syndrome (no MDD in last 2

years)With persistent MDD (MDD met continuously in last 2

years- used to be called chronic depression)

MILD: just meeting criteria and impairment is minorMODERATE: between mild and severeSEVERE: many criteria met, marked impairment and

serious distress

Chronic Versus Nonchronic Depressions

Support for dysthymia versus MDD distinction:Milder symptoms, but dysthymia more severe on almost all

other variables (e.g., greater suicidality and comorbidity, lower self-esteem)

Validity of chronic–nonchronic MDD distinction less clear:However, some meaningful differences (e.g., chronic has earlier

onset, poorer work and social functioning)

Support for broader chronic-nonchronic distinction:Meaningful differences (e.g., chronic associated with greater childhood

adversity, earlier age of onset)

Chronic depression aggregates specifically in familiesDistinction relatively stable over time

Forms of Chronic Depression

Virtually no differences found between different forms of chronic depression (on variables like: comorbidity, personality, familial psychopathology, course, outcome)

Thus, distinctions among various forms of chronic depression do not appear to be meaningful, in contrast to chronic– nonchronic distinction

Decision made to combine different forms of chronic depression into single category in DSM-IV

Dysthymia versus Depressive Personality Disorder

Equivalent constructs in DSM-IIIDepressive PD was a provisional diagnosis in need of

further study of DSM-IV; it was defined in terms of traits (mostly cognitive) and did not require persistent depressed mood

Decision made not to include it in DSM-5 though it does appear to lie within the spectrum of chronic epressive disorders and does not require persistent depressed mood

Subtypes of Dysthymia

Several distinct etiological pathways

Early (< 21) & late (≥ 21) onset specifiers in DSM-IVEarly: Higher familial loading, childhood adversity, and so on Late: Greater association with stressful life events

Subtypes within early-onset proposed:Subaffective vs. character spectrumStrong familial liability vs. early adversity and increased

sensitivity of behavioral and neurobiological stress response systems

DSM-5 Changes

Now “Persistent Depressive Disorder”: Consolidation of DSM-IV criteria for chronic MDD and dysthymic disorder

Same as criteria for dysthymia in DSM-IV, except D criteria DSM-IV: “No MDE has been present during first 2 years of the

disturbance” DSM-5: “Criteria for a MDD may be continuously present for 2 years”

Epidemiology

Prevalence and Comorbidity

Dysthymia: 12 months 0.5%-2.5%; lifetime 0.9%-6.4%Chronic MDD: 12 months 1.5%; lifetime, 3.1%Chronic depression combined: Lifetime 4.6%

Prevalence of dysthymia and chronic MDD almost 2x greater in women than men

Higher in developed countries and among individuals with lower incomes

High comorbidity with anxiety, substance use, and personality disorders (especially avoidant, borderline, dependent PDs)

Impairment

Severity and chronicity contribute additively to functional impairment in depression Thus, dysthymia associated with equal or greater impairment

than nonchronic MDDDouble depression greater impairment than either alone

Impairment in many areas (e.g., work functioning and marital, family, and social relationships)

Significant impairment seen even after recovery

Course and Prognosis

Course and Prognosis

In a 10-year follow-up study of dysthymia and double depression… 74% recovery rate52 month median time to recovery71% relapsed after recovery6% developed manic or hypomanic episodes84% superimposed MDEs Predictors of greater depressive symptoms at 10 years:

Greater familial loading, history of poor maternal relationship, childhood sexual abuse

Comorbid PD predicted slower rate of improvement

Chronic Depression in Youth and Elderly

Dysthymia in Children and Adolescents

DSM-5: Minimum 1-year duration (versus 2 for adults); can have irritable instead of depressed mood

Children: 0.1% point prevalenceAdolescents: 0.5% prevalence; 3% lifetime

High comorbidity with anxiety and disruptive behavior disorders

CourseMost eventually have superimposed MDEsAlmost all eventually recover; median episode duration 4 yearsGreater risk of developing bipolar

Dysthymia and Older Adults (> 65)

Prevalence: 2%–6%Most late-onset (> 21)

Compared to nonelderly with dysthymia: Lower rates of Axis I and II comorbidity, higher rates of recent life events, more GMCs

Recovery rate: 12%–38% (15 months—6 years)

Predictors of poorer course: Greater symptom severity, social isolation and low social support, poor self-reported health

Psychosocial Factors

Early Maltreatment and Adversity

Predict poorer course and outcomeLink between adversity and chronic depression could be

explained by:Comorbidity with other mental disorders; however,

relationship remains after controlling for other disordersThird variable (e.g., genes related to both)

Future directions:Establish causal relationshipEtiological pathways (e.g., development of depressogenic cognitive

schemas)

Most maltreated children do not later develop chronic depression; need to look for moderators of association

Personality/Temperament and Chronic Stress

Low positive emotionality (PE) and high negative emotionality (NE) predict poorer course and outcome in chronic depressionAlso may predict development of chronic depression

Higher NE and lower PE in chronic than nonchronic depression and this personality seen after recovery as well as prior to illness

