sodic vertigo, 2 had vague somatic symptoms of unknown cause, 2 had ..... rCBF; LP, left parietal rCBF; LT, left temporal rCBF; La, left occipital rCBF. a p < 0.001.
Journal of Cerebral Blood Flow and Metabolism 9:410-416 © 1989 Raven Press, Ltd., New York
Regional Cerebral Blood Flow and Anxiety: A Correlation Study in Neurologically Normal Patients
G. Rodriguez, P. Cogorno, A. Gris, S. Marenco, C. Mesiti, F. Nobili, and G. Rosadini Institute of Neurophysiopathology, University of Genova, and Center for Cerebral Neurophysiology, National Research Council, Genova, Italy
Summary: Regional CBF (rCBF) was evaluated by the 133Xe inhalation method in 60 neurologically normal pa tients (30 men and 30 women) and hemispheric and re gional values were correlated with anxiety measurements collected by a self-rating questionnaire before and after the examination. Statistically significant negative corre lations between rCBF and anxiety measures were found. rCBF reduction for high anxiety levels is in line with re sults previously reported by others and could be related
to lower performance levels for moderately high anxiety scores as those reported in the present population. This could perhaps be explained by rearrangement of flow from cortical zones to deeper areas of the brain, classi cally known to be implicated in the control of emotions. However, these results should be interpreted cautiously, since they were obtained in patients and not in normal subjects. Key Words: Anxiety-Regional cerebral blood flow.
The first finding that suggested an effect of psy chological conditions on regional CBF (rCBF) was published by Prohovnik et aI. (1980). In fact, they reported a reduction of CBF values in the second resting rCBF measurement in normal subjects and proposed this could be attributed to habituation to the measurement procedure. From a neurophysio logical point of view, habituation to a set of stimuli as those present in the rCBF laboratory may be also partly explained by reduced levels of anxiety on the occasion of a second examination. That finding prompted further research on this topic both in nor mal subjects (Reivich et aI., 1983; Gur et aI., 1987) and in patients with panic disorder (Reiman et aI., 1984), also in the attempt to obtain a better under standing of the neurophysiological significance of the so-called resting condition. Gur et al. (1987) studied a group of 28 normal
subjects working in the laboratory and measured anxiety before and after the examination with the State-Trait Anxiety Inventory scale (STAI) (Spieg berger et aI., 1 970) and CBF both with positron emission tomography (PET) and with the inhalatory I33Xe method. They showed a direct relationship between CBF values and anxiety score for low anx iety; but when anxiety exceeded a certain value, an inverse relationship was present with decreasing CBF values for increasing anxiety. They related this finding to the classic notion of a positive cor relation between performance levels and anxiety within low ranges of anxiety and of a negative one over certain anxiety levels. They did not report the regional distribution of anxiety-CBF relationships. Reivich et aI. ( 1 983) showed that metabolic rates in the frontal cortex had a stronger relationship with anxiety than in other areas of the brain. Their data also suggested a special role for the right hemi sphere in those subjects with high anxiety scores, with higher metabolic rates in this hemisphere than in the left. The present article addresses the issue of rela tionships between anxiety and rCBF in 60 neuro logically normal subjects who underwent rCBF ex amination in our laboratory as a complement to di agnostic evaluation or as healthy volunteers.
Received July 26, 1988; accepted December 14, 1988. Address correspondence and reprint requests to Dr. G. Rodriguez at Institute of Neurophysiopathology, University of Genova, Ospedale San Martino, Viale Benedetto XV, 10, 16132 Genova, Italy.
Abbreviations used: ANOVA, analysis of variance; lSI, initial slope index; PET, positron emission tomography; rCBF, re gional CBF; STAI, State-Trait Anxiety Inventory.
