Childhood schizophrenia

Childhood schizophrenia (also known as childhood-onset schizophrenia, and very early-onset schizophrenia) is essentially the same in characteristics as schizophrenia that develops at a later age, but has an onset before the age of 13, and is more difficult to diagnose.[3] Schizophrenia is characterized by positive symptoms that can include hallucinations, delusions, and disorganized speech; negative symptoms, such as blunted affect and avolition and apathy, and a number of cognitive impairments.[1][4][5] Differential diagnosis is problematic since several other neurodevelopmental disorders, including autism-spectrum disorder, language disorder, and attention deficit hyperactivity disorder, also have signs and symptoms similar to childhood-onset schizophrenia.[4]

Childhood schizophrenia
Other names	Childhood type schizophrenia; schizophrenia, childhood type; childhood-onset schizophrenia (COS); very early-onset schizophrenia (VEOS); schizophrenic syndrome of childhood
Specialty	Child psychiatry (EU), Child and adolescent psychiatry (USA)
Symptoms	Hallucinations, delusions, disorganized behavior or catatonia, negative symptoms (i.e., avolition or reduced affect display)[1]
Usual onset	Before the age of 13 years
Types	Episodic-progredient/shiftlike childhood schizophrenia (malignant, paranoid and slow-progressive sub-types), continuous childhood schizophrenia, recurrent childhood schizophrenia (the rarest form – 5 % of all cases)[2]
Differential diagnosis	Major depressive disorder or bipolar disorder with psychotic or catatonic features, brief psychotic disorder, delusional disorder, obsessive–compulsive disorder and body dysmorphic disorder, autism spectrum disorder or communication disorders, other mental disorders associated with a psychotic episode
Medication	Antipsychotics
Frequency	​^1⁄5 of all forms of psychosis of the schizophrenia spectrum;[2] 1.66:1000 among children (0–14 years)[2]

The disorder presents symptoms such as auditory and visual hallucinations, strange thoughts or feelings, and abnormal behavior, profoundly impacting the child's ability to function and sustain normal interpersonal relationships. Delusions are often not systematized and vague.[6] Among the psychotic symptoms seen in childhood schizophrenia non-verbal auditory hallucinations are the most common, and include noises such as shots, knocks, bangs. Other symptoms can include irritability, searching for imaginary objects, or low performance. It typically presents after the age of seven.[7] About 50% of young children diagnosed with schizophrenia experience severe neuropsychiatric symptoms.[8] Studies have demonstrated that diagnostic criteria are similar to those of adult schizophrenia.[9][10] Neither DSM-5 nor ICD-11 list "childhood schizophrenia" as a separate diagnosis. Diagnosis is based on behavior observed by caretakers and, in some cases depending on age, self reports.

Classification of mental disorders

Diagnostic and Statistical Manual of Mental Disorders

DSM-III. American Psychiatric Association against childhood schizophrenia.

Childhood schizophrenia was not directly added to the DSM until 1968, when it was added to the DSM-II,[11] which set forth diagnostic criteria similar to that of adult schizophrenia.[12] "Schizophrenia, childhood type" was a DSM-II diagnosis with diagnostic code 295.8.[11] It's equivalent to "schizophrenic reaction, childhood type" (code 000-x28) in DSM-I (1952).[11] "Schizophrenia, childhood type" was successfully removed from the DSM-III (1980), and in the Appendix C they wrote: "there is currently no way of predicting which children will develop Schizophrenia as adults". Instead of childhood schizophrenia they proposed to use of "infantile autism" (299.0x) and "childhood onset pervasive developmental disorder" (299.9x).[13]

In the DSM-III-R (1987), DSM-IV (1994), DSM-IV-TR (2000), DSM-5 (2013) there are no "childhood schizophrenia". The rationale for this approach was that since the clinical picture of adult schizophrenia and childhood schizophrenia is identical, childhood schizophrenia should not be a separate disorder.[14] However, the section in schizophrenia's Development and Course in DSM-5, includes references to childhood-onset schizophrenia.[1]

International Classification of Diseases

In the International Classification of Diseases 8th revision (ICD-8, 1967) there was a category (295.8) "Other" in the schizophrenia section (295). "Other" includes: atypical forms of schizophrenia, infantile autism, schizophrenia, childhood type, NOS (Not Otherwise Specified), schizophrenia of specified type not classifiable under 295.0–295.7, schizophreniform attack or psychosis.

