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Brain-psychopathology relations in schizophrenia
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Biological psychiatry and everyday clinical practice
BIOL. PSYCHIATRY 1997;42: 1S-297S
Symposia
91. Biological psychiatry and everyday clinical practice
191-1 I Brain-psychopathology relations In schizophrenia N.C. Andreasen. Mental Health Clinical Research Center, Dept of Psychiatry, Iowa City. Iowa. USA ObJective: To review the applications of neuroscience and neuroimaging techniques to everyday clinical practice. Methods: A variety of new assessment techniques are currently available that permit clinicians to evaluate brain structure and function in patients suffering from schizophrenia These Include Magnetic Resonance (MR), Single Photon Emission Computed Tomography (SPECT), and Positron Emission Tomography (PET). Results: Structural imaging techniques may reveal a variety of abnormali• ties in patients suffering from schizophrenia, such as ventricular enlargement, prominent cortical sulci, or developmental anomalies such as cavum septi pellucidl. These may be associated with a worse prognosis, more prominent negative symptoms, a tendency to be treatment refractory, and sensitivity to medication side effects. Functional imaging techniques have been applied to the study of receptor occupancy and may offer a way to study dose-response relationships at some time in the future. Research findings may also have clinical applications in the future. These include observation of structural abnormalities such as decreased cerebral, frontal, or temporal lobe size and functional abnormalities such as anomalies In neural circuitry, areas of Increased flow during auditory hallucinations. and areas of decreased flow during the performance. Conclusions: The various Imaging techniques have advanced our knowl• edge of the neural mechanisms of schizophrenia and provided methods for examining the effects of treatment. While they do not have direct diagnos• tic applications, they may be useful for evaluating prognosis or monitoring treatment. . References (1) Nopoulos P, Swayze V, Flaum M, Ehrhardt JC, Yuh WTC and Andreesen NC (1996): Cavum eepU pellucldlln normale and patients with schizophrenia as detected by MRI. BioI PsychIatry '" prese. (2] Silberswelg OA, Stem E, Frith C, Cahill C, Holmes A, Grootoonk S, Seaward J, McKenna P, Chua SE, SChnorr L, Jones T and Frackowiak RSJ (1995): A functional neuroanatomy 01 hallucinations In schizophrenia. Nawrtl37S: 176-179. (3) Andreasen NC, Aashman L, Aaum M, Amdt S, Swayze V, O'leary OS, Ehrhardt JC and Yuh WTC (1994): Regional brain abnormalities In schizophrenia measured wl1h magnetic resonance Imaging. JAMA 272; 1763-1769.
191-21 Are biological markers useful In the practice of mood disorders? H.S. Akiskal. fntemational Mood Center. University of Califomia at san Diego. La Jolla. CA 92093.()603, USA Diligent search for the biological foundations of mood disorders has been one of the hallmarks of biological psychiatry during this past four decades. Despite the fact that some of the best minds that have ever worked in psychiatry-uslng methodological innovations of a rigorous nature-little progress has been made towards clinical application for everyday practice. Neuroendocrine markers have proven to be Insufficiently specific. Sleep EEG evaluation Is unwieldy and, again, Insufficiently specific. The same Is true for brain imaging. A$ for challenge tests for serotonin function, they have been related to violent suicidal attempts and completed suicide; but again, neither their sensitivity nor their specificity has been established. Indeed, serotonin dysfunction spans a range that includes personality disorders, anxiety disorders, mood disorders, eating disorders, sleep disorders. just to mention a few. Some have argued that our diagnostic categories should be dropped and patients be classified on the basis of the biological findings. Others have suggested that we should use both In our assessment of patients. In brief, there is no
consensus on how these biological markers can be useful to the clinician. I would submit that, other than certain thyroid tests in rapid-cycling and refractory depressive disorders, clinicians don't use any biological markers. Psychopharmacology Is the main area in which biological measures have found routine use. This Is primarily in monitoring lithium blood levels, and that is primarily to avert a potentially toxic blood level; antidepressant and anticonvulsant blood levels are not of definite utility clinically in most patients receiving them. This Is not to say that biological investigations of mood disorders have been unimportant. On the contrary, a great deal of exciting and intriguing data has been generated to argue for biological underpinnings in mood dis• orders. Perhaps the most attractive development Is In the area of molecular genetics but here again, definitive flndlngs are lacking. Nonetheless, these developments have brought about a major change In the thinking of psychi• atrists worldwide about the relevance of biological factors In the etiology and treatment of mood disorders. This. I submit has been the major Influence of biological research in mood disorders. Clinicians today pay special attention to diagnostiC nuances which may have differential Impact on what type of biological Interventions would be useful. I will conclude this presentation by illustrating these developments with the use of data on the prevalence of soft bipolar and mixed states In a multi-center French national study. Reference [I] Aklskal HS; The prevalent clinical spectrum 01 bipolar disorders: Beyond OSM-IV. J Clln Psychopharmacology 16[suppll]; 4&-148, 1996.
