Schizophrenia- biological and neuropsychological approacesh
VOICES IN HER HEADShe hears them,And she always has said,"They whisper when theyre mad,and they scream when they are just barely there.They hurt my thoughts,and destroy my brain."This poor girl lies awake at night,As she wonders to herself,"Are schizophrenics messengers of God?Is there even a God?Im doubting myself,The only person I know I can trust.At least,I thought I knew.Now maybe I am just insane."She goes about day to day,Acts like everything is fine,But the voices linger there,Even controlled by medicine.She still has stress,She still has fear,She still has anxiety,She still has schizophrenia. - Kimberly Anne
Presented by: Chairperson:Priya Puri & Aditi Majumdar Dr. Sujit Sarkhel1st Year Trainees Assistant ProfessorDept. of Clinical Psychology IOP, KolkataIOP, Kolkata Date: 05-03-2012
The schizophrenic disorders are characterized in general by fundamental and characteristic distortions of thinking and perception, and affects that are inappropriate or blunted. Clear consciousness and intellectual capacity are usually maintained although certain cognitive deficits may evolve in the course of time. The most important psychopathological phenomena include: • thought echo • thought insertion or withdrawal • thought broadcasting • delusional perception and delusions of control • influence or passivity • hallucinatory voices commenting or discussing the patient in the third person • thought disorders and negative symptoms.
Schizophrenia occurs with regular frequency nearly everywhere in the world in 1 % of population and begins mainly in young age (mostly around 16 to 25 years). Schizophrenia is defined by ◦ a group of characteristic positive and negative symptoms ◦ deterioration in social, occupational, or interpersonal relationships ◦ continuous signs of the disturbance for at least 6 months
Morel (1852): Reported a series of cases of severe intellectual deterioration starting in adolescence and he called it “demence précoce” Emil Kraepelin (1899): This illness develops relatively early in life, and its course is likely deteriorating and chronic; deterioration reminded dementia (“Dementia praecox”), but was not followed by any organic changes of the brain, detectable at that time. Eugen Bleuler (1911): He renamed Kraepelin‟s dementia praecox as schizophrenia he recognized the cognitive impairment in this illness, which he named as a “splitting”” of mind. Kurt Schneider: He emphasized the role of psychotic symptoms, as hallucinations, delusions and gave them the privilege of “the first rank symptoms” even in the concept of the diagnosis of schizophrenia.
History (cont…) disturbance of association autism ambivalence affective blunting Schneider‟s First-Rank Symptoms Audible thoughts Voices arguing or discussing Voices commenting on patients actions Somatic passivity Thought withdrawal Thought insertion Thought broadcasting Made feelings Made impulses or drives Made volitional acts Delusional perception
Diagnostic manuals: lCD-10 (“International Classification of Disease”, WHO) DSM-IV-TR (“Diagnostic and Statistical Manual”, APA) Clinical picture of schizophrenia is according to lCD-10, defined from the point of view of the presence and expression of primary and/or secondary symptoms (at present covered by the terms negative and positive symptoms): the negative symptoms are represented by cognitive disorders, having its origin probably in the disorders of associations of thoughts, combined with emotional blunting and small or missing production of hallucinations and delusions the positive symptom are characterized by the presence of hallucinations, delusions, disorganised speech and disorganised behaviour.
BIOLOGICAL APPROACHES Genetics of Schizophrenia… Genetic investigations are done in three ways: Family studies Twin studies Adoption studies
Family studies: The first systematic family study was carried out in Kraeplin‟s department by Ernst Rudin, who showed that the rate of dementia praecox was higher among the siblings of probands than in the general population. About 5-10 percent average life-time risk was seen in first-degree relatives of schizophrenics.
