No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Temporal lobe dysfunction and correlation of regional cerebral blood flow abnormalities with psychopathology in schizophrenia and major depression - A study with single photo emission computed tomography
Abstract
Studies of regional cerebral blood 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 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.
... Clinical assessment by means of PANSS (Positive and Negative Syndrome Scale) yields separate scores along a positive syndrome scale, negative syndrome scale, composite index, and general psychopathology scale (16). Though not all, in many studies, negative symptoms are found to be strongly associated with decreased frontal cortical blood flow (4,5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Some authors have argued that this hypofrontality may be related to the duration of the disease and long-term neuroleptic treatment. ...
... We found reduced cerebral blood flow in temporal regions in common with some other studies (7,8,14). Although particularly left temporal lobe pathologies were underscored in schizophrenics (20,21), we did not show any difference between left-right regional blood flow. Secondly, we found that different positive and negative symptoms were correlated with rCBF of different brain areas. ...
... In schizophrenia, frontal hypoperfusion is suspected to relate causally to negative symptoms (4,12,13,20,27). However, on the contrary to our prediction in the beginning, we did not find a correlation between any negative symptoms and frontal rCBF values. ...
Objective: Although most of the functional neuroimaging studies in schizophrenic patients have supported the hypothesis of frontal hypoperfusion, there are some studies which indicates that the perfusion of some other cortical regions are also affected. In this study, we aimed to investigate whether negative and positive symptoms of schizophrenia were related to abnormal blood perfusion in different cerebral areas. Method: Twenty drug-free patients (14 male, 6 female) who fully met DSM-IV criteria for schizophrenia and 17 age and sex matched healthy volunteers (12 male, 5 female) were included in the study. Symptoms of the patients were assessed by PANSS (Positive and Negative Symptom Scale) and regional CBF images were obtained by SPECT using 99mTc- HMPAO as a radiopharmaceutical. Results: We found frontal and temporal hypoperfusion in schizophrenic patients compared to the controls. As assessed with PANSS, ideas of grandiosity were correlated positively with the left temporal and parietal cortical perfusion values, and suspiciousness/persecution ideas were correlated negatively with all frontal and right temporoparietal rCBF values. There were negative correlation between emotional withdrawal scores and bilateral temporal rCBF values. We did not find any relation between reduced frontal perfusion and negative symptoms. Conclusion: Our results support the hypothesis that brain perfusion is reduced in frontal and temporal regions of schizophrenic patients. Furthermore, different positive and negative symptoms seem to originate from different brain areas, such as frontal, temporal and parietal regions.
... Similarly inconsistencies were reported from studies that demonstrated increased (Brodie et al 1984, Wolkin et al 1985) and decreased (Sheppard et al 1983) metabolism in the basal ganglia. Hypoperfusion of the temporal lobes were reported in a number of studies (Crow 1990, Paulman et al 1990, Catafau et al 1994) especially of the left temporal lobe (Klemm et al 1996). ...
... Studies that investigated the correlation of regional cerebral blood flow abnormalites with psychopathology in schizophrenia revealed interesting results (Gur et al 1995; Erkwoh et al 1999). Statistically significant correlations were found between negative symptoms of schizophrenia and left frontal hypoperfusion and between positive symptoms and left temporal hypoperfusion (Liddle et al 1992 Klemm et al 1996). Of particular interest are the studies that investigated the correlation between hallucinations and rCBF. ...
... to those with schizophrenia is similar to the higher rCBF to the right mid– temporal lobe detected in our comparison of alcohol-induced psychotic disorder patients with healthy volunteers. Hypoperfusion to the temporal lobes in schizophrenia as indicated in previous reports (Crow 1990, Paulman et al 1990, Catafau et al 1994, Klemm et al 1996) could also accentuate such a comparative finding. postulated that it is consistent with decreased rCBF to the frontal lobes reported in alcohol dependence (Moselhy et al, 2001). ...
Alcohol-induced psychotic disorder (also known as alcohol hallucinosis) is a complication of alcohol abuse that requires clinical differentiation from alcohol withdrawal delirium and schizophrenia. Although extensively described, few studies utilized standardized research instruments and brain-imaging has thus far been limited to case reports. The aim of this study was to prospectively compare four population groups (ie. patients with alcohol-induced psychotic disorder, schizophrenia, uncomplicated alcohol dependence and a healthy volunteer group) according to demographic, psychopathological and brainimaging variables utilizing (i) rating scales and (ii) single photon emission computed tomography (SPECT). The third component of the study was designed to investigate the (iii) effect of anti-psychotic treatment on the psychopathology and regional cerebral blood flow (rCBF) before and after six weeks of treatment with haloperidol. Effort was made to ensure exclusion of comorbid medical disorders, including substance abuse. The study provides further supportive evidence that alcohol-induced psychotic disorder can be distinguished from schizophrenia. Statistically significant differences in rCBF were demonstrated between the alcohol-induced psychotic disorder and other groups. Changes in frontal, temporal, parietal, occipital, thalamic and cerebellar rCBF showed statistically significant negative correlations with post-treatment improvement on psychopathological variables and imply dysfunction of these areas in alcohol-induced psychotic disorder. The study was unable to distinguish between pharmacological effects and improvement acccomplished by abstinence from alcohol. Thesis(DMed (Psychiatry))-- University of Stellenbosch, 2007. Stellenbosch: Stellenbosch University
... To summarize, many SPECT or PET studies in depressed patients show reduced blood fl ow or neuronal energy consumption/glucose metabolism in the anterior regions of the brain [58,59,[61][62][63][64][65][66][67]. The most consistent fi ndings in functional imaging studies are frontal and cingulate changes. ...
... Vascular depression may represent a discrete depressive sub-type in this population [76]. Although a large number of SPECT studies of depression have failed to detect global functional brain abnormalities, those studies are focusing on elderly depressed populations have shown reduced global cerebral blood fl ow [67,77]. Furthermore, a recent Nisopropyl-p-[ 123 I]iodoamphetamine ( 123 I-IMP) SPECT comparison of nine vascular depression (VD) patients with eleven non-vascular depression (non-VD) patients, who were scanned during illness and again after recovery, has shown that under both circumstances, VD patients had signifi cantly lower mean rCBF in the left anterior frontal region compared to non-VD patients [78]. ...
Background: Major depressive disorder (MDD) is one of the prevalent and disabling psychiatric disorders. MDD is a complex disorder with marked hetero-geneity in pathophysiology, diagnosis, and treatment. Currently, neuroimaging has given new insights into the structure and function of the brain in individuals with major depression. Methods: We did a Medline search with key words "major de-pressive disorder" combined with "neuroimaging" or "brain imaging" up to May 15, 2008. We reviewed all identifi ed published articles. Results: The most consistent fi ndings in the pathophysiology studies of MDD with neuroimaging are abnormalities in the anterior regions of the brain, especially frontal, limbic, and cin-gulate regions, which presenting with increased rate of white matter hyperintensities, defect of white matter integrity, reduced glial cell density, reductions in cerebral fl ow or glucose metabolism. Thus, MDD is a brain disorder proved by neuroimag-ing and other biological fi ndings. Findings of the regional abnormalities by neuro-imaging may have clinical utility in both diagnosis and treatment of depression. Neuroimaging in geriatric depression found more subcortical ischemic vascular lesion, which is called vascular depression. It is noteworthy that the involved regions of brain and the neural processing of facial expressions may differ between MDD and bipolar disorder. Interestingly, there are clear regional change pattern differences across unique treatments, including medication and cognitive behavior therapy, affecting similar region but in different ways. Conclusion: We conclude that the fi ndings of neuroimaging in individuals with MDD can help clinicians to get comprehensive understanding of depression in pathophysiology, diagnosis and treatment, and to ensure the quality of care in depression.
... Functional neuroimaging studies have revealed abnormalities in the brains of schizophrenic patients, especially in the frontal and temporal lobes, basal ganglia, and thalamus (Bertolino et al. 1996;Andreasen et al. 1997;Egan and Weinberger 1997;McClure et al. 1998). Frontal lobe dysfunction generally has been associated with "negative" symptoms and the disorganization syndrome (Liddle et al. 1992;Kaplan et al. 1993;Shioiri et al. 1994;Deicken et al. 1995), whereas temporal lobe dysfunction may be related to "positive" symptoms (Fukuzako et al. 1996;Klemm et al. 1996;Nordahl et al. 1996;Sabri et al. 1997). The effects of neuroleptic treatment on regional cerebral blood flow (rCBF) and metabolism are not yet clear . ...
... Only nine of the 15 patients studied by Keshavan group were diagnosed with schizophrenia, while the remaining six had other psychotic disorders. The VOI was located in the prefrontal cortex in their study; in ours the VOI was placed in the temporal lobe, which has been associated with positive symptoms representing reality distortion that are alleviated substantially by administration of neuroleptics (Fukuzako et al. 1996;Klemm et al. 1996;Nordahl et al. 1996;Sabri et al. 1997). In contrast, the frontal lobe reportedly has been associated with negative symptoms (psychomotor poverty) and disorganization syndromes that often resist neuroleptic treatment (Liddle et al. 1992;Kaplan et al. 1993;Shioiri et al. 1994;Deicken et al. 1995). ...
Using 31P magnetic resonance spectroscopy, we examined changes in the levels of phosphorus metabolites in the temporal lobes of 13 schizophrenic patients before and 12 weeks after initiating haloperidol treatment. Spectra were obtained from a volume of interest positioned in each temporal lobe. Findings were compared with those in 13 age- and gender-matched healthy subjects. Prior to treatment the patients showed higher levels of phosphodiesters (PDE) in both temporal lobes than healthy subjects. Haloperidol administration significantly reduced the excess of PDE in the left temporal lobe, although the PDE concentration remained somewhat higher bilaterally than in controls. Treatment was associated with a decline in the total symptom score according to the Brief Psychiatric Rating Scale and the score for positive symptoms showed a relatively high correlation with reduction in PDE level in the left temporal lobe. These preliminary results suggest that haloperidol may partially normalize disturbed metabolism or abnormalities in components of membrane phospholipids in the left temporal lobe of untreated schizophrenic patients, paralleling symptom alleviation.
... This pattern of relative memory deficit is consistent with recent studies showing that depressed individuals tend to show temporal lobe hypometabolism during resting baselines on functional imaging scans (cf. George, Ketter, & Post, 1993;Klemm et al., 1996). Furthermore, structural imaging methods have detailed hippocampal abnormalities in major depression (Krishnan et al., 1991) and, in some instances, have indicated that degree of hippocampal atrophy is related to length of depressive illness (Sheline, Wang, Gado, Csernansky, & Vannier, 1996). ...
Although memory deficits are associated with major depressive disorder, few studies have identified which patient characteristics predict impairment. Because recurrent depression appears related to more severe cerebral dysfunction, the present study tested whether recurrent depressed individuals have worse memory function than first-episode depressed individuals. Two groups of young-adult, nonpsychotic, depressed inpatients (20 single episode [SE] and 46 recurrent episode [RE]) were administered the California Verbal Learning Test within a broader battery of neuropsychological tests. The groups were equivalent in age, education, estimated IQ, severity of depression, and demographic composition. The RE group demonstrated memory deficits relative to both the SE group and published norms, but no other significant difference was found across the battery. Data indicate that abnormal memory performance is associated with recurrent depression, whereas memory deficits are not prominent in first-episode depressed individuals.
... In depression, there is increased blood perfusion in the subgenual ACC and lateral OFC, which normalizes in remission (Drevets, 2007). Abnormalities in CBF of depressed patients were found in the dorsolateral prefrontal cortex, rostral and ventral ACC, amygdala, and basal ganglia (Bonne et al., 2003;Drevets, 2000;Mayberg et al., 1999): most of the studies report reduced perfusion in these regions (Klemm et al., 1996;Mayberg et al., 1994;Videbech, 2000), although contradicting results have also been described reporting an increase in activity (Abou-Saleh et al., 1999;Maes et al., 1993). In our study, we found a significant CBF increase over time in the amygdala in both groups, but the CBF changes in the amygdala did not correlate with HAM-D changes in both study groups. ...
