2024 Psychotic Disorders.pdf

+ Schizophrenia Spectrum and Other Psychotic Disorders Dr. Nicole Kostiuk, R. Psych + Important Terms in Psychosis n Positive Symptoms: a symptom evident by its presence, refers generally to distorted reality n n Appear to involve excessive activity in some neural circuits that include dopamine as a...

+ Schizophrenia Spectrum and Other Psychotic Disorders Dr. Nicole Kostiuk, R. Psych + Important Terms in Psychosis n Positive Symptoms: a symptom evident by its presence, refers generally to distorted reality n n Appear to involve excessive activity in some neural circuits that include dopamine as a neurotransmitter Delusions: fixed beliefs, not amenable to change in light of conflicting evidence. May include a variety of themes n Bizarre vs. nonbizarre n Persecutory n Referential n Grandiose n Somatic n Religious** n Erotomania n Jealous + Important Terms in Psychosis n Hallucinations: perception-like experiences that occur without an external stimulus. n May occur in any sensory modality n Auditory, visual, tactile, gustatory, olfactory n Auditory is most common n n Voices, familiar and unfamiliar, perceived as distinct from own thoughts Visual less common** n Don’t tend to be clear + Important Terms in Psychosis n Disorganized Symptoms: can include speech, behaviour, affect, and thoughts n n Disorganized Thinking (Speech) n Disorganized thinking inferred from speech n Loose Associations n Tangentiality n Incoherent (rare) n Must impair effective communication Disorganized/Abnormal Motor Behaviour and Inappropriate Affect n Range of manifestations: childlike silliness to unpredictable agitation n Catatonic Behaviour: marked decrease in reactivity to environment n Laughing or crying at inappropriate times n Acting unusual; hoarding objects + Important Terms in Psychosis n Negative Symptoms: a symptom characterized by the absence of behaviours that are normally present, in areas such as speech, affect, and motivation n Not specific to schizophrenia Many neurological disorders that involve damage particularly to the frontal lobes n n Associated with poorer prognosis n Affective flattening n Avolition n Alogia n Anhedonia n Asociality: + Delusional Disorder n n A. The presence of one (or more) delusions with a duration of 1 month or longer n B. Criterion A for Schizophrenia has never been met n C. Apart from the impact of the delusions or its ramifications, functioning is not markedly impaired, and behaviour is not obviously bizarre or odd* n D. If manic of major depressive episodes have occurred, these have been brief relative to the duration of the delusional periods *If you do not bring up the specific topic/belief, you may not even notice + Schizophrenia n n A. Two (or more) of the following, each present for a significant period of time during a 1-month (or less if successfully treated). At least one of these must be 1, 2, or 3: n 1. Delusions n 2. Hallucinations n 3. Disorganized speech n 4. Grossly disorganized or catatonic behaviour n 5. Negative symptoms B. For a significant portion of time since onset, level of functioning in one or more major areas, such as work, interpersonal relations, or self-care, is markedly below the level achieved prior to the onset. Or there is a failure to achieve expected level of interpersonal, academic or occupational functioning + Schizophrenia n C. Continuous signs of the disturbance persist for at least 6 months. This period must include at least 1 month of Criterion A symptoms and may include prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by negative symptoms only. n D. Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out because either 1) no major depressive or manic episodes have occurred concurrently with the active-phase symptoms, or if mood episodes have occurred they have been present for a minority of the total duration. n E. Disturbance is not attributable to the physiological effects of a substance of another medical condition + n n Prior to DSM-5, diagnostic subtypes were used n Paranoid, disorganized, catatonic, undifferentiated, residual n Due to lack of empirical support these were removed and only the specifier “with catatonia” remained Catatonia: state characterized by significant motoric disturbance including symptoms such as; n Motor immobility or stupor n Excess motor activity that has no apparent purpose n Extreme negativism or mutism n Peculiar movements (posturing, stereotyped