Brain perfusion abnormalities in drug-naive, lactate-sensitive panic patients: A SPECT study

Cristofaro, Maria Teresa De; Sessarego, Antonella; Pupi, Alberto; Biondi, Francesco; Faravelli, Carlo

doi:10.1016/0006-3223(93)90004-w

Cited by 124 publications

(48 citation statements)

References 26 publications

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“…Deactivation of the parahippocampal region in healthy volunteers has been reported after panic attacks induced by lactate (Reiman et al, 1989) and CCK-4 (Javanmard et al, 1999), and with anxiety induced by presentation of combat-related images (Bremner et al, 1999b) and autobiographical memory scripts (Liotti et al, 2000). In addition, the abnormal asymmetry of resting activity in the parahippocampal gyri has been associated with panic disorder and with vulnerability to lactateinduced panic (Reiman et al, 1984(Reiman et al, , 1986Nordahl et al, 1990Nordahl et al, , 1998Bisaga et al, 1998;De Cristofaro et al, 1993). These studies suggest that anxiety can be associated with reduced parahippocampal activity, consistent with an anxiolytic effect of CBD and the increased activity in this region that we observed.…”

Section: Discussionmentioning

confidence: 99%

Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow

Crippa

Zuardi

Garrido

et al. 2003

Neuropsychopharmacol

257

224

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Animal and human studies have suggested that cannabidiol (CBD) may possess anxiolytic properties, but how these effects are mediated centrally is unknown. The aim of the present study was to investigate this using functional neuroimaging. Regional cerebral blood flow (rCBF) was measured at rest using 99m Tc-ECD SPECT in 10 healthy male volunteers, randomly divided into two groups of five subjects. Each subject was studied on two occasions, 1 week apart. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. SPECT images were acquired 90 min after drug ingestion. The Visual Analogue Mood Scale was applied to assess subjective states. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping (SPM). CBD significantly decreased subjective anxiety and increased mental sedation, while placebo did not induce significant changes. Assessment of brain regions where anxiolytic effects of CBD were predicted a priori revealed two voxel clusters of significantly decreased ECD uptake in the CBD relative to the placebo condition (po0.001, uncorrected for multiple comparisons). These included a medial temporal cluster encompassing the left amygdala-hippocampal complex, extending into the hypothalamus, and a second cluster in the left posterior cingulate gyrus. There was also a cluster of greater activity with CBD than placebo in the left parahippocampal gyrus (po0.001). These results suggest that CBD has anxiolytic properties, and that these effects are mediated by an action on limbic and paralimbic brain areas.

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Section: Discussionmentioning

confidence: 99%

Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow

Crippa

Zuardi

Garrido

et al. 2003

Neuropsychopharmacol

257

224

View full text Add to dashboard Cite

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“…Although the common and unique elements of pathophysiology underlying different human anxiety disorders are largely unknown, abnormalities of hippocampal structure and function have been observed in both PD and PTSD. Imaging studies of PD patients have consistently found abnormal bilateral asymmetries in cerebral blood flow and perfusion in the hippocampal areas (Reiman et al, 1984;Nordahl et al, 1990;De Cristofaro et al, 1993), as well as increased glucose metabolism (Bisaga et al, 1998). Imaging of GABA receptor binding revealed that a PD population had decreased benzodiazepine binding in the hippocampus (Bremner et al, 2000).…”

Section: Role Of the Hippocampus In Human Anxiety Disordersmentioning

confidence: 99%

Increased Fear Response to Contextual Cues in Mice Lacking the 5-HT1A Receptor

Klemenhagen

Gordon

David

et al. 2005

Neuropsychopharmacol

149

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Serotonin 1A receptor knockout (5-HT1AR KO) mice exhibit increased behavioral inhibition in conflict tests. To gain further insight into their anxiety-related phenotype, we subjected these mice to additional behavioral tests. First, we considered whether behavioral inhibition in these knockout mice is a consequence of reduced exploratory motivation. The knockout mice engage in normal exploration during a light-dark test and normal exploration of a novel object in a familiar environment, suggesting that the anxiety-related phenotype is not due to reduced exploratory drive. Second, we tested whether these mice exhibit increased behavioral inhibition in response to any aversive cues, or whether this response depends on cue modality. Knockout mice respond normally to discrete aversive cues in the Vogel lick-suppression test, arguing that their phenotype is restricted to conflict tests based on complex or spatial aversive cues. Third, to probe the processing of spatial aversive cues, we assessed fear conditioning to contextual cues. After contextual fear conditioning, knockout and wild-type (WT) mice express freezing responses when exposed to the training environment. However, when placed in an ambiguous environment containing both conditioned and novel cues, the freezing response of knockout mice does not significantly decrease as it does in WT mice, suggesting that the knockout fear response is biased toward threatening cues. We hypothesize that this inappropriate generalization of fearful behavior to a context containing both fearful and neutral stimuli, a phenomenon that occurs in a subset of human anxiety disorders such as panic disorder and post-traumatic stress disorder, underlies the anxiety phenotype of 5-HT1AR KO mice.

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“…To summarize, consistent with many neurobiologic theories of pathological fear and anxiety (32), most functional neuroimaging studies have found evidence of abnormal activity in frontal and limbic-paralimbic cortical areas in patients with a variety of anxiety disorders. In panic disorder, for example, abnormal hippocampal activity at baseline (33), and higher insular activation and decreased prefrontal activation during symptomatic periods, have been shown (34,35). Generally, patients with post traumatic stress disorder (PTSD) exhibit lower basal activation of the anterior cingulate and increased activation of paralimbic regions and the amygdalae, as well as greater decreases in frontal cortical regions during stressful tasks, such as trauma cues (36)(37)(38)(39)(40).…”

Section: Neuroimaging Studies Of Anxietymentioning

confidence: 99%

Anxiety, respiration, and cerebral blood flow: implications for functional brain imaging

Giardino

Friedman

Dager

2007

Comprehensive Psychiatry

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Brain functional imaging methods, such as fMRI, are sensitive to changes in cerebral blood flow (CBF) that are normally associated with changes in regional neural activation. However, other endogenous and exogenous factors can alter CBF independently of brain neural activity, thus complicating the interpretation of functional imaging data. The presence of an anxiety disorder, as well as change in state anxiety, is often accompanied by respiratory alterations that affect arterial CO 2 tensions and produce significant changes in CBF that are independent of task-related neural activation. Therefore, the effects of trait and state anxiety need to be given close consideration in interpreting functional imaging findings. In this paper, we review the dependence of most brain functional imaging methods on localized changes in CBF and the potentially confounding effects of anxiety-related alterations of respiration on interpreting patterns of functional activation. Approaches for addressing for these effects are discussed.

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Brain perfusion abnormalities in drug-naive, lactate-sensitive panic patients: A SPECT study

Cited by 124 publications

References 26 publications

Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow

Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow

Increased Fear Response to Contextual Cues in Mice Lacking the 5-HT1A Receptor

Anxiety, respiration, and cerebral blood flow: implications for functional brain imaging

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