**6. References**


Although most studies have been directed to the patients with OCD without MDD, in clinical practice OCD patients frequently have major depression as a comorbidity; approximately one-third of OCD patients also have MDD (Rasmussen and Eisen, 1992; Weismann et al., 1994), whereas 22-38% of patients with MDD have obsessive-compulsive symptoms (Kendell and DiScipio, 1970). Thus, notions acquired from studies performed on pure OCD patients without depression might deviate from the actual pathophysiology of OCD. Further, since SRIs and CBT are commonly effective for improvement of both OCD and MDD, exploration of the neuronal substrates shared by the two diseases might provide

Saxena et al. (1999) demonstrated that patients with concurrent OCD and MDD showed a significant reduction in metabolism in the hippocampus similar to that of patients with MDD alone. Furthermore, treatment with paroxetine for patients with concurrent OCD and MDD induced a reduction of rGMR in the ventral lateral prefrontal cortex, which was similar to the findings in patients with MDD alone, but did not show a decrease in the OFC and caudate nucleus like that seen in the patients with OCD alone (Saxena et al., 2002). These findings suggested that patients with concurrent OCD and MDD had the pathophysiology of MDD, and thus may constitute a distinctive subtype within OCD, such that both the etiologies of OCD and MDD should be considered carefully when devising a

Functional neuroimaging studies on OCD have provided much more consistent findings than structural MRI studies. That is, in patients with OCD, some important regions in the cortical and subcortical areas present with hyperactivity and are normalized by pharmacotherapy. Since improvements by SRIs and CBT occur in only about half of patients (responders), further neuroimaging studies controlled by treatment intervention are

Abercrombie HC, Schaefer SM, Larson CL, Oakes TR, Lindgren KA, Holden JE, Perlman SB,

Alexander GE, Crutcher MD. (1990). Functional architecture of basal ganglia circuits: neural

al-Mousawi AH, Evans N, Ebmeier KP, Roeda D, Chaloner F, Ashcroft GW. (1996). Limbic

Alptekin K, Degirmenci B, Kivircik B, Durak H, Yemez B, Derebek E, Tunca Z. (2001). Tc-

Andreasen NC, Rezai K, Alliger R, Swayze VW 2nd, Flaum M, Kirchner P, Cohen G, O'Leary

tomography and the Tower of London. *Arch Gen Psychiatry*, 49(12), 943-958.

substrates of parallel processing. *Trends Neurosci*, 13(7), 266-271.

without depression. *Psychiatry Res*, 1. 107(1), 51-56.

Turski PA, Krahn DD, Benca RM, Davidson RJ. (1998). Metabolic rate in the right amygdala predicts negative affect in depressed patients. *Neuroreport*, 5. 9(14), 3301-3307.

dysfunction in schizophrenia and mania. A study using 18F-labelled fluorodeoxyglucose and positron emission tomography. *Br J Psychiatry*, 169(4), 509-516.

99m HMPAO brain perfusion SPECT in drug-free obsessive-compulsive patients

DS. (1992). Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed

**5.3 Depression as a comorbidity with OCD** 

treatment strategy.

**5.4 Conclusion** 

strongly needed.

**6. References** 

very valuable information for understanding the etiology.


Resting State Blood Flow and Glucose Metabolism in Psychiatric Disorders 145

Buchsbaum MS, Wu JC, DeLisi LE, Holcomb HH, Hazlett E, Cooper-Langston K, Kessler R.

Buchsbaum MS, Haier RJ, Potkin SG, Nuechterlein K, Bracha HS, Katz M, Lohr J, Wu J,

Buchsbaum MS, Wu J, Siegel BV, Hackett E, Trenary M, Abel L, Reynolds C. (1997). Effect of

Buchsbaum MS, Tang CY, Peled S, Gudbjartsson H, Lu D, Hazlett EA, Downhill J, Haznedar

Buchsbaum MS, Buchsbaum BR, Hazlett EA, Haznedar MM, Newmark R, Tang CY, Hof PR.

Buchsbaum MS, Haznedar MM, Aronowitz J, Brickman AM, Newmark RE, Bloom R, Brand

Busatto GF, Zamignani DR, Buchpiguel CA, Garrido GE, Glabus MF, Rocha ET, Maia AF,

Clark C, Kopala L, Li DK, Hurwitz T. (2001). Regional cerebral glucose metabolism in nevermedicated patients with schizophrenia. *Can J Psychiatry*, 46(4), 340-345. Cleghorn JM, Garnett ES, Nahmias C, Firnau G, Brown GM, Kaplan R, Szechtman H,

Cleghorn JM, Franco S, Szechtman B, Kaplan RD, Szechtman H, Brown GM, Nahmias C,

Cohen RM, Gross M, Nordahl TE, Semple WE, Oren DA, Rosenthal N. (1992). Preliminary

Cohen RM, Nordahl TE, Semple WE, Andreason P, Litman RE, Pickar D. (1997). The brain

metabolic rate in schizophrenia. *Neuroreport*, 16. 9(3), 425-430.

computed tomography (SPECT). *Psychiatry Res,* 10. 99(1), 15-27.

acute untreated schizophrenia. *Psychiatry Res*, 28(2), 119-133.

disorder. *Arch Gen Psychiatry*, 49(7), 545-552.

in never-medicated schizophrenics. *Arch Gen Psychiatry*, 49(12), 935-942. Buchsbaum MS, Potkin SG, Siegel BV Jr, Lohr J, Katz M, Gottschalk LA, Gulasekaram B,

schizophrenic patients. *Biol Psychiatry*, 22(4), 479-494.

schizophrenia. *Am J Psychiatry*, 153(2), 191-199.

schizophrenia. *Am J Psychiatry*, 164(7), 1072-1081.

*Psychiatry*, 1. 41(1), 15-22.

*Schizophr Res*, 94(1-3), 293-305.

149(8), 1062-1069.

481-486.

