Schizophrenia-prof.fareed minhas


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Schizophrenia-prof.fareed minhas

  1. 1. Prof. Dr. Fareed A. Minhas Head, Institute of Psychiatry Rawalpindi General Hospital Rawalpindi
  2. 2. "Schizophrenia is a cruel disease. The lives of those affected are often chronicles of constricted experiences, muted emotions, missed opportunities, unfulfilled expectations. It leads to a twilight existence, a twentieth-century underground man... It is in fact the single biggest blemish on the face of contemporary medicine and social services; when the social history of our era is written, the plight of persons with schizophrenia will be recorded as having been a national scandal." - E. Fuller Torrey, M.D., Surviving Schizophrenia
  3. 3.  Characterized in general by fundamental and characteristic disorders in thinking and perception, and by inappropriate or blunted affect  Clear consciousness is usually maintained  Intellectual capacity retained though cognitive impairment may set in over time  Disorder of thinking, emotion, volition and perception along with disintegration of personality
  4. 4. Annual incidence between 0.1 and 0.5 per 1000 Onset characteristically between ages 15 & 45 Equal among men and women but mean age of onset is 5 years earlier in men Lifetime risk between 7.0 and 9.0 per 1000 Prevalence equal in various countries (WHO) In America alone, 2.2 million people are affected
  6. 6. Stigmatization • Knowledge of the illness lags behind facts ->”discrimination” • “Fear of violence” • “Fear of criminal intentions” • “Fear of unknown and aversion to illness Impact on the person’s life • Work limitations such as difficulty performing multiple tasks, interacting with co-workers, accepting criticism or supervision, customer service/contact. Perform inconsistently and may need work space with low stimulation(stress) • Interpersonal relationships are difficult, mostly live alone or with family
  7. 7. Impact on families • Sorrow – “We feel like we have lost our child” • Anxiety – “We are afraid to leave him alone or hurt his feelings” • Fear – “Will he harm himself or others?” • Shame and guilt – “Are we to blame? What will people think?” • Feelings of isolation – “No one can understand” • Bitterness – “Why did this happen to us?” • Ambivalence towards the affected person • Anger and jealousy of siblings • Depression / Sleeplessness / Weight loss / Social withdrawal • Total denial of the illness or its severity • Blaming each other • Marital discord / Divorce • Concerns for the future
  8. 8. Community costs • Schizophrenia costs Canadians more than $2.3 billion in direct health care costs and an additional $2 billion in support costs such as welfare, family benefits and community support services, for a total of $4.3 billion annually. The cost in terms of human suffering is immeasurable... • People with this disease use nicotine and street drugs excessively • Suicide rates are high (10 percent – mostly young males) • Studies show increased prevalence of various diseases in schizophrenics such as female breast cancer, MI (s) Infections, type II diabetes mellitus • Homelessness • Accidents
  9. 9. PARANOID SCHIZOPHRENIA • Commonest type • Predominant well-organized paranoid delusions • Thought processes and mood relatively spared • Disturbance of affect, volition, speech and catatonia mild / absent SIMPLE SCHIZOPHRENIA • Insidious development of odd behavior, social withdrawal and declining performance at work • Clear schizophrenic symptoms might be absent CATATONIC SCHIZOPHRENIA • Prominent psychomotor disturbances with alteration between hyperkinesis and stupor, or automatic obedience and negativism • Posturing / episodes of violent excitement
  10. 10. HEBEPHRENIC SCHIZOPHRENIA • Affective changes are prominent; delusions and hallucinations fleeting and fragmentary; behavior irresponsible and unpredictable • Mannerisms are common • Mood is shallow/inappropriate followed by giggling or selfsatisfied/self-absorbed smiling • Hypochondriacal complaints common • Thought is disorganized and speech rambling/incoherent OTHER CATEGORIES • Undifferentiated • Residual • Post-schizophrenia depression • Schizophreniform disorder not otherwise specified
