MAJOR DEPRESSION

1. Dr Parag Moon
Senior Resident,
Dept. of Neurology,
GMC, Kota.

2.  Major depressive disorder-one or more major depressive
episodes (i.e. at least 2 weeks of depressed mood or loss of
interest accompanied by at least 5 additional symptoms of
depression).
 Categorized into mild, moderate and severe.
◦ Mild to moderate depression-depressive symptoms and some
functional impairment.
◦ Severe depression-additional agitation or psychomotor retardation
with marked somatic symptoms.
 Dysthymic disorder-at least 2 years of depressed mood for
more days than not, accompanied by additional symptoms
that do not reach criteria for major depressive disorder.

3. 1. Depressed mood most of day, nearly every day, as indicated
by either subjective report (e.g., feels sad or empty) or
observation made by others (e.g., appears tearful).Children
and adolescents-irritable mood.
2. Markedly diminished interest or pleasure in all, or almost all,
activities most of day, nearly every day
3. Significant weight loss when not dieting or weight gain
(e.g.,change of more than 5% of body weight in month), or
decrease or increase in appetite nearly every day. Children-
no expected weight gains.
4. Insomnia or hypersomnia nearly every day

4. 5. Psychomotor agitation or retardation nearly every day.
6. Fatigue or loss of energy nearly every day
7. Feelings of worthlessness or excessive or inappropriate guilt
(which may be delusional) nearly every day (not merely self-
reproach or guilt about being sick)
8. Diminished ability to think or concentrate, or indecisiveness,
nearly every day.
9. Recurrent thoughts of death (not just fear of dying),
recurrent suicidal ideation without specific plan, or suicide
attempt or specific plan for committing suicide

5.  Not due to direct physiological effects of drug of abuse (Alcohol
Intoxication or Cocaine Withdrawal),
 Not due to side effects of medications or treatments (steroids) or
to toxin exposure.
 Not due to direct physiological effects of general medical
condition (hypothyroidism)
 Symptoms begin within 2 months of loss of loved one and do not
persist beyond these 2 months- considered to result from
Bereavement, unless associated with marked functional impairment
or include morbid preoccupation with worthlessness, suicidal
ideation, psychotic symptoms, or psychomotor retardation.

6. A) Reactive (neurotic) & endogenous depression:
 Reactive depression- symptoms in response to external
stressful stimuli
 C/F: anxiety, irritability, phobia & early insomnia,
 Endogenous depression- caused by factors within individual
which are independent of outside stimuli, more severity
 C/F: Loss of appetite, weight loss, constipation, decreased
libido, amenorrhea, early morning awakening (biological
symptoms).
B) Primary & secondary: secondary because of H/O previous
non affective psychiatric illness (schiz. , AN) or alcoholism,
medical illness, or taking certain drugs (e.g.. Steroids)
 No difference between them regarding prognosis &
response to treatment

7. A) Neurotic depression
B) Psychotic depression
 Cases of depression with so called biological symptoms &
severe forms come under Psychotic depression
 Milder forms come under neurotic depression

8. MOST useful classification
A) Unipolar (recurrent)
 Having depressive phases only
 Some of them may have manic episode later
 Manic episode might remain under diagnosed
B) Bipolar-
 Both manic & depressive episode in cyclic pattern
 May have only manic episodes

9. C) Seasonal affective disorder-
◦ Repetitive depressive episodes at the same time of year
◦ Symptoms- hypersomnia, increased appetite, increased
craving for carbohydrates.
◦ Onset- in winter
◦ Recovery- in spring or summer
◦ Cause: might be shortening in the day light
◦ Treatment; exposure to bright artificial light during hours of
darkness
D) Involutional depression:
◦ Occurs at the time of involution of sex glands.
◦ Occurs around 45 years of age
◦ C/F: agitation, hypochondriacal symptoms

10.  Fifth and fourth century B.C. persons with depressive
disorders were described as having a distinct disease and that
would eventually be named Melancholia
 Hippocrates characterized all fears and despondencies, if they
were prolonged, as symptoms of a disease process
 Only 42% of patients with major depression diagnosed
appropriately by their primary care physician (WHO)
 By year 2020, major depression will be second only to
ischemic heart disease in the amount of disability(WHO)

11.  Point prevalence- between 5% and 10% of people seen in
primary care settings.
 Women are affected twice as often as men.
 Fourth most important cause of disability worldwide
 Lifetime prevalence- 26% for women and 12% for men.
 1.5 to 3 times with a first-degree biological relative.
 84% had at least one comorbid condition, 61% had additional
psychiatric disorder and 58% comorbid medical illness
 Follows psychosocial stressor-death of a loved one, marital
separation, or Childbirth.