Table showing approximate lifetime risk of developing schizophrenia for relatives of a proband with schizophrenia Relationship Life-time risk (%) Parents 4.4% All siblings 8.5% Siblings (one parent schizophrenic) 13.8% Children 12.3% Children (both parents schizophrenic) 36.6% Half siblings 3.2% Nephews and nieces 2.2%
Twin Studies: Twin studies have also come to the conclusion that schizophrenia is heritable to some extent. Luxenberger (1928) found concordence in 11 of his 19 MZ pairs and in none of his 13 DZ pairs. Cardno and Gottesman (2000) found 50% concordence rates in MZ twins and 10% for DZ twins. A recent meta-analysis study by Sullivan et al., (2003) found the heritability (the proportion of liability to a disorder in a population that is attributed to genes) of schizophrenia to be about 73-90 per cent.
Adoption studies: Genetically related to Not Genetically related Study schizophrenics to schizophrenicsHeston 1966, 5 out of 47 adoptees (10.6%) None out of 50 developedWender, 1974 13 out of 69 (18.8%) 3 out of 28 (10.7%)Tienari 2000 17 out of 164 (10.4%) 4 out of 197 (2%)Adoption studies have therefore convincingly supported theresults of family and twin studies in demonstrating the significantrole of genetic factors in schizophrenia.
What are Neurotransmitters : Neurotransmitters are chemical base balls being tossed between the neurons back & forth. They are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse . They are also found at the axon endings of motor neurons, where they stimulate the muscle fibres. Neurotransmitters also communicate information throughout our brain and body. In other words, they tell the nerve cells next in line what to do, ie. Whether it should or not pass a message along. They also influence the production of other chemicals inside the neurons. They are produced by some glands such as pituitary and the adhrenal gland.
Neurotransmitters can be classified on the basis of excitatory and inhibitory actions & on the basis of molecular size. Excitatory : Dopamine, Acetylcholine, Norepinephrine, Epinephrine, Nitric oxide, glutamate Inhibitory : Serotonin,GABA, Dopamine, Acetylcholine, Nor epinephrine, 4 classes of small molecules of neurotransmitters : Amino acids, Monoamines, soluble gases, Acetylcholine, One class of large molecule neurotransmitters : Neuro peptides
Plays role in cognition (D1 &D4 receptors) voluntary movement ( D2 receptor), anticipatory desire & motivation, punishment, reward, sleep, mood. Has inhibitory role on the function of prolactin. Dopamine medication acts on sympathetic NS producing effects such as increased heart rate & BP In frontal lobe, DA controls the flow of information from other areas of the brain. Aggression stimulates DA release Libido can be increased by the drugs that affect DA Has a role in nausea & vomiting via interaction in the chemo receptor trigger zone DA induces sodium loss in kidney DA has a role in social anxiety. Decreased D2 receptor binding found in people with social anxiety
Help long term potentiation , neural plasticity involving learning & memory Free glutamatic acid present in cheese, soya sauce, & responsible for umami, one of the 5 basic tastes of human being – also found in food additives and flavor enhancers Precursor for the synthesis of inhibitory GABA Found in meat, egg ,fish, diary products
Key dopamine pathways in the brain 4 well-defined dopamine pathways in the brain involved in schizophrenia.They include-mesolimbic, mesocortical, nigrostriatal,and tuberoinfiindibular dopamine DA pathways. Mesolimbic dopamine pathway and the positive symptoms of schizophrenia This pathway projects from dopaminergic cell bodies in the ventral tegmental area of the brainstem to axon in the ventral striatum . terminals of nucleus accumbens have an important role in several emotional behaviors, including the positive symptoms of psychosis, such as delusions and hallucinations. also important for motivation, pleasure, and reward. It has been observed that diseases or drugs that increase dopamine will enhance or produce positive psychotic symptoms, whereas drugs that decrease dopamine will decrease or stop positive symptoms. For eg, stimulant drugs such as amphetamine and cocaine release dopamine and, if given repetitively, can cause a paranoid psychosis virtually indistinguishable from the positive symptoms of schizophrenia. All known antipsychotic drugs capable of treating positive psychotic symptoms are blockers of the D2 dopamine receptor. Hyperactivity of this pathway hypothetically accounts for positive psychotic symptoms. Hyperactivity of mesolimbic dopamine neurons may also play a role in aggressive and hostile symptoms in schizophrenia and related illnesses, especially if serotonergic control of dopamine is aberrant in patients who lack impulse control.