Background
Probiotics are suggested to improve depressive symptoms via the microbiota-gut-brain axis. We have recently shown a beneficial clinical effect of probiotic supplementation in patients with depression. Their underlying neural mechanisms remain unknown.
Methods
A multimodal neuroimaging approach including diffusion tensor imaging, resting-state functional MRI, and arterial spin labeling was used to investigate the effects of a four-weeks probiotic supplementation on fronto-limbic brain structure, function, and perfusion and whether these effects were related to symptom changes.
Results
Thirty-two patients completed both imaging assessments (18 placebo and 14 probiotics group). Probiotics maintained mean diffusivity in the left uncinate fasciculus, stabilized it in the right uncinate fasciculus, and altered resting-state functional connectivity (rsFC) between limbic structures and the temporal pole to a cluster in the precuneus. Moreover, a cluster in the left superior parietal lobule showed altered rsFC to the subcallosal cortex, the left orbitofrontal cortex, and limbic structures after probiotics. In the probiotics group, structural and functional changes were partly related to decreases in depressive symptoms.
Limitations
This study has a rather small sample size. An additional follow-up MRI session would be interesting for seeing clearer changes in the relevant brain regions as clinical effects were strongest in the follow-up.
Conclusion
Probiotic supplementation is suggested to prevent neuronal degeneration along the uncinate fasciculus and alter fronto-limbic rsFC, effects that are partly related to the improvement of depressive symptoms. Elucidating the neuronal mechanisms underlying probiotics' clinical effects on depression provide potential targets for the development of more precise probiotic treatments.
... Disruption of the genu is demonstrated in association with dPD [45,46], impulse control disorders [47,48], dementia [49] and deficits in different domains of cognitive performance such as executive function, attention and memory in PD [50,51]. The posterior part of CC, the splenium, interconnects the high-order association areas of temporo-parietal lobes which are also shown to be disrupted in depressed individuals [52][53][54]. Although one study using DTI tractography found intact interhemispheric connectivity comparing dPD to ndPD and healthy controls though with a sample size of 6 in each group [20], several studies have demonstrated that reduced integrity of CC is associated with more severe depressive symptoms [55][56][57]. ...
Depression is a significant disabling feature in Parkinson’s disease (PD). However, the neuropathology of this comorbidity is still unclear. In fact, few studies have tried to elucidate the neural correlates of depression in PD and have mostly examined specific regions of interest. In this study, we applied diffusion MRI connectometry, a powerful complementary approach to investigate alterations in whole white matter pathways regarding the severity of depressive symptoms. Using a multiple regression model, the correlation of severity of depressive symptoms assessed by the Hospital Anxiety and Depression Scale (HADS) with white matter connectivity was surveyed in 27 non-demented PD patients related to 26 age, sex, and educational level-matched healthy subjects. Results revealed areas, where white matter quantitative anisotropy (QA) was correlated with depression score in PD patients, without any significant association in healthy controls. The analysis showed a significant negative association (false discovery rate < 0.05) between scores on depression subscale of HADS in PD patients and QA of left Cingulum, Genu, and Splenium of the Corpus Callosum, and anterior and posterior limbs of the right internal capsule. This finding might improve our understanding of the neural basis of depression and its severity in PD.
... Disruption of the genu is demonstrated in association with dPD [45,46], impulse control disorders [47,48], dementia [49] and deficits in different domains of cognitive performance such as executive function, attention and memory in PD [50,51]. The posterior part of CC, the splenium, interconnects the high-order association areas of temporo-parietal lobes which are also shown to be disrupted in depressed individuals [52][53][54]. Although one study using DTI tractography found intact interhemispheric connectivity comparing dPD to ndPD and healthy controls though with a sample size of 6 in each group [20], several studies have demonstrated that reduced integrity of CC is associated with more severe depressive symptoms [55][56][57]. ...
... This points up a need for a more physiologically based taxonomy of mental disorders (e.g., Harro & Oreland, 1996). And finally, the emergence of imaging technologies such as PET, SPECT, and functional MRI is refocusing the attention of neuroscientists on the realm of brain function rather than structure (e.g., George et al., 1993;El-Hilu et al., 1997;Klemm et al., 1996). ...
This book chapter introduces neurofeedback into a world still shaped by the DSM Model of discrete disorders that are structurally rooted and grounded in a neurochemical model. It presents the case for the disregulation model, characterized by a small number of key failure modes that lie largely in the bioelectrical domain. Foundational is cerebral stability, followed by arousal regulation, setpoints of activation and autonomic balance. These are accessible to us via reinforcement techniques such as operant conditioning on the frequency-basis of neural organization.
Clinical results on populations of ADHD and learning disabled children furnish evidence of the success of the training protocols. A surprising result was startling gains in WISC-R IQ scores with the earliest protocols that were broadly adopted. The method is shown to generalize across the anxiety-depression spectrum and the more challenging disorders, including autism, Tourette Syndrome, traumatic brain injury, and early childhood developmental deficits.
... Neuroimaging studies have found negative symptoms to be associated with hypoactivity of the DLPFC (Sabri et al., 1997;Gonul et al., 2003;Klemm et al., 1996;Potkin et al., 2002). The increase of activation of the right PFC, including the right DLPFC, is the first evidence in schizophrenia patients to support the underlying rationale for rTMS treatment for negative symptoms: that it would increase activation of the frontal cortex. ...
... This points up a need for a more physiologically based taxonomy of mental disorders (e.g., Harro & Oreland, 1996). And finally, the emergence of imaging technologies such as PET, SPECT, and functional MRI is refocusing the attention of neuroscientists on the realm of brain function rather than structure (e.g., George et al., 1993;El-Hilu et al., 1997;Klemm et al., 1996). ...
This chapter discusses the electroencephalogram EEG Biofeedback, which is an emerging model for its global efficacy. EEG biofeedback has a favorable research history for both epilepsy and attention deficit hyperactivity disorder (ADHD). A model has been presented in the chapter in which ADHD and its comorbidities can be seen as a composite or spectrum disorder, grounded in the disregulation of basic neurophysiological mechanisms underlying attentional, cognitive, and effective function. This model has been extended so that much of psychopathology can be seen in neurophysiological terms such as “disorders of disregulation,” traceable to a relatively small number of characteristic failure modes of the brain acting as a control system. The EEG biofeedback training for a large variety of conditions has been accomplished to date with a parsimonious set of protocols. Such protocols had their origins in basic research, but have since been evolved and refined empirically. These protocols can be motivated by a straightforward partitioning of brain function in the spatial and frequency domains. Such remediation may result in the essentially complete amelioration of symptoms attendant to various disorders, many of which have been refractory to standard medical interventions. Clinical data indicate that broad generalization of these principles may be possible to the domain of psychopathology at large, including, among others, the dissociative disorders, addictions, eating disorders, and even personality disorders. Discovery and validation through research of the practical implications of brain regulation in the bioelectrical domain could potentially lead to a scientific revolution comparable to the development of pharmacotherapy in both the therapeutic and the scientific realm.
... In keeping with the large number of structural imaging studies, several imaging studies examined the functional brain correlates of negative symptoms in schizophrenia. Most positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies found that negative symptoms are strongly associated with decreased frontal and prefrontal metabolism at rest or during activation [55][56][57][58][59][60][61]. ...
Studies investigating neurobiological bases of negative symptoms of schizophrenia failed to provide consistent findings, possibly due to the heterogeneity of this psychopathological construct. We tried to review the findings published to date investigating neurobiological abnormalities after reducing the heterogeneity of the negative symptoms construct. The literature in electronic databases as well as citations and major articles are reviewed with respect to the phenomenology, pathology, genetics and neurobiology of schizophrenia. We searched PubMed with the keywords "negative symptoms," "deficit schizophrenia," "persistent negative symptoms," "neurotransmissions," "neuroimaging" and "genetic." Additional articles were identified by manually checking the reference lists of the relevant publications. Publications in English were considered, and unpublished studies, conference abstracts and poster presentations were not included. Structural and functional imaging studies addressed the issue of neurobiological background of negative symptoms from several perspectives (considering them as a unitary construct, focusing on primary and/or persistent negative symptoms and, more recently, clustering them into factors), but produced discrepant findings. The examined studies provided evidence suggesting that even primary and persistent negative symptoms include different psychopathological constructs, probably reflecting the dysfunction of different neurobiological substrates. Furthermore, they suggest that complex alterations in multiple neurotransmitter systems and genetic variants might influence the expression of negative symptoms in schizophrenia. On the whole, the reviewed findings, representing the distillation of a large body of disparate data, suggest that further deconstruction of negative symptomatology into more elementary components is needed to gain insight into underlying neurobiological mechanisms.
... Neuroimaging studies have found negative symptoms to be associated with left DLPFC (Klemm et al. 1996) and right DLPFC dysfunction (Wolkin et al. 1992;Potkin et al. 2002), and also with bilateral DLPFC dysfunction (Sabri et al. 1997;Gonul et al. 2003). Also, several studies have found negative symptoms to be associated with a diminished blood flow in the fronto-parietal brain circuits (Lahti et al. 2001;Gonul et al. 2003). ...
Background:
Few studies have investigated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment for negative symptoms of schizophrenia, reporting inconsistent results. We aimed to investigate whether 10 Hz stimulation of the bilateral dorsolateral prefrontal cortex during 3 weeks enhances treatment effects.
Method:
A multicenter double-blind randomized controlled trial was performed in 32 patients with schizophrenia or schizo-affective disorder, and moderate to severe negative symptoms [Positive and Negative Syndrome Scale (PANSS) negative subscale ⩾15]. Patients were randomized to a 3-week course of active or sham rTMS. Primary outcome was severity of negative symptoms as measured with the Scale for the Assessment of Negative Symptoms (SANS) and the PANSS negative symptom score. Secondary outcome measures included cognition, insight, quality of life and mood. Subjects were followed up at 4 weeks and at 3 months. For analysis of the data a mixed-effects linear model was used.
Results:
A significant improvement of the SANS in the active group compared with sham up to 3 months follow-up (p = 0.03) was found. The PANSS negative symptom scores did not show a significant change (p = 0.19). Of the cognitive tests, only one showed a significant improvement after rTMS as compared with sham. Finally, a significant change of insight was found with better scores in the treatment group.
Conclusions:
Bilateral 10 Hz prefrontal rTMS reduced negative symptoms, as measured with the SANS. More studies are needed to investigate optimal parameters for rTMS, the cognitive effects and the neural basis.
... Specifically, the reduction of the entire volume of the superior temporal gyrus correlates with the positive syndrome [67,68], whereas the decrease of its anterior part correlates with auditory hallucinations [69]. The abnormalities of regional cerebral blood flow in the left temporal lobe might also be related to the positive symptoms in SZ [70]. Interestingly, the SZ-like psychoses with positive symptoms in epilepsy are associated with the left temporal lobe lesions [71]. ...
... Using SPECT or positron emission tomography (PET) imaging, pathological perfusion asymmetries, especially in the frontal and temporal areas, have been documented in numerous studies, although the results have been inconsistent. For example, in patients with schizophrenia, unilateral (usually on the left side) or bilateral temporal lobe hypoperfusion [22, 29, 35] frequently associated with frontal lobe hypoperfusion [14, 22, 35], has been reported. In patients with depression, decreased or increased rCBF has been observed in the frontal area of one or both sides, occasionally accompanied by left temporal hypoperfusion [5, 17]. ...