Unspecified psychoses with origin specific to childhood (code 299.9) in the International Classification of Diseases 9th revision (ICD-9) includes "child psychosis NOS", "schizophrenia, childhood type NOS" and "schizophrenic syndrome of childhood NOS".[15]

"Childhood type schizophrenia" available in the Soviet adapted version of the ICD-9 (code 299.91) and the Russian adapted version of the 10th revision ICD-10 (code F20.8xx3).[16] This diagnosis is widely used by Russian psychiatrists.

Signs and symptoms

Main article: Schizophrenia

See also: Basic symptoms of schizophrenia

Schizophrenia is a mental disorder that is expressed in abnormal mental functions and disturbed behavior.

The signs and symptoms of childhood schizophrenia are nearly the same as adult-onset schizophrenia. Some of the earliest signs that a young child may develop schizophrenia are lags in language and motor development. Some children engage in activities such as flapping the arms or rocking, and may appear anxious, confused, or disruptive on a regular basis. Children may experience hallucinations, but these are often difficult to differentiate from just normal imagination or child play. Visual hallucinations are more commonly found in children than in adults.[1] It is often difficult for children to describe their hallucinations or delusions, making very early-onset schizophrenia especially difficult to diagnose in the earliest stages. The cognitive abilities of children with schizophrenia may also often be lacking, with 20% of patients showing borderline or full intellectual disability.[17]

Very early-onset schizophrenia refers to onset before the age of thirteen. The prodromal phase, which precedes psychotic symptoms, is characterized by deterioration in school performance, social withdrawal, disorganized or unusual behavior, a decreased ability to perform daily activities, a deterioration in self-care skills, bizarre hygiene and eating behaviors, changes in affect, a lack of impulse control, hostility and aggression, and lethargy.[17]

Auditory hallucinations are the most common of the positive symptoms in children. Auditory hallucinations may include voices that are conversing with each other or voices that are speaking directly to the children themselves. Many children with auditory hallucinations believe that if they do not listen to the voices, the voices will harm them or someone else. Tactile and visual hallucinations seem relatively rare. Children often attribute the hallucinatory voices to a variety of beings, including family members or other people, evil forces ("the Devil", "a witch", "a spirit"), animals, characters from horror movies (Bloody Mary, Freddy Krueger) and less clearly recognizable sources ("bad things," "the whispers").[18] Command auditory hallucinations (also known as imperative hallucinations) were common and experienced by more than ​¹⁄₂ of the group in a research at the Bellevue Hospital Center's Children's Psychiatric Inpatient Unit.[18] And voices repeat and repeat: "Kill somebody!", "Kill her, kill her!".[18] Delusions are reported in more than half of children with schizophrenia, but they are usually less complex than those of adults.[18] Delusions are often connected with hallucinatory experiences.[18] In a research delusions were characterized as persecutory for the most part, but some children reported delusions of control.[18] Many said they were being tortured by the beings causing their visual and auditory hallucinations, some thought disobeying their voices would cause them harm.[18]

Some degree of thought disorder was observed in a test group of children in Bellevue Hospital. They displayed illogicality, tangentialiry (a serious disturbance in the associative thought process), and loosening of associations.

Negative symptoms include apathy, avolition, and blunted emotional affect.

Pathogenesis

There is no known single cause or causes of schizophrenia, however, it is a heritable disorder.

Several environmental factors, including perinatal complications and prenatal maternal infections could cause schizophrenia.[9] These factors in a greater severity or frequency could result in an earlier onset of schizophrenia.[9] Maybe a genetic predisposition is an important factor too, familial illness reported for childhood-onset schizophrenic patients.[19]

Genetic

There is "considerable overlap" in the genetics of childhood-onset and adult-onset schizophrenia, but in childhood-onset schizophrenia there is a higher number of "rare allelic variants".[20] An important gene for adolescent-onset schizophrenia is the catechol-O-methyltransferase gene, a gene that regulates dopamine.[21] Children with schizophrenia have an increase in genetic deletions or duplication mutations and some have a specific mutation called 22q11 deletion syndrome, which accounts for up to 2% of cases.[22][23]