(1987). Positron emission tomography studies of basal ganglia and somatosensory cortex neuroleptic drug effects: differences between normal controls and

Lottenberg S, Jerabek PA, et al. (1992a). Frontostriatal disorder of cerebral metabolism

Marshall JF, Lottenberg S, Teng CY, et al. (1992b). Striatal metabolic rate and clinical response to neuroleptics in schizophrenia. *Arch Gen Psychiatry*, 49(12), 966-974. Buchsbaum MS, Someya T, Teng CY, Abel L, Chin S, Najafi A, Haier RJ, Wu J, Bunney WE

Jr. (1996). PET and MRI of the thalamus in never-medicated patients with

sertraline on regional metabolic rate in patients with affective disorder. *Biol* 

M, Fallon JH, Atlas SW. (1998). MRI white matter diffusion anisotropy and PET

(2007a). Relative glucose metabolic rate higher in white matter in patients with

J, Goldstein KE, Heath D, Starson M, Hazlett EA. (2007b). FDG-PET in neverpreviously medicated psychotic adolescents treated with olanzapine or haloperidol.

Rosario-Campos MC, Campi Castro C, Furuie SS, Gutierrez MA, McGuire PK, Miguel EC. (2000). A voxel-based investigation of regional cerebral blood flow abnormalities in obsessive-compulsive disorder using single photon emission

Szechtman B. (1989). Increased frontal and reduced parietal glucose metabolism in

Garnett ES. (1992). Toward a brain map of auditory hallucinations. *Am J Psychiatry*,

data on the metabolic brain pattern of patients with winter seasonal affective

metabolic patterns of clozapine- and fluphenazine-treated patients with schizophrenia during a continuous performance task. *Arch Gen Psychiatry*, 54(5),


Bench CJ, Friston KJ, Brown RG, Scott LC, Frackowiak RS, Dolan RJ. (1992). The anatomy of

Bench CJ, Friston KJ, Brown RG, Frackowiak RS, Dolan RJ. (1993). Regional cerebral blood

Bhardwaj R, Chakrabarti S, Mittal BR, Sharan P. (2010). A single photon emission

Biver F, Goldman S, Delvenne V, Luxen A, De Maertelaer V, Hubain P, Mendlewicz J,

Blumberg HP, Stern E, Ricketts S, Martinez D, de Asis J, White T, Epstein J, Isenberg N,

Blumberg HP, Stern E, Martinez D, Ricketts S, de Asis J, White T, Epstein J, McBride PA,

Bonne O, Louzoun Y, Aharon I, Krausz Y, Karger H, Lerer B, Bocher M, Freedman N, Chisin

Brockmann H, Zobel A, Joe A, Biermann K, Scheef L, Schuhmacher A, von Widdern O,

Brody AL, Saxena S, Silverman DH, Alborzian S, Fairbanks LA, Phelps ME, Huang SC, Wu

Brooks JO 3rd, Bonner JC, Rosen AC, Wang PW, Hoblyn JC, Hill SJ, Ketter TA. (2009a).

Brooks JO 3rd, Hoblyn JC, Woodard SA, Rosen AC, Ketter TA. (2009b). Corticolimbic

Brooks JO 3rd, Hoblyn JC, Ketter TA. (2010). Metabolic evidence of corticolimbic

Buchsbaum MS, Ingvar DH, Kessler R, Waters RN, Cappelletti J, van Kammen DP, King AC,

dysregulation in bipolar mania. *Psychiatry Res*, 28. 181(2), 136-140.

patients with schizophrenia. *Arch Gen Psychiatry,* 39(3), 251-259.

manic state of bipolar disorder. *Am J Psychiatry*, 156(12), 1986-1988.

caudate activity in bipolar mania. *Biol Psychiatry*, 1. 48(11), 1045-1052. Bonne O, Krausz Y, Gorfine M, Karger H, Gelfin Y, Shapira B, Chisin R, Lerer B. (1996).

Tc99m HMPAO SPECT. *J Affect Disord*, 16. 41(3), 163-171.

with bipolar depression. *Psychiatry Res*, 30. 172(3), 200-204.

with clinical dimensions. *Psychol Med*, 23(3), 579-590.

depression. *Biol Psychiatry*, 15. 36(6), 381-388.

bipolar disorder. *World J Biol Psychiatry*, 11(2 Pt 2), 334-343.

*Psychol Med,* 22(3), 607-615.

122(1), 49-57.

91(3), 127-139.

*Res*. 43(5), 497-502.

*Psychiatry Res,* 30. 173(2), 107-112.

melancholia--focal abnormalities of cerebral blood flow in major depression.

flow in depression measured by positron emission tomography: the relationship

computerized tomography (SPECT) study of regional cerebral blood flow in

Lotstra F. (1994). Frontal and parietal metabolic disturbances in unipolar

McBride PA, Kemperman I, Emmerich S, Dhawan V, Eidelberg D, Kocsis JH, Silbersweig DA. (1999). Rostral and orbital prefrontal cortex dysfunction in the

Eidelberg D, Kocsis JH, Silbersweig DA. (2000). Increased anterior cingulate and

Cerebral hypoperfusion in medication resistant, depressed patients assessed by

R. (2003). Cerebral blood flow in depressed patients: a methodological comparison of statistical parametric mapping and region of interest analyses. *Psychiatry Res*, 20.

Metten M, Biersack HJ, Maier W, Boecker H. (2009). The value of HMPAO SPECT in predicting treatment response to citalopram in patients with major depression.

HM, Maidment K, Baxter LR Jr. (1999). Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine. *Psychiatry Res*, 11.

