Task 8 - Suzanne Q. PDF

Task 8 - Suzanne Q. Introductory chapters Psychosis - being unable to tell the difference between what is real and what is unreal (e.g. hearing voices, believing that the thoughts one has are broadcasted over TV, so other people kn...

Task 8 - Suzanne Q. Introductory chapters Psychosis - being unable to tell the difference between what is real and what is unreal (e.g. hearing voices, believing that the thoughts one has are broadcasted over TV, so other people know what you are thinking). Schizophrenia - a type of psychotic disorder. People with schizophrenia sometimes think & communicate clearly, have an accurate view of reality, and function well in daily life. However, during the active phase of their illness, their thinking & speech are disorganized, they lose touch with reality, an d they have difficulty caring for themselves. Lifetime prevalence of schizophrenia is 0.5-2% worldwide. Typical age of onset of psychotic disorders is late teenage or early adult years. Instead of pursuing their education, career, and/or family, psychotic people may need e.g. continual services, including resi dential care, rehabilitation, subsidized income for life, because schizophrenia tends to be chronic. Nations spend up to 3% of their healthcare budgets treating people with psychotic disorders, and 10s of billions of dollars m ore are lost in declines in productivity. Symptoms, diagnosis and course of schizophrenia DSM-5 refers to the schizophrenia spectrum to reflect the 5 domains of symptoms that define psychotic disorders. Their number, severity & duration distinguish psychotic disorders from each other. Positive symptoms - characteristics of psychotic symptoms that reflect an excess or distortion of normal functions - delusions, hallucinations, disorganized thoughts (speech), and disorganized/abnormal motor behavior (including catatonia - a marked decrease in reactivity to the environment). Negative symptoms are characteristic of reduction or loss of normal functions - e.g. diminished emotional expression & avolition (decrease in motivated self-initiated purposeful activities) are particularly prominent in schizophrenia. Positive symptoms Delusions - ideas that an individual believes are true but that are highly unlikely and often impossible. Ordinary self-deceptions (e.g. that one is going to win the lottery) differ from delusions in at least 3 ways: Self-deceptions are possible, whereas delusions are not (e.g. it's possible that you will win the lottery but it is not possible that your body is dissolving and floating into space). People with self-deceptions think about them occasionally, while people with delusions tend to be preoccupied with them, looking for evidence in support of their beliefs, attempting to convince others of those beliefs, and perhaps taking actions based on them (e.g. filing lawsuits against people they believe are trying to control their mind). People with self-deceptions tend to acknowledge that their beliefs may be wrong, but people holding delusions often are resistant to arguments or facts that contradict their delusions (e.g. by viewing others' arguments as a conspiracy to silence them and thus as evidence of the truth of their beliefs). Nihilistic delusion - belief that some aspects of either the world or oneself stopped existing (e.g. a belief that one is dead) or a major catastrophe will occur. Erotomanic delusions - a belief that another person is in love with the believer. Delusions tend to be complex & elaborate, with the person clinging to these beliefs for long periods. Delusions differ across cultures: for example, British schizophrenics' delusions tend to focus on being controlled by TV, radios and computers, but Pakistani schizophrenics' delusions are more likely to involve being controlled by black magic. Within cultures, delusions differ across time based on sociocultural factors: for example, delusional content in the US disproportionately focused on Germans during WW2, Communists during the Cold War, and technology in recent years Odd/impossible beliefs that are part of a culture's shared belief system are not considered delusions, unless people hold ext reme manifestations of them. Hallucinations - unreal sensory experiences that can involve any of the senses. Hallucinations tend to occur in normal people as well, but they are brief and occasional, usually occurring when one is tired, stressed or under the influence of drugs. Normal hallucinations also do not impair daily functioning in any way. Psychopathology Page 1  drugs. Normal hallucinations also do not impair daily functioning in any way. Hallucinations of people with schizophrenia tend to be more frequent, persistent, complex, more bizarre and often more entwin ed with delusions. They are not caused simply by sleep deprivation, stress or drugs. Auditory hallucinations are the most common hallucinations (in 70% of schizophrenics), consists of a voice speaking one's thoughts aloud, or commenting a one's behavior, or many voices speaking about the person in third person, or issuing commands/instructions. Voices often have a negative quality, criticizing, threatening, or telling one to hurt themselves or others. Schizophrenics may talk back to the voices as if they talk back to people who are actually in the room with them. When schizophrenics claim to hear 'voices' this is associated with neural activation in auditory & speech generation brain areas. Visual hallucinations are the second most common type, often accompanied by auditory hallucinations. They can take the diffuse shape of perception of colors & shapes that are not present or be very specific, such as perceiving that a particular person is present when they are not. Tactile hallucinations involve the perception that something is happening to the outside of the person's body (e.g. bugs are crawling up his back). Somatic hallucinations involve the perception that something is happening inside the person's body (e.g. worms are eating his intestines). Olfactory & gustatory hallucinations involve experiencing smells that are not present or foods that taste unusually. Study: 60% of people with visual hallucinations were diagnosed with schizophrenia or schizoaffective disorders, but 25% were diagnosed with depression and 15% with bipolar disorder. The content of hallucinations can be culturally specific: for example, Asians may see the ghosts of ancestors haunting them, but this hallucinations is not common among Europeans. Some psychotic people are convinced that their hallucinations are real, but many are aware that they may not be real. Individuals diagnosed with schizophrenia have a reality-monitoring deficit (a problem distinguishing between what actually occurred and what did not) and a self- monitoring deficit (inability to distinguish between thoughts & ideas generated by themselves and those generated by other people). Formal thought disorder - a label for the disorganized thinking of people with schizophrenia. This is normally inferred from the person's speech. Loose associations (a.k.a. derailment) - a common form of disorganization in schizophrenia - the tendency to slip from one topic to a seemingly unrelated topic with little coherent transition. Their answers to questions may be tangential rather than relevant (tangentiality). They suggest (1) difficulty inhibiting associations between thoughts and following the first association that comes to mind and (2) difficulties in understanding the full context of a conversation, being unable to distinguish the full meaning of a conversation/sentence from its detail. Neologisms - words that are made up from the person that mean something only to him, frequently constructed by condensing or combining sev eral words. Clanging - a form of speech pattern in schizophrenia where thinking is driven by word sounds. For example, rhyming may lead to the appea rance of logical connections where none in fact exists. Word salads - when the language of a psychotic person is so disorganized that these seems to be no link between one phrase and the next. For example: Much of abstraction has been left unsaid and undone in these products milk syrup, and others, due to economics, differentials, subsidies, bankruptcy, tools, buildings, bonds, national stocks, foundation craps, weather, trades, government in levels of breakages and fuses in electronics too all formerly states not necessarily factuated. Men with schizophrenia tend to show more severe deficits in language than women, possibly because language is controlled more bilaterally in women than in men => women can use both sides to compensate for deficits. Disorganized behavior in schizophrenia is variable and frightening to others. They may display unpredictable & apparently untriggered agitation - suddenly shouting, swearing or pacing rapidly. These behaviors may occur in response to hallucinations or delusions. People with schizophrenia often have trouble organizing their daily routines of bathing, dressing properly and eating regular ly. Since their memory & attention are impaired, it takes all their concentration to accomplish even on simple task (e.g. brushing teeth). They may engage in socially unacceptable behavior (e.g. public masturbation). Many schizophrenics are dirty, sometimes wearing few clothes on a cold day or heavy clothes on a very hot day. Catatonia - behavior that reflects unresponsiveness to the environment. It can range from no response to instructions (negativism), to showing a rigid, inappropriate, or bizarre posture, to a complete lack of verbal or motor responses. Catatonic excitement - the person shows purposeless and excessive motor activity for no apparent reason. Negative symptoms The presence of strong negative symptoms is more associated with poor outcome than the presence of strong positive symptoms, partly because negative symptoms are more persistent & more difficult to treat (they are less responsive to medication than positive symptoms). With medication, a person with schizophrenia may be able to overcome the hallucinations, delusions, and thought disturbances but may not be able to overcome the restricted affect and avolition. Thus, the person may remain chronically unresponsive, unmotivated, and socially isolated even when not acutely psychotic. Negative symptoms are less prominent in other psychotic disorders. Restricted affect (a.k.a. affective flattening)- a severe reduction in intensity or absence of emotional expression. People with schizophrenia show fewer facial expressions of emotion, may avoid eye contact, and are less likely to use gesture s to communicate emotional information than people without the disorder. Their voice may be flat, with little chance in emphasis, intonation, rhythm, tempo or loudness to indicate emotion or social engagement. Self-reports indicate that people with schizophrenia also experience less affect - they report significant anhedonia. However, in lab studies of their responses to standardized positive stimuli, they often report as much positive affect as people without the disorder. Study: people with schizophrenia showed less facial responsiveness to emotionally charged films than normal controls, but the y reported experiencing just as much emotion and showed even more physiological arousal. Therefore, they may be experiencing intense emotion that they cannot express. The self-reports of anhedonia may reflect limitations in self-report questionnaires or comorbid depression, which is common in schizophrenia. Avolition - an inability to initiate/persist at common, goal-directed activities (e.g. those at work, school and at home). Schizophrenics seem physically slowed down in their movements and seem unmotivated. They may sit around all day doing almost nothing, not even personal hygiene and grooming. Avolition may be expressed as asociality - a lack of desire to interact with other people (schizophrenics are often withdrawn & socially isolated). Psychopathology Page 2  Avolition may be expressed as asociality - a lack of desire to interact with other people (schizophrenics are often withdrawn & socially isolated). Some of this social isolation may be the result of stigma - many people with schizophrenia are shunned by their families and other people. Asociality should be diagnosed only when the individual has access to welcoming family & friends but shows no interest in socializing with them. Alogia - a lack of verbal fluency in which the individual gives very brief, empty replies to questions. Cognitive deficits Cognitive deficits in schizophrenia involve attention, memory and processing speed. These deficits contribute to hallucinations, delusions, disorganized thought and behavior and avolition, because they find it difficult to distinguish between thoughts in their mind that are relevant or irrelevant to the situation at hand. Information and stimulation constantly floods schizophrenics' consciousness and they are unable to filter out what is irrelev ant or determine the source of the information. Due to that, social relationships and work performance are severely affected, and daily functioning is impaired. The immediate relatives of people with schizophrenia also show many of these cognitive deficits to a less severe degree, even if they do not show symptoms of schizophrenia. Longitudinal studies suggest that these cognitive symptoms precede the acute symptoms of schizophrenia. Cognitive symptoms often do not improve over the course of the disorder or with treatment. Diagnosis The period that lasts >=1 month, during which the symptoms in criterion A are present, is called the acute/active phase of the disorder. Prodromal symptoms - symptoms before the acute phase. There is usually a slow deterioration from normal functioning to the delusional & dysfunctional thinking characteristic of schizophrenia. Residual symptoms - symptoms after the acute phase, when the individual usually ceases to show prominent signs of positive symptoms. When experiencing prodromal or residual symptoms, schizophrenics may be withdrawn and uninterested in others, and/or express beliefs that are unusual, but not delusional. They may have strange perceptual experiences (e.g. sensing another person in the room) without reporting full-blown hallucinations. They may speak in a somewhat disorganized way, but remain coherent. Their behavior may be peculiar (e.g. collecting scraps of paper) but not grossly disorganized. During the prodromal phase, family members & friends may perceive the person with schizophrenia as "gradually slipping away." If not treated, schizophrenia is chronic & episodic: after the first onset of an acute episode, people may have chronic residual symptoms interrupted by relapses into acute episodes. Prognosis Schizophrenia is one of the most severe and debilitating mental disorders, and many people with the disorder suffer symptoms and impairment for many years, even with treatment. 50-80% of people hospitalized for an episode of schizophrenia will be re-hospitalized sometime in their lives. Life expectancy of schizophrenic people is 10-20 years shorter than that of people without schizophrenia. People with schizophrenia suffer from infectious & circulatory diseases at a higher rate than do people without the disorder, due in part to underdiagnosis of physical illness, less access to care, higher rates of smoking, and being overweight due to diet, exercise, and side effects of medications. 5-10% of schizophrenic people commit suicide. The highest suicide rates are among those recently diagnosed or experiencing a fi rst psychotic episode. However, many people with schizophrenia do not show a progressive deterioration in functioning across the life span but inste ad stabilize within 5-10 years of their first episode, showing few or no relapses and regaining a moderately good level of functioning. A 15-year study found that 41% of people with schizophrenia had >=1 periods of complete recovery lasting at least 1 year, and many patients were able to maintain functioning even without antipsychotic medication. Schizophrenic women tend to have a better prognosis than men. In a 20-year study, 61% of women had periods of recovery, compared to 41% of men. Women are hospitalized less often than men and for briefer periods of time, show milder negative symptoms between periods of active-phase symptoms, and have better social adjustment when they are not psychotic. Women with schizophrenia also show fewer cognitive deficits than men with the disorder Onset in women is usually late 20s or early 30s, which is later than men (late teens or early 20s), which contributes to them having better prior histories than men (e.g. graduating from college, developing good social skills, establishing a family etc.). Estrogen may affect dopamine regulation in protective ways for women. In both men and women with schizophrenia, functioning seems to improve with age. Psychopathology Page 3 In both men and women with schizophrenia, functioning seems to improve with age. This may be due to finding stabilizing treatments, or learning to recognize early symptoms of a relapse and seek earlier trea tment before the acute phase. It may also be because the aging of the brain reduces dopamine levels (which are implicated in schizophrenia). Schizophrenia tends to have a more benign course in developing countries than in developed countries, which may be due to the social environment. In developing countries, broader and closer family networks surround people with schizophrenia Families in some developing countries also score lower on measures of hostility, criticism, and overinvolvement than do famil ies in some developed countries. Other psychotic disorders Schizoaffective disorder - a mix of schizophrenia and a mood disorder. People with the disorder simultaneously experience psychotic symptoms and mood symptoms meeting the criteria for a major depressive or manic episode. Mood symptoms must be present for the majority of the period of illness, but at least 2 weeks of hallucinations/delusions without mood symptoms are required. Schizophreniform disorder - requires that A, D & E criteria for schizophrenia are met for a duration from 1 month (brief psychotic episode duration) to 6 months (schizophrenia duration). Functional impairments are not necessary for a diagnosis of schizophreniform disorder. 