Schizophreniahdusjhshsjksskskjsnnsjsjn.pptx

Psychiatry

1. History Emil Kraepelin (1856) He first separated organic and non-organic ( primary psychotic) He described two major groups of primary psychotic disorders: The manic depressive psychosis and dementia praecox (dementia of the young) He believed that dementia praecox was a loss of the inner unity of the activities of intellect, emotion, and volition. paranoia, catatonia, and hebephrenia were defined as subtypes of the same illness. Eugen Bleuler In 1911, he coined the term schizophrenia He proposed the name to denote a “splitting” of psychic functions, which he considered to be the core feature of the illness. His four primary symptoms (“the Four As”) were abnormal associations, autistic behavior and thinking, abnormal affect, and ambivalence. hallucinations, delusions, social withdrawal, and diminished drive were considered as secondary manifestations of the illness Thus, according to Bleuler, the most obvious and striking manifestations of schizophrenia were only “accessory symptoms.” Schizophrenia

2. Kurt Schneider identified group of symptoms that were the most characteristic of the illness.

3. Mental Status Examination General Description The appearance of a patient with schizophrenia can range from that of a completely disheveled, screaming, agitated person. Their behavior may become agitated or violent, apparently in an unprovoked manner. Waxy flexibility, once a common sign in catatonia, has become rare. Other obvious behavior may include odd clumsiness or stiffness in body movement. Patients with schizophrenia are often poorly groomed, fail to bathe, and dress much too warmly for the prevailing temperatures. PRECOX FEELING. Some experienced clinicians report a precox feeling, an intuitive experience of their inability to establish an emotional rapport with a patient.

4. Psychotic Symptoms Hallucination 5 to 8% of the general population experience hallucinations or persecutory delusions, and other reviews cite figures of up to 15 percent of the general population as hearing voices. Auditory hallucinations are the most common type, followed by visual hallucinations, and tactile (or haptic), olfactory, and gustatory hallucinations are less common. Cenesthetic Hallucinations- unfounded sensations of altered states in bodily organs. AUDITORY HALLUCINATIONS . In schizophrenia, auditory hallucinations are clearly the most common type of hallucination. ~70% Patients generally believe that their hallucinations are real manifestations of someone, somewhere, talking to them or transmitting a voice or voices. patients are often distressed and frightened, or angered by these experiences, and can have a complicated sense of guilt, depression Voices are the most common kind of hallucination and tend to be clear and understood, but unintelligible sounds of whispers or distant conversations are not rare. When it is voices that are heard, single words are probably the most common. most patients will experience a decrease in the frequency of their hallucinations or a change in the nature of their hallucinatory experience. As a person gets used to the presence of these voices, the hallucinatory voice or voices can become companions, and given the frequent social isolation that is experienced in schizophrenia

5. Command auditory verbal hallucinations violent crimes committed by people with severe mental illnesses have led to an increased popular and clinical focus on the phenomenon of command verbal auditory hallucinations. Command auditory verbal hallucinations are very common, present at some phase of the illness. the voice is believed to be a real communication from someone else, especially if there is an identity for that person voices have benevolent intentions toward the patient or the action described will help the patient. the voice has some omnipotence or other power greater than the patient. there is are adverse consequences to the patient for not complying the command is for a nonviolent action. if the hallucinatory experience is congruent with his or her delusional beliefs, the person is more likely to comply with the commands.

6. Visual hallucinations. less common than auditory hallucinations The most commonly reported are formed images of animate objects, people, or parts of people (especially heads and faces), religious images, animals. The content of auditory and visual hallucinations is often dependent on the culture of the person experiencing hallucinations Olfactory, gustatory, and tactile hallucinations 15 to 25% of people with schizophrenia. sense of bugs crawling on or under the skin (formication), are found in a variety of mental illnesses. the experience tends to be unpleasant for most patients, with the smells of rotting meat, garbage, and feces common, and the taste of blood or metal frequently described.

7. Thought Thought content Disorders of thought content reflect the patient’s ideas, beliefs, and interpretations of stimuli. The phrase loss of ego boundaries describes the lack of a clear sense of where the patient’s own body, mind, and infuence end and where those of other animate and inanimate objects begin. Delusions, the most obvious example of a disorder of thought content, are varied in schizophrenia and may assume persecutory, grandiose, religious, or somatic forms Form of thought Disorders of the form of thought are objectively observable in patients’ spoken and written language The disorders include looseness of associations, derailment, incoherence, tangentiality, circumstantiality, neologisms, echolalia, verbigeration, word salad, and mutism. Although looseness of associations was once described as pathognomonic for schizophrenia Thought process assess the patient’s thought process by observing his or her behavior. Disorders of thought process include flight of ideas, thought blocking, impaired attention, poverty of thought content, poor abstraction abilities, perseveration, idiosyncratic associations. Thought control, in which outside forces are controlling what the patient thinks or feels, is common, as is thought broadcasting, in which patients think others can read their minds or that their thoughts are broadcast through television sets or radios.

8. Violence Suicide Violent behavior (excluding homicide) is common among untreated schizophrenia patients. Delusions of a persecutory nature, previous episodes of violence, and neurological deficits are risk factors for violent or impulsive behavior. Management includes appropriate antipsychotic medication. Emergency treatment consists of restraints and seclusion. Acute sedation with lorazepam 1 to 2 mg intramuscularly, repeated every hour as needed Suicide is the single leading cause of premature death among people with schizophrenia. Suicide attempts are made by 20 to 50% of the patient and 5 to 6% of schizophrenic patients die by suicide. Factors for suicide: MDE: The most important factor is the presence of a major depressive episode; 80 percent of schizophrenia patients may have a major depressive episode at some time in their lives; greatest risk is a young man who once had high expectations, declined from a higher level of functioning, realizes that his dreams are not likely to come true, and has lost faith in the effectiveness of treatment. command hallucinations drug abuse clozapine may have particular efficacy in reducing suicidal ideation in schizophrenia patients

9. Orientation Patients with schizophrenia are usually oriented to person, time, and place. The lack of such orientation: investigate the possibility of a medical or neurological brain disorder Memory usually intact in MSE, but there can be minor cognitive deficiencies Cognitive Impairment subtle cognitive dysfunction in the domains of attention, executive function, working memory, and episodic memory. seems already to be present when patients have their first episode and appears largely to remain stable over the course of early illness. also present in attenuated forms in nonpsychotic relatives of schizophrenia patients Judgment and Insight patients with schizophrenia are described as having poor insight into the nature and the severity of their disorder. The so-called lack of insight is associated with poor compliance with treatment Reliability A patient with schizophrenia is no less reliable than any other psychiatric patient.

10. Neurological Findings . Nonlocalizing signs include dysdiadochokinesia , astereognosis , primitive reflexes, and diminished dexterity. The presence of neurological signs and symptoms correlates with increased severity of illness, affective blunting, and a poor prognosis. Other abnormal neurological signs include tics, stereotypies , grimacing, impaired fine motor skills, abnormal motor tone, and abnormal movements

11. Eye Examination patients with schizophrenia have an elevated blink rate. The elevated blink rate is believed to reflect hyperdopaminergic activity. In primates, blinking can be increased by dopamine agonists and reduced by dopamine antagonists. Speech The inability of schizophrenia patients to perceive the prosody of speech or to inflect their own speech can be seen as a neurological symptom of a disorder in the nondominant parietal lobe. Other parietal lobe–like symptoms in schizophrenia include the inability to carry out tasks (i.e., apraxia ), right–left disorientation, and lack of concern about the disorder.

