A Textbook of Clinical Pharmacology and Therapeutics

●Schizophrenia 110 ●Behavioural emergencies 114

CHAPTER 19

SCHIZOPHRENIA AND

BEHAVIOURAL EMERGENCIES

SCHIZOPHRENIA

INTRODUCTION

Schizophrenia is a devastating disease that affects approxi-
mately 1% of the population. The onset is often in adolescence
or young adulthood and the disease is usually characterized by
recurrent acute episodes which may develop into chronic dis-
ease. The introduction of antipsychotic drugs such as chlorpro-
mazinerevolutionized the treatment of schizophrenia so that
the majority of patients, once the acute symptoms are relieved,
can now be cared for in the community. Previously, they would
commonly be sentenced to a lifetime in institutional care.

PATHOPHYSIOLOGY

The aetiology of schizophrenia, for which there is a genetic pre-
disposition, is unknown, although several precipitating factors
are recognized (Figure 19.1). Neurodevelopmental delay has
been implicated and it has been postulated that the disease is
triggered by some life experience in individuals predisposed by
an abnormal (biochemical/anatomical) mesolimbic system.

There is heterogeneity in clinical features, course of disease

and response to therapy. The concept of an underlying

neurochemical disorder is advanced by the dopamine theory

of schizophrenia, summarized in Box 19.1. The majority of

antipsychotics block dopamine receptors in the forebrain.

5-Hydroxytryptamine is also implicated, as indicated in Box

19.2. Glutamine hypoactivity, GABA hypoactivity and α-adren-

ergic hyperactivity are also potential neurochemical targets.

About 30% of patients with schizophrenia respond inad-

equately to conventional dopamine D 2 receptor antagonists. A

high proportion of such refractory patients respond to clozap-

ine, an ‘atypical’ antipsychotic drug which binds only tran-

siently to D 2 receptors, but acts on other receptors, especially

muscarinic, 5-hydroxytryptamine receptors (5HT 2 ) and D 1 ,

and displays an especially high affinity for D 4 receptors. The

D 4 receptor is localized to cortical regions and may be over-

expressed in schizophrenia. Regional dopamine differences

may be involved, such as low mesocortical activity with high

mesolimbic activity. Magnetic resonance imaging (MRI) stud-

ies indicate enlargement of ventricles and loss of brain tissue,

whilst functional MRI and positron emission tomography

(PET) suggest hyperactivity in some cerebral areas, consistent

with loss of inhibitory neurone function.

012345

Odds Ratio

Winter

Urban

Place/time of birth

Infection

Prenatal

Obstetric

Influenza

Respiratory

Rubella

Poliovirus

CNS

Famine

Bereavement

Flood

Unwantedness

Maternal depression

Rhesus Incompatibility

Hypoxia

CNS damage

Low birth weight

Pre-eclampsia

Family history

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Figure 19.1:Predispositions to

schizophrenia. Redrawn with permission

from Sullivan PF. The genetics of

schizophrenia.PLoS Medicine2005; 2 : e212.