Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-23T11:01:53.991Z Has data issue: false hasContentIssue false

Changes in neurocognitive functioning during transition to manifest disease: comparison of individuals at risk for schizophrenic and bipolar affective psychoses

Published online by Cambridge University Press:  02 February 2015

S. Metzler*
Affiliation:
The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, Switzerland
D. Dvorsky
Affiliation:
The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, Switzerland Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Switzerland
C. Wyss
Affiliation:
The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, Switzerland Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Switzerland
M. Müller
Affiliation:
The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, Switzerland Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Switzerland
M. Gerstenberg
Affiliation:
The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, Switzerland Department of Child and Adolescent Psychiatry, University of Zurich, Switzerland
N. Traber-Walker
Affiliation:
The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, Switzerland Department of Child and Adolescent Psychiatry, University of Zurich, Switzerland
S. Walitza
Affiliation:
Department of Child and Adolescent Psychiatry, University of Zurich, Switzerland
A. Theodoridou
Affiliation:
The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, Switzerland Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Switzerland
W. Rössler
Affiliation:
The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, Switzerland Collegium Helveticum, a joint Research Institute between the University of Zurich and the Swiss Federal Institute of Technology Zurich, Switzerland Institute of Psychiatry, Laboratory of Neuroscience (LIM 27), University of Sao Paulo, Sao Paulo, Brazil
K. Heekeren
Affiliation:
The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, Switzerland Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Switzerland
*
* Address for correspondence: S. Metzler, Ph.D., The Zurich Program for Sustainable Development of Mental Health Services (ZInEP), University Hospital of Psychiatry Zurich, Switzerland. (Email: [email protected])

Abstract

Background

Neurocognitive deficits are important aspects of schizophrenic disorder because they have a strong impact on social and vocational outcomes. Previously it was assumed that cognitive abilities progressively deteriorate with illness onset. However, recent research results have contradicted this with observations of continuous or even improved performance in individuals at risk for psychosis or manifest schizophrenia. The objective of our longitudinal study was to examine neurocognitive functioning in help-seeking individuals meeting basic symptoms or ultra-high-risk criteria for schizophrenic psychosis (HRSchiz) or risk criteria for affective psychosis (HRBip). The progression of cognitive functioning in individuals converting to psychosis was compared with that of at-risk individuals who did not convert during the follow-up period.

Method

Data were available from 86 study participants who completed neurocognitive and clinical assessments at baseline and, on average, 12.8 (s.d. = 1.5) months later. Neurocognitive measures were grouped according to their load in factor analysis to five cognitive domains: speed, attention, fluency, learning and memory, and working memory.

Results

Neurocognitive functioning in HRSchiz and HRBip individuals generally improved over time. Subjects converting to manifest psychosis displayed a stable neurocognitive profile from baseline to follow-up. Compared with non-converters, they had already demonstrated a significantly lower level of performance during their baseline examinations.

