People with psychosis (the psychosis group) were recruited at the time of
their first clinical contact for psychotic symptoms at a general academic
hospital (the Hospital Clinic of Barcelona). As part of the Spanish national
health system, the hospital offers psychiatric services for all who live in
the surrounding catchment area, Esquerra Eixample, in the city of Barcelona.
Esquerra Eixample is a relatively homogeneous middle/upper-middle class
neighbourhood in the centre of the city. Although it is also possible to seek
private care outside of the assigned catchment area, the Hospital Clinic is a
regional referral center for psychosis, and in a survey of 2968 admissions to
the emergency department of a large general hospital in an adjoining catchment
area, there were no individuals with psychosis from Esquerra Eixample.
The psychosis group had a maximum cumulative (lifetime) antipsychotic
exposure of 1 week, and no antipsychotic use in the 30 days prior to the
study. Participants with psychosis were allowed to receive anti-anxiety
medication (lorazepam) the night before blood was drawn, to a maximum of 3 mg,
but not on the day of assessment.
The healthy control group (the control group) were recruited using
advertisements. We attempted to match the control group to the psychosis group
on BMI, age, gender, smoking habit (average number of cigarettes per day), and
residence in the catchment area (yes/no) of the Hospital Clinic. All of the
participants were White residents of Spain except for one Asian and one North
African person in each of the groups. The control group had no current or
prior diagnosis of any Axis I
psychiatric disorder, after being assessed with the structured clinical
interview for Axis I DSM–IV psychiatric disorders
Additional inclusion and exclusion criteria for all participants were: age
from 18 to 64 years; no history of diabetes or other serious medical or
neurological condition associated with glucose intolerance or insulin
resistance (e.g. Cushing’s disease); not taking a medication associated
with insulin resistance (hydrochlorothiazide, furosemide, ethacrynic acid
(available in the USA), metolazone, chlortalidone, beta blockers,
glucocorticoids, phenytoin, nicotinic acid, ciclosporine, pentamidine or
narcotics); no history of cocaine use in the previous 30 days; and have not
previously received an antipsychotic or antidepressant medication. Additional
exclusion criteria for the control group were no lifetime diagnosis of
schizophrenia or major depressive disorder and no current diagnosis of
adjustment disorder. All participants gave informed consent for participation
in the study, which was conducted under the supervision of the institutional
review boards of the authors’ institutions.
Masked to glucose measures, individuals from the two groups that had been
recruited were chosen in such a way to assure good matching as a group on
gender, age, BMI and smoking habit, and to have an equal number of people in
each group. This entailed omitting 6 people from the psychosis group,
primarily because of a lower BMI, as well as 22 people in the control group,
for purposes of matching.
A secondary, confirmatory analysis was also conducted in which all of the
participants who had been recruited were included, and the matching variables
were used as covariates.
Metabolic and psychiatric assessment
All participants were given a 2 h, 75 g oral glucose tolerance test, which
began between 08.00 and 09.00 after an overnight fast. Fasting insulin,
glycosylated haemoglobin (HbA1c), C-reactive protein,
interleukin-6, adiponectin, and cortisol blood concentrations were also
recorded. Adiponectin was recorded for 38 participants in the psychosis group
and 48 in the control group, as it was included after the study began. Height,
weight, and waist and hip circumference, when wearing underwear and without
shoes, were recorded between the baseline and two blood samples.
Serum insulin concentrations were measured in duplicate by monoclonal
immunoradiometric assay (Medgenix Diagnostics, Fleunes, Belgium). No
cross-reaction with proinsulin was detected. Glycosylated haemoglobin
was determined by high-performance liquid chromatography
(HA 8121, Menarini Diagnostici, Firenze, Italy; normal range 3.4–5.5%).
Cortisol was measured using a radioimmunoassay (Immuchem, Ivoz-Ramet,
Belgium). Body mass index was calculated using the formula (weight (kg)/height
)). Homoeostatic model assessments (HOMA) of steady state
beta-cell function, insulin sensitivity and insulin resistance were calculated
as percentages of a normal reference population of young people without
diabetes. The HOMA calculator version 2.2
was used to calculate the HOMA indices.
Glucose tolerance was categorised according to American Diabetes
- normal tolerance was defined by a fasting plasma glucose concentration at
baseline <5.6 mmol/l (100 mg/dl) and a 2 h concentration <7.8 mmol/l
- impaired fasting glucose was defined as glucose levels of 5.6–7.0
mmol/l (100–125 mg/dl) in fasting individuals;
- impaired glucose tolerance was defined as 2 h glucose levels of
7.8–11.1 mmol/l (140–199 mg/dl) on the 75 g oral glucose tolerance
- a diagnosis of diabetes was defined by a fasting plasma glucose ≥7.0
mmol/l (126 mg/dl) or a 2 h glucose equal or greater to 11.1 mmol/l (200
All participants were interviewed using the Spanish translation of the
Structured Clinical Interview for DSM–IV Axis I disorders, clinician
They were also administered the Dartmouth Assessment of Lifestyle
quantifies substance misuse. Socioeconomic status of the family of origin was
assessed with the Hollingshead–Rendlich
The two matched groups were compared using the non-paired Student’s
t-test, or the χ2 test for comparisons of proportions.
Significance was defined as P<0.05 for all statistical tests, and
these were performed using SPSS version 12.0 for Windows.
Two multiple regression analyses were performed. In the first, the two
matched groups (n=50 in each group) were included, whereas in the
second analysis, all of the individuals who had been recruited (i.e. not only
those in the two matched groups; n=56 people with psychosis and
n=72 controls) were included. The dependent variable was glucose
concentration at 2 h; the independent variables were diagnosis (individuals
with psychosis v. controls as a 0/1 variable), age, gender, BMI,
smoking (average number of cigarettes per day), residence in the catchment
area (as a 0/1 variable), cortisol blood levels and socioeconomic status.
As interleukin-6 values were not normally distributed, we evaluated this
variable as a category, with high or abnormal values defined as interleukin-6
>5 μ/ml and low or normal values <5