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Specific Types of Primary Psychotic Disorders

This page explains Primary Psychotic disorders.

Psychiatry - Classification & Disorders

General Considerations and Differential Diagnosis:

When a patient presents with a psychotic syndrome the first order of business is to establish if the presenting symptoms are due to another psychiatric or somatic condition. In other words, a psychotic syndrome is classified as "primary psychosis" only after other possible underlying pathologies have been ruled out.

In terms of somatic contributors, the main suspects should include processes that may affect the brain either acutely or chronically, in which case a diagnosis of psychotic disorder due to a general medical condition is appropriate. A substance induced psychotic disorder should be diagnosed if there is a likely cause and effect relationship between a substance (including medication, OTC products or illicit drugs) and the psychotic presentation. Psychiatric underlying pathologies include severe depressive and bipolar disorder, which may present with mood congruent psychotic features. As discussed, under stress, some personality disorders may present with transient psychotic symptoms.

The differential diagnosis between different primary psychotic disorders should take into account the type and duration of symptoms. Virtually identical symptoms are seen in schizophrenia, brief psychotic disorder, and schizophreniform disorder. The symptom duration differentiates brief psychotic disorder (1 day to <1 month) from schizophreniform disorder (1 month <6 months) and schizophrenia (>6 months). Delusional disorder is differentiated from schizophrenia based on prominent, non-bizarre delusions without any other associated symptoms. When distinct psychotic episodes are present but affective symptoms account for the majority of the clinical presentation a diagnosis of schizoaffective disorder should be considered.


Conceptual History and Diagnostic Classification • 1853: Morel’s curious cases of Démence Précoce: Bénédict Morel5 introduces the concept of Démence Précoce, literally "early dementia", described a distinct syndrome affecting teenagers and young adults. The syndrome is characterized by bizarre behavior and mental function, withdrawal and self neglect starting in adolescence. • 1868: Kahlbaum’s Katatonie: Karl Ludwig Kahlbaum6 and Ewald Hecker7 publish Die Gruppierung der psychischen Krankheiten (The Classification of Psychiatric Dis-eases). By considering the longitudinal course of psychiatric symptoms in addition to the clinical presentation Kahlbaum and Hecker were the first to describe and name a number of psychiatric syndromes including cyclothymia, dysthymia, paranoia, catatonia, and hebephrenia. Kahlbaum’s Katatonie was characterized by stereotyped movements, outbursts of excitement and stupor. • 1870: Ewald Hecker’s hebephrenia and cyclothymia: Hecker differentiates between hebephrenia, a disorder that begins in adolescence with erratic behavior followed by a rapid decline of all mental functions, and cyclothymia, a cyclical mood disorder. • 1891: Arnold Pick8 reports on a case of a psychotic disorder which he calls Dementia Praecox • 1893: Emil Kraepelin’s9 Dementia Praecox: Kraepelin new classification of mental disorders distinguishes between dementia praecox and mood disorder (termed manic depression and including both unipolar and bipolar depression). • Dementia Praecox: A "sub-acute development of a peculiar simple condition of mental weakness occurring at a youthful age." • Distinct from catatonia and dementia paranoides. • Kraepelin’s concept relied heavily on course (chronic versus episodic) and prognosis • 1899: hebefrenia, catatonia and dementia paranoides as subtypes of dementia praecox. • 1919: Kraepelin writes that "it is becoming increasingly clear that we cannot distinguish satisfactorily between these two illnesses and this brings home the suspicion that our formulation of the problem may be incorrect." • 1908: Eugen Bleuler10’s Schizophrenia gk. skhizein "to split"+ phren (gen. phrenos) "diaphragm, heart, mind", where "split mind" referred to being split off from reality and unable to distinguish what is real from what is not real. Of note, Bleuler never implied that people with schizophrenia have split personalities; he proposed the term of schizophrenia to describe the separation of function between personality, thinking, memory, and perception. • Bleuler 4 A's: flattened Affect, Autism, impaired Association of ideas and Ambivalence. • Bleuler proposal for a new name also stemmed from his dissatisfaction with the implica-tions of dementia praecox label. Bleuler noted that schizophrenia was NOT a dementia, as some of his patients improved. • 1887 – 1967: Kurt Schneider11 described the first rank symptoms (FRS), thought to be specific for schizophrenia psychosis. He included thought insertion/broadcast/withdrawal, made feelings/impulses/actions/somatic sensations (a type of delusion), third person auditory hallucinations (running commentary or arguments), delusional perception, and thought echo (echo de la pensee or gendankenlautwerden) – a type of hallucination. Only 58% of patients with a diagnosis of schizophrenia experience at least one FRS, while 20% never experience FRS. Furthermore, 10% of patients with a diagnosis of schizophrenia experience FRS. • Modern positive and negative symptoms based classification systems: • Positive symptoms include distortions or excesses of normal functioning such as, hallucinations, delusions, disorganized thinking and speech, and inappropriate affect. Frequently hallucinations are auditory in nature; rarely they may be visual, tactile or olfactory. Delusions are fixed false beliefs held despite negative evidence, and are not consistent with cultural norms. Types include persecutory, referential, somatic, grandiose, etc. Positive symptoms are generally more responsive to treatment than negative symptoms. • Negative symptoms involve a decrease or absence of normal behavior. They include affective flattening, impoverishment of speech and language, avolition, amotivation, lack of interest, anhedonia, and social isolation. • Modern classifications: • Andreasen's Positive and Negative Symptoms Type • Crow Type I and II: • Type I – positive symptoms, good response to treatment, relatively better outcome • Type II – negative symptoms, poorer response to treatment, relatively poor outcome, MRI changes.