  11. 11. • POSITIVE SYMPTOMS (Delusions, Hallucinations) • NEGATIVE SYMPTOMS (apathy, lack of drive, social withdrawal) THE ACUTE SYNDROME SYMPTOM • Lack of insight into illness FREQUENCY (%) • Auditory hallucinations 97 • Ideas of reference 74 • Suspiciousness 70 • Flatness of affect 66 • Voices speaking to the patient 66 • Delusional Mood 65 • Delusions of persecution 64 • Thought alienation 64 • Thoughts spoken aloud 52
  12. 12. THE CHRONIC SYNDROME CHARACTERISTIC FREQUENCY % • Social withdrawal 74 • Under activity 56 • Lack of conversation 54 • Slowness 48 • Over activity 41 • Odd ideas / behavior 34 • Depression 34 • Neglect of appearance 30 • Odd postures and movements 25 • Threats or violence 23 • Socially embarrassing behavior 8 • Suicidal attempts 4
  13. 13. VARIATION OF THE CLINICAL PICTURE • Different features may predominate within a syndrome eg. In the acute syndrome one may have a predominant paranoid delusion and another may have a thought disorder • Some may have features of both syndromes • Depressive symptoms / Water intoxication FACTORS MODIFYING CLINICAL FEATURES • Amount of social stimulation of the patient – under stimulated ones have mostly negative symptoms and over stimulated ones positive symptoms • Social background – previously religious delusions were common • Intelligence – people of low intelligence exhibit simpler forms
  14. 14. Minimum of one very clear symptom(two or more if less clear) belonging to any one of the groups (a)-(d) or from at least two of the groups (e)-(h) during a period of one month or more (a) Thought echo/ insertion or withdrawal and broadcasting (b) Delusions of control,influence,passivity; delusional perception (c) Hallucinatory voices as a running commentary, third-person or somatic hallucinations (d) Persistent delusions that are inappropriate and impossible (e) Persistent hallucinations or over-valued ideas (f) Breaks/interpolations in train of thought, neologisms (g) Catatonic behavior such as waxy flexibility/negativism/stupor (h) Negative symptoms eg. Marked apathy, paucity of speech (i) Significant consistent change in personal behavior eg idleness
  15. 15. A. CHARACTERISTIC SYMPTOMS OF ACTIVE PHASE (delusions/hallucinations/disorganized speech/catatonia/alogia) B. SOCIAL/OCCUPATIONAL DYSFUNCTION in at least one major area of functioning such as work, interpersonal relations or self-care C. DURATION persistent for at least 6 months…with at least one month of symptoms of criterion A D. SCHIZOAFFECTIVE AND MOOD DISORDER EXCLUSION E. SUBSTANCE/GENERAL MEDICAL CONDITION EXCLUSION F. RELATIONSHIP TO A PERVASIVE DEVELOPMENTAL DISORDER
  16. 16. ORGANIC SYNDROMES (drug-induced states, temporal lobe epilepsy, acute brain syndrome of the elderly, dementia) MOOD DISORDER PERSONALITY DISORDER CHILDHOOD AUTISM – ASPERGER’S SYNDROME
  17. 17. Study commenced in 1990 investigating about 20% genomes in large families of history of schizophrenia in east Quebec show association areas on chromosomes • 11q / 3q / 18q / 6p •STRONG EVIDENCE FOR SCHIZOPHRENIA SUSCEPTIBILITY GENE 6P22-P24 AND 11Q21-22 Anticipation (increasing severity or early age of onset of disease in successive generations) is found in Schizophrenia A recent study by molecular biologists at UC Irvine isolated a gene, hSKCa3 located on 22q, which leads to an increased risk to schizophrenia. This isolated gene contains a characteristic CAG repeat American Journal of Genetics(Miziade M et al)
  18. 18. There is a strong genetic component however only 48% concordance among identical twins says that is not all…
  20. 20. SHOWS A SIGNIFICANT INCREASED NUMBER OF DOPAMINE RECEPTORS IN A SCHIZOPHRENIC BRAIN ROLE OF AMINO ACIDS IN SCHIZOPHRENIA • Glutamate neurotransmitters might have a role – evidence of increased presynaptic/postsynaptic uptake sites for glutamate in orbito-frontal cortex and decreased density of glutamate receptors in the left hippocampus (SEE NEXT SLIDE)