12. negative symptoms The most common negative symptoms are avolition and anhedonia . Avolition is the loss of will or drive. An inability to initiate and persist in goal-directed activities. Avolition in particular seems associated with deficits in grooming and hygiene, and it seriously impairs educational and vocational progress

13. anhedonia is “Lack of enjoyment from, engagement in, or energy for life’s experiences; deficits in the capacity to feel pleasure and take interest in things. Social withdrawal is sometimes referred to as “passive or apathetic social withdrawal” and includes indifference to social relationships and decreases in the drive to socialize.

14. Affective blunting, consisting of both an inability to understand or recognize displays of emotion from others and an inability to express emotion, is an important predictor of functional impairment in schizophrenia. Blunted affect - “reduction in the intensity of emotional expression. Alogia is a decrease in verbal communication, or “poverty of speech,” and it is found in up to 25 percent of people with schizophrenia.

15. Basic assessments • Comprehensive assessment of both patients and caregivers • Complete history with information from all possible sources • Physical examination‑ record data such as blood pressure, weight and wherever indicated body mass index and waist circumference • Mental state examination • Establish diagnosis according to current diagnostic criteria • Differential diagnosis by ruling out secondary psychoses • Areas to be evaluated: symptom‑severity,symptom‑dimensions

16. Basic investigations: haemogram , blood sugars and lipid levels, liver functions, renal functions, electrocardiogram (focus on QTc ) Assessments of caregivers: knowledge and understanding of the illness, attitudes and beliefs regarding treatment, impact of the illness on them, personal and social resources Ongoing assessments: response to treatment, side effects, treatment adherence, the impact of patient’s immediate environment, disability assessments, other health‑care needs, ease of access and relationship with the treatment team

17. Additional/Optional assessments • Use of standardized rating scales to rate all aspects of the illness • Psychological testing for cognitive functions • Neuroimaging especially in those with first‑episode psychosis, neurological signs, non‑response to treatment and elderly patients

18. Genetics of Schizophrenia Family studies relatives of probands have an increased risk of developing the disorder. The risk of developing schizophrenia is higher in siblings and children of probands than in other classes of relatives, reaching a lifetime risk of 10 percent or more. a large proportion of parents display features of the extended phenotype of schizophrenia (e.g., schizotypal personality disorder).

19. high familial loading of schizophrenia with siblings showing 8- to 10-fold increased risk of developing schizophrenia compared to the rest of the population. The estimated risk of schizophrenia among the offspring of mating between two affected parents is particularly high.

20. Twin studies Twins together share many aspects of their environment. Monozygotic (MZ) twins share all of their genes while dizygotic (DZ) twins share, on average, 50 percent. a higher concordance in MZ twins implies that the disorder is, at least partly, genetic. The two methods of estimating the concordance rate are the pairwise method and the probandwise method.

21. the pairwise method, concordance is simply the number of concordant pairs divided by the total number he probandwise concordance rate is given by the number of affected co-twins divided by the number of probands. Probandwise concordance rates are preferred by geneticists as they are technically more correct and directly comparable to the population risks reported in family studies.

22. Adoption studies One disadvantge of the twin method is that there tend to be greater similarities in the environments shared by MZ twins compared to DZ twins. It is difficult to separate the contribution of factors in families because children share both genes and environment with their parents and siblings. One way to control for environmental factors is by conducting adoption studies. similarity between adopted children and their biological parents should be higher than the similarity between adopted children and their adoptive parents

23. Advances in the molecular genetics of schizophrenia Family, twin, and adoption studies have demonstrated that genetics play an important role in schizophrenia This means that 80 percent of the variation in the trait is due to variation in genetic factors. identification of risk at the level of DNA variation initially proved challenging and difficult to replicate. techniques, including GWA studies, copy number variant (CNV) analysis, and next generation sequencing

24. GWA Studies GWA studies examine common alleles throughout the genome for association with a particular trait. SNPs are highly correlated with neighboring SNPs. It is not necessary to genotype all of them in order to gain a nearly complete coverage of common variation in the genome

25. CNVs and Schizophrenia CNVs are deletions or duplications of chromosomes . The earliest report of a rare CNV associated with an increased risk of schizophrenia was a deletion on chromosome 22q11.2 to cause a severe congenital disorder described variably as Disgorger, Velo-Cardio-Facial disorder. Carriers of this CNV were shown to have up to 30 percent risk of developing schizophrenia or other psychotic disorders.

26. The first new CNV locus to be identified was NRXN1. NRXN1 codes for a cell adhesion molecule, neurexin 1, which is specific to synapses in the brain, where it mediates interactions between pre- and postsynaptic structures. It plays a vital role in the formation, maintenance, and release of neurotransmitters at synapses . All the CNVs increase the risk of developing intellectual deficit, developmental delay, autism spectrum disorders, and various congenital malformations and somatic diseases.

27. Penetrance of CNVs high risk of developing schizophrenia associated with these CNVs suggests that they could be informative for genetic counseling. The rate of CNVs in patients suffering from schizophrenia is about 5 percent. This is at least twice higher than among controls.

28. Sequencing Studies GWA studies are used to detect common variation, particularly SNPs. genotyping platforms used can also detect CNVs. these platforms will not detect rare mutations such as single nucleotide variants (SNVs) and small insertions and deletions

29. Pleiotropy An important implication of recent studies is that genetic risk does not recognize the current definitions of disease. pleiotropy with respect to diagnosis has been demonstrated for common alleles at the level of individual SNPs, genes, and the en masse effects of multiple common risk alleles. whether current diagnostic categories are the best phenotypes for future genetic studies. Aiming to understand relationships between genetic risk and clinical outcome, and to best understand pathophysiology.

30. Convergence onto biological mechanisms Results from GWA studies, CNV, and sequencing studies all point to a functionally related set of synaptic proteins involved in synaptic plasticity, learning, and memory. GWA studies and sequencing studies, the current findings offer numerous entry points for neuroscientists to probe the biological basis of schizophrenia.

31. Risk counseling It is understandable that individuals may wish to know how likely they, or their children, are to develop a psychotic illness, particularly if they have affected relatives. It may be possible to use polygenic risk scoring to stratify individuals into high, medium, and low-risk groups. increased genetic risk of developing schizophrenia may be accounted for by rare alleles of large effect and multiple common alleles of small effect.

32. RISK FACTORS FOR THE ONSET OF SCHIZOPHRENIA Genetic Risk: Indirect Evidence from Epidemiological Studies Family Studies Family studies compare the morbidity risk the proportion of affected to unaffected relatives. first-degree relatives of probands to have a higher morbidity risk for schizophrenia

33. 2. Adoption Studies biological relatives to be at a higher risk of schizophrenia than the adoptive relatives. higher rates of schizophrenia in the adopted offspring of affected mothers

34. 3. Twin Studies twin pairs are equally exposed to environmental risk factors for schizophrenia. The concordance rate for monozygotic twins was higher in twins with an early rather than a late onset of schizophrenia. higher monozygotic concordance rates for the hebephrenic subtype compared to the paranoid type.