Dorsolateral and dorsomedial prefrontal gray matter density changes associated

metabolic dysregulation in euthymic older adults with bipolar disorder. *J Psychiatr* 

Johnson JL, Manning RG, Flynn RW, Mann LS, Bunney WE Jr, Sokoloff L. (1982). Cerebral glucography with positron tomography. Use in normal subjects and in


Resting State Blood Flow and Glucose Metabolism in Psychiatric Disorders 147

Erkwoh R, Sabri O, Steinmeyer EM, Bull U, Sass H. (1997). Psychopathological and SPECT findings in never-treated schizophrenia. *Acta Psychiatr Scand*, 96(1), 51-57. Fitzgerald PB, Laird AR, Maller J, Daskalakis ZJ. (2008). A meta-analytic study of changes in

Geller DA, Biederman J, Reed ED, Spencer T, Wilens TE. (1995). Similarities in response to

Gonul AS, Kula M, Eşel E, Tutuş A, Sofuoglu S. (2003a). A Tc-99m HMPAO SPECT study of

Gonul AS, Kula M, Sofuoglu S, Tutus A, Esel E. (2003b). Tc-99 HMPAO SPECT study of

Gonul AS, Kula M, Bilgin AG, Tutus A, Oguz A. (2004). The regional cerebral blood flow

Goodwin GM, Cavanagh JT, Glabus MF, Kehoe RF, O'Carroll RE, Ebmeier KP. (1997).

Gur RC, Gur RE. (1995). Hypofrontality in schizophrenia: RIP. *Lancet,* 3. 345(8962), 1383-

Guze BH, Baxter LR Jr, Schwartz JM, Szuba MP, Liston EH. (1991). Electroconvulsive

Hansen ES, Hasselbalch S, Law I, Bolwig TG. (2002). The caudate nucleus in obsessive-

Hazlett EA, Buchsbaum MS, Byne W, Wei TC, Spiegel-Cohen J, Geneve C, Kinderlehrer R,

Hazlett EA, Buchsbaum MS, Kemether E, Bloom R, Platholi J, Brickman AM, Shihabuddin L,

Hill K, Mann L, Laws KR, Stephenson CM, Nimmo-Smith I, McKenna PJ. (2004).

Hirschfeld RM, Montgomery SA, Aguglia E, Amore M, Delgado PL, Gastpar M, Hawley C,

Therapy and Brain Glucose Metabolism. *Convuls Ther*, 7(1), 15-19.

of the thalamus in schizophrenia. *Am J Psychiatry*, 161(2), 305-314.

depression and normal controls. *Acta Psychiatr Scand*, 90(4), 298-303. Elshahawi HH, Essawi H, Rabie MA, Mansour M, Beshry ZA, Mansour AN. (2011).

versus recurrent episodes. *J Affect Disord*, 130(1-2), 180-191.

brain activation in depression. *Hum Brain Mapp*, 29(6), 683-695.

disorder. *J Am Acad Child Adolesc Psychiatry*, 34(1), 36-44.

non-deficit syndrome. *Psychiatry Res*, 30. 123(3), 199-205.

*Neuropsychopharmacol Biol Psychiatry*, 28(6), 1015-1021.

*Psychiatry Clin Neurosci*, 253(1), 29-33.

with mania. *Br J Psychiatry*, 170, 426-430.

PET study. *Int J Neuropsychopharmacol*, 5(1), 1-10.

spectrum. *Am J Psychiatry*, 156(8), 1190-1199.

*Acta Psychiatr Scand*, 110(4), 243-256.

1384.

computerized tomography in obsessive-compulsive disorder compared with major

Cognitive functions among euthymic bipolar I patients after a single manic episode

fluoxetine in the treatment of children and adolescents with obsessive-compulsive

regional cerebral blood flow in drug-free schizophrenic patients with deficit and

regional cerebral blood flow in olanzapine-treated schizophrenic patients. *Eur Arch* 

changes in major depressive disorder with and without psychotic features. *Prog* 

Uptake of 99mTc-exametazime shown by single photon emission computed tomography before and after lithium withdrawal in bipolar patients: associations

compulsive disorder. Reduced metabolism following treatment with paroxetine: a

Haznedar MM, Shihabuddin L, Siever LJ. (1999). Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia

Tang C, Byne W. (2004). Abnormal glucose metabolism in the mediodorsal nucleus

Hypofrontality in schizophrenia: a meta-analysis of functional imaging studies.

Kasper S, Linden M, Massana J, Mendlewicz J, Möller HJ, Nemeroff CB, Saiz J, Such P, Torta R, Versiani M.(2002). Partial response and nonresponse to antidepressant therapy: current approaches and treatment options. *J Clin Psychiatry*, 63(9), 826-837.


Corson PW, O'Leary DS, Miller DD, Andreasen NC. (2002). The effects of neuroleptic

Crespo-Facorro B, Cabranes JA, López-Ibor Alcocer MI, Payá B, Fernández Pérez C, Encinas

Culha AF, Osman O, Dogangün Y, Filiz K, Suna K, Kalkan ON, Gulfizar V, Beyza A. (2008).

Dazzan P, Morgan KD, Orr KG, Hutchinson G, Chitnis X, Suckling J, Fearon P, Salvo J,

Desco M, Gispert JD, Reig S, Sanz J, Pascau J, Sarramea F, Benito C, Santos A, Palomo T,

Dierks T, Linden DE, Jandl M, Formisano E, Goebel R, Lanfermann H, Singer W. (1999).

Diler RS, Kibar M, Avci A. (2004). Pharmacotherapy and regional cerebral blood flow in children with obsessive compulsive disorder. *Yonsei Med J,* 29. 45(1), 90-99. Dolan RJ, Bench CJ, Liddle PF, Friston KJ, Frith CD, Grasby PM, Frackowiak RS. (1993).

Drevets WC, Videen TO, Price JL, Preskorn SH, Carmichael ST, Raichle ME. (1992). A functional anatomical study of unipolar depression. *J Neurosci*, 12(9), 3628-3641. Drevets WC, Price JL, Simpson JR Jr, Todd RD, Reich T, Vannier M, Raichle ME. (1997).

