Medical Pharmacology: Antipsychotic Drugs

**Schneiderian first-rank symptoms**
Schneiderian first-rank symptoms (FRS) are a set of specific psychotic experiences described by the German psychiatrist Kurt Schneider in 1959, who proposed that their presence was strongly indicative of schizophrenia in the absence of organic illness. They were historically considered almost unique to schizophrenia, though their diagnostic weight has been revised over time. The symptoms fall into a few broad categories. Passivity experiences involve the feeling that one's thoughts, feelings, impulses, or bodily movements are being controlled or imposed by an external force, sometimes called "made" experiences (e.g., "made" feelings or "made" actions). Thought alienation includes thought insertion (the belief that thoughts are being placed into one's mind by an outside agent), thought withdrawal (the sense that thoughts are being removed), and thought broadcasting (the conviction that one's thoughts are being transmitted to and experienced by others). Delusional perception refers to a two-stage phenomenon where a normal perception is followed immediately by a fully formed, self-referential delusional meaning for example, seeing a red car and suddenly "knowing" it means you have been chosen for a special mission. Finally, there are specific auditory hallucinations: hearing voices that comment on one's actions in the third person, voices that converse with each other about the patient, or hearing one's own thoughts spoken aloud
(1) Mellor, C.S. (1970). First-rank symptoms of schizophrenia. British Journal of Psychiatry 117(536), 15–23. (2) Schneider, K. (1959) Clinical Psychopathology, Grune & Stratton, New York

References
Owen MJ, Sawa A, Mortensen PB. Schizophrenia. Lancet. 2016;388(10039):86–97. doi: 10.1016/S0140-6736(15)01121-6. https://pubmed.ncbi.nlm.nih.gov/26777917/ Lichtenstein P, Yip BH, Björk C, et al.. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet. 2009;373(9659):234–239. doi: 10.1016/S0140-6736(09)60072-6. https://pubmed.ncbi.nlm.nih.gov/19150704/ Cross-Disorder Group of the Psychiatric Genomics Consortium. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet. 2013;45(9):984–994. doi: 10.1038/ng.2711. https://pubmed.ncbi.nlm.nih.gov/23933821/ van Os J, Kapur S. Schizophrenia. Lancet. 2009;374(9690):635–645. doi: 10.1016/S0140-6736(09)60995-8. https://pubmed.ncbi.nlm.nih.gov/19700006/ Goodwin FK, Jamison KR. Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression (2nd ed.). Oxford University Press. 2007. ISBN: 978-0195135794. https://global.oup.com/academic/product/manic-depressive-illness-9780195135794 Keck PE Jr, McElroy SL, Havens JR, et al.. Psychosis in bipolar disorder: phenomenology and impact on morbidity and course of illness. Compr Psychiatry. 2003;44(4):263–269. doi: 10.1016/S0010-440X(03)00080-2. https://pubmed.ncbi.nlm.nih.gov/12923706/ Menezes NM, Arenovich T, Zipursky RB. A systematic review of longitudinal outcome studies of first-episode psychosis. Psychol Med. 2006;36(10):1349–1362. doi: 10.1017/S0033291706007951. https://pubmed.ncbi.nlm.nih.gov/16756689/ Perkins DO, Gu H, Boteva K, Lieberman JA. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry. 2005;162(10):1785–1804. doi: 10.1176/appi.ajp.162.10.1785. https://pubmed.ncbi.nlm.nih.gov/16199825/ Ventura J, Subotnik KL, Nuechterlein KH. Negative symptoms are the predominant predictor of functional impairment in the early course of schizophrenia. Schizophr Res. 2009;107(1):13–19. doi: 10.1016/j.schres.2008.09.026. https://pubmed.ncbi.nlm.nih.gov/18986795/ Harding CM, Brooks GW, Ashikaga T, et al.. The Vermont longitudinal study of persons with severe mental illness, I: Methodology, study sample, and overall status 32 years later. Am J Psychiatry. 