Mesocortical dopamine pathway This pathway projects from the ventral tegmental area but projects to the areas of the prefrontal cortex. Branches of this pathway into the dorsolateral prefrontal cortex are hypothesized to regulate cognition and executive functioning whereas areas projecting to ventromedial parts of prefrontal cortex are hypothesized to regulate emotions and affect. many researchers believe that cognitive and some negative symptoms of schizophrenia may be due to a deficit of dopamine activity in mesocortical projections to dorsolateral whereas affective and other negative symptoms of schizophrenia may be due to a deficit of dopamine activity in mesocortical projections to ventromedial prefrontal
Theoretically, increasing dopamine in the mesocortical dopamine pathway might improve the negative, cognitive, and affective symptoms of schizophrenia. However, since there is hypothetically an excess of dopamine elsewhere in the brain within the mesolimbic dopamine pathway, any further increase of dopamine in that pathway would actually worsen positive symptoms. Thus, this state of affairs for dopamine activity in the brain of schizophrenic patients poses a therapeutic dilemma: how do we increase dopamine in the mesocortical pathway while, at the same time, also decreasing dopamine activity in the mesolimbic dopamine pathway? Mesolimbic dopamine pathway, reward, and negative symptoms Dopamine function in schizophrenia may be more complicated than just "too high" in mesolimbic areas and "too low" in mesocortical areas. Instead, they may be better characterized as "out of tune" or "chaotic." A similar phenomenon may be occurring in the mesolimbic dopamine system, with one subset of mesolimbic dopamine neurons out of tune and hyperactive, mediating positive symptoms, and another set of mesolimbic dopamine neurons out of tune but hypoactive, mediating some negative symptoms and malfunctioning reward mechanisms. The mesolimbic dopamine pathway is not only the postulated site for the positive symptoms of psychosis but is also thought to be the site of the brains reward system or pleasure center. When a patient with schizophrenia loses motivation and interest and has anhedonia and lack of pleasure, such symptoms could also implicate a deficient functioning of the mesolimbic dopamine pathway not just deficient functioning in the mesocortical dopamine pathway.
Nigrostriatal dopamine pathway nigrostriatal dopamine pathway, projects from dopaminergic cell bodies in the brainstem substantia nigra via axons terminating in the basal ganglia or striatum. The nigrostriatal dopamine pathway is a part of the extrapyramidal nervous system, and controls motor movements. Deficiencies in dopamine in this pathway cause movement disorders, including Parkinsons disease. Dopamine deficiency in the basal ganglia can also produce akathisia (a type of restlessness) and dystonia (twisting movements, especially of the face and neck). These movement disorders can be replicated by drugs that block dopamine-2 receptors in this pathway. Hyperactivity of dopamine in the nigrostriatal pathway is thought to underlie various hyperkinetic movement disorders such as chorea, dyskinesias, and tics. Chronic blockade of dopamine-2 receptors in this pathway may result in a hyperkinetic movement disorder known as neuroleptic-induced tardive dyskinesia. Thus in schizophrenia, the nigrostriatal pathway in untreated patients may be relatively preserve.
Tuberoinfundibular dopamine pathway project from the hypothalamus to the anterior pituitary . Normally, these neurons are active and inhibit prolactin release. If the functioning of tuberoinfundibular dopamine neurons is disrupted by lesions or drugs, prolactin levels can also rise. Elevated prolactin levels are associated with galactorrhea (breast secretions), amenorrhea (loss of ovulation and menstrual periods), and possibly other problems such as sexual dysfunction. Such problems can occur after treatment with many antipsychotic drugs that block dopamine-2 receptors Thus in untreated schizophrenia, the function of the tuberoinfundibular pathway may be relatively preserved
Amphetamine releases dopamine at the synapse and causes positive symptoms of schizophrenia in non schizophrenic individuals Levodopa increases central dopamine concentrations and causes positive symptoms of schizophrenia in non schizophrenic individuals Disulfiram inhibits dopamine metabolism and exacerbates schizophrenia All effective anti psychotic drugs are dopamine2 receptor antagonists Antipsychotic efficacy correlates significantly with D2 receptor occupancy Increased and asymmetric brain D2 receptor densities have been reported in living schizophrenic patients, using PET Increased concentrations of D2 receptors and of dopamine have been found in postmortem brain tissue from schizophrenic patients.