191-41 eating Is biological psychiatry addressing the treatment of disorders, OCD and OCD spectrum disorders? E. Hollander, C.M. Wong, C.M. DeCaria, B.A. Aronowitz, L Margolin. CompulsIve fmpulslve & Anxiety Dis. err., Dept. Psychiatry, Mt. Sinai School of Medicine. New York. NY. USA Biological psychiatry has explored the functional neuroclrcuitry. seroton• erglc sensitivity, and neuropsychiatry of eating disorders, OCD and OCD spectrum disorders. These disorders share certain features, Including phe• nomenological overlap (intrusive thoughts, compulsive behaviors), course of Illness, associated features, comorbidity, and selective efficacy with sero• tonin reuptake Inhibitors and specific behavioral therapies. In addition, there may be overlap of biological markers of serotonergic function and frontal hyperactivity. Method: Patients with OCD. body dysmorphlc disorder, pathological gam• bling and autism (OCD spectrum disorders) were contrasted on 1) selective efficacy to serotonin reuptake Inhibitors vs. norepinephrine reuptake in• hibitors; 2) behavioral responslvlty to the partial 5 HT 2C agonist M-CPP; 3) anterior cingulate and frontal activity on PET and ReBF; and 4) neuropsy• chiatric abnormalities by soft-sign and neuropsychological testing. Results: Patients on the compulsive end of the spectrum (I.e. OCD, BOD) are characterized by Increased behavioral sensitivity to M-CPP (obsesso• geniclanxiogenlc response) selective, delayed and persistent response to SSRI's, and Increased frontaVcingulate activation. In contrest, patients on the Impulsive end of the spectrum (I.e. pathological gamblers. borderline person• ality disorder) are characterized by a high, dlsinhlbited response to M-CPP, a rapid and transient response to SSRI's, and evidence of hypofrontality. Bulimic and binge eating disorder patients reflect the Impulsive end of the spectrum, phenomenologically and biologically. whereas anorectic patients reflect the compulsive end of the spectrum. References [I] Hollander E. (1993) Obsessive Compulsive Related Dlsorr:Jsrs. American Psychiatric
Prell, Inc. Washington D.C. [2) Hollander, E, DeCaria CM, Nltescu A, Gully R, Suckow RF, Cooper Ta, Gorman J, Klein OF, UebowItz M. Serctonerglc Function In Obsessfve.Compulsive OIsotder. Be• havioral MId neuroendocrine rtlsponses to oral m-Chlorophenytplperazlne and Fen• f1uramJnein patients and heanhy II'()/unteers. Arch Gen Psychiatry. 1992; 49: 21-28. (3) Hollander E, & BenzaQuen SO. ,. there a distinct OCD spectrum? CNS Spec1ruma. 1996; 1(1): 17-26.
Biological psychiatry and everyday clinical practice
BIOL. PSYCHIATRY 1997;42: 1S-297S
Symposia
91. Biological psychiatry and everyday clinical practice
191-1 I Brain-psychopathology relations In schizophrenia N.C. Andreasen. Mental Health Clinical Research Center, Dept of Psychiatry, Iowa City. Iowa. USA ObJective: To review the applications of neuroscience and neuroimaging techniques to everyday clinical practice. Methods: A variety of new assessment techniques are currently available that permit clinicians to evaluate brain structure and function in patients suffering from schizophrenia These Include Magnetic Resonance (MR), Single Photon Emission Computed Tomography (SPECT), and Positron Emission Tomography (PET). Results: Structural imaging techniques may reveal a variety of abnormali• ties in patients suffering from schizophrenia, such as ventricular enlargement, prominent cortical sulci, or developmental anomalies such as cavum septi pellucidl. These may be associated with a worse prognosis, more prominent negative symptoms, a tendency to be treatment refractory, and sensitivity to medication side effects. Functional imaging techniques have been applied to the study of receptor occupancy and may offer a way to study dose-response relationships at some time in the future. Research findings may also have clinical applications in the future. These include observation of structural abnormalities such as decreased cerebral, frontal, or temporal lobe size and functional abnormalities such as anomalies In neural circuitry, areas of Increased flow during auditory hallucinations. and areas of decreased flow during the performance. Conclusions: The various Imaging techniques have advanced our knowl• edge of the neural mechanisms of schizophrenia and provided methods for examining the effects of treatment. While they do not have direct diagnos• tic applications, they may be useful for evaluating prognosis or monitoring treatment. . References (1) Nopoulos P, Swayze V, Flaum M, Ehrhardt JC, Yuh WTC and Andreesen NC (1996): Cavum eepU pellucldlln normale and patients with schizophrenia as detected by MRI. BioI PsychIatry '" prese. (2] Silberswelg OA, Stem E, Frith C, Cahill C, Holmes A, Grootoonk S, Seaward J, McKenna P, Chua SE, SChnorr L, Jones T and Frackowiak RSJ (1995): A functional neuroanatomy 01 hallucinations In schizophrenia. Nawrtl37S: 176-179. (3) Andreasen NC, Aashman L, Aaum M, Amdt S, Swayze V, O'leary OS, Ehrhardt JC and Yuh WTC (1994): Regional brain abnormalities In schizophrenia measured wl1h magnetic resonance Imaging. JAMA 272; 1763-1769.