2/3 of people with schizophreniform disorder will eventually receive a diagnosis of schizophrenia or schizoaffective disorder. Brief psychotic disorder - a sudden onset of an episode delusions, hallucinations, disorganized speech and/or disorganized behavior, lasting for 1 day to 1 month, after which the symptoms completely remit. 1 in 10000 women experience brief psychotic episodes shortly after giving birth. Although risk of relapse is high, most people show an excellent outcome. Delusional disorder - a disorder that involves delusions lasting at least Psychopathology Page 4  Delusional disorder - a disorder that involves delusions lasting at least 1 month regarding real-life situations (e.g. being followed, poisoned, deceived by a spouse or having a disease). Unlike schizophrenia, people with this disorder do not show any other psychotic symptoms. Other than delusion-caused behaviors, they do not act oddly or have difficulty functioning. Lifetime prevalence is 0.2% and females are more affected than males. Onset is later in life than most disorders: an average age of first admission to a psychiatric facility is 40-49. Biological theories Genetic contributors to schizophrenia Heritability of schizophrenia is high (maybe around 80%) and it is believed that many different genes are responsible for dif ferent symptoms of the disorder. As genetic similarity to a person with schizophrenia decreases, an individual's risk of developing schizophrenia also decreases. The children of 2 parents with schizophrenia and MZ twins of people with schizophrenia share the greatest number of genes with people with schizophrenia, and hence have the greatest risk (about 46%). A first-degree relative of a person with schizophrenia, who shares about 50% of genes with them, has about a 10% chance of developing the disorder. A niece or nephew (25% shared genes) has only a 3% chance of developing schizophrenia. The general population has a risk of 1-2%. Family members of people with schizophrenia have a higher risk of bipolar disorder (and vice versa), suggesting shared genetic factors. Adoption studies also show a significant genetic influence (biological relatives of adoptees with schizophrenia are 10 times more likely to have schizophrenia than biological relatives of adoptees who did not have schizophrenia). However, even when a person carries a genetic risk for schizophrenia, many other biological & environmental factors may influ ence if and how he manifests the disorder. Case study: Genain quadruplets, who shared the same genes and family environment, all developed schizophrenia but their speci fic symptoms, onset, course and outcomes varied substantially. Epigenetic differences also explain schizophrenia incidence. They most likely involve effects of stress. Structural and functional brain abnormalities There is a gross reduction in gray matter in the cortex of schizophrenics, particularly in the medial, temporal, superior tem poral and prefrontal areas. People who are at risk for schizophrenia because of family history but have not developed the disorder yet show abnormal acti vity in the PFC. Abnormalities in the development of the PFC (which undergoes major development in adolescence to young adulthood) may help ex plain the emergence of the disorder during this period. Deficits in PFC functioning in schizophrenia may not be due to a reduction in numbers of neurons, but to disrupted connection s between neurons in the glutamatergic, GABAergic and dopaminergic pathways, and to a reduction in the dendritic spines of neurons which reduces the c onnectivity between these cells. This reduced connectivity in the PFC, which is responsible for executive functioning, may give rise to the disordered speech & behavioral disorganization. Psychopathology Page 5  This reduced connectivity in the PFC, which is responsible for executive functioning, may give rise to the disordered speech & behavioral disorganization. People with schizophrenia also show abnormal hippocampal activation during tasks that require them to encode information for storage in memory or to retrieve information from memory. There are also abnormalities in the volume & shape of the hippocampus and at the cellular level. Similar hippocampal abnormalities are found in the first-degree relatives of people with schizophrenia. Schizophrenics also have lower volume & abnormal activity of the basal ganglia & limbic structures. Abnormalities in the neural activity in the temporal lobe & limbic system are more associated with positive symptoms. Positiv e symptoms are also associated with reduced volume of temporal cortex & hippocampus. People with schizophrenia also show reductions & abnormalities in white matter, particularly in areas associated with working memory. These white-matter abnormalities are present before development of overt schizophrenic symptoms, suggesting that they are early signs of the disorder rather than consequences of the disease process. White-matter abnormalities can impair the ability of various areas of the brain to work together, which could lead to the severe de ficits seen in schizophrenia. People with schizophrenia also show enlarged ventricles, which suggests atrophy in other brain tissue. People with schizophrenia with enlarged ventricles tend to show social, emotional, and behavioral deficits long before they d evelop the core symptoms of schizophrenia. They also tend to have more severe symptoms than other people with schizophrenia and are less responsive to me dication. The neuroanatomical abnormalities in schizophrenia are caused by genetic and epigenetic factors, in addition to birth complic ation, traumatic brain injury, viral infections, nutritional deficiencies, and deficiencies in cognitive stimulation. One birth complication that may be especially important in neurological development is perinatal hypoxia (oxygen deprivation at birth or in the few weeks before or after birth). 30% of people with schizophrenia have a history of perinatal hypoxia. Most people who experience perinatal hypoxia do not develop schizophrenia => it interacts with genetic factors to produce the disorder. Rates of schizophrenia are also higher among people whose mothers were exposed to viral infections while pregnant. The link i s especially strong when the exposure happened during the second trimester of pregnancy, which is crucial for the development of the CNS. Schizophrenic people are more likely to be born in the spring months, making the chance higher for their mothers to contract influenza and other viruses at critical phases of fetal development if they are pregnant during the fall or winter. Neurotransmitters Original dopamine theory - schizophrenia symptoms are caused by excess dopamine levels, particularly in the PFC & limbic system. Phenothiazines (a.k.a. neuroleptics), which block dopamine receptors, reduce symptoms of schizophrenia. Drugs that increase dopamine levels (e.g. amphetamines) tend to increase the incidence of positive symptoms of schizophrenia (a.k.a. amphetamine psychosis). People with schizophrenia have more dopamine receptors & higher levels of dopamine in some brain areas (e.g. basal ganglia). This theory has been proven to be too simplistic: Many schizophrenics do not respond to neuroleptics. Those who respond experience relief mostly from positive symptoms => dopamine levels do not explain negative symptoms. Dopamine levels change soon after drug therapy begins, while changes in symptoms take longer, suggesting another determinant of symptoms. Revised dopamine theory - different types of dopamine receptors & different levels of dopamine in various areas of the brain can account for the symptoms of schizophrenia. There is excess dopamine activity in the mesolimbic pathway (subcortical pathway involve in salience & processing of rewards) Abnormal functioning of this area may lead people to attribute salience to otherwise innocuous stimuli, contributing to hallucinations and delusions and to deficits in motivation. Atypical