September 2004, Vol 26, No. 9
Update Article

Diagnosis and management of schizophrenia and schizophrenia-like disorders in primary care

K Y Mak 麥基恩

HK Pract 2004;26:392-399

Summary

Schizophrenia is a multifactorial disorder subject to certain risk factors (genetic, neuro-developmental and psychosocial) which interact to push the individual to tip over the threshold for the clinical manifestation of the syndrome. Primary care doctors can play an important role in identifying at-risk individuals within the community,the prompt diagnosis of first episodes and in the proper referral of schizophrenic patients. Follow-up care of stabilized patients is also feasible, and continued support and advice to the carers are also of great importance. An update information regarding the clinical syndromes, the aetiology and the management of schizophrenia and schizophrenia-like disorders is presented.

摘要

精神分裂症是多因素引起的疾病，有關的危險因素包括遺傳、神經發育和心理社交等等，它們相互影響，而令病人出現一系列的臨床的病徵。基層醫生的角色很重要，他們要識別出社區中的高危的人群；及早診斷首次發病的病人；提供適當的治療或轉介；為病情穩定的病人做覆診，此外，為向照顧者提供持續的支援和意見也很重要。本文闡述精神分裂症和類似病症的臨床綜合症狀、成因和治療方法。

Introduction

In many countries, schizophrenic disorder is regarded as a medical term for "madness", though the term was originally coined by Bleuler to mean a disconnection or splitting of the psychic functions. Throughout the past century, the clinical description of schizophrenia has undergone quite a lot of changes, and the present day definition is restricted by various specific diagnostic criteria. Nevertheless, schizophrenic disorders remain the classical, severe and most disabling among all mental disorders.

Prevalence

A WHO study showed that similar typical cases occurred in nine countries, including Taiwan.1 According to the study, the prevalent rate increased from 1850 onwards, but there was an apparent decrease of new typical cases in recent decade. The quoted life-time prevalence ranges from 0.2 to 2.0%, but a more realistic estimate should be 0.5 to 1%. The incident rate, however, is estimated to be 1 to 2 per 10,000 of the total population per year, and is slightly higher in men than women. The risk increases among the relatives of the schizophrenics (Table 1). The peak age of onset is 21 to 25 in men but 24 to 30 in women.

Aetiology

The current consensus is that schizophrenia is a "neurodevelopmental" disorder with abnormalities in the brain even during foetal development, but post-natal psychological and social factors are also important in determining its clinical onset and manifestation.

1.

Biological factors

There is an increased incidence among the family members of schizophrenic patients, up to a ten-fold increase for siblings and children of an affected patient. The concordance rate among monozygotic twins is about 50%, compared to 7% for dizygotic twins. Furthermore, cross-fostering studies found that the rate was greater among the biological relatives of the schizophrenic adoptees, than of controls, but not increased amongst the schizophrenic adoptees' parents. Genetic studies have suggested multiple genes of relatively small effects. Currently, there are about ten susceptibility genes identified, including alleles or haplotypes for GRN3, COMT, etc.3 that predispose a person for the disorder when under stress or injury.

More patients are born in winter months,4 and perinatal complications such as hypoxia5 and viral infection during pregnancy are implicated.6 Recently, velo-cardio-facial syndrome (VCFS) patients with deletion of 22q11 gene (cleft palate, mental retardation, congenital heart disease and hypocalcaemia) have a 30% chance of developing psychotic symptoms, usually of early onset.

Neuro-imaging studies indicated that the frontal region, the subcortical region and the connections between them are involved. Some schizophrenics have enlarged cerebral ventricles and reduced hippocampal volume, especially the left side.7 Positive symptoms are associated with dopaminergic hyperactivity in the mesolimbic pathway, while hypoactivity in the mesocortical pathway may underlie cognitive and negative symptoms. Amphetamine type of drugs (and cannabis abuse) can often induce a psychosis resembling schizophrenia in susceptible individuals,8 pointing to the dopamine system, but the novel antipsychotics suggest that the serotonin system and the glutamate system may also be involved.9
   

2.

