Two-dimensional Proton Echo-Planar Spectroscopic Imaging of Brain Metabolic Changes During Lactate-Induced Panic

Dager, Stephen R.; Friedman, Seth D.; Heide, Aaron C.; Layton, Matthew E.; Richards, Todd L.; Artru, Alan A.; Strauss, Wayne; Hayes, Cecil E.; Posse, Stefan

doi:10.1001/archpsyc.56.1.70

Cited by 75 publications

(62 citation statements)

References 33 publications

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“…This confirms and extends the findings of prior studies showing elevated brain lactate responses during metabolic challenges in patients with PD. 16,[28][29][30] Increased local oxygen availability, rather than hypoxia, in response to stimulus-induced neural activation is one of the most well-established observations in neuroscience. 44,45 Since the hypoxia model attributes the consistently elevated brain lactate responses observed in PD to ischemic hypoxia, 16,20,21 it predicts that the characteristic elevation of brain lactate would not be observed in the visual cortex in PD patients during visual stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…Three studies of sodium lactate infusions and one study of hyperventilation have all observed significantly greater increases in brain lactate in PD patients. 16,[28][29][30] Some investigators proposed that the abnormal lactate response resulted from a disturbance in the dynamics of lactate metabolism in PD, 14 while others attributed it to cerebral hypoxia due to an exaggerated cerebral vasoconstriction response to alkalosis in PD. 16,20,21 It is well known that lactate accumulates under hypoxic conditions.…”

Section: Introductionmentioning

confidence: 99%

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Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study

et al. 2008

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Converging evidence suggests that patients with panic disorder have a metabolic disturbance that may influence the regulation of arousal systems and confer vulnerability to 'spontaneous' panic attacks. The consistent finding of elevated brain lactate responses to various metabolic challenges in panic disorder appears to support this model, although the mechanism of this effect is not understood. Several mechanisms have been proposed to account for elevated brain lactate responses in panic disorder, including (1) brain hypoxia due to excessive cerebral vasoconstriction, and (2) a metabolic disturbance affecting lactate metabolism. Recent studies have shown that neural activation (for example, sensory stimulation) causes local lactate accumulation in the presence of increased oxygen availability. The current study used proton magnetic resonance spectroscopic measures of visual cortex lactate changes during visual stimulation in 15 untreated patients with panic disorder and 15 matched volunteers to critically test these two proposed mechanisms of elevated brain lactate responses in panic disorder. Visual cortex lactate/N-acetylaspartate increased during visual stimulation in both groups. The increase was significantly greater in the panic patients than in the comparison group. There were no group differences in end-tidal pCO 2 . The finding that visual stimulation leads to significantly greater visual cortex lactate responses in panic patients is not predicted by the hypoxia model. These results suggest that a metabolic disturbance affecting the production or clearance of lactate is the cause of the elevated brain lactate responses consistently observed in panic disorder and provide further support for metabolic models of vulnerability to this illness.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study

et al. 2008

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“…Notably, a more rapid and substantial rise in brain lactate has been observed in panic patients as compared with control subjects (Dager et al 1999), but the difference between patients and controls may also be due to different responsiveness to a given concentration (Pohl et al 1994;Rifkin et al 1981).…”

Section: In Patients With Panic Disorder or Premenstrual Dysphoria Amentioning

confidence: 99%

Respiratory Responses to Intravenous Infusion of Sodium Lactate in Male and Female Wistar Rats