410
411
rCBF-ANXIETY CORRELATIONS MATERIALS AND METHODS Sixty patients who underwent rCBF examination in the course of diagnostic procedures of various kinds were selected from a consecutive series of �860. Selection cri teria were as follows: normal neurological examination performed on the same day as rCBF examination; no his tory of psychiatric illness or cerebrovascular disease; no pharmacological treatment presumably able to interfere with responsiveness to anxiety or with CBF (benzodiaz epines, l3-blockers, etc.); no acquaintance with the mea surement procedure (no selected patient had ever under gone an rCBF examination). The sample was formed of 30 men (ranging from age 19 to 76, mean ± SD 44.5 ± 14.6 years) and 30 women (age range 22-76 years, mean ± SD 49.7 ± 15.1 years). Med ical history revealed that 3 patients previously had had loss of consciousness presumably of cardiac origin, 16 were hypertensives with well-controlled blood pressure levels, 7 suffered from migraine, 4 had liver cirrhosis without hepatic encephalopathy, 5 had various forms of essential epilepsy, 1 had hyperlipemia, 2 were boxers un dergoing rCBF examination as a control, 6 suffered epi sodic vertigo, 2 had vague somatic symptoms of unknown cause, 2 had suffered mild head trauma, 3 were well controlled type II diabetics, and finally 9 were healthy volunteers who underwent rCBF examination as a part of the normative population of the laboratory. rCBF examinations were performed with the 133Xe in halation technique (Obrist et al., 1967, 1975) in a dark and quiet room with closed eyes. The patient breathed a i33Xe-air mixture (4-6 mCi/L) via a tight-fitting facemask for the first minute of examination and room air for the ensuing 10 min. Thirty-two detectors (16 over each hemi sphere) placed in fixed reproducible positions recorded radioactive counts from the head, thus obtaining washout curves that yielded CBF values by a two-compartment analysis (Obrist et aI., 1975) performed by a Digital PC 350 computer. In the present report only the value of the initial slope index (lSI) (Risberg et aI., 1975) was consid ered, since it is a parameter reliable also in cerebral pa thology. Expired end-tidal Peo2 was continuously moni tored during the examination period by a capnograph. All subjects were normocapnic (mean Peoz 39.6 ± 3.8 mm Hg). As suggested by Blauenstein et al. (1977), lSI values were never corrected for the individual Peoz val ues. For each subject 10 rCBF absolute lSI values were obtained: the mean hemispheric values derived from the average of 16 probe values and 4 regional values for each hemisphere obtained averaging the values of 5 frontal, 3 temporal, 6 parietal (including 2 values from pararolandic areas), and 2 occipital probes. Moreover, an average value across all regions was computed (global lSI). The same rCBF values were also computed in a sample of 60 normal controls belonging to the normative popula tion of the laboratory. They were matched as closely as possible according to sex and age of the patients. Anxiety was measured by the STAI (Spiegberger et al., 1970). The Italian version of the test was used (Spieg berger et aI., 1976). This self-rating questionnaire consists of two parts of 20 items each. The patient is asked to reply to the first part according to his/her feelings in the mea surement situation (this measures state anxiety), while the second part should be answered according to the psy chological situation of the subject in his/her everyday life
(this measures the personality trait of the patient in re acting anxiously to stressful situations). The measures for both parts of the questionnaire are identically scaled, with scores ranging from 1 to 4 for each item (thus, total trait and state anxiety scores range potentially from 20 to 80). The whole questionnaire was administered a first time after the patient had entered the examination room and following a brief description of the examination proce dure. Only the patient and the examiner stayed in the room while the questionnaire was completed. The part of the questionnaire concerning state anxiety was repeated immediately after the examination. We will refer to the former set of measurements as STAI-l and TRAIT and to the latter as STAI-2. All questionnaires were evaluated by one of the authors (P.c.), and raw values were stan dardized according to age and sex of the single patients. Moreover, a further standardization was obtained consid ering the patients as general medical subjects and correct ing their values according to the relative population val ues reported by Spiegelberger et al. (1976): mean scores for general medical subjects, 42.4 ± 13.8 for state anxiety and 41.9 ± 12.7 for trait anxiety. Moreover, for each patient an average anxiety measure across STAI-l, STAI2, and TRAIT values was computed.
Statistics For statistical computations, the absolute lSI values were used for the male and the female groups separately, while in the whole group rCBF values were considered as standardized values. The standardization procedure [z-transformation: (single rCBF value - mean)/SDj was carried out in each subgroup of males and females so as to make the CBF values comparable. In fact, systematic gender-related rCBF differences have been reported in the literature (Our et aI., 1982; Rodriguez et aI., 1988). An analysis of variance (ANOVA) was performed for each variable between the mean measures of male and female patients and between average rCBF values of pa tient groups and of normal male and female subjects, re spectively, to detect significant differences between the sexes and between patients and normals. Kendall's T test was employed to demonstrate signifi cant correlations between rCBF variables (dependent variables) and STAI-I, STAI-2, TRAIT, average anxiety, age, and Peoz values of all the patients (independent vari ables). Also correlations among the anxiety measures, age, and Peo2 were computed. These correlation indexes were computed both in the whole group (considering the z-transformation of rCBF values) and in the subgroups of males and females separately (considering absolute lSI values). Also Pearson's linear regressions were computed for all those correlation indexes that resulted in statistically sig nificant differences, and differences between slopes of regions in the same hemisphere and between slopes of homologous regions in the two hemispheres were evalu ated by a t test.
