PRESENTER : DR SOUMITRA DAS,JR2/TDMC,ALAPPUZHA.

CHAIRPERSON:DR REKHA MATHEW

Negative symptoms are the loss or reduction of certain normal functions or behaviors – impairment of normal affect and emotion – of normal social interaction, purpose, and motivation.

Acta Psychiatr Scand 2007: 115: 4–11DOI: 10.1111/j.1600-0447.2006.00947.x

The Scale for the Assessment of Negative Symptoms (SANS; Andreasen 1982) assesses five symptom areas: Affective flattening,Alogia, AvolitionAnhedoniaApathy,Asociality, Attention.

The Positive and Negative Syndrome Scale (PANSS; Kay et al. 1987) includes two items:

Difficulty in Abstract Thinking Stereotyped Thinking

1) Deficits in the perception of emotion (i.e., difficulty judging and interpreting the emotional displays of others)

2) Deficits in the expression of emotion (i.e., difficulty conveying one’s emotional experience to others)

3) Deficits in the experience of emotion (i.e., difficulty with the subjective feeling of emotion)

Source of chronic disabilityImperfections of psychiatric therapeuticsWorse quality of life.Worse social functioningWorse interpersonal relationWorse work capacityWorse outcome overallMost distressing for family members

Ref.Bow-Thomas CC et al. Predicting quality of life from symptomatology in schizophrenia at exacerbation and stabilization. Psychiatry Res1999;86:131–142.

FROM ONSET

RESPOND LESS DEFINITELY

TYPES – - PHASIC / ENDURING - PRIMARY / SECONDARY

POOR PREMORBIDINSIDIOUS ONSETPOOR NEUROPSYCHSEVERE GLOBAL PSYCHOPATHOLOGY

Longitudinal perspective, three components of primarynegative symptoms :a. a premorbid component: present before the first psychotic episode , associated with poor premorbid function

b. a psychotic-phasic or nonenduring component: only in association with positive symptoms , restricted to the period around a psychotic exacerbation of schizophrenic illness

c. a post psychotic deterioration component: persistent negative symptoms that occur after a psychotic episode, reflect deterioration ,decline from premorbid levels of functioning.

NEED TO DIFFERENTIATE???!!##CAUSES

BETTER RESPONSE-POSITIVE PSYCHOTIC

SYMPTOMS-EPS – DRUGS-DEPRESSION-CATATONIA

-DEMORALIZATION-LACK OF ENVIRONMENTAL

STIMULATION

Krapelin: A weakening to those emotional activities, which permanently form the mainsprings of volition, leading to the symptoms listed above.

Bleuler : Fundamental symptoms present in every case and in every period of the illness, as well as accessory symptoms that may also appear in other illnesses.

Mostly negative symptoms – loss of the continuity of associations, loss of affective responsiveness, loss of attention, loss of volition, ambivalence, and autism .

National Institute of Mental Health (NIMH) MATRICS initiative (Measurement and

Treatment Research to Improve Cognition in Schizophrenia)

NIMH agree that “improved recognition and awareness of negative symptoms are the first step to improving function in patients with negative symptoms of schizophrenia”

NIMH(2005)-supported consensus meeting, schizophrenia experts agreed that negative symptoms are a distinct domain of schizophrenia.

Not widely assessed in every-day clinical practice

Difficult to see, when they are mild. Negative symptoms

Insidious – they are reductions or losses in normal behaviors that may be subtle.

Not obvious to the patient or to their friends, relatives, or caregivers, and so may not be brought to the attention of the clinician.

.

The separation between cognitive and negative symptoms, and between affective and negative symptoms, is less clear.

Cognitive symptom scales (SANS, PANSS negative subscale) include measures of cognitive function.

Overlap between negative and affective symptoms also exists, with suicidality, loss of interest and pleasure, and apathy common to both negative symptom schizophrenia and depression.