Oral cenesthopathy is a somatic delusion or hallucination involving the oral area and is categorized as a delusional disorder, somatic type. The pathophysiology of this intractable condition remains obscure. In this study, we clarified the pathophysiology of oral cenesthopathy by evaluating regional brain perfusion. We performed single photon emission computed tomography (SPECT) using (99m)Tc-ethylcysteinate dimer in 16 subjects (cenesthopathy:control = 8:8). The SPECT images were visually assessed qualitatively, and quantitative analyses were also performed using a three-dimensional stereotactic region-of-interest template. The visual assessment revealed a right > left perfusion asymmetry in broad areas of the brain among the patients. The quantitative analysis confirmed that the regional cerebral blood flow values on the right side were significantly larger than those on the left side for most areas of the brain in the patients. A comparison of the R/(R + L) ratios in both groups confirmed the significant brain perfusion asymmetry between the two sides in the callosomarginal, precentral, and temporal regions in the patients. Qualitative evaluation of the SPECT images revealed right > left brain perfusion asymmetry in broad regions of the brain. Moreover, the quantitative analyses confirmed the perfusion asymmetry between the two sides in the frontal and temporal areas. Those may provide the key for elucidation of the pathophysiology of oral cenesthopathy.
... Psychosen demonstrieren [Flor-Henry 1969, Manchanda et al. 1996, Mendez et al. 1993, Perez et al. 1985, Senqoku et al. 1983, Sherwin 1981 Epilepsien konnte jedoch in anderen Studien nicht nachgewiesen werden. [Adachi et al. 2002b, Onuma et al. 1995, Schmitz und Wolf 1995, Schmitz et al. 1999 Temporallappens auch ein veränderter Blutfluss im Frontallappen [Catafau et al. 1994, Klemm et al. 1996. Baumgartner et al. benutzten [ Hippokampusstruktur nicht nachgewiesen werden konnte [Marsh et al. 2001]. ...
Bisher wurde die Prävalenz psychopathologischer Auffälligkeiten bei fokalen pharmakoresistenten Epilepsien und das Outcome des psychiatrischen Status nach epilepsiechirurgischen Interventionen nur in wenigen, meist kleineren Studien untersucht. Um die Prävalenz und Prognose inter- sowie periiktaler psychiatrischer Störungen bei Epilepsiekranken im epilepsiechirurgischen Procedere zu bestimmen, wurden zwischen 1999 und 2002 am Epilepsiezentrum der Universität Freiburg 154 erwachsene Epilepsiechirurgiekandidaten psychiatrisch nach einem standardisierten Protokoll präoperativ untersucht. Innerhalb der gleichen Zeitspanne unterzogen sich 84 dieser Patienten einem epilepsiechirurgischen Eingriff und wurden 3- und 12 Monate postoperativ psychiatrisch vorgestellt.
In der Querschnittsanalyse der präoperativen Psychopathologie erfüllten 60% der Patienten die Kriterien einer ICD-10- oder einer epilepsietypischen psychiatrischen Diagnose. Es zeigte sich somit eine 2- bis 4-fache Prävalenzrate psychiatrischer Diagnosen im Vergleich zur Allgemeinbevölkerung. Die epilepsietypische dysphorische Störung war mit einer Prävalenz von 27% das häufigste psychiatrische Syndrom. Dabei waren Frauen signifikant häufiger betroffen als Männer. Es zeigte sich ein spezifischer Zusammenhang zwischen der dysphorischen Störung und den temporo-mesialen sowie frontalen Anfallsursprüngen. Gleichzeitig wurden positive Korrelationen zwischen der Prävalenz der dysphorischen Störung und der Frequenz der komplex-fokalen Anfälle sowie der Präsenz von Angstaura festgestellt. Diese Befunde weisen auf eine besondere Rolle der temporo-fronto-limbischen Strukturen bei der Pathogenese der dysphorischen Störung hin. Ferner ergab sich eine spezifische Assoziation der Epilepsiepsychosen mit dem Vorhandensein von Fieberkrämpfen in der Vorgeschichte, mit linksseitigen temporo-mesialen Anfallsursprüngen sowie bilateraler und multifokaler EEG- oder MRT-Pathologie. Persönlichkeitsstörungen wurden insbesondere bei den Patienten mit schweren, therapierefraktären und frühmanifesten Epilepsieformen festgestellt.
In der Längsschnittsanalyse des postoperativen psychiatrischen Outcomes entwickelten 18% der Fälle „de novo“ interiktale affektive Syndrome, deren Inzidenz innerhalb der ersten drei postoperativen Monate am höchsten war und die oft mit intermittierenden, wechselnd depressiv-dysphorischen und milden euphorischen Zuständen einhergingen. Andererseits wurde bei keinem der Patienten ein „de novo“ auftretendes paranoid-halluzinatorisches Syndrom postoperativ beobachtet. Darüber hinaus beobachteten wir bis zu einem Jahr postoperativ keine weiteren klinischen Manifestationen der präoperativ festgestellten postiktalen Psychosen. Ferner kamen 48% der präoperativ diagnostizierten affektiven Syndrome bzw. 62% der präoperativ festgestellten dysphorischen Störungen zu weitgehender Remission innerhalb des ersten postoperativen Jahres. In unserer Studie war die Remission der präoperativ festgestellten Psychopathologie mit einem besseren Anfallsoutcome sowie mit einem verbesserten psychosozialen Status assoziiert. Es zeigte sich kein signifikanter Zusammenhang zwischen dem postoperativen psychiatrischen Outcome und der Lateralität oder Lokalisation der Epilepsiechirurgie.
... These studies applied diverse methodologies. Studies involving resting measure of CBF with PET [ 15 O] (Andreasen et al. 1997), PET [ n C]fluorodeoxyglucose (Bertollo et al. 1996), and SPECT 99m Tc-hexamethylpropyleneamine oxime (Kawasaki et al. 1996; Klemm et al. 1996a; Miller et al. 1997; Sabri et al. 1997) have ...
Brain laterality in schizophrenia has been examined through the application of functional neuroimaging methods. These methods have included the 133Xenon technique for measuring cerebral blood flow (CBF); positron emission tomography for assessing rates of glucose metabolism, CBF, and neuroreceptor functioning; single photon emission computerized tomography for studying CBF and neuroreceptors; and functional magnetic resonance imaging for measuring changes attributable to CBF. This article highlights the application of this technology in schizophrenia research, emphasizing more recent studies that have evaluated hemispheric differences. There is evidence for lateralized abnormalities in some studies that have examined this dimension. In general, the results implicate abnormalities in left hemispheric activity. Recent advances in basic and clinical neuroscience provide an opportunity for focused application of functional imaging in neurobiological studies of schizophrenia.
... This pattern of relative memory deficit is consistent with recent studies showing that depressed individuals tend to show temporal lobe hypometabolism during resting baselines on functional imaging scans (cf. George, Ketter, & Post, 1993;Klemm et al., 1996). Furthermore, structural imaging methods have detailed hippocampal abnormalities in major depression (Krishnan et al., 1991) and, in some instances, have indicated that degree of hippocampal atrophy is related to length of depressive illness (Sheline, Wang, Gado, Csernansky, & Vannier, 1996). ...
Although memory deficits are associated with major depressive disorder, few studies have identified which patient characteristics predict impairment. Because recurrent depression appears related to more severe cerebral dysfunction, the present study tested whether recurrent depressed individuals have worse memory function than first-episode depressed individuals. Two groups of young-adult, nonpsychotic, depressed inpatients (20 single episode [SE] and 46 recurrent episode [RE]) were administered the California Verbal Learning Test within a broader battery of neuropsychological tests. The groups were equivalent in age, education, estimated IQ, severity of depression, and demographic composition. The RE group demonstrated memory deficits relative to both the SE group and published norms, but no other significant difference was found across the battery. Data indicate that abnormal memory performance is associated with recurrent depression, whereas memory deficits are not prominent in first-episode depressed individuals.
... These studies have shown that functional and structural dysfunction is related to deficits in the superior and middle temporal gyri (Shenton et al., 1992; Turetsky et al., 1995; McGuire et al., 1996 McGuire et al., , 1998 ). Positive symptoms have also been linked to the temporal cortex in schizophrenia in rCBF resting state studies (Klemm et al., 1996 ). In the present study, no activation deficits were found in the STG in patients with schizophrenia. ...
Functional brain imaging studies of working memory (WM) in schizophrenia have yielded inconsistent results regarding deficits in the dorsolateral prefrontal (DLPFC) and parietal cortices. In spite of its potential importance in schizophrenia, there have been few investigations of WM deficits using auditory stimuli and no functional imaging studies have attempted to relate brain activation during auditory WM to positive and negative symptoms of schizophrenia. We used a two-back auditory WM paradigm in a functional MRI study of men with schizophrenia (N = 11) and controls (N = 13). Region of interest analysis was used to investigate group differences in activation as well as correlations with symptom scores from the Brief Psychiatric Rating Scale. Patients with schizophrenia performed significantly worse and were slower than control subjects in the WM task. Patients also showed decreased lateralization of activation and significant WM related activation deficits in the left and right DLPFC, frontal operculum, inferior parietal, and superior parietal cortex but not in the anterior cingulate or superior temporal gyrus. These results indicate that in addition to the prefrontal cortex, parietal cortex function is also disrupted during WM in schizophrenia. Withdrawal-retardation symptom scores were inversely correlated with frontal operculum activation. Thinking disturbance symptom scores were inversely correlated with right DLPFC activation. Our findings suggest an association between thinking disturbance symptoms, particularly unusual thought content, and disrupted WM processing in schizophrenia.
... The current data suggest that temporal lobe change may be associated with the more chronic and progressive course of schizophrenia. Greater decreases in functional activity in the temporal lobe have also been associated with higher levels of symptomatology in SPECT studies (e.g., Klemm et al., 1996; Kawasaki et al., 1996). The temporal lobes, along with the frontal lobes and basal ganglia, have long been targeted as structures of special interest in schizophrenia (for review, see Buchsbaum, 1990; Buchsbaum and Hazlett, 1998). ...
We studied two subtypes of schizophrenia. the Kraepelinian subtype (n = 10) characterized by an unremitting and severe course and the non-Kraepelinian subtype (n = 17) characterized by a remitting course and some periods of self-care. Patients were assessed with positron emission tomography (PET) with 18F-deoxyglucose (FDG) and high-resolution magnetic resonance imaging (MRI). A group of 32 age- and sex-matched normal volunteers served as comparison subjects. During the FDG tracer uptake period, patients performed a serial verbal learning task. MR images were segmented into gray, white and cerebrospinal fluid regions, and warped to average normal coordinates. PET images were coregistered to the MR images and similarly warpedfor analysis. Kraepelinian subtype patients were characterized by lower metabolic rates in the temporal lobe and cingulategyrus. and lower fronto/occipital ratios than non-Kraepelinian subtype patients. Exploratory statistical probability mapping alsorevealed lower metabolic rates in the right striatum in Kraepelinian versus non-Kraepelinian patients. These differences couldnot be attributed to differences in age, symptom severity, task performance during FDG uptake, or severity of involuntary movements. Factor analysis of the cortical surface identified significantly lower temporal lobe metabolic rates in Kraepelinian patients than non-Kraepelinian patients. A combined frontal/temporal deficit or greater cortical change may be associated with poorer longitudinal course.
Background
Major depression is a common comorbidity in cancer patients. Oncology clinics lack practical, objective tools for simultaneous evaluation of cancer and major depression. Fludeoxyglucose F-18 positron emission tomography–computed tomography (FDG PET/CT) is universally applied in modern medicine.
Methods
We used a retrospective analysis of whole-body FDG PET/CT images to identify brain regional metabolic patterns of major depression in multiple myeloma patients. The study included 134 multiple myeloma (MM) patients, 38 with major depression (group 1) and 96 without major depression (group 2).
Results
In the current study, Statistic Parameter Mapping (SPM) demonstrated that the major depression patient group (n = 38) had significant regional metabolic differences (clusters of continuous voxels) as compared to the non-major depression group (n = 96) with the criteria of height threshold T = 4.38 and extent threshold > 100 voxels. The five significant hypo- and three hyper-metabolic clusters from the computed T contrast maps were localized on the glass-brain view, consistent with published brain metabolic changes in major depression patients. Subsequently, using these clusters as features for classification learner, the fine tree and medium tree algorithms from 25 classification algorithms best fitted our data (accuracy 0.85%; AUC 0.88; sensitivity 79%; and specificity 88%).
