Temporal lobe dysfunction and correlation of regional cerebral blood flow abnormalities with psychopathology in schizophrenia and major depression — A study with single photon emission computed tomography

PSYCHIATRY RESEARCH ELSEVIER

NEUROIMAGING Psychiatry Research: Neuroimaging Section 68 (1996) 1-10

Temporal lobe dysfunction and correlation of regional cerebral blood flow abnormalities with psychopathology in schizophrenia and major depression - - A study with single photon emission computed tomography Edzard Klemm* a, Peter Danos b, Frank Griinwald a, Siegfried Kasper c, Hans-Jiirgen MSller d, Hans-Jiirgen Biersack a aDepartment of Nuclear Medicine, Universityof Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany bDepartment of Psychiatry, Universityof Magdeburg Leipziger-Str. 44, D-39120 Magdeburg, Germany ¢Department of Psychiatry, Universityof Vienna, W'dhringerG iirte118-20, A-1090 Vienna, Austria dDepartment of Psychiatry, Universityof Munich, Nussbaumstr. 7, D-80336 Munich, Germany Received 8 May 1995; revised 2 May 1996; accepted 28 July 1996

Abstract Studies of regional cerebral bood flow in both schizophrenic and depressed patients have yielded contradictory findings. Single photon emission computed tomography (SPECT) was used to compare brain-perfusion patterns in 17 patients with schizophrenia and 12 patients with major depression and to evaluate the relationship of the findings to psychopathology. The images were analyzed both visually and quantitatively. Twelve of the 17 schizophrenic patients and 8 of the 12 depressed patients showed a pathological blood flow pattern. Hypoperfusion of the left temporal lobe was observed in seven of the schizophrenic and five of the depressed patients. Five of the schizophrenic patients also had a hypoperfusion of the left frontal lobe. Separation of both diagnostic cohorts in two subgroups with pathological and normal cerebral blood flow patterns revealed significantly higher levels of symptomatology in the group with hypoperfusion in the SPECT image. The analysis of different cerebral regions revealed statistically significant correlations in schizophrenic patients between left frontal hypoperfusion and negative symptoms. In contrast, left temporal hypoperfusion was significantly related to positive symptoms in schizophrenia. Our data suggest that left-sided temporal lobe dysfunction is related both to schizophrenia and major depression. The localization of hypoperfusion seems to be associated with the type of psychopathology (positive vs. negative symptoms in schizophrenia). Thus, the results support the model of paralimbic and prefrontal dysfunction in both diseases. Copyright © 1996 Elsevier Science Ireland Ltd. Keywords: SPECT; Laterality; Temporal lobe; Frontal lobe; Positive and negative symptoms

*Corresponding author. Tel.: +49 228 2875180 or 2875183; fax: +49 228 2876615. 0925-4927/96/$15.00 Copyright © 1996 Elsevier Science Ireland Ltd. All rights reserved PII S0925-4927(96) 02837-5

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E. Klemm et al./Psychiatry Research: Neuroimaging 68 (1996) 1-10

I. Introduction In 1974, Ingvar and Franz6n first described perfusion abnormalities assessed with the intracarotid 133xenon technique in the frontal lobes of schizophrenic patients. Later studies with computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission tomography (SPECT) have demonstrated a variety of abnormalities of different brain regions in both schizophrenic and depressed patients. The inconsistency of findings may reflect methodological issues, selection of subjects, number of patients, and diagnostic heterogeneity. More recently, temporal lobe metabolic abnormalities have been described in schizophrenic (Wolkin et al., 1985; Wiesel et al., 1987; DeLisi et al., 1989; Buchsbaum, 1990; Paulman et al., 1990; Tamminga et al., 1992; Friston et al., 1992; Siegel et al., 1993) and depressed (Baxter et al., 1989; Schlegel et al., 1989; Sackeim et al., 1990; Yazici et al., 1992; Austin et al., 1992; Bench et al., 1992; Devous et al., 1993; Mayberg et al., 1994) patients. Only recently have the concomitant psychopathological features been taken into account with respect to the metabolic patterns in such studies. To compare brain-perfusion patterns in subjects with schizophrenia and major depression and to evaluate the relationship to the severity of clinical symptoms, we analyzed the results of single photon emission computed tomography with 99mTc_hexamethylpropylene amine oxime (HMPAO) in 17 schizophrenic and 12 depressed patients during the acute state of illness. 2. Methods