Negative symptoms may keep the patient quiet, self-contained, and out of trouble, so caregivers may see them as the better aspects of the disease rather than as

factors that reduce the patient’s ability to function and participate in a normal life

Hatfield AB: Psychological costs of schizophrenia to the family. Soc Work 23:355–359, 1978>BEHAVIOR DISTRESSING TO FAMILYLacks motivation, Handles money poorly, Shows poor grooming and personal care Unusual eating and sleeping habits, Forgets to do things, Talks without making senseArgues too much Thinks people talk about him/her, Hears voices,Breaks and damages things. Refuses to take medication

Reduced quantity of speech with few words or non-verbal responses

Seemingly normal speech quantity but conveying little meaning

CROW TYPE 1 : positiveCROW TYPE2 : later negative Revised > Independent and can coexistNewly classified, TYPE 1: hyperdopaminergia and response

to medicines, TYPE2: structural brain changes,

developmental impairment, possible hypodopaminergia

DOPAMINESome investigators have found lower concentrations of cerebrospinal fluid (CSF) homovanillic acid (HVA)

A deficit of cortical dopamine activity in negative schizophrenia

Deficient mesocortical dopamine activity may contribute to the hypofrontality

Reduced prefrontal dopamine function (negative symptoms) >>>>>leading to relative hyperactivity of subcortical dopamine (positive symptoms, consistent with the classical dopamine hypothesis).

Introduction of atypical antipsychotics (e.g., clozapine, risperidone, olanzapine, quetiapine, sertindole, ziprasidone), which are potent 5-HT2A antagonists and have been shown to be effective in treating negative symptoms

Ritanserin (a potent 5-HT2 antagonist) was found to induce a significant reduction in negative symptoms such as anergia and anxiety/depression

Lower 5-HIAA concentrations in patients with schizophrenia have also been found to be correlated with negative symptoms

Muscarinic hyperactivity > negative symptoms,

Reduced cholinergic activity > positive symptoms (Tandon and Greden 1989)

Anticholinergic agents are reported to elevate mood, energize, stimulate, and improve socialization in persons with schizophrenia, regardless of whether they are taking antipsychotic medication.

Increased cholinergic activity is associated with REM latency and reduced slow-wave sleep.

Presence of negative symptoms is significantly correlated with shortened REM latency (Tandon et al. 1991a, 1992) and decreased slow-wave sleep (Ganguli et al. 1987; Tandon et al. 1989; van Kammen et al.)

Glutamate agonists (i.e., glycine and d-cycloserine) can improve negative symptoms when added to conventional antipsychotics.

OTHERS : NE , Cholecystokinin

Negative symptoms are associated with reduced gray matter volume in temporal lobe.

Reductions in gray matter volume in left temporal and anterior amygdala complex(Sigmundsson T et al)

Both gray and white matter tissue loss relative to normal controls in left hemisphere structures comprising the temporal lobe, anterior cingulate, and medial frontal cortex(Sanfilipo M et al)

Sanfilipo et al. (40) reported similar rates of prefrontal white matter loss (11–15%) in patients who had high negative symptom scores.

Prominent decrements in frontal lobe volume that were related to negative symptoms.

Recently, with refinements in MRI with diffusion tensor imaging, reduced white matter integrity was found in inferior frontal regions (Wolkin A et al Am J Psychiatry 2003;160:572–574)

Reduced blood flow in the right hemisphere, temporal and ventral prefrontal cortex (PFC) (Potkin SG et al. Am J Psychiatry 2002;159:227–237.)

Different pattern of glucose metabolism in patients with predominantly negative symptoms .

Negative symptoms is their frequent presence at the very beginning of the schizophrenia disease course, as prodromal symptoms.

11% of patients met the criteria for the deficit syndrome (general state of executive dysfunction, often associated with subjective sense of fatigue)

A neurodegenerative process may also contribute to the disease progression and the worsening of negative symptoms with age

1. Negative symptoms constitute an integral component of schizophrenic psychopathology. They are not, however, specific to schizophrenia.