12. A) Biological- monoaminergic theory(NE, DA, 5HT) (already
dealt with)
B) Psychosocial
◦ Recent stressful life events,
◦ Personality factors
◦ Early environment- (maternal deprivation, relationship with parents)
◦ Learned helplessness
C) Cognitive theories depressive cognitions, negative
thoughts,
negative view of self & regarding future.

13.  Loss of interest or pleasure of some degree-nearly always present,
 Less interested in hobbies, "not caring anymore," or not feeling any
enjoyment in activities previously considered pleasurable.
 Family members- social withdrawal or neglect of pleasurable
avocations.
 Reduction from previous levels of sexual interest or desire.
 Appetite-reduced, and many individuals feel that they have to
force
 Some may have increased appetite, crave specific foods.
 Significant loss or gain in weight.

14.  Decreased energy, tiredness, and fatigue.
 Efficiency-reduced.
 Sense of worthlessness or guilt-unrealistic negative
evaluations of one's worth or guilty preoccupations or
ruminations over minor past failings.
 Report impaired ability to think, concentrate, or make
decision.
 Easily distracted or complain of memory difficulties.

15.  Thoughts of death, suicidal ideation, or suicide attempts
 Belief that others would be better off if person were dead, to
transient but recurrent thoughts of committing suicide, to
actual specific plans of how to commit suicide.
 Transient (1- to 2-minute), recurrent (once or twice a week)
thoughts.
 Appearance: neglected dress & grooming
 Facial features: turning downwards of corners of mouth,
vertical furrowing of centre of brow, shoulders bent & head
inclined forwards, direction of gaze downwards, gestural
movements decreased

16.  Sleep disturbance-insomnia
 Typically have middle insomnia (waking up during night and
having difficulty returning to sleep) or terminal insomnia
(waking too early and being unable to return to sleep).
 Initial insomnia (difficulty falling asleep).
 Oversleeping(hypersomnia)-prolonged sleep episodes at night
or increased daytime sleep.
 Psychomotor changes-agitation or retardation.
 Speech-decreased in volume, inflection, amount, or variety of
content, or muteness.

17.  Sleep EEG abnormalities- 40%-60% of outpatients and in up to
90% of inpatients with MDD.
1) Sleep continuity disturbances, such as prolonged sleep latency, increased
intermittent wakefulness, and early morning awakening
2) Reduced non—rapid eye movement (NREM) stages 3 and 4 sleep (slow-wave
sleep), with shift in slow-wave activity away from NREM period
3) Decreased rapid eye movement (REM) latency (shortened duration of the
first NREM period)
4) Increased phasic REM activity (number of actual eye movements during REM)
5) Increased duration of REM sleep early in night.

18.  Chronic insomnia or fatigue
 Chronic pain
 Multiple or unexplained somatic complaints, “thick charts”
 Chronic medical illnesses (e.g., diabetes, arthritis)
 Acute cardiovascular events (myocardial infarction, stroke)
 Recent psychological or physical trauma
 Other psychiatric disorders
 Substance abuse disorders
 Family history of mood disorder

19.  Nations (Native American)
 Male
 Advanced age
 Single or living alone
 Prior suicide attempt
 Family history of suicide
 Family history of substance abuse
 Medical illness Psychosis
 Hopelessness

21. A) Pharmacotherapy-
I) Antidepressants-
TCA
MAO inhibitors
Newer antidepressant- SSRI, SNRI, SDRI
II) Lithium
III) Augmentation therapies
B) Psychosocial therapies
C) ECT

22.  Characteristic three-ring nucleus
 Clinical effects
◦ Normalization of mood and resolution of neurovegetative
symptoms
 Biochemical effects
◦ Inhibit monoamine uptake at nerve terminals
◦ May potentiate action of drugs that cause neurotransmitter release
 Temporal delay of weeks for clinical effects, although
biochemical effects are immediate