Conclusion
This study demonstrated that whole-body FDG PET/CT scans could provide added value for screening for major depression in cancer patients in addition to staging and evaluating response to chemoradiation therapies.
This article gives in his second part a critical review of the clinical applications of SPECT with perfusion markers and receptor ligands in dementing disorders and psychosis. In addition this review discusses clinical applications of SPECT investigations with perfusion markers in inflammatory diseases of the central nervous system and in brain trauma.
Objective: To explore the role of single photon emission computed tomography (SPECT) in diagnosis and location of brain dysfunction in schizophrenia and major depression. Methods: Regional cerebral blood flow (rCBF) of 39 patients (27 with schizophrenia and 12 with major depression) who suffered from the diseases and did not take medicine and 10 normal controls were examined by SPECT. The 27 patients with schizophrenia were tested with positive and negative syndrome (PANSS) and 12 patients with depression were tested with Homilton (HAMD). Results: The positive rates of rCBF abnormality in positive symptom group of schizophrenia, negative symptom group of schizophrenia and depression group were 54.54%, 75.00% and 83.33%, respectively. The decrease of rCBF in patients with schizophrenia and depression was the main feature. The rCBF abnormality in schizophrenia group involved temporal, frontal, parietal lobes and there was a correlation between the reduction of rCBF in frontal and negative symptom of schizophrenia. The decrease of rCBF in patients with depression was in the temporal or frontal lobes and rCBF abnormality was mainly in the left brain. Conclusion: There were different features in rCBF abnormality between subtypes of schizophrenia and depression. SPECT is very important in diagnosis and study of location of brain dysfunction in schizophrenia and depression.
One of the fundamental prerequisites of the successful schizophrenia treatment is represented by an adequately significant impact on the negative symptoms of schizophrenia. The current majority opinion is that rTMS could be an efficient non-pharmacological method in the treatment of the negative symptoms of schizophrenia. However, the problem consists in the low amount of patients included, different profile of negative symptoms, variable stimulating parameters or the absence of longer monitoring of the stimulating effect survival in the majority of the studies. The meta-analyses indicate that the effect rate is mild to moderate (d=0.43 to 0.68) according to the character of studies included into the statistical analysis. It may be summarized that there will be higher probability of the rTMS effect on the negative symptoms in case of 10Hz stimulating frequency and longer stimulation period, reaching at least three, ideally four to six weeks. Although rTMS bears a promising potential, especially for the augmenting treatment of the negative symptoms which are resistant to the treatment with antipsychotic drugs, further studies are needed to verify a genuine clinically significant efficacy of rTMS in this clinical indication.
Repetitive transcranial magnetic stimulation, which is used in psychiatry primarily for the treatment of the depressive disorder, isolated auditory hallucinations or obsessively compulsive disorder, represents a new therapeutic modality able to affect negative schizophrenia symptoms thanks to its unique ability to modulate neuronal activity of the cortical cerebral areas and neuronal circuits which are included into the pathophysiology of schizophrenia not only directly but also indirectly, by means of transsynaptic transfer. Theoretical substantiation of the repetitive transcranial magnetic stimulation efficacy in the event of negative schizophrenia symptoms lies in the fact that the high-frequency repetitive transcranial magnetic stimulation shows an activating impact on the neurons of the cerebral cortex. Negative correlation between the activity of the frontal cortex and severity of negative symptoms has been repeatedly demonstrated. Another, no less important fact consists in the effect of dopamine release from the mesolimbic and mesostriatal cerebral system by high-frequency stimulation of the frontal cortex. The mesolimbic brain structures play a key role in the pathogenesis of negative schizophrenic symptoms. Most of the studies have arrived at the conclusion that repetitive transcranial magnetic stimulation is an efficient method in the treatment of negative symptoms of schizophrenia. In our own study, whose objective was to show the impact of high frequency repetitive transcranial magnetic stimulation applied over the area of the left prefrontal cortex using the maximum stimulating intensity on the alleviation of the intensity of negative schizophrenia symptoms. Every patient was stimulated 15 times on workdays of three consecutive weeks. The real stimulation treatment led to a statistically significant decrease in the intensity of negative schizophrenia symptoms. The authors ascribe the rate of reduction of the negative symptoms intensity, which they consider clinically significant, to the number of 15 stimulation sessions, which was one of the highest number of stimulation sessions in the studies dealing with this issue. A valuable contribution for the assessment of rTMS application in the treatment of negative symptoms is brough about by meta-analyses. They have shown that the rate of effect is mild to moderate (d=0.43 to 0.68) based on the character of studies included into the statistic analysis. To sum it up, there will be higher probability of the repetitive transcranial magnetic stimulation effect on negative symptoms if 10 Hz stimulating frequency and a longer stimulation period in the extent at least three, ideally four to six weeks is used. Although rTMS represents a promising potential, especially for the augmenting treatment of negative symptoms resistant to antipsychotic drugs treatment, further studies are necessary for the verification of really clinically significant efficacy of rTMS in this clinical indication.
Parkinson's disease is frequently accompanied by depression which can have a negative effect on a patient's cognitive performance, quality of life and activities of daily living. Because Parkinson's disease and depression have a number of symptoms in common, it is sometimes difficult to distinguish the two disorders. Furthermore, the overlapping pathophysiology may make it difficult to treat depressive symptoms without influencing the patients motor or cognitive functions. This narrative review summarises our current knowledge concerning the epidemiology, etiology, pathophysiology and treatment of depression inpatients with Parkinson's disease. Clearly, however, many questions remain unanswered. In particular, research is needed into the efficacy of currently available treatments for depression so that it becomes possible to develop evidence-based guidelines.
This paper describes the guideline for perfusion brain imaging with SPECT-technique published by the Association of the Scientific Medical Societies in Germany (AWMF).The purpose of this guideline is to provide practical assistance for indication, examination procedures, findings and their interpretation also reflecting the present state of the art. Information and instruction are given regarding indication, preparation of the patients and examination procedures of brain perfusion SPECT, including preparation and quality control of the tracer as well as the radiation dosimetry, technical performance of image acquisition with the gamma-camera and image processing. Also advices for interpretation of findings are given. In addition, possible pitfalls are described.
Single photon emission tomography (SPECT) with 99mTc-HMPAO was used to compare regional cerebral blood flow (rCBF) in patients with unipolar and bipolar depression. The study group consisted of 10 unipolar depressed patients and seven bipolar depressed patients who met the DSM-III-R criteria for major depressive disorder (MDD). Nine physically and mentally healthy volunteers served as control subjects. SPECT images were obtained in the patients at two time points: (1) during the major depressive episode before patients had received medication; and (2) at the beginning of the remitted state while patients were receiving antidepressant medication. During the depressive episode, unmedicated unipolar depressed patients showed relatively increased left frontal rCBF compared both with the control subjects and the bipolar patients (P
In zahlreichen Studien wird darauf hingewiesen, daß bei älteren Patienten eine depressive Verstimmung zu selten diagnostiziert wird. Ältere Depressive zeigen im Vergleich zu jüngeren Depressiven oft wenig charakteristische psychopathologische Symptome. Häufig werden somatische Beschwerden und kognitive Beeinträchtigungen angegeben, die diagnostisch schwer einzuordnen sind. Oft wird eine zerebrovaskuläre Störung als wesentliche Ursache einer depressiven Verstimmung im Alter angesehen. Kürzlich haben Alexopoulos et al. (1997) das Konzept einer vaskulären Depression (VD) entwickelt, das sich deutlich vom Konzept der Depression nach Schlaganfall, das v.a. von Robinson and Starkstein vertreten wird, unterscheidet. Dieses neue Konzept wird kritisch diskutiert und hinsichtlich seiner klinischen Anwendbarkeit überprüft. Klinisch ist es. da es nicht wie die ICD-10 Leitlinien einen meist nur schwer nachweisbaren zeitlichen Zusammenhang zwischen Auftreten der psychopathologischen Symptomatik und einem zerebrovaskulären Ereignis fordert, praktikabler. Dennoch erscheint die Unterteilung der vaskulären Depression anhand der CT/MRI-Befunde in zwei Untertypen sinnvoller. Der Typ I (Makroangiopathie) entspricht weitgehend der Depression nach Schlaganfall, während der Typ II der Beschreibung von Alexopoulos et al. gleicht und meist mit einer Mikroangiopathie einhergeht. Mögliche sich hieraus ergebende Therapieansätze sind noch nicht untersucht worden. Auch bedarf das Konzept der vaskulären Depression, das bisher nur auf zwei klinischen Studien basiert, einer weiteren Bestätigung.
Objective:
Despite the development of second-generation antipsychotic drugs, treatment-resistant symptoms still represent a serious problem in schizophrenia. The aim of the present article was to review studies with repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia and draw conclusions for clinical decision making.
Method:
Literature for this review was identified by searching MEDLINE and ISI Web of Science up to the year 2011.
Results:
Five open studies, 13 sham-controlled studies, and 2 meta-analysis and 2 review articles were included in the present paper. The effect size of the high frequency repetitive transcranial magnetic stimulation (rTMS) over the left prefrontal cortex in the treatment of negative symptoms of schizophrenia is thought to be mild to moderate (Cohen d = 0.43-0.68).
Conclusion:
Despite the promising results of some rTMS studies, the potential of rTMS for the treatment of negative symptoms is currently relatively unclear. Large clinical studies are therefore needed, especially large multicentric studies such as depression rTMS studies.
Structured psychiatric interviews were administered to 60 children with complex partial seizure disorder (CPS). 40 children with primary generalized epilepsy with absences (PGE), and 48 control children, aged 5 to 16 years. Significantly more patients with epilepsy had psychiatric diagnoses compared with the control children. There were no statistically significant differences, however, in the number of patients with CPS and PGE with psychiatric diagnoses. Other than a schizophrenia-like psychosis found only in the patients with CPS, the two groups of patients had similar psychiatric diagnoses. The presence of psychopathology was related to significantly lower IQ scores and socioeconomic status, but not to seizure-related factors. These findings suggest that the psychopathology of children with CPS and PGE reflects different subtle neuropsychological deficits.
We have not encountered any brain single-photon emission tomography (SPET) study performed in adolescent depressed patients
in the literature. Therefore, we used technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) brain SPET in adolescent patients with major depressive disorder (MDD) to examine the possible changes in cerebral
perfusion and the possible association between perfusion indices and clinical variables. Fourteen adolescent out-patients
(nine females, five males; mean±SD age: 13.11±1.43 years; range: 11–15 years) fulfilling the DSM-IV criteria for MDD and 11
age-matched healthy control subjects (six females, five males; mean±SD age: 13.80±1.60 years; range: 12–15 years) were included
in the study. 99Tc-HMPAO brain SPET was performed twice in the patient group and once in the control group. The first SPET investigation was
performed under non-medicated conditions and the second was performed after depressive symptoms had subsided. A relative perfusion
index (PI) was calculated as the ratio of regional cortical activity to the whole brain activity. We found significant differences
between the PI values of the untreated depressed patients and those of the controls, indicating relatively reduced perfusion
in the left anterofrontal and left temporal cortical areas. No significant differences in regional PI values were found between
the remitted depressed patients and the controls. Our study suggests that adolescent patients with MDD may have regional cerebral
blood flow deficits in frontal regions and a greater anterofrontal right-left perfusion asymmetry compared with normal subjects.
The fact that these abnormalities in perfusion indices have a trend toward normal values with symptomatic improvement suggests
that they may be state-dependent markers for adolescent MDD.
