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Retinal dysfunction of contrast processing in major depression also apparent in cortical activity

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Abstract

Depressive disorder is often associated with the subjective experience of altered visual perception. Recent research has produced growing evidence for involvement of the visual system in the pathophysiology of depressive disorder. Using the pattern electroretinogram (PERG), we found reduced retinal contrast response in patients with major depression. Based on this observation, the question arises whether this change has a cortical correlate. To evaluate this, we analyzed the visual evoked potential (VEP) of the occipital cortex in 40 patients with depressive disorder and 28 healthy controls. As visual stimuli, checkerboard stimuli of 0.51° check size, 12.5 reversals per second and a contrast of 3–80 % was used. In addition to the PERG, we recorded the VEP with an Oz versus FPz derivation. The amplitude versus contrast transfer function was compared across the two groups and correlated with the severity of depression, as measured by the Hamilton Depression Rating Scale and the Beck Depression Inventory. Patients with major depression displayed significantly reduced VEP amplitudes at all contrast levels compared to control subjects (p = 0.029). The VEP amplitude correlated with psychometric measures for severity of depression. The degree of depression reduced the contrast transfer function in the VEP to a lesser extent than in the PERG: While the PERG is reduced to ≈50 %, the VEP is reduced to 75 %. Our results suggest that depression affects the cortical response in major depression, but less so than the retinal responses. Modified contrast adaptation in the lateral geniculate nucleus or cortex possibly moderates the increased losses in the retina.

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References

  1. WHO (2004) WHO | The global burden of disease: 2004 update. In: WHO. http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/. Accessed 13 Nov 2013

  2. Lopez AD, Murray CCJL (1998) The global burden of disease, 1990–2020. Nat Med 4:1241–1243. doi:10.1038/3218

    Article  CAS  PubMed  Google Scholar 

  3. Nestler EJ, Hyman SE (2010) Animal models of neuropsychiatric disorders. Nat Neurosci 13:1161–1169. doi:10.1038/nn.2647

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. American Psychiatric Association (2000) Diagnostic statistical manual of mental disorders: DSM-IV-TR, Revised. American Psychiatric Association, Washington, DC

    Google Scholar 

  5. Randrup A, Bræstrup C (1977) Uptake inhibition of biogenic amines by newer antidepressant drugs: relevance to the dopamine hypothesis of depression. Psychopharmacology 53:309–314. doi:10.1007/BF00492370

    Article  CAS  PubMed  Google Scholar 

  6. Chaudhury D, Walsh JJ, Friedman AK et al (2013) Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature 493:532–536. doi:10.1038/nature11713

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Kessler RC, Chiu WT, Demler O, Walters EE (2005) Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R). Arch Gen Psychiatry 62:617–627. doi:10.1001/archpsyc.62.6.617

    Article  PubMed Central  PubMed  Google Scholar 

  8. Tye KM, Mirzabekov JJ, Warden MR et al (2013) Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature 493:537–541. doi:10.1038/nature11740

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Ebert D, Ebmeier KP (1996) The role of the cingulate gyrus in depression: from functional anatomy to neurochemistry. Biol Psychiatry 39:1044–1050. doi:10.1016/0006-3223(95)00320-7

    Article  CAS  PubMed  Google Scholar 

  10. Ebert D, Berger M (1998) Neurobiological similarities in antidepressant sleep deprivation and psychostimulant use: a psychostimulant theory of antidepressant sleep deprivation. Psychopharmacology 140:1–10

    Article  CAS  PubMed  Google Scholar 

  11. Lammers CH, Diaz J, Schwartz JC, Sokoloff P (2000) Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments. Mol Psychiatry 5:378–388

    Article  CAS  PubMed  Google Scholar 

  12. Klimek V, Schenck JE, Han H et al (2002) Dopaminergic abnormalities in amygdaloid nuclei in major depression: a postmortem study. Biol Psychiatry 52:740–748. doi:10.1016/S0006-3223(02)01383-5

    Article  CAS  PubMed  Google Scholar 

  13. Nestler EJ, Carlezon WA Jr (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59:1151–1159. doi:10.1016/j.biopsych.2005.09.018

