THE BIOLOGICAL BASIS OF PSYCHIATRIC ILLNESS
DEBOROAH KREISS, PH.D.
My research interests concern the biological basis of psychiatric illness. In particular, I am interested in investigating the nature of maladaptive information processing that underlies several mental disease states, such as attention deficit disorder, schizophrenia, drug addiction, and obsessive compulsive disorder. My current research approach is to investigate the effects of selective serotonin reuptake inhibitors (SSRI's) upon brain function. SSRI's are known to affect communication between cells of the brain by prolonging the effects of serotonin-releasing cells. SSRI's, such as Prozac and Paxil, are quite successful for the treatment of a number of psychiatric disorders, such as depression, anxiety, phobia, panic attacks, anorexia nervosa, and obsessive-compulsive disorder. An unresolved issue about the therapeutic action of SSRI's is why several weeks of exposure is required before the symptoms of psychiatric illness are alleviated. By examining how repeated exposure to SSRI's alters brain function, I hope to gain insight into the dys-function that underlies mental disease states.
Although the effects of SSRI's have been examined in areas of the brain associated with emotion and mood, relatively little investigative effort has been devoted towards examination of effects of these drugs on another part of the brain, the basal ganglia. The basal ganglia is a group of interconnected structures that play a critical role in the control of movement. Recent research has shown that the output of the basal ganglia not only influences the "motor" aspects of behavior (i.e. sequencing and executing muscle commands), but also the "cognitive" aspects of behavior (i.e. planning and selection of behavioral routines). Understanding the effects of SSRI's on the basal ganglia will facilitate the development of more successful approaches for treating mental disease states involving motor dysfunction (e.g. obsessive compulsive disorder and Tourette's syndrome) and for treating psychiatric patients with concurrent movement disorders (e.g. Parkinson's disease). I plan to assess the effects of long term exposure to SSRI's on structures of the basal ganglia in the rat brain using electrophysiological techniques which enable the electrical activity of neurons to be measured in the whole animal.
Research Interests
- the biological basis of mental illness
- the neurological components determining symptom expression
- the physiological mechanisms mediating the therapeutic effects of psychoactive agents
Experimental Approaches
- Determination of neurotransmitter systems and receptor subtypes affecting rat behavior using pharmacologically selective agents
- Identification of neuronal regions and circuits mediating behavior via comparison of c-FOS protein expression in the brain tissue of behaviorally expressive and non-expressive rats
- Examination of the effects of psychotherapeutic agents upon the firing rate and pattern of behaviorally relevant neuronal populations using i n vivo electrophysiology
Sample Publications
- Allers KA, Bergstrom DA, Ghazi LJ, Kreiss DS, and Walters JR (2005). MK801 and amantadine exert different effects on subthalamic neuronal activity in a rodent model of Parkinson's disease. Experimental Neurology 191: 104-118
- Allers KA, Kreiss DS , and Walters JR (2002). Neuronal Firing Patterns in the Subthalamic Nucleus: Effects of dopamine receptor stimulation on multisecond oscillations. In The Basal Ganglia IV, A.M. Graybiel, M.R. DeLong, S.T. Kitai (Eds) Kluwer Academic/Plenum Publishers, New York pp. 245-254
- Allers KA, Kreiss DS, and Walters JR (2000). Multisecond oscillations in the subthalamic nucleus: Effects of apomorphine and dopamine cell lesion. Synapse 38:38-50
- Kreiss DS , Mastropietro CW, Rawji SS, and Walters JR (1997) The response of subthalamic nucleus neurons to dopamine receptor stimulation in a rodent model of Parkinson's disease. Journal of Neuroscience. 17:6807-6819
- Kreiss DS and Lucki I. (1997) Chronic administration of the 5-HT 1A receptor agonist 8-OH-DPAT differentially desensitizes 5-HT 1A autoreceptors of the dorsal and median raphe nuclei. Synapse. 25:107-116
- Kreiss DS , Anderson LA, and Walters JR. (1996) Apomorphine and dopamine D 1 receptor agonists increase the firing rates of subthalamic nucleus neurons. Neuroscience. 72:863-876
- Kreiss DS , Bergstrom DA, Gonzalez AM, Huang KX, Sibley DR, and Walters JR. (1995) Dopamine receptor agonist potencies for inhibition of cell firing correlate with dopamine D 3 receptor binding affinities. European Journal of Pharmacology. 277:209-214
- Kreiss DS and Lucki I. (1995) Effects of acute and repeated administration of antidepressant drugs on extracellular levels of 5-hydroxytryptamine measured in vivo. Journal of Pharmacology and Experimental Therapeutics. 274:866-876
- Kirby LG, Kreiss DS , Singh A, and Lucki I. (1995) The effect of 5,7-dihydroxytryptamine lesions on basal and fenfluramine-induced serotonin release in striatum. Synapse. 20:99-105
- Kreiss DS and Lucki I. (1994) Differential regulation of serotonin (5-HT) release in the striatum and hippocampus by 5-HT 1A autoreceptors of the dorsal and median raphe nuclei. Journal of Pharmacology and Experimental Therapeutics. 269:1268-1279
- Kreiss DS and Lucki I. (1994) Discriminative stimulus properties of the serotonin uptake inhibitor sertraline. Experimental and Clinical Psychopharmacology. 2:1-12
- Lucki I, Singh A, and Kreiss DS. (1994) Antidepressant-like behavioral effects of serotonin receptor agonists. Neuroscience and Biobehavioral Review. 18:85-95
- Kreiss DS , Wieland S, and Lucki I. (1993) The presence of a serotonin uptake inhibitor alters pharmacological manipulations of serotonin release. Neuroscience. 52:295-301
- Kreiss DS and Lucki I. (1992) Desensitization of 5-HT 1A autoreceptors by chronic administration of 8-OH-DPAT as assessed with in vivo microdialysis. Neuropharmacology. 31:1073-1075
- Doty RL, Kreiss DS , and Frye RE. (1990) Human odor intensity perception: Correlation with frog epithelial adenylate cyclase activity and transepithelial voltage response. Brain Research. 527:130-134