Current classification – ICD 10/ DSM-IV-TR

Common ICD/DSM types: • Paranoid schizophrenia: • Prominent delusions, auditory hallucinations • Usually minimal thought disorder or negative symptoms • Catatonic schizophrenia is characterized by prominent psychomotor symptoms e.g., violent excitement, posturing, waxy flexibility, automatic obedience, perseveration, stupor. • Residual schizophrenia or "defect state", when positive symptoms give way to negative symptoms. • Simple schizophrenia refers to insidious development of negative symptoms without positive symptoms DSM IV only: • Disorganized schizophrenia: mainly thought disorder, and negative symptoms, without prominent positive or affective symptoms. ICD 10 only: • Hebephrenic schizophrenia: affective abnormality, thought disorder, mannerisms. May have chronic course.

Epidemiology and Risk Factors

The life time prevalence of schizophrenia is between 0.5-1.5% in the general population and is one of the ten leading causes of disability worldwide. Of note, this 1 in 100 rate has been shown to be remarkably constant across different historical periods and across different cultures. The annual incidence is reported to be in the range of 0.5 to 5 per 10,000. The onset of schizophrenia is usually between the ages of 20-45. Most times, the course of the disorder is chronic and characterized by a gradual, progressive deterioration. However partial or complete recovery is reported to occur for 30-60% of patients following a first episode of schizophrenia.* About 20-40% of patients with schizophrenia attempt suicide at least once during their lifetime, and about 10-15% die of suicide. The prevalence in males and females is equal.14 The following risk factors have been reported for schizophrenia: • Men tend to be diagnosed earlier than women (males age 15-25 years, females age 25 – 35 years) • Seasonality: winter birth excess • Schizoid and schizotypal personality disorders • A family history of schizophrenia or major affective disorders • A family with a high level of expressed emotions (EE) • Schizophrenia tends to be more frequent in urban areas and in developed countries • Lower socioeconomic status • Schizophrenia is more frequent in recent immigrants (deprivation, stress of immigration may increase risk)

Genetic Considerations

The rate of schizophrenia is increased in families with affected members. Mode of Transmis-sion is unknown and likely to be multi-factorial, possibly polygenic. 70% of the heritability of schizophrenia is genetic. Adoption studies have shown an increased incidence of schizophrenia spectrum disorders among adopted offspring of schizophrenic parents. When one parent has schizophrenia there is a twelve fold increase in the risk of developing the disorder; with one affected sibling there is a 9 fold increase in risk; for monozygotic, identical twins the rate of concordance is around 50%. Working memory appears to be heritable and showed significant associations with DISC1, reelin, and AKT1 in schizophrenia.


While there are no structural or functional brain changes specific to schizophrenia or other psychotic disorders a number of abnormalities are reported. Enlarged ventricles, deep cortical sulci, diffuse gray and white matter loss, increased neuronal density, decreased synapse density, and an overall decrease in brain size have been reported in schizophrenia studies using structural brain imaging (CT, structural and diffusion sensor MRI studies) or postmortem observations. Smaller frontal and temporal lobes, lower volume hippocampus, thalamus, corpus callosum, and anterior cingulate, as well as larger caudate and putamen have been reported in schizophrenia. Decreased activation in dorsolateral prefrontal cortex (during working memory task), and increased activation of the superior temporal gyrus (during auditory hallucinations) have been also reported in functional brain imaging (fMRI and PET) studies.