antipsychotics (newer drugs for schizophrenia) may work to reduce schizophrenic symptoms by blocking dopamine receptors in the mesolimbic system. There is low dopamine activity in the mesocortical pathway (from ventral tegmental area to PFC). Low dopamine activity here may lead to the negative symptoms: lack of motivation, inability to care for oneself, affect restriction. Negative symptoms are associated with structural & functional abnormalities in the PFC. Phenothiazines do not effectively alleviate the negative symptoms, which may be explained by this revision. Other neurotransmitters may also play a role in schizophrenia. Serotonin neurons regulate dopamine neurons in the mesolimbic pathway, and some of the newest drugs for treating schizophreni a bind to serotonin receptors. Abnormal GABA levels have also been found in schizophrenia. Glutamate abnormalities may also play a role, as there are many glutamatergic pathways that link the cortex, limbic system an d thalamus, which behave abnormally in schizophrenia. Drugs that block glutamate receptors (e.g. ketamine) cause hallucinations and delusions in otherwise healthy individuals. Cannabis Schizophrenics use cannabis significantly more often than the general population and cannabis use has been shown to precede p sychotic symptoms. Cannabis use increases the risk of psychotic symptoms, but has a greater impact on those that already have a vulnerability to schizophrenia. THC can release dopamine and increase it to levels triggering psychotic episodes. Regular cannabis use can also affect the course of brain maturational processes associated with schizophrenia, and results in smaller cerebellar white-matter volume in schizophrenic patients who use cannabis regularly. Psychopathology Page 6 schizophrenic patients who use cannabis regularly. Psychosocial perspectives Behavioral theories Behavioral theorists have suggested that the odd behaviors of schizophrenics were developed because they were reinforced. Evidence is not particularly strong, but the fact that inappropriate behaviors can be reduced and socially acceptable behavio rs can be developed using operant conditioning suggests that at least some of the unusual behaviors schizophrenics engage in may be under control of reinforcem ent contingencies. Stress and relapse Sociogenic hypothesis - individuals low in SES experience significantly more life stressors, and these stressors are associated with unemployment, po or education, crime and poverty. Study: researchers followed a group of people with schizophrenia for 1 year, interviewing them every 2 weeks to determine whe ther they had experienced any stressful events and/or any increase in their symptoms. Those who experienced relapses of psychosis were more likely than those who did not to have experienced negative life events in the month before their relapse. Stressful events in adulthood may be especially important among people who experienced adverse events in childhood. Immigration is a major stressor linked to increased risk for episodes in schizophrenia. This relationship has been attributed to language difficulties, unemployment, poor housing and low SES. Many of the life events that people with schizophrenia experience prior to relapse actually may be caused by prodromal sympto ms (e.g. social withdrawal) that occur just before their relapse into psychosis. Social drift, social labeling and urban birth People with schizophrenia are more likely than people without schizophrenia to experience chronically stressful circumstances (e.g. living in impoverished inner-city neighborhoods and having low-status occupations or being unemployed. Social drift (a.k.a. downward shift) - because schizophrenia symptoms interfere with a person’s ability to complete an education and hold a job, people with schizophrenia tend to drift downward in social class compared to the class of their family of origin. Social-selection theory - the link between schizophrenia and low SES is due to social drift. Both directions (social status & environments schizophrenia) are likely and supported by evidence. Social labeling - development and maintenance of psychotic symptoms are influenced by the diagnosis itself. When someone is diagnosed with schi zophrenia: Others will begin to behave differently towards him and define any deviant behavior as a symptom of schizophrenia. The person may assume the role of someone who has a disorder, and fall into a self-fulfilling prophecy, in which the diagnosis leads to the maintenance of pathological symptoms. Study: 8 people without any psychopathology present themselves at psychiatric hospitals complaining of psychotic symptoms. These healthy people were immediately diagnosed with schizophrenia, and were later treated in an authoritarian & uncaring way by hospital staff. They began to feel powerless, bored and uninterested. Once they had left the hospital, they still had great difficulty being viewed and treated as 'normal'. People with schizophrenia and psychosis in general are more likely to have been born in a large city than in a small town. This link has been mostly explained with higher overcrowding & prevalence of infectious diseases in urban areas. Schizophrenia and the family Double-bind hypothesis - psychosis may develop in families where communication is ambiguous and acts to double -bind the child (e.g. show affection and later reject the child as being a sign of weakness). This leaves the individual in a conflict situation in which they may eventually withdraw from all social interaction. With more research, the double-bind hypothesis was replaced by another construct: Communication deviance (CD) - a general term used to describe communications that would be difficult for ordinary listeners to follow and leave them puzzle d ant unable to share a focus of attention with the speaker. These communications include: 1. Abandoned or abruptly ended remarks or sentences. 2. Inconsistent references to events or situations. 3. Using words or phrases oddly or wrongly 4. The use of peculiar logic. CD is a stable characteristic of families with children who develop psychotic symptoms. When children that are biologically predisposed to schizophrenia are adopted & raised in homes with adoptive parents who have no biological predisposition, CD is an independent predictor of the adopted child developing psychotic symptoms. Expressed emotion (EE) in family interactions are associated with multiple episodes of schizophrenia. Families high in EE are overinvolved with one another, are overprotective of the family member with schizophrenia, and expres s self-sacrificing attitudes toward the family member while at the same time being critical, hostile, and resentful toward him or her. Although these family members do not doubt their loved one’s illness, they talk as if the ill family member can control his s ymptoms, often having ideas about how he can improve those symptoms. A number of studies using different methods have shown that people with schizophrenia whose families are high in EE are more likely to suffer relapses of psychosis than are those whose families are low in expressed emotion. More recently, a longitudinal study of individuals at high risk for schizophrenia found that those living in a family charact erized by low warmth and high criticism (components of high EE) were more likely to develop the full syndrome of schizophrenia than were those living in a family wit h greater warmth and less criticism. The stress caused by EE may trigger cortisol release in the HPA system, which is known to increase dopamine activity and may thus reactivate symptoms in vulnerable individuals. Psychopathology Page 7 The link between high levels of family expressed emotion and higher relapse rates has been replicated in studies of several c ultures, including those of Europe, the United States, Mexico, and India. In developing countries, levels of expressed emotions of families are lower than that of families in developed countries. This may be one reason why people with schizophrenia from developing countries have fewer relapses than do those from developed countries. The hostility and intrusiveness in some families of people with schizophrenia may result from the schizophrenia rather than c ontribute to its relapse. Moreover, family members with high expressed emotion are themselves more likely to have some form of psychopathology => schiz ophrenic people in these families may have a greater genetic loading for psychopathology. The best evidence that family expressed emotion does influence relapse in people with schizophrenia is that interventions to reduce family expressed emotion tend to reduce the relapse rate in family members with schizophrenia Cognitive perspectives Difficulties in