movements) n Echolalia or echopraxia + Course of Schizophrenia n Premorbid n n Evidence of cognitive, emotional, and behaviour signs prior to prodromal phase of illness Prodromal n Often experiencing subthreshold positive psychotic symptoms or brief intermittent symptoms n Numerous behaviours of concern n n Again, pretty nonspecific n Functional impairments become noted n Neuropsychological deficits present First Episode n Full threshold psychotic symptoms n Acute n Residual + Course Onset earlier for males than females Early to mid-20’s vs. late 20’s Earlier is bad news More likely to include deficits in verbal abilities Psychotic symptoms tend to diminish over the life course Due to normal age-related declines in dopamine activity? DSM-5 + Course Effect of age of onset is likely related gender Males Worse premorbid adjustment Lower educational achievement More prominent negative symptoms and cognitive impairment In general a worse outcome Women Later illness onset Lower negative symptom severity Greater affective symptoms Better social, cognitive, and premorbid functioning + Pediatric n Childhood onset: onset prior to age 13 n Early Onset: onset between 13 and 17 n Presentation is similar to that in young adults: diagnostic criteria is reliable n Delusions/hallucinations may be simpler n n Visual hallucinations more common Tend to have gradual onset and prominent negative symptoms + Geriatric n Issues regarding: n Late Onset n Progressive Decline + Late Onset Schizophrenia n More common in women n Indications of better premorbid functioning n Appears to be less cognitive impairment n n Similar pattern though Typical symptoms and course n n n n n Especially paranoia Less negative symptoms/disorganization Prognosis may not be as unfavourable Antipsychotics equally effective n But elderly more susceptible to side-effects Similar risk of relapse n Query impact of sensory loss n Etiology may be different than in typical onset n n Other explanations Different condition? + Progressive Decline § Severity of neuron loss does not seem to increase in proportion to duration of illness § Suggests pathology is established at the time of initial clinical presentation, and does not necessarily progress § n Supports idea that schizophrenia is a neurodevelopmental disorder Is schizophrenia also a neurodegenerative condition? n In late life, subgroup of individuals with schizophrenia show unusually rapid cognitive decline n Evidence is somewhat inconclusive n Alternative Explanations + Diathesis-Stress Model n Diathesis: genetic vulnerability n Increased probability for the disorder proportional to the percentage of genes shared with an affected individual Banich and Compton (2018) Cognitive Neuroscience. Cambridge Univ Press: New York + Heritability of Schizophrenia § Heritability ranges from 80 to 85% § § § strong indicator of a biological basis for schizophrenia Adoption studies § Adult schizophrenics that were adopted as children are likely to have schizophrenic biological relatives. Twin studies § Concordance rates for schizophrenia are higher for identical than for fraternal twins: § 50% chance for identical twin § 9% chance other sibling + Genetics n Significant associations with schizophrenia for more than 100 gene loci n n n Account for only a portion of the liability overall; with many false positives Hundreds or maybe thousands of common genetic variants, each with small effects, are probably involved in multiple pathogenic pathways to the disorder Genetic risks for schizophrenia are shared with many other psychiatric disorders n n n n ADHD Major Depressive Disorder Bipolar Disorder Autism Spectrum Disorder + n Parents, siblings, and off-spring of individuals with schizophrenia show similar, yet attenuated (reduced), intermediate phenotypes of the illness n n Relatives of individuals with schizophrenia manifest neurocognitive deficits in attentional, perceptual-motor, episodic memory, and executive function performance compared with normal controls. Inheritance n Many complex genes of small effect, n Rare mutations with larger effects n Complex interactions of genes with other genes n Interaction of genes with the environment + Premorbid Intelligence and Pervasive Developmental Disorders n Are considered risk factors but may just co-occur as a result of shared biological risk n Retrospective studies of individuals who develop schizophrenia have found: n Increased rates of IDs and ASDs in