Background
Psychotic disorders are characterized by aberrant neural connectivity. Alterations
in gyrification, the pattern and degree of cortical folding, may be related to the
early development of connectivity. Past gyrification studies have relatively small
sample sizes, yield mixed results for schizophrenia, and are scant for psychotic bipolar
and schizoaffective (SZA) disorders and for relatives of these conditions. Here, we
examine gyrification in psychotic disorder patients and their first-degree relatives
as a possible endophenotype.
Methods
Regional local gyrification index (LGI) values, as measured by FreeSurfer software,
were compared between 243 control subjects, 388 psychotic disorder probands, and 300
of their first-degree relatives. For patients, LGI values were examined grouped across
psychotic diagnoses and then separately for schizophrenia, SZA, and bipolar disorder.
Familiality (heritability) values and correlations with clinical measures were also
calculated for regional LGI values.
Results
Probands exhibited significant hypogyria compared with control subjects in three brain
regions and relatives with Axis II cluster A disorders showed nearly significant hypogyria
in these same regions. Local gyrification index values in these locations were significantly
heritable and uncorrelated with any clinical measure. Observations of significant
hypogyria were most widespread in SZA.
Conclusions
Psychotic disorders appear to be characterized by significant regionally localized
hypogyria, particularly in cingulate cortex. This abnormality may be a structural
endophenotype marking risk for psychotic illness and it may help elucidate etiological
underpinnings of psychotic disorders.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Endophenotypic studies in schizophrenia: Promise and challenges.Schizophr Bull. 2006; 33: 1-2
- Endophenotypes in schizophrenia: A selective review.Schizophr Res. 2009; 109: 24-37
- Intermediate phenotypes in schizophrenia: A selective review.Dialogues Clin Neurosci. 2005; 7: 165-179
- Time for a shift in focus in schizophrenia: From narrow phenotypes to broad endophenotypes.Br J Psychiatry. 2005; 187: 203-205
- The endophenotype concept in psychiatry: Etymology and strategic intentions.Am J Psychiatry. 2003; 160: 636-645
- Endophenotypes for psychiatric disorders: Ready for primetime?.Trends Genet. 2006; 22: 306-313
- Endophenotype: A conceptual analysis.Mol Psychiatry. 2010; 15: 789-797
- Brain connectivity and gyrification as endophenotypes for schizophrenia: Weight of the evidence.Curr Top Med Chem. 2012; 12: 2393-2403
- Schizophrenia: A disconnection syndrome?.Clin Neurosci. 1995; 3: 89-97
- Linking mind and brain in the study of mental illnesses: A project for a scientific psychopathology.Science. 1997; 275: 1586-1593
- Schizophrenia, neuroimaging and connectomics.Neuroimage. 2012; 62: 2296-2314
- Specification of cerebral cortical areas.Science. 1988; 241: 170-176
- A tension-based theory of morphogenesis and compact wiring in the central nervous system.Nature. 1997; 385: 313-318
- Developmental mechanics of the primate cerebral cortex.Anat Embryol (Berl). 2005; 210: 411-417
- The development of gyrification in childhood and adolescence.Brain Cogn. 2010; 72: 36-45
- Gyrification and neural connectivity in schizophrenia.Dev Psychopathol. 2011; 23: 339-352
- On the genetic architecture of cortical folding and brain volume in primates.Neuroimage. 2010; 53: 1103-1108
- Global and temporal cortical folding in patients with early-onset schizophrenia.J Am Acad Child Adolesc Psychol. 2008; 47: 1125-1132
- Increased parahippocampal and lingual gyrification in first-episode schizophrenia.Schizophr Res. 2010; 123: 137-144
- Folding of the prefrontal cortex in schizophrenia: Regional differences in gyrification.Biol Psychiatry. 2011; 69: 974-979
- Aberrant cortical gyrification in schizophrenia: A surface-based morphometry study.J Psychiatry Neurosci. 2012; 37: 399-406
- Differential effects of surface area, gyrification and cortical thickness on voxel based morphometric deficits in schizophrenia.Neuroimage. 2012; 60: 693-699
- Dissociable morphometric differences of the inferior parietal lobule in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2012; 262: 579-587
- Diagnostic discontinuity in psychosis: A combined study of cortical gyrification and functional connectivity [published online ahead of print April 24].Schizophr Bull. 2013;
- Gyrification of Broca’s region is anomalously lateralized at onset of schizophrenia in adolescence and regresses at 2 year follow-up.Schizophr Res. 2013; 147: 39-45
- Sulcogyral patterns and morphological abnormalities of the orbitofrontal cortex in psychosis.Prog Neuropsychopharmacol Biol Psychiatry. 2013; 44C: 168-177
- The visual cortex in schizophrenia: Alterations of gyrification rather than cortical thickness--a combined cortical shape analysis.Brain Struct Funct. 2013; 218: 51-58
- Morphometry of structural disconnectivity indicators in subjects at risk and in age-matched patients with schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2013; 263: 15-24
- Reduced cortical folding in individuals at high risk for schizophrenia: A pilot study.Schizophr Res. 2005; 75: 309-313
- Disturbed frontal gyrification within families affected with schizophrenia.J Psychiatr Res. 2007; 41: 805-813