Drevets WC. (1999). Prefrontal cortical-amygdalar metabolism in major depression. *Ann N Y* 

Drevets WC. (2000). Neuroimaging studies of mood disorders. *Biol Psychiatry,* 15. 48(8), 813-

Drevets WC, Price JL, Bardgett ME, Reich T, Todd RD, Raichle ME. (2002). Glucose

Ebmeier KP, Blackwood DH, Murray C, Souza V, Walker M, Dougall N, Moffoot AP,

Edmonstone Y, Austin MP, Prentice N, Dougall N, Freeman CP, Ebmeier KP, Goodwin GM.

plasma cortisol levels. *Pharmacol Biochem Behav,* 71(3), 431-447.

disease specificity? *J Neurol Neurosurg Psychiatry*, 56(12), 1290-1294.

study. *Eur Arch Psychiatry Clin Neurosci*, 249(3), 156-161.

schizophrenia. *Psychiatry Res*, 15. 122(2), 125-135.

52(9), 855-962.

127(Pt 1), 143-153.

824-827.

829.

33(7), 487-495.

*Acad Sci*, 29. 877, 614-637.

medications on basal ganglia blood flow in schizophreniform disorders: a comparison between the neuroleptic-naïve and medicated states. *Biol Psychiatry*, 1.

M, Ayuso Mateos JL, López-Ibor JJ Jr. (1999). Regional cerebral blood flow in obsessive-compulsive patients with and without a chronic tic disorder. A SPECT

Changes in regional cerebral blood flow demonstrated by 99mTc-HMPAO SPECT in euthymic bipolar patients. *Eur Arch Psychiatry Clin Neurosci*, 258(3), 144-151. Davidson LL, Heinrichs RW. (2003). Quantification of frontal and temporal lobe brain-

imaging findings in schizophrenia: a meta-analysis. *Psychiatry Res*, 15. 122(2), 69-87.

McGuire PK, Mallett RM, Jones PB, Leff J, Murray RM. (2004). The structural brain correlates of neurological soft signs in AESOP first-episode psychoses study. *Brain*,

Molina V. (2003). Cerebral metabolic patterns in chronic and recent-onset

Activation of Heschl's gyrus during auditory hallucinations. *Neuron*, 22(3), 615-621.

Dorsolateral prefrontal cortex dysfunction in the major psychoses; symptom or

Subgenual prefrontal cortex abnormalities in mood disorders. *Nature*, 24. 386(6627),

metabolism in the amygdala in depression: relationship to diagnostic subtype and

O'Carroll RE, Goodwin GM. (1993). Single-photon emission computed tomography with 99mTc-exametazime in unmedicated schizophrenic patients. *Biol Psychiatry*, 1.

(1994). Uptake of 99mTc-exametazime shown by single photon emission

computerized tomography in obsessive-compulsive disorder compared with major depression and normal controls. *Acta Psychiatr Scand*, 90(4), 298-303.


Resting State Blood Flow and Glucose Metabolism in Psychiatric Disorders 149

Kim JJ, Mohamed S, Andreasen NC, O'Leary DS, Watkins GL, Boles Ponto LL, Hichwa RD.

Kimbrell TA, Ketter TA, George MS, Little JT, Benson BE, Willis MW, Herscovitch P, Post

Kohn Y, Freedman N, Lester H, Krausz Y, Chisin R, Lerer B, Bonne O. (2007). 99mTc-

electroconvulsive therapy in major depression. *J Nucl Med*, 48(8), 1273-1278. Konarski JZ, Kennedy SH, McIntyre RS, Rafi-Tari S, Soczynska JK, Mayberg HS. (2007).

Konarski JZ, Kennedy SH, Segal ZV, Lau MA, Bieling PJ, McIntyre RS, Mayberg HS. (2009).

Krishnan KR, McDonald WM, Escalona PR, Doraiswamy PM, Na C, Husain MM, Figiel GS,

Krüger S, Seminowicz D, Goldapple K, Kennedy SH, Mayberg HS. (2003). State and trait

Krüger S, Alda M, Young LT, Goldapple K, Parikh S, Mayberg HS. (2006). Risk and

bipolar patients and their healthy siblings. *Am J Psychiatry*, 163(2), 257-264. Lahti AC, Holcomb HH, Weiler MA, Medoff DR, Tamminga CA. (2003). Functional effects

Lahti AC, Weiler MA, Medoff DR, Tamminga CA, Holcomb HH. (2005). Functional effects

Lehrer DS, Christian BT, Mantil J, Murray AC, Buchsbaum BR, Oakes TR, Byne W,

Liddle PF, Lane CJ, Ngan ET. (2000). Immediate effects of risperidone on cortico-striato-

Lucey JV, Costa DC, Blanes T, Busatto GF, Pilowsky LS, Takei N, Marks IM, Ell PJ, Kerwin

Lucey JV, Costa DC, Busatto G, Pilowsky LS, Marks IM, Ell PJ, Kerwin RW. (1997). Caudate

RW. (1995). Regional cerebral blood flow in obsessive-compulsive disordered patients at rest. Differential correlates with obsessive-compulsive and anxious-

regional cerebral blood flow in obsessive-compulsive disorder, panic disorder and

cerebral blood flow in schizophrenia. *Br J Psychiatry*, 160, 179-186.

thalamic loops and the hippocampus. *Br J Psychiatry*, 177, 402-407.

positron emission tomography. *Am J Psychiatry*, 157(4), 542-548.

severities of unipolar depression. *Biol Psychiatry*, 1. 51(3), 237-252.

depressed subjects. *Psychiatry Res*, 15. 155(3), 203-210.

acute mood challenge. *Biol Psychiatry*, 1. 54(11), 1274-1283.

with schizophrenia. *Psychiatry Res*, 30. 139(1), 19-30.

avoidant dimensions. *Br J Psychiatry*, 167(5), 629-634.

553-557.

53(7), 601-608.

(2000). Regional neural dysfunctions in chronic schizophrenia studied with

RM. (2002). Regional cerebral glucose utilization in patients with a range of

HMPAO SPECT study of cerebral perfusion after treatment with medication and

Relationship between regional brain metabolism, illness severity and age in

Predictors of nonresponse to cognitive behavioural therapy or venlafaxine using glucose metabolism in major depressive disorder. *J Psychiatry Neurosci*, 34(3), 175-180.