childhood n Language, motor, and social abnormalities + Environmental Factors Associated with Increased Incidence n Season of birth n Population density n Viral Epidemics n Latitude n Socioeconomic Status n Obstetric Complications n Substance Abuse + Season of Birth Late winter and early spring births associated with higher risk of schizophrenia Relative number of schizophrenic births is especially high if the temperature was lower than normal during the previous autumn + Population Density Seasonality effect occurs primarily in cities but is rarely found in the countryside Viruses are more readily transmitted in regions with high population densities + Viral Epidemics Increased incidence of schizophrenia is found in babies born a few months after an influenza epidemic, whatever the season It is likely that only a small proportion of all cases may have neurodevelopmental disturbances caused by viral pathology (Torrey, et al., 2007) + Latitude People born farther from the equator are more likely to develop schizophrenia Also true for MS Magnifying the seasonality effect? + Socioeconomic Status n Occurs at higher rates in families in which n Parents are unmarried/divorced n Low income/increased poverty + Obstetric Complications n Maternal infection during pregnancy n Maternal malnutrition n Labor and delivery complications n Prematurity n Low birth weight + Maternal Malnutrition Increased incidence of schizophrenia found in offspring of women who were pregnant during a famine related to German blockade of the Netherlands during World War II Due to thiamine deficiency? Buildup of toxins when mother began eating normal diet again? Interestingly, the increased incidence occurred in the offspring who were in the second trimester when the blockade ended + Maternal Stress A higher incidence of schizophrenia in the offspring of women who learned that their husbands had been killed in combat during World War II + Substance Use n Substance use has been associated with increased risk n Especially frequent cannabis use in adolescence + Schizophrenia as a Neurodevelopmental Disorder n n Multiple neurodevelopmental factors are suspected n Flaws in cell migration n Lack of development of synaptic connections n Pruning problems Evidence for neurodevelopmental abnormalities include: n premorbid behavioural and neurological signs n adverse prenatal and perinatal events n reduced dendritic complexity and lower spine and synapse density on cortical pyramidal neurons n cortical and subcortical reductions in gray matter volume n decreased white matter integrity + Reduced Synaptic Connectivity n Gray matter volume normally increases until age 5 n Pruning begins in adolescence n Hypothesis: vulnerable individual has; n Too few synapses to begin with n Onset of normal pruning results in severe impairments + And/Or Excessive Pruning n Individuals with schizophrenia have an overly aggressive pruning process n Predisposing genotypes may interact with normal developmental periods that occur later, resulting in abnormal or excessive synaptic pruning processes during late adolescence + Brain Abnormalities in Schizophrenia n Neurological Signs n Neuroanatomic Findings n Reduced Connectivity n Electrophysiology n Functional Abnormalities n Neurochemistry n Neuropsychological Test Results + Evidence for Brain Abnormality in Schizophrenia: Neurological Signs § 36-75% of schizophrenics exhibit neurological signs that suggest the presence of brain damage § e.g., nystagmus § More frequent in schizophrenia than in other psychiatric populations + Neuroanatomic Findings n Many hypotheses about specific neuroanatomic deficits, but none of these have been well validated n Marked by widespread changes in cortex n Cortical thinning n Decreased neuropil n Reductions in white matter integrity n Abnormalities in subcortical structures n Ventricular enlargement n Ventricular enlargement and prominence of cortical sulci are most robust findings n Approximately 1/3 will have and cause is unknown + Evidence for Brain Abnormality in Schizophrenia: CT and MRI Subcortical tissue loss demonstrated by enlargement of the lateral and third ventricles n Reduction in cortical gray matter (Bilder, 2014) n Reduction of markers of white matter integrity such as in MRI DTI (Bilder, 2014) n The most frequent structures demonstrating morphological abnormalities have involved the temporal lobes, frontal lobes and basal ganglia n Variability across