Nejm 2003;349:1738; 1994;330:681; 1993;329:555

Cause:Polygenic; twin studies show heritable component amounts to ~70% of risk; also multifactorial nongenetic contributors, which cause abnormalities in neural circuits and cognitive mechanisms (Njem 1999;340:645); possibly maternal Fe deficiency (Arch Gen Psych 2008;65:1136)

Pathophys:Psychosis (hallucinations, delusions, disorder in form of thought) linked to increased brain dopaminergic activity; incidence and symptomatology similar across cultures. Back-to-front gray matter atrophy. Loss of inhibitory interneurons.

L superior temporal gyrus and L medial temporal lobe are areas most consistently shown to have volumetric deficits (Am J Psych 2005;162:2233)

(Nejm 1999;340:603) 1% of general population; incidence increased × 10 if parent or sibling has schizophrenia; increased urban prevalence may be artifact of care sources distribution

Sx:Bizarre irrational behavior

Si:Inappropriate affect, though may be entirely appropriate to delusions and hallucinations; loose associations; primary process (nonrational, magical, childlike); diminished sociality, drive, and emotional responsiveness; ambivalence

Recurrent psychotic episodes usually beginning at age 17-24 yr, with residual sx between psychotic episodes

Cognitive dysfunction including decreased focus and short-term memory, suicide completion~10%, high rates of medication noncompliance, high rates of nicotine dependence, obesity, nutritional deficiencies, homelessness, and substance abuse. 20% shorter life expectancy than general public.

r/o substance abuse and/or dependence, delirium (Delirium (Organic Brain Syndrome), prescription drug toxicity (Long list—Med Let 2002;44:59), bipolar manic disorder, brief reactive psychosis, dissociative disorders including very rare dissociative identity disorder or multiple personality disorder (voices are those of the other personalities)

Lab:

1st onset psychosis warrants organic w/u: imaging, EEG, TSH, electrolytes, tox screen, mercury, etc. Monitor glucose, lipids, BMI, EKG, and for extra-pyramidal sx. (Am J Psych 2004;161:1334)

Rx:

(Antipsychotics) (Ann IM 2001;134:47; Nejm 1996;334:34); 2+ antipsychotics not clearly better than one at a time (Nejm 2006;354:472). Antipsychotics take 6-8 weeks to reach full efficacy. No improvement in 1-4 weeks should prompt dose increases, followed by different agent (Nejm 2003;349:1746)

1st:

• Olanzapine (Zyprexa) 10-20 mg/d (vs “weight gain and cost make no better than Haldol”—Jama 2003;290:2693)
• Risperidone (Risperdal) (Med Let 1994;36:33), start at 0.5-1 mg po bid, increase to 2 mg po bid in 3 d; 30% relapse rate at 1 yr compared to 60% w haloperidol (Nejm 2002;346:16)
• Quetiapine, aripiparazole, ziprazidone

2nd: Other antipsychotics (Antipsychotics) like chlorpromazine (Thorazine), fluphenazine (Prolixin), etc, and haloperidol (Haldol)

3rd: Clozapine (Clozaril) (Med Let 1993;35:16) 12.5 mg po qd gradually increasing to 300-400 mg qd, reserved for treatment-resistant cases

Estrogen transdermally reduced pos and neg sx in women (Arch Gen Psych 2008;65:998)

Psychosocial: Nonmedication interventions are extremely important in achieving stability; proven interventions include family intervention, supported employment, and assertive community treatment (APA guideline Feb, 2004)