Boyko OB, Ellinwood EH, Nemeroff CB. (1992). Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations. *Arch Gen Psychiatry*, 49(7),

influences on mood regulation in bipolar disorder: blood flow differences with an

resilience markers in bipolar disorder: brain responses to emotional challenge in

of antipsychotic drugs: comparing clozapine with haloperidol. *Biol Psychiatry*, 1.

of single dose first- and second-generation antipsychotic administration in subjects

Kemether EM, Buchsbaum MS. (2005). Thalamic and prefrontal FDG uptake in never medicated patients with schizophrenia. *Am J Psychiatry*, 162(5), 931-938. Lennox BR, Park SB, Medley I, Morris PG, Jones PB. (2000). The functional anatomy of auditory hallucinations in schizophrenia. *Psychiatry Res*, 20. 100(1), 13-20. Liddle PF, Friston KJ, Frith CD, Hirsch SR, Jones T, Frackowiak RS. (1992). Patterns of


Hirschfeld RM, Lewis L, Vornik LA. (2003). Perceptions and impact of bipolar disorder: how

Hoehn-Saric R, Pearlson GD, Harris GJ, Machlin SR, Camargo EE. (1991). Effects of

Hoehn-Saric R, Schlaepfer TE, Greenberg BD, McLeod DR, Pearlson GD, Wong SH. (2001).

Ho Pian KL, van Megen HJ, Ramsey NF, Mandl R, van Rijk PP, Wynne HJ, Westenberg HG.

Horga G, Parellada E, Lomeña F, Fernández-Egea E, Mané A, Font M, Falcón C, Konova AB,

Horwitz B, Swedo SE, Grady CL, Pietrini P, Schapiro MB, Rapoport JL, Rapoport SI. (1991).

Hurwitz TA, Clark C, Murphy E, Klonoff H, Martin WR, Pate BD (1990). Regional cerebral glucose metabolism in major depressive disorder. *Can J Psychiatry*, 35(8), 684-688. Ingvar DH, Franzén G. (1974). Abnormalities of cerebral blood flow distribution in patients

Ishizaki J, Yamamoto H, Takahashi T, Takeda M, Yano M, Mimura M. (2008). Changes in

Jacobsen LK, Hamburger SD, Van Horn JD, Vaituzis AC, McKenna K, Frazier JA, Gordon

Joe AY, Tielmann T, Bucerius J, Reinhardt MJ, Palmedo H, Maier W, Biersack HJ, Zobel A.

Kendell RE, Discipio WJ. (1970). Obsessional symptoms and obsessional personality traits in

Kessing LV. (1998). Cognitive impairment in the euthymic phase of affective disorder.

Ketter TA, Kimbrell TA, George MS, Dunn RT, Speer AM, Benson BE, Willis MW, Danielson

A, Frye MA, Herscovitch P, Post RM. (2001). Effects of mood and subtype on cerebral glucose metabolism in treatment-resistant bipolar disorder. *Biol Psychiatry*,

with chronic schizophrenia. *Acta Psychiatr Scand*, 50(4), 425-462.

childhood onset schizophrenia. *Psychiatry Res*, 31. 75(3), 131-144.

responding to fluvoxamine. *Psychiatry Res*, 28. 138(2), 89-97.

hallucinations. *J Psychiatry Neurosci*, 1. 36(5), 312-321.

depression. *Int J Geriatr Psychiatry*, 23(8), 805-811.

current findings. *Curr Psychiatry Rep*, 9(6), 512-520.

*Psychol Med*, 28(5), 1027-1038.

15. 49(2), 97-109.

patients with depressive illnesses. *Psychol Med*, 1(1), 65-72.

161-174.

221-237.

*Psychiatry*, 148(9), 1243-1245.

responders. *Psychiatry Res*, 30. 108(2), 89-100.

far have we really come? Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder. *J Clin Psychiatry*, 64(2),

fluoxetine on regional cerebral blood flow in obsessive-compulsive patients. *Am J* 

Cerebral blood flow in obsessive-compulsive patients with major depression: effect of treatment with sertraline or desipramine on treatment responders and non-

(2005). Decreased thalamic blood flow in obsessive-compulsive disorder patients

Pavia J, Ros D, Bernardo M. (2011). Differential brain glucose metabolic patterns in antipsychotic-naïve first-episode schizophrenia with and without auditory verbal

Cerebral metabolic pattern in obsessive-compulsive disorder: altered intercorrelations between regional rates of glucose utilization. *Psychiatry Res*, 40(4),

regional cerebral blood flow following antidepressant treatment in late-life

CT, Lenane MC, Rapoport JL, Zametkin AJ. (1997). Cerebral glucose metabolism in

(2006). Response-dependent differences in regional cerebral blood flow changes with citalopram in treatment of major depression. *J Nucl Med*, 47(8), 1319-1325. Keener MT, Phillips ML. (2007). Neuroimaging in bipolar disorder: a critical review of


Resting State Blood Flow and Glucose Metabolism in Psychiatric Disorders 151

Molina V, Gispert JD, Reig S, Sanz J, Pascau J, Santos A, Desco M, Palomo T. (2005d).