studies likely the result of methodological differences n + Hallucinations and External Perceptions Activate the Same Regions of the Brain § Neuroimaging studies of hallucinations: § difficult because they require the patient to be scanned at the time of the hallucinations. § Consistently, auditory hallucinations are associated with activation of the primary auditory cortex and Wernike’s area Pliszka, S (2016) Neuroscience for the Mental Health Clinician (2nd Ed), New York, Guilford Press. + Evidence for Brain Abnormality in Schizophrenia § Ventriculomegaly especially the temporal horns of lateral ventricles and the left temporal horn may be more severely affected than the right § This selective enlargement suggests that structures adjacent to the temporal horn bear the brunt of the pathology, including temporal cortex, hippocampus and amygdala § Decreased volume most notably in the hippocampus, parahippocampal gyrus, amygdala and inner pallidal segment + Less Connectivity o Reduced gray matter o Diffusion Tensor Imaging o Decreased structural integrity of the large white tracks o Postmortem studies and Magnetic Resonance Spectroscopy o Reduced dendritic spines on neurons o Decreased glutamate and GABA release o Decreased synaptic protein messenger RNA + Grey Matter Reductions Present at First Onset n n These deficits are present at first episode and become worse over time. The deficits are particularly pronounced in those with childhoodonset schizophrenia (Rapoport, Giedd, & Gogtay, 2012). Pliszka, S (2016) Neuroscience for the Mental Health Clinician (2nd Ed), New York, Guilford Press. + Evidence for Brain Abnormality in Schizophrenia: Electrophysiology § Base rate of EEG abnormalities in controls is about 0-10% § Base rate in non-schizophrenic psychiatric populations is about 10- 20% § Base rate in schizophrenia is about 2040% § No distinct pathognomonic pattern + Evidence for Brain Abnormality in Schizophrenia: Neuroimaging n n Frontal, temporal, and basal ganglia dysfunction have all been demonstrated on cerebral perfusion measures n SPECT regional cerebral blood flow n PET regional glucose metabolism Studies tend to show “hypofrontality” + Evidence for Brain Abnormality in Schizophrenia: fMRI Findings were compatible with research using other methods, e.g., abnormalities in frontotemporolimbic regions Selected studies demonstrated intact functioning in posterior cortical regions on various tasks but a failure to recruit the frontal regions compared to normals, e.g., mental arithmetic + Neurochemistry in Schizophrenia: Role of Dopamine n Positive symptoms are reduced by drugs that block dopamine receptors (dopamine antagonists) n Drugs that produce positive symptoms are dopamine agonists n n n Genes may code for abnormally sensitive post-synaptic receptors or pre-synaptic receptors n n Prevent reuptake of dopamine Increase dopamine synthesis Locations of 5 dopamine receptor genes is known n No evidence to link schizophrenia to any Antipsychotics medication reduces positive symptoms + Increased Dopamine Synthesis and Reception § Advent of positron emission tomography (PET) allowed for the ability to image dopamine release and dopamine receptors in the brain. § Extensive review of PET studies concluded that there is evidence for excessive dopamine in schizophrenia. § Relative to controls, persons with schizophrenia show an increase in dopamine synthesis presynaptically, coupled with a modest increase in the density of postsynaptic D2 receptors. § Persons with schizophrenia also show increased release of dopamine in response to administration of amphetamine. + First Generation Antipsychotics and Dopamine o FGAs (e.g., haloperidol) block D2 receptors o Block in all pathways o Nigrostriatal pathway o Mimic effects of Parkinson’s Disease o Generally, the negative symptoms of schizophrenia are left untouched. + Dopamine May Not be the Only Issue Antipsychotics medication reduces positive symptoms but not negative symptoms So what is causing those? Disturbance in dopamine may be a secondary effect in the disorder. SGAs generally had more potency at blocking serotonin 2A (5-HT2A) receptors than FGAs, and this was hypothesized to underlie their increased benefit But 5-HT2A anatagonists do not have any beneficial effect on schizophrenia + Neuropsychological Assessment Results n Meta-analyses reveal moderate to severe deficits across virtually all functions, with memory, attention, and executive