RESULTS Table 1 shows mean values for all the variables in the male and in the female groups, both for patients and for normal sex- and age-matched controls. The anxiety scores for normal controls are missing but
J Cereb Blood Flow Metab, Vol. 9, No.3, 1989
G. RODRIGUEZ ET AL.
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TABLE 1. Mean ± SD values for all variables considered in two subgroups of patients and for regional CBF values in normal controls from normative group of laboratory Men
Women
(30 subjects)
(30 subjects) --------
Normal
Age (yrs) Peo2 (mm Hg) CBF (mlllOO glmin) Global lSI Right hemisphere Left hemisphere
Patients
controls
Right parietal
44.5 ± 14.2 38.5 ± 4.9
38.9 ± 3.2
38.2 ± 3.7
49.8 ± 5.5
51.8 ± 6.5
53.7 ± 6
53.8 ± 6.4
49.9 ± 5.5
51.9 ± 6.7
53.7 ± 6.2
53.8 ± 6.6
48.5 ± 5.8
50.5 ± 6.9
53 ± 6.3
49.8 ± 5.8
51.7 ± 6.8
53.7 ± 8.2
51.4 ± 7.3
51.6 ± 5.9
53.6 ± 8.1
51.1 ± 7.1
Left occipital
49.6 ± 5.2 48.8 ± 5.8
STAI-I
49.6 ± 7
49 ± 6.1
Right occipital Left frontal
49 ± 5.6
Left parietal Left temporal
53.7 ± 6.2
55.3 ± 6.4 53 ± 6.3
53.8 ± 6.7 55.1 ± 7.8 52.8 ± 7
53.8 ± 6.6
51 ± 6.9
52.4 ± 6.3
53.7 ± 6.6
51 ± 6.8
53.2 ± 6.3
53.3 ± 7
54.5 ± 6.5
53 ± 6.3
54 ± 6.7
51.1 ± 6.9
54.7 ± 7.6 53 ± 7.1
53.8 ± 6.5
50.5 ± 7.4
49 ± 8.5
46.3 ± 8
STAI-2 TRAIT
49.7 ± 14.9
44.5 ± 14.6
49.3 ± 6.2
Right temporal
49.7 ± 15.1
controls
40.9 ± 5.3
51.7 ± 6.3
Right frontal
Normal Patients
50.3 ± 7.3
50 ± 8.7
lSI, initial slope index; STAI-I, state anxiety before the examination; STAI-2, state anxiety after the examination; TRAIT, trait anxiety. The analysis of variance between patients and normals was not significant and neither was that between male and female patients.