2.1. Patients and clinical assessment

We evaluated 17 schizophrenic patients and 12 patients with unipolar major depression (including 5 patients with delusional depression) diagnosed according to DSM-III-R criteria (American Psychiatric Association, 1987). Bipolar subjects were excluded. All patients were females. The study was approved by the local ethical committee. Mean age in the schizophrenic patients was 41.0 (S.D. = 8.0, range = 18-64) years; in the de-

pressed subjects, it was 53.5 (S.D. = 15.3, range --29-77) years. Mean duration of disease was 6.8 (S.D. = 7.2) years in the schizophrenic patients and 9.9 (S.D.= 8.9) years in the depressed patients. All but two schizophrenic and one depressed individual were right-handed. All but one patient were being treated with neuroleptics, antidepressants or benzodiazepines, and had been on a stable medication regimen for > 3 weeks. The only exception was a patient with major depression who was free of medication and who had been treated with the antidepressant doxepine (100 mg/day) up to 6 months before the SPECT study. All but seven patients had a CT scan, two had only an MRI scan, and four had both an MRI and a CT scan. The findings were normal except for a slight degree of cortical atrophy in three patients (in the fight frontal pole in one patient) and a pons infarction in one patient. To exclude patients with a primary organic etiology, we performed electroencephalographic and routine laboratory analyses as well as an extensive psychopathological examination. Clinical symptoms on the morning of the SPECT examination were rated with the Positive and Negative Syndrome Scale (PANSS; Kay et al., 1986) and the Hamilton Rating Scale for Depression (HRSD; Hamilton, 1967). The scores were not obtained at precisely the moment of tracer injection but reflected the patient's state on the morning of the study. In schizophrenic patients, the total PANSS score was 102.2 + 20.7 (mean + S.D.), the score for positive symptoms was 21.0 + 9.0, that for negative symptoms was 27.0 + 10.0, and that for general psychopathology was 55.0 + 11.0. In the whole group of depressed subjects, the mean total score of the HRSD was 22.7 + 7.2. Patients with delusional depression had a positive symptom score of 13.0 _+4.2 vs. a score of 8.3 + 1.5 in nondelusional depression; for the total score of the PANSS and the HRSD, the scores were 83.8 + 13.6 vs. 62.6 + 11.7, and 26.6 + 6.8 vs. 20.0 + 6.5, respectively. 2.Z SPECT technique and evaluation After giving informed consent, the patients underwent SPECT following intravenous injection

E. Klemm et al. / Psychiatry Research: Neuroimaging 68 (1996)1-10

of 20 mCi 99mTc-HMPAO. Subjects were in a resting state, with their eyes open. The perfusion agent was supplied by Amersham International, U.K., and labeled according to the manufacturer's recommendation. A rotating double-headed gamma camera (Dynascan, Picker, full-width half-maximum= 12-15 mm) equipped with a low-energy high resolution parallel-hole collimator was used to obtain 64 frames with a 64 x 64 matrix within 30 rain. After application of a Metz filter and attenuation correction, activity levels in coronal, sagittal, and transaxial slices parallel to the orbitomeatal line were calculated. To achieve a proper image of the temporal lobe, transversal slices parallel to the temporal lobe plane were reconstructed. The images were analyzed both by visual evaluation and quantitatively. Visual interpretation of the SPECT images was performed by three experienced nuclear medicine specialists. Diminished perfusion (hypoperfusion) was defined by markedly reduced tracer uptake in one or more brain regions relative to the remaining regions as determined by three experienced nuclear medicine specialists. Quantitative analysis confirmed the determinations made by visual inspection. For quantitative analysis, regions of interest (ROIs) of the same size and shape (4 pixels, 1 pixel corresponding to 6 x 6 mm) were drawn on 30 cerebral areas including the basal ganglia and the cerebellum by an investigator who was unaware of diagnosis, visual findings and psychopathology. The ROIs were defined by selecting three transversal slices parallel to the orbitomeatal line (one within the basal ganglia plane on the midventricular level, one 2.4 cm above the basal ganglia plane, and one towards the cerebellum), one transversal slice parallel to the temporal lobe plane, two coronal slices through the basal ganglia and the temporal lobe (each perpendicular to its corresponding transversal plane), and two sagittal slices 1.2 cm lateral to the median slice on both sides. Anatomical regions were assigned according to an anatomic atlas for computed tomography (Matsui and Hirano, 1978). The regional activity was calculated as the mean of two corresponding ROIs, and normalized both to the whole slice across the basal ganglia and the

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cerebellum. Intrarater reliability was > 95%, and interrater reliability > 94%.