functions demonstrating most robust impairments. n n 1.0 to 1.5 SD below average of matched controls Intelligence: n n Global premorbid cognitive deficits and cognitive decline accompany onset of frank illness. n Following resolution of first episode, intellectual ability tends to remain stable Fluid intellectual abilities requiring attention, working memory, abstraction, and processing speed are more impaired than crystallized abilities. n Smaller relative deficits on academic achievement tests than fluid intellectual abilities. + Information Overload § Attention/Concentration: deficits are fundamental feature. § Particularly when intensity or complexity of task demands are higher, but not when lower § Slowed reaction time § Poor vigilance, impaired sustained concentration and selective attention. § Easily overloaded by processing demands suggest they deplete available resources at a lower level, regardless of task modality. + n Processing Speed: reduced consistently. One of the most significant deficits in terms of effect size n Language: n Basic abilities preserved. n Higher level relatively intact n Language processing can be affected n Measures emphasizing initiation, generation, and speed of processing, reveal impairments. n Formal thought disorder may disrupt speech (e.g., idiosyncratic word usage, incongruous combinations) + n Memory: deficits in declarative memory are among the most severe impairments; characterized by deficits in encoding, consolidation, organization, and retrieval. n Recall but not recognition is impaired (not universal) n n n n Particularly when strategies are required n Do not make normal semantic categorical clustering Conclusion: patients with schizophrenia fail to spontaneously use strategies for effective performance Nonverbal Memory: less studied n n Some studies show equivalent deficiencies Typically show comparable levels of impairment Procedural Memory: seem intact + n Visuospatial Abilities: typically better preserved, unless task is timed and requires good attention and psychomotor skills n Executive Funtions: significant overlap between clinical features of schizophrenia and those associated with frontal system dysfunction (e.g., reduced spontaneity, avolition, mental rigidity, lack of social judgment), no surprise that deficits are severe (significant overlap with working memory and attention domains) + n Sensorimotor: n n Antipsychotic treatment n Parkinsonian symptoms (tremor, bradykinesia, bradyphrenia) and akathisia (motor restless and agitation) n Usually reversible n Tardive dyskinesia is potentially irreversible n Catatonia has declined in prevalence n Olfactory deficits associated with increased severity of negative symptoms Emotion and Personality: n n n Social cognitive domains n Emotion processing n Social perception n Theory of mind Key determinant of functional disability in people with schizophrenia. Anosognosia not uncommon n Predicts non-adherence to treatment + Frontal and Temporal-limbic Pattern Consistent with frontal-subcortical Impairments in spontaneous use of strategies Similar to patients with frontal lobe dysfunction Some researchers have suggested a more “generalized deficit” Significantly lower PIQ and VIQ More diffuse impairments Possible deteriorating course + Confounds to Interpretation of Neuropsychological Findings § Much of what we know about brain functions are based on stroke or lesion data § However, schizophrenia is likely neurodevelopmental § How well does lesion data even apply? § Different neuropsychological profiles in patients § Frontal, lateralized, and diffuse § 60% demonstrate intact performance § Impairments more common in patients with predominantly negative symptoms + Medical Comorbidities n Common complicating factor; 20% reduction in lifespan n Greater cardiovascular morbidty n Increased cigarette smoking n n COPD and tuberculosis n Obesity n Diabetes mellitus n Hypertension n Hyperlipidemia n Malnutrition n Sedentary lifestyle Antipsychotic medication increases risk of metablolic syndrome n Increases risk for heart attack and cerebrovascular accidents + Mortality Rate n 2-3 fold increased mortality rate n Increased risk of suicide n n 12 times higher than in general population n High-risk behaviours n Accidents n Substance abuse Mortality gap between schizophrenia and general population has actually widened n Suggests people with schizophrenia have not experienced improved health