  22. 22.  People with schizophrenia have smaller and lighter brains  Evidence of enlarged cerebral ventricles  Cytoarchitectural disturbances have been noted  There is evidence of regional cortical loss – volume changes in gray matter 3D profile of gray matter loss in brains of teenagers with early-onset disease.TEMPORAL and FRONTAL areas most affected (red shows maximum effect). These areas are responsible for memory, hearing, motor functions and attention
  23. 23. Frontal composite variability of normal and schizophrenic brains by gender Shows Significant structural variability suggestive of changes Normal vs. Schizophrenia – Composite variability among 15 male subjects
  24. 24. VOLUME OF INTEREST superimposed over three orthogonal slices of the schizophrenic brain – it is simply a sphere of 60 mm radius between midline decussations of ant. And post. commissures Variability in the sulcal anatomy of the brain between normal and schizophrenic brains is also noted
  25. 25. 3D average surface representation and variability maps of the lateral ventricles highest variability in the posterior horns noted : MRI imaging showing differences in brain ventricle size in twins - one schizophrenic, one not. (image courtesy NIH Dr. Daniel Weinberger, Clinical Brain Disorders Branch)
  26. 26. Coronal MR scans from a normal comparison subject (left), and chronic schizophrenic (right). Note increase in CSF in right amygdalahippocampal complex. (image courtesy of Harvard University Schizophrenia Project
  27. 27. N SCZ HYPOFRONTALITY : At rest DISARRAY of the hippocampal cytoarchitecture and cingulate gyrus During card sorting
  28. 28.  “Soft signs” have been reported in many studies – commonly stereognosis, graphaesthesia, balance and proprioception probably due to defects in integration of proprioceptive and other sensory information (Rochford et al-1970/Sanders et al-1992)  Movement disorders common such as dyskinesias and extrapyramidal or parkinsonian signs. Initially the argument was that these are side-effects of anti-psychotic drugs but now a prevalence of 12% of spontaneous dyskinesias has been found in 9 different recent studies of people who never received antipsychotics. Also 23% prevalence of parkinsonian signs is found in the same category.  Decreased pain perception exact mechanism not studies
  29. 29.  EEGs of schizophrenics show increased theta activity, fast activity and paroxysmal activity with scalp electrodes. More abnormal EEGs were seen in patients never treated. Using deep implanted electrodes – spike abnormalities in septal region and secondarily in the hippocampus and amygdala. Also there was abnormality in ‘deep frontal’ and ‘subthalmic’ regions  Evoked potential response (p300) makes use of the person’s ability to identify a target stimulus among irrelevant stimuli and this is lower in schizophrenics and their first-degree relatives  Eye-tracking studies – defective performance by schizophrenics (Freidman et al-1992 and Muir et al-1992)
  30. 30.  Cognitive deficits proven by various studies. Studies using subjects who never received anti-psychotics also show significant results.  Main areas of deficit are verbal learning and memory. Less commonly, attention and vigilance as well as visuo-motor processing.  Latest study by Schuepbach et all in 2002 in which 20 patients compared to 21 controls showed significant deficits on the Stroop test for selective attention
  31. 31.  Use of comparatively new and technically complex methods – POSITRON EMISSION TOMOGRAPHY (PET) ; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY (SPECT) and FUNCTIONAL MAGNETIC RESONANCE IMAGING (fMRI)  10 studies conducted to date of patients without anti- psychotic treatments. 8 show significant deficits in the dorsolateral prefrontal cortex at the onset on disease  Decreased blood flow in prefrontal and frontal areas
  32. 32.  PERINATAL FACTORS : Birth complications, season, influenza  CHILDHOOD DEVELOPMENT/ ANTECEDENTS : Greater hostility towards strangers, reading and speech difficulties  PERSONALITY FACTORS : Asthenic built, schizoid traits  SEX AND AGE OF ONSET : Myelination of frontal and temporal cortex around puberty, sex hormone changes