Psychological factors

Schizophrenic patients often have a premorbid personality of a schizoid or schizotypal type, and there is frequently a past history of behavioural problems in childhood concerning with relational, motor skills and academic issues.

Cognitive deficits have been found in many patients even before their onset of the disorder. David et al10 investigated the link between low IQ and later development of psychosis, and suggested that low IQ compromises information processing leading eventually to schizophrenia. Others have hypothesised that a failure of selective attention may result in delusions that try to connect (though erroneously) disparate bits of information.11 Impairment of executive function and working memory is also found, but perhaps a result rather than the cause of schizophrenia.
   

3.

Social factors

Bateson et al12 found that relatives of patients often spoke with "double-bind" messages, while Fromm-Reichmann13 blamed the mothers as "schizophrenogenic", and Lidz et al14 found skewed or schimatic marriages of parents. However, research did not show any consistent findings, and the parental behaviour is often a maladaptive response to their psychotic children's abnormal behaviour. Nevertheless, Wahlberg et al15 did find communication deviance in the parents of adopted high-risk children increased the vulnerability to schizophrenia. Lastly, Hirsch & Leff16 found that high "expressed emotions" parents (especially emotional over-involvement, excessive critical comments and hostility) could lead to frequent relapses of the disorder.

There is some sort of significant stress related to various life events that precede the clinical presentation of the disorder. For example, there was an increased incidence of schizophrenia among the immigrants, such as the African-Caribbeans in the United Kingdom,17 and there are often reports of loss of job or love affairs among the first onset patients. But again, these events can be due to self-selection or the social outcome secondary to the handicaps incurred by the psychotic symptoms.

In summary, the occurrence of a clinical syndrome of schizophrenia is often an interaction between the three groups of causes during the development of a person.

Clinical features

Schizophrenia can be diagnosed by its specific symptoms and behaviours, even in the primary care sector. By definition, there should be some deterioration from a previous level of functioning (such as work, social relations and self-care), and the duration should last at least six months. It should not be a result of Affective Disorder, Organic Mental Disorder or Mental Retardation. The onset may be abrupt though the majority of patients display some prodromal phase.

1.

The prodromal phase

This stage is characterised by social isolation and withdrawal, with marked impairment in role functioning and in personal hygiene and grooming. Sometimes, there is some unusual or peculiar behaviour that is difficult to be understood by outsiders. At times, there may be an emotional outburst difficult to control by others or even by self. It is at the level of primary care that patients with this phase of disorder often present.
   

2.

The active phase

By the time the patients present at the psychiatric clinics, the clinical picture is often dominated by the so-called positive symptoms which include:
   
  i. Reality distortion: characterised by delusions and hallucinations. The former is fixed, false and often bizarre beliefs despite evidence to the contrary. For example, being controlled by alien forces or energy, that one's thoughts are being broadcasted, inserted or withdrawn. The contents can be persecutory, somatic, grandiose, religious, nihilistic or otherwise. Hallucinations, on the other hand, are imaginary or anomalous perceptions without actual objects of sensory stimulation. They are mostly auditory (hearing) in nature, but can be visual, tactile, olfactory or taste. The voices are often of the third person as if others were talking about him or her, or are criticizing the patient's ordinary activities (running commentary).
     
  ii. Thought disturbances, distinguished by the presence of disorganized and markedly illogical thinking, as evidenced by incoherence or irrelevant remarks. There is often a marked loosening of associations between expressed ideas, presenting as illogical thinking or talking past the point. Sometimes the structure and coherence of thought is lost resulting in jumbled words. Others may use certain words in unusual or special ways ("metonyms") and a few will invent special new words ("neologisms") incomprehensible by others.
     
  At this stage, the patients would frequently exhibit emotions of anxiety and dysphoria, but theses are often overshadowed by the above more bizarre symptoms.
   

3.