191-21 Are biological markers useful In the practice of mood disorders? H.S. Akiskal. fntemational Mood Center. University of Califomia at san Diego. La Jolla. CA 92093.()603, USA Diligent search for the biological foundations of mood disorders has been one of the hallmarks of biological psychiatry during this past four decades. Despite the fact that some of the best minds that have ever worked in psychiatry-uslng methodological innovations of a rigorous nature-little progress has been made towards clinical application for everyday practice. Neuroendocrine markers have proven to be Insufficiently specific. Sleep EEG evaluation Is unwieldy and, again, Insufficiently specific. The same Is true for brain imaging. A$ for challenge tests for serotonin function, they have been related to violent suicidal attempts and completed suicide; but again, neither their sensitivity nor their specificity has been established. Indeed, serotonin dysfunction spans a range that includes personality disorders, anxiety disorders, mood disorders, eating disorders, sleep disorders. just to mention a few. Some have argued that our diagnostic categories should be dropped and patients be classified on the basis of the biological findings. Others have suggested that we should use both In our assessment of patients. In brief, there is no
consensus on how these biological markers can be useful to the clinician. I would submit that, other than certain thyroid tests in rapid-cycling and refractory depressive disorders, clinicians don't use any biological markers. Psychopharmacology Is the main area in which biological measures have found routine use. This Is primarily in monitoring lithium blood levels, and that is primarily to avert a potentially toxic blood level; antidepressant and anticonvulsant blood levels are not of definite utility clinically in most patients receiving them. This Is not to say that biological investigations of mood disorders have been unimportant. On the contrary, a great deal of exciting and intriguing data has been generated to argue for biological underpinnings in mood dis• orders. Perhaps the most attractive development Is In the area of molecular genetics but here again, definitive flndlngs are lacking. Nonetheless, these developments have brought about a major change In the thinking of psychi• atrists worldwide about the relevance of biological factors In the etiology and treatment of mood disorders. This. I submit has been the major Influence of biological research in mood disorders. Clinicians today pay special attention to diagnostiC nuances which may have differential Impact on what type of biological Interventions would be useful. I will conclude this presentation by illustrating these developments with the use of data on the prevalence of soft bipolar and mixed states In a multi-center French national study. Reference [I] Aklskal HS; The prevalent clinical spectrum 01 bipolar disorders: Beyond OSM-IV. J Clln Psychopharmacology 16[suppll]; 4&-148, 1996.
191-41 eating Is biological psychiatry addressing the treatment of disorders, OCD and OCD spectrum disorders? E. Hollander, C.M. Wong, C.M. DeCaria, B.A. Aronowitz, L Margolin. CompulsIve fmpulslve & Anxiety Dis. err., Dept. Psychiatry, Mt. Sinai School of Medicine. New York. NY. USA Biological psychiatry has explored the functional neuroclrcuitry. seroton• erglc sensitivity, and neuropsychiatry of eating disorders, OCD and OCD spectrum disorders. These disorders share certain features, Including phe• nomenological overlap (intrusive thoughts, compulsive behaviors), course of Illness, associated features, comorbidity, and selective efficacy with sero• tonin reuptake Inhibitors and specific behavioral therapies. In addition, there may be overlap of biological markers of serotonergic function and frontal hyperactivity. Method: Patients with OCD. body dysmorphlc disorder, pathological gam• bling and autism (OCD spectrum disorders) were contrasted on 1) selective efficacy to serotonin reuptake Inhibitors vs. norepinephrine reuptake in• hibitors; 2) behavioral responslvlty to the partial 5 HT 2C agonist M-CPP; 3) anterior cingulate and frontal activity on PET and ReBF; and 4) neuropsy• chiatric abnormalities by soft-sign and neuropsychological testing. Results: Patients on the compulsive end of the spectrum (I.e. OCD, BOD) are characterized by Increased behavioral sensitivity to M-CPP (obsesso• geniclanxiogenlc response) selective, delayed and persistent response to SSRI's, and Increased frontaVcingulate activation. In contrest, patients on the Impulsive end of the spectrum (I.e. pathological gamblers. borderline person• ality disorder) are characterized by a high, dlsinhlbited response to M-CPP, a rapid and transient response to SSRI's, and evidence of hypofrontality. Bulimic and binge eating disorder patients reflect the Impulsive end of the spectrum, phenomenologically and biologically. whereas anorectic patients reflect the compulsive end of the spectrum. References [I] Hollander E. (1993) Obsessive Compulsive Related Dlsorr:Jsrs. American Psychiatric
Prell, Inc. Washington D.C. [2) Hollander, E, DeCaria CM, Nltescu A, Gully R, Suckow RF, Cooper Ta, Gorman J, Klein OF, UebowItz M. Serctonerglc Function In Obsessfve.Compulsive OIsotder. Be• havioral MId neuroendocrine rtlsponses to oral m-Chlorophenytplperazlne and Fen• f1uramJnein patients and heanhy II'()/unteers. Arch Gen Psychiatry. 1992; 49: 21-28. (3) Hollander E, & BenzaQuen SO. ,. there a distinct OCD spectrum? CNS Spec1ruma. 1996; 1(1): 17-26.