    Article  CAS  PubMed  Google Scholar 

  14. Krishnan V, Han M-H, Graham DL et al (2007) Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131:391–404. doi:10.1016/j.cell.2007.09.018

    Article  CAS  PubMed  Google Scholar 

  15. Krishnan V, Nestler EJ (2010) Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry 167:1305–1320. doi:10.1176/appi.ajp.2009.10030434

    Article  PubMed Central  PubMed  Google Scholar 

  16. Wilson RS, Nag S, Boyle PA et al (2013) Brainstem aminergic nuclei and late-life depressive symptoms. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2013.2224

    PubMed Central  PubMed  Google Scholar 

  17. Bubl E, Tebartz van Elst L, Gondan M et al (2009) Vision in depressive disorder. World J Biol Psychiatry 10:377–384

    Article  PubMed  Google Scholar 

  18. Bubl E, Kern E, Ebert D et al (2010) Seeing gray when feeling blue? Depression can be measured in the eye of the diseased. Biol Psychiatry 68:205–208

    Article  PubMed  Google Scholar 

  19. Bubl E, Ebert D, Kern E et al (2012) Effect of antidepressive therapy on retinal contrast processing in depressive disorder. Br J Psychiatry 201:151–158. doi:10.1192/bjp.bp.111.100560

    Article  PubMed  Google Scholar 

  20. Teranishi T, Negishi K, Kato S (1983) Dopamine modulates S-potential amplitude and dye-coupling between external horizontal cells in carp retina. Nature 301:243–246

    Article  CAS  PubMed  Google Scholar 

  21. Ghilardi MF, Marx MS, Bodis-Wollner I et al (1989) The effect of intraocular 6-hydroxydopamine on retinal processing of primates. Ann Neurol 25:357–364. doi:10.1002/ana.410250407

    Article  CAS  PubMed  Google Scholar 

  22. Pereda A, Triller A, Korn H, Faber DS (1992) Dopamine enhances both electrotonic coupling and chemical excitatory postsynaptic potentials at mixed synapses. PNAS 89:12088–12092

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Ikeda H, Head GM, Ellis CJ (1994) Electrophysiological signs of retinal dopamine deficiency in recently diagnosed Parkinson’s disease and a follow up study. Vision Res 34:2629–2638

    Article  CAS  PubMed  Google Scholar 

  24. Tebartz van Elst L, Greenlee MW, Foley JM, Lucking CH (1997) Contrast detection, discrimination and adaptation in patients with Parkinson’s disease and multiple system atrophy. Brain 120(Pt 12):2219–2228

    Article  PubMed  Google Scholar 

  25. Langheinrich T, Tebartz van Elst L, Lagreze WA et al (2000) Visual contrast response functions in Parkinson’s disease: evidence from electroretinograms, visually evoked potentials and psychophysics. Clin Neurophysiol 111:66–74

    Article  CAS  PubMed  Google Scholar 

  26. Bach M (2007) The Freiburg visual acuity test-variability unchanged by post hoc re-analysis. Graefes Arch Clin Exp Ophthalmol 245:965–971

    Article  PubMed  Google Scholar 

  27. Bach M (2000) Freiburg evoked potentials. http://www.michaelbach.de/ep2000.html

  28. American Clinical Neurophysiology Society (2006) Guideline 5: guidelines for standard electrode position nomenclature. J Clin Neurophysiol 23:107–110

    Article  Google Scholar 

  29. Bach M, Meigen T, Strasburger H (1997) Raster-scan cathode-ray tubes for vision research-limits of resolution in space, time and intensity, and some solutions. Spat Vis 10:403–414

    Article  CAS  PubMed  Google Scholar 

  30. Meigen T, Bach M (1999) On the statistical significance of electrophysiological steady-state responses. Doc Ophthalmol 98:207–232

    Article  CAS  PubMed  Google Scholar 

  31. Bach M, Meigen T (1999) Do’s and don’ts in Fourier analysis of steady-state potentials. Doc Ophthalmol 99:69–82

    Article  CAS  PubMed  Google Scholar 

  32. WaveMetrics (2014) WaveMetrics—scientific graphing, data analysis, curve fitting and image processing software. http://www.wavemetrics.com/index.html. Accessed 11 Nov 2014