35. Relationship to Subclinical-Psychoses Phenotypes schizotypal, schizoid, and paranoid personality disorders are found to co-occur, they have been grouped together under the Cluster A personality disorder . First-degree relatives of patients with schizophrenia find rates in the relatives of the probands that are two to four times the rates found in the control families.

36. Relationship to Other Psychotic Disorders and Bipolar Disorder possible familiar coaggregation of bipolar disorder and schizophrenia in families. schizoaffective disorder occurs at increased rates in the families of probands with schizophrenia and bipolar disorder. suggesting at least some genetic no independence. schizophrenia and bipolar disorder partly share common genetic determinants. any psychiatric disorder among first degree relatives increased the individual’s risk of schizophrenia.

37. Genetic model of liability for schizophrenia The family, adoption, and twin studies provide evidence for the involvement of a major genetic component in the liability for schizophrenia. polygenetic threshold model, which assumes that the risk of schizophrenia is due to additive effects of multiple small genes at different loci.

38. Causal Criteria for the Onset of Schizophren ia Strength of the association Dose–response relationship (biological gradient) Temporal association Consistency of findings Specificity of effect Biological plausibility Coherence Analogy

39. Risk Factors Operating during Early Development Paternal Age advanced paternal age to the risk of schizophrenia in offspring. There is a higher risk of schizophrenia (around three to four times) in the offspring of fathers who are older than 50 years, at the time of conception. increased risk of schizophrenia in younger fathers (younger than 20 years)

40. gene–environment interactions, there is a stronger association between paternal age and schizophrenia in people without a family history. advancing paternal age results in accumulation of de novo mutations in the germ cells of older fathers. advancing paternal age interferes with the deoxyribonucleic acid (DNA)-methylation process of gene expression.

41. Season of Birth Winter birth in people who later develop schizophrenia is a epidemiological finding. indicator for some seasonally fluctuating environmental factor seasonal variation in exposure to intrauterine viral infections around the time of birth, or variation in light, temperature/weather, or external toxins. higher rates of winter births in patients who developed schizophrenia later in life;

42. Pregnancy and Birth Complications some relationship between pregnancy and birth complications and the development of schizophrenia. The term pregnancy and birth complications covers a broad range of pre- and perinatal events. Pregnancy, birth, and neonatal complications do not act independently of one another; interaction effects.

43. history of fetal hypoxia was associated with increased structural brain abnormalities (reduced gray matter and increased ventricular size) among patients with schizophrenia. gene–environment correlation whereby the genetic liability for schizophrenia in the parent increases the likelihood of social adversity that is associated with obstetric complications.

44. Other Putative Prenatal Risk Factors prenatal exposure to toxoplasmosis, poliovirus, and other common respiratory infections. There may be higher rates of schizophrenia in the offspring of mothers who experienced significant levels of stress during pregnancy. Nutritional deficiency in pregnancy may also increase the risk of schizophrenia in offspring. The effect may be due to cytokines and chemokines, which mediate host response to infection. rhesus incompatibility increases the risk of developing schizophrenia; this may not be through the direct toxic effect of hyperbilirubinemia on the developing brain but rather via maternal–fetal genotype incompatibility effects

45. RISK FACTORS OPERATING DURING CHILDHOOD AND ADOLESCENCE Urban Birth and Upbringing twofold increase in risk of schizophrenia in urban as compared to rural settings. It is urban exposure prior to the onset of the disorder that seems to be more important rather than the level of exposure at the time of illness onset.

46. Migration incidence studies found a higher risk of schizophrenia in almost all immigrant groups than that in the majority population. The selective migration of people at increased risk of schizophrenia is possible. There is no difference in the age of onset in migrant groups as compared to the majority population.

47. Cannabis Use cannabis intoxication is associated with transient psychotic symptoms in some individuals. higher rates of cannabis use among patients with schizophrenia as compared with controls. controversy remains about whether cannabis is a risk factor for the development of schizophrenia or other psychotic disorders.

48. A family study of adolescents with acute psychosis found a 10-fold increase in the morbidity risk for schizophrenia in relatives of probands who tested positive for cannabis use.

49. Stressful life events and early childhood trauma excess of stressful life events in the few weeks prior to the onset of psychotic and affective disorders. threefold increased risk of psychosis in those exposed to adult life events. stressful life events over a more sustained period before the onset of psychosis. Early childhood trauma describe a range of severe adverse experiences including sexual, physical, and emotional abuse, and neglect. psychotic experiences and psychotic disorder is increased almost threefold in those exposed to early childhood trauma.

50. Premorbid vulnerability indicators/markers Premorbid Indicators: Early Developmental Abnormalities individuals who develop schizophrenia as adults are more likely to manifest motor/language, cognitive abnormalities during childhood and adolescence. delays in attainment of developmental milestones for children, who later develop schizophrenia. severe motor/language abnormalities tend to predict an earlier age of onset for schizophrenia. motor abnormalities may be markers of underlying genetic liability.

51. developmental cognitive alterations similarly reflect the influence of genetic factors associated with schizophrenia. the children who later develop schizophrenia are more likely to show signs of social maladjustment. for example, poor relationships with other children, social isolation, lone play, and social anxiety as compared to their peers. Developmental abnormalities may be most useful as a possible measurable indicator of genetic liability for schizophrenia.

52. Premorbid Indicators: Psychopathology/Vulnerable Mental States Childhood Psychiatric Disorders significant psychopathology prior to adult onset psychosis. adult schizophreniform disorder, which was preceded by a number of different childhood disorders, including anxiety, depression, conduct/oppositional disorder, and attention-deficit/hyperactivity disorder (ADHD).

53. Subclinical Psychotic Experiences subclinical psychotic experiences may be vulnerability markers (or even precursors) for the later development of psychotic disorders. delusional beliefs and hallucinatory experiences at the age of 11 years would predict schizophreniform psychiatric disorder 15 years later . impairments in motor, language, and cognitive ability, suggesting that the pervasive and persistent psychotic experiences may be indicators of an underlying ongoing psychotic process, reflecting increased genetic liability.

54. a positive predictive of around 40 percent for persistent subclinical symptoms to estimate onset of future psychotic disorders.

55. Risk Factor for the Persistence of Schizophrenia strong evidence that childhood cognitive ability is associated with outcome; lower intelligence has been shown to predict unfavorable clinical and functional outcomes. high familiar morbidity risk for schizophrenia, obstetric complications, and early developmental abnormalities, which are strongly associated with a negative symptoms , insidious onset, unremitting course, and functional deterioration, which are strongly linked to the neurodevelopment model of schizophrenia

56. familiar morbidity risk of affective disorder, adverse life events, and migrant status, which have less specific association with the schizophrenia syndrome and whose clinical correlates suggest less prominent negative symptoms, acute onset, remitting course, and better functional outcomes, which may be linked to a mechanism of social stress sensitivity.

57. Empirically based model of schizophrenia The lack of a sufficiently validated operational definition for schizophrenia . The disorder has a complex time course with a broad range of age of onset. The most common course pattern is episodic (single or multiple), with delusions and hallucinations being prominent symptoms. these symptoms are also relatively prevalent in the general population.

58. risk factors for schizophrenia probably operate throughout the life course, perhaps even prior to birth. static unidirectional cause–effect linear association mediated by the complex interplay of environmental and biological risk factors that are continuously distributed in the general population.

