Secondary Schizophrenia (12 page)

hallucinations in individuals with visual deprivation
stimulation of the former, but not the latter, results
(usually ocular disease) and preserved cognitive status
in complex, lifelike visual phenomena
[91].
However,
[84].
In 1769, Charles Bonnet described complex VHs
much like CBS, visual acuity appears to play a key role,
in his cataract-affected grandfather of people, fantas-with Chapman and colleagues showing that impaired
26

tical birds and buildings
[85].
In CBS, characteristic
visual acuity was highly predictive of VHs and that
Chapter 3 – Secondary hallucinations

optical correction and cataract surgery improved out-ocortical glutamatergic afferent stimulation of layer V

come the most
[92].

pyramidal cortical neurons
[102, 103].
This results in
The synucleinopathies such as Lewy Body demen-the characteristic intensification and distortion of sentia (DLB) and Parkinson’s disease with dementia
sory experience respectively
[103].

(PDD) also show elevated rates of VHs, with a preva-

Humans have used anticholinergic substances in
lence of 9% to 45%, and are associated with cog-cultural and religious rituals to attach and enhance
nitive impairment and disease severity but generally
meaning to experience and seek “enlightenment,” par-not medication
[93].
In a study matching DLB and
ticularly through the VHs induced by belladonna or
PDD patients with AD sufferers on degree of cogni-datura species, which contain anticholinergic com-tive impairment and visual acuity, Mosimann and col-pounds such as scopolamine and atropine. Anticholin-leagues
[94]
showed that PDD and DLB sufferers had
ergic intoxication may result in hallucinations through
significantly impaired visual processing compared to
modulation of thalamocortical flow as well as through
AD and commensurately higher rates of VHs (PDD

a direct action on the cortex. Acetylcholine in the cor-75%, DLB 90%, AD 8%). Both PDD and DLB are asso-tex may act to increase signal to noise ratio, and block-ciated with cortical Lewy bodies and marked choliner-age of this may result in increased cortical “noise” and
gic deficit in areas involved in visual perception
[95,

the intrusion of background cortical activity into per-

96]
, loss of serotonergic and cholinergic neurons in
ception as well as affecting central cholinergic mech-brainstem nuclei that modulate transmission of visual
anisms of attention, consistent with the PAD model
information
[97,
98]
, and impaired contrast vision due
of VHs
[104].
Those antidepressants with prominent
to disrupted retinal dopaminergic function
[99],
each
anticholinergic properties have also been implicated
of which have already been described as factors in the
in causing complex VHs, particularly those which
development of VHs. Additionally, visual perceptual
also enhance serotonergic transmission
[105],
and this
changes in DLB and PDD are suggestive of a deficit in
may occur through an imbalance in relative sero-the ventral (“what”) visual pathway
[94],
which when
tonin:acetylcholine activity much like that described in
combined with the cholinergic deficits in attention,
Parkinson’s disease and other synucleinopathies
[105].

satisfy criteria for the PAD model – a combination
Disregulated acetylcholine release may also under-of visuoperceptual and attentional-executive impair-lie the hallucinogenic potential of some dopaminer-ments – of VHs, as previously described
[100].

gic compounds, such as the amphetamines, through
D2 agonism in the nucleus accumbens and resultant

substance-related states

[106].

Substance intoxication

Substance withdrawal

The most potent hallucinogenic substances are those
Visual hallucinations are common in both alcohol
that produce significant alterations in serotonergic and
[107]
and benzodiazepine
[108]
withdrawal states,
cholinergic activity. Lysergic acid (LSD) is perhaps the
as well as withdrawal from the increasingly used
most well-known of the hallucinogenic serotoninergic
illicit substance, gamma-hydroxybutyrate
[109].
The
compounds, whose hallucinogenic potential is directly
common mechanism appears to be alterations to the
proportional to their affinity for 5HT2A postsynaptic
balance between inhibitory gamma amino butyric
receptors
[57].
Hallucinations caused by LSD and the
acid (GABA)-ergic and excitatory glutamatergic
related serotonergic compound mescaline characteris-receptor systems, as chronic administration of these
tically begin as intensification of experience, visual dis-compounds causes downregulation of inhibitory
tortions and colored shapes, progressing to complex
GABA receptors
[110, 111],
and chronic alcohol use in
VHs of people and animals
[101].
Their partial ago-particular results in regionally-specific upregulation
nist effect at these receptors in the locus ceruleus –
of the NMDA-subtype of the glutamatergic system
that receives an array of somatosensory information
[112].
Similar NMDA and GABA receptor changes
which it projects on to the neocortex – enhances sen-have been seen in the visual cortical system after
sory responses and the salience of external stimuli; its
deafferentation
[113],
and it has been suggested that

effect at cortical receptors increases excitatory thalam-these neurotransmitter changes are central to the
Introduction – Section 1

deafferentation hypothesis of VHs in CBS
[114],

with sleep disorders such as narcolepsy
[118]
and REM

with GABAergic medication being one recognized
sleep behavior disorder
[119].