  33. R Development Core Team (2014) R: A language and environment for statistical computing. http://www.R-project.org. Accessed 18 Aug 2014

  34. Ben-Shlomo G, Bach M, Ofri R (2007) Temporal and spatial frequencies interact in the contrast transfer function of the pattern electroretinogram. Vision Res 47:1992–1999. doi:10.1016/j.visres.2007.04.009

    Article  CAS  PubMed  Google Scholar 

  35. Normann C, Schmitz D, Fürmaier A et al (2007) Long-term plasticity of visually evoked potentials in humans is altered in major depression. Biol Psychiatry 62:373–380. doi:10.1016/j.biopsych.2006.10.006

    Article  PubMed  Google Scholar 

  36. Joost W, Bach M, Schulte-Mönting J (1992) Influence of mood on visually evoked potentials: a prospective longitudinal study. Int J Psychophysiol 12:147–153

    Article  CAS  PubMed  Google Scholar 

  37. Ohzawa I, Sclar G, Freeman RD (1982) Contrast gain control in the cat visual cortex. Nature 298:266–268. doi:10.1038/298266a0

    Article  CAS  PubMed  Google Scholar 

  38. Heinrich TS, Bach M (2001) Contrast adaptation in human retina and cortex. IOVS 42:2721–2727

    CAS  Google Scholar 

  39. Heinrich TS, Bach M (2002) Contrast adaptation in retinal and cortical evoked potentials: no adaptation to low spatial frequencies. Vis Neurosci 19:645–650. doi:10.1017/S0952523802195095

    PubMed  Google Scholar 

  40. Solomon SG, Lennie P (2005) Chromatic gain controls in visual cortical neurons. J Neurosci 25:4779–4792. doi:10.1523/JNEUROSCI.5316-04.2005

    Article  CAS  PubMed  Google Scholar 

  41. Hadjiconstantinou M, Neff NH (1984) Catecholamine systems of retina: a model for studying synaptic mechanisms. Life Sci 35:1135–1147. doi:10.1016/0024-3205(84)90184-X

    Article  CAS  PubMed  Google Scholar 

  42. Vasile RG, Duffy FH, McAnulty G et al (1989) Abnormal visual evoked response in melancholia. Biol Psychiatry 25:785–788. doi:10.1016/0006-3223(89)90250-3

    Article  CAS  PubMed  Google Scholar 

  43. Vasile RG, Duffy FH, McAnulty G et al (1992) Abnormal flash visual evoked response in melancholia: a replication study. Biol Psychiatry 31:325–336. doi:10.1016/0006-3223(92)90226-P

    Article  CAS  PubMed  Google Scholar 

  44. Henry GM, Buchsbaum M, Murphy DL (1976) Intravenous l-DOPA plus carbidopa in depressed patients: average evoked response, learning, and behavioral changes. Psychosom Med 38:95–105

    Article  CAS  PubMed  Google Scholar 

  45. Buchsbaum MS, Kammen DPV, Murphy DL (1977) Individual differences in average evoked responses to d- and l-amphetamine with and without lithium carbonate in depressed patients. Psychopharmacology 51:129–135. doi:10.1007/BF00431728

    Article  CAS  PubMed  Google Scholar 

  46. Zhao Y, Kerscher N, Eysel U, Funke K (2001) Changes of contrast gain in cat dorsal lateral geniculate nucleus by dopamine receptor agonists. NeuroReport 12:2939–2945

    Article  CAS  PubMed  Google Scholar 

  47. Bartel P, Blom M, van der Meyden C, de Sommers K (1988) Effects of single doses of diazepam, chlorpromazine, imipramine and trihexyphenidyl on visual-evoked potentials. Neuropsychobiology 20:212–217. doi:10.1159/000118502

    Article  CAS  PubMed  Google Scholar 

  48. Bulens C, Meerwaldt JD, van der Wildt GJ, Keemink CJ (1989) Visual contrast sensitivity in drug-induced Parkinsonism. J Neurol Neurosurg Psychiatry 52:341–345

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Parkinson D (1989) Evidence for a dopaminergic innervation of cat primary visual cortex. Neuroscience 30:171–179