59. Neurodevelopmental Model of Schizophrenia schizophrenia is the behavioral outcome of early brain development, the full effect of which is not manifest until adolescence or early childhood. Children who later develop schizophrenia also have higher rates of minor physical anomalies, indicative of disruption of ectoderm development. absence of inflammatory reactions in the brains abnormal neuronal migration during corticogenesis

60. reduced neuronal size, spine density in the cortex and hippocampus. There is generally a long latency period between exposure to known risk factors and onset to schizophrenia.

61. Integrated Model of Schizophrenia Socio environmental risk factors in the etiology of schizophrenia . Neuro developmental model is extended to, and combined with, socio developmental, cognitive, neurobiological, G × E, and epigenetic hypotheses. exposure to trauma during childhood may lead to the development of negative schematic beliefs and, thereby, predispose individuals to a paranoid way of thinking, sensitized dopamine system, may increase liability to psychotic disorder. susceptibility genes for schizophrenia may have specific developmental correlates that influence brain development across the life course

62. Epigenetic aberrations may originate from three sources acting individually or in combination: (1 ) inherited through the germline (2) influence of environmental factors acting across different developmental stages (3) generated via biological events. Such epigenetic modification of DNA and chromosomal proteins may have a significant impact on regulation of gene expression via neurochemical changes rather than the structural changes to the brain.

63. Cellular and Molecular Neuropathology of Schizophrenia Cytoarchitectural changes Whole Brain Reduced prefrontal and temporal lobe volumes in individuals with high genetic load for developing schizophrenia. Gray matter volume reductions may be progressive in the initial stages of the illness. changes in cellular morphology in the prefrontal cortex (PFC), thalamus, and medial temporal lobe

64. different types of glia may play roles in schizophrenia pathology. enlargement of the third and lateral ventricles in subjects with schizophrenia. Family studies show that enlarged ventricular volume is also found in unaffected relatives who share genetic material

65. Prefrontal Cortex prominent deficits in certain cognitive functions that depend on the PFC. prefrontal lobe volume is reduced in schizophrenia. neuronal loss in the PFC with no evidence of change in glial numbers. gray matter that has been found to be approximately 3 to 12 percent smaller in schizophrenia

66. Hippocampal Formation Reductions in hippocampal or amygdala-hippocampal volumes in schizophrenia that may be lateralized to the left side. Smaller hippocampal volumes have been shown to be present at the time of disease onset. reduced hippocampal volumes can be identified at the beginning of the illness. reduced number and smaller size of neurons in the entorhinal cortex.

67. Thalamus In the mediodorsal nuclei, total neuronal counts are decreased. reductions in neuron number are reported to be in the parvocellular and densocellular parts. Basal Ganglia volumetric increases of the caudate– putamen complex in schizophrenic patients. increase in the number of synapses in the caudate and putamen, suggesting increased neuronal activity in the basal ganglia.

68. White matter changes in schizophrenia The white matter comprises axons and their myelin sheaths and glial cells, together comprising about half of the brain by volume. increases in both gray and white matter with the majority of myelination occurring within the first few years of life. decrease in oligodendrocyte pathway–related genes.

69. NRG signaling is involved in nervous system development by modulating a wide array of processes, including glial differentiation, axonal–glial signaling, and myelination. decrease in oligodendrocyte number Brodmann areas 9 and 24 along with abnormal oligodendrocyte morphology.

70. decreases of myelin associated genes, myelin-associated glycoprotein (MAG), myelin and lymphocyte protein (MAL) Astrocytes play an important role in the synaptic metabolism of neurotransmitters such as glutamate, γ aminobutyric acid (GABA), and monoamines, and could contribute to synaptic dysfunction in schizophrenia.

71. Dopamine hyperdopaminergic activity may be responsible for the positive symptoms in schizophrenia. blockade of dopamine receptor subtype 2 reduced psychotic symptoms. reduction in dopamine transmission in the PFC was associated with cognitive deficits such as those found in schizophrenia.

72. dopaminergic hyperactivity in subcortical regions, but hypoactivity in prefrontal cortical regions. D1 expression in the PFC and striatum have been largely negative. D3 receptor expression was found to be increased in the ventral striatum

73. Glutamate Brain regions repeatedly implicated in the pathophysiology of schizophrenia include the PFC, hippocampus, and thalamus. The major connections between these brain regions are glutamatergic. Glutamate is the major excitatory amino acid neurotransmitter in the brain and is known to activate both ionotropic and metabotropic glutamate receptors. Among the mGluRs in schizophrenia, mGluR2 and 3 have been implicated in schizophrenia in animal and human models of schizophrenia.

74. γ- Aminobutyric Acid GABAergic involvement is found in reduced expression of presynaptic markers in subpopulations of interneurons in cortical brain regions. Increased GABAA receptor binding has been reported in the prefrontal and cingulate cortices and the hippocampus. GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD).

75. reduced synthesis and reuptake of GABA in these neurons and, thereby, altered GABAergic transmission at the chandelier cell– pyramidal cell synapses GABA neurons involved in dendritic spine formation, is also decreased in the PFC and hippocampus in schizophrenia.

76. Acetyl Choline decreased levels of nicotinic and muscarinic receptors are reported in the hippocampus, frontal cortex, thalamus, and striatum in schizophrenia. cholinergic neurotransmission is known to be integral to cognition and memory, functions disrupted in schizophrenia. Decreases in M1 and M4 receptors have been reported in the PFC and striatum in schizophrenia. cholinergic dysfunction in schizophrenia.

77. Neuronal Migration and Neurogenesis During the second trimester of fetal development, neurons migrate upward from the ventricular wall to their target cortical layer. Initial postmortem studies in cortical tissue from schizophrenic individuals found ectopic neurons and abnormal cytoarchitecture in the PFC and entorhinal cortex. impairment of neuronal migration of these particular cells into the cortex during their critical developmental period (second trimester) in schizophrenia .

78. Spinogenesis and Pruning Adult schizophrenia subjects have fewer synaptic connections in specific brain regions cortical synaptic density reaches a maximum at 2 to 4 years of age when it is about double adult levels, with reduction in the number of synapses (synaptic pruning) toward adult levels occurring mainly during adolescence. schizophrenia is a defect of excessive pruning during adolescence. reduced spine density in certain brain regions in schizophrenia could be related to altered development and stabilization of dendritic spines.

79. Myelination Myelination is critical for the proper axonal conductance and communication between brain regions. The first 2 years of life the rapid myelination of axonal fibers that continue into adulthood following a region-specific course. In the PFC,, myelination occurs well into the second decade of life. abnormalities in myelin-related genes are observed in schizophrenia.

80. Risk Genes Schizophrenia is a highly heritable and polygenic illness. role of a large number of common alleles of small effect size and rare CNVs of large effect size in schizophrenia.

81. Epigenetics Modification of the chromatin structure of DNA is associated with reversible modifications of DNA rather than with inherited variability within the DNA sequences and is called epigenetic modification. Epigenetic regulation of chromatin can occur via several mechanisms including processes such as DNA methylation and posttranslational modifications of histones.

82. Environmental factors can also influence epigenetic changes and, of relevance to schizophrenia, maternal malnutrition, certain intrauterine conditions, and viral infections, can lead to hypermethylation of DNA.

