Psychosis, a syndrome with many causes, traditionally refers to an impaired ability to distinguish between false and real perceptions and beliefs. Schizophrenia is the prototypical psychotic disorder. The most common psychotic symptoms are positive symptoms such as abnormal perceptions (including illusions and hallucinations), false beliefs, including a wide variety of delusional thoughts (e.g., paranoid delusions, delusions of reference, grandiose, somatic, etc.), and disorganized thinking. In addition, patients with schizophrenia might have prominent negative symptoms such as aﬀective flattening, alogia (decreased thought/speech production), and avolition, together with amotivation, anhedonia and social isolation. Disorganized or bizarre behavior is a separate symptom dimension of the disorder. Aﬀective symptoms can also be present and cognitive and social deficits are common.
This page focuses on primary psychotic disorders, as illustrated by schizophrenia, meaning that the clinical picture of psychosis is not deemed to be secondary to other processes. It is important to note that in addition to the primary psychoses a number of psychiatric and somatic conditions aﬀecting the brain homeostasis can produce psychotic symptoms.
Patients with personality disorders (PDs) can present with overt psychotic symptoms in response to stress (e.g., paranoid PD, schizotypal PD, borderline PD). Schizoid PD is consid-ered a risk factor and might precede Schizophrenia and Delusional Disorder. With regards to mood disorders, severe psychotic depression can present with mood congruent (e.g., nihilistic delusions, delusional guilt) and/or auditory hallucinations making critical and negative comments. At the opposite end of the spectrum, severe mania can present with grandiose and religious delusions, delusions of special powers, and auditory hallucinations (God’s or angelic voices). Late life psychosis can be present in the later stages of dementia disorders. Conditions that aﬀect the brain structure, either acutely [e.g., rapidly growing brain tumors, traumatic brain injury, strokes, infectious/inflammatory processes such as tertiary syphilis, multiple sclerosis or systemic lupus erythematosus (SLE)], or chronically [e.g., nutrient and vitamin deficiencies such as B12, niacin deficiency (pellagra), etc.] can present with a variety of psychotic symptoms. Last but not least, a number of drugs (prescribed and illicit) can be associated with psychotic symptoms either during treatment/intoxication or withdrawal.
This page will first review the definitions of the diﬀerent types of psychotic symptoms, as the basis for the discussion about the approach (including initial assessment as well as short and long-term treatment plans) to a patient with a generic psychotic syndrome. For the remainder of the chapter schizophrenia is used as the foundation for the discussion of clinical diagnosis, diﬀerential diagnosis, epidemiology, pathophysiology, genetics and treat-ment. Pertinent details of schizophrenia-related disorders will be discussed (compared and contrasted whenever the case) within the confines of the broader schizophrenia mainframe.
Clinical Manifestations and Definition of Terms
• Positive Symptoms
are thought of as an excess of normal function. Overvalued misperceptions that become illusions and hallucinations and overvalued ideas that become delusions (fixed ideas) are classical examples of positive symptoms.
• Negative Symptoms
refer to a lack of what is considered to be normal function. Normally, a degree of volitional ability is expected; therefore decreased or absent volition(avolition) is a negative symptom. Similarly, a lack of motivation (amotivation), a lack of ability to enjoy things (anhedonia), or decreased ability to engage in social activities (social isolation) are other classical negative symptoms.
refers to two extreme (and fundamentally opposite) states. Agitated cata-tonia refers to a state of excessive, extreme behavioral agitation (not in response to internal stimuli), while catatonic immobility refers to extreme negativism (the patientactively resists any attempts to have his extremities or whole body moved) or catalepsy (waxy flexibility). Other catatonic symptoms include posturing (assuming strange body postures), grimacing, mannerisms, stereotyped movements, echolalia (where the patient repeats in parrot-like fashion the words of another person), and echopraxia (where the patient imitates in mirror-like fashion the movements of another person).
• Disorganized thinking (formal thought disorder)
refers to an alteration in the thought process. Normally the flow of thinking is coherent, linear and goal directed. In psychotic patients the associations may be loose to the point of being non-existent. The psychotic patient’s thought form may present with tangentiality (ideas are only marginally connected) or circumstantiality (the patient responds to questions moving in gradually more focused, concentric circles until eventually reaching the answer). In extreme cases, even the structure of the sentence might be lost which results in word salad.
• Disorganized behavior
refers to the patient diﬃculty to complete most goal oriented activities. A range of behaviors have been described: actively responding to inner stimuli (e.g., talking to oneself or shouting for no apparent reason), aimless, repetitive movements and activities, poor ability to maintain one’s basic hygiene and perform routine actives of daily living (which often results in a disheveled appearance, and poor grooming and hygiene), or uncensored public sexual activity (being naked, or masturbating in public).
• Active phase
refers to a period of time when a combination of the above symptoms are prominently manifested.
• Prodromal and residual phases
refer to periods of time of attenuated symptoms that either precede (prodromal) or follow (residual) the active phase period.