2.3. Statistics For statistical evaluation, Mann-Whitney's U test was applied to all calculations. P values below 0.05 were estimated as statistically significant. The analysis was performed using the Statistica software package (Microsoft Corporation) on a personal computer. 3. Results

3.1. SPECT findings and psychopathology Twelve of the 17 schizophrenic patients and 8 of the 12 depressed patients showed a pathological cerebral blood flow pattern. The major finding was hypoperfusion of the left temporal lobe in both schizophrenic and depressed patients. Hyopoperfusion of the left temporal lobe was observed in seven of the schizophrenic patients and in five of the depressed patients. Left frontal hypoperfusion was found in five schizophrenic patients and four depressed patients. Diminished perfusion of the right frontal lobe was observed in three depressed subjects. Moreover, in both schizophrenic and depressed patients, there was a markedly left-sided preponderance of diminished blood flow (see Table 1). To correlate SPECT findings in schizophrenic patients with psychopathology, the schizophrenic patients were divided (without knowledge of PANSS scores) into two subgroups with and without any abnormal SPECT finding, with and without temporal hypoperfusion, and with and without frontal hypoperfusion. Schizophrenic patients with a pathological cerebral perfusion pattern were found to have significantly higher PANSS positive symptoms (z = 2.58, P = 0.010) and total scores (z = 2.21, P = 0.027) compared with patients with normal SPECT findings (see Fig. 1 and Table 2). The positive symptom subscores for conceptual disorganization (z = 2.53, P = 0.011), hallucinatory behavior (z = 2.32, P---0.020), and suspiciousness/persecution (z = 2.63, P = 0.008) also showed this correlation. The subscore for

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Table 1 Frequency of hypoperfusion in 17 patients with schizophrenia and 12 patients with major depression Region

Side

Schizophrenia

Depression

Frontal

Right Left Right Left Right Left Right Left Right Left

1 5 1 7 2 5 1 3 -1

3 4 1 5 I 1 -1 1 1

1 8 3

1 4 3

12 5 17

8 4 12

Temporal Parietal Occipital Basal ganglia Pathological (*)

Right Left Right + Left TOTAL

Normal (*) Total (*) (*) Patients.

excitement approached significance (z = 1.95, P = 0.051). Moreover, when hypoperfusion of the most relevant cerebral regions was related to clinical syndrome profiles, we found that the PANSS scores for positive symptoms were significantly correlated with left temporal hypoperfusion (z = 2.49, P = 0.013). In contrast, the PANSS negative symptoms subscale (z = 2.05, P---0.040), general psychopathology subscale (z = 2.74, P = 0.006), and total scores (z = 2.85, P = 0.004) were all significantly related to hypoperfusion of the left frontal region in schizophrenic patients (see Table 2 for details; d.f. -- 15 for all calculations). Similarly, when the depressed patients were divided into two subgroups with pathological and normal SPECT findings, the depressed patients with hypoperfused cortical areas had higher H R S D scores than those with normal blood flow (z = 1.95, d.f. = 10, P -- 0.051; see Fig. 1). The duration of illness was not significantly related to pathological blood flow anywhere in the brain or in a specific brain region ( P > 0.05).

3.2. Quantitative and visual assessment of SPECT images To compare the results of visual interpretation

with those of quantitative analysis, two groups with pathological vs, normal regional cerebral blood blow patterns were formed for the brain areas in which hypoperfusion was most commonly found (left temporal, left frontal, and left parietal lobes). Due to the installation of a new high resolution dedicated brain camera, retrospective quantitative evaluation was available only in 10 schizophrenic and 7 depressed patients. Statistical analysis with the Mann-Whitney U test revealed significant differences between the regional cerebral blood flow in patients with visually determined hypoperfusion and those with visually determined normal blood flow for the relevant regions (left temporal: z = 2.71, d.f. = 15, P = 0.007; left frontal: z = 2.38, d.f.= 15, P= 0.017; left parietal: z = 2.42, d.f. = 15, P --- 0.015). The mean values (median and quartile range in parentheses) for hypoperfused areas were: left temporal 1.183 (1.176, 0.061), left frontal 1.137 (1.160, 0.104), and left parietal 1.130 (1.171, 0.171). The corresponding values for normal flow were: left temporal 1.309 (1.268, 0.075), left frontal 1.274 (1.258, 0.082), and left parietal 1.277 (1.223, 0.058). Because the quantitative results confirmed the visual assessments, because image asymmetry can be detected by the eye very readily (Devous, 1989), and because the subjectivity of interpreta-