attention, inhibition & adherence to rules of communication may lead schizophrenics to conserve their limited cognitive resources. One way to do this is to use certain biases or thinking styles for understanding the overwhelming information streaming throu gh their brain. Delusions may arise as the schizophrenic tries to explain strange perceptual experiences and jumps to conclusions based on limited evidence. Hallucinations may arise from a hypersensitivity to perceptual input, coupled with a tendency to attribute experiences to ext ernal sources. Rather than thinking "I'm hearing things", the person with schizophrenia will think "Someone is trying to talk to me." The negative symptoms may arise from expectations that social interactions will be aversive and from the need to withdraw & c onserve cognitive resources. Schizophrenics sometimes fail to make simple associations between relevant events (e.g. sticking to the theme of a conversati on), but on other occasions make associations that are irrelevant (e.g. during clanging). These tendencies may reflect attention deficits, where the person cannot focus attention on relevant aspects of the environme nt, or attends too much to irrelevant aspects. Schizophrenics are highly distractable, and perform poorly at cognitive tasks when they are also presented with irrelevant, d istracting stimuli or information. Interestingly, they perform better than non-schizophrenic controls on tasks where attending to distracting stimuli can improve performance. Orienting response - a physiological reaction including changes in skin conductance, brain activity, heart rate and blood pressure, which occurs n aturally when a healthy individual is presented with a novel or salient stimulus, indicating that the stimulus is being attended to and processed. 50% of schizophrenics show abnormalities in their orienting reactions, suggesting that they are not attending to or processin g important environmental stimuli. Deficits in the orienting response are correlated to both positive & negative symptoms. Negative priming effect - non-clinical participants show increased reaction times when asked to name a target word they have previously been asked to ignor e. Schizophrenics fail to show this negative priming effect, and perform just as well whether they have been asked to ignore the relevant prime or not. The inability to filter out irrelevant stimuli or ignore distractions correlated highly with positive symptoms of schizophren ia. Paranoid schizophrenia (characterized by delusions of persecution) has been associated with 4 types of cognitive biases: Attentional biases towards threatening stimuli (similar to those in anxiety disorders). Schizophrenics with persecutory delusions show attentional biases toward emotionally meaningful or paranoia-relevant stimuli. However, they are slower to locate angry faces than control participants, suggesting that they adopt an avoidance strategy that involves avoiding fixating on threatening stimuli. Attributional biases - people with persecutory delusions tend to be biased toward stable and global attributions for negative events (like depressed people), but also attribute positive events to internal causes and negative events to external causes. Study: the tendency to attribute negative events to external causes was only there when there was a perceived threat to the self. These attributional biases act to maintain paranoid beliefs and persecutory delusions. Reasoning biases in the form of jumping to conclusions without sufficient evidence. Jumping to conclusions may create a biased reasoning process that leads to the formation & acceptance of delusional beliefs and eventually lead to delusional symptoms. Interpretational bias - a tendency to interpret cognitive intrusions (e.g. hearing voices) as threatening in some way (e.g. 'I must be mad', 'The Dev il is talking to me'). The misinterpretation causes anxiety, negative mood and physiological arousal, which produces more auditory hallucinations, which are in turn interpreted negatively etc. As these voices are increasingly interpreted as external & uncontrollable, schizophrenics start developing a 'relationship' with them, the nature of which may determine the level of distress and disability. There are several types of relationships that schizophrenics have with their voices. Often this is a 'power struggle', in which the sufferer is constantly trying to regain power over their voices. Threat-anticipation model of persecutory delusions - 4 factors contribute to the development of cognitive biases involved in persecutory ideation: Anomalous experiences (e.g. hallucinations) that do not have a simple & obvious explanation, and are thus open to biased inte rpretations. Anxiety, depression and worry that would normally cause a bias toward negative thinking and threatening interpretations of ev ents. Even in healthy populations, anxiety increases the tendency to jump to conclusions and to generate & reinforce paranoid ideation. In schizophrenia, there is a significant association between state anxiety & jumping to conclusions Reasoning biases that lead one to seek confirmatory evidence for their persecutory interpretations rather than question them (e.g. jumping to conclusions). Social factors (e.g. isolation & trauma) that add to the feelings of threat, anxiety & suspicion. Theory of mind deficits have been found to be an important factor in the development & maintenance of psychotic delusional be liefs. If individuals diagnosed with schizophrenia are unable to infer the intentions or mental states of others, then they may begi n to believe that others are either hiding their intentions or their intentions are hostile. TOM deficits are a stable marker of the condition of schizophrenia across time. They have also been identified in the prodrom al stages of psychosis. Cognitive interventions based on these views are more successful than simply providing support in schizophrenia. These therapies help patients identify & cope with stressful circumstances associated with the development & worsening of sym ptoms. Psychopathology Page 8  These therapies help patients identify & cope with stressful circumstances associated with the development & worsening of sym ptoms. They also teach patients to dispute their delusional beliefs or hallucinatory experiences. Negative symptoms are treated by helping patients develop expectations that being more active and interacting more with other people will have positive benefits. Treatment Biological treatments Insulin coma therapy - used in the 1930s to threat schizophrenia - people are given massive doses of insulin until they went into a coma. Insulin coma therapy, ECT and prefrontal lobotomy were used for schizophrenia treatment but they had little effect. Until the 1950s most schizophrenics received custodial care (hospitalization or restraint) where they were bathed, fed, and prevented from hurting themselves, often with the use of physical restraint. Few received treatment that actually reduced their symptoms & improved their functioning. In the 1950s, chlorpromazine (Thorazine) was introduced, which was an effective drug treatment for schizophrenia. It belongs to a class of drugs called the phenothiazines, which block dopamine receptors. They calm agitation and reduce hallucinations & delusions in schizophrenia. These are first-generation antipsychotic drugs, a.k.a. typical antipsychotics, a.k.a. neuroleptics. Thanks to these drugs, by 1971 the number of schizophrenics who required hospitalizations reduced to half of what would be ex pected without the use of the drugs. After the phenothiazines, other classes of typical antipsychotic drugs were introduced, including butyrophenones (e.g. Haldol ) and thioxanthenes (e.g. Navane). About 25% of schizophrenics do not respond to typical antipsychotics. In responders, positive symptoms improve more than nega tive symptoms. If the drug is discontinued, 78% of schizophrenics relapse within 1 year and 98% relapse within 2 years, compared to about 30 % who continue on their medications. Typical antipsychotics also have significant side effects: grogginess, dry mouth, blurred vision, drooling, sexual dysfunctio n, visual disturbances, weight gain or loss, constipation, menstrual irregularities, depression, akinesia (slowed motor activity, monotonous speech & an expressionless fa ce), Parkinson's-like symptoms, tardive dyskinesia (a neurological disorder that involves involuntary movements of the tongue, face, mouth or jaw, occurs in >20% of people who use phenothiazines long-term). In order to reduce side effects, the lowest dose that still keeps active symptoms at bay is prescribed (maintenance dose). Unfortunately, maintenance dose usually does not restore a person to full functioning. More recently, the second-generation antipsychotic drugs (a.k.a. atypical antipsychotics) have been found to relieve positive symptoms while inducing fewer intolerable side effects than the typical antipsychotics. Clozapine - binds specifically to the D4 dopamine receptor and also influences other neurotransmitters (e.g. serotonin). Clozapine reduces both negative & positive symptoms in many schizophrenics, even in ones who never responded to the phenothiazines. Side effects include dizziness, nausea, sedation, seizures, hypersalivation, weight gain and tachycardia. 