1.1. Studies with Single Photon Emission Computed Tomography (SPECT) in schizophrenia research have utilized different approaches to normalization of data, such as cerebellar ratio and whole brain ratio methods, leading to conflicting findings.2.2. The authors compared these two methods to test the hypofrontality hypothesis of schizophrenia.3.3. Eighteen chronic and medicated DSM-IV schizophrenic patients and 10 healthy controls underwent two SPECT examinations using 99mTc-HMPAO as a tracer at baseline and during frontal activation while applying the Wisconsin Card Sorting Test.4.4. The hypofrontality hypothesis was supported with both indexes of relative perfusion, although the whole brain ratio method appeared to be more reliable and specific than the cerebellar ratio method.5.5. Further studies are required to confirm these preliminary results on the specificity and sensitivity of both methods.
Das Klassifikationsschema der Schizophrenien nach Positiv- und Negativsymptomatik (Andreasen 1987) hat sich sowohl im wissenschaftlichen als auch im klinischen Kontext weitestgehend durchgesetzt. Hierbei ist Negativsymptomatik
zumeist charakterisiert durch Affektverflachung, Antriebsminderung, Anhedonie, sozialen Rückzug und Gedankenverarmung. Aufgrund
der hohen Bedeutung für langfristige Rehabilitation und Wiedereingliederung stellt die Aufklärung der neurobiologischen Grundlagen
von Negativsymptomatik eine große Herausforderung dar. Obwohl das Konzept einer Unterteilung in Positiv- und Negativsymptomatik
bereits längere Zeit existiert, sind die zugrunde liegenden neurobiologischen Prozesse für diese klinischen Subsyndrome bislang
nur wenig bekannt.
Technologic advances in functional brain imaging have provided exciting and informative insights into the functional neuroanatomy and neurochemistry of schizophrenia. Using MR spectroscopy, it has been possible to examine in vivo brain metabolism and to relate observed changes to physiological processes occurring at a cellular level. Positron emission tomography and single photon emission computed tomography have revealed disturbances of cerebral blood flow and glucose metabolism in patients with schizophrenia. More recently, these tools have also proved most useful in studying the relative receptor occupancy of typical and atypical antipsychotic medications.
One of the fundamental prerequisites of the successful schizophrenia treatment is represented by an adequately significant impact on the negative symptoms of schizophrenia. Since the present pharmacotherapy has probably reached its limit in this area, there is a logical effort to utilize other, non-pharmacological methods. One of the most promising supplements that has been for a long time verified in the clinical practice is rTMS. Most of the studies have arrived at the conclusion that rTMS is an efficient method in the treatment of negative symptoms of schizophrenia. A valuable contribution to the assessment of the rTMS application in the treatment of negative symptoms is represented by meta-analyses. The meta-analyses indicate that the effect is mild to moderate (d=0.43 to 0.68). To sum it up, there will be higher probability of the rTMS effect on negative symptoms if 10 Hz stimulating frequency and a longer stimulation period in the extent at least three, ideally four to six weeks is used.
Repetitive transcranial magnetic stimulation (rTMS) is increasingly being investigated as a potential treatment for a number of psychiatric disorders, including schizophrenia. Previous rTMS studies have targeted the left-side prefrontal cortex (PFC) in the treatment of negative symptoms, with inconsistent findings. Some imaging evidence suggests right-sided or bilateral PFC involvement in negative symptoms, areas yet to be investigated for rTMS treatment. The study therefore aimed to assess the efficacy of bilateral high-frequency rTMS in the treatment of negative symptoms.
A 2-arm double-blind randomized controlled trial was conducted with 20 patients with a diagnosis of schizophrenia or schizoaffective disorder, and moderate-to-severe treatment-resistant negative symptoms. Participants received a 3-week course of high-frequency bilateral rTMS or sham. Twenty trains (5 seconds duration) of 10 Hz rTMS at 110% of the RMT were administered to each PFC daily, 5 days a week.
No significant group or time differences in the Scale for the Assessment of Negative Symptoms (SANS) scores or cognitive outcomes were evident. However, a trend for greater reduction in scores on the autistic preoccupation scale of the Positive and Negative Symptom Scale for the active group compared to the sham group was observed (P = .05).
No substantial benefit of high-frequency bilateral rTMS was seen in the treatment of the negative symptoms of schizophrenia. Further research is required to explore whether rTMS may have benefits specific to particular cognitive or symptom domains.
Complex dynamical networks are ubiquitous in many fields of science from engineering to biology, physics, and sociology. Collective behavior, and in particular synchronization,) is one of the most interesting consequences of interaction of dynamical systems over complex networks. In this thesis we study some aspects of synchronization in dynamical networks. The first section of the study discuses the problem of synchronizability in dynamical networks. Although synchronizability, i.e. the ease by which interacting dynamical systems can synchronize their activity, has been frequently used in research studies, there is no single interpretation for that. Here we give some possible interpretations of synchronizability and investigate to what extent they coincide. We show that in unweighted dynamical networks different interpretations of synchronizability do not lie in the same line, in general. However, in networks with high degrees of synchronization properties, the networks with properly assigned weights for the links or the ones with well-performed link rewirings, the different interpretations of synchronizability go hand in hand. We also show that networks with nonidentical diffusive connections whose weights are assigned using the connection-graph-stability method are better synchronizable compared to networks with identical diffusive couplings. Furthermore, we give an algorithm based on node and edge betweenness centrality measures to enhance the synchronizability of dynamical networks. The algorithm is tested on some artificially constructed dynamical networks as well as on some real-world networks from different disciplines. In the second section we study the synchronization phenomenon in networks of Hindmarsh-Rose neurons. First, the complete synchronization of Hindmarsh-Rose neurons over Newman-Watts networks is investigated. By numerically solving the differential equations of the dynamical network as well as using the master-stability-function method we determine the synchronizing coupling strength for diffusively coupled Hindmarsh-Rose neurons. We also consider clustered networks with dense intra-cluster connections and sparse inter-cluster links. In such networks, the synchronizability is more influenced by the inter-cluster links than intra-cluster connections. We also consider the case where the neurons are coupled through both electrical and chemical connections and obtain the synchronizing coupling strength using numerical calculations. We investigate the behavior of interacting locally synchronized gamma oscillations. We construct a network of minimal number of neurons producing synchronized gamma oscillations. By simulating giant networks of this minimal module we study the dependence of the spike synchrony on some parameters of the network such as the probability and strength of excitatory/inhibitory couplings, parameter mismatch, correlation of thalamic input and transmission time-delay. In the third section of the thesis we study the interdependencies within the time series obtained through electroencephalography (EEG) and give the EEG specific maps for patients suffering from schizophrenia or Alzheimer's disease. Capturing the collective coherent spatiotemporal activity of neuronal populations measured by high density EEG is addressed using measures estimating the synchronization within multivariate time series. Our EEG power analysis on schizophrenic patients, which is based on a new parametrization of the multichannel EEG, shows a relative increase of power in alpha rhythm over the anterior brain regions against its reduction over posterior regions. The correlations of these patterns with the clinical picture of schizophrenia as well as discriminating of the schizophrenia patients from normal control subjects supports the concept of hypofrontality in schizophrenia and renders the alpha rhythm as a sensitive marker of it. By applying a multivariate synchronization estimator, called S-estimator, we reveal the whole-head synchronization topography in schizophrenia. Our finding shows bilaterally increased synchronization over temporal brain regions and decreased synchronization over the postcentral/parietal brain regions. The topography is stable over the course of several months as well as over all conventional EEG frequency bands. Moreover, it correlates with the severity of the illness characterized by positive and negative syndrome scales. We also reveal the EEG features specific to early Alzheimer's disease by applying multivariate phase synchronization method. Our analyses result in a specific map characterized by a decrease in the values of phase synchronization over the fronto-temporal and an increase over temporo-parieto-occipital region predominantly of the left hemisphere. These abnormalities in the synchronization maps correlate with the clinical scores associated to the patients and are able to discriminate patients from normal control subjects with high precision.
Patients with schizophrenia often fail to respond to standard antipsychotic medications or have a partial treatment response. Few treatment options are available for these patients. Repetitive transcranial magnetic stimulation (rTMS) was developed and investigated over the last 10 years as a potential treatment option for various psychiatric conditions.
Increasingly, studies are focusing on potential applications of rTMS in schizophrenia. To date, most of these studies were symptom-specific rather than focused on the treatment of the disorder in general. The most extensive literature focuses on the use of low-frequency stimulation to attempt to disrupt or reduce the intensity of persistent refractory auditory hallucinations. This research tends to suggest that rTMS could have a role in this subset of patients. There is also preliminary but limited evidence that rTMS could have a role in reducing the negative symptoms of schizophrenia and perhaps in augmenting cognitive function. These findings also highlight the pressing need for further research including multisite studies to confirm the value of these options.
The aims of the present study were to investigate regional cerebral blood flow (rCBF) in heroin-dependent patients during withdrawal and to assess the relation between these changes and duration of heroin consumption and withdrawal data. The rCBF was measured using brain SPECT with 99mTc-HMPAO in 16 heroin-dependent patients during heroin withdrawal. Thirteen patients received levomethadone at the time of the SPECT scans. The images were analyzed both visually and quantitatively. A total of 21 hypoperfused brain regions were observed in 11 of the 16 patients. The temporal lobes were the most affected area, hypoperfusions of the right and left temporal lobe were observed in 5 and 5 patients, respectively. Three of the patients had a hypoperfusion of the right frontal lobe, 2 patients showed perfusion defects in the left frontal lobe, right parietal lobe and left parietal lobe. The results of the quantitative assessments of the rCBF were consistent with the results of the qualitative findings. The stepwise regression analysis showed a significant positive correlation (r = 0.54) between the dose of levomethadone at the time of the SPECT scan and the rCBF of the right parietal lobe. Other significant correlations between clinical data and rCBF were not found. The present results suggest brain perfusion abnormalities during heroin withdrawal in heroin-dependent patients, which are not due to the conditions of withdrawal.
In this work with the SPECT we tried to define the most possible the disfuntions that could exist in a group of patients with severe recurrent depression.
The sample is compound for fifteen patients (2 men and 13 woman) diagnosed of recurrent depression according CIE-10 with equal distribution between melancholic depressions and depressions with psychotic symptoms congruents and not congruents with the state of mood. The mean age of the group is of 55.4 years. All the patients have been studied with de SPECT (Tc-HMPAO) during the first week of hospitalization. The severity of the depressive syndrome was studied with the questionnaire for depression of Beck and the state of anxiety was studied with the questionnaire of anxiety of Spielberger. All the patients were severes depressives and anxious according to the questionnaires.
We appreciated disfunction, hypocaptation, in frontoorbital zones, well bilateral (mainly in recurrent depressions with psychotic symptoms) or only in the left frontal side (areas of Brodmann 10 and 11) mainly in recurrent melancholies. We also found that in almost all the patients existed hypocaptation in the left angular circunvolution (areas of Brodmann 37 and 39). In the recurrent melancholies the localization of the hypocaptation is fundamentally posterior parietotemporal in the left side.
In the recurrent serious depressions the hypocaptation is located to prefrontal level with tendency to bilateral being and/or posterior parietotemporal left side, that in the melancholies the localization of the hypocaptation is fundamentally posterior parietotemporal in the left side and it could imply that when the severity clinic gets complicated with psychotic symptoms the hypocaptation is located in a bigger number of places (prefrontal and left posterior parietotemporal) in relation to what it happens in the melancholic depressions. It seems to exist relationship between depressive and anxious severity and localization of the hypocaptation.
Studies using single photon emission computed tomography (SPECT) have found low cerebral blood flow (CBF) in frontal and parietal cortices in patients with chronic opiate dependence. In the present study, SPECT with 99mTc-HMPAO as tracer was used to compare 27 detoxified opiate addicts with nine healthy control subjects. All the subjects were evaluated with clinical psychiatric (DSM-IV), psychometric and neuropsychological measures. Compared with normal control subjects, the addicts showed a non-significant reduction of whole brain perfusion values. Significant hypoperfusion in the right frontal and left temporal lobes was found in addicts with comorbid depression, and a significant decrease in CBF in the right frontal lobe was observed in those with antisocial tendencies. A significant negative correlation emerged between Depression subscale scores on the Minnesota Multiphasic Personality Inventory and left temporal CBF in the patients. No significant correlations were found, however, between measures of cognition and CBF in opiate addicts. The asymmetrical findings in CBF that characterized the addicts relative to normal control subjects may be more closely related to mood and behavioral traits than to substance abuse, per se.