Neuroanatomical

Neuroimaging studies have found differences between the medicated brains of individuals with schizophrenia and neurotypical brains, though research does not know the cause of the difference.[24] In childhood-onset schizophrenia, there appears to be a faster loss of cerebral grey matter during adolescence.[24][25]

Diagnosis

In 2013, the American Psychiatric Association released the fifth edition of the DSM (DSM-5). According to the manual, to be diagnosed with schizophrenia, two diagnostic criteria have to be met over much of the time of a period of at least one month, with a significant impact on social or occupational functioning for at least six months. The DSM diagnostic criteria outlines that the person has to be experiencing either delusions, hallucinations, or disorganized speech. In other words, an individual does not have to be experiencing delusions or hallucinations to receive a diagnosis of schizophrenia. A second symptom could be negative symptoms, or severely disorganized or catatonic behavior.[26] Only two symptoms are required for a diagnosis of schizophrenia, resulting in different presentations for the same disorder.[26]

In practice, agreement between the two systems is high.[27] The DSM-5 criteria puts more emphasis on social or occupational dysfunction than the ICD-10.[28] The ICD-10, on the other hand, puts more emphasis on first-rank symptoms.[29][30] The current proposal for the ICD-11 criteria for schizophrenia recommends adding self-disorder as a symptom.[31]

First rank symptoms

First-rank symptoms are psychotic symptoms that are particularly characteristic of schizophrenia, which were put forward by Kurt Schneider in 1959.[32] Their reliability for the diagnosis of schizophrenia has been questioned since then.[33] A 2015 systematic review investigated the diagnostic accuracy of first rank symptoms:

First rank symptoms for schizophrenia[34]

Summary
These studies were of limited quality. Results show correct identification of people with schizophrenia in about 75-95% of the cases although it is recommended to consult an additional specialist. The sensitivity of FRS was about 60%, so it can help diagnosis and, when applied with care, mistakes can be avoided. In lower resource settings, when more sophisticated methods are not available, first rank symptoms can be very valuable.[34]
Summary accuracy % (95% CI) Prevalence median (range) Implications Quality and comments Diagnosis of schizophrenia from all other diagnoses Sensitivity 57.0 (50.4, 63.3) Specificity 81.4 (74.0, 87.1) 48% (15% to 84%) Prevalence of 48%: 48 out of every 100 people with all other mental health diagnoses will have schizophrenia. The result means that, of these, 21 will not be identified as having schizophrenia by use of FRS (43% of 48). Then, of the 52 people really without schizophrenia, 10 may be incorrectly diagnosed with schizophrenia by the FRS. Diagnosis of schizophrenia from other types of psychosis Sensitivity 58.0 (50.3, 65.3) Specificity 74.7 (85.2, 82.3) 57% (24% to 84%) Prevalence of 57%: 57 out of every 100 people with other types of psychosis will have schizophrenia. The result means that, of these, 24 will not be identified as having schizophrenia by use of FRS (42% of 57). Then, of the 43 people really without schizophrenia, 13 may be incorrectly diagnosed with schizophrenia by the FRS. For all three estimates there are important issues regarding patient selection, use of index test and reference standard. This raises doubts about the accuracy of these findings. Also most studies were not conducted in an everyday clinical setting. Diagnosis of schizophrenia from non-psychotic disorders Sensitivity 61.8 (51.7, 71.0) Specificity 94.1 (88.0, 97.2) 55% (19% to 89%) With a prevalence of 55%, 55 out of every 100 people with non-psychotic disorders will have schizophrenia. Of these, 21 will not be identified as having schizophrenia by use of FRS (38% of 55). Then, of the 45 people really without schizophrenia, 3 may be incorrectly diagnosed with schizophrenia by the FRS.

