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Neuropsychology of
Depression
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Clinical case
Diagnostic criteria
Clinical Features
Cognitive Deficits
Neuroanatomical differences
Lynn
• 50 year old, right handed woman
• 1 yr. history of gradually progressive cognitive
difficulties
– Decreased vocabulaty, word-finding, inability to multi-task,
poor short-term memory
• Poor work evaluations, and work is more
“effortful”
• Mild difficulty managing finances
• Dx question: dementia vs. depression
History
• Family issues beginning in teen years
– 1st psychiatric hospitalization age 16
• Diagnoses
– Major Depression
– Bi-polar depression
– Personality Disorder
• Major Depressive Episode 9 months ago
– Out of work 2 months
– Currently resolved
– Current tx: pharmacotherapy and psychotherapy
• Early onset AD in mother and maternal
grandmother
Mood
Disorders
Thought
Disorders
Major
Depressive
Disorder (MDD)
Bipolar
Disorders
(BPD)
Dysthymic
Disorder
MDD w/
Psychotic
Features
BPD w/
Psychotic
Features
Schizoaffective
Disorder
Generalized
Anxiety
Disorder
Anxiety
Disorders
Schizophrenia
Schizotypal
Personality
Disorder
Schizoid
Personality
Disorder
Borderline
Personality
Disorder Obsessive
Compulsive
Disorder
Panic
Disorder
Agoraphobia
Post-Traumatic
Stress Disorder
Simple
Phobias
Fine Line Between Normal Mood &
Disorders
• Hypo-motivated, low
pleasure:
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Gloomy, incapable of fun
Humorless
Pessimistic, skeptical
Guilt-prone, low self-esteem
Introverted, restricted social life
Sluggish, inactive, passive
Few interests
Long sleeper (> 10 hrs/night)
Thoughtful, deeply emotional
• Hyper-motivated
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Cheerful, exuberant
jocular
Optimistic, carefree
self-assured
Extroverted, people-seeker
High energy level, several plans,
lots of ideas
Versatile with broad interests
Short sleeper (< 5 hrs/night)
Flighty, impulsive, over-confident
Over-involved, meddlesome
What is abnormal?
Major Depression
No
Yes
N
‘Often
Sad’
‘Often
Tearful’
‘+ Sad ‘+ Can’t ‘+ Interferes
< 2 wks’ Cheer Up’ w/ Functioning’
Sadness
DSM-V Depressive Disorders
• Disruptive mood dysregulation
disorder
• Major Depressive disorder
• Persistent depressive disorder
(dysthymia)
• PMDD
• Substance/medication-induced
depressive disorder
• Depressive Disorder due to
another medical condition
1)
Sad, empty, or
irritable mood
2)
Somatic and
cognitive changes
that affect capacity
to function
Vary in duration, timing,
and/or etiology
Major Depressive Disorder
•  2 weeks of 5 or more of the following representing
a change from previous functioning (one must be
depressed mood or loss of interest or pleasure):
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Depressed mood, most of the day
Markedly diminished interest or pleasure in most or almost all, activities,
Weight loss or gain (or ↑↓ in appetite)
Sleep disturbance (hyper- or hyposomnia)
Feeling worthless, excessive guilt
Diminished energy, fatigue
Trouble concentrating or indecisiveness
Psychomotor agitation or retardation
Recurrent thoughts of death, suicidal ideation without a specific plan,
suicide attempt or a specific plan for committing suicide
• Clinically significant distress or impairment
• Not attributable to direct physiologic effects of drug or
medical condition
• Never been a manic or hypomanic episode
Bipolar and Related Disorders
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Bipolar I
Bipolar II
Cyclothymic disorder
Substance/medication-induced bipolar and
related disorder
• Bipolar and related disorder due to another
medical condition
Manic Symptoms
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Increased self-esteem or grandiosity
Decreased need for sleep
Increased talking or pressure of speech
Racing thoughts or flight of idea
Distractibility
Agitation or increased goal-directed activity
Excessive involvement in pleasurable activities with
high potential for adverse consequences
Manic Episode
• Distinct period of 1 week of elevated, expansive, or
irritable mood
• At least 3 manic symptoms (4 if mood only irritable)
• Causes significant impairment in functioning
• Not due to a general medical condition or caused by
drug use
Hypomanic episode
• Distinct period of 4 consecutive days of elevated,
expansive, or irritable mood
• At least 3 manic symptoms (4 if mood only irritable)
• Unequivocal change in functioning that is
uncharacteristic of the individual
• Mood disturbance and change in function are
observable by others.