83. Structural Brain Imaging in Schizophrenia

84. Computed Tomographic Studies enlarged lateral ventricles in schizophrenia . Magnetic Resonance Imaging Studies MRI became the most powerful tool for visualizing soft tissue contrast in the brain (e.g., gray and white matter). MRI has no known adverse effects, with only a few contraindications. Diffusion Tensor Imaging Studies Diffusion tensor imaging (DTI) is a relatively new imaging technology for evaluating brain structure. Prior to the advent of DTI, it was difficult to characterize white matter abnormalities in schizophrenia because white matter appears uniform and homogeneous in conventional MR scans.

85. Mr findings in schizophrenia deficits in the medial temporal lobe volumetric reductions in medial temporal lobe structures, most notably in the amygdala, hippocampus, parahippocampal gyrus and proximal neocortical areas. third ventricle enlargement parietal lobe volume reduction frontal lobe volume reduction occipital lobe volume reduction thalamus and cerebellar volume reduction Basal ganglia showed abnormalities

86. Chronic Schizophrenia impairments in face recognition (fusiform gyrus and amygdala) hallucinations (STG), deficit and nondeficit symptoms (prefrontal cortex) impairments in social cognition (anterior cingulate) language disturbances (medial temporal lobe measures) formal thought disorder (STG, posterior temporal lobe)

87. volume decrease over time, especially in white matter. Cortical surface measures deconstruct global cortical volume into two primary components: cortical thickness and cortical surface area decreased gyrification commonly observed in frontal, temporal, and parietal cortices, as well as in multiple subcortical structures and the cerebellum.

88. Summary MRI has proven to be an extremely powerful tool in identifying structural abnormalities in schizophrenia. Differences in cortical and subcortical structures are reported at all stages of the disorder. the majority of evidence points to schizophrenia being a neurodevelopmental disorder. lack of loss of neurons, and lack of gliosis, would all tend to suggest that schizophrenia is not a neurodegenerative disorder

89. The Application of DTI to Schizophrenia With DTI, it is now possible to characterize white matter abnormalities in schizophrenia. involvement of oligodendrocytes, the neural cells that provide protection to axons and improve communication between brain areas, in the pathophysiology of schizophrenia. white matter fiber tract abnormalities in schizophrenia, particularly in frontotemporal tracts

90. neurobiological nature of white matter changes in schizophrenia (1) axonal and/or myelin integrity disruptions caused by either disease itself, medications, or other environmental factors (2) orientation/coherence disruptions likely associated with neurodevelopmental factors (3) genetically programmed age-/development-related abnormalities affecting axonal growth and maturation (4) cell/axonal density abnormalities originating from faulty pruning (5) neuroinflammation that would be associated with psychosis onset.

91. Functional Brain Imaging in Schizophrenia

92. Blood Oxygenation Level–Dependent Imaging The technique relies on magnetic susceptibility effects of deoxyhemoglobin, which cause regional signal decreases in imaging sequences that are sensitive to susceptibility. The increase in image intensity corresponds to a local decrease in deoxyhemoglobin.

93. Arterial Spin Labeling magnetization tagging of endogenous arterial water to determine perfusion of brain tissue by comparing images obtained with and without labeling of the arterial supply.

94. Major Findings in fMRI Studies in Schizophrenia Cognition greater impairment in executive functions and in learning and memory. These deficits have been related to frontotemporal systems. Abnormal activations in ventromedial and superior temporal lobe, prefrontal cortices, and limbic structures were documented with memory and executive tasks. Verbal learning deficits are well established in schizophrenia. decreased activation of the frontal cortex, especially the inferior prefrontal region.

95. frontal lobe function , deficits in working memory and cognitive control in schizophrenia. language-processing tasks to examination of the hippocampus and parahippocampal gyrus and evaluating long-term memory. functional neuroimaging studies in schizophrenia have revealed abnormalities in both frontal and temporal activities. reduced temporal– dorsolateral prefrontal cortex connectivity in schizophrenia could underlie encoding deficits

96. Emotion. Social cognition, the cognitive processes involved in perception, interpretation, and processing of social information, is core domain of deficit in schizophrenia. limbic response in identification of facial emotions is diminished response in schizophrenia. increased amygdala activation for fear was associated in patients both with failure to identify the emotion and with more severe flat affect

97. Impaired emotional functioning is a prominent feature of schizophrenia. decreased activation in left amygdala and bilateral hippocampus for the emotion condition. Activity in left amygdala correlated with positive symptoms. abnormal activation in patients’ ventral striatum and amygdala and increased tonic activation of the amygdala. abnormal activation of amygdala is the disruption of memory processes. There is considerable evidence that the amygdala interacts closely with the hippocampus in the formation of episodic memory.

98. Molecular Brain Imaging in Schizophrenia Molecular imaging techniques include PET, SPECT, and fMRI . These are all functional brain imaging techniques to visualize the metabolism and other physiological processes in the living brain.

99. Molecular Imaging of Dopamine in Schizophrenia Estimation of the Binding of Dopamine D2 -Like Receptors. binding of D2 -like receptors is typically made by a single PET or SPECT scan at high specific activity to measure the so-called binding potential (BP). Estimation of Absolute Dopamine D2 -Like Receptor Density two PET scans have the unique ability to measure absolute receptor density .

100. Dopamine Precursor Estimates. Dopamine precursor measures using [ 18F] fluorodopa or [ 11C] dopa were among the first markers of dopamine neurotransmission. Measuring Intrasynaptic Dopamine Molecular Imaging after Dopamine Depletion

101. Molecular Imaging of Serotonin in Schizophrenia Estimation of the Density of the Serotonin 5-HT2A Receptors postmortem studies have suggested decreased 5-HT2A binding in the prefrontal cortex decreases in prefrontal cortex in drug-naive schizophrenic patients Estimation of the Density of Serotonin 5-HT1A Receptors increases in binding in multiple brain regions, including medial temporal cortex using PET postmortem studies, which suggest increases in 5-HT1A in cortical areas.

102. Estimation of the Density of the SERT. postmortem studies have shown decreases in SERT in frontal cortex and in cingulate cortex.

103. Molecular Imaging of Cholinergic Receptors in Schizophrenia Estimation of the Density of Muscarinic Acetylcholine Receptors. muscarinic acetylcholine receptor system using SPECT and antagonist of muscarinic receptors, has shown a very marked decrease of mAChR in schizophrenia Estimation of the Density of Nicotinic Acetylcholine Receptors. decreases in nicotinic acetylcholine receptors (nAChRs) observed in postmortem studies are also observed with PET imaging. So high prevalence of smoking among patients with schizophrenia

104. Molecular Imaging of Histamine H1 Receptors in Schizophrenia Molecular imaging with doxepin has shown reductions of BP values for H1 receptors in the frontal and prefrontal cortices and the cingulate gyrus among patients with schizophrenia.

105. Molecular Imaging Studies of the Glutamate System in Schizophrenia reductions of glutamate that lead to negative symptoms. blockade of the NMDA receptor by glutamate antagonist may precipitate positive symptoms of schizophrenia, as has been shown by the administration of ketamine to humans. Blockade of the NMDA receptors by glutamate antagonists may precipitate positive symptoms of schizophrenia and produce DAR in the lateral prefrontal and the anterior cingulate cortex

106. Neurocognition in Schizophrenia

107. Neurocognition as a Core Feature of Schizophrenia The severity of this impairment is greatest in the domains of memory, attention, working memory, problem solving, processing speed, and social cognition. These deficits are present prior to the initiation of antipsychotic treatment. Neurocognitive deficits are better able to explain important functional outcomes such as work performance and independent living than positive or negative symptoms.