DSM-5

The definition of schizophrenia remained essentially the same as that specified by the 2000 version of DSM (DSM-IV-TR), but DSM-5 makes a number of changes:[26]

• Subtype classifications were removed.[28]
• Catatonia is no longer so strongly associated with schizophrenia.[35]
• In describing a person's schizophrenia, it is recommended that a better distinction be made between the current state of the condition and its historical progress, to achieve a clearer overall characterization.[28]
• Special treatment of Schneider's first-rank symptoms is no longer recommended.[28]
• Schizoaffective disorder is better defined to demarcate it more cleanly from schizophrenia.[28]
• An assessment covering eight domains of psychopathology – including reality distortion, negative symptoms, thought and action disorganization, cognition impairment, catatonia, and symptoms similar to those found in certain mood disorders, such as whether hallucination or mania is experienced – is recommended to help clinical decision-making.[36]

The same criteria are used to diagnose children and adults.[9][10] Diagnosis is based on reports by parents or caretakers, teachers, school officials, and others close to the child.

A professional who believes a child has schizophrenia usually conducts a series of tests to rule out other causes of behavior, and pinpoint a diagnosis. Three different types of exams are performed: physical, laboratory, and psychological. Physical exams usually cover the basic assessments, including but not limited to; height, weight, blood pressure, and checking all vital signs to make sure the child is healthy.[37] Laboratory tests include electroencephalogram EEG screening and brain imaging scans. Blood tests are used to rule out alcohol or drug effects,[37] and thyroid hormone levels are tested to rule out hyper- or hypothyroidism. A psychologist or psychiatrist talks to a child about their thoughts, feelings, and behavior patterns. They also inquire about the severity of the symptoms, and the effects they have on the child's daily life. They may also discuss thoughts of suicide or self-harm in these one-on-one sessions.[37] Some symptoms that may be looked at are early language delays, early motor development delays and school problems.[37]

Many people with childhood schizophrenia are initially misdiagnosed as having pervasive developmental disorders (autism spectrum disorder, for example).[5]

Age of first episode of psychosis

Childhood schizophrenia manifests before the age of 13 and is also known as very early-onset. Onset before the age of 18 is known as early-onset schizophrenia.

Differential diagnosis

Childhood schizophrenia onset is usually after a period of normal, or near normal, child development.[38] Before the first psychosis there has been described in which strange interests, beliefs and social impairment occur, which could be confused with the deficits of autism spectrum disorder.[38] Hallucinations and delusions are typical for schizophrenia, but not features of autism spectrum disorder.[38] In children hallucinations must be separated from typical childhood fantasies.[38]

Prevention

Further information: Early intervention in psychosis

Research efforts are focusing on prevention in identifying early signs from relatives with associated disorders similar with schizophrenia and those with prenatal and birth complications. Prevention has been an ongoing challenge because early signs of the disorder are similar to those of other disorders. Also, some of the schizophrenic related symptoms are often found in children without schizophrenia or any other diagnosable disorder.[39]

Treatment

Current methods in treating early-onset schizophrenia follow a similar approach to the treatment of adult schizophrenia. Although modes of treatment in this population is largely understudied, the use of antipsychotic medication is commonly the first line of treatment in addressing symptoms. Recent literature has failed to determine if typical or atypical antipsychotics are most effective in reducing symptoms and improving outcomes.[40] When weighing treatment options, it is necessary to consider the adverse effects of various medications used to treat schizophrenia and the potential implications of these effects on development.[41] A 2013 systematic review compared the efficacy of atypical antipsychotics versus typical antipsychotics for adolescents:

Atypical compared with typical antipsychotics (only short term)[42]

Summary
There is not any convincing evidence suggesting that atypical antipsychotic medications are superior to the older typical medications for the treatment of adolescents with psychosis. However, atypical antipsychotic medications may be more acceptable because fewer symptomatic adverse effects are seen in the short term. Little evidence is available to support the superiority of one atypical antipsychotic medication over another.[42]
Outcome Findings in words Findings in numbers Quality of evidence Global state Worse or no improvement There is no clear difference between the newer atypical antipsychotic drugs and the typical drugs for this global outcome. These findings are based on data of low quality. RR 3.3 (0.41 to 26.81) Low Adverse effects Anticholinergic adverse effects Atypical probably reduces the chance of experiencing dry mouth, constipation, and blurred vision but often doses of the older drugs are such that these type of adverse effects are to be expected. Lower doses of control drug could have offset this risk. Data are based on moderate quality evidence. RR 0.2 (0.05 to 0.8) Moderate Leaving the study because of adverse effects Use of atypical drugs may increase the chance of leaving early because of adverse effects, but the difference between the treatments is not clear. Data supporting this finding are based on moderate quality evidence. RR 3.3 (0.41 to 26.81) Moderate

