Schizophrenia Spectrum Disorders PDF

Schizophrenia Spectrum Disorders Fabio Sambataro, MD, PhD [email protected]  Deprecated jargon Terms no longer in use since 1980 (DSM-III) because they are not atheoretic Psychosis more severe form of mental disorder disturbance of self-awareness and...

Schizophrenia Spectrum Disorders Fabio Sambataro, MD, PhD [email protected]  Deprecated jargon Terms no longer in use since 1980 (DSM-III) because they are not atheoretic Psychosis more severe form of mental disorder disturbance of self-awareness and external reality most frequent psychotic symptoms are delusions, hallucinations, confusion severe mood impairment altered behavior Neurosis minor mental disorders absence of psychotic symptoms presence of symptoms closer to normal (anxiety, phobias, mild mood deflection) The overall personality structure is less compromised. Borderline intermediate psychopathological condition, close to the borders of psychosis neurotic symptoms (intense, prolonged and pervasive anxiety, hysterical manifestations, neurasthenia etc.) psychotic symptoms (reference ideas, paranoid ideation, etc.) transient cognitive disturbances with occasional confusional episodes impulsive and aggressive behaviors, typical of psychopathic personalities. Psychosis  Psychosis is a state defined by a loss of contact with reality  The ability to perceive and respond to the environment is significantly disturbed; functioning is impaired  Symptoms may include hallucinations (false sensory perceptions) and/or delusions (false beliefs)  Psychosis may be substance-induced or caused by brain injury, but most psychoses appear in the form of schizophrenia History  "Dementia Praecox": Emil Kraepelin (1856-1926)  Subjects who presented with delusions, cognitive impairment at a young age with progressive and chronic course  Distinguished from Alzheimer's and senile dementia  Distinguished from manic-depressive illness (occurs at any age, course episodic, with less deterioration)  "Schizophrenia": Bleuler Eugen (1857-1939):  Literally: "Scission of the mind"  A fundamental and unifying alteration was the separation of function between personality, thinking, memory and perception  4 A's: flattened Affect, Autism, impaired Association of ideas and Ambivalence.  Chronic course or recovery differently from dementia History  In the early 20th century, the psychiatrist Kurt Schneider listed the forms of psychotic symptoms that he thought distinguished schizophrenia from other psychotic disorders.  First-rank symptoms or Schneider’s first-rank symptoms:  delusions of being controlled by an external force  the belief that thoughts are being inserted into or withdrawn from one's conscious mind  the belief that one's thoughts are being broadcast to other people  hearing hallucinatory voices that comment on one's thoughts or actions or that have a conversation with other hallucinated voices.  Their pathognomonic value has been questioned by recent findings. History  In the early 1970s, a collaboration between European and USA psychiatrists leads to the formulation of DSM-III criteria.  The two approaches remained somewhat different in the field of schizophrenia.  European school emphasized the specificity of the schizophrenia experience (School of Germany),  USA underscored the presence of common risk factors between schizophrenia and the severe bipolar disorder (spectrum-approach). Epidemiology  Schizophrenia affects approximately 1 in 100 people in the world  the incidence rate of schizophrenia seems consistent across the world for the last half-century.  Despite the received wisdom that schizophrenia occurs at similar rates worldwide, its prevalence varies across the world, within countries, and at the local and neighborhood level.  It causes approximately 1% of worldwide disability.  Gender differences ◼ Incidence: 1.4 times more frequently in males than females ◼ Age of onset: appears earlier in men - the peak ages of onset are 20–28 years for males and 26–32 years for females.  Onset in childhood is much rarer, as is onset in middle or old age. Epidemiology  The financial and emotional costs are enormous  Sufferers have an increased risk of suicide and physical – often fatal – illness  Schizophrenia appears in all socioeconomic groups, but is found more frequently in the lower levels  Leading theorists argue that the stress of poverty causes the disorder  Other theorists argue that the disorder causes victims from higher social levels to fall to lower social levels and remain at lower levels ◼ This is called the “downward drift” theory  Rates of diagnosis differ by marital status  3% of divorced or separated people  2% of single people  1% of married people ◼ It is unclear whether marital problems are a cause or a result Epidemiology  Risk factors  Living in an urban area  Immigration  Obstetrical complications  Late winter-early spring birth – Perhaps reflecting exposure to influenza virus during neural development  Advanced paternal age at conception – May be associated with an increased risk of de novo mutations Epidemiology  Risk factors  Prenatal stress ◼ Dutch famine in 1944 (malnutrition) had a higher chance of having a child who would later develop schizophrenia. ◼ Lower than average birth weight has been one of the most consistent findings, indicating slowed fetal growth possibly mediated by genetic effects. ◼ Low birthweight (measured prospectively with regard to psychopathology) was associated with enlarged ventricles on CT-Scans in a sample at risk for schizophrenia over 30 years later. The risk of enlarged ventricles on brain scan was greatly increased if the subjects had also a higher genetic load for schizophrenia. ◼ Animal models ◼ intrauterine growth restriction in guinea pigs results in specific neurological