23. “Tertiary” TCAs  Inhibit 5-HT uptake
imipramine (weaker inhibition of NE uptake)
amitriptyline
clomipramine
“Secondary” TCAs  Inhibit NE uptake
desipramine (weaker inhibition of 5-HT uptake)
nortriptyline

24.  Dry mouth
 Constipation
 Dizziness
 Tachycardia
 Urinary retention
 Impaired sexual function
 Orthostatic hypotension
 Contraindications
◦ QTc greater than 450 msec
◦ Conditions worsened by muscarinic blockade (eg myasthenia gravis, BPH)
◦ Pre-existing orthostatic hypotension
◦ Seizure disorder

25.  Irreversibly inhibit monoamine oxidase enzymes
 2 isoforms
◦ MAO-A (norepinephrine, serotonin, tyramine)
◦ MAO-B (dopamine)
 Effective for major depression, panic disorder, social phobia
 Drug interactions and dietary restrictions limit use

26.  Irreversible, non-selective MAOIs
◦ phenelzine
◦ isocarboxazid
◦ tranylcypromine
 Selective MAO-B inhibitors
◦ deprenyl (selegiline)
◦ loses its specificity for MAO-B in antidepressant doses
 Reversible monoamine oxidase inhibitors (RIMAs)
◦ Moclobemide – not approved
◦ Appears to be relatively free of food/drug interactions

27.  Currently marketed medications
◦ fluoxetine.
◦ sertraline.
◦ paroxetine
◦ fluvoxamine
◦ citalopram
◦ escitalopram
 Selectively inhibit 5-HT (not NE) uptake
 Differ from TCAs by having little affinity for muscarinic, as well as
many other neuroreceptors

28.  Much higher therapeutic index than TCAs or MAO-I’s
 Much better tolerated in early therapy
 Equal or almost equal in efficacy to TCAs
 Side effects
◦ Nausea
◦ Sexual dysfunction
 Delayed ejaculation/anorgasmia
◦ Anxiety
◦ Insomnia

29.  Venlafaxine, Duloxetine:
◦ relatively devoid of antihistaminergic, anticholinergic, and
antiadrenergic properties
◦ nonselective inhibitor of both NE and 5-HT uptake.
 Adverse effects:
◦ GI
◦ Sexual dysfunction
◦ Hypertension (venlafaxine)

30.  Trazodone
◦ mixed 5-HT agonist/antagonist
 1 antagonist
 H1 antagonist
 Nefazodone
◦ 5 HT2 antagonist
 Bupropion
◦ Inhibits uptake of DA and NE
◦ antismoking properties probably involves parent molecule
◦ Lacks sexual side effects
◦ Seizure risk

31.  Mirtazapine
◦ 2 antagonist
◦ 5H2 and 5HT3 antagonist
◦ Net effect selective increase in 5HT1A function
◦ H1 antagonist
 Advantages: sedation, no adverse sexual effects

32.  Pharmacodynamic
◦ Additive effects with alcohol and other sedating drugs
◦ MAOI interactions
 Pharmakokinetic
◦ Cytochrome P450-2D6 inhibition
 Fluoxetine and paroxetine
 Increased levels of TCAs, antipsychotics, warfarin
◦ Cytochrome P450-3A4 inhibition
 Nefazodone and fluvoxamine
 Increased levels of terfenadine, astemizole, cisapride – can cause
fatal arrhythmias

33.  LITHIUM : useful in recurrent as well bipolar depression.
 Claimed to be useful in suicidal depression
 Dose range- 900- 1200 mg/day
 Can be used in resistant cases to augment therapy

34. A) Psychotherapies:
 Supportive psychotherapy
 Interpersonal psychotherapy
B) Cognitive therapies: to modify patient’s faulty ways of
thinking about life situations
C) Behavioral therapies:
Social skills training
Problem solving skills

35.  Identify automatic, maladaptive thoughts and distorted beliefs
that lead to depressive moods.
 Learn strategies to modify these beliefs and practice adaptive
thinking patterns.
 Use a systematic approach to reinforce positive coping
behaviours.
 8-12 sessions

36.  Identify significant interpersonal/relationship issues that led
to, or arose from, depression (unresolved grief, role disputes,
role transitions, social isolation).
 Focus on 1 or 2 of these issues, using problem-solving,
dispute resolution, and social skills training.
 12-16 sessions