- Relationship between gyrification and functional connectivity of the prefrontal cortex in subjects at high genetic risk of schizophrenia.Curr Pharm Des. 2012; 18: 434-442
- Cortical folding difference between patients with early-onset and patients with intermediate-onset bipolar disorder.Bipolar Disord. 2009; 11: 361-370
- Cortical folding in patients with bipolar disorder or unipolar depression.J Psychiatry Neurosci. 2009; 34: 127-135
- Prefrontal gyral folding and its cognitive correlates in bipolar disorder and schizophrenia.Acta Psychiatr Scand. 2009; 119: 192-198
- Cortical complexity analysis of patients with bipolar disorder using three-dimensional gyrification index.Conf Proc IEEE Eng Med Biol Soc. 2008; 2008: 3933-3936
- Changes in gyrification over 4 years in bipolar disorder and their association with the brain-derived neurotrophic factor valine(66) methionine variant.Biol Psychiatry. 2009; 66: 293-297
- Gyral and sulcal cortical thinning in adolescents with first episode early-onset psychosis.Biol Psychiatry. 2009; 66: 1047-1054
- Cortical folding in Broca’s area relates to obstetric complications in schizophrenia patients and healthy controls.Psychol Med. 2012; 42: 1329-1337
- Aberrant cortical gyrification in schizophrenia: A surface-based morphometry study.J Psychiatry Neurosci. 2012; 37: 399-406
- Consistency and interpretation of changes in millimeter-scale cortical intrinsic curvature across three independent datasets in schizophrenia.Neuroimage. 2012; 63: 611-621
- Phenomenology of first-episode psychosis in schizophrenia, bipolar disorder, and unipolar depression: A comparative analysis.Clin Schizophr Relat Psychoses. 2012; 6: 145-151
- The familial transmission of bipolar illness.Arch Gen Psychiatry. 1987; 44: 441-447
- The structure of psychosis: Latent class analysis of probands from the Roscommon Family Study.Arch Gen Psychiatry. 1998; 55: 492-499
- Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: A population-based study.Lancet. 2009; 373: 234-239
- Bipolar disorder, schizoaffective disorder, and schizophrenia overlap: A new comorbidity index.J Clin Psychiatry. 2009; 70: 1432-1438
- Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia.Mol Psychiatry. 2002; 7: 405-411
- Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology.Schizophr Bull. 2005; 32: 9-16
- Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.Nature. 2009; 460: 748-752
- Reimagining psychoses: An agnostic approach to diagnosis.Schizophr Res. 2013; 146: 10-16
- Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level.Biol Psychiatry. 2007; 62: 784-792
- A multivariate perspective on schizotypy and familial association with schizophrenia: A review.Clin Psychol Rev. 2011; 31: 1169-1182
- Lithium-induced increase in human brain grey matter.Lancet. 2000; 356: 1241-1242
- Increased gray matter volume in lithium-treated bipolar disorder patients.Neurosci Lett. 2002; 329: 243-245
- Effects of antipsychotics on brain structure.Curr Opin Psychiatry. 2006; 19: 145-150
- Bilateral hippocampal volume increase in patients with bipolar disorder and short-term lithium treatment.Neuropsychopharmacology. 2007; 33: 361-367
- Increased volume of the amygdala and hippocampus in bipolar patients treated with lithium.Neuroreport. 2008; 19: 221-224
- A longitudinal study of the effects of lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients.J Clin Psychiatry. 2009; 70: 699-705
- Lithium-induced gray matter volume increase as a neural correlate of treatment response in bipolar disorder: A longitudinal brain imaging study.Neuropsychopharmacology. 2010; 35: 1743-1750
- A systematic review of the effects of antipsychotic drugs on brain volume.Psychol Med. 2010; 40: 1409-1422
- Long-term antipsychotic treatment and brain volumes: A longitudinal study of first-episode schizophrenia.Arch Gen Psychiatry. 2011; 68: 128-137
- Antipsychotic medications and brain volume: Do we have cause for concern?.Arch Gen Psychiatry. 2011; 68: 126-127
- Structured Interview for DSM-IV Personality: SIDP-IV.American Psychiatric Press, Washington, DC1997
- Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives.Am J Psychiatry. 2013; 170: 886-898
- User’s Guide for the Structured Clinical Interview for DSM-IV Axis I Disorders: SCID-1 Clinician Version.American Psychiatric Association, Washington, DC1997
- The positive and negative syndrome scale (PANSS) for schizophrenia.Schizophr Bull. 1987; 13: 261-276
- A new depression scale designed to be sensitive to change.Br J Psychiatry. 1979; 134: 382-389
- A rating scale for mania: Reliability, validity and sensitivity.Br J Psychiatry. 1978; 133: 429-435
- FreeSurfer.Neuroimage. 2012; 62: 774-781
- An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.Neuroimage. 2006; 31: 968-980
- A surface-based approach to quantify local cortical gyrification.IEEE Trans Med Imaging. 2008; 27: 161-170
- Circular analysis in systems neuroscience: The dangers of double dipping.Nat Neurosci. 2009; 12: 535-540
- Multipoint quantitative-trait linkage analysis in general pedigrees.Am J Hum Genet. 1998; 62: 1198-1211
- Wide Range Achievement Test 4 Professional Manual.Psychological Assessment Resources, Lutz, FL2006
- Four Factor Index of Social Status. 1975; (Available at:) (Accessed November 2013.)