1987;144(6):718–726. doi: 10.1176/ajp.144.6.718. https://pubmed.ncbi.nlm.nih.gov/3591988/ Penttilä M, Jääskeläinen E, Hirvonen N, et al.. Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis. Br J Psychiatry. 2014;205(2):88–94. doi: 10.1192/bjp.bp.113.127753. https://pubmed.ncbi.nlm.nih.gov/25252316/ Penttilä M, Jääskeläinen E, Hirvonen N, et al.. Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis. Br J Psychiatry. 2014;205(2):88–94. doi: 10.1192/bjp.bp.113.127753. https://pubmed.ncbi.nlm.nih.gov/25252316/ Kirkpatrick B, Fenton WS, Carpenter WT Jr, Marder SR. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull. 2006;32(2):214–219. doi: 10.1093/schbul/sbj053. https://pubmed.ncbi.nlm.nih.gov/16481659/ Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time?. Arch Gen Psychiatry. 2007;64(10):1123–1131. doi: 10.1001/archpsyc.64.10.1123. https://pubmed.ncbi.nlm.nih.gov/17909124/ Mitchell AJ, Vancampfort D, Sweers K, et al.. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders: a systematic review and meta-analysis. Schizophr Bull. 2013;39(2):306–318. doi: 10.1093/schbul/sbr148. https://pubmed.ncbi.nlm.nih.gov/22207632/ Pompili M, Gonda X, Serafini G, et al.. Epidemiology of suicide in bipolar disorders: a systematic review of the literature. Bipolar Disord. 2013;15(5):457–490. doi: 10.1111/bdi.12087. https://pubmed.ncbi.nlm.nih.gov/23755739/ Tohen M, Hennen J, Zarate CM Jr, et al.. Two-year syndromal and functional recovery in 219 cases of first-episode major affective disorder with psychotic features. Am J Psychiatry. 2000;157(2):220–228. doi: 10.1176/appi.ajp.157.2.220. https://pubmed.ncbi.nlm.nih.gov/10671390/ Ketter TA, Calabrese JR. Stabilization of mood from below versus above baseline in bipolar disorder: a new nomenclature. J Clin Psychiatry. 2002;63(2):146–151. doi: 10.4088/jcp.v63n0208. https://pubmed.ncbi.nlm.nih.gov/11874217/ Judd LL, Akiskal HS, Schettler PJ, et al.. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59(6):530–537. doi: 10.1001/archpsyc.59.6.530. https://pubmed.ncbi.nlm.nih.gov/12044195/ Miklowitz DJ, Otto MW, Frank E, et al.. Psychosocial treatments for bipolar depression: a 1-year randomized trial from the Systematic Treatment Enhancement Program. Arch Gen Psychiatry. 2007;64(4):419–426. doi: 10.1001/archpsyc.64.4.419. https://pubmed.ncbi.nlm.nih.gov/17404119/ Hayes JF, Marston L, Walters K, et al.. Mortality gap for people with bipolar disorder and schizophrenia: UK-based cohort study 2000–2014. Br J Psychiatry. 2017;211(3):175–181. doi: 10.1192/bjp.bp.117.202606. https://pubmed.ncbi.nlm.nih.gov/28684404/ Yatham LN, Kennedy SH, Parikh SV, et al.. CANMAT and ISBD 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97–170. doi: 10.1111/bdi.12609. https://pubmed.ncbi.nlm.nih.gov/29536616/ Andreasen NC, Carpenter WT Jr, Kane JM, et al.. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;162(3):441–449. doi: 10.1176/appi.ajp.162.3.441. https://pubmed.ncbi.nlm.nih.gov/15741458/ Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology. 1998;12(3):426–445. doi: 10.1037/0894-4105.12.3.426. https://pubmed.ncbi.nlm.nih.gov/9673998/ Mesholam-Gately RI, Giuliano AJ, Goff KP, et al.. Neurocognition in first-episode schizophrenia: a meta-analytic review. Neuropsychology. 2009;23(3):315–336. doi: 10.1037/a0014708. https://pubmed.ncbi.nlm.nih.gov/19413443/ Goldman-Rakic PS. Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neurosci. 1994;6(4):348–357. doi: 10.1176/jnp.6.4.348. https://pubmed.ncbi.nlm.nih.gov/7841806/ Green MF, Kern RS, Braff DL, Mintz J. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the 'right stuff'?. Schizophr Bull. 2000;26(1):119–136. doi: 10.1093/oxfordjournals.schbul.a033430. https://pubmed.ncbi.nlm.nih.gov/10755673/ Bora E, Murray RM. Meta-analysis of cognitive deficits in ultra-high risk to psychosis and first-episode psychosis: do the cognitive deficits progress over, or after, the onset of psychosis?. Schizophr Bull. 2014;40(4):744–755. doi: 10.1093/schbul/sbt085. https://pubmed.ncbi.nlm.nih.gov/23770934/ Reichenberg A, Weiser M, Rabinowitz J, et al.. A population-based cohort study of premorbid intellectual, language, and behavioral functioning in patients with schizophrenia, schizoaffective disorder, and nonpsychotic bipolar disorder. Am J Psychiatry. 2002;159(12):2027–2035. doi: 10.1176/appi.ajp.159.12.2027. https://pubmed.ncbi.nlm.nih.gov/12450953/ Schaefer J, Giangrande E, Weinberger DR, Dickinson D. The global cognitive impairment in schizophrenia: consistent over decades and around the world. Schizophr Res. 2013;150(1):42–50. doi: 10.1016/j.schres.2013.07.009. https://pubmed.ncbi.nlm.nih.gov/23911259/ Harvey PD, Silverman JM, Mohs RC, et al.. Cognitive decline in late-life schizophrenia: a longitudinal study of geriatric chronically hospitalized patients. Biol Psychiatry. 1999;45(1):32–40. doi: 10.1016/S0006-3223(98)00273-X. https://pubmed.ncbi.nlm.nih.gov/9894574/ Keefe RS, Bilder RM, Davis SM, et al.. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry. 2007;64(6):633–647. doi: 10.1001/archpsyc.64.6.633. https://pubmed.ncbi.nlm.nih.gov/17548746/ Arts B, Jabben N, Krabbendam L, van Os J. Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives. Psychol Med. 2008;38(6):771–785. doi: 10.1017/S0033291707001675. https://pubmed.ncbi.nlm.nih.gov/17922938/ Bora E, Yucel M, Pantelis C. Cognitive endophenotypes of bipolar disorder: a meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. J Affect Disord. 2009;113(1–2):1–20. doi: 10.1016/j.jad.2008.06.009. https://pubmed.ncbi.nlm.nih.gov/18684514/ Bora E, Yucel M, Pantelis C. Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study. Br J Psychiatry. 2009;195(6):475–482. doi: 10.1192/bjp.bp.108.055731. https://pubmed.ncbi.nlm.nih.gov/19949194/ Simonsen C, Sundet K, Vaskinn A, et al.. Neurocognitive profiles in bipolar I and bipolar II disorder: differences in pattern and magnitude of dysfunction. Bipolar Disord. 2008;10(2):245–255. doi: 10.1111/j.1399-5618.2007.00492.x. https://pubmed.ncbi.nlm.nih.gov/18271904/ Hill SK, Reilly JL, Keefe RS, et al.. Neuropsychological impairments in schizophrenia and psychotic bipolar disorder: findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. Am J Psychiatry. 2013;170(11):1275–1284. doi: 10.1176/appi.ajp.2013.12101298. https://pubmed.ncbi.nlm.nih.gov/23771170/ Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet. 1997;349(9063):1436–1442. doi: 10.1016/S0140-6736(96)07495-8. https://pubmed.ncbi.nlm.nih.gov/9164317/ Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia?. Am J Psychiatry. 1996;153(3):321–330. doi: 10.1176/ajp.153.3.321. https://pubmed.ncbi.nlm.nih.gov/8610818/ Rosa AR, Reinares M, Michalak EE, et al.. Functional impairment and disability across mood states in bipolar disorder. Value Health. 2010;13(8):984–988. doi: 10.1111/j.1524-4733.2010.00768.x. https://pubmed.ncbi.nlm.nih.gov/20659274/ Cardno AG, Gottesman II. Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am J Med Genet. 