The chronic phase

After the acute phase, the clinical syndrome becomes chronic, and is characterized by negative symptoms and disorders of motor activity.
     
  a. Negative symptoms: characterised by the following 5 "A"s:
    i. Affective flattening or blunting: includes decreased spontaneous movement, poor eye contact, etc.
    ii. Alogia: poverty of speech and its content, blocking and delayed response.
    iii. Avolition-apathy: includes poor personal hygiene and physical anergia. iv. Anhedonia-asociability: decreased interests and sexual activity, etc.
    v. Attention deficit: impaired readiness to respond and recall of immediate memory.
       
  b. Motor symptoms: with various manifestations
    i. There can be psychomotor poverty symptoms including stupor and excitement (the catatonic syndrome). A patient in stupor is immobile, mute, unresponsive but fully conscious, and may change (occasionally fairly quickly) to uncontrolled motor activity and excitement. Rarely, the patient may develop a special muscle tone that allows the body to be manipulated into an awkward posture ("waxy flexibility") which is then maintained for a long period without obvious distress or discomfort ("catalepsy"). An extreme case is the "pillow test" whereby the patient can maintain his head at the raised posture even after the pillows have been removed.
    ii. Stereotypy is a repeated movement that does not appear to be goal orientated e.g. rocking the body forwards and backwards. But if the behaviour is goal-directed, it is called mannerism e.g. raising the hand as if a salute to somebody.
    iii. Ambitendence refers to an ambivalent movement that before its completion would switch into the opposite movement. An example is the walking in and stepping out of the door repeatedly without entering the room.
       
 

It should be noted that the acute and chronic symptoms described above can exist together during the different stages of the disorder. As a result of these symptoms, the social behaviour of the patients becomes eccentric and dysfunctional, often to their disadvantage.

With such a complex symptomatology, schizophrenia is sometimes further classified into subtypes, depending on the predominant clinical symptoms at the time of evaluation. When features of more than one subtype are present, the following hierarchy should apply:
       
  a. catatonic type - immobility or excessive motor activity, extreme negativism, peculiarities of voluntary movement, echolalia or echopraxia.
  b. disorganized type - disorganized speech or behaviour, flat or inappropriate affect.
  c. paranoid type - preoccupied with delusions or hallucinations.
  d. undifferentiated type - no prominent features as stated in the above 3 categories.
  e. residual type - full clinical syndrome of schizophrenia in the past but no longer so.
     
In a way, the acute-chronic syndromes described above are similar to the "Type I & II" division by Crow et al.18 Type I has an acute onset with positive symptoms, and has good social functioning during the remissions. Type II on the other hand has an insidious onset with negative symptoms, and has a relatively poor outcome, because of structural changes (especially ventricular enlargement) of the brain. Last but not the least, Liddle19 described three overlapping clinical syndromes (reality disturbance, disorganization, psychomotor poverty) each linked to particular patterns of neuropsychological deficits and regional cerebral blood flow.

Schizophrenia-like disorders

According to the DSM-IV, if the duration of the illness is less than one month, the diagnosis should be Brief Psychotic Disorder. But if the duration is between one to six months, the diagnosis should be Schizophreniform Disorder. Both conditions, however, are grouped under the Acute and Transient Psychotic Disorders in the ICD-10.

Sometimes, a Schizoaffective Disorder is diagnosed when, during an uninterrupted period of illness, there is, at some time, either a Major Depressive Episode, a Manic Episode, or a Mixed Episode Disorder concurrent with symptoms that meet the diagnostic criteria for schizophrenia, lasting for a substantial portion of the duration of the illness. During the same period of illness, there have been delusions or hallucinations for at least two weeks in the absence of prominent mood symptoms. However, if the depression develops after the psychotic symptoms subside, the clinical syndrome is better called Post-Schizophrenic Depression.

There are some patients who do not have the definitive symptoms of schizophrenia. If these attenuated psychotic symptoms (e.g. non-delusional ideas of reference, persecutory beliefs and unusual thinking) are long-standing, it is called Schizotypal Disorder in the ICD-10 (or Schizotypal Personality Disorder as in the DSM-IV). The ICD-10 also recognized a type called Simple Schizophrenia when there are only negative symptoms without psychotic features.