37. A) Indication:
 Depression with suicidal ideation
 Depression with psychotic symptoms
 Resistant depression- not responding to various drug
combinations in full doses
B) Frequency & number of treatments:
 First 3 treatment on alternate day then twice a week
 6-12 depending upon response

38.  Mild to moderately severe MDD-psychotherapies are as
effective as antidepressant medications.
 Combined treatment with pharmacotherapy and
psychotherapy-no more effective than either therapy alone.
 Combined treatment-chronic or severe episodes, patients
with co-morbidity, and patients not responding to
monotherapy.(Level 1)

39.  Recommend lifestyle management for all patients with
depression.
 Regular exercise
 Adequate housing
 Healthy regular meals
 Stress management strategies
 Sleep hygiene
 Engaging in at least one pleasurable activity a day
 Avoiding substance use
 Keeping a daily mood chart

40.  Assess and discuss self-management goals, challenges and
progress.
 Provide patient education and self-management materials plus
community resources list.
 Review treatment plan and modify if no response to
antidepressants after 3-4 weeks
 At least three follow-up visits in first 12 weeks of antidepressant
treatment.
 At least one follow-up visit in first 12 weeks of referral for
psychotherapy
 Continued antidepressant treatment for 6 months after remission,
at least 2 years for those with risk factors.

41.  Encourage adherence to continued treatment even and
especially after remission.
 Discuss relapse risk factors, symptoms and prevention.
 Discuss and plan gradual discontinuation of antidepressants.
 Discuss need for social network of family, friends and
community.

43.  SIGECAPS Mnemonic for Symptom Criteria for Major Depressive
Episode
 S – sleep disturbance (insomnia, hypersomnia)
 I – interest reduced (reduced pleasure or enjoyment)
 G – guilt and self-blame
 E – energy loss and fatigue
 C – concentration problems
 A – appetite changes (low appetite/weight loss or increased
appetite/weight gain)
 P – psychomotor changes (retardation, agitation)
 S – suicidal thoughts

44. Thank you

45.  Practice guidelines for depressive disorders; American
psychiatric association;Oct 2010
 Diagnostic and statistical manual for mental diseases Fivth
edition
 Kaplan textbook of Psychiatry

46. A. Presence of one (or more) of the following symptoms. At least one
of these must be 1,2 or 3:
1. Delusions.
2. Hallucinations.
3. Disorganized speech (e.g., frequent derailment or incoherence).
4. Grossly disorganized or catatonic behavior.
B. Duration at least 1 day but less than 1 month, with eventual full
return to premorbid level of functioning.
C. Not better explained by major depressive or bipolar disorder with
psychotic features or another psychotic disorder such as
schizophrenia or catatonia and is not attributable to physiological
effects of substance (drug of abuse, medication) or another medical
condition.

47. A)Two (or more) of the following, each present for a significant
portion of time during 1-month period (or less if successfully
treated).
At least one of these must be (1), (2) or (3):
1. Delusions.
2. Hallucinations.
3. Disorganized speech (e.g., frequent derailment or
incoherence).
4. Grossly disorganized or catatonic behavior.
5. Negative symptoms (i.e., diminished emotional expression or
avolition).

48. B. Episode of the disorder lasts at least 1 month but less than 6
months.
C. Schizoaffective disorder and depressive or bipolar disorder
with psychotic features ruled out because either
1 ) No major depressive or manic episodes have occurred concurrently
with the active-phase symptoms
2) If mood episodes have occurred during active-phase symptoms, they
have been present for a minority of the total duration of the active and
residual periods of the illness.
D. Disturbance is not attributable to the physiological effects of
a substance (e.g., drug of abuse, a medication) or another
medical condition.