outcomes, unlike the rest of the population + Prognosis n Risk factors for poor prognosis n Cognitive Impairment n Negative symptoms n Younger age of onset n Insidious onset with poor premorbid functioning n Family history n Increased number of relapses n Poor compliance with treatment n Poor social support n Trauma history + Schizoaffective Disorder n A. An uninterrupted period of illness during which there is a major mood episode (major depressive or manic) concurrent with Criterion A of Schizophrenia. The major depressive episode must include Depressed Mood n B. Delusions or hallucinations for 2 or more weeks in the absence of a major mood episode during the lifetime duration of the illness n C. Symptoms that meet criteria for a major mood episode are present for the majority of the total duration of the active and residual portions of the illness n D. Not attributable to the effects of a substance or medical condition + Other Psychotic Disorders n Substance-Induced: delusions and/or hallucinations that developed during or soon after substance intoxication or withdrawal of a substance that is capable of producing the symptoms (e.g., cocaine, methamphetamines, alcohol). Symptoms should not persist for a substantial period of time (e.g., 1 month) after the cessation of use/intoxication/withdrawal** n Schizophreniform: same symptoms as Schizophrenia, but have not yet lasted 6 months but have lasted at least 1 month n Brief Psychotic Disorder: Criterion A symptoms of Schizophrenia that last at least 1 day but less than 1 month, with return to premorbid levels of functioning + Psychotic Disorders n Assessment n Observation/Interview n Poor historians in acute states n Collateral n MMPI-2 n n PAI n n Scale 6 and 8 SCZ and PAR scales PANSS + Differential Diagnosis n Comorbid illness is common, with syndromal overlap including depression, OCD, and anxiety n Can be difficult to distinguish from schizoaffective disorder and mood disorders with psychotic features n n Primary bases is interview and history taking Substance use also complicates diagnosis and management + Medications n Treatment n n Acute phase; mainly medical intervention n Conventional antipsychotics n Atypical antipsychotics Antipsychotic medication ameliorates positive symptoms, but does not help with cognitive or negative symptoms typically Serious side-effects: extrapyramidal or Parkinsonian n Akinesia n Tardive dyskinesia Some have adverse effects on cognition (particularly at high doses) Also motor symptoms (EPS) which are dose related n n n n Use of medications such as cholinesterase inhibitors and stimulants to treat neuropsychological deficits in other disorders have inconsistent results n Use of stimulants (act on dopamine!) can help with attention problems theoretically but may increase vulnerability to psychotic episode + Treatment n Reducing the gap between onset of psychosis and treatment initiation improves outcomes n Less psychotic breaks and increased medical compliance leads to better outcomes n Compliance is a serious problem n LAI + Polypharmacy is the Rule, not the Exception n Adjunct medications typically prescribed: n Mood stabilizers/antidepressants n n Sedatives n n Address movement disorders Soporifics n n Address agitation Anticholinergic n n To address mood disorder and emotional labilitiy Address sleep disturbance Beware drug interactions and impact on cognition! + Neuroleptic Malignant Syndrome Uncommon but life-threatening. Occurs within hours or days of exposure Acronym FEVER + Agranulocytosis n Rare n Potentially fatal n Acute lowering of white blood cell n Occurs particularly in patients treated with clozapine n Requires regular blood work + Treatment n Avatar Therapy n Cognitive remediation strategies have shown improvements in multiple domains of cognition, but are insufficient for improvement in daily living skills. n n Also need to target strategy-based interventions for adaptive behaviours in order to improve functional outcomes Employment: helping indivudals return to work is associated with reduced symptoms, better overall functioning, improved quality of life n Individual placement with supportive services + Treatment n Token economies n Successful, but expensive n Movement towards de-institutionalization n Improve medication compliance n Reduce relapse n Increase skills and adaptive functioning n Increase social skills n Increase self-care n Increase insight into disorder n Family therapy