E. Klemm et al. / PsychiatryResearch: Neuroimaging 68 (1996) 1-10 Table 2 Psychopathological scores in relationship to SPECT findings in 17 patients with schizophrenia (PANSS and its subscales) SPECT

Hypoperfusion

Normal SPECT

U test (d.f. = 15)

n

Median

QR

n

Median

QR

z

P

PANSS (total score) A n y / n o abnormality Left temporal p./n. Left frontal p./n.

12 7 5

111.0 114.0 128.0

39.0 38.5 16.5

5 10 12

84.0 94.5 88.0

18.0 26.0 19.0

2.21 1.56 2.85

0.027* 0.118 0.004**

Positioe symptoms A n y / n o abnormality Left temporal p./n. Left frontal p./n.

12 7 5

23.0 27.0 27.0

11.0 10.0 12.0

5 10 12

12.0 15.5 17.0

4.0 9.5 11.0

2.58 2.49 1.00

0.010'* 0.013' 0.317

Negative symptoms Any/no abnormality Left temporal p./n. Left frontal p./n.

12 7 5

25.5 27.0 38.0

22.0 19.0 15.0

5 10 12

26.0 26.0 25.0

4.5 12.5 8.0

0.10 0.10 2.05

0.916 0.922 0.040*

General psychopathology A n y / n o abnormality Left temporal p./n. Left frontal p./n.

12 7 5

58.5 60.0 65.0

14.0 19.0 9.5

5 10 12

41.0 52.0 50.0

7.0 17.5 12.0

1.90 0.98 2.74

0.058 0.329 0.006"*

Note. SPECT, single photon emission computed tomography; PANSS, Positive and Negative Syndrome Scale; HRSD, Hamilton Rating Scale for Depression; QR, quartile range; p., pathological SPECI" (hypoperfusion); n., normal SPECT. Mann-Whitney U test: **P < 0.01; *P < 0.05. See text for results for positive symptom subscales (section 3.1).

NORM.

PATH. Io IL

NORM.

PATH. 0

5

10

15

20

25

PSYCHOPATHOLOGICAL SCORE

Fig. 1. Relationship between psychopathological scores and abnormal versus normal SPECT findings. Top: schizophrenia (significantly higher mean score for positive symptoms of the PANSS [P = 0.010, Mann-Whitney U test]) in the group with abnormal SPECT results; bottom: major depression (higher mean HRSD total score in patients with pathological SPECT findings; the difference just attains a statistically significant level [P = 0.051, Mann-Whitney U test]). SPECT, single photon emission computed tomography. NORM, normal; PATH, pathological. PANSS, Positive and Negative Syndrome Scale; HRSD, Hamilton Rating Scale for Depression.

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tion can be minimized by using consensus ratings by multiple experienced specialists (Devous, 1989), further analyses were based on the visual findings which were available for all patients. Moreover, intrarater and interrater reliabilities were both quite high ( > 95% and > 94%, respectively). 4. Discussion

The major findings of our study are as follows: (1) The left temporal lobe was the major site of hypoperfusion both in schizophrenia and major depression; (2) the severity of psychopathology was significantly correlated with hypoperfusion of certain cerebral regions both in schizophrenia and in major depression; (3) the localization of perfusion abnormality was associated with distinct clinical subsyndromes. In functional imaging studies of schizophrenia, interest focused initially on hypofrontality, the mostly commonly - - although not universally - reported finding (Ingvar and Franz6n, 1974; Buchsbaum et al., 1982, 1984, 1990; Weinberger et al., 1986; Cohen et al., 1987; Volkow et al., 1987; Wiesel et al., 1987; Andreasen et al., 1992; Wolkin et al., 1992; Siegel et al., 1993; Batista et al., 1995). More recently, attention has also been directed towards temporal lobe involvement (Wolkin et al., 1985; Wiesel et al., 1987; DeLisi et al., 1989; Buchsbaum, 1990; Crow, 1990; Paulman et al., 1990; Tamminga et al., 1992; Friston et al., 1992; Siegel et al., 1993). It should be noted, however, that enlargement of the third ventricle in schizophrenia was demonstrated very early by pneumoencephalography (Haug, 1962). Concerning the temporal lobe, MRI studies demonstrated a reduction of volume greater on the left side (Johnstone et al., 1989) not only in chronic patients but even in patients in their first episodes of schizophrenia (Bogerts et al., 1990). Neuropathological studies confirmed an enlargement of the temporal horn, particularly affecting the left hemisphere (Crow, 1990). The findings of Falkai and Bogerts (1986) were replicated by Jeste and Lohr (1989), who described the left anterior hippocampal gyrus as the most affected region. Our functional imaging result of hypoperfusion of the left temporal lobe in schizophrenia corre-