Lastly, if some underlying organic disease e.g. temporal lobe epilepsy is found that causes the schizophrenia-like symptoms, the patient is said to suffer from an Organic Psychosis. Likewise, if the primary cause is due to a medication or substance, it is called Substance-Induced Psychosis.

Management

The current trend is on functional recovery of the patient besides symptom removal. In the past, schizophrenia has been managed only within the specialist psychiatric setting, but in recent years primary care physicians are of increasing importance in providing continuous care, especially when the patient's mental state is well stabilized. In a way, primary care doctors have a special role in detecting the prodromal symptoms, in making prompt diagnosis, and in persuading the patients for early treatment. Besides, they are in a good position to and may be better equipped to rule out primary or comorbid physical diseases and to detect substance abuse. Basically, management can be divided into three stages, viz.:

1.

Prevention

So far, there is no specific method to prevent schizophrenia except some genetic counselling when one or both partners suffer from the disorder. Some would advocate the treatment of prodromal symptoms if they are present in the relatives of the patients20 in order to prevent or delay progression to psychosis. However, this triggers an ethical dilemma as the majority of these prodromal relatives will not develop psychosis. Perhaps those with ultra high-risk factors (including a positive family history, schizotypal personality, substance abuse, and presence of some subclinical psychotic symptoms such as ideas of reference, unusual thought content, perceptual abnormalities, functional decline and social withdrawal) may worth such prophylactic therapy.

In a way, the primary care doctors have a unique position in society as the first contact point in mental health promotion in the community. The main emphasis should be on mental health education, advocating better coping skills towards stress, and the avoidance of high expressed emotions in the family. For example, the high emotion expression mother should be discouraged from getting in touch with the schizophrenic son for long period at home.

As regards definitive therapy, the current emphasis is on early treatment of first episode,21 with prevention of relapse as discussed below.
   

2.

Treatment

Hospital or home treatment depends on the danger of the patient to self or others, and sometimes on the social circumstances including the support from the relatives. Despite the relatively poor living circumstances and supervision at home, not many patients or relatives prefer hospitalization.
   
 

a.

Acute phase

Early prompt treatment is essential. The mainstay of therapy is antipsychotics, either with typical or atypical neuroleptics. While all antipsychotics have the common function of a dopamine DA2 blockade,22 there are differential side-effect profiles. Generally speaking, the atypicals are relatively more efficacious with effects on negative and mood symptoms in addition to less serious side-effects. In the U.K., these atypicals are recommended as first line treatment for new-onset schizophrenia.23 They can be given orally or by injections (short to medium acting and depot long-acting) depending on the compliance of the patients. For the refractory patients, clozapine may be tried but agranulocytosis has to be watched out for. Some medications (e.g. thioridazine, sertindole) are contraindicated in patients with certain cardiac conditions or receiving medications known to prolong the QT interval. The more common side-effects of the various medications are shown in Table 2. Electro-convulsive therapy is suggested when there is no response to medications despite adequate or high dosage and adequate duration of treatment, or when the patient cannot tolerate the side-effects of the medications, but there is still controversy over its use. Psychotherapy except perhaps supportive psychotherapy is not very useful at this stage, while open confrontation, contradicting arguments or psychoanalytic interpretation should be avoided.

Since most antipsychotics have anti-anxiety properties, additional anxiolytics are rarely needed. As regard coexisting depressive symptoms, antidepressants may be tried but tricyclics may worsen psychotic symptoms. The purer selective serotonin reuptake inhibitors are theoretically superior and safer, but their true efficacy still requires vigorous evaluation,24 especially when the atypical antipsychotics seem to have inherent antidepressant property.
     
 

b.

