Secondary Schizophrenia (151 page)

nia, schizoaffective disorder, and bipolar disorders
[2,

The DSM-III described these as Brief Reactive Psy-

22]
. However, the disorders are not a homogeneous
chosis
[17]
and in the DSM-IV, the term reactive was
group. For example, in about 30% of patients, there
dropped to Brief Psychotic Disorder
[4].
As noted ear-may be persistent behavioral, affective, or perceptual
lier, in the DSM-III and -IV, some cases of APD may
changes of a mild kind, although these do not inter-be diagnosed as Schizophreniform Disorder and oth-fere much with overall function
[22].
Likewise, much
ers as Psychosis NOS
[18].

variability in the long-term course and prognosis was
noted by Singh and colleagues
[29]
in patients who
Incidence, prevalence, risk factors,

initially presented with an APD. In a 20-year follow-up study of “atypical psychoses,” Otsuka and col-

course, and outcome

leagues
[30]
observed that there were three patterns of
There are no true community-based epidemiological
course and outcomes. Whereas descriptions of Group
studies of APD and hence no estimate of true inci-II and Group III are similar to manic depression and
dence. Their incidence may vary significantly based
schizophrenia, respectively, Group I had an interest-on the setting, such as hospitals, clinics, and prac-ing course. Patients recurrently presented with con-tices, and between developed and developing coun-fusion, dream-like states, and paranoid hallucinatory
tries. Within treatment-seeking samples, as many as
symptoms, which lasted a few days to 4 weeks, and
381

8%–20% of patients with a nonaffective, nonorganic
were completely improved between episodes. Thus, the
Related Concepts – Section 4

phenomenology of this group of psychoses is very dif-nial recording coincident with acute psychosis
[37].

ferent from schizophrenia and manic depression and
Sharp and Hendren
[38]
raise the possibility that acute
often consists of an acute crescendo onset, confusion,
psychosis is a limbic ictal phenomena occurring in
dream-like state, visual hallucinations, transient para-brains vulnerable to hyperexcitable states and may
noid states, and rapidly changing mood states, all of
not be reflected in increased electrical activity but
which resolve in a relatively short period of time. It
nevertheless is accompanied by increased metabolic
is reasonable to conclude from this literature that the
activity and blood flow. These authors implicate a
term “APD” encompasses a heterogeneous group of
dysfunctional glutamate system resulting from lower
disorders.

inhibitory activity of the reticular nucleus in the thalamus, leading to increased firing from the anterior
Biological abnormalities in acute

thalamic nucleus – this in turn induces increased firing by neurons in the cingulated cortex and, eventu-

psychotic disorders

ally, injury to the limbic cortical neurons. Sharp and
The ICD and DSM require that organicity including
Hendren
[38]
cite phencyclidine and ketamine stud-delirium be ruled out before making the diagnosis of
ies as well as the effects of GABAergic anticonvulsants
APD; however, this is often an arbitrary judgment on
in preventing such injury in support of this proposal.

the part of the clinician. For example, fever is com-Earlier, Monroe
[39],
Tucker and colleagues
[40],
and
monly associated with APD
[27, 31,
32],
and, puer-Innui and colleagues
[41]
also reported EEG evidence
perium, with its well-recognized physiologic changes,
supportive of a relation between seizure pathology and
is an especially vulnerable period for APD
[27,
33].

ATPD. Mitsuda
[42]
and Hatotani
[43],
in the context
Within ATPD as defined by the ICD-10, Marneros and
of the Japanese concept of atypical psychoses, believe
Pillman
[22]
found about 35% of patients to have a
such psychoses to be positioned between schizophre-comorbid somatic disorder, including endocrine, neu-nia and epilepsy. Rottig and colleagues
[44]
(part of the
rological, and cardiovascular disorders, although there
studies summarized by Marneros and Pillman
[22])

was no particular pattern of somatic comorbidity nor
did not find EEG evidence to support this notion.

could they assign any etiological role to the med-About 30% of their patients did show nonspecific EEG

ical disorder. Further, the somatic comorbidity was
abnormalities but these abnormalities were not dif-no different in comparison cohorts with schizophre-ferent from the comparison groups of schizophrenia
nia or schizoaffective disorder
[22].
Some patients (in
and schizoaffective disorder. These authors concluded
all three groups) had abnormal thyroid and B12 lev-there was no support for an epileptic or cerebral irrita-els. In the same study, about 28% of ATPD patients
ble pathology unique to ATPD. However, there was no
had nonspecific radiological findings with head CT

healthy or nonpsychotic control group, and it is plau-or MRI but again not significantly different from
sible that the pathology they found is shared by many
schizophrenia or schizoaffective disorder. Other stud-psychotic disorders. Further, standard scalp EEG may
ies looking for possible neurobiological abnormali-not be the best way of assessing limbic irritability.

ties in APD have reported variably positive findings.

Hoffler and colleagues found increased cerebral atro-

Acute psychosis in general medical and

phy in patients with cycloid psychoses
[34].
Srikanth
and colleagues reported a good correlation of BPRS

neurological conditions

scores with increased viral antibody titers, suggesting
Acute psychosis sometimes occurs as part of a general
a possible etiological role for the infection
[35].
In a
medical or neurological disorder and if judged to be
later prospective study of APD from the same center,
directly due to the medical condition, a diagnosis of
Janakiramaiah and colleagues
[36]
reported elevated
“Organic Psychosis” is made in the ICD and “Psychosis
antibody titers to CMV, HSV-1, Mumps, Measles, Vari-Secondary to a General Medical Condition” in the
cella, or Japanese encephalitis in 50% of 22 cases of
DSM. It is beyond the scope of this chapter to catalog
brief psychotic disorder.

all medical disorders known to present with psychosis.