49. A. Two (or more) , each present for significant portion of time during 1 -month
period (or less if successfully treated) at least one of these must be (1 ), (2), or (3):
1. Delusions.
2. Hallucinations.
3. Disorganized speech (e.g., frequent derailment or incoherence).
4. Grossly disorganized or catatonic behavior.
5. Negative symptoms (i.e., diminished emotional expression or avolition).
B. Level of functioning in one or more major areas, such as work, interpersonal
relations, or self-care, is markedly below level achieved prior to onset (failure to
achieve expected level of interpersonal, academic, or occupational functioning).
C. Continuous signs of the disturbance persist for at least 6 months which must
include at least 1 month of symptoms (or less if successfully treated) that meet
Criterion A (i.e., active-phase symptoms)

50. D. Schizoaffective disorder and depressive or bipolar disorder with
psychotic features ruled out because either
1 ) No major depressive or manic episodes occurred concurrently with
active-phase symptoms, or
2) If mood episodes occurred during active-phase symptoms, they have
been present for a minority of total duration of the active and residual
periods of illness.
E. Not attributable to physiological effects of substance (drug of abuse, a
medication) or another medical condition.
F. History of autism spectrum disorder or a communication disorder of
childhood onset, the additional diagnosis of schizophrenia is made only if
prominent delusions or hallucinations, in addition to the other required
symptoms of schizophrenia, are also present for at least 1 month (or less if
successfully treated).

51.  A. Uninterrupted period of illness during which there is a major
mood episode (major depressive or manic) concurrent with
Criterion A of schizophrenia.
 Note: Major depressive episode must include Criterion A1 :
Depressed mood.
 B. Delusions or hallucinations for 2 or more weeks in the absence
of a major mood episode (depressive or manic) during the lifetime
duration of the illness.
 C. Symptoms that meet criteria for a major mood episode are
present for the majority of the total duration of the active and
residual portions of the illness.
 D. Not attributable to effects of substance (drug of abuse, a
medication) or another medical condition.

52.  Manic Episode
 A. A distinct period of abnormally and persistently elevated, expansive,
or irritable mood and abnormally and persistently increased goal-
directed activity or energy, lasting at least 1 week and present most of
the day, nearly every day (or any duration if hospitalization is necessary).
 B. During the period of mood disturbance and increased energy or
activity, three (or more) of the following symptoms (four if the mood is
only irritable) are present to a significant degree and represent a
noticeable change from usual behavior:
1. Inflated self-esteem or grandiosity.
2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).
3. More talkative than usual or pressure to keep talking.
4. Flight of ideas or subjective experience that thoughts are racing.
5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant
external stimuli), as reported or observed.

53. 6. Increase in goal-directed activity (either socially, at work or school, or
sexually) or psychomotor agitation (i.e., purposeless non-goal-directed
activity).
7. Excessive involvement in activities that have a high potential for
painful consequences (e.g., engaging in unrestrained buying sprees,
sexual indiscretions, or foolish business investments).
 C. Mood disturbance is sufficiently severe to cause marked
impairment in social or occupational functioning or to
necessitate hospitalization to prevent harm to self or others,
or there are psychotic features.
 D. Not attributable to the physiological effects of a substance
(drug of abuse, a medication, other treatment) or to another
medical condition.

54. A. Distinct period of abnormally and persistently elevated,
expansive, or irritable mood and abnormally and persistently
increased activity or energy, lasting at least 4 consecutive days
and present most of the day, nearly every day.
B. During period of mood disturbance and increased energy and
activity, three (or more) of the following symptoms (four if the
mood is only irritable) have persisted, represents a noticeable
change from usual behavior, and have been present to a
significant degree:
1. Inflated self-esteem or grandiosity.
2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).
3. More talkative than usual or pressure to keep talking.
4. Flight of ideas or subjective experience that thoughts are racing.
5. Distractibility (i.e., attention too easily drawn to unimportant or
irrelevant external stimuli), as reported or observed.

55. 6. Increase in goal-directed activity (either socially, at work or school, or
sexually) or psychomotor agitation.
7. Excessive involvement in activities that have a high potential for painful
consequences (e.g., engaging in unrestrained buying sprees, sexual
indiscretions, or foolish business investments).
C. Episode is associated with an unequivocal change in functioning
that is uncharacteristic of the individual when not symptomatic.
D. Disturbance in mood and the change in functioning are observable
by others.
E. Episode is not severe enough to cause marked impairment in social
or occupational functioning or to necessitate hospitalization. If there
are psychotic features, episode is, by definition, manic.
F. Not attributable to the physiological effects of a substance (e.g., a
drug of abuse, a medication, other treatment).

