Panic Disorder Research

Brain Lactate and Treatment of Outcome in Panic Disorder

The overall objective of this research has been to identify brain abnormalities from panic disorder diagnosis and treatment outcome.  We are using proton-planar spectroscopic imaging (PEPSI) during psyschological challenges, using intravenous lactate infusion or regulated hypeventilation (hypocapnea), to measure brain metabolic changes that may help to establish the pathophysiological underpinnings of panic disorder and provide a better understanding of treatment refractoriness and relapse in this disorder.  In a series of Magnetic Resonance Spectroscopy (MRS) studies we have determined evidence of brain lactate abnormalities in individuals with panic disorder, which appear to be independent of or only indirectly related to state-dependent symptoms.


  • Kim JE, Dager SR, Lyoo IK: The role of the amygdala in the pathophysiology of panic disorde: evidence from neuroimaging studies. Biol Mood Anxiety Disord. 2012 Nov 20;2(1):20. doi: 10.1186/2045-5380-2-20. PMID: 23168129 [PubMed] Free PMC Article
  • Dager SR. The vexing role of baseline: Implications for neuroimaging studies of panic disorder Int J Psychophysiol. 78(1):20-26, 2010. PMID: 20097237
  • Dager SR, Oskin NM, TL Richards TL, Posse S. Research Applications of Magnetic Resonance Spectroscopy (MRS) to Investigate Psychiatric Disorders.  Topics in Magnetic Resonance Imaging. 19(2):81-96, 2008.

  • Kucewicz JC, Dunmire B, Giardino ND, Leotta DF, Paun M, Dager SR, Beach KW.  Tissue Pulsatility Imaging of Cerebral Vasoreactivity During Hyperventilation. Ultrasound Med Biol. 34(8):1200-8, 2008. PMID: 18336991

  • Giardino ND, Friedman S, Dager SR. Every Breath You Take: Anxiety and its implications for functional brain imaging. Compr Psychiatry 48(2):103-12, 2007  PMID: 17292699 .

  • Han DH, Renshaw PF, Dager SR, Chung A, Hwang J, Daniels MA, Lee YS, Lyoo IK. Altered cingulate white matter connectivity in panic disorder patients.  J Psychiatric Research. 42(5):399-407, 2008. PMID: 17482647

  • Friedman S, Jensen J, Frederick B, Artru A, Renshaw P, Dager SR. Brain changes to hypocapnia using rapidly interleaved phosphorus-proton magnetic resonance spectroscopy at 4 Tesla. J Cereb Blood Flow Metab. 27(3):646-53, 2007.  PMID 16896347
  • Friedman SF, Mathis M, Hayes C, Renshaw PF, Dager SR. Brain pH response to hyperventilation in panic disorder: preliminary evidence for altered acid-base regulation. Am J Psychiatry 163:710- 715, 2006.
  • Giardino N, Friedman S, Sparks BF, Petropoulos H, Dunner, P Renshaw PF, Dager SR.  A Comparison of Hippocampus and Amygdala Volumes in Patients with Bipolar Disorder, Panic Disorder, and Healthy Controls.  Depression and Anxiety 22: 212-213, 2005.
  • Dager SR. Affective and Emotional Disorders: View of the Pathophysiology from Psychiatry and Implications for Imaging. ASNR Neuroradiology Education and Research Foundation Syllabus: 77-80, 2004.
  • Nazemi H and Dager SR:  Coping strategies of panic and control subjects undergoing lactate infusion during MRI confinement.  Comp Psychiatry 44(3):190-197, 2003. PMID: 12764706

  • Layton ME, Friedman SD, Dager SR:  Brain metabolic changes during lactate-induced panic:  effects of gabapentin treatment.  Depression and Anxiety 14:251-254, 2001.  PMID: 11754135

  • Hwang J, Lyoo IK, Friedman SD, Oh JS, Lee JY, Kim SJ, Dager SR. Amygdalar and hippocampal shape alterations in panic disorder. (in preparation)
  • Pande AC, Pollack MH, Crockatt J, Greiner M, Chouinard G, Lydiard B, Taylor CB, Dager SR, Shiovitz T:  Placebo-Controlled Study of Gabapentin Treatment in Panic Disorder.  J Clin Psychopharmacology 20(4):467-471, 2000
  • Friedman SD, Dager SR, Richards TL, Petropoulos H, Posse S:  Modeling Brain Compartmental Lactate Response to Metabolic Challenge: Feasibility Study. Psych Research/Neuroimaging 98(1):55-66, 2000.
  • Dager SR, Friedman SD, Heide A, Layton ME, Richards TL, Artru AA, Strauss WL, Hayes C, Posse S:  Two-Dimensional Proton Echo-Planar Spectroscopic Imaging of Brain Metabolic Changes During Lactate-Induced Panic.  Arch Gen Psychiatry 56:70-77, 1999.
  • Layton ME, Dager SR:  “Advances in the Treatment of Panic Disorder.”  In:  Psych Clin North America (5):183-209, 1998.
  • Dager SR, Richards T, Strauss WL, Artru A:  Single-Voxel 1H MRS Investigation of Brain Metabolic Changes During Lactate-Induced Panic.  Psychiatric Research: Neuroimaging 76:89-99, 1997.

  • Dager SR, Layton M, Richards TL:  Neuroimaging Findings in Anxiety Disorders.  Sem Clin Neuropsychiatry 1(1):48-60, 1996.

  • Dager SR, Marro KI, Peterson J, Richards TL:  Applications of Magnetic Resonance Spectroscopy to Investigate Panic Disorder.  In: NMR Spectroscopy in Psychiatric Brain Disorders. Nasrallah H. and Pettegrew J. (eds). American Psychiatric Association Press, Number 47, pp. 147-177, 1995.

  • Dager SR, Strauss W, Marro KI, Richards TL, Metzger G, Artru AA:  1H MRS Investigation of Hyperventilation in Panic and Control Subjects.  Am J Psychiatry 152:666-672, 1995  (featured article with accompanying editorial).

  • Dager SR, Marro KI, Richards TL, Metzger G:  Preliminary Application of Magnetic Resonance Spectroscopy to Investigate Lactate-Induced Panic.  Am J Psychiatry 151:57-63, 1994.

Selective Readings:

The vexing role of baseline Implications for neuroimaging studies of panic disorder.

Anxiety respiration and cerebral blood flow implications for functional brain imaging.

Amygdala and panic