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Several studies have independently suggested that patients with schizophrenia are more likely to have an enlarged cavum septum pellucidum (CSP) and an absent adhesio interthalamica (AI), respectively. However, neither finding has been consistently replicated and it is unclear whether there is an association between these two midline brain abnormalities. Thus, we compared the prevalence of absent AI and the prevalence, size and volume of CSP in 38 patients with schizophrenia and 38 healthy controls using magnetic resonance imaging (MRI). There were no between group differences in the presence or volume of CSP; however, an enlarged CSP was commoner among patients than controls. There was also a positive correlation between CSP ratings and volumes. No differences in the presence or absence of the AI were found between patients and controls; however, an absent AI was commoner in male patients with schizophrenia than females. There was absolutely no overlap between the presence of a large CSP and an absence of AI. In conclusion, our findings are in line with several case series and other MRI investigations that have shown a higher incidence of putatively developmental brain abnormalities in patients with schizophrenia, particularly in males, and support the neurodevelopmental model of this disorder.
While recent research points to the potential benefits of clinical intervention before the first episode of psychosis, the logistical feasibility of this is unclear.
To assess the feasibility of providing a clinical service for people with prodromal symptoms in an inner city area where engagement with mental health services is generally poor.
Following a period of liaison with local agencies to promote the service, referrals were assessed and managed in a primary care setting. Activity of the service was audited over 30 months.
People with prodromal symptoms were referred by a range of community agencies and seen at their local primary care physician practice. Over 30 months, 180 clients were referred; 58 (32.2%) met criteria for an at risk mental state, most of whom (67.2%) had attenuated psychotic symptoms. Almost 30% were excluded due to current or previous psychotic illness, of which two-thirds were in the first episode of psychosis. The socio-demographic composition of the 'at risk' group reflected that of the local population, with an over-representation of clients from an ethnic minority. Over 90% of suitable clients remained engaged with the service after 1 year.
It is feasible to provide a clinical service for people with prodromal symptoms in a deprived inner city area with a large ethnic minority population.
It is unknown whether prodromal services improve outcomes in those who go on to develop psychosis, and whether these patients are demographically different from the overall first-episode population.
To compare sociodemographic features, duration of untreated psychosis, hospital admission and frequency of compulsory treatment in the first year after the onset of psychosis in patients who present to prodromal services with patients who did not present to services until the first episode of psychosis.
We compared two groups of patients with first-episode psychosis: one who made transition after presenting in the prodromal phase and the other who had presented with a first episode.
The patients who had presented before the first episode were more likely to be employed and less likely to belong to an ethnic minority group. They had a shorter duration of untreated psychosis, and were less likely to have been admitted to hospital and to have required compulsory treatment.
Patients who develop psychosis after being engaged in the prodromal phase have a better short-term clinical outcome than patients who do not present until the first episode. Patients who present during first episodes may be more likely to have sociodemographic features associated with relatively poor outcomes.
Although translational medicine has become a priority for medical science, advances in neuroscience have failed to be translated for the benefit of patients. In populations at high risk of psychosis, neuroimaging could stratify those mostly likely to develop psychosis. This is an example of potentially translatable psychiatry.
Sexual dysfunction is common in psychotic disorder but it is not clear
whether it is intrinsic to the development of the illness or secondary to
To compare sexual function in people at ultra-high risk (UHR) of a
psychotic disorder, patients with first-episode psychosis predominantly
taking antipsychotic drugs and healthy volunteers.
Sexual function was assessed in a UHR group (n = 31), a
group with first-episode psychosis (n = 37) and a
matched control group of healthy volunteers (n = 56)
using the Sexual Function Questionnaire.
There was a significant effect of group on sexual function
(P<0.001). Sexual dysfunction was evident in 50%
of the UHR group, 65% of first-episode patients and 21% of controls.
