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Negative symptoms of schizophrenia
   Negative symptoms represent absence or diminution of normal
    intellectual function and expression . Krapelin considered it loss of
    functioning while bleuler emphasized it qualitative loss of
    organization . Hughling Jackson believed that negative symptom
    represented pure loss of function while positive symptoms
    represented exaggeration of normal function . They are subtler
    and difficult to diagnose.
   Later Crow said positive symptoms found in type 1 schizophrenia
    and negative symptoms are found in type 2 schizophrenia and
    associated with insidious onset , poor premorbid adjustment , a
    poor response to treatment , impaired cognition and structural
    brain abnormalities.
   Can be primary or secondary
   Primary negative symptom comprise a core feature intrinsic to
    schizophrenia itself.
   Secondary negative symptoms are attributable to or temporally
    related to the effect of such factors as unrelieved positive
    symptoms , adverse effects of antipsychotic drugs or social
    isolation imposed by schizophrenia. They often subside with
    resolution of causative factor.
    Carpenter et al. (1988) divided primary negative symptoms into
    nonenduring and enduring (deficit) subtypes suggesting they
    should be present for 12 months to be classified as deficit
    symptoms. Möller et al. (1994) suggested that 6 months was more
    pragmatic .Kirkpatrick et al. (1989) further specified deficit
    symptoms into the deficit syndrome
   Persistent negative symptoms are those which have been present
    for > 6 months and when they are enduring and not secondary to
    any other cause they constitute deficit syndrome.
   Deficit syndrome is characterized by ---
   a. at least 2 of following 6 negative symptom must be present
   1. restricted affect 2. diminished emotional range 3. poverty of
    speech 4. curbing of interest 5. diminished sense of purpose 6.
    diminished social drive
   b. above symptoms have been present for preceding 12 month and
    always were present during period of clinical stability
   c. negative symptoms are primary i.e. not secondary to factors
    other than disease process like -
   1.anxiety 2. drug effect 3. suspiciousness 4. mental retardation 5.
    depression.
   d. patient meets DSM criteria for schizophrenia
Negative symptoms of schizophrenia
   Poor communication – reduced capacity to initiate
    or respond to speech , meager or impoverished
    content of speech .
   Psychomotor retardation – slow or restricted
    physical movements.
   It has been seen that patients with negative
    symptoms are more likely to have been born in
    winter (opler et al 1984), to have poor premorbid
    cognitive and social adjustment ( opler et al 1984)
    ,to respond inadequately to neuroleptics (brier et al
    , johnston et al 1987), to have family history of
    schizophrenia ( kay, opler , fiszbein 1986), to show
    morphological brain abnormalities ( andreasen et
    al 1982 , weinberger et al 1980).
Negative symptoms of schizophrenia
   Weinberger (1987) proposed dysregulation of
    dopamine system . Putative hypofunction of
    prefrontal dopamine system could provide a
    possible neurobiologic mechanism for negative
    symptom and increased subcortical dopamine
    activity might account for positive symptom and
    movement disorder. The combination of positive
    and negative symptom common in schizophrenia
    could result from reduced prefrontal dopamine
    function , leading to relative hyperactivity of
    subcortical dopamine , which would normally be
    modulated by prefrontal system .
Negative symptoms of schizophrenia
Negative symptoms of schizophrenia
  A. SELF RATING INSTRUMENTS –
  1. Subjective experience of deficits in
   schizophrenia(SEDS, Liddle and Barnes , 1988) –
   consists of 21 items arranged in 6 groups namely
   abnormal thinking and concentration , disturbance
   of affect , impaired will and decreased energy
   , disturbance of perception , intolerance of stress &
   disturbance of voluntary movements.
  2. Subjective deficit syndrome scale ( SDSS, Bitter
   et al 1989 , Jaeger et al 1990 ) -
  based of experimental subscale of subclinical
symptom
  scale. Based exclusively on self report.
   B . Observer rated instruments –
   1. Brief psychiatric rating scale ( BPRS , overall and graham
    1962) – 7 point scale based on 16 or 18 items depending on
    version
   2. Krawiecka – Manchester scale ( KMS , krawiecka et al 1977 )
    – 5 point 8 item scale. Four items namely incoherence or
    irrelevance of speech , poverty of speech or muteness, flattened
    or incongruous affect and psychomotor retardation are based
    on patient’s response to questions. Four other items depression
    , anxiety , delusion and hallucination based on rater’s
    observation.
   3. Scale for assessment of negative scale ( SANS ) – it is
    enlargement of affective flattening scale ( andreasen ,1979).it is
    6 point scale based on 30 items from five symptom complexes –
    alogia , affective flattening , avolition – apathy , anhedonia -
    asociality , attention al impairment.
   4. Positive and negative syndrome scale ( PANSS , kay 1987 ) –
    it consist of 30 items scale 18 adapted from BPRS and 12 from
    psychopathology rating schedule rated on 7 point scale.
   5. Negative symptom rating scale ( NSRS
    , iager ,1985 ) - 7 point scale based on 10 items
    divided into 4 subscales two including two
    items and 3 including 3 items . a. thought
    process through speech , judgment b. cognition
    through memory , attention and orientation. c.
    volition through grooming , motivation and
    motion d. affect and relatedness through
    emotional response and expressive relatedness.