abnormalities similar to those that may be involved in the development of schizophrenia, ◼ ventricular enlargement ◼ reduced hippocampal volume Epidemiology  Risk factors  Prenatal stress (continued) ◼ It has been hypothesized since the 1970s that brain hypoxia before, at or immediately after birth may be a risk factor for the development of schizophrenia. ◼ physiological hypoxia that prevails in normal embryonic and fetal development, or pathological hypoxia, may exert an effect by regulating or dysregulating genes involved in neurodevelopment. ◼ over 50% of the candidate genes for susceptibility to schizophrenia are genes implicated in the "ischemia–hypoxia regulation and/or vascular expression". Epidemiology  Risk factors  Cannabis ◼ Increased risk ◼ family history can contribute ◼ Psychotomimetic effects of acute infusions of delta-9-tetrahydrocannabinol  Cigarette smoking during pregnancy ◼ genetic risk may be associated but not a causative factor  Immigration ◼ four-fold increase, also second-generation immigrants ◼ Possible explanations: ◼ overdiagnosis in immigrant populations ◼ Social discrimination ◼ Ethiopian immigrants to Israel; Moroccan immigrants to Holland; Caribbean immigrants to the United Kingdom ◼ Vitamin D deficiency, especially among individuals who move to more northern latitudes. The Clinical Picture of Schizophrenia  Schizophrenia produces many “clinical pictures”  The symptoms, triggers, and course of schizophrenia vary greatly  Some clinicians have argued that schizophrenia is actually a group of distinct disorders that share common features What Are the Symptoms of Schizophrenia?  Symptoms can be grouped into three categories: Positive Negative Cognitive symptoms symptoms symptoms Delusions Hallucinations Disorganized thinking/speech Grossly disorganized or abnormal motor behavior What Are the Symptoms of Schizophrenia? Positive symptoms These “pathological excesses” are bizarre additions to a person's behavior Positive symptoms include: Delusions – faulty interpretations of reality Delusions may have a variety of bizarre content: being controlled by others; persecution; reference; grandeur; control Hallucinations – sensory perceptions that occur in the absence of external stimuli Most common are auditory Seem to be spoken directly to, or overheard by, the hallucinator Hallucinations can involve any of the other senses: tactile, somatic, visual, gustatory, or olfactory Heightened perceptions People may feel that their senses are being flooded by sights and sounds, making it impossible to attend to anything important Inappropriate affect – emotions that are unsuited to the situation What Are the Symptoms of Schizophrenia? Positive symptoms Disordered thinking and speech May include loose associations, neologisms, perseverations, and clang Loose associations (derailment): “The problem is insects. My brother used to collect insects. He's now a man 5 foot 10 inches. You know, 10 is my favorite number; I also like to dance, draw, and watch TV.” Neologisms (made-up words): “It is an amorition law” Perseveration Patients repeat their words and statements again and again Clang (rhymes): How are you? “Well, hell, it's well to tell” How's the weather? “So hot, you know it runs on a cot” Psychomotor symptoms Awkward movements, repeated grimaces, odd gestures The movements seem to have a magical quality These symptoms may take extreme forms, collectively called catatonia Include stupor, rigidity, posturing, and excitement What Are the Symptoms of Schizophrenia? Negative symptoms These “pathological deficits” are characteristics that are lacking in an individual Negative symptoms include: Poverty of speech (alogia) Reduction of quantity of speech or speech content May also say quite a bit but convey little meaning Blunted and flat affect Show less emotion than most people Avoidance of eye contact Immobile, expressionless face Monotonous voice, low and difficult to hear Anhedonia – general lack of pleasure or enjoyment  What Are the Symptoms of Schizophrenia? Negative symptoms Loss of volition (motivation or directedness) Feeling drained of energy and interest in normal goals Inability to start or follow through on a course of action Ambivalence – conflicted feelings about most things Social withdrawal May withdraw from social environment and attend only to their own ideas and fantasies Seems to lead to a breakdown of social skills, including the ability to accurately recognize other people's needs and emotions Approximately 15-25 percent of individuals with schizophrenia display primarily negative symptoms What Are the Symptoms of Schizophrenia? Cognitive symptoms Impairments in: Attention Speed of processing Executive functions Working-memory Verbal fluency (linked to a semantic memory deficit). Lack of Awareness of Symptoms in Individuals with Schizophrenia Diagnosing schizophrenia according to DSM-5 A. Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated). At least one of these must be (1),(2) or (3): 1.Delusions 2.Hallucinations 3.Disorganized speech (e. g. , frequent derailment or incoherence) 4.Grossly disorganized or catatonic behavior 5.Negative symptoms (i.e., diminished emotional expression or avolition) B. For a significant portion of the time since the onset to the disturbance, 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 when the onset is childhood or adolescence, there is failure to achieve expected level of interpersonal, academic or occupational functioning). C. Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms (or less if successfully treated) that meet Criterior A (i.e., active –phase symptoms) and may include periods of prodromal or residual symptoms. Diagnosing Schizophrenia according to DSM-5 D. Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out. E. The disturbance is not attributable to the physiological effects of a substance (e. g., a drug of abuse , a medication) or another medical condition. F. If there is a history of autism spectrum disorder or a communication disorder of childhood onset, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations, in addition to the other required symptoms of schizophrenia, are also present for at least 1 month (or less if successfully treated). Diagnosing schizophrenia according to DSM-IV The DSM-IV contains five sub-classifications of schizophrenia:  Paranoid type: Delusions or auditory hallucinations are present, but thought disorder, disorganized behavior, or affective flattening are not. Delusions are persecutory and/or grandiose, but in addition to these, other themes such as jealousy, religiosity, or somatization may also be present.  Disorganized type: Where thought disorder and flat affect are present together.  Catatonic type: The subject may be almost immobile or exhibit agitated, purposeless movement. Symptoms can include catatonic stupor and waxy flexibility  Undifferentiated type: Psychotic symptoms are present but the criteria for paranoid, disorganized, or catatonic types have not been met.  Residual type: Where positive symptoms are present at a low intensity only.  What Is the Course of Schizophrenia?  Schizophrenia usually first appears between the late teens and mid-30s  Many sufferers experience three phases:  Prodromal – beginning of deterioration; mild symptoms ◼ Social withdrawal and isolation ◼ Inappropriate affect ◼ Poor communication patterns ◼ Neglect of personal grooming  Active – (Psychotic) Full-blown symptoms  Residual – a return to prodromal-like levels ◼ One-quarter of patients fully recover; three- quarters continue to have residual problems What Is the Course of Schizophrenia?  Each phase of the disorder may last for days or years  A fuller recovery from the disorder is more likely in people:  Gender: Women have a better outcome  later onset (during middle age)  Being married  Higher education level  With good premorbid functioning  Whose disorder was triggered by stress  presence of depressive symptoms  prevalence of positive symptoms  family morbidity for mood disorders  With abrupt onset  Who receive early treatment  Peer support and work opportunities What Is the Course of Schizophrenia?  Increased optimism regarding course of the disorder  Follow-up study results  10 year study ◼ Majority improved over time; minority deteriorated  15 year study ◼ 40% showed periods of substantial recovery ◼ Sizable minority were not on medication Development and course  Lack of insight (close to anosognosia) worsens prognosis  no treatment compliance, relapse, involuntary admissions, functional impairment  Onset can be abrupt, but is generally gradual and insidious  Emotional, behavioral, intellectual and language symptoms are frequent in childhood.  Depressive symptoms are frequent at onset  Males:  worse pre-morbid adjustment, lower education, more negative symptoms and cognitive symptoms, worse outcome.  Females:  more affective-like symptoms, more positive symptoms, less negative symptoms. Etiology of Schizophrenia  Best understood using a multipath model  Integration of heredity, psychological characteristics, cognitive processes, and social adversities  Each dimension interacts with the others Multipath Model of Schizophrenia How Do Theorists Explain Schizophrenia?  As with many other disorders, biological, psychological, and sociocultural theorists have proposed explanations  Biological explanations have received the most research support  A diathesis-stress relationship may be at work  People with a biological predisposition will develop schizophrenia only if certain kinds of stressors or events are also present Biological Views  Genetic and biological studies of schizophrenia have dominated clinical research in the last several decades  These studies have revealed the key roles of inheritance and brain activity and have opened the door to important changes in treatment Biological Views Genetic factors Following the principles of a diathesis-stress approach, genetic researchers believe that some people inherit a biological predisposition to schizophrenia This disposition (and disorder) are triggered by later exposure to extreme stress This theory has been supported by studies of relatives, twins, and adoptees, and by genetic linkage studies and molecular biology Biological Views Genetic factors Family pedigree studies have repeatedly found that schizophrenia is more common among relatives of people with the disorder The more closely related they are to the person with schizophrenia, the greater their likelihood for developing the disorder General population: 1% Second-degree relatives: 3% First-degree relatives: 10% Factors other than genetics may explain these findings Biological Views Genetic factors It is likely that many genes are involved, each of small effect and unknown transmission and expression. Evidence is emerging that the genetic architecture of schizophrenia involved both common and rare risk variation. A greater than average number of rare deletions or duplications of tiny DNA sequences within genes (copy number variants; CNV) are linked to increased risk for schizophrenia, especially in those "sporadic" cases not linked to family history of schizophrenia, and that the genetic factors and developmental pathways can thus be different in different individuals. Assuming a hereditary basis, one question from evolutionary psychology is why genes that increase the likelihood of psychosis evolved, assuming the condition would have been maladaptive from an evolutionary point of view. genes are involved in the evolution of language and human nature? Biological