Molina V, Tamayo P, Montes C, De Luxán A, Martin C, Rivas N, Sancho C, Domínguez-Gil

Molina V, Solera S, Sanz J, Sarramea F, Luque R, Rodríguez R, Jiménez-Arriero MA, Palomo

Ngan ET, Lane CJ, Ruth TJ, Liddle PF. (2002). Immediate and delayed effects of risperidone

Penadés R, Boget T, Lomeña F, Mateos JJ, Catalán R, Gastó C, Salamero M. (2002). Could the

Perani D, Colombo C, Bressi S, Bonfanti A, Grassi F, Scarone S, Bellodi L, Smeraldi E, Fazio

Périco CA, Skaf CR, Yamada A, Duran F, Buchpiguel CA, Castro CC, Soares JC, Busatto GF.

study using statistical parametric mapping. *Neurosci Lett*, 26. 384(3), 265-270. Potkin SG, Buchsbaum MS, Jin Y, Tang C, Telford J, Friedman G, Lottenberg S, Najafi A,

Potkin SG, Alva G, Fleming K, Anand R, Keator D, Carreon D, Doo M, Jin Y, Wu JC, Fallon

striatum and frontal cortex. *J Clin Psychiatry*, 55 Suppl B, 63-66.

time. *Ann N Y Acad Sci*, 462, 249-262.

with symptom change. *J Neurol Neurosurg Psychiatry*, 72(1), 106-110. Nee LE, Caine ED, Polinsky RJ, Eldridge R, Ebert MH (1980). Gilles de la Tourette syndrome: clinical and family study of 50 cases. *Ann Neurol*, 7(1), 41-49. Pan L, Keener MT, Hassel S, Phillips ML. (2009). Functional neuroimaging studies of bipolar

cognitive performance in schizophrenia. *Psychiatry Res*, 30. 173(2), 88-93. Nakatani E, Nakgawa A, Ohara Y, Goto S, Uozumi N, Iwakiri M, Yamamoto Y, Motomura

clinical improvement. *Psychopharmacology (Berl)*, 178(1), 17-26.

*Neuropsychopharmacol Biol Psychiatry*, 15. 32(4), 948-954.

major depression. *Br J Psychiatry*, 184, 306-311.

endophenotypes. *Int Rev Psychiatry*, 21(4), 368-379.

rehabilitation? *Acta Psychiatr Scand*, 105(3), 202-208.

Cerebral metabolic changes induced by clozapine in schizophrenia and related to

A. (2008). Clozapine may partially compensate for task-related brain perfusion abnormalities in risperidone-resistant schizophrenia patients. *Prog* 

T. (2009). Association between cerebral metabolic and structural abnormalities and

K, Iikura Y, Yamagami T. (2003). Effects of behavior therapy on regional cerebral blood flow in obsessive-compulsive disorder. *Psychiatry Res*, 30. 124(2), 113-120. Navarro V, Gastó C, Lomeña F, Torres X, Mateos JJ, Portella MJ, Masana G, Marcos T.

(2004). Prognostic value of frontal functional neuroimaging in late-onset severe

on cerebral metabolism in neuroleptic naïve schizophrenic patients: correlations

disorder: examining the wide clinical spectrum in the search for disease

hypofrontality pattern in schizophrenia be modified through neuropsychological

F. (1995). [18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic correlation study after treatment. *Br J Psychiatry*, 166(2), 244-250.

(2005). Relationship between regional cerebral blood flow and separate symptom clusters of major depression: a single photon emission computed tomography

Gulasekaram B, Costa J, et al. (1994). Clozapine effects on glucose metabolic rate in

JH. (2002). A PET study of the pathophysiology of negative symptoms in schizophrenia. Positron emission tomography. *Am J Psychiatry*, 159(2), 227-237. Potkin SG, Basile VS, Jin Y, Masellis M, Badri F, Keator D, Wu JC, Alva G, Carreon DT,

Bunney WE Jr, Fallon JH, Kennedy JL. (2003). D1 receptor alleles predict PET metabolic correlates of clinical response to clozapine. *Mol Psychiatry*, 8(1), 109-113. Prohovnik I, Sackeim HA, Decina P, Malitz S. (1986). Acute reductions of regional cerebral

blood flow following electroconvulsive therapy. Interactions with modality and

healthy controls on single photon emission computerised tomography. *Psychiatry Res*, 14. 74(1), 25-33.


Lynch MR. (1992). Schizophrenia and the D1 receptor: focus on negative symptoms. *Prog* 

Mah L, Zarate CA Jr, Singh J, Duan YF, Luckenbaugh DA, Manji HK, Drevets WC. (2007).

Mann JJ. (2005). The medical management of depression. *N Engl J Med*, 27, 353(17), 1819-

Martinot JL, Hardy P, Feline A, Huret JD, Mazoyer B, Attar-Levy D, Pappata S, Syrota A.

Mayberg HS, Brannan SK, Mahurin RK, Jerabek PA, Brickman JS, Tekell JL, Silva JA,

a potential predictor of treatment response. *Neuroreport*, 3. 8(4), 1057-1061. McGuire PK, Bench CJ, Frith CD, Marks IM, Frackowiak RS, Dolan RJ. (1994). Functional anatomy of obsessive-compulsive phenomena. *Br J Psychiatry*, 164(4), 459-468. Merikangas KR, Ames M, Cui L, Stang PE, Ustun TB, Von Korff M, Kessler RC. (2007). The

US adult household population. *Arch Gen Psychiatry*, 64(10), 1180-1188. Milak MS, Parsey RV, Lee L, Oquendo MA, Olvet DM, Eipper F, Malone K, Mann JJ. (2009).

Miller DD, Rezai K, Alliger R, Andreasen NC. (1997). The effect of antipsychotic medication

Miller DD, Andreasen NC, O'Leary DS, Watkins GL, Boles Ponto LL, Hichwa RD.

Modell JG, Mountz JM, Curtis GC, Greden JF. (1989). Neurophysiologic dysfunction in basal

obsessive-compulsive disorder. *J Neuropsychiatry Clin Neurosci*, 1(1), 27-36. Molina V, Sanz J, Reig S, Martínez R, Sarramea F, Luque R, Benito C, Gispert JD, Pascau J,

Molina V, Sanz J, Sarramea F, Benito C, Palomo T. (2005b). Prefrontal atrophy in first

Molina V, Gispert JD, Reig S, Pascau J, Martínez R, Sanz J, Palomo T, Desco M. (2005c).

cerebral blood flow in schizophrenia. *Biol Psychiatry*, 15. 49(8), 704-715. Min SK, An SK, Jon DI, Lee JD. (1999). Positive and negative symptoms and regional

*Neuropsychopharmacol Biol Psychiatry*, 16(6), 797-832.

confirmation. *Am J Psychiatry*, 147(10), 1313-1317.