108. Profile and Magnitude of Neurocognitive Impairment Associated with Schizophrenia Attention/Vigilance Vigilance refers to the ability to maintain attention over time. A standard vigilance test used in many studies is the Continuous Performance Test (CPT). This type of CPT reveals moderately severe vigilance impairments in patients with schizophrenia. Impairments in vigilance can result in difficulty following social conversations and an inability to follow important instructions regarding treatment, therapy, or work functions. social deficits, community functioning, and skills acquisition.

109. Verbal Learning and Memory Verbal memory functioning includes abilities associated with learning new information, retaining newly learned information over time, and recognizing previously presented material. The tests used to measure learning typically involve the ability to learn lists of words or written passages. patients with schizophrenia can recall only about five. Patients are also impaired in recalling more engaging verbal material, such as stories. people with schizophrenia forget more verbal material that they have learned

110. Visual Learning and Memory Most tests expose subjects to one or more verbal figures and require the subjects to draw them from memory or to indicate which among an array of figures was previously presented. visual information is not as easily expressed as verbal information

111. Reasoning and Problem Solving most well-known test in schizophrenia is the Wisconsin Card Sorting Test (WCST). patients are given a deck of cards with various numbers of colored shapes on them and are asked to match their cards to four “key” cards that also have shapes on them that differ by color, form (i.e., shape), and number. The first principle to which the subject needs to learn to sort the cards is color. the very poor performance of patients with schizophrenia on the WCST . the reduced activity of the dorsolateral prefrontal cortex during performance of this test led to hypothesis of frontal hypoactivation in schizophrenia.

112. WCST measures a variety of neurocognitive functions including vigilance as well as visual memory and is not a “pure” measure of executive functions. Patients with schizophrenia who are impaired on measures of reasoning and problem-solving often have difficulty adapting to the rapidly changing world around them.

113. Speed of Processing Many neurocognitive tests require subjects to process information rapidly and can be compromised by impairments in processing speed. A standard example of this type of task is the Wechsler Adult Intelligence Scale Digit Symbol Test. Each numeral (1 through 9) is associated with a different simple symbol. Subjects are required to copy as many of the symbols associated with the numerals as possible in 120 seconds.

114. brief measures of processing speed have a very important role in characterizing relevant aspects of neurocognitive impairment. Psychomotor slowing has the potential to affect many different aspects of everyday life as well as hampering performance on many other cognitive testing measures.

115. Verbal Fluency Most of tests of verbal fluency measure either phonological fluency (also referred to as letter fluency) or semantic fluency. Phonological fluency refers to a patient’s ability to produce as many words as possible beginning with a particular letter (e.g., “F”) within, for instance, 60 seconds. Semantic fluency refers to the ability to produce words within a particular meaning-based category, such as “animals. Impaired verbal fluency can damage functioning in social and vocational settings by making communication difficult and awkward.

116. Immediate/Working Memory Immediate memory refers to the ability to maintain a limited amount of information “online” for a brief period of time. digits forward is an example of immediate memory. Working memory is a core component of the neurocognitive impairment in schizophrenia and is related to functional outcomes. variety of other neurocognitive domains impaired in schizophrenia, such as attention, planning, memory, and intelligence. neural circuitry that includes prefrontal cortical regions mediates aspects of working memory functions, and that this circuitry may be impaired in schizophrenia.

117. Social Cognition Theory-of-mind skills and social and emotional perception have been focus on social cognition in schizophrenia. Theory-of-mind is the ability to infer about another’s intentions and/or to understand the mental states of others. Individuals with schizophrenia perform poorly on measures of theory-of-mind abilities. facial affect recognition suggest that individuals with schizophrenia have stable deficits on tests of facial affect perception compared with healthy controls.

118. Tests of social cue perception use more dynamic stimuli that require multiple sensory modalities, such as watching videotapes of persons interacting. social cognition is more strongly related to social impairments in schizophrenia. neurocognitive impairment and social deficits is almost entirely mediated by impairments in social cognition.

119. Prevalence of Neurocognitive Deficits in Schizophrenia About 15 percent of patients with schizophrenia are rated as “unimpaired” by clinical neuropsychological assessment. neurocognitive impairment is a core feature of the illness. neurocognitive impairment interferes with the everyday lives of patients in many important ways, from limiting social relationships to reducing the likelihood of employment.

120. NATURAL HISTORY OF NEUROCOGNITIVE IMPAIRMENT In most patients, detectable deficits may be present in childhood, followed by a decline in neurocognitive function that occurs sometime prior to the first episode. many individuals with schizophrenia demonstrate no obvious neurocognitive deficits prior to the onset of psychosis.

121. The Genetics of Neurocognition in Schizophrenia First-degree relatives of individuals with schizophrenia are impaired on a variety of neurocognitive measure. overall intelligence quotient (IQ) and working memory demonstrating phenotypic correlations with the presence of schizophrenia that appear slightly higher than other aspects of neurocognition.

122. Deficits in Children at Risk for Schizophrenia attention deficits can predict which children will develop schizophrenia in the future. Low educational test scores in verbal, nonverbal, and mathematics at all ages assessed were significant risk factors. neurocognitive functions are significantly impaired in adolescents who are later hospitalized for schizophrenia.

123. Prodrome “ultrahigh” risk for schizophrenia by virtue of their family history of schizophrenia in a first-degree relative. olfactory identification and verbal memory deficits may help predict which individuals at ultrahigh risk will develop schizophrenia. cognitive impairments are present at the time of the detection of prodrome

124. Positive Symptoms Those patients who have more intact neurocognitive abilities may be better able to recall and express their internal state including detailed delusions and hallucinations. significant correlations of positive symptoms with working memory, source monitoring, and auditory distractibility

125. Negative Symptoms tests of verbal fluency and the negative symptom of “poverty of speech” both measure the level at which a patient generates speech. Deficient motor skills are represented in both the negative symptom and the neurocognitive dysfunction domain. impaired motor skills lie at the core of negative symptoms in schizophrenia. pupillary response can measure engagement in a task. If the neurocognitive deficits of schizophrenic patients were due to lack of interest or motivation, their pupillary response would be low throughout the period of neurocognitive assessment.

126. neurocognitive deficits may cause reduced motivation or the appearance of reduced motivation.

127. Formal Thought Disorder Deficits in semantic memory may lie at the heart of the neurocognition– thought disorder relation. severity of the impairment of the “semantic network” in schizophrenic patients, predicted the severity of their formal thought disorder. patient’s inability to have verbal information available (referred to as semantic priming) may be the most important neurocognitive factor in formal thought disorder. deficits in working memory and attentional focus.

128. Affective Symptoms many patients with schizophrenia also report depressed mood if not a full depressive disorder, and since depression is associated with some neurocognitive impairment. Higher depression scores are significantly correlated with poorer verbal memory, which remains even when psychomotor retardation and processing speed performance.

129. Relationship of Neurocognitive Impairment to Functioning Neurocognitive impairments are also correlated with deficits in the performance of specific skills critical for independent living. The three types of functional outcome that most studies of neurocognitive deficits have examined are community (social and occupational) outcome the ability to solve simulations of interpersonal interactions psychosocial rehabilitation programs.