Views Genetic factors Common variants findings -Genome Wide association studies 108 genes identified 76,755 SCZ, 243,649 HC 287 genomic loci Sullivan et al., Nature Review Genetics 12 Trubetskoy et al., Nature 2022 Schizophrenia: risk factors Biological Views  Neurodevelopmental hypothesis Symptoms often appear soon after puberty, when the brain is undergoing significant maturational changes. Some investigators believe that the disease process of schizophrenia begins prenatally, lies dormant until puberty, and then causes a period of neural degeneration that causes the symptoms to emerge. Since some cases display significant premorbid problems, a minority "deficit syndrome" subtype of schizophrenia is proposed to be characterized by early poor adjustment and behavioral problems, as compared to non-deficit subtypes. Biological Views Biochemical abnormalities Over the past four decades, researchers have developed a dopamine hypothesis to explain their findings on schizophrenia: Certain neurons using dopamine fire too often, producing symptoms of schizophrenia This theory is based on the effectiveness of antipsychotic medications Originally developed for treatment of allergies, antipsychotic drugs were found to cause a Parkinson's disease-like tremor response in patients Parkinson's patients had abnormally low levels of dopamine, which caused their shaking This relationship between symptoms suggested that symptoms of schizophrenia were related to excess dopamine Biological Views Biochemical abnormalities In schizophrenia, messages traveling from dopamine-sending neurons to dopamine-receptors (particularly D2) may be transmitted too easily or too often An appealing theory, because certain dopamine receptors are known to play a key role in guiding attention Dopamine may be overactive in people with schizophrenia because of a larger-than-usual number of dopamine receptors (particularly D2) or their dopamine receptors may operate abnormally Autopsy findings have found an unusually large number of dopamine receptors in people with schizophrenia Imaging studies have revealed particularly high occupancy levels of dopamine at D-2 receptors in patients with schizophrenia Biological Views Biochemical abnormalities Though enlightening, the dopamine hypothesis has certain problems It has been challenged by the discovery of a new type of antipsychotic drug (“atypical” antipsychotics), which are more effective than traditional antipsychotics and also bind to D1 receptors and to serotonin receptors It has also been challenged by theorists who claim that excessive dopamine activity contributes primarily to the positive symptoms of schizophrenia These symptoms respond particularly well to conventional antipsychotic drugs that bind to D2 receptors Still other studies suggest that negative symptoms may be related to abnormal brain structure, rather than to dopamine overactivity Biological Views Biochemical abnormalities Biological Views Biochemical abnormalities Biological Views Biochemical abnormalities Biological Views Biochemical abnormalities The NMDA receptor hypofunction hypothesis of schizophrenia This hypothesis arises also from the observation that when NMDA receptors are made hypofunctional from NMDA antagonists phencyclidine (PCP) or ketamine, symptoms very similar to schizophrenia are produced. Differently from amphetamines that only produce positive symptoms, NMDA produce also negative cognitive and affective symptoms of schizophrenia. Also, glutamate hypothesis of schizophrenia may be put in relation with dopaminergic one. Hypofunction of NMDA receptors in intracortical GABA neurons causes and hypofunction in inhibition of cortico-brainstem glutamate signalling, which in turns hyperstimulates dopamine release in the mesolimbic pathway. Biological Views Biochemical abnormalities A) Cortico (PFC)-brain stem (regulates neurotransmitters release) (NEGATIVE) B) Cortico (PFC) – striatum/accumbens C) Ventral hyppocampus – accumbens (POSITIVE) D) Thalamo-cortical (PFC) E) Cortico (PFC) –thalamic F) Intracortical (PFC) Glutamate G) Intracortical (PFC) GABA (POSITIVE- NEGATIVE) Biological Views Abnormal brain structure During the past decade, researchers have also linked schizophrenia (particularly cases dominated by negative symptoms) to abnormalities in brain structure For example, brain scans have found that many people with schizophrenia have enlarged ventricles – the brain cavities that contain cerebrospinal fluid This enlargement may be a sign of poor development or damage in related brain regions People with schizophrenia have also been found to have smaller temporal and frontal lobes, smaller amounts of grey matter, and abnormal blood flow to certain brain areas  Biological Views Abnormal brain structure Abnormalities in at-risk subjects and both first-episode and chronic patients. Overall grey matter, white matter and whole brain volume are decreased, At the beginning of the disease, in the hippocampus, thalamus, the left uncus/amygdala region, the bilateral insula and the anterior cingulate are reduced. In chronic schizophrenia more extensive volume reductions are observed in the cortex, particularly in medial and left dorsolateral prefrontal cortex, but also in the left superior temporal gyrus. in relatives Hippocampal volume reductions are found. Indicating a heritable component. Volume increases in first-episode schizophrenia are restricted to parts of the putamen in chronic schizophrenia spread throughout the dorsal striatum. These increases are not heritable and are probably a consequence of antipsychotic drug action. In addition to volume changes, abnormalities in cortical thickness, gyrification and subcortical shapes have been reported. Biological Views Abnormal microstructure Corresponding to these