means ± SD for a sample of general medical sub jects (Spiegberger et aI., 1 976) are reported above. The one-way ANOV A between the male and fe male groups and between patient and normal groups showed no significant difference for all considered variables. Correlations In the total group (see Table 2), z-transformed rCBF values correlated negatively with STAI-2 in hemispheric, frontal, and temporal regions bilater ally and right occipital and parietal areas. Also neg ative correlations between rCBF values and aver age anxiety scores were significant, except in the
right temporal and left occipital areas. Global lSI correlated negatively with the average anxiety score (p < 0.05; see Fig. O. No significant correlations with ST AI-l or TRAIT were found. All flow variables were positively correlated with Peo2 with degrees of significance ranging from p < 0.05 in the left frontal region to p < 0.01 in all other regions. All regions correlated negatively and sig nificantly with age (p < 0.01 in the right hemi sphere, in the frontal regions bilaterally, and in the left temporal region; p < 0.05 in all other regions) except for the right occipital area. In the male group (Table 3), STAI-2 correlated negatively with mean right hemispheric values, with right frontal, right parietal (p < 0.05), and right oc cipital values (p < 0.01 ). No correlation was found between STAI-l , TRAIT, average anxiety, and rCBF. Peo2 values correlated positively with all rCBF values with p < 0.05. Age was negatively correlated with both mean hemispheric values (p < 0.05) and with all rCBF measures (p < 0.05 and p < 0.0 1 for left frontal and left occipital areas, respec tively). In the female group (Table 4), mean hemispheric values were significantly and negatively correlated with STAI-l (p < 0.05), and so were all regional values (p < 0.05), except left parietal and left tem poral areas. TRAIT was correlated negatively with frontal rCBF values bilaterally and with left tempo ral CBF values (p < 0.05). The average anxiety score correlated negatively (p < 0.05) with both hemispheres and with frontal and temporal rCBF bilaterally, more so in the right frontal area (p < 0.01 ). Peoz correlated positively with all rCBF mea sures with significance levels varying from p < 0.0 1 for right hemispheric, right parietal, and temporal areas to p < 0.05 for all other regions. Correlations
TABLE 2. Correlation coefficients (Kendall's T) between anxiety measures and standardized regional CBF (rCBF)
values in the whole group (60 patients)
STAI-2 STAI-I STAI-2 TRAIT AVGSTAI Age
0.51a
TRAIT 0.47a 0.43a
Age
Peo2
ZGI
ZMR
ZML
ZRF
ZRP
ZRT
ZRO
ZLF
ZLP
ZLT
ZLO
-0.05
-0.10
-0.14
-0.15
-0.12
-0.16
-0.15
-0.12
-0.14
-0.14
-0.13
-0.15
-0.07
0.07
0.01
-0.13
-0.13
-0.16
-0.06
0.14
0.07
-0.13
-0.2Ib
-O.22b
-0.20h
-0.24'
-0.21h
-0.17b
-0.23'
-0.2Ib
-0.16
-0.22b
·-0.10
-0.19b
-0.20b
-0.19b
-0.24'
-0.19b
-0.16
-0.18b
-0.20b
-0.17b
-0.21b
0.24c
O.22b
0.03
Peo2
-0.22b 0.26'
-0.22'
0.27'
-0.13
-0.2Ib 0.23'
-0.16
-0.24' 0.22c
-0.11
-0.19b 0.26c
-0.09
-0.19b 0.27c
-0.09
-0.16
-0.14
-0.24c
-0.10
-0.22b 0.24c
-0.11
-0.11
-0.23'
-0.21b
0.25c
0.25c
rCBF values were standardized within groups of men and women. Significance levels are reported near the corresponding correlation coefficient. STAI-I, state anxiety before the examination; STAI-2, state anxiety after the examination; TRAIT, trait anxiety; AVGSTAI. mean of the three anxiety measures; ZGI, zed score of global initial slope index values; ZMR, zed score of mean right hemispheric CBF; ZML, zed score of mean left hemispheric CBF; ZRF, zed score of right frontal rCBF; ZRP, zed score of right parietal rCBF; ZRT, zed score of right temporal rCBF; ZRO, zed score of right occipital rCBF; ZLF, zed score of left frontal rCBF; ZLP, zed score of left parietal rCBF; ZLT, zed score of left temporal rCBF; ZLO, zed score of left occipital rCBF. a p < 0.001.
b P < 0.05.
'p < 0.01.
J Cereb Blood Flow Metab. Vol. 9, No.3, 1989
rCBF-ANXIETY CORRELATIONS
3
lSI
(z-Iransform) *
2
o -I
-2
o
-3 +----r---,----�--r_--� 35 30 40 45 50 55 60 65 70 Average Anxlely
o
Females
*
Males
FIG. 1. Linear regression between zed-transformed global initial slope index (lSI) values and the average across state anxiety scores before and after the examination and trait anxiety scores (average anxiety) in the whole group of pa tients studied. The zero on the y-axis corresponds to the respective means of male and female groups.