sponds well with these structural abnormalities and the above-cited findings of PET and SPECT investigations. Perceptual disturbances such as auditory or visual hallucinations, disturbances in the sense of reality, and episodic fear are well-known symptoms in patients with temporal lobe lesions and schizophrenia-like psychoses associated with complex partial seizures of temporal origin (FlorHenry, 1979). Moreover, psychosis-like disorders appear more often in cases with left-sided than right-sided lesions, at least following head injury (Hillbom, 1960). Interestingly, in a group of 15 male schizophrenic patients (Barta et al., 1990), the volume of the left superior temporal gyrus was inversely correlated with severity of hallucinations. The close connections between the parahippocampal gyrus, middle and superior temporal gyrus, dorsolateral prefrontal cortex, cingulum, thalamus, insula and amygdala (Alexander et al., 1986) may be an explanation of these findings. The importance of prefrontal structures in schizophrenia is still a matter of discussion (Buchsbaum, 1990; Andreasen et al., 1992). As in many other but not all functional brain-imaging studies (for review, see Andreasen et al., 1992; Buchsbaum, 1995), we found a considerable degree of frontal hypoactivity. Hypofrontality has even been described in neuroleptic-naive schizophrenic patients (Wiesel et al., 1987; Andreasen et al., 1992; Siegel et al., 1993; Batista et al., 1995). Thus, in these cases the appearance of hypofrontality seems to be related to the disease. The so-called negative symptoms of schizophrenia such as blunted affect, emotional withdrawal and lack of spontaneity and abstract thinking resemble to a certain degree the features of frontal lesions, particularly after head injury. In our schizophrenic patients, scores for negative symptoms, general psychopathology, and the total score of the PANSS all were significantly related to hypoperfusion of the left frontal region. With regard to hypofrontality and negative symptoms of schizophrenia, similar results were obtained by Liddle et al. (1992), who found an association of psychomotor poverty and disorganization with altered perfusion of the prefrontal cortex and many

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others (Volkow et al., 1987; Andreasen et al., 1992; Tamminga et al., 1992; Wolkin et al., 1992; Siegel et al., 1993). The parietal lobe does not seem to have attracted much interest in studies of schizophrenic patients. In our schizophrenic group, we observed parietal hypoperfusion seven times (see Table 1). Decreased glucose metabolism within this region has also been described by Wiesel et al. (1987), Cleghorn et al. (1989), and Tamminga et al. (1992). Since parietal lobe areas are important in the processing of complex information, a function that is disturbed in some schizophrenic patients, these findings warrant further investigation in this disease. In the field of mood disorders, functional brain imaging studies also have yielded contradictory results concerning the topographic patterns of abnormal findings (Buchsbaum et al., 1984; Gur et al., 1984; Post et al., 1987; Baxter et al., 1989; Schlegel et al., 1989; Silverski61d and Risberg, 1989; Sackeim et al., 1990; Delvenne et al., 1990; Yazici et al., 1992; Austin et al., 1992; Bench et al., 1992; Devous et al., 1993; Mayberg et al., 1994). With respect to metabolic abnormalities of the left frontal lobe, our results are consistent with the PET findings of Baxter et al. (1989) and Martinot et al. (1990). Buchsbaum et al. (1984) also described anteroposterior gradients of glucose metabolism in patients with affeetive disorder. Dysfunction of both temporal lobes was observed by Post et al. (1987) in a PET study and by Devous et al. (1993) in a SPECT study. Mayberg et al. (1994) found hypoperfusion in paralimbic areas of patients with unipolar depression besides hypoperfusion of the frontal lobe using SPECT. As in the present study, disturbed function in both the frontal and temporal lobes was described by Sackeim et al. (1990), Bench et al. (1992), Yazici et al. (1992), and Austin et al. (1992). Some studies of depressed patients reported preponderant involvement of the left hemisphere (Baxter et al., 1989; Delvenne et al., 1990; Bench et al., 1992; Yazici et al., 1992) similar to that found in schizophrenic and bipolar depressed patients (Baxter et al., 1989). The frontal lobe dysfunction suggested by these studies agrees with