Structured psychiatric interviews were administered to 60 children with complex partial seizure disorder (CPS), 40 children with primary generalized epilepsy with absences (PGE), and 48 control children, aged 5 to 16 years. Significantly more patients with epilepsy had psychiatric diagnoses compared with the control children. There were no statistically significant differences, however, in the number of patients with CPS and PGE with psychiatric diagnoses. Other than a schizophrenia-like psychosis found only in the patients with CPS, the two groups of patients had similar psychiatric diagnoses. The presence of psychopathology was related to significantly lower IQ scores and socioeconomic status, but not to seizure-related factors. These findings suggest that the psychopathology of children with CPS and PGE reflects different subtle neuropsychological deficits.
In 17 antipsychotic-naive schizophrenic patients, the scores of positive and negative symptoms of schizophrenia were correlated with relative regional cerebral perfusion measured by 99m-Tc-ECD (ethyl cysteinate dimer) single photon emission computed tomography (SPECT). Scans were performed in subjects at rest. The negative symptom dimension was significantly correlated with a decreased level of perfusion in the left thalamic region. Other non-significant trends were also observed; the positive symptom dimension was related to decreased perfusion in the left temporal region and to increased perfusion in the right frontal region, while the negative symptom dimension was related to increased perfusion in the left frontal region. These findings suggest that the positive and negative symptoms of schizophrenia are related to dysfunctions in different regions of the brain and different lateralized patterns of dysfunction.
Psychomotor slowing is a fundamental clinical feature of severe depression and is thought to reflect dysfunction within prefrontal-subcortical circuits. This study utilised a split-dose single photon emission computerised tomography (SPECT) scanning technique in association with a two-stage test of psychomotor speed. Twenty-five patients with primary depressive disorders were injected with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) whilst performing each component of a two-stage psychomotor task. The first stage, 'simple reaction time' (RT) and the second stage, 'choice reaction time' (CRT), were each followed by 30-min SPECT scans. Regions of interest (ROIs) corresponding to the left and right neo-striatum (caudate-putamen) were drawn, and regional cerebral blood flow (rCBF) values were calculated. Importantly, the change in rCBF measure in the left neo-striatum was inversely correlated with RT (r = -0.48, P < 0.05). That is, the patients with the greatest psychomotor slowing initially showed the least increase in rCBF during the CRT condition. This effect was independent of age. The study demonstrates that a simple two-stage motor paradigm can be used to elicit rCBF correlates of psychomotor slowing in patients with primary depression. Such rCBF findings may implicate the neo-striatum in the neurobiology of major depression.
The objective of this study was to examine the central nervous system changes that may occur after acceleration/deceleration injuries in motor vehicle accidents.
Occupants of motor vehicles involved in a collision often develop a disabling syndrome consisting of head, neck, and back pain; impaired short-term memory and concentration; fatigue and a loss of stamina; poor balance; and a change in personality. Injury victims experience a loss of motivation, emotional lability, and a decrease in libido. The major features of this injury syndrome are subjective, and there usually are few objective findings on physical examination. The pathogenesis of this syndrome is poorly understood, but it is hypothesized that the collision impact produces an inertial strain injury to the anterior regions of the brain which depresses the functions of the frontotemporal lobes, at the same time, sensitizing somatosensory neural afferent systems. Damage to the orbital surfaces of the frontotemporal lobes, in particular, impairs the gating mechanisms that normally limit sensory input to the brain and further promotes central sensitization. The psychiatric disorders that emerge in the wake of these injuries are likely grounded in these pathologic events.
The current literature on the biomechanics of head injury and the associated brain imaging findings in minor head injury are reviewed. A summary of some of the biochemical sequelae of strain injury to the brain is also provided, with an emphasis on the changes in energy metabolism and excitatory amino acid release.
Early intervention to arrest the injury-induced metabolic cascade, and treatment with agents that activate cerebral metabolism may mitigate the symptoms of this injury syndrome.
In order to investigate cerebral perfusion changes induced by neuroleptic drugs, we performed 99Tc(m) hexamethyl propyleneamine oxime (HMPAO) single-photon emission computed tomography (SPET). Fifteen patients (nine drug naive, six non-naive) diagnosed by using the DSM-III-R criteria, and 10 right-handed age and sex matched normal volunteers were included in this study. The SPET study was performed with 740 MBq 99Tc(m)-HMPAO by using a 128 x 128 matrix, 30 s/frame for a total 64 view over 360 degrees before and after 1 month of neuroleptic treatment. A semiquantitative method was used for the analysis. Patients were clinically assessed using the Brief Psychiatric Rating Scale (BPRS). There was no significant regional cerebral blood flow (rCBF) difference between the patient group and control group in whole-brain regions except in the left temporal lobe. Although clinical scores of the patients improved after neuroleptic treatment no statistically significant difference was found in the rCBF between pre- and post-treatment. Moreover, there was no statistically significant correlation between the rCBF and BPRS in any region. These results suggest that there was a discrepancy between the clinical situation and rCBF in schizophrenia and the lateralized temporal lobe blood flow, which may have important implications for the evaluation of patients with schizophrenia.
The aim of this preliminary study is to investigate the regional blood flow in response to ECT (electroconvulsive therapy) and to identify any responsive-pattern to the treatment.
Single longitudinal prospective study of cohorts.
For this preliminary study ten patients, female sex, mean age 70.8 years with major mood disorder (CID-10 investigation criteria) were studied after signature consent.
The intervention consisted in the administration of bilateral brief pulse ECT three times a week, during 6 to 12 sessions according to the standards of the Psychiatric Department of the Santiago Hospital in Victoria.
Clinical evaluation of depression was evaluated by Hamilton Depression Scale, Montgomery and Asberg Scale, Newcastle Scale and regional cerebral blood flow (rCBF) using the HMPAO-SPECT.
The pattern of distribution on the regional cerebral flow during the ECT showed changes from the basal pattern in all patients. All patients had a relative increased perfusion of the temporal lobes and basal ganglia. Other changes from the basal study were areas of decreased perfusion of the occipital lobe (6 patients) and parietal lobe (3 patients).
Brain perfusion SPECT study of the patients with major depression shows changes during ECT. Further analysis are needed to understand the relationship between mechanisms of treatment and recovery in affective illness.
1. Negative schizophrenic and unipolar depressive patients were clinically assessed. In addition to this SANS and HRSD tests were administered. 2. SPECT and AEP measurements were provided. SPECT resulted in quantified brain blood perfusion, by means of average "count/pixel" values in the brain regions of interest. AEPs resulted in stored multichannel signal waveforms. 3. Statistical analyses of blood perfusion measurement data revealed an overall similarity between these two disorders in the majority of brain regions. An exception to this are the regions: inferior temporalis, inferior occipitalis, hippocampus and the anterior basal ganglia. Both diagnostic groups manifested hypofrontality. In general, hypoperfusion of the left hemisphere was found, albeit displaying different patterns in the two groups investigated. 4. AEP latencies were prolonged and found to be similar in both diagnostic groups, whilst AEP amplitudes were smaller in schizophrenics compared to depressives.
Postnatal treatment between 8 to 21 days of age with clomipramine (15 mg/kg, twice daily) produces an animal model that has many of the behavioral hallmarks of depression. In this study, we investigated the enduring behavioral and neurochemical effects of this early treatment in adult animals. Locomotor activity was increased in clomipramine-treated males, but not females, relative to vehicle-treated subjects. Increases in anxiety-like behavior in the elevated plus maze also were observed in clomipramine-exposed adults, but no sex differences were detected. Clomipramine-treated animals had shifts in the laterality of monoamines in limbic regions with lower serotonin levels on the right side while vehicle-treated animals had lower serotonin on the left side. The lateralization of dopamine content demonstrated the same pattern. This decline in monoaminergic content is consistent with clinical studies demonstrating decrements in serotonin as well as alterations in the lateralization of function in individuals with major depressive order.
Positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose was performed in nine chronic schizophrenic patients both when medication-free and when medicated with neuroleptics. Total brain cortex, temporal cortex, and basal ganglia glucose use was significantly increased with medication; however, there was no change in anterior/posterior metabolic gradientsKeywords: Basal ganglia; Neuroleptics; Schizophrenia; Temporal cortex.
Depletion of dopamine in a circumscribed area of association cortex in rhesus monkeys produces an impairment in spatial delayed
alternation performance nearly as severe as that caused by surgical ablation of the same area. This behavioral deficit can
be pharmacologically reversed with dopamine agonists such as L-dopa and apomorphine. These data provide direct evidence that
dopamine plays an important role in a specific cortical function.
Positron emission tomography was used to study the relationship between rCBF and symptom profiles in 30 schizophrenic patients. Factor analysis confirmed that the symptoms segregated into three syndromes--psychomotor poverty, disorganisation, and reality distortion--described previously. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in paralimbic and association cortex, and in related subcortical nuclei. The study confirmed predictions that psychomotor poverty and disorganisation are associated with altered perfusion at different loci in the pre-frontal cortex, and reality distortion with altered perfusion in the medial temporal lobe. The perfusion patterns suggest that the abnormalities of brain function underlying each of the three syndromes are not confined to single loci, but involve distributed neuronal networks.
Regional cerebral blood flow at rest was measured in 38 patients with major depressive disorders and 16 controls by SPECT with inhalation of xenon-133. All subjects had been withdrawn from medication. The mean hemispheric cerebral blood flow was not statistically different between the controls and the different subgroups of depressed patients defined either by biological markers or clinical characteristics. However, the predominantly cortical blood flow, measured on the outer cerebral rim of the third tomographic slice, was significantly lower on the left hemisphere in bipolar patients when compared with normals and unipolar patients. The same lateralisation was observed in patients with an endogenous depression according to the Newcastle scale.
With evidence that determinants of psychosis are present early and influence brain development, and in the absence of a significant
environmental contribution, schizophrenia may be regarded as a genetic encephalopathy. Morphological abnormalities are particularly apparent in the temporal lobe and on the left side of the brain, and in a number
of studies significant diagnosis × side interactions have been detected. Such interactions suggest an intimate relationship
between the disease process and the mechanisms that determine asymmetrical brain development. These mechanisms presumably
relate to the human capacity for speech and communication, and they may have played a critical role in the evolution of the
human brain. A candidate locus for an asymmetry determinant and the psychosis gene within the exchange region of the sex chromosomes
is proposed. Some sex differences in schizophrenia (e.g., with respect to age of onset and brain structure) may relate to
subtle differences in the rate of asymmetry development in the two sexes.
Local cerebral uptake of glucose labelled with fluorine-18 was measured by positron emission tomography in 13 patients with schizophrenia and 37 right-handed volunteers. Patients received no medication for a minimum of 31 days and a mean of 30 weeks. The subjects were administered the labelled deoxyglucose just after the beginning of a 32-minute sequence of blurred numbers as visual stimuli for the Continuous Performance Test. In normal controls, task performance was associated with increases in glucose metabolic rate in the right frontal and right temporoparietal regions; occipital rates were unchanged. Patients with schizophrenia showed both absolutely and relatively reduced metabolic rates in the frontal cortex and in the temporoparietal regions compared with normal controls.
Temporal lobe structure has been assessed by magnetic resonance imaging in groups of patients with schizophrenia (n = 21) bipolar affective disorder (n = 20) and normal controls (n = 21). In the temporal lobe area a significant (p less than 0.05) diagnosis by side interaction was present, the area being less on the left than on the right side in patients with schizophrenia in contrast to findings in the two other groups. Lateral ventricular and temporal horn area did not distinguish the groups as a whole. However, there was a significant (p less than 0.05) relationship between lateral ventricular area and poor outcome, and in an analysis confined to males, patients with schizophrenia (n = 15) were found to have significantly (p less than 0.05) enlarged temporal horns.