between rCBF variables, age, and STAI-2 were not significant. In all the groups, highly significant correlations were present among the various anxiety measures (p < 0.00 1 for all correlations, except between STAI-l and TRAIT in the female group and STAI-2 and TRAIT in the male group, p < 0.0 1 ), while no significant correlations between anxiety measures, age, or Peoz were found. In no case did the 1 test reveal any significant differences between the slopes of statistically sig nificant regression lines. DISCUSSION The mean STAI-I and STAI-2 values (Table I) showed moderately high levels of anxiety as com pared with the mean values of general medical sub jects reported by Spiegelberger et al. (1 976) or with mean values for 1 4 normal male subjects undergo ing rCBF examination as reported by Gur et al. (1 987). This is compatible with the fact that the sub jects were patients who underwent for the first time rCBF examination and were sometimes worried about its outcome. Also the mean TRAIT values could be explained in this view and are in the range of values considered as normal for general medical subjects (Spiegberger et aI., 1 976). It may be worth while noting that the standard deviation of anxiety measures was more or less a sixth of the mean value, and consequently it may be deduced that the responses to the questionnaire varied widely from subject to subject. This may be due to the inhomo geneous condition of the patients included in this study, who were healthy only in nine cases and had a wide range of illnesses in the other cases. There-
413
fore, it is probable that a wider variety of expecta tions and fears was expressed in replying to the questionnaire than expected in a fully normal sam ple of subjects. In turn, the psychological condition of each subject at the moment of the examination might have varied more relevantly than in a normal group, thus influencing rCBF values in a somewhat unpredictable manner, the "resting condition" be ing quite variable in this respect. This explains why interpretation of the present results should be un dertaken cautiously and cannot be considered as representative of normal subjects. As shown in Table 1 , the rCBF values of the ex amined patients did not differ significantly from those of sex- and age-matched normal subjects. Moreover, rCBF values in female patients were slightly higher than in males, though not signifi cantly so. This trend toward higher values in fe males than in males is consistent with previous re ports in the literature (Gur et aI., 1 982; Rodriguez et aI., 1 988) and explains why we preferred to z transform rCBF values within male and female groups in examining the correlations of the whole group. Correlations STAI measures were expected to correlate with rCBF since they express the psychological attitude of the patient at the moment of the examination, and it is well known that anxiety has manifold bio logical correlates within the central nervous sys tem, including those concerning neurotransmitter systems (File, 1 987), performance levels (Eysenck, 1 985), and the electroencephalogram (Buchsbaum et aI., 1 985). Indeed, in the whole group (Table 2), significant correlations were found between the average anxi ety measure and most rCBF values, with the high est significance level for the right frontal region. However, there were no statistically significant dif ferences (I test) between the slopes of the regres sion lines calculated for rCBF-anxiety correlations. STAI-2 also correlated negatively and signifi cantly with most cerebral regions, with highest sig nificance in the right frontal lobe. Nevertheless, also in this case there were no significant differ ences between the slopes of the regression lines. In the male group (Table 3), only the STAI2/rCBF correlations reached statistical significance. This happened only for right hemispheric mean val ues, right frontal, right parietal, and, quite unex pectedly, right occipital rCBF values (p < 0.01 in stead of p < 0.05 as in the other significant regions). In the female group (Table 4), the correlations between STAI-l and rCBF were significant, while
J Cereb Blood Flow Metab. Vol. 9, No.3, 1989
G. RODRIGUEZ ET AL.
414
7) between anxiety measures and regional CBF (rCBF) values in the male group (30 patients)
TABLE 3. Correlation coefficients (Kendall's
STAI-2 0.45a
TRAIT 0.57a 0.39b
Age
Peo2
-0.12
-0.02 -0.12
TRAIT
0.14 -0.03
AVGSTAI
-0.01
STAI-1 STAI-2
Age
0.18 -0.01 -0.07
Peo2
01
MR
ML
-0.10 -0.29c
-0.05 -0.23
-om
-0.03
-0.01
-0.13 -0.33b
-0.16 -0.31C
-0.13
-0.07 -0.25c
0.25C
0.27c
-0.31" 0.27c
RF
RP
RT
RD
LF
LP
LT
-0.08
-0.07
-0.09
-0.08
0.03
-0.23
-0.22
-0.22
-0.11
-0.28c -0.05
-0.28c
-0.02 -0.15
0.02 -0.33b
0.01
-0.16 -0.30c
-0.17 -0.32c
-0.07 -0.26c
0.02 -0.15 -0.27c
-0.08
0.25c
-om
0.25c
0.27c
0.25c
-0.02 -0.13 -0.35b 0.25c
La
0.01
-0.09
0.07
-0.14 -0.31c
-0.14 -0.29c
-0.Q2 -0.33b
0.25c
0.25c
0.25c
Significance levels are reported under the corresponding correlation coefficient. STAI-I, state anxiety before the examination; STAI-2, state anxiety after the examination; TRAIT, trait anxiety; AVGSTAI, mean of the three anxiety measures;
01,
global initial slope index values; MR, mean right hemispheric
CBF; ML, mean left hemispheric CBF; RF, right frontal rCBF; RP, right parietal rCBF; RT, right temporal rCBF; RO, right occipital rCBF; LF, left frontal rCBF; LP, left parietal rCBF; LT, left temporal rCBF; La, left occipital rCBF. a p < 0.001. b P < 0.01. P < 0.05.