Within the UHR group, sexual dysfunction was more marked in those who
subsequently developed psychosis than in those who did not. Across all
groups the severity of sexual dysfunction was correlated with the
severity of psychotic symptoms (P<0.001). Within the
first-episode group there was no significant difference in sexual
dysfunction between patients taking prolactin-raising v.
Sexual dysfunction is present prior to onset of psychosis, suggesting it
is intrinsic to the development of illness unlikely to be related to the
prolactin-raising properties of antipsychotic medication.
Early specialised care may improve short-term outcome in first-episode non-affective psychosis, but it is unclear if these benefits endure.
To assess the long-term effect of early intervention in psychosis.
Individuals with first-episode psychosis were randomised to specialised care or care as usual (trial number: ISRCTN73679874). Outcome after 5 years was assessed by case-note review.
There were no significant differences in the admission rate (coefficient 0.096, 95% CI −0.550 to 0.742, P = 0.770) or the mean number of bed days (coefficient 6.344, 95% CI −46 to 58.7, P = 0.810).
These findings that specialist intervention did not markedly improved outcome at 5 years accord with those from a larger OPUS study. The sample size of this study was small and these results should be generalised with caution. More research is needed.
The pattern of brain morphological changes at the early stages of schizophrenia may depend on the age at onset of illness; in children and adolescents with schizophrenia, grey matter deficits are seen in the parietal lobe whereas in individuals with adult onset these are more widespread.
To examine whether white matter is similarly affected.
Diffusion tensor imaging was used to compare fractional anisotropy measures in individuals with adolescent-onset (n = 17) and adult-onset schizophrenia (n = 17) with those in age- and gender-matched controls.
Compared with their respective controls, individuals with adolescent-onset schizophrenia showed fractional anisotropy decrease in parietal regions; individuals with adult onset showed additional fractional anisotropy reductions in frontal, temporal and cerebellar regions. A differential effect of age at onset (adolescent v. adult) was noted bilaterally in medial prefrontal white matter.
White matter abnormalities in frontal regions in schizophrenia may depend on developmental stage at the time of illness onset.
People with prodromal symptoms have a very high risk of developing psychosis.
To use functional magnetic resonance imaging to examine the neurocognitive basis of this vulnerability.
Cross-sectional comparison of regional activation in individuals with an ‘at-risk mental state’ (at-risk group: n=17), patients with first-episode schizophreniform psychosis (psychosis group: n=10) and healthy volunteers (controls: n=15) during an overt verbal fluency task and an N-back working memory task.
A similar pattern of between-group differences in activation was evident across both tasks. Activation in the at-risk group was intermediate relative to that in controls and the psychosis group in the inferior frontal and anterior cingulate cortex during the verbal fluency task and in the inferior frontal, dorsolateral prefrontal and parietal cortex during the N-back task.
The at-risk mental state is associated with abnormalities of regional brain function that are qualitatively similar to, but less severe than, those in patients who have recently presented with psychosis.
Grey matter changes have been described in individuals who are pre- and peri-psychotic, but it is unclear if these changes are accompanied by changes in white matter structures.
To determine whether changes in white matter occur prior to and with the transition to psychosis in individuals who are pre-psychotic who had previously demonstrated grey matter reductions in frontotemporal regions.
We used magnetic resonance imaging (MRI) to examine regional white matter volume in 75 people with prodromal symptoms. A subset of the original group (n=21) were rescanned at 12–18 months to determine white matter volume changes. Participants were retrospectively categorised according to whether they had or had not developed psychosis at follow-up.
Comparison of the baseline MRI data from these two subgroups revealed that individuals who later developed psychosis had larger volumes of white matter in the frontal lobe, particularly in the left hemisphere. Longitudinal comparison of data in individuals who developed psychosis revealed a reduction in white matter volume in the region of the left fronto-occipital fasciculus. Participants who had not developed psychosis showed no reductions in white matter volume but increases in a region subjacent to the right inferior parietal lobule.
The reduction in volume of white matter near the left fronto-occipital fasciculus may reflect a change in this tract in association with the onset of frank psychosis.
It remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis.
To investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ).
Evaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239).
Primary (P<0.001), motor coordination (P<0.001), and motor sequencing (P<0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ.
Higher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.
White-matter hyperintensities have been associated with both schizophrenia and mood disorders, particularly bipolar disorder, but results are inconsistent across studies
To examine whether white-matter hyperintensities are a vulnerability marker for psychosis or are specifically associated with bipolar disorder
T2-weighted magnetic resonance imaging data were acquired in 129 individuals with first-episode psychosis (either affective or non-affective psychoses) and 102 controls who were randomly selected from the same geographical areas. Visual white-matter hyperintensity ratings were used for group and subgroup comparisons
There were no statistically significant between-group differences in white-matter hyperintensity frequency or severity scores. No significant correlations were found between white-matter hyperintensity scores and duration of illness, duration of untreated psychosis, or severity of psychotic, manic or depressive symptoms
White-matter hyperintensities are not associated with vulnerability to psychosis in general, or specifically with affective psychoses. Further, first-episode psychosis investigations using more quantitative methods are warranted to confirm these findings
Obsessive-compulsive disorder (OCD) may be related to a dysfunction in
frontostriatal pathways mediating inhibitory control. However, no
functional magnetic resonance imaging (fMRI) study has tested this in
To test whether adolescents with OCD in partial remission would show
abnormal frontostriatal brain activation during tasks of inhibition.
Event-related fMRI was used to compare brain activation in 10 adolescent
boys with OCD with that of 9 matched controls during three different
tasks of inhibitory control.
During a ‘stop’ task, participants with OCD showed reduced activation in
right orbitofrontal cortex, thalamus and basal ganglia; inhibition
failure elicited mesial frontal underactivation. Task switching and
interference inhibition were associated with attenuated activation in
frontal, temporoparietal and cerebellar regions.
These preliminary findings support the hypothesis that paediatric OCD is
characterised by a dysregulation of frontostriatothalamic brain regions
necessary for motor inhibition, and also demonstrate dysfunction of
temporoparietal and frontocerebellar attention networks during more
cognitive forms of inhibition.
Neuroanatomical abnormalities are a well-established feature of
schizophrenia. However, the timing of their emergence and the extent to
which they are related to vulnerability to the disorder as opposed to
psychotic illness itself is unclear
To assess regional grey matter volume in the at-risk individuals who
subsequently developed psychosis
Magnetic resonance imaging data from at-risk individuals who developed
psychosis (n = 12) within the following 25 months were
compared with data from healthy volunteers (n=22) and
people with first-episode psychosis (n=25)
Compared with healthy volunteers, individuals who subsequently developed
psychosis had smaller grey matter volume in the posterior cingulate
gyrus, precuneus, and paracentral lobule bilaterally and in the left
superior parietal lobule, and greater grey matter volume in a left
parietal/posterior temporal region. Compared with first-episode patients,
they had relatively greater grey matter volume in the temporal gyrus
bilaterally and smaller grey matter volume in the right lentiform
Some of the structural brain abnormalities in individuals with an at-risk
mental state may be related to an increased vulnerability to psychosis,
while others are associated with the development of a psychotic
Virtual reality provides a means of studying paranoid thinking in
controlled laboratory conditions. However, this method has not been used
with a clinical group
To establish the feasibility and safety of using virtual reality
methodology in people with an at-risk mental state and to investigate the
applicability of a cognitive model of paranoia to this group
Twenty-one participants with an at-risk mental state were assessed before
and after entering a virtual reality environment depicting the inside of
an underground train
Virtual reality did not raise levels of distress at the time of testing
or cause adverse experiences over the subsequent week. Individuals
attributed mental states to virtual reality characters including hostile
intent. Persecutory ideation in virtual reality was predicted by higher
