Schizophrenia is the most severe psychiatric disorder.  It has many causes.  Genetics studies have found in associated with an increasing large number of genetic abnormalities, suggesting that many different genetic defects can result in causing the disease.  Schizophrenia is also associated with many other factors, especially those affecting the brains of fetuses or infants, such at in utero infections, and early head trauma.  Children born of older parents, over age 40, are also somewhat more likely to be afflicted.  Drug abuse, e.g. marijuana, LSD, stimulants, etc., etc., also causes cases exactly like schizophrenia, but should officially be diagnosed at drug-induced psychotic states.

While treatment of schizophrenia is less than perfect, several new add-on approach have me quite excited.  We can do better.

Diagnosis

The diagnosis of schizophrenia requires two or more of the following: delusions, hallucinations (usually hearing voices), disorganized speech (incoherence, disconnected thinking), grossly disorganized or catatonic behavior, and negative symptoms (flat affect or mood, lack of thought, social withdrawal, loss of interest in previously pleasurable activities).  These symptoms have to last for at least one month and the person has to have his illness for at least six months for it to be considered schizophrenia.  Before six months are up, it is considered a schizophreniform disorder, which usually goes on to last over six months and then receive the diagnosis of schizophrenia.  There must also be a marked deterioration in at least one area of life, work, school, interpersonal, or self-care.  If there is a simultaneous severe depression or mania, the diagnosis of Schizoaffective Disorder or Mood Disorder with Psychotic Features is made instead.

Schizophrenia Decreasing in Finland: Persons aged 16-25 with schizophrenia declined from 0.69 per 1000 in 1954-5 cohort vs. 0.43 in 1964-5 and equally among sexes. Suvisaari, APA 5/99.

Females Later Onset: 10,972 outpatients across 10 European countries. Age at onset of schizophrenia was 27.6 years for males and 30.6 years for females. Forty-two percent of patients were female. In general, there were no meaningful differences in clinical severity between males and females. Social functioning was better in females (higher proportion of females were living independently [58% vs. 41%] and were involved in a relationship [41% vs 22%]). Haro JM, Gasquet I, Lépine JP, et al. Gender differences in schizophrenia: results from the schizophrenia outpatient health outcomes study (SOHO). Program and abstracts of the 15th European College of Neuropsychopharmacology Congress; October 5-9, 2002; Barcelona, Spain. Abstract P.2.092.

Fertility Lower in Schizophrenia Families: Finland 1950-9 study found very low fertility of schizophrenia (0.80) not offset by minimally higher fertility of siblings. Fertility of patients with schizophrenia, their siblings, and the general population: a cohort study from 1950 to 1959 in Finland. Haukka J, Suvisaari J, Lonnqvist J. Am J Psychiatry 2003 Mar;160(3):460-3

Mortality High in Schizophrenia: With haloperidol, thioridazine, and risperidone, the rate of cardiac arrest and ventricular arrhythmias and all cause mortality was two to five times higher than in the comparison groups. The findings confirm that all cause mortality in schizophrenia is relatively high. Avoid doses of thioridazine over 100 mg per day and not to use the drug concurrently with any other that can lengthen the QT interval, such as erythromycin, azithromycin, and amitriptyline and other antidepressants.

Suicide Infrequent and Not Increased in Placebo Groups: In 31 studies, 7152 patients were included: 1888 in placebo groups (398.2 person-years) and 5264 in active compound groups (981.3 person-years). One suicide occurred in the placebo groups (0.05%, or an incidence rate of 251 per 100,000 years of exposure) and 1 in the active compound groups (0.02%, or an incidence rate of 102 per 100,000 years of exposure). This difference was not statistically significant. Two attempted suicides occurred in the placebo groups (0.11%, or an incidence rate of 502 per 100,000 years of exposure) and 11 in the active compound groups (0.21%, or an incidence rate of 1121 per 100,000 years. Suicide risk in placebo vs. active treatment in placebo-controlled trials for schizophrenia. Storosum JG, van Zwieten BJ, Wohlfarth T, de Haan L, Khan A, van den Brink W. Arch Gen Psychiatry. 2003 Apr;60(4):365-8

Voices, Paranoia Schizophrenia Prodrome: Dr. Murray's group has recently completed an interesting study in which children aged 11 years were interviewed, and then reinterviewed at age 26 years. In their study, 3.7% of the patients met Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for schizophreniform disorder. Children who had answered yes to 1 of 4 questions at age 11 concerning a) their mind being read, b) having had a message from the TV/radio, c) people following them, or d) hearing a voice had a 16-fold higher risk for schizophrenia, clearly suggesting prodromal symptoms may exist at a very early stage. Poulton R, Caspi A, Moffitt TE, et al. Children's self-reported psychotic symptoms and adult schizophreniform disorder: a 15 year longitudinal study. Arch Gen Psychiatry. 2000;57:1053-1058

Emotional Deficits Don't Improve: In a study of 13 first episode schizophrenics, deficits in emotion perception were present at illness onset of schizophrenia and showed minimal response to effective antipsychotic treatment. Effects of antipsychotic treatment on emotion perception deficits in first-episode schizophrenia. Herbener ES, et al. University of Illinois at Chicago. . Am J Psychiatry. 2005 Sep;162(9):1746-8.