56. A. Criteria have been met for at least one hypomanie episode and at
least one major depressive episode.
B. There has never been a manic episode.
C. Occurrence of hypomania episode(s) and major depressive
episode(s) is not better explained by schizoaffective disorder,
schizophrenia, schizophreniform disorder, delusional disorder, or
other specified or unspecified schizophrenia spectrum and other
psychotic disorder.
D. Symptoms of depression or the unpredictability caused by
frequent alternation between periods of depression and hypomania
causes clinically significant distress or impairment in social,
occupational, or other important areas of functioning.

57. A. Depressed mood for most of the day, for more days than not, as
indicated by either subjective account or observation by others, for at
least 2 years.
 Note: In children and adolescents-irritable and duration at least 1
year.
B. Presence, while depressed, of two (or more) of the following:
1. Poor appetite or overeating.
2. Insomnia or hypersomnia.
3. Low energy or fatigue.
4. Low self-esteem.
5. Poor concentration or difficulty making decisions.
6. Feelings of hopelessness.

58. C. During 2-year period (1 year for children or adolescents), individual has
never been without symptoms in Criteria A and B for more than 2 months
at time.
D. Criteria for a major depressive disorder may be continuously present for
2 years.
E. There has never been a manic episode or a hypomanie episode, and
criteria have never been met for cyclothymic disorder.
F. Disturbance is not better explained by a persistent schizoaffective
disorder, schizophrenia, delusional disorder, or other specified or
unspecified schizophrenia spectrum and other psychotic disorder.
G. Not attributable to the physiological effects of a substance (drug of
abuse, a medication) or another medical condition (e.g. hypothyroidism).
H. The symptoms cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning.

59.  A. Recurrent unexpected panic attacks. A panic attack is an abrupt surge of
intense fear or intense discomfort that reaches a peak within minutes, and
during which time four (or more) of the following symptoms occur;
1. Palpitations, pounding heart, or accelerated heart rate.
2. Sweating.
3. Trembling or shaking.
4. Sensations of shortness of breath or smothering.
5. Feelings of choking.
6. Chest pain or discomfort.
7. Nausea or abdominal distress.
8. Feeling dizzy, unsteady, light-headed, or faint.
9. Chills or heat sensations.
10. Paresthesias (numbness or tingling sensations).
11. Derealization (feelings of unreality) or depersonalization (being detached from oneself).
12. Fear of losing control or “going crazy.”
13. Fear of dying

60. B. At least one of the attacks has been followed by 1 month (or
more) of one or both of following:
1. Persistent concern or worry about additional panic attacks or their
consequences (e.g., losing control, having a heart attack, “going crazy”).
2. A significant maladaptive change in behavior related to the attacks
(e.g., behaviors designed to avoid having panic attacks, such as
avoidance of exercise or unfamiliar situations).
C. Not attributable to the physiological effects of a substance
(e.g., a drug of abuse, a medication) or another medical
condition (e.g. hyperthyroidism, cardiopulmonary disorders).
D. The disturbance is not better explained by another mental
disorder

61. A. Excessive anxiety and worry (apprehensive expectation), occurring more
days than not for at least 6 months, about a number of events or activities
(such as work or school performance).
B. The individual finds it difficult to control the worry.
C. The anxiety and worry are associated with three (or more) of the
following six symptoms (with at least some symptoms having been present
for more days than not for the past 6 months);
 Note: Only one item is required in children.
1. Restlessness or feeling keyed up or on edge.
2. Being easily fatigued.
3. Difficulty concentrating or mind going blank.
4. Irritability.
5. Muscle tension.
6. Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying
sleep).

62. D. The anxiety, worry, or physical symptoms cause clinically
significant distress or impairment in social, occupational, or
other important areas of functioning.
E. The disturbance is not attributable to the physiological effects
of a substance (drug of abuse, a medication) or another medical
condition (e.g., hyperthyroidism).
F. The disturbance is not better explained by another mental
disorder

63. A. One or more symptoms of altered voluntary motor or sensory
function.
B. Clinical findings provide evidence of incompatibility between
the symptom and recognized neurological or medical
conditions.
C. The symptom or deficit is not better explained by another
medical or mental disorder.
D. The symptom or deficit causes clinically significant distress
or impairment in social, occupational, or other important areas
of functioning or warrants medical evaluation.