The authors studied 10 female patients and 12 healthy female controls with positron emission tomography (PET) using 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) as a tracer. The patients were recruited through general practitioners, consultation-liason psychiatrists and other health-care specialists working in the catchment area of Turku University Central Hospital. All patients had been investigated in several somatic clinics during the years, but no formal somatic diagnoses accounting for their symptoms had been established. To minimize the confounding effect of another psychiatric disorder, a careful investigation was made to exclude comorbid Axis I psychiatric illness. Potential cases were interviewed by a psychiatrist resident, who elicited the basic information about each patient’s illness history, symptoms, symptom attribution, social background and relationships as well as treatments and diagnostic procedures. The medical records of the patients were reviewed as part of the diagnostic procedure by the resident. The Symptom Checklist (SCL-90) was obtained from each patient.12 The patients scored near the range of a Finnish normal population in all but somatization subscale.13 Patients’ mean scores of the SCL are presented in Table 2. The first phase results were audited by a research psychiatrist, who performed clinical interview and confirmed or rejected the diagnosis of somatization disorder or undifferentiated somatoform disorder. A few patients with comorbid Axis I disorder were excluded at this second selection phase from the study. The third phase consisted of two psychiatrists, who independently and blind from each other, set the diagnosis for the selected patient on the basis of all the collected written information. A patient who was classified as suffering from undifferentiated somatoform disorder or somatization disorder by both evaluators was included. The controls were volunteers without any history of illness or long-lasting vague symptoms causing distress or functional impairment. Their current state of health was good.
Table 2. SCL-90 scores
|SCL interpersonal sensitivity||0.96||0.56|
|SCL phobic anxiety||0.27||0.33|
|SCL paranoid ideation||0.69||0.60|
The 240-item Finnish version of the TCI was obtained from the study subjects (n = 22) and scores reflecting different temperament traits were calculated and included in the statistical analysis. The raw scores of the study subjects’ TCI temperament traits as well as mean and SD are presented in Table 3. TCI is a self-report test evaluating temperament and character dimensions of the personality. The TCI has been studied in clinical and non-clinical samples and empiric data supports its psychometric characteristics.14 Four temperament traits, namely Novelty-seeking (NS), Harm avoidance (HA), Reward dependence (RD) and Persistence (P), are thought to be part of the psychobiological model of personality.15 Those traits are assumed to be genetically independent from each other, moderately heritable, and relatively stable over a lifetime as well as universal across different groups.14,16 Novelty-seeking is defined as a tendency to react actively to novel stimuli. Harm avoidance is viewed as a bias in the inhibition of behaviors, such as pessimistic worry, passive dependent behaviors or fatigability. Reward dependence is defined as a bias in the maintenance or continuation of ongoing behaviors. Persistence is a tendency to perseverance despite frustration and fatigue.
Table 3. Temperament raw scores, mean and standard deviation of temperament and character inventory
|Mean ± SD||17.6 ± 3.0||18.5 ± 5.4||12.9 ± 2.2||4.1 ± 1.0|
| 1||25|| 9||17||1|
| 4||12|| 6||19||7|
| 5||27|| 8||18||3|
| 7||16|| 3||12||4|
| 9||27|| 5||14||7|
|Mean ± SD||22.3 ± 4.7||11.8 ± 7.1||15.4 ± 3.0||4.0 ± 2.0|
Image acquisition and processing
The subjects selected for the study stopped psychopharmacologic medication, enzyme-inducing agents, caffeine and alcohol intake as well as smoked tobacco at least 7 days prior to the PET scan. All subjects fasted 4 h or more before the PET scan.
On the day of the PET study, an intravenous line was inserted in each forearm, one for venous blood assessment (three blood glucose and 21 radioactivity samples) and the other for tracer (FDG). A warming cushion was bound around the forearm to ensure proper blood flow during the collection of blood samples. Subject positioning was handled with 3-D laser alignment with reference to the orbitomeatal line parallel to the detector rings.
All the subjects were scanned with the GE Advance tomography (General Electrics Medical Systems, Milwaukee, USA) at Turku PET Center, Turku, Finland. The scanning was performed in a dimly lit room with minimal auditory stimulation. The subjects were awake during the scan. At the time of the tracer injection the scanning started taking 50 min of 2-D dynamic imaging in 10–5 min frames. The time course of fluorine-18 radioactivity was determined from 21 venous samples (1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 25, 30, 35, 40, 45, 50 min after tracer injection), and blood glucose level from the three venous samples (0, 30 and 50 min after tracer injection).
FDG was synthesized with slight modifications according to the method described by Hamacher et al.17 The radiochemical purity exceeded 99%, and the specific radioactivity at the end of the synthesis was >75 GBq (2 Ci/µmol). The subjects were given 5 mL of the solution with a dose of about 3.7 MBq/kg (0.1 mCi/kg) of -FDG intravenously in 1 min.
A total of 35 continuous transaxial slices (4.25 mm) were acquired with 18-ring bismuth germinate whole-body scanner with an axial field of view of 14.8 cm. The resolution was 4.2 mm full width at half maximum in all directions. All data were corrected for dead time, tracer decay, and measured photon attenuation and reconstructed with fitted activity curve by patpar in 128 × 128 pixel by pixel matrices.
Magnetic resonance imaging (MRI) was done on all participants as anatomic reference (1.5 Tesla instrument). All MRI were macroscopically stated as normal by a neuroradiologist – no infarctions, atrophy, dilatation of ventricles, hyperintensities or other abnormalities were seen. A reconstructed PET image and MRI were fitted with Amirfit software (Turku PET Centre, Turku, Finland) to obtain equal slice levels. This program fits the images according to the surface of the brain.
ROI were drawn individually at least on four consecutive slices in the gray matter structures (frontal cortex) and basal ganglia (putamen, caudate) as well as thalamus. The ROI were identified by visual inspection with reference to the neuroanatomical atlas of Aquilonius and Eckernäs and to the fitted MRI.18 The average glucose consumption was calculated for each ROI. The image was scaled to a global cerebral glucose metabolic rate of µmol/100 g tissue/minute by multiplying with blood glucose. The lumped constant value used was 0.81.19 This constant corrects the difference between glucose and fluorodeoxyglucose. The average regional cerebral metabolic rate of glucose (MRGlc) of left and right hemisphere ROI (e.g. left + right caudate nucleus/2) was used in the statistical analysis. Every MRI reference image was viewed by a neuroradiologist not knowing the subjects status (patient/volunteer).