Key glutamate pathways in the brain and the NMDA receptor hypofunction hypothesis of schizophrenia Glutamate is a excitatory neurotransmitter & is sometimes called the Master Switch as it is capable of exciting almost all neurons in the brain.There are five glutamergic pathways, all relate to glutamatergic pyramidal neurons in the prefrontal Cortex. Corticobrainstem glutamate pathways and the NMDA receptor hypofunction hypothesis of schizophrenia descending glutamatergic pathway projects from cortical pyramidal neurons to brainstem neurotransmitter centers, including the raphe for serotonin, the ventral tegmental area (VTA) and substantia nigra for dopamine, and the locus coeruleus for norepinephrine. This pathway is a key regulator of neurotransmitter release. It acts as a brake on the mesolimbic dopamine pathway. This normally results in inhibition of dopamine release from the mesolimbic pathway. A major current hypothesis for schizophrenia involves NMDA receptors in this pathway when NMDA receptors are made hypofunctional by means of the NMDA receptor antagonist phencyclidine (PCP)- produces a psychotic condition in normal humans very similar to the positive symptoms of schizophrenia. To a lesser extent, the NMDA receptor antagonist ketamine can also produce a schizophrenia-like psychosis in normals. This has led to the hypothesis that NMDA receptors specifically in the corticobrainstem glutamate projection might be hypoactive in untreated schizophrenia & thus cannot do their job of inhibiting mesolimbic dopamine neurons. This led to mesolimbic dopamine hyperactivity as a result. That is, mesolimbic dopamine hyperactivity that produces positive symptoms of schizophrenia may actually be the consequence of NMDA receptor hypoactivation in corticobrainstem glutamate projections.
NMDA receptors in corticobrainstem glutamate projections that regulate mesocortical dopamine pathways may also be hypoactive in schizophrenia. As it has been seen PCP also mimics the cognitive, negative and affective symptoms of schizophrenia. That is, normal humans who take PCP and render their NMDA receptors hypofunctional not only experience positive symptoms but also affective symptoms such as blunted affect, negative symptoms &cognitive symptom. Normally, these descending corticobrainstem glutamate neurons act as accelerators to mesocortical dopamine neurons. This means that corticobrainstem glutamate neurons normally function as accelerators of these mesocortical dopamine neurons; therefore they excite them. The consequence of this neuronal circuitry is that when corticobrainstem projections to mesocortical dopamine neurons have NMDA receptor hypoactivity, they lose their excitatory drive and become hypoactive. This could hypothetically explain why mesocortical dopamine neurons are hypoactive and thus their link to the cognitive,negative, and affective symptoms of schizophrenia.
NMDA ReceptorNMDA Receptor regulation of Hypofuncn. In Cortico-Mesocortical DA pathways: Brainstem Projection :Excitation Hypoactivity of Mesocortical OA pathways
Thalamocortical glutamate pathways An ascending glutamate pathway starts from the thalamus and innervates pyramidal neurons and is known as the thalamocortical pathway A properly functioning thalamic filter prevents too much sensory input from penetrating the thalamus into the cortex, so that information processing can occur in an orderly manner when descending corticobrainstem glutamate pathways have hypofunctioning NMDA receptors in the ventral tegmental area, this creates mesolimbic dopamine hyperactivity and positive symptoms of psychosis.