treatment for CBS
[115]
. Downregulation of the
Abnormalities of auditory perception in which
GABAergic system may “release” the excitatory
there is misperception or distortion may also occur in
neurotransmitter system, resulting in (particularly)
CNS disease. Hyperacusis is reported in a number of
dopamine release
[109].
An “illness model” for
organic states such as delirium, migraine, epilepsy, and
GABAergic withdrawal hallucinations exists in the
alcohol withdrawal
[120,
121,
122].
Common sounds
form of the extremely rare enzyme disorder, succinic
may be misinterpreted in delirium. For example, the
semialdehyde dehydrogenase (SSADH) deficiency,
noise of a busy hospital ward can be interpreted as a
where a defect in the catabolic pathway of GABA
crowd discussing the patient’s poor prognosis. Audi-results in decreased gabaergic inhibition and increased
tory perceptions can also be split from accompany-glutamatergic excitatory activity; in adult SSADH defi-ing visual cues in CNS disorders such as delirium –
ciency sufferers, VHs and other psychotic symptoms
for instance, the sound from a television may not be
are a very common presenting symptom
[116].

associated with the images of its source
[123].
Auditory illusions may also occur but are less well defined
Secondary auditory hallucinations:

[124]
and often relate to abnormalities of sound location rather than identification.

Spectrum of auditory perceptual

Just like visual hallucinations occur on a spectrum
Simple sounds lack the multifaceted structure of more
from simple to complex, and indicate differing under-complex sounds such as music or the spoken voice. The
lying pathology, auditory hallucinations also appear
quality of simple sounds depends on basic character-to be dimensional in their complexity and the degree
istics such as pitch (or sound-wave frequency), tone
to which the individual perceives them as a true per-and intensity (loudness). Combinations of frequen-cept. Simple auditory hallucinations comprise basic,
cies are responsible for harmonics or overtones which
unstructured sounds that are usually unformed and
give sounds their recognizable character, sometimes
tonally uncomplicated. They may include whistling,
referred to as timbre. Sound processing involves a
buzzing, and ringing sounds or simple environmen-complex interaction of perception, memory, and emotal sounds such as running water or vehicular traf-tion in order for a sound to be identified. This complex
fic. Tinnitus is perhaps the most commonly reported
interaction can be different in each individual, generat-form of simple auditory disorder of perception. Com-ing different perceptions of sounds, often to the extent
plex auditory hallucinations involve music, voices (sin-that the same sounds may be perceived as pleasant or
gle or multiple), or spoken words. Auditory hallucina-unpleasant in different persons.

tions involving spoken words are known as hallmarks
Simple auditory hallucinosis can occur in a variety
of psychiatric illness such as schizophrenia. However,
of disorders. This includes alcohol withdrawal
[125]

disorders of auditory perception occur in a number of
and other forms of intoxication, delirium, CNS infec-normal and disease states.

tions, complex partial seizures, brainstem lesions, and
deafness
[126, 127].
The best-studied phenomenon is
Auditory hallucinations in normal

tinnitus.

Tinnutus may be perceived in one or both ears or
individuals

in the head. Although the term tinnutus is derived
Perception of sound without a source can occur in
from the Latin tinnire (to ring) it may also present as
normal or nondisease physiological states. Perhaps
buzzing, hissing, humming, beeping, whistling, click-the best-described circumstance is abnormalities of
ing, or roaring sounds
[128].
Tinnitus can have many
auditory perception associated with sleep. As with
different causes, but most commonly results from oto-VHs, auditory hallucinations (AHs) can be experi-logic disorders – the same conditions that cause hear-enced both on waking (hypnopompic) or on falling
ing loss. The most common cause is noise-induced
asleep (hypnogogic) and are reported in general popu-hearing loss, resulting from exposure to excessive

lation samples
[117].
The prevalence of AHs increases
or loud noises. Ototoxic medications may also be
Chapter 3 – Secondary hallucinations

responsible
[129].
Neuropathy as well as brainstem
Functional neuroimaging studies have shown changes
and central lesions (such as demyelination in MS) may
in the auditory cortex using positron emission tomog-also produce tinnitus. Unilateral tinnitus is a hall-raphy (PET)
[142],
magnetoencephalography (MEG)
mark of tumors of the cerbellopontine angle such as
[143]
and fMRI
[144]
in tinnitus patients as well as the
acoustic neuroma. Pulsatile tinnitus is associated with
inferior colliculus
[145].
Using high resolution MRI
glomus tumors of cranial nerves and other vascular
and voxel-based morphometry, Muhlau and others
tumors such as haemangiomas of the middle ear, or
were able to show changes in subcallosal grey matter,
arteriovenous malformations
[130].
Patients with tem-in particular the ventral striatum and nucleus accum-poromandibular joint dysfunction
[131]
and palatal
bens
[133].

myoclonus
[132]
may also report tinnitus. This may
It is likely that simple auditory hallucinations can
result from intermittent deformation of the structures
arise from both central and peripheral lesions. Most
of middle and inner ear by muscle contraction. Tran-at risk are those whose CNS disease (for example,
sient tinnitus can also occur after irritation of the audi-white matter changes in the elderly) represents a vul-tory system (loud music) but also in near to abso-nerable substrate onto which a further insult, such as
lute silence in the absence of any central or peripheral
hearing loss, is superimposed. Given that generation
pathology
[133].

of simple auditory hallucinosis may involve lesions in
Although extensively investigated, the underlying
the cochlea, brainstem, cortical and limbic structures,
mechanisms involved in producing tinnitus remain
careful history, examination and investigations should
unconfirmed
[134].
The structures of the inner ear
evaluate all of these structures.