130. Neurocognitive Impairment and Unemployment Patients enrolled in competitive employment show superior performance of working memory, sustained attention, problem solving, and episodic memory when compared to unemployed patients. neurocognitive performance plays a more important role than clinical symptoms in the ability of patients with schizophrenia to work and in the ability to benefit from work support programs.

131. Neurocognitive Impairment and Quality of Life Reductions in quality of life are more strongly associated with neurocognitive deficits than other symptomatic features of the illness. more severe executive and memory deficits are related to decreased use of coping mechanisms. Quality of life is often defined by the quality of a person’s social, occupational, and interpersonal aspects of life, all of which are related to neurocognitive functioning.

132. Neurocognitive Impairment and Relapse Prevention Decreased medication compliance in schizophrenic patients has been shown to be related to poor performance on tests of attention and visual memory. Neurocognitive functions have been shown to be the strongest predictors of patients’ ability to manage medications. memory impairment was the strongest predictor of partial compliance.

133. Neurocognitive Impairment and Medical Comorbidity Neurocognitive deficits related to organization (such as reasoning and problem solving) directly affect patients’ ability to seek treatment of medical problems. neurocognitive impairments directly affect new-onset medical problems in older patients.

134. Impact of Antipsychotic Treatment on Neurocognition Larger doses of conventional antipsychotics cause lethargy, somnolence, and extrapyramidal symptoms, all of which impair neurocognition. anticholinergic medications that are used to control side effects cause additional neurocognitive impairment. “atypical” antipsychotic treatments provide greater neurocognitive benefit to patients with schizophrenia than first-generation antipsychotics

135. Cognitive Remediation neurocognitive remediation produces moderate improvements in neurocognitive performance and, when combined with psychiatric rehabilitation, also improves functional outcomes. neurocognitive improvement in schizophrenia will be an enhanced neuroplasticity, which is often experience dependent. A variety of cognitive remediation programs have been developed to address neurocognitive deficits in schizophrenia

136. Psychiatric Rehabilitation Psychiatric rehabilitation uses three basic approaches: creating opportunities, providing supports, and increasing skills. People with mental disorders have always been discriminated against, stigmatized, and treated unfairly in nearly every society. Psychiatric rehabilitation aims to increase opportunities for normative housing, education, employment, socialization, leisure. The second basic approach to psychiatric rehabilitation is to provide intensive supports. People with mental illness often need extra supports to succeed initially in functional roles.

137. HOUSING FIRST Homelessness and Housing people become homeless, repeatedly hospitalized, and incarcerated because of severe mental illness, poor treatment, or a combination of both. schizophrenia complicated by poverty and drug addiction, need safe housing, supports, and treatment. Housing First has emerged as the most prominent model of supported housing. Housing First integrates housing assistance with assertive community treatment, intensive case management, or some other team based approach to comprehensive services.

138. Individual placement and support Individual Placement and Support (IPS), also known as evidence-based supported employment, emphasizes the patient’s personal preferences for work, a rapid job search , and individualized supports as needed. IPS emphasizes regular jobs in the competitive labor market, owned by the employee rather than the rehabilitation program, paid at or above minimal wage, and supervised by the employer.

139. Several features of IPS Zero Exclusion Supported employment services are available for anyone who wants to work, regardless of symptoms, cognitive impairments, work history, substance use, or other personal characteristics. (2) Competitive Employment The great majority of patients who seek work want competitive employment, particularly if they are encouraged to believe that they can work. (3) Rapid Job Search Rapid job search typically results in finding a first job within 4 months.

140. (4) Systematic Job Development targeted job development to help find jobs that match people’s skills and preferences. ( 5) Integration of Rehabilitation and Mental Health Treatment Supported employment should be an integral component of mental health treatment (6) Patient Preferences Services are based on patients’ preferences and choices. ( 7) On-going Support The multidisciplinary team provides a range of supports over time, with greater intensity as needed during times of crisis.

141. (8) Individualized Benefits Counseling Many patients who receive disability, welfare, or other benefits fear they could lose these benefits if they work.

142. Technology Use among People with Schizophrenia 80 to 94 percent of people with schizophrenia access the internet regularly, use email, and make good use of social networking websites, online forums, chat rooms, and blogs. Mobile-cellular technology is pervasive—one of the fastest adopted technologies in human history. Web-Based Interventions People with schizophrenia, their family members, and their supporters can access a range of resources on the internet

143. Coping with Voices, a self directed web-based Cognitive Behavioral Intervention, addresses the functional impact and distress caused by auditory hallucinations. Schizophrenia Online Access to Resources (SOAR) is a multifamily intervention for people with schizophrenia and their supports. The key elements of the SOAR intervention include empathic engagement of users, education about illness and treatments, and use of coping strategies. SOAR offers three therapy forums: one for people with schizophrenia, one for support persons, and one for both groups.

144. The HORYZONS system is an online platform developed for long-term recovery of people experiencing a first episode of psychosis. The system delivers several evidence-based and interactive psychosocial interventions and facilitates a moderated online peer-to-peer social networking environment Mobile Health Mobile devices can support the delivery of healthcare in a variety of formats, enabling patients and providers to send and receive calls and text messages, access websites, provide clinical decision support.

145. FOCUS, the first smart phone intervention specifically designed for people with schizophrenia. The FOCUS system can be activated to prompt users multiple times a day with questions about their symptoms, social functioning, mood, medication adherence, and sleep, which appear on the devices touch screen. Patients who used FOCUS experienced significant reduction in symptoms of psychosis, general psychopathology, and depression.

146. Short Message Service (SMS) or text messaging or approaches have also been used to support psychiatric rehabilitation with patients with schizophrenia. Mobile Assessment and Treatment for Schizophrenia (MATS) is a mobile phone intervention employed to administer questions in the areas of medication adherence, social functioning, and management of auditory hallucinations

147. Virtual Reality. Virtual reality (VR) refers to multimedia techniques in which individuals engage in computer-generated scenarios on a computer screen or head-mounted stereoscopic display that creates a highly immersive 3D environment. VR has been used primarily to facilitate exposure therapy for people with anxiety disorders, but several studies have demonstrated its potential utility in supporting rehabilitation for people with psychosis.

148. Medical Health in Schizophrenia Medical causes of excess mortality in schizophrenia Cardiovascular Disease persons with schizophrenia have an increased prevalence of all key modifiable cardiovascular and metabolic risk factors, including obesity, smoking, hypertension, dyslipidemia, and hyperglycemia.

149. Diabetes Mellitus The prevalence of type 2 diabetes mellitus is substantially higher in individuals with schizophrenia. prevalence estimates ranging from two to four times higher. hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system may contribute to at least acute hyperglycemia drug-naive schizophrenia patients.

150. Infectious Disease infectious disease remains a substantial cause of mortality for persons with and without schizophrenia. the rate of human immunodeficiency virus (HIV) infection has been estimated at 3 percent in patients with a severe mental illness. higher incidence of tuberculosis among patients with schizophrenia.

151. Cancer increased risk of cancer associated with schizophrenia. reduced incidence of multiple types of cancer in the first degree relatives of schizophrenia patients. Obesity- and smoking-related cancers have previously been reported to be more prevalent in schizophrenia patients.