*Res*, 14. 74(1), 25-33.

1834.

*Psychiatry*, 15. 61(6), 765-775.

*Psychiatry Res*, 15, 173(1), 63-70.

*Psychiatry*, 186, 203-208.

*Psychiatr Res*, 39(2), 117-127.

tomography. *Biol Psychiatry*. 1. 41(5), 550-559.

SPECT study. *Psychiatry Res*, 30. 90(3), 159-168.

in schizophrenia. *Int Clin Psychopharmacol*, 20(1), 13-18.

healthy controls on single photon emission computerised tomography. *Psychiatry* 

Regional cerebral glucose metabolic abnormalities in bipolar II depression. *Biol* 

(1990). Left prefrontal glucose hypometabolism in the depressed state: a

McGinnis S, Glass TG, Martin CC, Fox PT. (1997). Cingulate function in depression:

impact of comorbidity of mental and physical conditions on role disability in the

Pretreatment regional brain glucose uptake in the midbrain on PET may predict remission from a major depressive episode after three months of treatment.

on relative cerebral blood perfusion in schizophrenia: assessment with technetium-99m hexamethyl-propyleneamine oxime single photon emission computed

(2001).Comparison of the effects of risperidone and haloperidol on regional

cerebral perfusion in antipsychotic-naive schizophrenic patients: a high-resolution

ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of

Desco M. (2005a). Hypofrontality in men with first-episode psychosis. *Br J* 

episodes of schizophrenia associated with limbic metabolic hyperactivity. *J* 

Olanzapine-induced cerebral metabolic changes related to symptom improvement


Resting State Blood Flow and Glucose Metabolism in Psychiatric Disorders 153

Schilder P. (1938). The organic background of obsessions and compulsions. Am J Psychiatry,

Schroder J, Buchsbaum MS, Siegel BV, Geider FJ, Lohr J, Tang C, Wu J, Potkin SG. (1996).

Schwartz JM, Stoessel PW, Baxter LR Jr, Martin KM, Phelps ME. (1996). Systematic changes

Shenton ME, Dickey CC, Frumin M, McCarley RW. (2001). A review of MRI findings in

Shihabuddin L, Buchsbaum MS, Hazlett EA, Haznedar MM, Harvey PD, Newman A,

Skaf CR, Yamada A, Garrido GE, Buchpiguel CA, Akamine S, Castro CC, Busatto GF. (2002).

Steinberg JL, Devous MD SR, Paulman RG, Gregory RR. (1995). Regional cerebral blood

Stoll AL, Renshaw PF, Yurgelun-Todd DA, Cohen BM. (2000). Neuroimaging in bipolar

Strakowski SM, DelBello MP, Adler C, Cecil DM, Sax KW. (2000). Neuroimaging in bipolar

Swann AC. (2010). Approaches to preventing relapse in bipolar disorder: addressing nonadherence and prodromal symptoms. *J Clin Psychiatry*, 71(12), e35. Swedo SE, Rapoport JL, Cheslow DL, Leonard HL, Ayoub EM, Hosier DM, Wald ER. (1989).

Swedo SE, Pietrini P, Leonard HL, Schapiro MB, Rettew DC, Goldberger EL, Rapoport SI,

Takano H, Motohashi N, Uema T, Ogawa K, Ohnishi T, Nishikawa M, Kashima H, Matsuda

disorder: what have we learned? *Biol Psychiatry*, 15. 48(6), 505-517.

of obsessive-compulsive disorder. *Arch Gen Psychiatry*, 53(2), 109-113. Scottish Schizophrenia Research Group. (1998). Regional cerebral blood flow in first-episode

*Affect Disord*, 17(3), 211-218.

*Schizophr Res*, 19(1), 41-53.

*Scand*, 97(6), 440-449.

68(2-3), 295-305.

*Schizophr Res*, 17(3), 229-240.

*Psychiatry*, 49(9), 690-694.

*Psychiatry*, 190, 63-68.

disorder. *Bipolar Disord*, 2(3 Pt 1), 148-164.

chorea. *Am J Psychiatry*, 146(2), 246-249.

schizophrenia. *Schizophr Res,* 15. 49(1-2), 1-52.

verbal learning task. *Arch Gen Psychiatry*, 55(3), 235-243.

94, 1397–1414.Schlegel S, Aldenhoff JB, Eissner D, Lindner P, Nickel O. (1989). Regional cerebral blood flow in depression: associations with psychopathology. *J* 

Cerebral metabolic activity correlates of subsyndromes in chronic schizophrenia.

in cerebral glucose metabolic rate after successful behavior modification treatment

schizophrenia patients before and after antipsychotic drug treatment. *Acta Psychiatr* 

Schnur DB, Spiegel-Cohen J, Wei T, Machac J, Knesaurek K, Vallabhajosula S, Biren MA, Ciaravolo TM, Luu-Hsia C. (1998). Dorsal striatal size, shape, and metabolic rate in never-medicated and previously medicated schizophrenics performing a

Psychotic symptoms in major depressive disorder are associated with reduced regional cerebral blood flow in the subgenual anterior cingulate cortex: a voxelbased single photon emission computed tomography (SPECT) study. *J Affect Disord*,

flow in first break and chronic schizophrenic patients and normal controls.