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the fact that certain traits of depression resemble posttraumatic frontal lesions and negative symptoms of schizophrenia. They also have been described in poststroke depression (Robinson et al., 1984; Schwartz et al., 1987). In contrast, no major abnormalities in unipolar depressed patients were described by Gur et al. (1984) in the resting state or by Silverski61d and Risberg (1989). With respect to lateralization, neither Buchsbaum et al. (1984) nor Mayberg et al. (1994) observed major lateralization of their pathological findings. If schizophrenia and major depression are associated with abnormal patterns of cerebral perfusion, it is not unlikely that the intensity of clinical symptoms correlates with cerebral dysfunction. Similar to our results, several authors also found this link in depression (Mathew et al., 1980; Post et al., 1987; Schlcgel et al., 1989; Sackeim et al., 1990; Austin et al., 1992; Bench et al., 1992; Yazici et al., 1992; Devous et al., 1993). In contrast, Mayberg et al. (1994) did not confirm these findings except for psychomotor slowing, which was negatively correlated with frontal and cingulate perfusion. Thus far, the causes of metabolic abnormalities in frontal and temporal areas in depression and schizophrenia are not fully elucidated. Prefrontal and temporoparietal bundles, which form an associational network that subserves motivational, attentional, arousal and integrative cognitive functions, may account for at least some of the symptomatology of schizophrenia and depression. These fibers are closely connected with limbic and paralimbic areas as well as with the medial dorsal thalamic nucleus (Goldman-Rakic, 1987). This pattern of connectivity may also explain the paranoid symptoms that occur in a small number of patients with major depression. Concerning the dopamine hypothesis of schizophrenia (Crow, 1980) and the importance of dopamine activity in the prefrontal cortex (Brozoski et al., 1979), the observation of increased dopamine in the left, but not the right, amygdala (Roberts and Crow, 1987) is of special interest with respect to lateralization. Since the prefrontal region is a site of convergence for limbic neuronal activity with highly processed associative information, it may be part of a network serving t h e integration of thought

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and emotion (Mesulam, 1986). However, specific neural networks that manifest typical abnormalities in certain subgroups of schizophrenic or depressed patients have not yet been identified. The influence of medication on cerebral perfusion patterns was not controlled in the present investigation. In imaging studies of neuroleptic treatment effects, Berman et al. (1986), Paulman et al. (1990), Szechtman et al. (1988), and Resnick et al. (1988) did not find changes in cerebral metabolism, while Wolkin et al. (1985) observed increased metabolic rates in nearly all cortical regions in neuroleptie-treated schizophrenic patients except for the frontal lobe. Buchsbaum et al. (1987) observed increased metabolism only in the basal ganglia. In contrast, brain metabolic variables seem to more widely affected by treatment with antidepressants (Baxter et al., 1989; Martinot et al., 1990; Dub6 et al., 1993). However, in the depressed patients studied by Martinot et al. (1990), hypofrontality persisted after successful treatment despite clinical improvement, suggesting the hypofrontality not to be state dependent. SilverskiSld and Risberg (1989) did not find a major influence of antidepressant treatment. Taken together, the data presented here suggest that left-sided temporal and frontal lobe dysfunctions are related both to schizophrenia and major depression, and are also related to the extent and quality of their psychopathology. Thus, these findings do not appear to have diagnostic specificity. The results support the view that fronto-paralimbie-striatal structures seem to have a crucial role in the expression of symptoms both in schizophrenia and depression. Similar studies may help to provide further insight into the pathogenesis of such disorders and to develop more successful treatments. Acknowledgements This study was supported in part by a grant to E.K. by the Fritz Thyssen Stiftung, Cologne. References Alexander, G.E., DeLong, M.R. and Strick, P.L. (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9, 35-381.

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