Olsson

Annerbrink

et al. 2002

Neuropsychopharmacology

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In patients with panic disorder or premenstrual dysphoria, anxiety attacks can be triggered by intravenous administration of sodium lactate. Since respiratory symptoms, such as hyperventilation and shortness of breath, are characteristic features of spontaneous as well as lactate-induced panic, an involvement of central or peripheral chemoreceptors in this reactionIn patients with panic disorder (Liebowitz et al. , 1985Pitts and McClure 1967) or premenstrual dysphoria (Facchinetti et al. 1992;Sandberg et al. 1993), but not in healthy controls, intravenous (i.v.) administration of sodium lactate elicits an anxiety reaction strongly resembling spontaneous panic attacks. The anxiogenic effect of sodium lactate has been attributed to changes in calcium concentrations (Pitts and McClure 1967), pH (Grosz andFarmer 1972), redox activity (Carr et al. 1986), pCO 2 (Gorman et al. 1988a), and osmolarity (Jensen et al. 1991;Peskind et al. 1998). However, all these theories and findings have also been questioned, and the mechanism by which sodium lactate elicits panic attacks hence is as yet unexplained.Likewise, the reason why patients with panic disorder or premenstrual dysphoria differ from controls with respect to sensitivity to lactate is a matter of controversy. Notably, a more rapid and substantial rise in brain lactate has been observed in panic patients as compared with control subjects (Dager et al. 1999), but the difference between patients and controls may also be due to different responsiveness to a given concentration (Pohl et al. 1994;Rifkin et al. 1981).Panic attacks are almost always associated with hyperventilation and respiratory discomfort, such as shortness of breath; it has thus been suggested that lactate-induced as well as spontaneous panic attacks may be due to an activation of a hyperresponsive suffocation alarm system involving activation of central or peripheral chemoreceptors (Klein 1993). Supporting this concept, an anxiety-provoking effect similar to that of lactate has been observed after inhalation of CO 2 in panic disorder subjects and in women with premenstrual dysphoria (Gorman et al. , 1988aGriez et al. 1987;Harrison et al. 1989;Kent et al. 2001;Papp et al. 1997;Perna et al. 1994;Woods et al. 1986).We have previously reported that intravenous administration of sodium lactate to Wistar rats, but not to rats of the Sprague-Dawley strain, elicits an increase in blood pressure and variable effects on heart rate (Wikander et al. 1995). Such cardiovascular response is in line with the assumption that lactate induces a stimulation of central or peripheral chemoreceptors. In the present study, the effect of sodium lactate on respiratory rate and tidal volume in freely moving, unrestrained male and female rats of the Wistar strain was explored. Given the previous reports suggesting that spontaneous panic attacks are menstrual cycle-dependent (Basoglu et al. 2000;Breier et al. 1986;Cameron et al. 1988;Cook et al. 1990;Klein 1993), that panic disorder may improve during pregnancy (Hertzberg and Wa...

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“…Clinical neuroscientists have begun to use 1H-MRS measures of brain lactate responses to characterize normal and clinical populations, although the strengths and limitations of this method are not well understood. Elevated brain lactate responses to metabolic challenges have consistently been observed in patients with panic disorder (Dager et al, 1995;Dager et al, 1999;Maddock, 2001), and these findings have recently been extended to include elevated visual cortex lactate responses to visual stimulation (Maddock and Buonocore, 2005). Richards and colleagues reported elevated lactate in left frontal regions in dyslexic boys during an oral language task and later showed normalization with treatment (Richards et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: A proton magnetic resonance spectroscopy study at 1.5 Tesla

Maddock¹,

Buonocore²,

Lavoie³

et al. 2006

Psychiatry Research: Neuroimaging

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Proton magnetic resonance spectroscopy (1H-MRS) studies showing increased lactate during neural activation support a broader role for lactate in brain energy metabolism than was traditionally recognized. 1H-MRS measures of brain lactate responses have been used to study regional brain metabolism in clinical populations. This study examined whether variations in blood glucose influence the lactate response to visual stimulation in the visual cortex. Six subjects were scanned twice, receiving either saline or 21% glucose intravenously. Using 1H-MRS at 1.5 Tesla with a long echo time (TE=288 msec), the lactate doublet was visible at 1.32 ppm in the visual cortex of all subjects. Lactate increased significantly from resting to visual stimulation. Hyperglycemia had no effect on this increase. The order of the slice-selective gradients for defining the spectroscopy voxel had a pronounced effect on the extent of contamination by signal originating outside the voxel. The results of this preliminary study demonstrate a method for observing a consistent activity-stimulated increase in brain lactate at 1.5 Tesla and show that variations in blood glucose across the normal range have little effect on this response.

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Two-dimensional Proton Echo-Planar Spectroscopic Imaging of Brain Metabolic Changes During Lactate-Induced Panic

Cited by 75 publications

References 33 publications

Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study

Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study

Respiratory Responses to Intravenous Infusion of Sodium Lactate in Male and Female Wistar Rats

Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: A proton magnetic resonance spectroscopy study at 1.5 Tesla

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