dopamine hyperactivity reduces the thalamic filter and permits the escape of excessive sensory information coming into the thalamus, thus allowing it to get into the cortex by means of ascending thalamocortical neurons. There is hypothetical NMDA receptor hypofunction in the descending corticostriatal glutamate pathway as well. This reduces the excitatory drive on the GABA neurons that create the thalamic filter. Coupled with the excessive dopamine drive from mesolimbic neurons, the thalamic filter fails, and too much information escapes diffusely into the cortex, where it can cause cortical manifestations of hallucinations or may also create other cortical symptoms such as cognitive, affective, & negative symptoms of schizophrenia. Corticothalamic glutamate pathways A third descending glutamatergic pathway, projects directly to the thalamus, where it may provide sensory and other types of inputs Hypofunction of NMDA receptors at this level may also cause Dysregulation of the information that arrives in the cortex due to sensory overload and a malfunctioning of cortical glutamate input directly to the thalamic filter. Corticocortical glutamate pathways Inn this pathway one pyramidal neuron communicates with another via the neurotransmitter glutamate. When NMDA receptor function normally,corticocortical glutamate loops communicate effectively &p process info effectively. NMDA receptor hypofunction in cortical pyramidal neurons can impair communication between neurons by causing hypoactivation of loop(bet DLPFC & VMPFC),hyperactivation of loop(OFC& VMPFC)or partial hypo or hyperactivation of these loops.
NMDA Receptor Regulation of Cortical PyramidalNeurons:Efficient Information Processing
Most common ways of examining 5HT functions in schizophrenia havebeen based on studying 5 Hydroxy-indole acetic acid (5-HIAA) levels inCSF, 5HT uptake in platelets and 5HT receptor functions by various 5HTreceptor binding ligands in the experimental animals, throughneuroimaging in vivo and post-mortem human brains.The results of CSF 5-HIAA level studies have been inconsistent.Most ofthe studies did not notice any change in schizophrenics as compared withthe normal.Earlier studies did notice a decreased level of 5-HIAA in schizophrenicbrains(Ashcroft et al.,1966).In the suicidal schizophrenic patients CSF 5-HIAA levels have beensignificantly low in comparison with that of non-suicidal patients.(Cooperet al.,1992;vanPrag,1983) A mild increase in the platelet 5HT2A receptorhas been seen in suicidal schizophrenic patients.In some other studies 5-HIAA levels were also found inversely related tothe cerebral atrophy.Some studies have found elevated CSF 5-HIAA levels in the patients witha family history of schizophrenia .Other studies have found a positive correlation of CSF 5-HIAA withpeculiar mannerism and posturing in schizophrenic patients.
In addition,reduced levels of 5-HIAA and 5HT in various brain areas like hypothalamus,hippocampus have also been found. Most of the post-mortem human brain studies have found down regulation of the 5HT2A receptor in the frontal lobe. The positive psychotic symptoms can also be due to the serotonin- dopamine interactions.Serotonin hypofunction in the prefrontal cortex of schizophrenic brains is quite evident(Harrison,1999).Serotonin hypofunction can disinhibit the striatal and other subcortical dopamenergic neurons leading to the emergence of positive symptoms.OTHER NEUROTRANSMITTER STUDIES Norepinepinephrine-neuronal degeneration within the norepinephrine reward system could account for Anhedonia. GABA-has a regulatory effect on dopamine activity,& the loss of inhibitary GABAergic neurons could lead to hyperactivity of dopaminergic neurons. Acetylcholine and Nicotine-decreased muscarnic and nicotonic receptors in the caudate putamen,hippocampus &selected regions of the prefrontal cortex have been found.These receptors play role in the regulation of neurotransmitter systems involved in cognition,which is impaired in schizophrenia.
Limbic System :Reduced volume of hippocampus, amygdale & parahippocampalgyrus are found as well as left temporal horn enlargement. It may berelated to reduced cell no. or cell size inhippocampus/parahippocampal gyrus /entorhinal cortex. White matterin hippocampal gyrus is also reduced. The cytoarchitecure isdisturbed, there being increased vertical axon numbers & deficits insmall interneurons in the cingulate gyrus & abnormal cellarrangements in the hippocampus.
In the basal ganglia, some researchers find no changes in areas such as caudate, putamen, nucleus accumbens and external segment of the globas pallidus; others have reported increased striated volume and reduced globus pallidus ( internal segment) volume. Increased striatal volume is thought to be an effect of treatment with antipsychotics
In the thalamus, there is volume and cell number reductions or smaller whole thalamic volume.