    Article  CAS  PubMed  Google Scholar 

  50. De Keyser J, Ebinger G, Vauquelin G (1989) Evidence for a widespread dopaminergic innervation of the human cerebral neocortex. Neurosci Lett 104:281–285. doi:10.1016/0304-3940(89)90589-2

    Article  PubMed  Google Scholar 

  51. Müller CP, Huston JP (2007) Dopamine activity in the occipital and temporal cortices of rats: dissociating effects of sensory but not pharmacological stimulation. Synapse 61:254–258. doi:10.1002/syn.20366

    Article  PubMed  Google Scholar 

  52. Volkow ND, Tomasi D, Wang G-J et al (2009) Hyperstimulation of striatal D2 receptors with sleep deprivation: implications for cognitive impairment. Neuroimage 45:1232–1240. doi:10.1016/j.neuroimage.2009.01.003

    Article  PubMed Central  PubMed  Google Scholar 

  53. Volkow ND, Tomasi D, Wang G-J et al (2012) Evidence that sleep deprivation downregulates dopamine D2R in ventral striatum in the human brain. J Neurosci 32:6711–6717. doi:10.1523/JNEUROSCI.0045-12.2012

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Buchsbaum MS, Gerner R, Post RM (1981) The effects of sleep deprivation on average evoked responses in depressed patients and in normals. Biol Psychiatry 16:351–363

    CAS  PubMed  Google Scholar 

  55. Vijayraghavan S, Wang M, Birnbaum SG et al (2007) Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nat Neurosci 10:376–384. doi:10.1038/nn1846

    Article  CAS  PubMed  Google Scholar 

  56. Volkow ND, Wang GJ, Fowler JS et al (1997) Effects of methylphenidate on regional brain glucose metabolism in humans: relationship to dopamine D2 receptors. Am J Psychiatry 154:50–55

    Article  CAS  PubMed  Google Scholar 

  57. Cools R, D’Esposito M (2011) Inverted-u-shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry 69:e113–e125. doi:10.1016/j.biopsych.2011.03.028

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Landau AM, Chakravarty MM, Clark CM et al (2011) Electroconvulsive therapy alters dopamine signaling in the striatum of non-human primates. Neuropsychopharmacology 36:511–518. doi:10.1038/npp.2010.182

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Baldinger P, Lotan A, Frey R et al (2014) Neurotransmitters and electroconvulsive therapy. J ECT 30:116–121. doi:10.1097/YCT.0000000000000138

    Article  CAS  PubMed  Google Scholar 

  60. Russo SJ, Nestler EJ (2013) The brain reward circuitry in mood disorders. Nat Rev Neurosci 14:609–625. doi:10.1038/nrn3381

    Article  CAS  PubMed  Google Scholar 

  61. Seifritz E, Müller MJ, Annen O et al (1997) Effect of sleep deprivation on neuroendocrine response to a serotonergic probe in healthy male subjects. J Psychiatr Res 31:543–554

    Article  CAS  PubMed  Google Scholar 

  62. Goldapple K, Segal Z, Garson C et al (2004) Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry 61:34–41. doi:10.1001/archpsyc.61.1.34

    Article  PubMed  Google Scholar 

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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    Authors and Affiliations

    1. Department of Psychiatry and Psychotherapy, Albert-Ludwigs-Universität, Hauptstr. 5, 79104, Freiburg, Germany

      Emanuel Bubl, Elena Kern, Dieter Ebert, Andreas Riedel & Ludger Tebartz van Elst

    2. Section Visual Function, Eye Center, University Medical Center, Killianstr. 5, 79104, Freiburg, Germany

      Michael Bach

    3. Sections for Visual Function and Experimental Neuropsychiatry, University Medical School of Freiburg, Freiburg, Germany

      Ludger Tebartz van Elst & Michael Bach

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    1. Emanuel Bubl
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    2. Elena Kern
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    3. Dieter Ebert
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    Correspondence to Emanuel Bubl.

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    L. Tebartz van Elst and M. Bach have contributed equally to this study.

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    Bubl, E., Kern, E., Ebert, D. et al. Retinal dysfunction of contrast processing in major depression also apparent in cortical activity. Eur Arch Psychiatry Clin Neurosci 265, 343–350 (2015). https://doi.org/10.1007/s00406-014-0573-x

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