Madaan et al. wrote that studies report efficacy of typical neuroleptics such as thioridazine, thiothixene, loxapine and haloperidol, high incidence of side effects such as extrapyramidal symptoms, akathisia, dystonias, sedation, elevated prolactin, tardive dyskinesia.[43]

Prognosis

A very-early diagnosis of schizophrenia leads to a worse prognosis than other psychotic disorders.[44] The primary area that children with schizophrenia must adapt to is their social surroundings. It has been found, however, that very early-onset schizophrenia carried a more severe prognosis than later-onset schizophrenia. Regardless of treatment, children diagnosed with schizophrenia at an early age suffer diminished social skills, such as educational and vocational abilities.

The grey matter in the cerebral cortex of the brain shrinks over time in people with schizophrenia; the question of whether antipsychotic medication exacerbates or causes this has been controversial. A 2015 meta-analysis found that there is a positive correlation between the cumulative amount of first generation antipsychotics taken by people with schizophrenia and the amount of grey matter loss, and a negative correlation with the cumulative amount of second-generation antipsychotics taken.[45][46]

Epidemiology

Schizophrenia disorders in children are rare.[7] Boys are twice as likely to be diagnosed with childhood schizophrenia.[47] There is often an disproportionately large number of males with childhood schizophrenia, because the age of onset of the disorder is earlier in males than females by about 5 years.[5] People have been and still are reluctant to diagnose schizophrenia early on, primarily due to the stigma attached to it.[39]

While very early-onset schizophrenia is a rare event, with prevalence of about 1:10,000, early-onset schizophrenia manifests more often, with an estimated prevalence of 0.5%.[43]

History

Until the late nineteenth century, children were often diagnosed as suffering from psychosis like schizophrenia, but instead were said to suffer from "pubescent" or "developmental" insanity. Through the 1950s, childhood psychosis began to become more and more common, and psychiatrists began to take a deeper look into the issue.[12]

Sante De Sanctis first wrote about child psychoses, in 1905. He called the condition "dementia praecocissima" (Latin, "very premature madness"), by analogy to the term then used for schizophrenia, "dementia praecox" (Latin, "premature madness).[48] Sante de Sanctis characterized the condition by the presence of catatonia.[49] Philip Bromberg thinks that "dementia praecocissima" is in some cases indistinguishable from childhood schizophrenia, and Leo Kanner believed that "dementia praecocissima" encompassed a number of pathological conditions.[49]

Theodor Heller discovered a new syndrome dementia infantilis (Latin, "infantile madness") in 1909.[50] In the modern ICD-10 "Heller syndrome" is classified under the rubric F84.3 "other childhood disintegrative disorder".

Also in 1909, Julius Raecke reported on ten cases of catatonia in children at the Psychiatric and Neurological Hospital of Kiel University, where he worked. He described symptoms similar to those previously recorded by Dr. Karl Ludwig Kahlbaum, including "stereotypies and bizarre urges, impulsive motor eruptions and blind apathy."[50] He also reported refusal to eat, stupor with mutism, uncleanliness, indications of waxy flexibility and unmotivated eccentricity, and childish behavior.[50]

A 1913 paper by Karl Pönitz, "Contribution to the Recognition of Early Catatonia",[51] recounts a case study of a boy who manifested "typical catatonia" from the age of twelve, characterizing him as showing a "clear picture of schizophrenia."[50]

Before 1980 the literature on "childhood schizophrenia" often described a "heterogeneous mixture" of different disorders, such as autism, symbiotic psychosis or psychotic disorder other than schizophrenia, pervasive developmental disorders and dementia infantilis. At the current time, however, some researchers, regarded autism (autistic disorder) and schizophrenia as two distinct entities.

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Further reading

• Tiffin PA, Welsh P (November 2013). "Practitioner review: schizophrenia spectrum disorders and the at-risk mental state for psychosis in children and adolescents--evidence-based management approaches". Journal of Child Psychology and Psychiatry, and Allied Disciplines. 54 (11): 1155–75. doi:10.1111/jcpp.12136. PMID 24102356.