1. Lateral & 3rd ventricular enlargement has been found in structural neuro images.2. In the brain stem, a reduced nigral volume and a trend for reduced locus coeruleus volume are taken as an indication of a dopaminergic/ nonadhrenergic underactivity.
In the cortex, contradictory results arereported in whether there is reduction ofcortical volume . There appears to be shapeabnormalities in the corpus callosum with thecorpus callosum being thicker in female &thinner in male. Data regarding cortical sulcal enlargement are split, with some reporting sulcal enlargement in the frontal and temporal lobes whereas others have found more diffuse enlargement . more specific measures of cortical volume typically show reduction of temporal & less consistently, frontal lobe volume.
The notion that the temporal & frontal lobes may play a particularly important role in Schizophrenia has been supported by findings from other areas. For example, neurological damage to the temporal lobes sometimes produces positive psychotic symptoms such as hallucinations, while damage to the frontal lobes is associated with negative symptoms such as apathy, social withdrawal and blunted effect. In neuropsychological testing, patients with Schizophrenia typically show impaired frontal & temporal lobe functions. Magnetic Resonance Spectroscopy has seen specific reductions in N- acetyl aspartate in dorsolateral prefrontal cortex and hippocampal area, probably reflecting neuronal pathology in these locations. An imbalance between phosphomondesters and phosdiesters has been described in the frontal cortex. These studies, combined with volumetric data, lend support to the theory that there may be selective deficits in frontal and temporal regions.
Other structural neuroimaging findings: Decrease in brain weight, brain length and volume of the cerebral hemisphere Grey matter appears to be reduced more than white matter Structural abnormalibility of the cerebellum.
Reduced frontal blood flow has been found Hypofrontality – Decreased activity in the frontal lobe, particularly in dorsolateral pre frontal cortex- related to cognitive impairment & -ve symptoms. Elevated and reduced blood flow has been reported in temporal lobe The most common finding is an association between resting blood flow and +ve psychotic symptoms. For example :1. One report found a correlation between increased psychopathology and blood flow to the left parahippocampal gyrus2. A second found a similar correlation between +ve symptoms and left temporal lobe blood flow.3. More specific correlation have been seen for auditory hallucinations and activation of Broca‟s area and medical temporal region
Positive symptoms are associated with medial temporal flow Affective and negative symptoms of schizophrenia may involve areas of the prefrontal cortex, such as orbital, medial, and ventral areas.These brain areas, along with the amygdala, nucleus accumbens, and other regions, comprise a "ventral"system involved in emotional processing. This ventral system interacts with "dorsal"system that includes the DLPFC and modulates the output from the ventral system ventral system includes orbital, ventral, and medial areas of prefrontal cortex, amygdala and nucleus accumbens- brain regions that are all important for the identification and appraisal of emotional stimuli and for generating an appropriate emotional response. dorsal system includes not just the DLPFC but also the hippocampus.the dorsal system maintain the emotional response from the ventral system & modulate it. it selects an appropriate behavioral output in response not only to emotions but also to demands from the environment and from theindividuals internal goals. Schizophrenia has long been recognized as having impairments in the ability to identify and accurately interpret emotions from overt sources, including facial expressions. This may be due to inefficient information processing within the ventral system and can be measured by imaging the response of the amygdala to emotional input, especially from facial expressions. Whereas normals may activate the amygdala in response to scary or fearful or emotionally charged faces.patients with schizophrenia may not.
This may represent distortion of reality as well as an impairment in recognizing negative emotions and in decoding negative emotions in schizophrenia. Failure to mount the "normal"emotional response to a scary face can also represent an inability to interpret social cues and may lead to distortions in judgment and reasoning in schizophrenia. neutral face or neutral stimulus may provoke little activation of the amygdala in a normal person.but overreaction in a schizophrenic patient is seen,who may mistakenly judge people negatively or conclude wrongly that another holds strong unfavorable impressions of him or her or may even be threatening. The activation of emotional processing in the amygdala when it is inappropriate may accompany the symptom of paranoia and lead to impaired interpersonal functioning, including problems in social communication. Psychomotor proverty syndrome is associated with underactivity of prefrontal cortex andleft parietal cortex & overactivity of bilateral caudate nuclei.