High prevalence of obsessive-compulsive symptoms in patients with Sydenham's

Rapoport JL, Grady CL. (1992). Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy. *Arch Gen* 

H. (2007). Changes in regional cerebral blood flow during acute electroconvulsive therapy in patients with depression: positron emission tomographic study. *Br J* 


Rasmussen SA, Eisen JL. (1992). The epidemiology and differential diagnosis of obsessive

Remington G, Agid O, Foussias G. (2011). Schizophrenia as a disorder of too little dopamine: implications for symptoms and treatment. *Expert Rev Neurother*, 11(4), 589-607. Rosenberg R, Vorstrup S, Andersen A, Bolwig TG. (1988). Effect of ECT on Cerebral Blood Flow in Melancholia Assessed with SPECT. *Convuls Ther*, 4(1), 62-73. Rubin RT, Villanueva-Meyer J, Ananth J, Trajmar PG, Mena I. (1992). Regional xenon 133

Rubin RT, Ananth J, Villanueva-Meyer J, Trajmar PG, Mena I. (1995). Regional 133xenon

Rubinsztein JS, Fletcher PC, Rogers RD, Ho LW, Aigbirhio FI, Paykel ES, Robbins TW,

Sabri O, Erkwoh R, Schreckenberger M, Cremerius U, Schulz G, Dickmann C, Kaiser HJ,

Sachdev P, Brodaty H, Rose N, Haindl W. (1997). Regional cerebral blood flow in late-onset

Saxena S, Brody AL, Schwartz JM, Baxter LR. (1998). Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder. *Br J Psychiatry,* Suppl (35), 26-37. Saxena S, Brody AL, Maidment KM, Dunkin JJ, Colgan M, Alborzian S, Phelps ME, Baxter

Saxena S, Brody AL, Ho ML, Alborzian S, Ho MK, Maidment KM, Huang SC, Wu HM, Au

Saxena S, Brody AL, Ho ML, Alborzian S, Maidment KM, Zohrabi N, Ho MK, Huang SC,

Saxena S, Brody AL, Maidment KM, Smith EC, Zohrabi N, Katz E, Baker SK, Baxter LR Jr.

Saxena S, Gorbis E, O'Neill J, Baker SK, Mandelkern MA, Maidment KM, Chang S, Salamon

cerebral blood flow and cerebral technetium 99m HMPAO uptake in unmedicated patients with obsessive-compulsive disorder and matched normal control subjects. Determination by high-resolution single-photon emission computed tomography.

cerebral blood flow and cerebral 99mTc-HMPAO uptake in patients with obsessive-compulsive disorder before and during treatment. *Biol Psychiatry*, 1.

Sahakian BJ. (2001). Decision-making in mania: a PET study. *Brain*, 124 (Pt 12),

Steinmeyer EM, Sass H, Buell U. (1997). Regional cerebral blood flow and negative/positive symptoms in 24 drug-naive schizophrenics. *J Nucl Med,* 38(2),

schizophrenia: a SPECT study using 99mTc-HMPAO. *Schizophr Res,* 30. 27(2-3), 105-117.

LR Jr. (1999). Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder.

SC, Baxter LR Jr. (2001). Cerebral metabolism in major depression and obsessivecompulsive disorder occurring separately and concurrently. *Biol Psychiatry*, 1.50(3),

Wu HM, Baxter LR Jr. (2002). Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder vs major depression. *Arch* 

(2004). Cerebral glucose metabolism in obsessive-compulsive hoarding. *Am J* 

N, Brody AL, Schwartz JM, London ED. (2009). Rapid effects of brief intensive cognitive-behavioral therapy on brain glucose metabolism in obsessive-compulsive

compulsive disorder. *J Clin Psychiatry*, 53 Suppl, 4-10.

*Arch Gen Psychiatry*, 49(9), 695-702.

*Neuropsychopharmacology*, 21(6), 683-693.

*Gen Psychiatry*, 59(3), 250-261.

*Psychiatry*, 161(6), 1038-1048.

disorder. *Mol Psychiatry*, 14(2), 197-205.

38(7), 429-437.

2550-2563.

181-188.

159-170.


**8** 

*1Bulgaria 2Switzerland* 

**The Memory, Cognitive and** 

 **and Neuroimaging Studies** 

*1Institute of Neurobiology, Bulgarian Academy of Sciences* 

Roumen Kirov1 and Serge Brand2

**Psychological Functions of Sleep:** 

**Update from Electroencephalographic** 

*2Depression Research Unit, Psychiatric Hospital of the University of Basel* 

Sleep is a universal biological feature in almost all, if not in all species, and represents a global state of immobility with greatly reduced responsiveness to environmental stimuli, which can be distinguished from coma or anaesthesia by its rapid reversibility (Cirelli & Tononi, 2008). It is by no means a dormant state. When it is prevented, the body tries to recover the lost amount. The existence of sleep rebound after deprivation reveals that sleep is not simply a period of reduced activity or alertness regulated by circadian or ultradian rhythms (Dinges et al., 2005). Notably, in most vertebrates and all mammal species, including man, sleep displays a specific architecture roughly described as a cyclic occurrence of rapid eye movement (REM) sleep and non-REM sleep. Further, dramatic changes in brain electrophysiology, neurochemistry and functional anatomy biologically distinguish the different sleep stages from one another (Hobson & Pace-Schott, 2002; Pace-Schott & Hobson, 2002). Also, human and animal neurophysiologic studies have shown that the magnitude of changes in brain metabolism and neuronal activity in many discrete brain structures during certain sleep stages exceeds that during most of the waking periods (Gottesmenn, 1999; Maquet et al., 1996; Nofzinger et al., 1997; Steriade & Timofeev, 2003). Although the precise functions of sleep are still beyond comprehensive understanding (Cirelli & Tononi, 2008), many studies point to the critical role of sleep for physiological functioning and adaptation. Its vital importance is well documented by the fact that its deprivation in rodents and flies can cause death more quickly relative to food deprivation (Rechtschaffen, 1998). Thus, sleep is shown to serve many energetic and metabolic, immune, thermoregulatory, cardiovascular, and respiratory functions, all responsible for normal brain and body homeostasis (Siegel, 2009; Tononi & Cirelli, 2006). Notably, along with these functions, sleep is shown to play a key role for important cognitive and psychological processes, among which learning and memory have been most intensively studied (Diekelmann & Born, 2010; Rasch & Born, 2007; Stickgold, 2005; Walker, 2008; Walker & Stickgold, 2006; 2010). Accordingly, an extensive body of research has revealed a cruicial

**1. Introduction** 