• Local cerebral uptake of deoxyglucose labeled with fluorine 18 was measured by positron emission tomography in 16 patients with schizophrenia and 11 patients with affective disorder. Patients received no medication a minimum of 14 days and an average of 39.8 days. The subjects were administered the deoxyglucose 18F just before receiving a 34-minute 1/s series of unpleasant electrical stimuli to the right forearm while resting with eyes closed in a darkened, acoustically attenuated psychophysiologic testing chamber. Following monitored stimulation in the controlled environment, subjects were scanned and images converted to values of glucose use in micromoles per 100 g per minute according to Sokoloff's model. Data were analyzed with a four-way analysis of variance (ANOVA) with independent groups (normals, schizophrenics, and affectives) and repeated measures for slice level (supraventricular, midventricular, and infraventricular), hemisphere (right, left), and anteroposterior position (four sectors). Both normal subjects and patients showed a significant anteroposterior gradient in glucose use with highest values in the frontmost sector. Patients both with schizophrenia and with affective illness showed less of an anteroposterior gradient especially at superior levels, which was statistically confirmed by ANOVA. Absolute glucose levels in patients, which were actually higher in posterior regions rather than lower in frontal regions, were the largest contributors to the effect. Neither group differences in whole brain glucose use nor left-right asymmetries reached statistical significance. These results are consistent with our earlier reports of a relative hypofrontal function in schizophrenia compared with controls. This report extends this finding to affective illness, sharing a lack of diagnostic specificity with many biologic measures.
• This study examines whether the duration of treatment with antipsychotic drugs influences the regional distribution of cerebral [18F]2-fluoro-2-deoxy-D-glucose utilization as measured by positron emission tomography. Two groups of schizophrenic patients are compared with normal volunteers (n =10). One group (n = 5) consisted of patients treated for one year, and the second (n=12) of patients medicated for four to 14 years (mean ± SD duration, 7.4±3.4 years). The first group was also examined before patients received their first dose ever of antipsychotic medication. One year of medication was not sufficient to alter the schizophrenic profile of cerebral cortical glucose activity but did elevate activity of the corpus striatum. Medication for 7.4 years also did not alter the schizophrenic pattern of frontal hyperactivity and posterior hypoactivity, although deviations from control values appeared less marked than after one year. On the other hand, in patients medicated for 7.4 years, there was perhaps an even greater increase in the activity of the corpus striatum and of the thalamus. Thus, duration of exposure to antipsychotic medication may affect the pattern of cerebral glucose activity; possibly, even longer exposure may contribute to the hypofrontality noted by others, although this can be confounded with the duration of illness as a factor. In considering the biological significance of the observed profile of cortical glucose activity, we introduce the concept of cerebral metabolic tone. We suggest that a disturbance of this tonus may account for some symptoms of schizophrenia and could be consistent with the hypothesis of abnormal developmental changes in the brains of schizophrenics.
DEPRESSIVE disorders are conditions whose high prevalence1,2 and frequent need for medical intervention3 require increased understanding in the general medical community. Antidepressants are prescribed with increasing frequency by a wide range of medical practitioners and a recent listing of the most prescribed drugs included seven antidepressants.4 Data from an ongoing National Institute of Mental Health epidemiologic study,2 using diagnostic criteria from DSM-III,5 indicate that in the general population there is a six-month prevalence of depressive disorders (bipolar and unipolar) of about 5%. Furthermore, over 75% of persons with recent depressive disorders have sought medical treatment of some type in the last six months and nearly half of all mental health—related visits made by depressed individuals are to general medical practitioners.3 These figures constitute a compelling reason for all physicians to be familiar with the typology of depressive disorders.
In psychiatry, as in all fields
• The "hypofrontality hypothesis" has been supported by many neuroimaging studies, but not all, perhaps because of heterogeneity of samples. The present study examined three different samples that permitted assessment of a variety of confounders, such as effects of long-term treatment, chronicity of illness, and presenting phenomenology: (1) 13 neuroleptic-naive schizophrenic patients, (2) 23 nonnaive schizophrenic patients who had been relatively chronically ill but were medication free for at least 3 weeks, and (3) 15 healthy normal volunteers. Regional cerebral blood flow was measured using single-photon emission computed tomography with xenon 133 as the tracer. The control condition consisted of looking at undulating colored shapes on a video monitor, while the experimental task was the Tower of London. We observed the Tower of London to be a relatively specific stimulant of the left mesial frontal cortex (probably including parts of the cingulate gyrus) in healthy normal volunteers. Both the neuroleptic-naive and the nonnaive patients lacked this area of activation, as well as a related one in the right parietal cortex (representing the circuitry specifically activated by the Tower of London). Decreased activation occurred only in the patients with high scores for negative symptoms. These results suggest that hypofrontality is related to negative symptoms and is not a long-term effect of neuroleptic treatment or of chronicity of illness.
• We studied hippocampal sections from 13 schizophrenic patients, 9 nonschizophrenic patients, and 16 normal controls from the Yakovlev brain collection. The three groups were similar in age, gender distribution, and brain weight. Most patients had never received neuroleptics, and the two patient groups had had similar types of leukotomies. We used a semiautomated image analysis system to compute volume and pyramidal-cell density in each of the four sectors of the cornu ammonis, CA1 through CA4, in the right and left hippocampi. Sections from schizophrenic patients had almost consistently the lowest volume and pyramidal-cell density in all sectors. The differences were greatest in left CA4, with schizophrenic patients having significantly lower pyramidal-cell density than normal controls and significantly lower volume than leukotomy controls. Our findings confirm the results of several recent studies showing hippocampal pathologic features in schizophrenia. Our study suggests, however, that the hippocampal neuropathologic findings in schizophrenia may be more subtle and more localized than those reported previously.
The objective of this study was to search for regional cerebral blood flow (rCBF) abnormalities in adolescents with initial-stage schizophrenia by means of brain single-photon emission tomography (SPET) using technetium-99m hexamethylpropylene amine oxime (HMPAO). SPET studies were performed on a homogeneous sample of 15 carefully selected adolescents with a recent diagnosis of schizophrenia, and without previous electroconvulsive or antipsychotic drug treatment. Computed tomography (CT) and electro-encephalographic (EEG) studies were performed in all patients. Qualitative and semiquantitative analysis of99mTc-HMPAO SPET studies showed an impaired rCBF in 12 patients (80%). The most common pattern was a decreased uptake of99mTc-HMPAO in the frontal lobes, usually in the left hemisphere. Conventional and quantitative EEG was positive in 12 (80%) and 15 (100%) patients, respectively. CT findings were positive in two patients (13%). There was a high level of concordance between SPET and EEG results and between SPET and clinical features (P>0.05). This study suggests that previously untreated patients in the first stages of schizophrenia present functional abnormalities that are revealed by brain SPET.
To investigate whether volume reduction of the hippocampal formation of schizophrenics, as described previously, is paralleled by loss of neurons and fibre systems, tissue volumes and cell numbers of all parts of the hippocampal formation in post mortem brains of 13 schizophrencis and 11 agematched controls belonging to the Vogt collection were determined.
Volumes of the whole hippocampal formation (P < 0.01), the whole pyramidal band (P < 0.001) and the hippocampal segments CA1/CA2 (P < 0.01), CA3 (P < 0.05), CA4 (P < 0.01) were decreased, whereas no significant volume reduction of the alveus and fimbria hippocampi and presubiculum/subiculum could be found. The perforant path showed a trend towards volume reduction (P < 0.1).
The absolute number of pyramidal cells (tissue volume × cell density) was diminished in CA1/CA2 (P < 0.05), CA3 (P < 0.05) and CA4 (P < 0.05), but was not significantly changed in the prosubiculum/subiculum, the presubiculum/parasubiculum and the granular cell layer of the dentate fascia.
Pyramidal cell loss in CA1/CA2, CA3, CA4 was more distinct in the paranoid patients than in catatonics. The findings are discussed with respect to current hypotheses of limbic dysfunction in schizophrenia.
Pathomorphology of the limbic system has been described in postmortem studies of schizophrenia. To determine whether this could be detected in living patients and was not secondary to the treatment or the chronicity of the disease itself, we measured the volumes of the hippocampus-amygdala complex and adjoining temporal horns of 34 patients in their first episode of schizophrenia and 25 normal volunteers using T1 weighted contiguous coronal magnetic resonance images of 3.1 mm width. The results demonstrate abnormal medial temporal lobe morphology in a subgroup of patients at the onset of their illness. There were clear laterality effects and sex differences: hippocampal tissue was significantly smaller only in the left hemisphere of male patients, whereas enlargement of the whole temporal horn or its anterior portion was present on the left side in both sexes. Dysfunction of the limbic mesiotemporal structures might explain some of the clinical features of the disease.
Our previous observation of a disturbed subcortical-to-cortical gradient of activity in schizophrenia was further elucidated by examining glucose metabolism in three subcortical structures: lenticular nucleus, caudate nucleus, and thalamus. Local cerebral glucose metabolism was determined with 18F- fluorodeoxyglucose using positron emission tomography (PET) in a sample of 20 unmedicated schizphrenics and 18 normal volunteers. Repeated evaluations were performed for 12 schizophrenics following treatment with psychotropic medications and for 11 controls. Unmedicated schizophrenics had lower cortical and caudate absolute metabolic rates. Subcortical-to-cortical ratios for the lenticular nucleus and thalamus were increased in schizophrenics compared with controls, reflecting a preservation of activity in these structures relative to decreased cortical metabolism. When patients were grouped by length of medication-free period before the initial study, there was a trend for patients who had been medication free < 6 months to have higher subcortical ratios. However, there were no consistent effects of medication in the subsample of patients whose PET studies were repeated following treatment. The results demonstrate relative hypermetabolism in structures implicated in dopamine pathways. An understanding of the physiological significance of this finding awaits the combined measurement of metabolic activity and neuroreceptors in schizophrenics.
Using [11C]-deoxy-D-glucose and positron emission tomography (PET), the authors measured brain metabolism in 18 patients with chronic schizophrenia to assess which of the metabolic measures from two test conditions was more closely related to the patients' differing clinical characteristics. The two conditions were resting and activation, and an eye tracking task was used. Patients with more negative symptoms showed lower global metabolic rates and more severe hypofrontality than did the patients with fewer negative symptoms. Differences among the patients were distinguished by the task: sicker patients failed to show a metabolic activation response. These findings suggest that cerebral metabolic patterns reflect clinical characteristics of schizophrenic patients.
In this essay many lines of evidence relevant to the problem of the organization of the cerebral mood systems are surveyed: the study of penetrating head injuries, cerebrovascular accidents, cerebral tumors, psychiatric surgery, bilateral and unilateral nondominant and dominant ECT, temporal lobe epilepsy, the psychometrical and neuropsychological correlates of the endogenous psychoses, the power spectral EEG characteristics of depressive and manic psychoses, dichotic stimulation in the manic-depressive syndrome, the patterns of lateralized cognitive activation in normals, the electrodermal characteristics of depression, the differential hemispheric reactivity of the right and left brain in normals and depressives under carotid barbiturization, the characteristics of REM sleep, the lateralization of pain and of the orgasmic response in relation to mood, the evidence for the presence of lateralized neurochemical as well as neurophysiological and neuropsychological asymmetry in the nervous system, and the intrication of sinistrality, cerebral visuospatial organization, and gender. The synthesis of extremely diverse types of evidence not normally considered in the same perspective does not pretend to be a systematic review of the various fields discussed. Yet because certain underlying principles of cerebral organization and disorganization are in this manner suggested, it may have some heuristic value.