c
those between STAI-2 and rCBF were not. In this group also the average anxiety score significantly correlated with rCBF measures, particularly so in the right frontal lobe (p < 0.0 1 instead of p < 0.05 as in the other significant regions). The present results are consistent with the find ings by Gur et al. ( 1 987) who hypothesized a nega tive CBF-anxiety correlative trend for higher anxi ety levels, although the laboratory staff they exam ined had much lower anxiety levels (between 28 and 40) than the present group of patients (between 32 and 70). The reason for such a negative trend is unknown, but a hypothesis may be proposed. Gen erally, it is thought that subcortical structures such as the hypothalamus, hippocampus, and cingulate gyrus are implicated in the control of emotions and perhaps of the anxiety response, together with other structures like the amygdala, septum, and part of the midbrain (Kuhar, 1 986). This assumption could find partial confirmation in the data by Reiman et al. ( 1 984) who showed a focal abnormal ity in the parahippocampal gyrus in patients with panic disorder studied by PET. It could be sus pected that a rearrangement of rCBF could happen with an increase, due to a higher metabolic demand, in the regions of the so-called limbic system and consequent slight reduction in cortical areas, as first suggested by Gur et aI. ( 1 987). The 133Xe inhalation method we used allows us to obtain information
TABLE 4. Correlation coefficients (Kendall's
STAI-2 STAI-I STAI-2
0.5 6a
Age
Peo2
01
MR
ML
RF
RP
RT
RO
LF
LP
LT
La
-0.06
-0.19
-0.26c
-0.28c
-0.25c
-0.31c
-0.30c
-0.26c
-0.24
0.10
-0.19
-0.17
-0.18
-0.22
-0.11
-0.11
-0.21 -0.25C
-0.24 -0.25c
-0.23 -0.30c -0.35b
-0.19
-0.17
-0.22
-0.21 -0.28c
-0.21 -0.26c -0.27c
-0.25c -0.14
-0.23 -0.25C
-0.28c -0.25 -0.28c
- 0.24
0.49a
-0.28c -0.15
-0.12 0.33b
-0.13 0.35b
-0.13 0.29c
-0.12 0.32b
-0.08 0.35b
0.19
-0.14 -0.15
AVGSTAI
0.12
-0.18
Peo2
7) between anxiety measures and regional rCBF values in the female group (30 patients)
0.38b
TRAIT
TRAIT Age
only about cortical rCBF; therefore, no confirma tion of this hypothesis is possible according to our data. The analysis of regional values showed signifi cant correlations between anxiety measures and frontal rCBF values in all the groups studied. The frontal regions reached the highest level of statisti cal significance among the other rCBF-anxiety cor relations, both in the female and in the total patient groups. However, slopes of regression lines were not significantly different in right frontal regions as compared with all other regions in the same hemi sphere or with the contralateral frontal lobe. Keep ing in mind that rCBF, at least in normal conditions, is correlated with cerebral metabolism (Raichle et aI., 1 976), these findings are in line with results re ported by Reivich et al. ( 1 983), who hypothesized greater involvement of the frontal regions and of the right hemisphere in high anxiety states. As to their finding of asymmetrical metabolic rates with higher values in right frontal regions, it could be noted that in our study only females seemed to have slightly higher rCBF values in right frontal areas as com pared with the left. Such a difference, however, was not significant (Table 1 ), and data were obtained with a method and data analysis with much lower resolution power than the PET study conducted by the authors cited. A more marked involvement of the frontal lobes may be expected since they are
0.17
-0.19
0.29c
-0.19
-0.29c
-0.19
-0.09
-0.18 0.25c
-0.13 0.31c
0.29c
Significance levels are reported under the corresponding correlation coefficient. Abbreviations as in Table 3.