Etiopathological Theories

Neurodevelopmental Theories Impaired fetal or neonatal brain development may sow the seeds for the onset of psychotic symptoms in later life. Patients with schizophrenia have a lower than average IQ, and often subtle/soft neurological signs. A number of parental risk factors have been reported including multiparity, maternal bleeding during pregnancy, small baby size for gestational age, increased paternal age, and severe stress to mother during first trimester. In addition, the following environmental risk factors have been associated with increased risk of developing psychotic illness later in life: late winter birth, prenatal exposure to famine, in-utero exposure to analgesics, and cannabis use.

Biological factors

Electrophysiology • P50 sensory gating deficits: following an auditory stimulus schizophrenia patients fail to gate a subsequent stimulus that follows closely (within the normal 50 msec suppression). • Reduced P300 evoked response potential (ERP) [oddball deficit paradigm]: schizophrenia patients fail to respond to an odd ball stimulus administered during a series of otherwise identical stimuli. • Prepulse Inhibition (PPI) Paradigm. Neurotransmitters
Dopamine (DA) • Hypothesis: excessive DA activity in mesolimbic and cortical brain regions. Schizophrenia is the result of a dopaminergic hyper-salient state 15 • Supporting evidence: • Postmortem studies: increase DA receptors in schizophrenia • HVA (dopamine metabolite) in plasma, CSF and severity of psychosis/response to neuroleptics • DA Agonists • Amphetamines release DA at synapses and cause positive symptoms (in people who do not have schizophrenia) • L-dopa increases central DA concentrations and causes positive symptoms • DA Antagonists: All effective antipsychotics are D2 receptor antagonists; efficacy correlates with D2 occupancy • Limitations: • Amphetamines and L-dopa do not produce negative symptoms • Antipsychotics are ineffective in 30% of patients • Antipsychotics block D2 receptors instantly but antipsychotic effect not evident for days Primary Psychotic Disorders Serotonin • Hypothesis: serotonin excess • LSD and psilocybin are potent 5HT receptor agonists and cause positive symptoms of schizophrenia (in people who do not have schizophrenia) • Atypical antipsychotics are potent 5HT2 receptor antagonists • Limitations: LSD produces visual hallucinations which are uncommon in schizophrenia Excitatory amino acids (EAAs): glutamate and aspartate • Hypothesis: EAAs deficit • Phenylcyclidine (PCP), which antagonizes EAA receptors, can produce positive and negative symptoms in people without schizophrenia • Glutamate agonists (e.g., glycine), may be modestly therapeutic in schizophrenia Psychological Factors
• Freud: delusions as a way of making sense of a disturbed internal world ("I need to respond with aggression to protect myself as everyone is attacking me"). • Klein: failure to resolve the paranoid/schizoid position • Cameron: loss of conceptual boundaries • Goldstein: concrete thinking • Difficulties in filtering sensory input (see also electrophysiological findings) Familial/Social Factors
• Probably more important in precipitating schizophrenia than causing it • Lidz’s marital schism/marital skew • Bateson’s double bind theory • High expressed emotion Social Factors • Social adversity in childhood and fetal life associated with risk of developing schizophrenia and other psychoses later in life • Risk factors for psychoses later in life (in developed countries): • households receiving social welfare benefits • unemployment • single-parent households • low socioeconomic status • rented apartments

Clinical Diagnosis

According to DSM-IV Schizophrenia is diagnosed when the patient presents with a com-bination of positive (delusions and hallucinations) and negative symptoms, which have been present for at least 6 months and have resulted in significant dysfunction. It is also accepted that disorganized speech/behavior and/or catatonic symptoms, when combined with other positive or negative symptoms, can count toward a diagnosis of schizophrenia. Schizophrenia is a diagnosis of exclusion; in other words, it is required that there are no other medical, psychiatric, or substance-induced conditions that would explain the patient’s diagnosis better than schizophrenia.

Differential Diagnosis

Early in the disease course, other etiologies of psychosis should be excluded. These include treatable conditions such as tertiary syphilis, vitamin deficiencies, brain tumor, drug and medication intoxication, chronic infection, and mood disorders. While neuroimaging studies (CT and MRI) do not show a single specific pattern with schizophrenia or related disorders and may be normal early in the course of the disease a screening CT is recommended for patients with a first episode of primary psychosis, especially for late or acute onsets. An affective psychosis (mania or depression with psychotic features) should be ruled out if affective symptoms preceded psychotic symptoms or are dominating the clinical picture at the time of presentation. A diagnosis of schizoaffective disorder is appropriate if historically the course has been dominated by affective symptoms and there are at least some episodes of "pure" psychosis i.e., independent of the affective background. Symptom duration will separate brief psychotic disorder (<1 month), schizophereniform disorder (<6 months), and schizophrenia (>6 months).


