Overview and Risk Factors
Schizophrenia is characterized by the presence of delusions and/or hallucinations, as well as disorganized speech and behavior. It is also marked by the loss of normal functions, particularly emotional expression, productivity of thought and speech, and goal-directed behavior. Although it is discussed here as a single entity, schizophrenia is likely composed of a group of disorders that are heterogenous in origin, despite similar symptomatology. An excess of brain dopamine activity is presumed to underlie these symptoms, but its etiology is likely multifactorial and remains an area of ongoing research.
The disorder affects about 1% of people worldwide. Schizophrenia occurs in people of all social classes, although patients are often socially and economically marginalized as a result of the disease and its accompanying stigma, resulting in lowered socioeconomic status.
Risk Factors
Age. The onset of schizophrenia is typically before age 35, and the illness persists throughout life. Although the lifetime risk for men and women is similar, onset is often later in women than in men, with a second peak onset around menopause, suggesting a protective role for estrogen. Peak onset for men is age 10-25, and for women is age 25-35. Less than 10% of women present after age 40 (usually perimenopausally).
Genetic Factors. Approximately half of monozygotic twins are affected when the other twin has schizophrenia. The risk to dizygotic twins is around 15%, and first-degree relatives have about a 10% risk. However, no specific gene has been isolated, and several genes may play a role.
Early Developmental Influences. Analgesic use during the second trimester1 or hypertension and diuretic use during the third trimester of pregnancy may be associated with increased risk of schizophrenia for the newborn.2 Fetal malnutrition, paternal age over 50 years,3 and winter/spring births (presumably related to viral infections) are also associated with increased risk. Persons who were not breast-fed for at least 2 weeks have been shown to have increased prevalence of schizophrenia,4 and a child with a genetic predisposition to schizophrenia may have a further increased risk if a childhood head injury occurs.
Toxoplasma gondii. This organism may infect the central nervous system and may be associated with schizophrenia.
Diagnosis and Treatment
Diagnosis
The history will clarify acute symptoms, and physical examination may help rule out other causes of psychosis. The diagnostic criteria of the American Psychiatric Association call for 2 or more of the following, each present for a significant portion of time during a 1-month period:
- Delusions.
- Hallucinations.
- Disorganized speech.
- Grossly disorganized or catatonic behavior.
- Negative symptoms: affective flattening, reduced productivity of thought or speech, or reduced goal-directed behavior.
To establish the diagnosis, the patient must also demonstrate marked social or occupational dysfunction, signs of illness must be present for at least 6 months, and the condition cannot be attributable to substance abuse, a medical condition, or other mental health problems, such as depression and bipolar disorder.
Schizophrenia cannot be diagnosed through laboratory tests or imaging. However, some brain-imaging studies reveal increased ventricular and decreased frontal lobe volume.
Treatment
Treatment for schizophrenia is lifelong and multidisciplinary, aiming to reduce symptoms, maximize functioning, and prevent relapse. This is often challenging, because affected individuals may not recognize their illness or seek treatment, and may stop treatment because of undesirable side effects, limited financial resources, or lack of access to mental health services.
Ideally, a person can maintain a fairly normal lifestyle once properly treated. Emotional and physical support is an important component of treatment, and patients often have superior outcomes when direct family or community support is a part of their overall treatment plan.
Pharmacologic Therapy
Medications are the most effective treatment. Discontinuing medication will typically lead to recurrence of symptoms. However, relapse is common even with continuous treatment. The disease is characterized by a waxing and waning of symptoms, necessitating close follow-up and continued support.
First-generation antipsychotics, such as haloperidol or chlorpromazine, can be very effective, but they carry greater risk of tardive dyskinesia and other undesirable side effects, compared with newer drugs.