Post-acute phase

Maintenance treatment is often necessary as the majority of the patients relapse without treatment. The duration of treatment varies between 6 months to 2 years for first episode patients. So far, "targeted maintenance" is more cost-effective than "interrupted" treatment.25 If compliance to oral medications is poor, depot injections are recommended. Social support should be provided continuously to cope with stress (especially significant life-events). In contrast to the acute treatment, psychotherapy especially cognitive-behavioural therapy has been of increasing use to change the abnormal behaviour of the patients and to improve compliance to therapy. In case of aggression or suicidal behaviour, primary care physicians should consult the specialists for advice.
     

3.

Rehabilitation

For those with refractory or residual symptoms (especially negative symptoms), psychosocial rehabilitation in the community is recommended, especially for the chronic and disabled patients. Community mental health professionals should join force with primary care doctors in keeping schizophrenic patients away from the hospitals. The main emphasis is to maximise the remaining potential of the patients, and to cover their various needs. Obviously, social services (finance and housing, childcare, etc.) are useful and vocational training (in the form of sheltered or supported employment) can encourage independence. Social skills training and stress management as well as family psychoeducation and intervention are found effective in improving functioning and in preventing relapses.26 Last but not the least, recreational services provision is a bonus for a better quality of life. Many of these services are provided by non-government organizations, and they would welcome close working relations with primary care doctors.
   
Throughout all these stages, there should also be psychological and social support to the relatives or the carers who have taken up the burden of care from the hospital. Primary care doctors, who know the patients and their families well, are in a good position to be advocates. Empowerment of the patients and their relatives are worthwhile initiatives, in line with the trend in human (patient) rights. In recent years, efforts have been put to campaign against the stigma attached to mental disorders.

Outcome

The age of onset is usually during adolescence or early adulthood. Most of the patients run a relapsing course with persistent symptoms. Approximately 50% relapsed within two years despite treatment, while 30% would not relapse for two years even without treatment. 35% have attempted suicide during their lifetime, and 10% died from suicide (another 5% would die from other unnatural causes including accidents and poverty). Compared with the normal population, the schizophrenic patients have a high incidence of violent acts but a shorter life expectancy. Nevertheless, there are both good and poor prognostic factors (Table 3).

For "first episode schizophrenia", there is an 80% chance of a second episode, while 15% of the remaining does not regain normal functioning. Unfortunately, only about 5% can be considered recovered. There is a sub-group of patients that are of ultra-high risk of relapse, those with a positive family history (especially first degree relatives), non-specific or attenuated symptoms, and decreased functioning (e.g. a 30 points lost /year in the GAF scale).

Conclusion

Primary care doctors have in the past been rather reluctant in the management of schizophrenic patients in their clinical practice. But with better training in the management of psychological disorders in the community setting, and with the availability of newer and safer antipsychotic medications, they are more capable and willing in the continuous care of such psychotic patients, especially when backed up by specialist consultant psychiatric services. In fact, they are unique in the early recognition of prodromal symptoms or first-episode schizophrenics, and prompt and appropriate referral or treatment will alter the course of the disorder from a gloomy, devastating and deteriorating picture to a more optimistic, functional and meaningful one. A well-integrated and seamless liaison teamwork between psychiatrists and primary care doctors could effectively alleviate the many unnecessary stigma and hurdles in the management of psychotic patients in the society.

Key messages

  1. Schizophrenia and schizophrenia-like disorders are serious mental disorders, and early recognition and treatment are important.
  2. Properly trained primary care doctors are becoming more important in the early detection of these disorders, including the prodromal phase.
  3. Medications for these disorders have improved significantly during the past few decades, and can be safely applied even in the primary care setting for uncomplicated patients with stable mental conditions.
  4. Psychotherapy and psychosocial rehabilitation are also important in the post-acute phase of treatment.
  5. A well coordinated team of mental health specialists and primary care doctors can be instrumental in preventing relapse and successful reintegration of the patients into society.

K Y Mak, MBBS(HK), MD(HK), MHA, FRCPsych
Honorary Professor,
Department of Psychiatry, The University of Hong Kong.

Correspondence to : Professor K Y Mak, Department of Psychiatry, The University of Hong Kong, Queen Mary Hospital, Hong Kong.

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