macroscopic alterations in the brain of schizophrenia patients are changes in local microcircuits. In prefrontal cortex, pyramidal neurons - the main source of excitatory cortical- cortical neurotransmission - are reduced in size and packed more densely, indicating a reduction in axon terminals and dendritic spines that occupy the space between neurons that may be a consequence of exuberant synaptic pruning during adolescence. In the hippocampus, cell bodies of pyramidal neurons are smaller and dendritic spines are reduced. In the thalamus, some studies indicate reductions in neuron number. Taken together, these findings are in reasonable agreement with structural imaging results. Biological Views Abnormal functional imaging Cortical and subcortical information processing is functionally abnormal in both first-episode and chronic schizophrenia. In dorsolateral prefrontal cortex, during executive tasks schizophrenic patients show relatively inefficient prefrontal activation. Alterations are also evident in brain activations during performance of: perceptual salience tasks (ventral striatum) - emotional regulation tasks (amygdala and its connections with PFC) social cognition tasks (medial PFC, temporo-parietal junction and amygdala) Biological Views Abnormal functional imaging Dysconnection hypothesis Hippocampal-prefrontal connectivity: The hippocampal formation provides input to the dorsolateral prefrontal cortex neonatal hippocampal formation lesions in animals induce prefrontal cortex abnormalities post-pubertally, indicating a causal role of the interaction between these two regions in schizophrenia. selectively vulnerable to some early neurodevelopmental disturbances, such as obstetrical insults. Striatal connectivity: Multiple parallel interactions between prefrontal cortex, thalamus and striatum form feedback loops critical for basic information processing; these feedback loops are disturbed in schizophrenia patients. This prefrontal-neostriatal system is modulated by midbrain dopaminergic neurons. Biological views: environment  The phenomenon of 'fetal programming' could account, at least partially, for familial patterns observed in epidemiological studies.  Indeed, intra-uterine growth is a complex outcome that is influenced by a wide range of factors including fetal genotype, maternal physiology and behavior as well as the function of that crucial interface - the placenta. Biological Views Viral problems Some of the evidence comes from animal model investigations and other is circumstantial large number of people with schizophrenia were born in winter months mothers of children with schizophrenia were more often exposed to the influenza virus during pregnancy than mothers of children without schizophrenia a link between schizophrenia and a particular group of viruses found in animals ? Psychological Views  When schizophrenia investigators began to identify genetic and biological factors linked to schizophrenia, clinicians largely abandoned psychological theories  During the past few decades, however, psychological factors are again being considered important ◼ Leading psychological explanations come from the psychodynamic, behavioral, and cognitive perspectives  1956 Gregory Bateson and colleagues ◼ connected to the family system dysfunction and stemming from double bind situations where a person receives different or contradictory messages. ◼ Madness was therefore an expression of this distress.  Tim Crow has argued that schizophrenia may be the evolutionary price we pay for a left brain hemisphere specialization for language. ◼ Since psychosis is associated with greater levels of right brain hemisphere activation and a reduction in the usual left brain hemisphere dominance, our language abilities may have evolved at the cost of causing schizophrenia when this system breaks down. Sociocultural Views  Sociocultural theorists believe that three main social forces contribute to schizophrenia:  Multicultural factors  Social labeling  Family dysfunction  Although these forces are considered important in the development of schizophrenia, research has not yet clarified what their precise causal relationships might be Sociocultural Views  Multicultural Factors  Rates of the disorder differ between racial and ethnic groups ◼ As many as 2.1% of African Americans are diagnosed, compared with 1.4% of Caucasians ◼ One possibility to explain this finding is that African Americans are more prone to develop the disorder ◼ Yet another explanation may lie in the economic sphere ◼ African Americans are more likely to be poor and, when economic differences are controlled for, rates of schizophrenia become closer ◼ Consistent with the economic explanation, Hispanic Americans who also are, on average, economically disadvantaged, appear to have a much higher likelihood of being diagnosed than White Americans Sociocultural Factors  Multicultural Factors  Rates also differ between countries, as do the course and outcome of the disorder ◼ Some theorists believe the differences partly reflect genetic differences from population to population ◼ Others argue that the psychosocial environments of developing countries tend to be more supportive than developed countries, leading to more favorable outcomes for people with schizophrenia Sociocultural Factors  Multicultural Factors  Sociocultural Views  Social labeling  Many sociocultural theorists believe that the features of schizophrenia are influenced by the diagnosis itself ◼ Society labels people who fail to conform to certain norms of behavior ◼ Once assigned, the label becomes a self-fulfilling prophecy  The dangers of social labeling have been well demonstrated ◼ Example: Rosenhan “pseudo-patient” study ◼ 8 pseudopatients presented themselves at various mental