Second-generation (atypical) antipsychotics, such as risperidone, olanzapine, ziprasidone, aripiprazole, and quetiapine, generally carry less risk of tardive dyskinesia and neuroleptic malignant syndrome, and may be more effective than first-generation drugs at preventing relapse. Olanzapine often results in significant weight gain (on the order of 20-30 pounds) as well as the development of metabolic syndrome and its accompanying health consequences. Aripiprazole and ziprasidone are the least likely to cause weight gain and sedation. Risperidone now carries a black box warning for increased risk of cerebrovascular events. Sedation is often a side effect of risperidone, quetiapine, and olanzapine, although it subsides with continued use.
Clozapine may be used for refractory cases. It also helps treat suicidal ideation, an important consideration given that as many as 40% of persons with schizophrenia will attempt suicide. Physicians need special authorization to use clozapine. Clozapine has several serious potential adverse effects, including life-threatening agranulocytosis, making weekly blood draws mandatory. Additional adverse effects include weight gain, anticholinergic effects, and increased risk of seizures.
Nonpharmacologic Therapy
Cognitive-behavioral therapy and family therapy are intended to help the patient and family identify warning signs of relapse and its consequences and improve treatment adherence. Family therapy has been shown to reduce relapse and rehospitalization.5
Group therapy, job training, and social skills training may improve quality of life and social functioning.6,7
Nutritional Considerations
Among the sequelae of schizophrenia is an increased risk of cardiovascular disease. The greater risk results from several factors: patients' diets are often poor; smoking and physical inactivity are common; and antipsychotic medications may contribute to weight gain, hyperglycemia, and hypertriglyceridemia;8-11 As a result, patients benefit from heart-healthy diets. Evidence indicates that behavioral interventions can improve weight control in persons with schizophrenia.9,12
Aside from cardiovascular risk, there may be other reasons for patients with schizophrenia to avoid typical "Western" (ie, high-fat, high-sugar) diets. These diets reduce hippocampal expression of brain-derived neurotrophic factor (BDNF), an important growth and maintenance factor for dendrites, which is reduced in the prefrontal cortex of patients with schizophrenia. Low concentrations of BDNF have also been implicated in both coronary atherosclerosis and insulin-resistance syndrome.13 The latter is twice as common in schizophrenia patients as it is in the U.S. adult population, and helps explain the greater incidence of coronary heart disease in these patients.14 Clarification of these issues awaits further research.
Regarding the causation of schizophrenia, epidemiologic studies have adduced interesting but inconclusive links between schizophrenia and environmental factors, including diet. Some evidence indicates that maternal exposure to Toxoplasma gondii is a risk factor for schizophrenia in offspring.15,16 Humans can become infected with T gondii in a variety of ways, including ingestion of animal tissues. T gondii can also be spread when cat litter is not promptly cleaned.
Researchers have speculated that Westernized diets may play a role, citing a lower prevalence of schizophrenia in unindustrialized cultures and Asian populations (although underreporting may contribute to this difference). During the Industrial Revolution, intakes of saturated fat, meat, dairy products, and refined sugars paralleled an increase in schizophrenia.8 Such possibilities remain speculative.
Several studies have suggested that individuals with schizophrenia have lower levels of certain polyunsaturated fats in the central nervous system, compared with other people, and that eicosapentanoic acid supplements may reduce symptoms of schizophrenia, as measured by the Positive and Negative Symptoms Scale (PANSS) (Peet, 2004). However, these studies were generally small and need to be repeated in larger, well-controlled studies.
One group of investigators has found a reduction in tardive dyskinesia symptoms with the use of branched-chain amino acid formulas.18-20 Tardive dyskinesia is associated with deficient clearance of phenylalanine, an excess of which may increase production of catecholamines and indolamines, which may drive the hyperkinetic movements of tardive dyskinesia.18 Branched-chain amino acids compete with phenylalanine at the blood-brain barrier, reduce the entry of phenylalanine into the CNS, and subsequently reduce production of catecholamines and indolamines.
Orders
See Basic Diet Orders chapter.