• Cognitive Symptoms:
Memory (more specifically working memory), attention, concen-tration, processing speed, problem solving (executive functioning), and social cognition are a few of the many cognitive domains shown to be impaired in schizophrenia.
is a multidimensional concept referring to awareness of illness, specific symptoms and their consequences, as well as need for treatment. Insight refers to the patient’s ability to understand that some of his or her non-reality based experiences (usually hallucinatory experiences and delusional representations) are secondary to having schizophrenia rather than reality. Awareness and attribution of both current and past symptoms represent specific aspects of insight. Additional dimensions of insight include a more global understanding of the diagnosis and need for treatment.
Approach to the Patient with Acute Psychosis
The following major issues should be kept in the forefront:
1. What is the most accurate diagnosis?
2. Is there a treatable or reversible component to the psychosis?
3. Is the patient safe?
4. Can the physician help to alleviate the positive symptoms?
5. Can the physician help to alleviate the negative, cognitive symptoms and insight deficits to improve social/functional outcomes?
The history should clarify the onset (acute versus gradual), tempo (slow/protracted versus rapid), chronology, course (persistent versus episodic), and type of symptoms.
Onset and tempo
An acute or subacute onset of psychosis may represent delirium, psychosis due to a general medical condition, or a substance induced psychosis and should trigger the search for intoxication, infection, or metabolic derangement.
According to the Diagnostic and Statistical Manual of Mental Disorders IV Text Revi-sion (DSM-IV-TR) a diagnosis of schizophrenia requires the presence of a combination of prominent positive, negative, disorganized thinking (formal thought disorder), catatonia, or behavior type of symptoms for at least a month (active phase), with a total duration of the episode (including active phase, and some type of prodromal or residual symptoms) for at least 6 months and resulting in social and occupational dysfunction.
A schizophrenia-like presentation that lasts more than a month but less than 6 months would be more appropriately diagnosed as schizophreniform disorder. Brief psychotic disorder
should be diagnosed when the total duration of symptoms is shorter than a month. Schizoaﬀective disorder
trumps schizophrenia if in addition to stand alone episodes of psychotic symptoms there is also a long history of aﬀective symptoms, and the aﬀective symptoms occurred for a longer time than the psychotic symptoms.
Refers to the temporal rapport between the diﬀerent symptoms. Clarifying what started and what followed are essential in ruling out phenomenologically overlapping disorders. If it is determined that the psychotic symptoms followed a medical condition or drug (prescribed or illicit) psychotic disorder due to a general medical condition, substance induced psychotic disorder, or delirium
need to be considered first. Mood disorder with psychotic symptoms
is diagnosed if the history shows that psychotic symptoms always occurred in the context of already present, and most often severe aﬀective (depressive and manic) symptoms.
A clearly episodic course is most times indicative of a primary aﬀective disorder. Unfortu-nately, schizophrenia tends to be chronic, with some level of residual symptoms following the active phase for most patients. However, for schizophrenia, after one year since the onset of the acute phase symptoms, DSM allows for a number of course based specifiers including: single episode with partial/total remission, episodic with/without inter-episode residual symptoms, and continuous.
Physical and Neurological Examination
A thorough general and neurological examination is recommended.
General physical examination
Is recommended to first rule out a systemic disease that may be responsible for the psychotic syndrome. A number of non-specific physical abnormalities including an arched palate, narrow or wide–set eyes or subtle ear malformations are more frequently reported in patients with schizophrenia than in the general population. For patients treated with antipsychotics a physical exam will document the general state of health and is important to exclude side eﬀects of medication. Side eﬀects include orthostatic hypotension, hypersalivaton (secondary to clozapine), anticholinergic syndrome (dry mouth, and tachycardia secondary to anticholinergics), hyperprolactinemia (lactation secondary to D2 antagonism), and metabolic syndrome (most common with clozapine and olanzapine).
Is recommended to rule out neurological conditions that may present with psychotic man-ifestations; of note, abnormal focal neurological signs are not typically found in primary psychotic disorders. Such findings should prompt the clinician to do a more extensive neuro-logical work-up. In addition, a neurological exam is necessary to exclude the presence of soft
neurological signs and abnormal involuntary movements. Soft (neurological) signs, while not pathognomonic, are frequently seen in schizophrenia, where "soft" denotes the absence of a clearly localized ("hard") central nervous pathology that can explain the observed deficits. They include:
• Sensory function integration abnormalities
include poor audio—visual integration, astere-ognosis (the inability to identify an object by touch without visual input), and agraphaes-thesia (the inability to recognize writing on the skin purely by the sensation of touch).
• Motor function integration abnormalities
might include balance and gait abnormalities, poor coordination, intention tremor, finger—thumb opposition diﬃculties.