Conclusions

Our data provide no evidence for a progressive cognitive decline in individuals at risk of psychosis. In line with the neurodevelopmental model, our findings suggest that cognitive deficits are already present very early, before or during the prodromal stage of the illness.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Addington, J, Barbato, M (2012). The role of cognitive functioning in the outcome of those at clinical high risk for developing psychosis. Epidemiology Psychiatric Science 21, 335342.Google Scholar
Andreasen, NC, Pressler, M, Nopoulos, P, Miller, D, Ho, BC (2010). Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs. Biological Psychiatry 67, 255262.Google Scholar
Angst, J, Adolfsson, R, Benazzi, F, Gamma, A, Hantouche, E, Meyer, TD, Skeppar, P, Vieta, E, Scott, J (2005). The HCL-32: towards a self-assessment tool for hypomanic symptoms in outpatients. Journal of Affective Disorders 88, 217233.Google Scholar
Aschenbrenner, A, Tucha, O, Lange, K (2000). Regensburger Wortflüssigkeits-Test. Handanweisung. Hogrefe: Göttingen.Google Scholar
Aster, M, Neubauer, A, Horn, R (2006). Wechsler Intelligenztest für Erwachsene (WIE): Deutschsprachige Bearbeitung und Adaptation des WAIS-III von David Wechsler. Harcourt Test Services: Frankfurt am Main.Google Scholar
Barbato, M, Colijn, MA, Keefe, RS, Perkins, DO, Woods, SW, Hawkins, KA, Christensen, BK, Addington, J (2013). The course of cognitive functioning over six months in individuals at clinical high risk for psychosis. Psychiatry Research 206, 195199.Google Scholar
Bechdolf, A, Ratheesh, A, Wood, SJ, Tecic, T, Conus, P, Nelson, B, Cotton, SM, Chanen, AM, Amminger, GP, Ruhrmann, S, Schultze-Lutter, F, Klosterkotter, J, Fusar-Poli, P, Yung, AR, Berk, M, McGorry, PD (2012). Rationale and first results of developing at-risk (prodromal) criteria for bipolar disorder. Current Pharmaceutical Design 18, 358375.Google Scholar
Beck, LH, Bransome, ED Jr., Mirsky, AF, Rosvold, HE, Sarason, I (1956). A continuous performance test of brain damage. Journal of Consulting and Clinical Psychology 20, 343350.Google Scholar
Becker, HE, Nieman, DH, Wiltink, S, Dingemans, PM, van de Fliert, JR, Velthorst, E, de Haan, L, van Amelsvoort, TA, Linszen, DH (2010). Neurocognitive functioning before and after the first psychotic episode: does psychosis result in cognitive deterioration? Psychological Medicine 40, 15991606.Google Scholar
Bora, E, Lin, A, Wood, SJ, Yung, AR, McGorry, PD, Pantelis, C (2014). Cognitive deficits in youth with familial and clinical high risk to psychosis: a systematic review and meta-analysis. Acta Psychiatrica Scandinavica 130, 115.CrossRefGoogle ScholarPubMed
Bora, E, Murray, RM (2013). 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? Schizophrenia Bulletin 40, 744755.CrossRefGoogle ScholarPubMed
Bowie, CR, McLaughlin, D, Carrion, RE, Auther, AM, Cornblatt, BA (2012). Cognitive changes following antidepressant or antipsychotic treatment in adolescents at clinical risk for psychosis. Schizophrenia Research 137, 110117.Google Scholar
Brewer, WJ, Francey, SM, Wood, SJ, Jackson, HJ, Pantelis, C, Phillips, LJ, Yung, AR, Anderson, VA, McGorry, PD (2005). Memory impairments identified in people at ultra-high risk for psychosis who later develop first-episode psychosis. American Journal of Psychiatry 162, 7178.Google Scholar
Brewer, WJ, Wood, SJ, Phillips, LJ, Francey, SM, Pantelis, C, Yung, AR, Cornblatt, B, McGorry, PD (2006). Generalized and specific cognitive performance in clinical high-risk cohorts: a review highlighting potential vulnerability markers for psychosis. Schizophrenia Bulletin 32, 538555.Google Scholar
Cannon, M, Moffitt, TE, Caspi, A, Murray, RM, Harrington, H, Poulton, R (2006). Neuropsychological performance at the age of 13 years and adult schizophreniform disorder: prospective birth cohort study. British Journal of Psychiatry 189, 463464.Google Scholar
Cohen, P, Cohen, J (1984). The clinician's illusion. Archives of General Psychiatry 41, 11781182.Google Scholar