What to Tell the Family
Schizophrenia is a lifelong illness that requires medication and support from both mental health professionals and family members. Persons with schizophrenia are at greater than average risk for cardiovascular disease from a combination of medication, sedentary lifestyle, poor diet, and smoking. Family members can support the affected member by providing a healthful diet and a smoke-free environment, and by encouraging participation in regular physical activity. The potential benefits of additional nutritional interventions is a matter of ongoing research.
References
1. S¸rensen HJ, Mortensen EL, Reinisch JM, Mednick SA. Association between prenatal exposure to analgesics and risk of schizophrenia. Br J Psychiatry. 2004;185:366-371.
2. S¸rensen HJ, Mortensen EL, Reinisch JM, Mednick SA. Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring? American Journal of Psychiatry. 2003;160:464-468.
3. Byrne M, Agerbo E, Ewald H, Eaton WW, Mortensen PB. Parental age and risk of schizophrenia. Archives of General Psychiatry. 2003;60:673-678.
4. S¸rensen HJ, Mortensen EL, Reinisch JM, Mednick SA. Breastfeeding and risk of schizophrenia in the Copenhagen Perinatal Cohort. Acta Psychiatr Scand. 2005;112:26-29.
5. Bustillo J, Lauriello J, Horan W, Keith S. The psychosocial treatment of schizophrenia: an update. Am J Psychiatry. 2001;158:163-175.
6. Eckman TA, Wirshing WC, Marder SR, et al. Technique for training schizophrenic patients in illness self-management: a controlled trial. Am J Psychiatry. 1992;149:1549-1555.
7. Marder SR, Wirshing WC, Mintz J, et al. Two-year outcome of social skills training and group psychotherapy for outpatients with schizophrenia. Am J Psychiatry. 1996;153:1585-1592.
8. Peet M. Diet, diabetes and schizophrenia: review and hypothesis. Br J Psychiatry. 2004;184(suppl 47):S102-S105.
9. Faulkner G, Soundy AA, Lloyd K. Schizophrenia and weight management: a systematic review of interventions to control weight. Acta Psychiatr Scand. 2003;108:324-332.
10. Mahadik SP, Evans D, Lal H. Oxidative stress and role of antioxidant and omega-3 essential fatty acid supplementation in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2001;25:463-493.
11. Haupt DW, Newcomer JW. Hyperglycemia and antipsychotic medications. J Clin Psychiatry. 2001;62(suppl 27):15-26, discussion 40-41.
12. O'Keefe CD, Noordsy DL, Liss TB, Weiss H. Reversal of antipsychotic-associated weight gain. J Clin Psychiatry. 2003;64:907-912.
13. Chaldakov GN, Fiore M, Stankulov IS, et al. NGF, BDNF, leptin, and mast cells in human coronary atherosclerosis and metabolic syndrome. Arch Physiol Biochem. 2001;109:357-360.
14. Cohn T, Prud'homme D, Streiner D, Kameh H, Remington G. Characterizing coronary heart disease risk in chronic schizophrenia: high prevalence of the metabolic syndrome. Can J Psychiatry. 2004;49:753-760.
15. Brown AS, Schaefer CA, Quesenberry CP Jr, Liu L, Babulas VP, Susser ES. Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring.
Am J Psychiatry. 2005;162:767-773.
16. Torrey EF, Yolken RH. Toxoplasma gondii and Schizophrenia. Emerg Infect Dis. 2003;9:1375-1380.
17. Peet M. Nutrition and schizophrenia: beyond omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2004;70:417-422.
18. Richardson MA, Bevans ML, Read LL, et al. Efficacy of the branched-chain amino acids in the treatment of tardive dyskinesia in men. Am J Psychiatry. 2003;160:1117-1124.
19. Richardson MA, Small AM, Read LL, Chao HM, Clelland JD. Branched chain amino acid treatment of tardive dyskinesia in children and adolescents. J Clin Psychiatry. 2004;65:92-96.
20. Richardson MA, Bevans ML, Weber JB, et al. Branched chain amino acids decrease tardive dyskinesia symptoms. Psychopharmacology (Berl). 1999;143:358-364.