Clinical Manifestations and Definition of Terms
In addition, a number of abnormal involuntary movements have been classically described in chronic schizophrenia (before the neuroleptic age) but have been much more prevalent since the introduction of antipsychotic dopamine antagonist drugs. These include:
which refers to low amplitude, high frequency movement typically involving the lower extremities. The patient reports a feeling of intolerable restlessness, specifically manifested as a need to continuously move one’s feet. The patient cannot stop pacing (paces in place when asked to sit or stand without walking),
which refers to a high amplitude, low frequency, spastic type of movement, typically involving an isolated muscle group, e.g., oculopharogyric crisis (eyes turned upwards), torticollis (neck turned sideways), laryngeal spasm (rare but serious as it might result in asphyxia), opisthotonus (arched back, rare, painful)
which refers to low amplitude, repetitive, moderate frequency, pseudo-parkinsonian movements that may involve any muscle group but most typically involve the fingers, hands, toes, feet, lips and lower face muscles (including perioral and mandibular muscles)
which refers to a low amplitude, high frequency, repetitive movement. Tremor of the hands and fingers can be spontaneous or can be elicited by asking the patient to put his arms in a horizontal position and stretch his fingers. In addition, a parkinsonian pill rolling tremor may also be observed. In patients taking lithium a fine tremor(very low amplitude, very high frequency) may be seen.
Mental Status Examination (MSE)
disheveled or bizarre appearance may be a clue to underlying psychosis. Impaired reality testing commonly results in poor grooming and hygiene.
paranoid patients may be unwilling to co-operate during an interview, while very psychotic patients my be unable to engage with the interviewer.
posturing, repetitive gestures, extreme psychomotor agitation (with-out any apparent precipitants or retardation) can indicate a catatonic presentation. Alternatively, the patient may present with psychomotor agitation in response to over-whelming internal stimuli (e.g., loud, demeaning voices or threatening visions) or because of severe paranoid ideation.
patient’s reported mood can vary from good to depressed or afraid.
paranoid patients present with guarded aﬀect, eyes scanning the room, and a closed up body language.
can be vague, circumstantial or overtly disorganized. At times nonsensical neologisms, word salad, clang (rhyming, nonsensical associations) are present.
may be positive for delusional ideation (most common ideas of references and paranoid delusions). In addition, the patient may harbor suicidal and violent thoughts due to his persistent psychotic symptoms or, at times, related to concomitant depressive symptoms.
auditory hallucinations can be commanding and order the patient to kill himself or other people. When visual hallucinations are present they tend to be unpleasant as a rule and are often overtly terrifying.
Insight and Judgement:
judgement is mostly impaired and the patient has very limited, if any, insight.
with the possible exception of decreased attention, other cognitive deficits may not be obvious during a cursory MSE.
In schizophrenia neuropsychological testing routinely reveals deficits in working memory, executive functioning, social functioning, processing speed, verbal fluency, and/or reaction time abnormalities. Unfortunately, the ability to test for these deficits routinely in clinical practice is limited by the lack of good, time eﬃcient screening cognitive instruments for schizophrenia and related disorders.
There are no tests that can rule in a diagnosis of schizophrenia or related disorders. The role of laboratory investigations are to rule out substance induced disorders and general medical conditions that can present with a psychotic syndrome; to establish a baseline and monitor physiological functions that can be aﬀected by, or can aﬀect the metabolism of psychotropic medications; and monitor drug levels when necessary.
Investigations to exclude a substance induced disorder or general medical condition:
• urine1 or blood toxicology screen: should be performed routinely in all patients presenting with new onset or exacerbated psychotic symptoms, as a number of illicit drugs can cause/worsen psychosis (e.g., hallucinogens, cocaine, stimulants, marijuana).
• Complete blood cell count2 (CBC): blood dyscrasias can point to an underlying vitamin deficit that may manifest with psychosis (e.g., pernicious or megaloblastic anaemia as a sign of vitamin B12/folate deficits)
• Rapid plasma reagin3 (RPR): done to rule out (tertiary) syphilis
• Thyroid panel4: indicated when there is a clinical suspicion for hypo or hyperthyroidism
• Brain Imaging:
• Structural brain imaging (CT or MRI) is indicated to rule out other brain pathologies (e.g., multiple strokes, demyelination, masses). Neuroimaging studies do not show a pattern of findings specific for schizophrenia or related disorders and may be normal early in the course of the disease. As schizophrenia progresses, enlarged ventricles and diﬀuse cortical atrophy becomes apparent. MRI scans may also show atrophy of the parahippocampal gyrus, dorsolateral prefrontal cortex, mesolimbic system, the anterior cingulate cortex, and planum temporalis asymmetry reversal or generalized reductions in grey and white matter.
• Functional brain imaging studies (PET and functional MRI) demonstrate abnormalities in the same regions. However, none of these changes are pathognomonic for schizophrenia or related disorders.
A liver function panel and chemistry panel (to document renal function) are recommended to establish a baseline for physiological functions that can aﬀect the metabolism of psychotropic medications. Other tests that may be indicated to monitor side eﬀects of psychotropic medication include a blood glucose level, a lipid panel, and an ECG (as some antipsychotics have the potential of prolonging the QTc interval). A prolactin level should only be measured when prolactinemia is suspected on clinical grounds.
The following drug levels need monitoring: lithium (0.7 to 1.2 mEq/L), carbamazepine (5 to 12 mcg/mL), and valproic acid (50 to 100 mcg/mL). A clozapine level above 350 ng/mL is recommended to establish compliance and has been shown to correlate with improved eﬃcacy for refractory schizophrenia. There is no clear evidence of a therapeutic range for other antipsychotics.
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