152. Pulmonary Disease Chronic Lower Respiratory Disease, including COPD, is the third leading cause of death. Increased abdominal adiposity, seen in many patients with schizophrenia, can contribute to the risk of COPD. Oral health in schizophrenia People with schizophrenia have poor dental health. patients with schizophrenia brush their teeth irregularly, leading to functional difficulties such as difficulty with chewing and eating

153. Modifiable risk factors in patients with schizophrenia Overweight and Obesity Increased adiposity is associated with increased morbidity and mortality from hypertension, dyslipidemia, type 2 diabetes mellitus. Obesity is roughly twice as prevalent in people with schizophrenia, in comparison to the general population. certain antipsychotics with clinically significant antagonism for histamine (H1) receptors, and to a lesser extent, α1-adrenoceptors, can increase risk of weight gain.

154. Hypertension Schizophrenia patients are about twice as likely to have hypertension as are members of the general population. rate of hypertension in schizophrenia patients range from 19 to roughly 47 percent. Increased adiposity and insulin resistance are associated with increased sympathetic nervous system activity and sodium retention, both of which can increase the risk of hypertension.

155. Dyslipidemia antipsychotic medications are associated with clinically significant increases in serum lipid concentrations. Insulin Resistance and Hyperglycemia The prevalence of insulin resistance in patients with schizophrenia has been estimated at 1.5 to 2 times the prevalence in the general population. Hyperglycemia in schizophrenia is common. insulin resistance to pancreatic β-cell failure and related hyperglycemia can progress to incident type 2 diabetes mellitus

156. Antipsychotics increase risk of insulin resistance and hyperglycemia in patients with schizophrenia. Metabolic Syndrome Antipsychotic medications are associated with risk of metabolic syndrome to differing degrees, again generally in proportion to their risk for weight gain. Smoking and Substance Abuse Cigarette smoking is a well-known risk factor associated with all the major disease.

157. over 70 percent of individuals with schizophrenia have a lifetime history of daily smoking. The co-occurrence of substance use, including nicotine, alcohol, marijuana, and other drugs is highly prevalent among individuals with schizophrenia. In patients with schizophrenia, substance-use disorders exacerbate the risk of medical comorbidities .

158. Recovery in Schizophrenia Recovery from chronic medical conditions usually results from: ► Being able to maintain self-image and have hope ► Being able to maintain wellness and responsibility for self-care ► Being able to do things that make life meaningful ► Being able to replace professional supports with natural supports.

159. Recovery “Mental Health Recovery is a journey of healing and transformation enabling a person with a mental health problem to live a meaningful life in a community of his or her choice while striving to achieve his or her full potential.”

160. Assertive Community Treatment (ACT) ACT is a comprehensive, individualized approach to delivering care for people whose functional impairments traditionally from chronic psychosis prevents them from effectively navigating their lives and health care.

161. Supported Employment (SE) SE’s core principles include obtaining competitive employment. employment has been associated with reduction in outpatient psychiatric treatment and improvement in self-esteem.

162. Cognitive-Behavioral Therapy (CBT) It has significant effect size for decreasing positive symptoms. CBT techniques to target psychotic symptoms include belief modification, focusing/reattribution, and normalizing psychotic experiences in context that client identifies specific symptoms that s/he would like to address.

163. Cognitive Remediation Cognitive Remediation, also known as cognitive training and cognitive rehabilitation, is “a behavioral training based intervention that aims to improve cognitive processes (attention, memory, executive function, social cognition, or metacognition ) with the goal of durability and generalization,”

164. Family Psychosocial Intervention Family Psychosocial Intervention to reduce high levels of criticism, hostility, or over involvement is promoted given people with schizophrenia from families with high expressive emotions have more frequent symptom relapses. illness education and associated coping skills training, crisis intervention, and emotional support for at least 6 to 9 months for clients who have ongoing contact with their families.

165. Housing First (HF) HF’s foundation is that permanent housing is a basic human right to be provided in tandem with a psychiatric rehabilitation approach that values client choice. Illness Self-Management Training Psychoeducation entails education about the nature of schizophrenia including its associated symptoms, the principles of the stress–vulnerability model, and treatment modalities along with their associated risks and benefits.

166. Wellness Recovery Action Planning (WRAP) WRAP is a peer-led, self-management intervention program for chronic mental health conditions. WRAP intervention has been associated with psychiatric symptom reduction and improvement in physical health, quality of life measures, and Recovery-orientated perspectives such as hopefulness.

167. Integrated Schizophrenia and Substance Use Disorder Treatment Models The founding principle of integrated care is a multidisciplinary team that contains both mental health and substance use specialists who provide coordinated mental health and substance use care for all aspects of the client’s life.

168. Motivational Interviewing (MI) MI’s aim is to resolve ambivalence as the means to stimulate behavioral change. Its elements include rapport building, reflective listening, assessing client’s motivation for change through use of open-ended questions, highlighting client’s change-related statements and efforts, demonstrating gap between baseline and desired behaviors, soliciting permission prior to providing assessment or recommendations, utilizing resistance as prompt to alter approach

169. Electroconvulsive Therapy (ECT) ECT is indicated for the treatment of schizophrenia when antipsychotic therapy has not been associated with a beneficial response. Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) rTMS is also recommended for acute treatment of auditory hallucinations when antipsychotic therapy has not been associated with a beneficial response.

170. four common stages in a book A Road to Recovery: Hope Empowerment Self-Responsibility Having Meaningful Roles in Life.

171. Stage 1: Hope Positive goal visualizing and goal setting incorporating what people are most passionate about and likely to persist with Exposure to new possibilities Working with peer staff who have achieved considerable Recovery as role models Sharing pain and suffering, willing to start by “meeting people where they are” avoiding empty reassurance and encouragement Hopeful staff.

172. Stage 2: Empowerment Client-driven, self-directed treatment plans Offering meaningful education and choices in a process of shared decision making instead of just informed consent Heavy consumer inclusion—“nothing about us without us” Skill building services Internalizing successes as self-pride and self-confidence.

173. Stage 3: Self-Responsibility Motivational interviewing and enhancement Creating opportunities for self-responsibility and learning from successes Self-help tools like WRAP Growth oriented risk taking.

174. Stage 4: Having Meaningful Roles in Life Supported services e.g., education, housing, Family connection Peer support and Community development

175. Role of psychiatrist Person-Centered Formulations instead of Illness-Centered Diagnoses Relationship-Based Services Trauma Informed Care Goal-Driven Medications and Treatment Shared Decision Making Activated Patients Promoting Their Own Recoveries Help Them Trust Us Help Them Regain Control of their Lives Help Them Rebuild their Life

176. Help Them Heal Take the Long View Help Them Move On Taking Strengths Seriously and Building Resilience Building Social Determinants of Health: Building protective factors Building self-efficacy Building resilience by finding strengths in struggles

177. Stigma/advocacy People with mental illness generally are very aware that such pejorative terms are frequently used to refer to people with schizophrenia. Most people with schizophrenia who have been released into the community in the wake of deinstitutionalization have encountered various forms of barriers to their being reintegrated into society.

178. How to reduce stigma??? the most powerful way to reduce discrimination is exposure to persons who are open about being in Recovery from serious mental illness. Whether or not you are ready to become open and honest about your psychiatric history, you can still join with others who have similar conditions. Regarding fighting the use of the demeaning words and phrases so often heard with reference to the mentally ill.