2. Data support the existence of a negative symptom syndrome that is distinct from a positive symptom syndrome in terms of clinical, prognostic, and neurobiological correlates (Robins and Guze 1970).

3. Positive and negative syndromes are not mutually exclusive and often coexist in the same patient.

4. Negative symptoms are not a unitary construct. They can be manifested as a consequence of a variety of conditions like depression,eps,f20 psychopathology.

ASSESSMENT / CLINICAL EVALUVATIONNEWER GENERATION

ANTIPSYCHOTICS!!!!!!!!!!LOWEST EFFECTIVE DOSECLOZAPINE BEST RESPONSE BUT

INCONSISTENTLY PROVENDRUG INDUCED STATE to be

remembered

Relatively longer trialNegative symptom improvement has been

observed within 6–8 weeks of treatment initiation (Goff et al. 1999; Heresco-Levy et al. 1999; Javitt et al. 1994).

Risperidone > conventional antipsychotics( North American multicenter study by Chouinard et al. 1993; Marder and Meibach 1994).

European multicenter study : No significant difference

Clozapine > conventional antipsychotics for the treatment of positive symptoms in treatment-resistant patients with schizophrenia (Buchanan et al. 1998; Kane et al. 1988; Pickar et al. 1992).

In BPRS FACTOR 2(superior), SANS(no diff)Improvement may be due to improvement in

positive symptoms.

GLYCINE RECEPTOR MODULATIOND-SERINED-CYCLOSERINE ,PIRACETAMASENAPINE – APA 2006MIRTAZAPINEDEPRENYLFLUOXETINE,FLUVOXAMINECARBAMAZEPINE,TOPIRAMATEOESTROGENBETA BLOCKERLITHIUM

GREATER BENEFICIAL EFFECT ON NEGATIVE SYMPTOMS

COGNITIVE IMPAIRMENT IS A CHALLENGE

- SPEED OF PROCESSING - ATTENTION AND VIGILANCE- WORKING MEMORY- VERBAL LEARNING- SOCIAL COGNITION- REASONING- PROBLEM SOLVINGREF : MATRICS(MEASUREMENT AND TREATMENT RESEARCH TO IMPROVE

COGNITION IN SCHIZOPHRENIA)

INDIVIDUAL

GROUP

PSYCHO SOCIAL TRAINING

HE/SHE IS WANTEDLY DOING IT

THE DISEASE IS CAUSING IT AND WE NEED TO SUPPORT

SUPPORTIVE >>> DYNAMICFAMILY INVOLVEMENTPSYCHOEDUCATION(NEG. SYMPTOMS)LOWERING EXPECTATIONCLEAR COMMUNICATIONPREDICTABLE ENVIRONMENTADEQUATE STIMULATION

GRADED TASK ASSIGNMENTTREATMENT ADHERENCEROLE MODELLINGACQUIRING NEW SKILLSMAINTAINANCEGENERALIZATION FROM TRAINING TO

REAL LIFE SETTING

Negative symptoms as the core deficit of schizophrenia

Perhaps even more important than the more readily recognized positive symptoms

Its easily misdiagnosed Treatment modalities are restricted.Newer agents are on trials but not so much

rewarding up to dateSocial psychiatry and psychosocial rehabilitation has a great role

Negative Symptom and Cognitive Deficit Treatment Response in Schizophrenia Edited by RICHARD S. E. KEEFE, PH.D. JOSEPH P. MCEVOY, M.D.(American Psychiatric Press)

Hans-Jürgen Möller ,Non-neuroleptic approaches to treating negative symptoms in schizophrenia(Received: 9 February 2004 / Accepted: 4 March 2004)

Sadock, Benjamin J.; Sadock, Virginia A.; Ruiz, Pedro,Kaplan & Sadock's Comprehensive Textbook of Psychiatry, 9th Edition