Correll, CU, Olvet, DM, Auther, AM, Hauser, M, Kishimoto, T, Carrión, RE, Snyder, S, Cornblatt, BA (2014). The Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P): description and validation in a psychiatric sample and healthy controls. Bipolar Disorder 16, 505522.Google Scholar
Cosway, R, Byrne, M, Clafferty, R, Hodges, A, Grant, E, Abukmeil, SS, Lawrie, SM, Miller, P, Johnstone, EC (2000). Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study. Psychological Medicine 30, 11111121.CrossRefGoogle ScholarPubMed
Crespo-Facorro, B, Rodriguez-Sanchez, JM, Perez-Iglesias, R, Mata, I, Ayesa, R, Ramirez-Bonilla, M, Martinez-Garcia, O, Vazquez-Barquero, JL (2009). Neurocognitive effectiveness of haloperidol, risperidone, and olanzapine in first-episode psychosis: a randomized, controlled 1-year follow-up comparison. Journal of Clinical Psychiatry 70, 717729.Google Scholar
Dunn, LM, Dunn, L (2003). Peabody Picture Vocabulary Test: Deutschsprachige Fassung für Jugendliche und Erwachsene. Swets Test Services: Frankfurt am Main.Google Scholar
Endicott, J, Spitzer, RL, Fleiss, JL, Cohen, J (1976). The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry 33, 766771.Google Scholar
Fioravanti, M, Carlone, O, Vitale, B, Cinti, ME, Clare, L (2005). A meta-analysis of cognitive deficits in adults with a diagnosis of schizophrenia. Neuropsychological Review 15, 7395.Google Scholar
Fusar-Poli, P, Bonoldi, I, Yung, AR, Borgwardt, S, Kempton, MJ, Valmaggia, L, Barale, F, Caverzasi, E, McGuire, P (2012a). Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Archives of General Psychiatry 69, 220229.Google Scholar
Fusar-Poli, P, Deste, G, Smieskova, R, Barlati, S, Yung, AR, Howes, O, Stieglitz, RD, Vita, A, McGuire, P, Borgwardt, S (2012b). Cognitive functioning in prodromal psychosis: a meta-analysis. Archives of General Psychiatry 69, 562571.Google Scholar
Fusar-Poli, P, Yung, AR, McGorry, P, van Os, J (2014). Lessons learned from the psychosis high-risk state: towards a general staging model of prodromal intervention. Psychological Medicine 44, 1724.Google Scholar
Giuliano, AJ, Li, H, Mesholam-Gately, RI, Sorenson, SM, Woodberry, KA, Seidman, LJ (2012). Neurocognition in the psychosis risk syndrome: a quantitative and qualitative review. Current Pharmaceutical Design 18, 399415.Google Scholar
Goldberg, TE, Keefe, RS, Goldman, RS, Robinson, DG, Harvey, PD (2010). Circumstances under which practice does not make perfect: a review of the practice effect literature in schizophrenia and its relevance to clinical treatment studies. Neuropsychopharmacology 35, 10531062.Google Scholar
Hambrecht, M, Lammertink, M, Klosterkotter, J, Matuschek, E, Pukrop, R (2002). Subjective and objective neuropsychological abnormalities in a psychosis prodrome clinic. British Journal of Psychiatry (Suppl.) 43, s30s37.Google Scholar
Hedman, AM, van Haren, NE, van Baal, CG, Kahn, RS, Hulshoff Pol, HE (2013). IQ change over time in schizophrenia and healthy individuals: a meta-analysis. Schizophrenia Research 146, 201208.CrossRefGoogle ScholarPubMed
Heinrichs, RW, Zakzanis, KK (1998). Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 12, 426445.Google Scholar
Helmstaedter, C, Lendt, M, Lux, S (2001). Verbaler Lern- und Merkfähigkeitstest (VLMT). Hogrefe: Göttingen.Google Scholar
Huber, G (1966). Reine Defektsyndrome und Basis-Stadien endogener Psychosen. Fortschritte der Neurologie – Psychiatrie 34, 409426.Google Scholar
Insel, TR (2010). Rethinking schizophrenia. Nature 468, 187193.Google Scholar
Jablensky, A (2007). Living in a Kraepelinian world: Kraepelin's impact on modern psychiatry. History of Psychiatry 18, 381388.Google Scholar
Kahn, RS, Keefe, RS (2013). Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiatry 70, 11071112.Google Scholar
Kay, SR, Fiszbein, A, Opler, LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.Google Scholar
Keefe, RS, Perkins, DO, Gu, H, Zipursky, RB, Christensen, BK, Lieberman, JA (2006). A longitudinal study of neurocognitive function in individuals at-risk for psychosis. Schizophrenia Research 88, 2635.Google Scholar
Keshavan, MS, DeLisi, LE, Seidman, LJ (2011). Early and broadly defined psychosis risk mental states. Schizophrenia Research 126, 110.Google Scholar