No Deterioration with Age: UCSD study of 290 schizophrenic outpatient 40-85yo. Among patients, aging was associated with decreased psychopathology, even after controlling for duration of illness. There was no accelerated aging-related decline on any measure in the patients. Yet, elderly patients were more impaired than comparison subjects on various measures. Schizophrenia in late life appears stable, but most elderly patients remain symptomatic and impaired. Acta Psychiatr Scand. 2003 May;107(5):336-43

Late Onset Schizophrenia Often a Prodrome for Dementia: An Australian study of 27 patients with late-onset schizophrenia found nine of them and none of 34 in the control group had developed dementia (5 Alzheimer type, 1 vascular, 3 dementia of unknown type) at 5-year follow-up. Long-term outcome of late-onset schizophrenia: 5-year follow-up study. Brodaty H, Sachdev P, Koschera A, Monk D, Cullen B. Br J Psychiatry. 2003 Sep;183:213-9

Rare Cases Schizophrenia's 1^st Symptom of Frontotemporal Dementia or SSPE: male in 50s 1^st FTD schiz case (Psychiatr Prax. 2003 May;30(Suppl 2):78-82) and 19yo male schiz was due to SSPE Subacute Sclerosising Pan-Encephalitis dx by EEG (Psychiatr Prax. 2003 May;30(Suppl 2):70-72). Neurol findings suggested both.

Job Placement & Support Better: Individual Placement and Support program participants were more likely than the comparison patients (usu psychosocial rehab for inner-city) to work (42% vs. 11%; P<.001; odds ratio, 5.58) and to be employed competitively (27% vs. 7%). Arch Gen Psychiatry 2002 Feb;59(2):165-72.

Factors Influencing Recovery: Factors influencing recovery included 1) family relationships, 2) substance abuse, 3) duration of untreated psychosis, 4) initial response to medication, 5) adherence to treatment, 6) supportive therapeutic relationships, 7) cognitive abilities, 8) social skills, 9) personal history and 10) access to care. 11/02 Internatl J Psychiatry, UCLA. (Very small study of only 23 highly atypical, college educated schizophrenics from better families.)

Schizophrenia Life-Time Suicide Rate 4.9%: In a meta-analysis of 32 studies of at least 2 years duration, with at least 90% follow-up, and reported suicides of 25 578 schizophrenic patients, authors conclude 4.9% will commit suicide during their lifetimes, usually near illness onset. The lifetime risk of suicide in schizophrenia: a reexamination. Palmer BA, Pankratz VS, Bostwick JM. Mayo Medical. Arch Gen Psychiatry. 2005 Mar;62(3):247-53.

Only 13% Schizophrenia Healthcare Costs in Hospital: Using nationally representative data over 2 years for 571,000 adults with schizophrenia living in the community,  there were $2.13 billion per year in direct medical expenses for schizophrenia with mean and median yearly per-patient expenses of $3726 and $1748, respectively. Inpatient care accounted for only 13% of costs, while ambulatory care and prescription drugs accounted for 75%. Medicaid incurred $1 billion spent on schizophrenia treatment. Mean per-person spending for schizophrenia patients with comorbidities ranged from $3913 per year for those with comorbid hypertension to $5618 per year for those with comorbid dyslipidemia. Mean annual total healthcare expenditures for patients with schizophrenia ranged from $5990 for those with no comorbid conditions to $12,292 for those with comorbid hypertension. Healthcare spending among community-dwelling adults with schizophrenia. McDonald M, et al. Pfizer, NY, NY. Am J Manag Care. 2005 Sep;11(8 Suppl):S242-7.

Olanzapine (Zyprexa) Disfavored Due to Side-effects; Ziprasidone (Geodon) and Aripiprazole (Abilify) Favored: The main side-effects of the atypicals are weight gain and metabolic effects, including disturbances in glucose metabolism and a risk of induced diabetes. However, the atypicals are not interchangeable: the risk of incurring these effects is high with clozapine and olanzapine, moderate with risperidone and quetiapine (but perhaps increasing at higher doses), and minimal with ziprasidone and aripiprazole. Atypical antipsychotics and the burden of disease. Simpson GM. LAC + USC Medical Center; Los Angeles. Am J Manag Care. 2005 Sep;11(8 Suppl):S235-41.

Thomas E. Radecki, M.D., J.D.

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