NEUROPSYCHOLOGICALAPPROACHES…… It is noteworthy that the first sentence of the description of schizophrenia in DSM-IV-TR includes references to neurocognitive disturbances: “the characteristics of schizophrenia involve a range of cognitive and emotional dysfunctions that include perception, inferential thinking, language and communication, behavioral monitoring, affect, fluency, and production of thought and speech, hedonic capacity, volition and drive, and attention.”
NEUROPSYCHOLOGICAL APPROACHES (cont…) What is Neuropsychology??? Neuropsychology studies the structure and function of the brain as they relate to specific psychological processes and behaviors.
NEUROPSYCHOLOGICAL APPROACHES (cont…) What is „Neurocognition‟???Sensation Perception Cognition Cognition - Set of interwoven processes such as memory ,language & problem solving , that we bring to bear to generate structures and strategies to apply to our perception. Neurocognition - A term used to describe cognitive functions closely linked to the function of particular areas, neural pathways, or cortical networks in the brain.
NEUROPSYCHOLOGICAL APPROACHES (cont…) attention Deficits in primary processes Information processing Memory Deficits in secondary processes Executive functions Thought disorder Deficits in meta-processes insight
NEUROPSYCHOLOGICAL APPROACHES (cont…) Vigilance refers to the ability to maintain attention over time. A standard vigilance test used in many studies is the Continuous Performance Test (CPT) patients with schizophrenia have moderately severe vigilance impairments Impairments in vigilance can result in: difficulty following social conversations social deficits, Problems in community functioning Impairment in skills acquisition
NEUROPSYCHOLOGICAL APPROACHES (cont…) Information processing refers to the processing of stimuli by the organism such that the meaning of the stimuli is extracted and the appropriate response is made. Schizophrenia is characterized by problems in stimulus processing and response programming stages of information processing Hallucinated voices may arise from disrupted speech perception
NEUROPSYCHOLOGICAL APPROACHES (cont…) Memory impairment is often the most striking feature of neurocognitive impairment in schizophrenia Verbal memory functioning includes, but is not limited to, abilities associated with learning new information, retaining newly learned information over time, and recognizing previously presented material. In general, patients show larger deficits in learning than in retention Can be understood by the connectionist theory. In schizophrenics network size does not affect the recall but connectivity does.
NEUROPSYCHOLOGICAL APPROACHES (cont…) Executive ability is the capacity to plan and implement goal directed action. The components of executive functions are: Working memory Inhibition Contextual processing Set shifting Planning
NEUROPSYCHOLOGICAL APPROACHES (cont…) Immediate/Working Memory deficits… Immediate memory refers to the ability to hold a limited amount of information “online” for a brief period of time (usually a few seconds). For example: digit forward. Some investigators consider working memory to be synonymous with immediate memory, whereas others describe that it should require some manipulation of the information being held online. For example: digit backward. Schizophrenics performed worse than normal controls on tests of working memory.
Immediate/Working Memory deficits (cont…) Working memory impairment accounted for impairment in strategic memory and not in recognition memory, indicating that it is an important component of impaired cognition in schizophrenia. Impairment in working memory emphasizes: o fronto-temporal dysfunction in schizophrenia o Dysfunctional neural network involving prefrontal and posterior brain regions
NEUROPSYCHOLOGICAL APPROACHES (cont…) Inhibition deficits… From a cognitive perspective, „„inhibition‟‟ is critical to the ability to control and regulate mental representations (thoughts) and behaviors. Control is the ability of the cognitive system to flexibly adapt its behaviour to the demands of particular tasks, favouring the processing of task-relevant information over other sources of competing information, and mediating task-relevant bahaviour over habitual or otherwise prepotent responses (Cohen et al, 1996)
Reduced inhibition was seen in patients with positive symptoms and may underlie the reality distortion and disorganization symptoms in schizophrenia. deficient inhibitory control has been assumed to play a pivotal role in the onset of hallucinations. new findings confirm that hallucinations are significantly associated with a deficit of intentional inhibition, while automatic inhibition remains intact.