hospitals ◼ mild auditory hallucinations, such as hearing voices saying “empty,” “hollow,” and “thud.” ◼ All were diagnosed with schizophrenia. ◼ After being admitted, they behaved normally. ◼ 52 days to be released, all but one with the diagnosis “schizophrenia—in remission.” ◼ contact with psychiatrists a total of 185 times and with nurses and attendants 1283 times, with responses received in just 4 and 0.5% ◼ Average daily contact with health personnel ranged from 3.9 to 25.1 minutes, with an average of 6.8 minutes. Sociocultural Views  Family dysfunctioning  One of the best-known family theories of schizophrenia focuses on double- bind communication: ◼ Some parents repeatedly communicate pairs of mutually contradictory messages that place the child in so-called double-bind situations; the child cannot avoid displeasing the parents because nothing the child does is right ◼ In theory, the symptoms of schizophrenia represent the child's attempt to deal with the double binds ◼ “You must love me” ◼ «Be spontaneous» Sociocultural Views  Family dysfunctioning  Double-bind messages typically consist of a “primary” verbal communication and an accompanying contradictory nonverbal “metacommunication”  According to the double-bind theory, a child repeatedly exposed to these communications will adopt a special strategy for coping with them and may progress toward paranoid schizophrenia  This theory is closely related to the psychodynamic notion of a schizophrenogenic mother ◼ It has been similarly unsupported by research, but is popular in clinical practice Sociocultural Views  Family dysfunctioning  A number of studies suggest that schizophrenia is often linked to family stress: ◼ Parents of people with the disorder often: ◼ Display more conflict ◼ Have greater difficulty communicating ◼ Are more critical of and overinvolved with their children than other parents ◼ Family theorists have long recognized that some families are high in “expressed emotion” – family members frequently express criticism and hostility and intrude on each other's privacy ◼ Individuals who are trying to recover from schizophrenia are almost four times more likely to relapse if they live with such a family Sociocultural Views  Family dysfunctioning  Expressed emotion Relationships Between Expressed Emotion and Relapse Rates Sociocultural Views  RD Laing's view  Most controversial explanation of schizophrenia  Argues that the disorder is actually a constructive process in which people try to cure themselves of the confusion and unhappiness caused by their social environment ◼ Laing believed that, left alone to complete this process, people with schizophrenia would indeed achieve a healthy outcome  Most theorists reject this notion; research has largely ignored it Sociocultural dimension  Environmental factors associated with the development of schizophrenia include the living environment, drug use and prenatal stressors.  Parenting style seems to have no major effect (the schizophrenogenic mother does not exist).  Living in an urban environment during childhood or as an adult increases the risk of schizophrenia by a factor of two  Other factors: ◼ social isolation and immigration related to social adversity  racial discrimination  family dysfunction  Unemployment  poor housing conditions. Cultural Issues with Schizophrenia  Culture affects how people view or interpret symptoms  Highly stigmatized in Japan ◼ Change in terminology in the year 2000 resulted in more patients being told of their disorder  Many psychiatrists in Turkey will not mention diagnosis to clients or family  Belief of supernatural causation in India Schizophreniform disorder: DSM-5 A. Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated). At least one of these must be (1),(2) or (3): 1. Delusions 2. Hallucinations 3. Disorganized speech (e. g. , frequent derailment or incoherence) 4. Grossly disorganized or catatonic behavior 5. Negative symptoms (i.e., diminished emotional expression or avolition) B. An episode of the disorder lasts at least 1 month but less than 6 months. When the diagnosis must be made without waiting for recovery, it should be qualified as “provisional”. C. Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out D. The disturbance is not attributable to the physiological effects of substance or another medical condition. Schizoaffective disorder: DSM-5 A. An uninterrupted period of illness during which there is a major mood episode (major depressive or manic) concurrent with Criterion A of schizophrenia. Note: the major depressive episode must include Criterion A1: Depressed mood. B. Delusions or hallucinations for 2 or more weeks in the absence of a major mood episode (depressive or manic) during the lifetime duration of the illness. 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. D.The disturbance is not attributable to the effects of a substance (e.g., a drug of abuse, a medication) or another medical condition Specify Whether: - Bipolar Type: This subtype applies if a manic episode is part of the presentation. Major depressive episodes may also occur. - Depressive Type: this Subtype applies if only major depressive episodes are part of the presentation.  