• Not severe enough to cause significant impairment in
functioning
• Not due to a general medical condition or caused by
drug use
Bipolar Subtypes
• Bipolar I
– One or more Manic Episodes, with or without a Major
Depressive Episode
• Bipolar II
– One or more hypomanic episodes and at least one Major
Depressive Episode
– no full Manic episodes
MANIA
MIXED EPISODE
HYPOMANIA
NORMAL
MOOD
DEPRESSION
Stahl S M, Essential
Psychopharmacology (2000)
Cognitive Deficits in MDD
• Subcortical-frontal pattern
– Attention
– Psychomotor speed
– Executive function
• Impacted by
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Severity
Age of onset
Number of prior episodes
Current state (remitted/in episode)
Depression
Neuropsychological Profile
Deficits (frontal-subcortical)
• Slowed information
processing
• Executive
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Attention/concentration
Verbal fluency
Cognitive flexibility
Problem solving
• Memory
– Encoding
– retrieval (vs. preserved
recognition)
Preserved
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Orientation
Language
Visuo-spatial
Motor (non-timed)
Epidemiology MDD
• Prevalence
– 1 yr: 6.7% (15.7 million adults in US)
– Lifetime: 16.2% (32-35 million adults in US)
• Females > Males (1.5-3x)
• Typical onset – late 20s
• Increases after puberty
• 1st onset in latelife not uncommon
– Often associated with neurological impairment
• Risk factors
– Lower SES
Epidemiology - BPD Bipolar
• Bipolar I
– .06% prevalence (1 yr)
– M=F
– Mean age 1st episode:
18y
– 90% of those with single
ME go on to have
recurrent mood
episodes
• Bipolar II
– .08% prevalence
– F> M (clinic samples)
– Mean age onset: mid
20s
– Most often begins with
MDE
– 12% initial dx MDD
– 5-15% rapid cycling
– 5-15% will experience
ME (bipolar I)
Risk Factors - MDD
• Early parental loss
• Adverse life events
– often trigger incidence/relapse
• ‘Neurotic’ personality style
• Chronic stress
Risk Factors - BPD
• Separated, divorced, or widowed individuals
have higher rates than married or single
• Higher education, fewer years of illness and
being married independently associated with
functional recovery
Gender differences - MDD
• F>M, but no difference in Sx, course, tx
response, or functional consequences
• Suicide attempt F>M
• Suicide completion M>F
Gender differences - BPD
• Females more likely to experience rapid
cycling and mixed states
• Comorbidity patterns differ
– f: eating disorder
– m: alcohol use disorder
• Females more likely to experience depressive
symptoms
• Childbirth may trigger hypomanic episode
– 10-20% in non-clinic samples
Consequences of disorder - MDD
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High individual variability
Severe - complete incapacity
Cognitive impairments
more pain, physical illness, decreased
functioning
• Comorbidities: SUD, Panic disorder, OCD,
eating disorders, BPD
Consequences of disorder
Bipolar I
• Lifetime suicide risk: 15X
– 36.3%
– ¼ all suicides
• 30% severe impairment
in work function
• Cognitive impairments
• Comorbidities
– Anxiety (3/4), ADHD,
impulse control/conduct,
SUD (1/2 alcohol)
Bipolar II
• Lifetime risk: 32.4%
– 1/3 report SA
– Lethality > BPI
• 15% inter-episode
dysfunction
• 20% no inter-episode
recovery
• Functional recovery < BPI
• Cognitive impairments
• Comorbidities
– 60% have 3 or more
– 75% anxiety disorder, 37% SUD
Sensitization Hypothesis of
Recurrence
• Bipolar/unipolar episodes more likely to recur
with
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higher number of prior episodes
milder/no stressors as number of episodes increase
earlier onset of illness
more severe early stressor
Post, 1992
Dienes, 2006
Multi-center (n=11)
Meta-analysis
of HC & Amyg.Volumes
Bipolar Disorder vs HC
Hallahan, 2011
Amygdala Changes
in New-onset
Adolescent BPD
Bitter, 2011
Independent
Of Mood State
Blood Flow Blue = BPD < Controls Red = BPD > Controls
Chen, 2011
BPD Patients in
Specific Mood
States
Blood Flow Blue = BPD < Controls Red = BPD > Controls
Chen, 2011
Lynn’s Test Results
SS
MMSE
28/30
SS
Hooper Visual Org Test
8
Digit Span
9
Trail Making A
5
Letter Number Sequencing
5
Trail Making B
3
Imm Verbal Memory
7
Phonemic Fluency
8
Imm Visual Memory
8
Category Fluency
5
Del Verbal Memory
11
Boston Naming Test
7
Delayed Visual Memory
13
Recognition
9
WMS-III