Browsing by Author "Harvey, Brian H."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    The new-generation antipsychotics - integrating the neuropathology and pharmacology of schizophrenia
    (Health & Medical Publishing Group, 1999) Harvey, Brian H.; Stein, Dan J.; Emsley, Robin A.
    Despite a well-established role for dopamine (DA) in the neuropathology of schizophrenia, and the evidence of a hyperdopaminergic state in the schizophrenic brain, many questions still remain. Typical agents acting predominantly on DA D2 receptors are only partially effective. New data now indicate that the interaction between DA and the various DA receptors as well as DA interaction with other transmitter systems, are more critical in deciding the therapeutic success of an antipsychotic than actions on DA alone. These interactions are closely associated with what is being documented regarding the neuro-anatomy, neurobiology and neuropsychology of the disorder. There have been major advances in the understanding of the neuropathology of schizophrenia that, while not replacing the original DA hypothesis, have forced a re-evaluation of our understanding of the disorder. In this paper we present the biochemical and neuropathological basis for schizophrenia and discuss six new atypical antipsychotics according to these theories. Drugs reviewed include clozapine, risperidone, olanzapine, ziprasidone, sertindole and quetiapine. While not a comparative analysis of these drugs, this paper is an appraisal of how their pharmacology correlates with our present knowledge of the disorder and highlights differences among the drugs in this group. These agents therefore possess specifically designed qualities, to varying degrees, promising a significant improvement over earlier agents in terms of treating positive and negative symptoms, with a minimal risk of extrapyramidal symptoms (EPS). These qualities include an emphasis on D2 selectivity, D1/D2 balance, DA/serotonin (5HT) balance, D3/D4 selectivity, DA/acetylcholine (Ach) balance and glutamate (Glu)/gamma-aminobutyric acid (GABA) balance. The drugs are discussed with reference to these criteria. Targeted drug design has created a goal-directed strategy with which to treat schizophrenia. These new antipsychotics appear to have several distinct advantages over their predecessors, and should make a major contribution to the treatment of schizophrenia and the re-integration of these patients into society.
  • Thumbnail Image
    Item
    Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram
    (BioMed Central, 2004-10) Carey, Paul D.; Warwick, James; Niehaus, Dana J. H.; Van der Linden, Geoffrey; Van Heerden, Barend B.; Harvey, Brian H.; Seedat, Soraya; Stein, Dan J.
    Background: Several studies have now examined the effects of selective serotonin reuptake inhibitor (SSRI) treatment on brain function in a variety of anxiety disorders including obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social anxiety disorder (social phobia) (SAD). Regional changes in cerebral perfusion following SSRI treatment have been shown for all three disorders. The orbitofrontal cortex (OFC) (OCD), caudate (OCD), medial pre-frontal/cingulate (OCD, SAD, PTSD), temporal (OCD, SAD, PTSD) and, thalamic regions (OCD, SAD) are some of those implicated. Some data also suggests that higher perfusion pre-treatment in the anterior cingulate (PTSD), OFC, caudate (OCD) and antero-lateral temporal region (SAD) predicts subsequent treatment response. This paper further examines the notion of overlap in the neurocircuitry of treatment and indeed treatment response across anxiety disorders with SSRI treatment. Methods: Single photon emission computed tomography (SPECT) using Tc-99 m HMPAO to assess brain perfusion was performed on subjects with OCD, PTSD, and SAD before and after 8 weeks (SAD) and 12 weeks (OCD and PTSD) treatment with the SSRI citalopram. Statistical parametric mapping (SPM) was used to compare scans (pre- vs post-medication, and responders vs non-responders) in the combined group of subjects. Results: Citalopram treatment resulted in significant deactivation (p = 0.001) for the entire group in the superior (t = 4.78) and anterior (t = 4.04) cingulate, right thalamus (t = 4.66) and left hippocampus (t = 3.96). Deactivation (p = 0.001) within the left precentral (t = 4.26), right mid-frontal (t = 4.03), right inferior frontal (t = 3.99), left prefrontal (3.81) and right precuneus (t= 3.85) was more marked in treatment responders. No pattern of baseline activation distinguished responders from non-responders to subsequent pharmacotherapy. Conclusions: Although each of the anxiety disorders may be mediated by different neurocircuits, there is some overlap in the functional neuro-anatomy of their response to SSRI treatment. The current data are consistent with previous work demonstrating the importance of limbic circuits in this spectrum of disorders. These play a crucial role in cognitive-affective processing, are innervated by serotonergic neurons, and changes in their activity during serotonergic pharmacotherapy seem crucial.
  • Thumbnail Image
    Item
    Symmetry symptoms in obsessive-compulsive disorder : clinical and genetic correlates
    (Associacao Brasileira de Psiquiatria, 2016) Lochner, Christine; McGregor, Nathaniel; Hemmings, Sian M. J.; Harvey, Brian H.; Breet, Elsie; Swanevelder, Sonja; Stein, Dan J.
    Objective: In obsessive-compulsive disorder (OCD), symmetry-related symptoms may be important. Although clinical correlates of symmetry-related symptoms have been identified in OCD, few data exist on genetic associations. Animal studies indicate involvement of dopamine in symmetry-related behavior, suggesting this may be relevant to analogous symptoms in OCD. Alterations in dopamine may also reflect environmental influences. However, the association of symmetry-related symptomatology, early adversity, and polymorphisms in dopaminergic genes has not been investigated in OCD. Methods: Clinical information and polymorphisms in key dopaminergic genes were compared between OCD patients with primary symmetry symptoms and those without. Results: OCD patients with primary symmetry symptoms comprised 46.6% (n=210) of the sample (n=451), and were older (p < 0.01), had longer illness duration (p < 0.01), higher OCD severity scores (p = 0.01), and greater comorbidity (p < 0.01) than those without. In Caucasians (n=343), genotype frequency differed significantly between groups for ANKK1 rs1800497, with more OCD patients with symmetry symptoms being homozygous for the A2 (CC) genotype (χ2 = 7.296; p = 0.026). Conclusion: Symmetry symptoms have some distinct clinical features and may represent a marker of severity in OCD. However, clinical associations, in combination with the association found with the ANKK1 rs1800497 A2 variant, suggest that primary symmetry symptoms may represent a distinctive clinical and psychobiological profile.