Longitudinal course of Schizoaffective disorder a. Bipolar disorder with psychotic features, a. Major depressive disorder with psychotic features b. Schizoaffective disorder, bipolar type. b. Schizoaffective disorder, depressive type. c. Post-schizophrenic depression d. Negative symptoms. Park et al, 2012 Delusional disorder: DSM-5 A. The presence of one (or more) delusions with a duration of 1 month or longer. B. Criterion A for Schizophrenia has never been met. Note: Hallucinations, if present, are not prominent and are related to the delusional theme (e.g., the sensation of being infested with insects associated with delusions of infestation). C. Apart from the impact of the delusion(s) or its ramifications, functioning is not markedly impaired and behavior is not obviously bizarre or odd. D. If manic or major depressive episodes have occurred, these have been brief relative to the duration of the delusional periods. E. The disturbance is not due to the direct physiological effects of a substance or another medical condition and is not better explained by another mental disorder, such as body dysmorphic disorder or OCD. Specify whether:  Erotomanic Type  Grandiose Type  Jealous Type  Persecutory Type  Somatic Type  Mixed Type  Unspecified Type: This subtype applies when the dominant delusional belief cannot be clearly determined or is not described i n the specific types Delusional disorder ❑ Social, work, marital status can be impaired according to the type of delusion ❑ There can be «factual» insight (describe that others see their beliefs as irrational), but no true insight (as per delusion definition) ❑ Irritable or dysphoric mood can occur ❑ Anger and violent behavior can occur with persecutory, jealous, and erotomanic types, with litigious, antagonist behavior and legal difficulties. ❑ Functioning is generally better than schizophrenia, and impairment is circumscribed to the areas related with delusion. Brief psychotic disorder: DSM-5 A. Presence of one (or more) of the following symptoms. At least one of these must be (1), (2), or (3): 1. Delusions 2. Hallucination 3. Disorganized speech (e.g. frequent derailment or incoherence) 4. Grossly disorganized or catatonic behavior B. Duration of an episode of the disturbance is at least 1 day but less than 1 month, with eventual full return to premorbid level of functioning. C. The disturbance is not better explained by major depressive or bipolar disorder with psychotic disorder such as schizophrenia or catatonia, and is not attributable to the physiological effects of a substance (e.g. a drug of abuse, a medication) or another medical condition. Brief psychotic disorder  Sudden onset (from non psychotic to psychotic state in less than 2 weeks), without prodrome  Emotional turmoil and overwhelming confusional symptoms  Rapid shifts from one intense affect to another  Level of impairment is severe, even if disorder is brief, but there is a restitutio ad integrum within 1 month  Increased risk of suicidal behavior  Typically onset in mid 30s, but possible across all life-span  Personality disorders predispose to brief psychotic disorders Catatonia associated to another psychiatric disorder  A. The clinical picture is dominated by three (or more) of the following symptoms: 1. Stupor (i.e., no psychomotor activity; not actively relating to environment) 2. Catalepsy (i.e., passive induction of a posture held against gravity) 3. Waxy flexibility (i.e., slight, even resistance to positioning by examiner) 4. Mutism (i.e, no, or very little, verbal response) 5. Negativism (i.e., opposition or no response to instructions or external stimuli) 6. Posturing (i.e., spontaneous and active maintenance of a posture against gravity) 7. Mannerism (i.e., odd, circumstantial caricature of normal actions) 8. Stereotypy (i.e., repetitive, abnormally frequent, non-goal-directed movements) 9. Agitation, not influenced bay external stimuli 10. Grimacing 11. Echolalia (i.e., mimicking another’s speech) 12. Echopraxia (i.e., mimicking another’s movements) Treatment of Schizophrenia  The primary treatment of schizophrenia is antipsychotic medications, often in combination with psychological and social supports.  Hospitalization may occur for severe episodes either voluntarily or involuntarily (compulsory treatment).  In Italy, involuntary psychiatric treatment can be done when ◼ the patient urgently needs treatment ◼ This treatment cannot be performed outside of hospital ◼ The patient refuses it.  Community support services including drop-in centers, visits by members of a community mental health team, supported employment and support groups are common. Treatment of Schizophrenia  Onset:  Antipsychotic medication  CBT psychotherapy  Family psychoeducation  Cognitive remediation  Social, community and work support  Intensive treatment in pre-psychotic status, high-risk status or at first onset reduces the impact of the illness on health and reduces chronicity, number of admissions, and relapses  Chronic illness  antipsychotic medication  Cognitive remediation?  Social, community and work support Psychosocial Therapy  Inpatient approaches  Milieu therapy (hospital as community and patients have responsibilities) and behavioral therapy can be beneficial ◼ Psychosocial skills training: increasing appropriate self-care, conversational skills, and job skills ◼ Undesirable behaviors are decreased through reinforcement and modeling techniques  Community homes can assist in transition from inpatient programs to community living Cognitive-Behavioral Therapy  Teach coping skills that allow clients to manage their positive and negative symptoms  18-month follow up results:  Those receiving CBT demonstrated more days of normal functioning compared to those treated with medication and contact with a psychiatric nurse Cognitive-Behavioral Therapy Steps  Engagement  Assessment  Identification of negative beliefs  Normalization  Collaborative analysis of symptoms  Development of alternative explanations  Recent approach  Teach clients to accept hallucinations in a nonjudgmental manner Interventions Focusing on Family Communication and Education  Normalize family experience  Demonstrate concern, empathy, sympathy  Educate family members about schizophrenia  Avoid blame  Identify strengths and competencies  Develop problem solving and stress management skills  Strengthen