  34. 34. According to the BIO-PSYCHO-SOCIAL MODEL BIOLOGICAL TREATMENT ANTI-PSYCHOTIC DRUGS Conventional or Standard Antipsychotics are phenothiazines, butyrophenones, diphenylbutyl pipiredines, thioxanthenes and substituted benzamides. These include: chlorpromazine (Thorazine); fluphenazine (Prolixin); haloperidol (Haldol); thiothixene (Navane); trifluoperazine (Stelazine); perphenazine (Trilafon) and thioridazine (Mellaril). Atypical Antipsychotics are newer drugs with fewer side effects and include risperidone (Risperdal); clozapine (Clozaril) and olanzapine (Zyprexa). Side-effects Commonly dry mouth, constipation, blurred vision and drowsiness. Less commonly decreased libido, menstrual changes Extrapyramidal effects : Parkinsonian tremors, Akathesias, Tardive dyskinesias and dystonias.Watch for ‘Neuroleptic Malignant Syndrome’
  35. 35. Anti-psychotic preparations available • Oral drugs – Tablets and suspensions • Injectables – Short acting( Haloperidol, zuclopenthixol acetate) or depot preparations(zuclopenthixol decanoate, fluphenazine)
  36. 36. ECTs Traditional indications are catatonic stupor and severe depressive symptoms in schizophrenia. ANTI-DEPRESSANTS AND MOOD STABILIZERS Depression is a part of the syndrome of schizophrenia. Value of use of anti-depressants is not proven, may be helpful in chronic syndrome but might worsen active psychosis. Value of lithium in treatment is uncertain. If a schizoaffective case, some benefit might be present. PSYCHOLOGICAL TREATMENT INDIVIDUAL PSYCHOTHERAPY FAMILY EDUCATION SELF-HELP GROUPS Good motivation and productivity from patient is essential
  37. 37. WORKING WITH RELATIVES working with emotional expressions within family is most beneficial BEHAVIORAL TREATMENT include ‘token economies’ and ‘cognitive behavior therapy’ (specially for positive symptoms as they are amenable to structured reasoning) SOCIAL TREATMENT REHABILITATION include social and vocational training and improvement of communication skills as the onset of the illness is at a point where they are training for skilled work. CASE MANAGEMENT (followed in US) Most consumers with severe or chronic schizophrenia will have a case manager. The role of the case manager is to assist in coordinating all the services that the consumer may need. See figure below as an example of how a case manager can work with other professionals and agencies.
  38. 38. Two different approaches to preventing schizophrenia that are currently being researched: 1. Preventative measures that are taken well prior to any measurable signs of the early phase of schizophrenia (also called the prodromal phase, in medical terms) 2. Preventative measures taken during the prodromal period of schizophrenia. (People typically show some early signs of schizophrenia well before the full development of schizophrenia). REDUCING THE CHANCE OF GETTING SCHIZOPHRENIA • Street Drugs increase risk of Schizophrenia particularly cannabis and marijuana • Enriched Educational, Nutrition and Social Environments Lower Risk of Schizophrenia • Essential fatty acid (EFA) deficiency and resulting lipid membrane abnormalities may increase risk of schizophrenia • Antioxidant Intake may reduce risks of schizophrenia and decrease side effects of medications
  39. 39. • Country life (vs. city living) before age 15 is associated with lower rates of schizophrenia REDUCING THE CHANCE OF GETTING IT AT BIRTH • Maternal infections during pregnancy are associated with increased risk of schizophrenia mostly flu • Pregnancy and baby delivery complications are associated with increased risk of schizophrenia • Season of Birth - Low Sunlight Exposure/Vitamin D is associated with higher risk of schizophrenia • Older Age of Father increases risk of Schizophrenia due to high levels of DNA damage in sperms of father • Lead and other Toxic Exposures to Pregnant Women Triples Risk of Schizophrenia for Child • X-Ray Radiation during Pregnancy may increase risk of schizophrenia for child