Higher levels of chronic stress & daily hassles in chronic than nonchronic depressionChronic stress appears to play causal role in onset or maintenance of

chronic depression (not reverse)Reduction or neutralization of ongoing difficulties and “fresh-start”

events associated with recovery

Cognitive and Interpersonal Factors

Similar cognitive factors seen as in nonchronic depression (e.g., stable and global attributions for negative events, ruminative response style)

Directionality of relationship between maladaptive cognitive processes and depression unclear

Interpersonal difficulties maintain and prolong depressive episodesSelf-propagating processes proposed to maintain depression

(e.g., negative feedback-seeking, excessive reassurance-seeking)

Predict development of chronic depression• Greater difficulties after recovery than nonchronic MDD and HCs• Directionality unclear

Genetic and Neurobiological Factors

Familial Aggregation/Genetics

Evidence of specificity of familial transmission in chronic depressionAlso higher rates of nonchronic MDD in relatives of probands

with chronic than nonchronic depression

Several findings suggest chronic depression characterized by a specific set of interacting genetic and environmental processesChildhood maltreatment moderates association between

5-HTTLR and chronic depression

Neurobiology

In major mood disorders, evidence of neuroendocrinology, sleep electrophysiology, and structural and functional brain abnormalities

In chronic depression:Similar HPA axis abnormalities Inconsistent findings for sleep electrophysiology abnormalities Similar structural and functional abnormalities

Too few studies to determine whether differences between chronic and nonchronic depression (e.g., whether any abnormalities are greater in or specific to chronic depression)

Assessment

Assessment: Overview

Challenging task! Usually psychological assessments focus on acute conditions Dysphoria is “normal” for these individuals, often seek

treatment for superimposed MDE

Requires careful history of current and past course of depression

Assessment: Tools

Structured diagnostic interviews (e.g., SCID):Generally only assess for current dysthymia Limited information on onset, course, interepisode

symptomatologyOften miss double depression

Rating scales (e.g., HAM-D) and self-reports:Course not adequately assessed to diagnose chronic

depressionDo not include the most common symptoms of dysthymiaRefer to differences from “normal” or “usual” stateCornell Dysthymia Rating Scale addresses these problemsGeneral Behavior Inventory (GBI) is the only self-report

measure explicitly developed for chronic mood disorders

Treatment

Treatment: Overview

Pharmacotherapy All antidepressants equally more efficacious than placeboLower placebo response in chronic than nonchronic MDDAntidepressants alone appear more efficacious than psychotherapy

alone

Indirect evidence that different approaches required Longer duration of psychotherapyMore likely to benefit from combined meds and therapy

Few predictors of differential response (to different meds or pharmacotherapy vs. psychotherapy)

CBASP higher remission for chronically depressed with childhood adversity, whereas meds superior for individuals without childhood adversity

Treatment preference impacts outcomes

Treatment: Psychotherapy

More efficacious than control conditions, but small effect sizeMinimum 18 sessions for optimal effects

Cognitive behavioral analysis system of psychotherapy (CBASP)Specifically designed for chronic depressionUses behavioral and cognitive techniques to help patients develop

better interpersonal problem-solving skills

Interpersonal therapy (IPT)Psychodynamically inspired therapy that focuses on current

interpersonal problems

One of few comparisons of CBASP and IPT found higher remission rate for CBASP at post, but similar effects at 1-year follow-up

Treatment: Nonresponse, Continuation and Maintenance

Nonresponse and partial remission to initial trial of treatment high among chronically depressedCan change medications or Switch to/add psychotherapy or pharmacotherapy

Continuation and maintenance treatmentImportant consideration due to high risk of relapse and

recurrenceAntidepressants lower risk of relapse and recurrence

compared to placebo Some evidence psychotherapy effective as maintenance

treatment

Summary and Future Directions

Summary

The various forms of chronic depression appear to be more alike than different, and may represent variants or different phases of the same underlying disorder

Chronic–nonchronic distinction appears to be meaningful

Still, some heterogeneity within chronic depressionAge of onset

Episodes can last for many years, but most patients eventually recoverRisk of recurrence highPredictors of poorer course and outcome: Family history, childhood

adversity, comorbid anxiety and PDs, chronic stress

Summary

Treatment challenges: Entrenched psychopathology, comorbidity, longstanding interpersonal deficits, chronic helplessness and hopelessness, depression becoming integrated into individual’s self-image and daily routine

Antidepressants and some psychotherapies (e.g., CBASP) found effective, and combination may be more effective

Maintenance treatment can prevent recurrences

Future Directions

Genetically informative studies (e.g., genome-wide association studies, gene-by-environment interactions)

Causal processes producing high psychiatric comorbidityEtiological pathways Protective factors, environmental variables that facilitate

recovery (e.g., “fresh-start” events)

Developing tools that better assess course

Psychotherapy: Identifying active ingredients, optimal parameters, specificity and range of effective treatments

Improve remission rates from meds and therapyHow to sequence and combine treatments to optimize

outcomes