   6. other scales – the schedule for deficit
    syndrome ( carpenter et al , 1988) , lewin-fog-
    melzer scale ( 1983) , pearlson scale (1984)
    , emotional blunting scale , wing scale
    (1961), pogue – giele – harrow scale (1984)
   Treatment begins with assessing factor that can cause secondary negative
    symptom . Treatment of secondary negative symptom will be treating their
    cause like antipsychotic for positive symptoms , antidepressant for depression
    , anxiolytic for anxiety , antiparkinsonian or antipsychotic dose reduction for
    extrapyramidal side effects. If they don’t resolve by such treatment than they
    are primary negative symptom . For primary negative symptom 2nd
    generation antipsychotics in low dose are prescribed.
   Low-dose amisulpride should be currently considered first-line treatment for
    patients with primary negative symptoms.
   Aripiprazole and olanzapine should be considered second-line treatments.
   Clozapine is not recommended for patients with primary, enduring negative
    symptoms.
   Trials with NMDA agonists, mirtazepine and SSRIs are promising but need
    more investigation.
    Mirtazepine, fluoxetine, fluvoxamine or paroxetine should be trialed as
    adjunctive medication in patients resistant to amisulpride and/or
    aripiprazole/olanzapine.
   Psychological interventions should be incorporated into the treatment
    package.
   In one RCT mirtazapine augmentation of risperidone was found to reduce
    negative symptom. In another study fluvoxamine has not been found effective
    . In another study once weekly dosing of D-cycloserin has been found to
    improve negative symptoms. Repeated transcranial magnetic stimulation has
    also been found to reduce severity of negative symptoms.
     1. Positive and negative syndromes in schizophrenia: assessment and
      research:By Stanley R. Kay
     2. Negative schizophrenic symptoms: pathophysiology and clinical
      implications :By John F. Greden, Rajiv Tandon
     3. CTP
     4. OTP
     5. Negative symptoms: the ‘pathology’ of motivation and goal-directed
      behaviour :Richard G. Brown and Graham Pluck ; Trends Neurosci. (2000)
      23, 412–417
     6. Clinical evaluation of negative symptoms in schizophrenia : Hans-
      Ju¨rgen Mo¨ller ; European Psychiatry 22 (2007) 380e386
     7. Schizophrenia Research 95 (2007) 151–157
     8. The deficit syndrome in schizophrenia: implications for the treatment
    of negative symptoms ; European Psychiatry 19 (2004) 21–26
     9. Drug treatment of the negative symptoms of schizophrenia : David J.
      King ; European Neuropsychopharmacology 8 (1998) 33–42
     Pharmacological treatment of primary negative symptoms in
      schizophrenia: A systematic review ; Schizophrenia Research 88 (2006) 5–
      25

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Negative symptoms of schizophrenia

  • 2. Negative symptoms represent absence or diminution of normal intellectual function and expression . Krapelin considered it loss of functioning while bleuler emphasized it qualitative loss of organization . Hughling Jackson believed that negative symptom represented pure loss of function while positive symptoms represented exaggeration of normal function . They are subtler and difficult to diagnose.  Later Crow said positive symptoms found in type 1 schizophrenia and negative symptoms are found in type 2 schizophrenia and associated with insidious onset , poor premorbid adjustment , a poor response to treatment , impaired cognition and structural brain abnormalities.  Can be primary or secondary  Primary negative symptom comprise a core feature intrinsic to schizophrenia itself.  Secondary negative symptoms are attributable to or temporally related to the effect of such factors as unrelieved positive symptoms , adverse effects of antipsychotic drugs or social isolation imposed by schizophrenia. They often subside with resolution of causative factor.
  • 3. Carpenter et al. (1988) divided primary negative symptoms into nonenduring and enduring (deficit) subtypes suggesting they should be present for 12 months to be classified as deficit symptoms. Möller et al. (1994) suggested that 6 months was more pragmatic .Kirkpatrick et al. (1989) further specified deficit symptoms into the deficit syndrome  Persistent negative symptoms are those which have been present for > 6 months and when they are enduring and not secondary to any other cause they constitute deficit syndrome.  Deficit syndrome is characterized by ---  a. at least 2 of following 6 negative symptom must be present  1. restricted affect 2. diminished emotional range 3. poverty of speech 4. curbing of interest 5. diminished sense of purpose 6. diminished social drive  b. above symptoms have been present for preceding 12 month and always were present during period of clinical stability  c. negative symptoms are primary i.e. not secondary to factors other than disease process like -  1.anxiety 2. drug effect 3. suspiciousness 4. mental retardation 5. depression.  d. patient meets DSM criteria for schizophrenia
  • 5. Poor communication – reduced capacity to initiate or respond to speech , meager or impoverished content of speech .  Psychomotor retardation – slow or restricted physical movements.  It has been seen that patients with negative symptoms are more likely to have been born in winter (opler et al 1984), to have poor premorbid cognitive and social adjustment ( opler et al 1984) ,to respond inadequately to neuroleptics (brier et al , johnston et al 1987), to have family history of schizophrenia ( kay, opler , fiszbein 1986), to show morphological brain abnormalities ( andreasen et al 1982 , weinberger et al 1980).