- Gyrification in first-episode schizophrenia: A morphometric study.Biol Psychiatry. 2004; 55: 141-147
- Abnormal cortical folding in high-risk individuals: A predictor of the development of schizophrenia?.Biol Psychiatry. 2004; 56: 182-189
- Increased prefrontal gyrification in a large high-risk cohort characterizes those who develop schizophrenia and reflects abnormal prefrontal development.Biol Psychiatry. 2007; 62: 722-729
- Schizophrenia, the heteromodal association neocortex and development: Potential for a neurogenetic approach.Trends Neurosci. 1996; 19: 171-176
- Schizophrenia: A disease of heteromodal association cortex?.Neuropsychopharmacology. 1996; 14: 1-17
- Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia.Proc Natl Acad Sci U S A. 2002; 99: 3228-3233
- Local cortical surface complexity maps from spherical harmonic reconstructions.Neuroimage. 2011; 56: 961-973
- Localised reductions in gyrification in the posterior cingulate: Schizophrenia and controls.Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31: 319-327
- Neurobiological investigations in cingulate cortex of schizophrenic brain.Schizophr Bull. 1993; 19: 537-549
- Abnormal cingulate modulation of fronto-temporal connectivity in schizophrenia.Neuroimage. 1999; 9: 337-342
- Anterior cingulate cortex pathology in schizophrenia and bipolar disorder.Acta Neuropathol. 2001; 102: 373-379
- Cingulate fasciculus integrity disruption in schizophrenia: A magnetic resonance diffusion tensor imaging study.Biol Psychiatry. 2003; 54: 1171-1180
- Anterior cingulate dysfunction: Implications for psychiatric disorders?.J Psychiatry Neurosci. 2003; 28: 350-354
- Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder.Brain Res. 2006; 1073–1074: 25-37
- Aberrant “default mode” functional connectivity in schizophrenia.Am J Psychiatry. 2007; 164: 450-457
- Anterior cingulate activation in antipsychotic-naïve first-episode schizophrenia.Acta Psychiatr Scand. 2007; 115: 155-158
- Meta-analysis of gray matter anomalies in schizophrenia: Application of anatomic likelihood estimation and network analysis.Biol Psychiatry. 2008; 64: 774-781
- Anterior cingulate cortex abnormalities associated with a first psychotic episode in bipolar disorder.Br J Psychiatry. 2009; 194: 426-433
- Surface-based morphometry of the anterior cingulate cortex in first episode schizophrenia.Hum Brain Mapp. 2008; 29: 478-489
- Anatomical abnormalities of the anterior cingulate cortex in schizophrenia: Bridging the gap between neuroimaging and neuropathology.Schizophr Bull. 2009; 35: 973-993
- Disrupted axonal fiber connectivity in schizophrenia.Biol Psychiatry. 2011; 69: 80-89
- Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia.Am J Psychiatry. 1990; 147: 1457-1462
- Reversal of asymmetry of the planum temporale in schizophrenia.Am J Psychiatry. 1995; 152: 715-721
- Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder.Biol Psychiatry. 1997; 41: 1-14
- Planum temporale asymmetry reversal in schizophrenia: Replication and relationship to gray matter abnormalities.Am J Psychiatry. 1997; 154: 661-667
- Personality and psychopathology: Working toward the bigger picture.J Pers Disord. 2003; 17: 109-128
- Reevaluating the distinction between Axis I and Axis II disorders: The case of borderline personality disorder.J Clin Psychol. 2005; 61: 1509-1523
- Do clinicians see Axis I and Axis II as different kinds of disorders?.Compr Psychiatry. 2006; 47: 496-502
- The behavioral genetics of personality disorder.Annu Rev Clin Psychol. 2008; 4: 247-274
- The joint structure of DSM-IV Axis I and Axis II disorders.J Abnorm Psychol. 2011; 120: 198-209
- Polymorphisms in genes involved in neurodevelopment may be associated with altered brain morphology in schizophrenia: Preliminary evidence.Psychiatry Res. 2009; 165: 1-9
Article info
Publication history
Published online: November 25, 2013
Accepted:
November 14,
2013
Received in revised form:
November 12,
2013
Received:
July 4,
2013
Identification
Copyright
© 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- An error in the text been detected in the article “Local Gyrification Index in Probands with PsychoticBiological PsychiatryVol. 77Issue 9
- PreviewDisorders and Their First-Degree Relatives” by Nanda et al. (2014; 76:447-455). Specifically, on page 453, column 1, the sentence that begins on line 3 currently reads: “Psychotic bipolar disorder patients had only one region of significant difference compared with control subjects.” It should, however, read: “Psychotic bipolar disorder patients had no regions of significant difference compared with control subjects.” This error was an oversight and no other portions of the paper are affected.
- Full-Text
- Preview