  40. 40. Natural course of Schizophrenia as typically described ICD 10 CLASSIFICATION -Continuous - Episodic+Progressive deficit - Episodic+Stable deficit - Episodic remittent / DSM IV CLASSIFICATION - Episodic with interepisodic residual symptoms - Episodic with no interepisodic residual symptoms - Incomplete remission - Continuous(+negative prominence) - Complete remission - Single episode+partial remission - Other - Single episode+full remission
  41. 41. Good prognostic factors : • Sudden onset • Married • Short episode • Good psychosexual adjustment • No previous history • Good previous personality • Prominent affective symptoms • Good work record • Paranoid type of illness • Good social relationships • Older age of onset • Good compliance  Poor prognostic signs : • Insidious onset • Single/separated/widow/divorced • Long episode • Poor psychosexual adjustments • Previous psychiatric history • Abnormal previous personality • Negative symptoms • Poor work record • Enlarged lateral ventricles/Male • Social isolation • Younger age at onset • Poor compliance
  42. 42. EARLY DETECTION AND INTERVENTION may contribute to lower incidence and prevalence of florid schizophrenia. These programs combine (1) early detection of psychotic features by family practitioners and other primary care providers and (2) close liaison with mental health professionals well trained in psychiatric assessment and treatment strategies effective in reducing the prevalence of established cases of schizophrenia. Long-term monitoring for signs of recurrence of these sub-threshold psychotic episodes, with further intervention as needed, appears essential to maintain these benefits. Schizophrenia Bulletin, 22(2): 271-282, 1996 Linszen D, Lenoir M, de Haan L, Dingemans P, Gersons B (1998). British Journal of Psychiatry 172 (Suppl 33): 84-89. NEWER ANTI-PSYCHOTICS are comparatively safer In 2001, Thompson's group produced the first time-lapse images revealing a wave of tissue loss rolling across the brains of schizophrenic children at the National Institute of Mental Health. first flicker of the disease -small part of the parietal cortex
  43. 43. Loss of upto 5 percent gray matter per year has been recorded compared to 1 percent per year in normal teenagers. •In 2002, Desmond Smith of the University of California, Los Angeles and his colleagues developed the technique called "voxelation" to study Parkinson's disease in a mouse model. The problem is that the trouble-making cells behind, schizophrenia, for example, could be a small group of upstarts in the brain's huge collection of specialised cells. And to make the matter worse, only a few of our 30,000 or genes may be misfiring in these cells. Smith is now dissecting brain slices for mapping. In five years, he expects to have a complete genetic map of the healthy human brain composed of 8000 voxels and a 300 voxel map of the healthy mouse brain. At the same time, they will begin developing genetic maps of abnormal brains.
  44. 44. • ADHERENCE TO TREATMENT is a special challenge for both the doctor and the patient as paranoia and lack of insight of the patient often interferes. • SIDE EFFECTS OF THE DRUGS make a person refuse treatment. • Long-acting depot preparations are available only for the older anti-psychotics. Future targets include development of intramuscular newer anti-psychotics. • Development of new drugs that act primarily on receptors other than the dopamine system • Development of community programmes that aid early detection of psychosis and protection of the rights of the mentally ill
  45. 45.  “The schizophrenic experience can be a terrifying journey through a world of madness no one can understand, particularly the person travelling through it. It is a journey through a world that is deranged, empty, and devoid of anchors to reality. You feel very much alone. You find it easier to withdraw than cope with a reality that is incongruent with your fantasy world. You feel tormented by distorted perceptions. You cannot distinguish what is real from what is unreal. Schizophrenia affects all aspects of your life. Your thoughts race and you feel fragmented and so very alone with your “craziness...” (Janice Jordan – an author)  “The worst thing about having schizophrenia is the isolation and the loneliness...”