levels of trait paranoia, anxiety, stress, immersion in virtual reality,
perseveration and interpersonal sensitivity
Virtual reality is an acceptable experimental technique for use with
individuals with at-risk mental states. Paranoia in virtual reality was
understandable in terms of the cognitive model of persecutory
In low-and middle-income countries people with schizophrenia are reported
to experience better outcomes than those in high-income countries
To examine structural brain differences in people with first-episode
psychosis and controls in Brazil
Magnetic resonance imaging using voxel-based morphometry was performed on
122 people with first-episode psychosis and 94 controls
There were significant decreases in grey matter in the left superior
temporal and inferior prefrontal cortices, insula bilaterally and the
right hippocampal region in first-episode psychosis
(P<0.05, corrected for multiple comparisons). The
subgroup of people with schizophrenia (n=62) exhibited a
similar pattern of decrease in grey matter relative to controls
Structural abnormalities reported in psychosis in high-income countries
are also present in first-episode psychosis in Brazil
The dopamine hypothesis has been the major pathophysiological theory of
psychosis in recent decades. Molecular imaging studies have provided
in vivo evidence of increased dopamine synaptic
availability and increased presynaptic dopamine synthesis in the striata of
people with psychotic illnesses. These studies support the predictions of
the dopamine hypothesis, but it remains to be determined whether
dopaminergic abnormalities pre-date or are secondary to the development of
psychosis. We selectively review the molecular imaging studies of the
striatal dopaminergic system in psychosis and link this to models of
psychosis and the functional subdivisions of the striatum to make
predictions for the dopaminergic system in the prodromal phase of
Grey matter and other structural brain abnormalities are consistently
reported in first-onset schizophrenia, but less is known about the extent
of neuroanatomical changes in first-onset affective psychosis
To determine which brain abnormalities are specific to (a) schizophrenia
and (b) affective psychosis
We obtained dual-echo (proton density/T2-weighted) magnetic resonance
images and carried out voxel-based analysis on the images of 73 patients
with first-episode psychosis (schizophrenia n=44,
affective psychosis n=29) and 58 healthy controls
Both patients with schizophrenia and patients with affective psychosis
had enlarged lateral and third ventricle volumes. Regional cortical grey
matter reductions (including bilateral anterior cingulate gyrus, left
insula and left fusiform gyrus) were evident in affective psychosis but
not in schizophrenia, although patients with schizophrenia displayed
decreased hippocampal grey matter and increased striatal grey matter at a
more liberal statistical threshold
Both schizophrenia and affective psychosis are associated with volumetric
abnormalities at the onset of frank psychosis, with some of these evident
in common brain areas
Little is known about the incidence of first-episode psychosis in urban
centres of low- or middle-income countries
To estimate the incidence of psychosis in São Paulo, a large metropolis
Prospective survey of first-episode psychosis among residents aged 18–64
years resident in a defined area of São Paulo, over a 30-month period
(July 2002- December 2004). Assessments were carried out with the SCID–I,
and diagnoses given according to DSM – IV criteria. Population at risk
was drawn from the 2000 Census data
There were 367 first-episode cases identified (51% women), and almost 40%
fulfilled criteria for schizophrenia or schizophreniform disorder. The
incidence rate for any psychosis was 15.8/100 000 person-years at risk
(95% CI 14.3–17.6). Incidence of non-affective psychoses was higher among
Incidence of psychosis in São Paulo was lower than expected for a large
First-episode psychosis is typically preceded by a prodrome in which
there is deterioration in global and social functioning
To examine whether the duration of the prodromal phase influences grey
and white matter volumes at the onset of psychosis
Eighty-two people were scanned using magnetic resonance imaging when they
developed a first episode of psychosis. The duration of the prodromal
phase was estimated from detailed interviews and medical records.
Voxel-based morphometry was used to assess neuroanatomical
A long prodromal phase was associated with smaller grey matter volumes in
the cingulate, frontal and left insular cortex, and with less white
matter volume bilaterally in the superior longitudinal and uncinate
fasciculi and the cingulum
The severity of volumetric abnormalities in first-episode psychosis was
greater in those with a long prodrome