Frontal lobe dysfunction is widely suspected to underlie negative symptoms of schizophrenia. This hypothesis is based largely on long-standing observations of the similarities between the effects of frontal lobe lesions and negative symptoms. However, there is little direct evidence specifically for such an association in schizophrenic patients. We measured the relationship between decreased relative prefrontal cortex glucose metabolism (hypofrontality) using positron emission tomography and evaluated the severity of negative symptoms in 20 chronic schizophrenics who underwent scanning while not receiving neuroleptic drugs. We found a close relationship between negative symptoms and prefrontal hypometabolism, particularly in the right dorsolateral convexity. This association was regionally specific. Furthermore, there was no evidence that this relationship was an artifact of age, cerebral atrophy, or severity of positive symptoms.
Synopsis
Using positron emission tomography (PET) and ¹⁵ Oxygen, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex ( P < 0·05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis ( P < 0·05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder.
Forty patients with a major depressive episode were investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, an intravenous ligand taken into brain in proportion to regional cerebral blood flow, thereby providing an estimate of regional metabolism. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. They also completed a range of neuropsychological tests. They were compared with 20 control subjects matched for age, gender, premorbid intelligence and education. The uptake of 99mTc-exametazime was expressed for a range of anatomically defined regions of interest relative to calcarine/occipital cortex. The depressed group showed reduced uptake in the majority of cortical and sub-cortical regions examined, most significantly in temporal, inferior frontal and parietal areas. Unexpectedly, there was a strong positive association between uptake and scores on the Newcastle scale, especially in cingulate areas and frontal cortex. After removing the variance attributable to the Newcastle ratings, however, there emerged the expected negative association between Hamilton scores and anterior tracer uptake. The associations between neuropsychological impairment and regional brain uptake of tracer in part reflected the pattern seen with the Newcastle scale: for example, impairment of memory function correlated with higher uptake into posterior cingulate areas. We propose that depressive illness may be characterised by two processes. One leads to an overall reduction in anterior neocortical function, perhaps related to symptom severity. The other mechanism is manifest as relatively increased function, most notably within cingulate and frontal areas of the cerebral cortex in association with psychotic symptoms. The findings offer new understanding of the brain states underlying depressive illness and a potential focus to subsequent neuropharmacological analysis.
Regional cerebral blood flow was investigated in 14 patients with major depression diagnosed according to the DSM-III-R criteria (six patients with single and eight patients with recurrent episodes) and in ten healthy volunteers. The mean ages of the patients and the controls were 33.5 +/- 2.7 and 31.6 +/- 2.6 years, respectively. The severity of the depression was assessed using the 17-item Hamilton Depression Scale (mean: 23.2 +/- 1.5). None of the patients was under medication. After administration of 500 MBq technetium-99m hexamethylpropylene amine oxime, a single photon emission tomography study was performed and then transaxial, sagittal and coronal slices were obtained. For the semiquantitative analysis of the data, the ratios of the mean counts/pixel to the whole slice were calculated for 24 regions on three consecutive transaxial slices in the orbitomeatal plane. Additionally, left/right and frontal/occipital ratios were calculated. Both sides of the temporal region had a significantly decreased cerebral blood flow (CBF) when compared to the controls. The left/right ratio of the prefrontal region was also significantly lower in the patients than in the controls. The Hamilton score had a negative correlation with blood flow in the anterofrontal and left prefrontal regions. According to our results, regional CBF seems to be decreased in the left prefrontal and in both temporal regions in major depression. The severity of depression is correlated with the reduction in CBF in the regions of the anterofrontal and left prefrontal cortex.
Regional cerebral blood flow (rCBF) was measured in 30 schizophrenic patients with severe, persistent and stable symptoms using positron emission tomography (PET). Directed and non-directed correlational analysis of the relationship between psychopathology and rCBF was used to identify brain structures implicated in three behavioural subsyndromes of schizophrenia. Psychopathology and neurophysiology (rCBF) exhibited high correlations in the left medial temporal region, mesencephalic, thalamic and left striatal structures. The highest correlations was in the left parahippocampal region. A canonical analysis of the same data highlighted the left parahippocampal region and left striatum (globus pallidus) as sites which linked the behavioural subsyndromes in terms of shared rCBF correlates.
Increasing seventy of psychopathology was associated with increased rCBF in these regions. Dismhibition of left medial temporal lobe activity mediated by fronto-limbic connections is a possible explanation for these findings; however, the prefrontal component appears to be critically dependent on the behavioural subsyndrome.
A hypothesis of psychosis localization in schizophrenia was derived from studying metabolic alterations in rat brain in response to phencyclidine hydrochloride administration. Since phencyclidine and its selective agonist dizocilpine maleate (MK801) induced overlapping and long-lasting metabolic alterations predominantly in limbic areas, the hypothesis developed that schizophrenic patients with psychosis would evidence functional abnormalities in limbic circuits compared with normal controls. Accordingly, 12 actively psychotic, drug-free patients with schizophrenia and matched normal controls underwent functional brain scans using positron emission tomography and fluorodeoxyglucose. Regions of interest were identified on five matched axial slices in each patient and control subject, and average metabolic rates were calculated. Patients with schizophrenia showed a significantly lower regional cerebral metabolic rate of glucose in the hippocampus and the anterior cingulate cortex than did normal controls, but not in neocortical areas or in the extrapyramidal system. When the group of schizophrenic patients was divided into deficit and nondeficit types, a preliminary exploratory analysis suggested thalamic, frontal, and parietal cortical hypometabolism in the deficit subgroup, with normal metabolism in the nondeficit patient group in those areas; in contrast, hippocampal and anterior cingulate cortical metabolism was reduced in both deficit and nondeficit subtypes. These results suggest that the limbic system, especially the hippocampus, is functionally involved in schizophrenic psychosis and that different manifestations of schizophrenia may involve different neuronal circuits.
Regional cerebral blood flow (rCBF) was assessed in 40 chronic male schizophrenic patients (20 medicated, 20 unmedicated) and 31 matched normal controls with Dynamic Single-photon Emission Computed Tomography (D-SPECT). Blind analyses of normalized color-coded tomograms revealed significant bifrontal and bitemporal rCBF deficits in the patient group. Frontal flow deficits were most prominent in paranoid patients (n = 21) and right temporal deficits were most prominent in nonparanoid patients (n = 19). These relative regional declines were observed within the context of significantly elevated hemispheric blood flow in schizophrenics compared with controls. Reduced left frontal rCBF was associated with neuropsychological impairment on the Wisconsin Card Sorting Test and Luria-Nebraska Battery. Increased hemispheric CBF was correlated with the presence of positive schizophrenic symptoms. Medication status was unrelated to rCBF. These findings demonstrate that hypofrontality has important implications for cognitive function in some schizophrenic individuals.
Functional brain imaging by either single photon emission computed tomography (SPECT) or positron emission tomography (PET) is now a well-established technique in the diagnosis and evaluation of the epilepsies. Perhaps only in stroke have these emerging technologies proven of greater significance. Scalp, cortical, or depth electroencephalographic (EEG) data previously have been the gold standards for the localization and subcharacterization of epileptic activity in the human brain. Yet, they are fraught with difficult interpretations, technical difficulties, and limitations in sampling accuracy. Both SPECT and PET have localizing power approaching that of combined scalp and depth EEG. In the following discussion, a brief overview of the results of PET investigations in epilepsy is presented as background and comparative material for the concurrent and, more recently, dominant role of SPECT in evaluating patients with seizure activity. SPECT results in the interictal state in partial and generalized seizure activity are reviewed followed by an analysis of the role of ictal SPECT imaging in epilepsy. Next, relationships among interictal hypoperfusion (or hypometabolism) and computed tomography, magnetic resonance imaging, neuropathology, clinical severity, and cognitive function are discussed. The role of perfusion or metabolism imaging in the management of antiepileptic pharmacotherapy is also discussed, and the potential for receptor imaging in the evaluation of the epilepsies is examined. Finally, application in pediatric epilepsy are presented.
Positron emission tomography studies with fluorodeoxyglucose in patients with schizophrenia are reviewed and findings in the frontal lobes, basal ganglia, and temporal lobes summarized from more than 20 published studies. Despite methodological and clinical population differences between studies, most reports indicate that patients with schizophrenia are more likely to be low in these areas than in the occipital lobe, cerebellum, or in white matter. This is consistent with blood flow and some neuroanatomical findings. Cluster analysis on our own sample suggests that patients may be low in all three areas rather than a pattern of three distinct clusters. Further study of individual symptom differences, medication effects, and of psychophysical tasks salient for these brain areas is indicated.
We measured regional cerebral blood flow with the xenon 133 inhalation technique in 41 patients with major depressive disorder and 40 matched, normal controls during an eyes-closed, resting condition. The depressed group had a marked reduction in global cortical blood flow. To examine topographic abnormalities, traditional multivariate analyses were applied, as well as a new scaled subprofile model developed to identify abnormal functional neural networks in clinical samples. Both approaches indicated that the depressed sample had an abnormality in topographic distribution of blood flow, in addition to the global deficit. The scaled subprofile model identified the topographic abnormality as being due to flow reduction in the depressed patients in selective frontal, central, superior temporal, and anterior parietal regions. This pattern may reflect dysfunction in the parallel distributed cortical network involving frontal and temporoparietal polymodal association areas. The extent of this topographic abnormality, as revealed by the scaled subprofile model, was associated with both patient age and severity of depressive symptoms.
The resting-state cerebral metabolic rates for glucose of 10 severely depressed patients (seven bipolar and three unipolar) were compared, before and after treatment with tricyclic antidepressants, to those of 10 control subjects of similar age by means of positron emission tomography and the fluorodeoxyglucose method. Significant left-right prefrontal asymmetry was present in the patients before but not after successful treatment, suggesting that medication can reduce this asymmetry. Also, significant hypofrontality and whole-cortex hypometabolism were found in the patients in the depressed state and persisted in the treated state, despite clinical improvement, suggesting that these abnormalities are not state dependent.
Regional cerebral blood flow (rCBF) was measured during rest and cognitive activation in 21 patients with a major depressive episode and 21 healthy subjects. Depressive patients had significantly lower rCBF during rest in the right global, frontal, parietal, occipital and temporal regions and in the left global and frontal regions. During mental activation patients showed significantly lower values in all right and left parietal regions. rCBF was correlated with the scores of the Brief Psychiatric Rating Scale (BPRS), the parietal regions. rCBF was correlated with the scores of the Brief Psychiatric Rating Scale (BPRS), the Bech-Rafaelsen Melancholia Scale (BRMS), the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A). The most significant negative correlations were obtained with the BPRS. Correlation analyses between each single item of the BPRS and CBF values revealed the strongest associations between emotional withdrawal and decreased CBF. Patients with 'reactive' features had higher CBF than patients without 'reactive' symptoms. Only patients without 'reactive' symptoms had a lower CBF than controls. 'Endogenous' features had no impact on CBF.
Forty-three depressed inpatients, referred for electroconvulsive therapy, and 30 manic patients were examined with clinical ratings and regional cerebral blood flow (rCBF) determinations. The depressed patients were mainly medication free, while most of the manic patients were medicated. Both patient groups showed a normal cerebral blood flow level and regional distribution compared with age- and sex-matched normal controls. In the depressed group and especially in the unipolar subgroup, a significant positive relationship was found between the mean rCBF and symptoms of depression and cognitive dysfunction. Eighteen of the depressed and 18 of the manic patients were reexamined in a euthymic state following treatment and recovery. Only minor and statistically nonsignificant flow changes were found in connection with the clinical improvement. In the manic patients, a significant negative relationship was found between neuroleptic dosage and rCBF.
Using positron emission tomography, we studied cerebral glucose metabolism in drug-free, age- and sex-matched, right-handed patients with unipolar depression (n = 10), bipolar depression (n = 10), obsessive-compulsive disorder (OCD) with secondary depression (n = 10), OCD without major depression (n = 14), and normal controls (n = 12). Depressed patients were matched for depression on the Hamilton Depression Rating Scale, and subjects with OCD without depression and OCD with depression had similar levels of OCD without depression and OCD with depression had similar levels of OCD pathology. We also studied si