communication Schizophrenia Spectrum and Other Psychotic Disorders Comparison of Some Schizophrenia Spectrum Disorders Psychotic disorders: symptom features Psychotic Symptoms Suggest Aberrant Assignment of Salience Hypothesis – Referential ideas result from erroneous pairing of salience with otherwise neutral percepts – Hallucinations result from abnormal attribution of salience to internal thoughts and memories. – Delusions result from further aberrant salience attribution during the attempt to understand the perceptual distortions. This hypothesis further suggests that there must be some manifestation of hyperdopaminergia or inappropriate DA release or activity in (at least) the mesolimbic projection. Dopamine hypothesis of SCZ  Suppression of motor activity and the PD-like syndrome provoked by the monoamine-depleting agent, reserpine  DA plays a major role in the control of extrapyramidal motor function, an observation related to the ability of the DA precursor, L-DOPA to alleviate PD-like bradykinesia  CPZ and HAL in rats suggested that neuroleptics block "monoaminergic receptors" and/or interfere with the release of monoamines  DA-releasing drugs provoke hallucinations  “a dopaminergic hypothesis of schizophrenia” = overactive dopaminergic pathways: neuroleptics act by blocking DA receptors (Van Rossum, 19 66).  THE DOPAMINE HYPOTHESIS OF SCHIZOPHRENIA: VERSION dopamine Multiple ‘‘hits’’ interact to result in III dysregulation—the final common pathway to psychosis in schizophrenia. The locus of dopamine dysregulation moves from being primarily at the D2 receptor level to being at the presynaptic dopaminergic control level Dopamine dysregulation is Howes and Kapur, 2009 linked to ‘‘psychosis’’ rather than schizophrenia In the striatum, dopamine dysregulation is hypothesized to alter the appraisal of stimuli, perhaps through a process of aberrant salience. Increased dopamine activity in the striatum of SZ may attribute INCENTIVE SALIENCE to otherwise irrelevant stimuli. This mechanism is postulated to underlie delusion formation In the PFC, chronic low levels of dopamine, and compensatory increase of D1 receptors, may play a role in cognitive impairment  DopAmine hyphotesis and onset of psychosis The effect of neurodevelopmental and sociodevelopmental risk factors for psychosis Model of the onset of psychosis Howes et al., TheLancet2014 Learning from Reward Using Prediction Error  The prediction error is the discrepancy between what is expected and what actually occurs.  This can be positive or negative, and can include information about the timing of the reward.  As the response becomes expected, the prediction error drops to zero. Prediction ERROR Prediction error in action Fletcher et al., NRN2008 Neural correlates of prediction error and relationship with aberrant signaling Boehme et al., JNeurosci15 Fletcher et al., NRN2008 Dopamine Functions in Motivation and Reward  Neurons in the ventral tegmental area have a baseline firing rate, that can be increased by an unexpected reward.  If the stimulus is preceded by a signal, the animal learns that the signal predicts the stimulus, and will react to the signal.  This predicted reward does not alter the firing rate of the neurons.  Striatal Parallel Pathways Motor Prefrontal Limbic Dorsolateral Anterior cingulate, Primary and motor prefrontal medial orbito- association areas frontal cortex cortex Hippocampus Caudate Ventral Putamen Globus striatum Pallidus Globus Pallidus Ventral pallidum Specific Specific Specific thalamic thalamic thalamic nuclei nuclei nuclei Midbrain dopaminergi c nuclei GRAY MATTER VOLUME (GMV) FINDINGS Meta-analysis of 15 studies using voxel based morphometry 390 patients and 364 healthy controls Significant areas of cell loss in mesial temporal structures, more prominently on the left. Honea et al., AJP2005 Temporal Lobe GMV deficits Honea et al., 2005 MEDIAL Temporal Lobe GMV deficits Hippocampal atrophy and related findings Hypofunction of dorsolateral prefrontal cortex. – Functional abnormalities in language systems Both cortical and subcortical dopaminergic function is implicated. Honea et al., 2005 ENIGMA Schizophrenia Working Group study on subcortical volumes 2028 schizophrenia patients 2540 healthy controls, 15 centers worldwide. van Erp et al., MolPsy2016  Results of Psychiatric GWAS Studies Genome Wide Association Study (GWAS) Cross-disorder association in psychiatric disorders Pair-wise cross-disorder Manhattan plot of primary polygene analysis fixed-effects meta-analysis SCZ BP MDD ADHD ASD Smoller, Lancet 13 Common Disease Common Variant model can explain a relevant portion of the heritability for Schizophrenia McCarthy et al., Nat Rev Gen 08 Schizophrenia: case studies  Positive symptoms  Over a month before he committed the Navy yard shooting, Aaron Alexis called police to report that three people—two males and a female—were following him. He explained that he was unable to sleep because these people talked to him through the walls, ceiling, and floors of his hotel room. He also reported that they were using a microwave to send vibrations into his body (Winter, 2013).  Erin’s therapists reminded him that he was a scientist and asked him to explain how it would be possible for rats to enter his brain. Erin had no explanation, but he was certain that he would soon lose functions controlled by the area of the brain that the rats were consuming. To prevent this from happening, he banged his head so that the “activated” neurons would “electrocute” the rats. Realizing he was not losing his sight even though the rats were eating his visual cortex, he entertained two possible explanations: Either his brain had a capacity for rapid regeneration or the remaining brain cells were compensating for the loss (Stefanidis, 2006).