1-2% of clozapine users develop agranulocytosis - a deficiency of granulocytes (substances produced by bone marrow that fight infection). This condition can be fatal and it thus warrants close monitoring of clozapine-taking patients). Due to these side effects, clozapine is often used only after other atypical antipsychotics have been tried. Other atypical antipsychotics, including risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), and ziprasidon e (Geodone, Zeldox) do not tend to induce agranulocytosis, but they can cause other side effects such as weight gain, diabetes risk, sexual dysfunction, sedatio n, low blood pressure, seizures, gastrointestinal problems, vision problems, and concentration problems. Study: using any of these 5 drugs, only 44.5% of patients experienced remission during an 18-month period. 6-month remission rates were highest for olanzapine (12.4%), followed by quetiapine (8.2%), perphenazine (6.8%), ziprasidone (6.5%), and risperidone (6.3%). Although atypical antipsychotics are superior to older medications, it is still unclear which of them are safest & most effec tive, and for which patients. Psychological & social treatments Many people who are able to control the positive symptoms of schizophrenia with drugs still experience many of the negative s ymptoms, particularly problems in motivation and in social interactions. Psychological interventions (e.g. social skills training) can help these individuals increase their social skills and reduce their isolation and apathy. Such interventions also can help people with schizophrenia and their families reduce the stress and conflict in their lives, thereby reducing the risk of relapse into psychosis. Psychological interventions can help people with schizophrenia understand their disorder, appreciate the need to remain on th eir medications, and cope more effectively with the side effects of the medications. Psychologists, social workers and other mental health professionals also assist schizophrenics with basic needs such as finding & holding a job, feeding & sheltering themselves, and obtaining necessary medical/psychiatric care. Personalized treatments that address behavioral, cognitive and social deficits and are tailored the each individual are used for schizophrenia. These treatments are given together with medication and increase patient's level of functioning & significantly reduce risk o f relapse. Cognitive treatments include helping schizophrenics recognize and change demoralizing attitudes they may have toward their il lness so that they will seek help when needed and participate in society to the extent that they can. For example, CBT for psychosis (CBTp) helps challenging delusional beliefs, developing non-psychotic meanings for symptoms (e.g. hallucinations), reducing negative symptoms by challenging low expectations. ▪ CBTp is based on the view that schizophrenics interpret cognitive intrusions as threatening, which causes a vicious cycle of safety behaviors (which prevent disconfirmation of the belief that the hallucinations are threatening - shouting at the voices to go away, lying down, drinking alcohol etc.) and more hallucinations. Reattribution therapy is an extension of CBTp, which helps schizophrenics reattribute their paranoid delusions to normal daily events rather than the threatening causes they believe to underlie them. Behavioral therapies use operant conditioning and modeling to teach schizophrenics skills such as initiating and maintaining conversations with others, asking for help or information from physicians, and persisting in an activity, such as cooking or cleaning. These interventions can be administered by the family, in which case the therapist teaches the family to ignore schizophrenia symptoms, and instead reinforce socially appropriate behavior by giving it attention and positive emotional responses. In residential treatment centers, token economies may be established, where patients can exchange tokens for special privileges by completing self-care Psychopathology Page 9  In residential treatment centers, token economies may be established, where patients can exchange tokens for special privileges by completing self-care tasks or engaging in appropriate conversations with others. Social interventions include increasing contact with supportive others, often through self-help support groups. These groups discuss the impact of the disorder on their lives, the frustration of trying to make people understand their disorder, their fear of relapse, their experiences with various medications, and other everyday concerns. Group members can help one another learn social and problem-solving skills by giving feedback and providing a forum in which individual members can role- play new skills. Although behavioral, cognitive, and social treatments can improve functioning, studies show that the effects can be rather sm all, especially in the long term. Personal therapy - a broad-based CBT program that is designed to help schizophrenics with the necessary skills needed to adapt to everyday living after discharge from the hospital. Clients are taught the following skills: Learning to identify relapse signs (e.g. social withdrawal) and what to do in such cases. Relaxation techniques designed to help with the anxiety & stress caused by challenges. Identifying appropriate behavioral & emotional responses to events, and learning new & adaptive responses. Identifying appropriate cognitions and dysfunctional thinking biases that may foster catastrophic & deluded thinking, and hel ping the client to prevent the latter. Learning to deal with negative feedback from others and to resolve interpersonal conflict. Learning how to comply with medication regimes. Cognitive remediation training (CRT) or cognitive enhancement therapy (CET) are programs that use computer-based or pencil-and-paper tasks to improve attention, memory and problem-solving, which have been impaired by the disorder. These treatments have significant effects on attention, problem solving, verbal WM, processing speed and social cognition, bu t rather modest effects on symptom reduction. However, CRT is particularly effective when combined with social skills training & supported employment, and can result in im provement in social & cognitive skills up to 24 months after entering such a program. Family-oriented therapies include basic psychoeducation on schizophrenia and training of family members to cope with their loved one 's inappropriate behaviors and the disorder's impact on their lives. They can also aim reducing EE and CD. Education includes the disorder's biological causes, its symptoms and the medications & their side effects. The goal is to reduce self-blame in family members, increase their tolerance for the uncontrollable symptoms of the disorder and allow them to monitor their family member's use of medication & side effects. Family members also learn communication skills to reduce harsh, conflictual interactions, as well as problem-solving skills to help manage issues in the family (e.g. lack of money), in order to reduce the overall level of stress in the family. They also learn behavioral techniques for encouraging appropriate behavior and discouraging inappropriate behavior on the par t of their family member with schizophrenia. When compared with drug therapy, family therapies are more effective at reducing relapse rates (24% for family therapy and 64% for drug therapy). Family therapies can also increase patients' adherence to taking antipsychotic medications. Assertive community treatment programs provide comprehensive services for schizophrenics, relying on the expertise of medical professionals, social workers and psychologists to meet the variety of patients' needs 24 hours a day. Provided help includes psychotherapy, assistance in dealing with everyday life and its stressors, guidance on making decision s, residential supervision and vocational training. Assertive outreach - a way of working with people with severe mental health problems who do not effectively engage with mental health services. Assertive outreach staff meets clients in their own environments (e.g. home, café, park or street) and the aim is to build a