J Cereb Blood Flow Me/ab. Vol. 9, No.3, 1989
-0.17
-0.15
0.29c
-0.17 -0.21 -0.09 0.25c
rCBF-ANXIETY CORRELATIONS functionally connected to the deep cerebral struc tures, which are supposed to play a key role in the control of emotions (Kuhar, 1986). On the other hand, the highest statistical signifi cance reached by the correlation between right oc cipital CBF and STAI-2 in the male group was un expected and no confirmations in the literature are present. Another interesting phenomenon from a psycho physiological point of view is that males and fe males show significant correlations between rCBF and different anxiety measures, respectively, the STAI-2 (the measure after the examination) and STAI-l (the measure before the examination). This may be due to a different attitude in responding to the questionnaire in the sexes. This hypothesis could be partly confirmed by the observation that while in males STAI-l is more closely related to TRAIT, in females the reverse is true. The patient is asked to reply to the 20 TRAIT items, reporting how he/she feels usually, in normal everyday life. The anxiety experienced at the moment of the first rCBF measurement should therefore be expected to be relatively unrelated to the TRAIT measure, al though a correlation between the two measures is inevitably present and in line with the classic liter ature on STAI measurements (Spiegelberger et aI., 1970, 1976; see Tables 2-4). Therefore, we think that the anxiety felt by the subjects during the min utes of examination was measured more reliably by the STAI-l score for female and the STAI-2 score for male patients. Nevertheless, this is only an overall impression of ours, since the t value of dif ferences between the slopes of regression lines for STAI-I-TRAIT and STAI-2-TRAIT correlations within sex did not reach statistical significance. Only weak correlations between rCBF and TRAIT measures were found in the frontal and left temporal regions of the female group. No correla tions at all were expected to be statistically signifi cant since there is no reason to suppose that a per sonality feature correlates with rCBF. Peo2 values were, not surprisingly, correlated to rCBF values of all regions studied and of both hemi spheres throughout the groups studied. The differ ences in significance levels in the various regions could be due to the fact that these patients were unhomogeneous for pathology and for rCBF values, and it is difficult to exclude that in some patients slight regional flow abnormalities could be present. This is another reason to consider with caution our results and to consider carefully possible differ ences from normal individuals. The inhomogeneous correlations of age with CBF values may be explained by the fact that the
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sampling of the patients was casual and did not con sider this factor as a criterion for inclusion or ex clusion of the patients. This resulted in a prepon derance of patients over 50 years old, especially in the female group, when the reduction of rCBF as a function of aging is not so marked as in young sub jects (Rodriguez et aI., 1989). However, a negative correlation trend was found in all patient groups. Peo2 and anxiety measures showed a nonsignifi cant trend to correlate negatively. This trend was expected since high levels of anxiety should bring about hyperventilation and consequently reduce Peo2• It may be that in particular subsets of patients with high levels of anxiety accompanied by pro nounced somatic symptoms, modifications of breathing could contribute to rCBF reduction. Finally, the correlations between age and anxiety measures were nonsignificant, as expected, since there is no reason to suppose that anxiety levels should change with age. Nevertheless, the unhomo geneous sampling of patients according to age could have played a role, as proposed for the age-CBF correlations. We also would like to stress that our data should be considered with caution, since only multiple sta tistical analysis could discriminate the effects of anxiety from those of age and Peo2• Moreover, sta tistical corrections would be needed to adjust for multiple comparisons, even though the rCBF and anxiety variables we studied are strictly intercorre lated with one another. In conclusion, correlations between anxiety and rCBF in neurologically normal patients in the sense of a reduction of CBF for increasing levels of anx iety have been demonstrated. These may be due to high anxiety levels in this series of subjects. The most involved regions seem to be right frontal ar eas. The finding of sex differences in the correlation of rCBF with anxiety measures before and after the examination (STAI-l and STAI-2, respectively) may have some relevance in psychological studies using this questionnaire in clinical settings. On the one hand, further research is needed to discriminate the possible effect of the single pathol ogies by which our patients were affected and also to identify the extent of the influence of other vari ables such as age of Peo2• On the other, the here reported results are quite consistent with other re search performed on healthy subjects. This is an indirect confirmation, together with the very slight rCBF differences between our patients and the age and sex-matched normal control groups, that our data should be reasonably near to physiology. The effect of anxiety on rCBF seems slight but significant, and it should be kept in mind when ex-
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