Hospitalization is recommended if the acute psychotic symptoms result in danger to self or others or significant impairment. Biological Traditionally, dopamine 2 (D2) antagonists (blockers), most often labelled as first generation (typical) neuroleptics, have been the pillar of schizophrenia treatment. • D2 blockers, by decreasing the presumably excessive mesolimbic dopamine, have estab-lished efficacy for positive psychotic symptoms; however, due to concomitant blockade of the frontostriatal dopamine pathway, where dopamine is presumably decreased all along in schizophrenia, they do not improve (and in some cases can worsen) negative, cognitive symptoms, and/or functional/social outcomes. • Due to an alteration of the physiological dopamine/acetylcholine ratio in the basal ganglia these drugs also have a number of extra-pyramidal adverse effects (EPSEs) both short term (acute dystonia, dyskinesia, akathisia) and long term (parkinsonism and tardive diskinesia). • Finally, following a dopamine blockade in the tuberoinfundibular system, there is a prolactin increase with common sexual side effects, including decreased sexual interest, sexual difficulties, lactation and (in men) gynaecomastia. • The side effects of typical neuroleptics can be stigmatizing and are a major reason for non-adherence to treatment. Some of the above issues have been resolved with the advent of the second generation antipsychotics (SGA) or atypical neuroleptics, a drug class that tends to share the mechanism of D2 and 5HT2 (serotonin) antagonism. We say "tends to share" rather than "share the characteristic" as the second generation drugs show a number of differences in terms of both receptor profile and affinities. To illustrate, the prototypical atypical neuroleptic is clozapine, a drug that has strong D4 and 5HT2A antagonism but only partial D2 antagonism. primary psychotic disorders • SGAs have fewer EPSEs and tend to be better for negative symptoms than typicals (not increasing negative symptoms). • Some of the atypicals (e.g., olanzapine, clozapine) increase the risk for metabolic adverse effects including significant weight gain, diabetes and dyslipidemia. • Clozapine is recommended for treatment resistant schizophrenia. • Generally SGAs, with the exception of olanzapine and clozapine, are first line treatments. This preference is based more on better tolerability (less EPSEs and cognitive adverse effects) than greater efficacy. On a case by case basis first generation antipsychotics(FGAs) may represent a reasonable alternative.18 Perphenazine and molindone efficacy and overall tolerability has been shown to be similar to SGAs. General prescribing principles: • Initial management may include use of sedative medication such as lorazepam. • IM medication may be required in a very disturbed, involuntary patient. • Depot (long-acting) neuroleptics are indicated when treatment adherence is problematic. • Polypharmacy is common yet not supported by evidence. • The goal of treatment is stability on monotherapy at the lowest effective dose. Psychological (Individual and Family Interventions) • Good evidence: • Education of patient and carers • Reduction of high expressed emotion: shown to affect relapse rates • Supportive, solution oriented psychotherapy • Unclear benefit: • Cognitive behavioral therapy • Cognitive and functional rehabilitation • Self–help unclear Social • Good evidence: • Regular intensive case management • Unclear benefit: • As needed case management • Consumer based organizations


15-25% of patients diagnosed with schizophrenia have one episode and no residual impairment. 25-40% have recurrent episodes and no residual impairment. 5-10% have recurrent episodes and develop significant non-progressive impairment. 30-40% have recurrent episodes and develop significant progressive impairment. Therefore, the majority of patients do not recover fully BUT DO NOT have a chronic unremitting course. There is little evidence that antipsychotics have altered the course of illness for most patients. However, evidence suggests that prolonged psychosis which is untreated has a bad prognosis. Suicide rate is up to 15%.19 Good prognostic factors: • Female gender • Older age of onset • Married • Higher socioeconomic status • Living in a developing (as opposed to developed) country • Good premorbid personality • No previous psych history • Good education and employment record • Acute onset, affective symptoms, good adherence to medication. Predicting risk of suicide: • Acute exacerbation of psychosis • Depressive symptoms • History of attempted suicide • Male gender • Command auditory hallucinations

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