long-term relationship between the client & mental health services. Community care programs help schizophrenics integrate more effectively into their local communities, comply with their medica tion regimes, and stay out of hospitals for longer. However, these services are difficult to resource & coordinate and very few people actually receive such services. The symptoms of schizophrenia are sometimes treated by folk/religious healers, according to cultural beliefs about the meanin g & causes of these symptoms. There are 4 models that traditional healers tend to follow in treating schizophrenic symptoms: Structural model - there are interrelated levels of experience (e.g. body, emotion, and cognition or the person, society, and culture) and sympt oms arise when the integration of these levels is lost. Healing thus involves reintegrating these levels through a change of diet or environment , the prescription of herbal medicines, or rituals. Social support model - symptoms arise from conflictual social relationships, and healing involves mobilizing a patient’s kin to support him through the crisis and reintegrating the patient into a positive social support network. Persuasive model - suggests that rituals can transform the meaning of symptoms for patients, diminishing their pain. Clinical model - the faith the patient has in the traditional healer to provide a cure for the symptoms is sufficient. The same or different? A phenomenological comparison of auditory verbal hallucinations in healthy and psychotic individuals - Daalman (2010) Auditory verbal hallucinations (AVHs) occur in 70% of schizophrenic patients. It is usually assumed that AVHs are the same phenomenon in individuals within a spectrum of severity, starting from schizophr enics (most severe) and moving through schizotypal/borderline PD patients to healthy people. However, it is currently unclear if the AVHs at different parts of this spectrum are phenomenologically distinct. There have been hypotheses about the AVHs that are specific to psychotic disorders: It has been hypothesized that voices perceived as coming from the external environment indicate psychotic disorder, while voi ces perceives as being inside the head are not. It has also been hypothesized that frequency of AVHs discriminates between psychotic & healthy people. However, there is not enough evidence for most of these hypotheses. Psychopathology Page 10 This study has 2 aims: Investigate if AVHs are the same phenomenon in the 2 extremes of the spectrum. Investigate which characteristics have most prominent diagnostic value in predicting the presence or absence of a psychotic d isorder. Method The phenomenology of AVHs was compared in 118 psychotic outpatients and 111 healthy individuals. All participants experienced AVHs at least once a month for over a year, but the healthy people had no professional, psychological or social dysfunction. Among the psychotic outpatients, 77.1% had schizophrenia, 3.4% schizoaffective disorder, and 19.5 had psychosis not otherwise specified. Hallucinations were measured with an auditory hallucinations scale, which addressed several phenological characteristics of a uditory hallucinations. Results & Discussion Characteristics of AVH The psychotic patients experienced less control, heard voices talking in the 3rd person more frequently, were older when they first heard a voice, and scored significantly higher on frequency, duration, distress and emotional valence of content than nonpatients. The most significant between-group difference was the emotional valence of the content of AVHs. Negative emotional valence had a predictive value of 88% for a psychotic disorder in this sample. No differences were found for perceived location (i.e. inside/outside the head), loudness, number of different voices, and personification. Attribution to external agency Healthy individuals had an external explanation significantly more often than patients. This is in contrast to expectations due to previous hypotheses. Predictors of a psychotic disorder based on the characteristics of AVHs Having control over the AVHs for most of the time, hearing voices less than once a day, age of onset before 16, and hearing v oices with a predominantly positive content are good predictors that a person does not have psychotic illness. Mean age of onset of AVHs was 12.4 years old for healthy individuals and 21.4 years old for psychotic patients. The used model estimates a 92% probability of a correct diagnosis using these characteristics. Speculations on pathophysiology Synaptic density peaks during childhood, followed by an extensive decrease of synapses (pruning) during adolescence, reaching normal levels in adulthood. The age of onset of AVHs in nonpsychotic individuals coincides with maximal synaptic density. In contrast, the age of onset of AVHs in psychotic patients coincides with pruning. Further research is needed to compare the biological basis of AVHs in both groups. Detecting and defusing cognitive traps: a metacognitive intervention in schizophrenia - Moritz (2010) Introduction For a long time psychotherapy has been considered to be a naïve approach to treating schizophrenia due to assumptions that th e condition is not amenable to psychological understanding and represents 'utter madness'. However, recent evidence on the success of CBT, psychoeducation for families, cognitive remediation, and social cognition pro grams has changed these views somewhat. Psychotherapy and medication should be considered as complementary instead of competing approaches, because psychotherapy imp roves insight & treatment adherence, while disorganization & agitation (that are higher when there is no medication) may undermine a good therapeutic r elationship. Metacognitive training for schizophrenia patients Schizophrenia patients lack metacognitive awareness not only for neuropsychological dysfunctions, but also for cognitive bias es. For example, despite objective jumping to conclusions (JTCs), they see themselves as indecisive. Psychopathology Page 11  For example, despite objective jumping to conclusions (JTCs), they see themselves as indecisive. Metacognitive training for schizophrenia (MCT) is an intervention that includes psychoeducation, cognitive remediation and CBT and targets these specific biases. It also focuses on social cognitive aspects. It is delivered in a group of 3-10 schizophrenia (spectrum) patients. It consists of several modules, each of which familiarizes group members with the respective topic (e.g. JTC) and then multiple exercises are done that aim to challenge the functionality of biased thinking styles and providing corrective feedback. Modules also include a case example that shows how cognitive biases can escalate to psychotic symptoms. The main goal is to raise awareness of these cognitive biases and prompt patients to reflect critically on their problem solving skills. There is recent evidence that severity of cognitive biases is linked to symptomatic & functional outcome, but that CBT has no major impact on cognitive biases or insight thereof. Cognitive biases in schizophrenia Unlike 'cold' cognitive deficits (e.g. lower speed and accuracy), cognitive biases relate to the appraisal, processing and se lection of information. While cognitive biases are adaptive to some degree, they can transform into cognitive traps when exaggerated. JTC in schizophrenia: findings from basic research 40-70% of patients with schizophrenia gather very little information before arriving at strong conclusions (they JTC). While more prominent in acute patients, JTC also remains in remitted patients and in nonpsychotic subjects with subclinical s chizophrenia. JTC is worsened under stress and in emotional context. Treatment of jumping to conclusions with MCT In the JCT modules of MCT, participants first discuss advantages (e.g. saving time) and disadvantages (e.g. errors) of JTC. Then, examples are provided of how JTC can cause everyday problems and false & falsifiable urban legends are presented that s erve as models for delusions (e.g. the fact that the US $1 bill contains symbols indicating that the US government is ruled by secret societies). It is made clear to patients how biased information selection, presentation of pseudo-evidence and JTC contribute to these legends. Attributional style and self-esteem in schizophrenia: findings from basic research Schizophrenics often blame other people and/or institutions for negative events rather than spreading blame over multiple sou rces. Treatment of attributional biases and poor self-esteem with MCT In the attribution module of MCT, participants are familiarized with the idea that 3 basic sources may promote a certain soci al attribution (myself, others, circumstances). The social consequences (especially disadvantageous ones) of extreme & monocausal attributional styles are highlighted (e.g. blaming others may lead to social rejection). Then, possible causes for described events are discussed, where both situational and personal factors are taken into account. Participants are encouraged to find & combine different possible explanations. Metamemory in schizophrenia: findings from basic research Memory problems are a core problem in schizophrenia: reduced memory vividness, vague autobiographical memory, overconfidence in memories (especially in false ones). Overconfidence in errors & higher error-proneness may result in knowledge corruption, whereby a large part of what the patient believes is true is actually not. Treatment of metamemory problems with MCT In the metamemory module of MCT, participants are first taught how to enhance memory retention via mnemonic strategies. Memory problems and false memories are emphasized by using various examples. The exercises aim to demonstrate the fallibility of human memory. Participants are encouraged to express doubt in their memories and to collect further proof, if their recollection is vague. Bias against disconfirmatory evidence in schizophrenia: findings from basic research A bias against disconfirmatory evidence (BADE) has been demonstrated in both first episode and chronic patients, as well as in healthy participants scoring high on delusional symptoms. Treatment of BADE with MCT First, examples show that persistence & stubbornness can be to some extent normal & helpful. Then, case examples are shown explaining how exaggerated incorrigibility has led to major problems. Participants are familiarized with confirmation bias. Theory of mind in schizophrenia: findings from basic research Severe ToM deficits have been found in psychotic patients. Treatment of deficits in ToM with MCT Different cues for social cognition (e.g. language) and their strength & fallibility are discussed. Participants are encouraged to gather several different cues for social inferences rather than to judge a book by its cover, or to decrease judgment confidence if multiple cues are not available. Metacognitive training: data on feasibility, subjective and objective effectiveness Psychopathology Page 12 In an initial study, 40 schizophrenics were randomly assigned to either MCT or a cognitive remediation program. Patients rated the MCT superior on all outcome criteria, and 4 parameters were significantly better: fun, recommendation to o thers, not being bored and usefulness in daily life. A second study compared MCT with an active control (group discussion about newspaper articles) in a sample of 30 schizophreni a patients. Patients in the MCT had a significantly higher decrease of positive symptoms & JTC. Subjective appraisal was better for the MCT than for the control intervention. Other studies on MCT show similar results. MCT+ - an individualized MCT which combines the focus of MCT on cognitive biases with a CBT -oriented approach. Study: MCT+ causes significantly greater improvements in positive symptoms and JTC compared to a cognitive remediation contro l intervention. Neuroimaging of cognitive disability in schizophrenia: Search for a pathophysiological mechanism - Ragland (2007) Introduction The vast majority of patients treated with the best drugs for schizophrenia (atypical psychotics) remain significantly cognit ively disabled, which strongly predicts poor functional outcomes. The paper reviews how neuroimaging has improved our understanding of cognitive disability in schizophrenia and map cognitive impairments to specific brain regions. Frontal lobe model An initial study found that schizophrenic patients, compared to healthy volunteers, had a reduced gradient of frontal to post erior blood flow, leading to the conclusion that schizophrenia is characterized by hypofrontality. A later study found that hypofrontality was greatest in patients with restricted affect who were withdrawn and mute. Despite replications, not all studies found evidence of hypofrontality, resulting in a critical view forming of the hypofront ality model. These early studies had no control over subjects' mental activity, which led to a transition to 'cognitive activation' paradi gms in which changes in cerebral blood flow were examined in relation to specific task demands. Wisconsin Card Sorting Test (WCST) - a measure of concept formation, cognitive flexibility, feedback processing and working memory that is sensitive to frontal lo be lesions. Several studies showed that patients failed to show a normal increase in blood flow in the DLPFC during WCST (but not in vari ous control tasks). This led to a reformulation of the hypofrontality hypothesis, stating that hypofrontality depends on the behavioral state of the patients during neuroimaging (specifically, it requires the person to be solving a prefrontal cognitive challenge). The results on the WCST studies were criticized, for example because the task measures several factors and it was unknown whi ch cognitive components were impaired in schizophrenia. Later, it was discovered that many cognitive & behavioral deficits could be explained by WM abnormalities. For example, disorganized speech & thought process could be a manifestation of the inability to maintain a linguistic schema in mind. Many studies using various methods confirmed this WM deficit in schizophrenic patients, and also in their unaffected relative s. Most fMRI studies showed DLPFC hypoactivity in schizophrenics during conditions requiring manipulation of information across WM delays. However, some studies did not find differences in task-related DLPFC hypoactivity between schizophrenics and controls. Recent studies have provided evidence of both hypo- and hyperactivity of the DLPFC in schizophrenia, supporting the idea of an inverse U-shaped function relating WM load to DLPFC activation. There is also evidence that WM abnormalities in schizophrenia are not restricted to the DLPFC, such as VLPFC, ACC and left frontal pole regions. This raised the idea that more anterior, ventral and medial regions may be recruited to compensate for difficulties in cognitive tasks, which suggested a network-level analysis. The ACC has also been shown to be abnormally active in schizophrenia during a variety of cognitive tasks. Temporal lobe model The other prominent theory of schizophrenia pathophysiology involves the left temporal cortex & underlying hippocampus as a s ite of brain dysfunction and memory impairment in schizophrenia. In healthy right-handed individuals, the left hemisphere is more involved in verbal, linguistic and analytic functions, while the right hemisp here is specialized for visuospatial and synthetic processes. Thought disorder features (e.g. analytic & language processing deficits) were suggestive of greater left hemispheric dysfunction. Studies of this model began to reveal a dynamic interplay between the PFC and temporal -limbic regions, leading to a currently prominent model of disrupted fronto - temporal connectivity. Study: unlike healthy participants who activated a right fronto-temporal network during word retrieval, patients had reduced hippocampal and abnormally increased frontal activation. Reductions in hippocampal volume and memory-related activation have been well documented in the schizophrenia literature. However, these abnormalities are invariably accompanied by abnormal modulation of PFC. Disrupted connectivity or loss of prefrontal control Psychopathology Page 13 Disrupted connectivity or loss of prefrontal control Several paths of evidence led to the formulation of the theory that there is a fronto-temporal networks dysfunction in schizophrenia. The awareness of reciprocal inter-connectivity between PFC regions and hippocampus grew. Impairment on frontal-lobe tasks (e.g. WCST) was found to sometimes result from temporal lobe pathology. When asked to rapidly generate words belonging to a specific phonemic (e.g. the letter 's') or semantic category (e.g. 'anima ls'), healthy subjects decrease superior temporal lobe activity while increasing prefrontal activity. Schizophrenic patients fail to modulate the superior temporal gyrus (STG) during word generation, leading to an abnormally ac tive STG. Even though there is growing evidence for the support of disrupted fronto -temporal connectivity in schizophrenia, current imaging methods are not polished enough to resolve real-time network activity with a high degree of spatial resolution. Due to these limitations, it is equally possible that the observed abnormalities can be explained with a more focal deficit in the DLPFC. This DLPFC deficit prevents it from controlling cognitive processing and leads to dysfunction in various brain regions. Psychopathology Page 14