Klosterkotter, J, Hellmich, M, Steinmeyer, EM, Schultze-Lutter, F (2001). Diagnosing schizophrenia in the initial prodromal phase. Archives of General Psychiatry 58, 158164.Google Scholar
Koenen, KC, Moffitt, TE, Roberts, AL, Martin, LT, Kubzansky, L, Harrington, H, Poulton, R, Caspi, A (2009). Childhood IQ and adult mental disorders: a test of the cognitive reserve hypothesis. American Journal of Psychiatry 166, 5057.Google Scholar
Lehrl, S (1989). Mehrfachwahl-Wortschatz-Intelligenztest (MWT-B). Perimed: Erlangen.Google Scholar
MacCabe, JH (2008). Population-based cohort studies on premorbid cognitive function in schizophrenia. Epidemiologic Reviews 30, 7783.Google Scholar
MacCabe, JH, Lambe, MP, Cnattingius, S, Sham, PC, David, AS, Reichenberg, A, Murray, RM, Hultman, CM (2010). Excellent school performance at age 16 and risk of adult bipolar disorder: national cohort study. British Journal of Psychiatry 196, 109115.Google Scholar
MacCabe, JH, Lambe, MP, Cnattingius, S, Torrång, A, Björk, C, Sham, PC, David, AS, Murray, RM, Hultman, CM (2008). Scholastic achievement at age 16 and risk of schizophrenia and other psychoses: a national cohort study. Psychological Medicine 38, 11331140.Google Scholar
Metzler, S, Dvorsky, D, Wyss, C, Müller, M, Traber-Walker, N, Walitza, S, Theodoridou, A, Rössler, W, Heekeren, K (2014). Neurocognitive profiles in help-seeking individuals: Comparison of risk for psychosis and bipolar disorder criteria. Psychological Medicine. Published online 17 June 2014. doi:10.1017/S0033291714001007.Google Scholar
Michie, PT, Kent, A, Stienstra, R, Castine, R, Johnston, J, Dedman, K, Wichmann, H, Box, J, Rock, D, Rutherford, E, Jablensky, A (2000). Phenotypic markers as risk factors in schizophrenia: neurocognitive functions. Australian and New Zealand Journal of Psychiatry 34, 7485.Google Scholar
Miller, TJ, McGlashan, TH, Rosen, JL, Cadenhead, K, Cannon, T, Ventura, J, McFarlane, W, Perkins, DO, Pearlson, GD, Woods, SW (2003). Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophrenia Bulletin 29, 703715.Google Scholar
Müller, M, Vetter, S, Weiser, M, Frey, F, Ajdacic-Gross, V, Stieglitz, RD, Rossler, W (2013). Precursors of cognitive impairments in psychotic disorders: a population-based study. Psychiatry Research 210, 329337.CrossRefGoogle ScholarPubMed
Niendam, TA, Bearden, CE, Johnson, JK, McKinley, M, Loewy, R, O'Brien, M, Nuechterlein, KH, Green, MF, Cannon, TD (2006). Neurocognitive performance and functional disability in the psychosis prodrome. Schizophrenia Research 84, 100111.CrossRefGoogle ScholarPubMed
Olvet, DM, Burdick, KE, Cornblatt, BA (2013). Assessing the potential to use neurocognition to predict who is at risk for developing bipolar disorder: a review of the literature. Cognitive Neuropsychiatry 18, 129145.Google Scholar
Pantelis, C, Velakoulis, D, McGorry, PD, Wood, SJ, Suckling, J, Phillips, LJ, Yung, AR, Bullmore, ET, Brewer, W, Soulsby, B, Desmond, P, McGuire, PK (2003). Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 361, 281288.Google Scholar
Priebe, S, Huxley, P, Knight, S, Evans, S (1999). Application and results of the Manchester Short Assessment of Quality of Life (MANSA). International Journal of Social Psychiatry 45, 712.Google Scholar
Pukrop, R, Schultze-Lutter, F, Ruhrmann, S, Brockhaus-Dumke, A, Tendolkar, I, Bechdolf, A, Matuschek, E, Klosterkotter, J (2006). Neurocognitive functioning in subjects at risk for a first episode of psychosis compared with first- and multiple-episode schizophrenia. Journal of Clinical and Experimental Neuropsychology 28, 13881407.Google Scholar
Reitan, RM, Wolfson, D (1985). The Halstead–Reitan Neuropsychological Test Battery: Therapy and Clinical Interpretation. Neuropsychological Press: Tucson.Google Scholar
Ruhrmann, S, Schultze-Lutter, F, Klosterkotter, J (2010). Probably at-risk, but certainly ill-advocating the introduction of a psychosis spectrum disorder in DSM-V. Schizophrenia Research 120, 2337.Google Scholar
Rüsch, N, Corrigan, PW, Heekeren, K, Theodoridou, A, Dvorsky, D, Metzler, S, Muller, M, Walitza, S, Rossler, W (2014). Well-being among persons at risk of psychosis: the role of self-labeling, shame, and stigma stress. Psychiatric Services 65, 483489.CrossRefGoogle ScholarPubMed