  • 7. Weinberger (1987) proposed dysregulation of dopamine system . Putative hypofunction of prefrontal dopamine system could provide a possible neurobiologic mechanism for negative symptom and increased subcortical dopamine activity might account for positive symptom and movement disorder. The combination of positive and negative symptom common in schizophrenia could result from reduced prefrontal dopamine function , leading to relative hyperactivity of subcortical dopamine , which would normally be modulated by prefrontal system .
  • 10.  A. SELF RATING INSTRUMENTS –  1. Subjective experience of deficits in schizophrenia(SEDS, Liddle and Barnes , 1988) – consists of 21 items arranged in 6 groups namely abnormal thinking and concentration , disturbance of affect , impaired will and decreased energy , disturbance of perception , intolerance of stress & disturbance of voluntary movements.  2. Subjective deficit syndrome scale ( SDSS, Bitter et al 1989 , Jaeger et al 1990 ) - based of experimental subscale of subclinical symptom scale. Based exclusively on self report.
  • 11. B . Observer rated instruments –  1. Brief psychiatric rating scale ( BPRS , overall and graham 1962) – 7 point scale based on 16 or 18 items depending on version  2. Krawiecka – Manchester scale ( KMS , krawiecka et al 1977 ) – 5 point 8 item scale. Four items namely incoherence or irrelevance of speech , poverty of speech or muteness, flattened or incongruous affect and psychomotor retardation are based on patient’s response to questions. Four other items depression , anxiety , delusion and hallucination based on rater’s observation.  3. Scale for assessment of negative scale ( SANS ) – it is enlargement of affective flattening scale ( andreasen ,1979).it is 6 point scale based on 30 items from five symptom complexes – alogia , affective flattening , avolition – apathy , anhedonia - asociality , attention al impairment.  4. Positive and negative syndrome scale ( PANSS , kay 1987 ) – it consist of 30 items scale 18 adapted from BPRS and 12 from psychopathology rating schedule rated on 7 point scale.
  • 12. 5. Negative symptom rating scale ( NSRS , iager ,1985 ) - 7 point scale based on 10 items divided into 4 subscales two including two items and 3 including 3 items . a. thought process through speech , judgment b. cognition through memory , attention and orientation. c. volition through grooming , motivation and motion d. affect and relatedness through emotional response and expressive relatedness.  6. other scales – the schedule for deficit syndrome ( carpenter et al , 1988) , lewin-fog- melzer scale ( 1983) , pearlson scale (1984) , emotional blunting scale , wing scale (1961), pogue – giele – harrow scale (1984)
  • 13. Treatment begins with assessing factor that can cause secondary negative symptom . Treatment of secondary negative symptom will be treating their cause like antipsychotic for positive symptoms , antidepressant for depression , anxiolytic for anxiety , antiparkinsonian or antipsychotic dose reduction for extrapyramidal side effects. If they don’t resolve by such treatment than they are primary negative symptom . For primary negative symptom 2nd generation antipsychotics in low dose are prescribed.  Low-dose amisulpride should be currently considered first-line treatment for patients with primary negative symptoms.  Aripiprazole and olanzapine should be considered second-line treatments.  Clozapine is not recommended for patients with primary, enduring negative symptoms.  Trials with NMDA agonists, mirtazepine and SSRIs are promising but need more investigation.  Mirtazepine, fluoxetine, fluvoxamine or paroxetine should be trialed as adjunctive medication in patients resistant to amisulpride and/or aripiprazole/olanzapine.  Psychological interventions should be incorporated into the treatment package.  In one RCT mirtazapine augmentation of risperidone was found to reduce negative symptom. In another study fluvoxamine has not been found effective . In another study once weekly dosing of D-cycloserin has been found to improve negative symptoms. Repeated transcranial magnetic stimulation has also been found to reduce severity of negative symptoms.
  • 14. 1. Positive and negative syndromes in schizophrenia: assessment and research:By Stanley R. Kay  2. Negative schizophrenic symptoms: pathophysiology and clinical implications :By John F. Greden, Rajiv Tandon  3. CTP  4. OTP  5. Negative symptoms: the ‘pathology’ of motivation and goal-directed behaviour :Richard G. Brown and Graham Pluck ; Trends Neurosci. (2000) 23, 412–417  6. Clinical evaluation of negative symptoms in schizophrenia : Hans- Ju¨rgen Mo¨ller ; European Psychiatry 22 (2007) 380e386  7. Schizophrenia Research 95 (2007) 151–157  8. The deficit syndrome in schizophrenia: implications for the treatment of negative symptoms ; European Psychiatry 19 (2004) 21–26  9. Drug treatment of the negative symptoms of schizophrenia : David J. King ; European Neuropsychopharmacology 8 (1998) 33–42  Pharmacological treatment of primary negative symptoms in schizophrenia: A systematic review ; Schizophrenia Research 88 (2006) 5– 25