Consequences of impaired inhibition: increased efforts to inhibit spontaneous recurrence unwanted cognitions of hallucinations (hallucinations) Paradoxically increased sense of involuntariness
NEUROPSYCHOLOGICAL APPROACHES (cont…) Contextual processing: It is a combination of both working memory and inhibition processes. The processing of context is closely linked to the concept of cognitive control Several performance deficits in schizophrenia may be understood in terms of functional impairment in maintaining contextual information over time and in using that information to inhibit inappropriate responses. Schizophrenic patients have been found to be performing poorly in context-sensitive conditions.
NEUROPSYCHOLOGICAL APPROACHES (cont…) Set shifting deficits: Set shifting refers to the ability to shift a cognitive set without explicit verbal instructions Wisconsin Card Sorting Test (WCST) is the most widely used test for set shifting ability. Schizophrenics are found to have specific deficit in concept formation and set-shifting (irrespective of intellectual deficit).
NEUROPSYCHOLOGICAL APPROACHES (cont…) Planning deficits: Planning is the capacity to undertake goal directed action to solve a novel task. Tower of London is a classic test employed to assess planning. Schizophrenics took more number of moves and their response speed was also slower Planning was not slower if adjusted to for overall slowing, but planning was inaccurate, suggesting deficits in problem solving ability in schizophrenics.
NEUROPSYCHOLOGICAL APPROACHES (cont…) Cognitive deficits in the areas of source memory, semantic processing self monitoring, response inhibition and theory of mind are associated with different aspects of thought disorder. Source memory: Memory for source of information is deficient in schizophrenia Schizophrenics tended to ascribe the word to an external source when they were in doubt Bias of misattributing internal events to external sources Misattribution was more prominent for emotionally salient words.
NEUROPSYCHOLOGICAL APPROACHES (cont…) Semantic processing: A direct relation was seen between impairment in verbal fluency and severity of thought disorder Schizophrenics are more cognitively biased towards emotional themes underlying their delusions. Comprehension, response monitoring and inhibition: Difficulties in comprehension, response monitoring and inhibition of irrelevant responses leads to confabulation in schizophrenia. Amount of confabulation is related to formal thought disorder and the inability to supress inappropriate responses.
NEUROPSYCHOLOGICAL APPROACHES (cont…) Theory of mind: Theory of mind is the capacity to infer another person‟s mental state. Theory of mind is deficient in schizophrenics. There is problem in meta-representation or an inability to divine another person‟s intention. These deficits are greater in schizophrenics with poorer premorbid IQ.
NEUROPSYCHOLOGICAL APPROACHES (cont…) Insight of patient towards symptoms of the illness is associated with cognitive dysfunctions It is related to impairment of executive functions Poor insight is correlated with higher perseveration and poorer abstract flexibility on WCST. Insight was present at moderate level of cognitive functioning but poor at either extremes. Low insight with low cognitive functioning is associated with poor abstraction Low insight with high cognitive functioning is associated defensive attitude towards illness. Associated with bilateral parietal deficits.
NEUROPSYCHOLOGICAL APPROACHES (cont…) Cognitive deficits are useful in identifying individuals at a higher risk for schizophrenia Deficits in intelligence, executive functions, mental control, learning and memory were found in first degree relatives of schizophrenics.
Executive community/daily function activities Episodic Social problem memory solving/instrument al skills Immediate verbal memory Psychosocial skills acquisition VigilanceN.B.:- A BLACK arrow indicates that at least four studies found a significant relationshipbetween the neurocognitive construct and the outcome domain;a BLUE arrow indicates that significant relationships were uncovered in two or threestudies.
By knowing the neuropsychological factors it becomes relatively easy to predict future possibilities of having schizophrenia. It helps in the management. Biological factors help us to know the role of different brain areas in the symptom manifestation.