Schultze-Lutter, F, Addington, J, Ruhrmann, S, Klosterkotter, J (2007). Schizophrenia Proneness Instrument, Adult Version (SPI-A). Giovanni Fioriti Editore: Rome.Google Scholar
Schultze-Lutter, F, Koch, E (2009). Schizophrenia Proneness Instrument, Child and Youth Version (SPI-CY). Giovanni Fioriti Editore: Rome.Google Scholar
Schutte, N, Malouff, J (1995). Sourcebook of Adult Assessment Strategies. Plenum Press: New York.Google Scholar
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R, Dunbar, GC (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59 (Suppl 20), 2233; quiz 34–57.Google ScholarPubMed
Shenton, ME, Dickey, CC, Frumin, M, McCarley, RW (2001). A review of MRI findings in schizophrenia. Schizophrenia Research 49, 152.Google Scholar
Simon, AE, Umbricht, D (2010). High remission rates from an initial ultra-high risk state for psychosis. Schizophrenia Research 116, 168172.CrossRefGoogle ScholarPubMed
Spreen, O, Strauss, E (1991). A Compendium of Neuropsychological Tests: Administration, Norms and Commentary. Oxford University Press: New York.Google Scholar
Stefanopoulou, E, Manoharan, A, Landau, S, Geddes, JR, Goodwin, G, Frangou, S (2009). Cognitive functioning in patients with affective disorders and schizophrenia: a meta-analysis. International Review of Psychiatry 21, 336356.Google Scholar
Trotta, A, Murray, RM, MacCabe, JH (2014). Do premorbid and post-onset cognitive functioning differ between schizophrenia and bipolar disorder? A Systematic Review and Meta-Analysis. Psychological Medicine 45, 381394.Google Scholar
van Os, J, Kapur, S (2009). Schizophrenia. Lancet 374, 635645.Google Scholar
Velthorst, E, Nieman, DH, Linszen, D, Becker, H, de Haan, L, Dingemans, PM, Birchwood, M, Patterson, P, Salokangas, RK, Heinimaa, M, Heinz, A, Juckel, G, von Reventlow, HG, French, P, Stevens, H, Schultze-Lutter, F, Klosterkotter, J, Ruhrmann, S (2010). Disability in people clinically at high risk of psychosis. British Journal of Psychiatry 197, 278284.Google Scholar
Wood, SJ, Brewer, WJ, Koutsouradis, P, Phillips, LJ, Francey, SM, Proffitt, TM, Yung, AR, Jackson, HJ, McGorry, PD, Pantelis, C (2007). Cognitive decline following psychosis onset: data from the PACE clinic. British Journal of Psychiatry (Suppl.) 51, s52s57.Google Scholar
Woodberry, KA, Giuliano, AJ, Seidman, LJ (2008). Premorbid IQ in schizophrenia: a meta-analytic review. American Journal of Psychiatry 165, 579587.Google Scholar
Yung, AR, McGorry, PD (1996). The prodromal phase of first-episode psychosis: past and current conceptualizations. Schizophrenia Bulletin 22, 353370.Google Scholar
Yung, AR, Nelson, B (2013). The ultra-high risk concept-a review. Canadian Journal of Psychiatry 58, 512.Google Scholar
Yung, AR, Nelson, B, Stanford, C, Simmons, MB, Cosgrave, EM, Killackey, E, Phillips, LJ, Bechdolf, A, Buckby, J, McGorry, PD (2008). Validation of ‘prodromal’ criteria to detect individuals at ultra high risk of psychosis: 2 year follow-up. Schizophrenia Research 105, 1017.Google Scholar
Yung, AR, Nelson, B, Thompson, AD, Wood, SJ (2010). Should a ‘Risk Syndrome for Psychosis’ be included in the DSMV? Schizophrenia Research 120, 715.Google Scholar
Yung, AR, Woods, SW, Ruhrmann, S, Addington, J, Schultze-Lutter, F, Cornblatt, BA, Amminger, GP, Bechdolf, A, Birchwood, M, Borgwardt, S, Cannon, TD, de Haan, L, French, P, Fusar-Poli, P, Keshavan, M, Klosterkotter, J, Kwon, JS, McGorry, PD, McGuire, P, Mizuno, M, Morrison, AP, Riecher-Rossler, A, Salokangas, RK, Seidman, LJ, Suzuki, M, Valmaggia, L, van der Gaag, M, Wood, SJ, McGlashan, TH (2012). Whither the attenuated psychosis syndrome? Schizophrenia Bulletin 38, 11301134.Google Scholar
Zipursky, RB, Lambe, EK, Kapur, S, Mikulis, DJ (1998). Cerebral gray matter volume deficits in first episode psychosis. Archives of General Psychiatry 55, 540546.Google Scholar
Zipursky, RB, Reilly, T, Murray, RM (2013). The myth of schizophrenia as a progressive brain disease. Schizophrenia Bulletin 39, 13631372.Google Scholar