2000;97(1):12–17. doi: 10.1002/(SICI)1096-8628(200021)97. https://pubmed.ncbi.nlm.nih.gov/10813800/ Kendler KS, McGuire M, Gruenberg AM, Walsh D. Schizotypal symptoms and signs in the Roscommon Family Study: their factor structure and familial relationship with psychotic and affective disorders. Arch Gen Psychiatry. 1995;52(4):296–303. doi: 10.1001/archpsyc.1995.03950160054009. https://pubmed.ncbi.nlm.nih.gov/7702447/ McGuffin P, Rijsdijk F, Andrew M, et al.. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry. 2003;60(5):497–502. doi: 10.1001/archpsyc.60.5.497. https://pubmed.ncbi.nlm.nih.gov/12742871/ Angst J. The bipolar spectrum. Br J Psychiatry. 2007;190:189–191. doi: 10.1192/bjp.bp.106.030957. https://pubmed.ncbi.nlm.nih.gov/17329735/ Bulik-Sullivan B, Finucane HK, Anttila V, et al.. An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015;47(11):1236–1241. doi: 10.1038/ng.3406. https://pubmed.ncbi.nlm.nih.gov/26414676/ Ruderfer DM, Fanous AH, Ripke S, et al.. Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. Mol Psychiatry. 2014;19(9):1017–1024. doi: 10.1038/mp.2013.138. https://pubmed.ncbi.nlm.nih.gov/24105046/ Smoller JW, Kendler K, Craddock N, et al.. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013;381(9875):1371–1379. doi: 10.1016/S0140-6736(12)62129-1. https://pubmed.ncbi.nlm.nih.gov/23453885/ Niemi LT, Suvisaari JM, Tuulio-Henriksson A, Lönnqvist JK. Childhood developmental abnormalities in schizophrenia: evidence from high-risk studies. Schizophr Res. 2003;60(2–3):239–258. doi: 10.1016/S0920-9964(02)00291-3. https://pubmed.ncbi.nlm.nih.gov/12591589/ Gandal MJ, Haney JR, Parikshak NN, et al.. Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science. 2018;359(6376):693–697. doi: 10.1126/science.aad6469. https://pubmed.ncbi.nlm.nih.gov/29439242/ Sekar A, Bialas AR, de Rivera H, et al.. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530(7589):177–183. doi: 10.1038/nature16549. https://pubmed.ncbi.nlm.nih.gov/26814963/ Sekar A, Bialas AR, de Rivera H, et al.. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530(7589):177–183. doi: 10.1038/nature16549. https://pubmed.ncbi.nlm.nih.gov/26814963/ Kasanin J. The acute schizoaffective psychoses. Am J Psychiatry. 1933;90(1):97–126. doi: 10.1176/ajp.90.1.97. https://doi.org/10.1176/ajp.90.1.97 Kendler KS, Gruenberg AM, Tsuang MT. Psychiatric illness in first-degree relatives of schizophrenic and surgical control patients: a family study using DSM-III criteria. Arch Gen Psychiatry. 1985;42(8):770–779. doi: 10.1001/archpsyc.1985.01790310022002. https://pubmed.ncbi.nlm.nih.gov/4015309/ Regier DA, Narrow WE, Clarke DE, et al.. DSM-5 field trials in the United States and Canada, Part II: test-retest reliability of selected categorical diagnoses. Am J Psychiatry. 2013;170(1):59–70. doi: 10.1176/appi.ajp.2012.12070999. https://pubmed.ncbi.nlm.nih.gov/23111466/ Craddock N, Owen MJ. The Kraepelinian dichotomy — going, going... but still not gone. Br J Psychiatry. 2010;196(2):92–95. doi: 10.1192/bjp.bp.109.073429. https://pubmed.ncbi.nlm.nih.gov/20118450/ Rimol LM, Hartberg CB, Nesvåg R, et al.. Cortical thickness and subcortical volumes in schizophrenia and bipolar disorder. Biol Psychiatry. 2010;68(1):41–50. doi: 10.1016/j.biopsych.2010.03.036. https://pubmed.ncbi.nlm.nih.gov/20497902/ Turetsky BI, Calkins ME, Light GA, et al.. Neurophysiological endophenotypes of schizophrenia: the viability of selected candidate measures. Schizophr Bull. 2007;33(1):69–94. doi: 10.1093/schbul/sbl060. https://pubmed.ncbi.nlm.nih.gov/17135482/