Common symptoms of APD such as perplexity,
The relation between the primary medical condition
confusion, dream-like states, and so on, are remi-and the psychosis is not always clear and, unlike the
niscent of epileptic phenomena. Epileptic discharges
Jasperian criteria for psychogenic psychoses, no clear
382

have been noted from the amygdala during intracra-criteria have been laid down in either system to assist
Chapter 31 – Acute brief psychosis – an organic syndrome?

PSYCHOLOGICAL STRESS

seizure disorder
[62, 63],
demyelinating disorders
[64,

Group II

Group V

65, 66],
infectious disorders, including meningitis-encephalitis
[35,
67, 68],
vascular conditions includ-Group I

ing migraine
[69, 70, 71, 72, 73],
and degenerative
VULNERABILITY

ACUTE PSYCHOSIS

Genetic, Early Developmental

disorders, including Parkinson’s Disease
[74].
A group
Group III

Group IV

of less-recognized disorders manifest acute psychosis,
albeit not in any consistent manner. Primary phospholipid syndrome (PAPS), in which antiphospholipids
PHYSIOLOGICAL STRESS

and other antibodies may induce coagulopathies, caus-

Figure 31.1
Vulnerability–stress model of APD.

ing arterial thrombosis and ischemic brain disorders
may include acute psychosis as a prominent manifes-the clinician in making this judgment. In any case, as
tation
[75].
Likewise, disorders with anticardiolipin
more has been learned about the neurobiology of psy-production may also manifest psychosis. Conversely,
choses, the organic-versus-functional dichotomy has
Schwartz and colleagues
[76]
have shown that in
become increasingly outdated. We discuss in the next
their cohort, 32% (11/34) of the unmedicated acute
section a classification of acute psychoses based in part
psychotic patients had antiphospholipid antibodies,
on overlapping etiopathology including biological and
including IgG-anti cardiolipin compared to 0% con-organic causes
(Figures 31.1
and
31.2).

trols. The recently identified syndrome of MELAS,
Acute psychotic disorders are seen during or after
which includes stroke-like phenomena, is also known
infectious diseases such as typhoid, malaria, and
to present with psychosis
[77, 78].
The pathologic
influenza, and many case series and reports have been
mechanism in these disorders may be intermittent and
published of acute psychosis in various infectious dis-transient vascular insufficiency to critical brain areas.

orders
[45, 46, 47, 48, 49, 50, 51].
Likewise, disorders with systemic effects, including the nervous system such as endocrine disorders
[52, 53, 54],
metabolic
Pathophysiology of acute psychotic

syndromes
[55, 56, 57]
, and connective tissue dis-

disorder and proposed

orders
[58],
are known to manifest with acute psychosis. A more direct association of APD with brain
etiopathological subgroups

pathology is evident in certain neurological disor-The exact pathophysiology of either the so-called
ders. These include but are not restricted to con-

“functional APDs” or those occurring in the con-genital and developmental conditions
[59, 60, 61],

text of general medical and neurological disorder is
SCHEMATIC OF ETIOPATHOLOGY OF APD

Figure 31.2
Schematic of etiopathology of APD.

PSYCHOLOGIC STRESS

DEVELOPMENTAL

+

++

+++

MILD

MODERATE

SEVERE

VULNERABILITY

+++

++

+

SEVERE

MODERATE

MILD

A P D

G E N E T I C

P H Y S I O L O G I C

S T R E S S

+

++

+++

FEVER

PUERPERIUM NEUROLOGIC

DISORDER

383

Related Concepts – Section 4

unknown. However, there may either be coarse brain
support for such a vulnerability-stress model in that
disease and/or a dysfunction in critical pathways serv-patients with APD and without a family history of
ing higher order cognitive processing and integra-schizophrenia had a greater number of stressful events
tion, leading to psychosis. It may be argued reasonably
before the acute psychosis. It also becomes evident that
that the same pathways implicated in the pathogene-for four of the five groups, the acute psychosis may be
sis of the positive symptoms of schizophrenia may be
described as partially or wholly biological in origin.

involved in both functional and organic APDs.

Further, it is likely that as far as the pathophysiol-It appears that as heterogeneous as APDs are, they
ogy of the core psychosis is concerned, it is common
might be conceived of as falling into the following five
to all five groups, which substantially overlaps with
etiopathological groups:

the pathophysiology of the two functional psychoses
1. Vulnerability Group with genetic or
of schizophrenia and psychotic mood disorders.

developmentally induced vulnerability to
In attempting to dissect the crucial anatomy of
psychosis

psychosis in these disorders, it may be posited that
2. Vulnerability – Psychologic Stress Group
there is a “psychosis circuit” involving the thalamus-3. Vulnerability – Physiologic Stress Group
prefrontal

cortex-anterior

cingulated

cortex

–

4. Neurotoxic Group

hippocampus – entorhinal cortex – paleostriatum –
thalamus
[71, 80]
. This is not to imply that other
5. Catastrophic – Psychosocial Stress Group
structures in the brain are not involved in psychosis
The first group is best denoted by those cases
but to emphasize that at the current time this circuit
that may spontaneously manifest psychosis – this may
has been most robustly related to psychosis. Other
be recurrent, and the vulnerability likely arises from
subcircuits and links may and probably do exist –
genetic or early developmental factors and is enduring.