What is schizophrenia: A neurodevelopmental or neurodegenerative disorder or a combination of both? A critical analysis

The etiology of schizophrenia has been the focus of intensive research for a long time. Perspectives have changed drastically with the development of new investigative techniques. Clinical observations made by Kraepelin, Clouston, Bender, and Watt are now being complemented by neuroimaging and genetic studies to prove the neurodevelopmental hypothesis. At the same time, neuropathological and longitudinal studies of schizophrenia often support a neurodegenerative hypothesis. To provide a theoretical basis to the available evidence, another hypothesis called the progressive neurodevelopmental model has also emerged. This review presents some key evidence supporting each of these theories followed by a critical analysis of each.

• Publication year

  2010

• Venue

  Indian Journal of Psychiatry

• Publication date

  Unknown publication date

• Fields of study

  Medicine, Psychology

• Identifiers
  DOI 10.4103/0019-5545.58891PMID 20174514PMCID 2824976
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• [Oxidative stress involvement in schizophrenia pathophysiology: a review].

  2006cited by this paper
• A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions.

  2006cited by this paper
• Prenatal developmental disturbances in the limbic allocortex in schizophrenics

  2005cited by this paper
• Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis.

  2005cited by this paper
• Ten year longitudinal study of neuropsychological functioning subsequent to a first episode of schizophrenia.

  2005cited by this paper
• Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia

  2005cited by this paper
• Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

  2003cited by this paper
• Morphometric studies of the entorhinal cortex in neuropsychiatric patients and controls: clusters of heterotopically displaced lamina II neurons are not indicative of schizophrenia [Schizophrenia Research 33 (1998) 125-132].

  2002cited by this paper
• Obstetric complications and schizophrenia: historical and meta-analytic review.

  2002cited by this paper
• Stability and course of neuropsychological deficits in schizophrenia.

  2001influential reference
• Association of schizophrenia with low maternal body mass index, small size at birth, and thinness during childhood.

  2001cited by this paper
• Is reduced dermatoglyphic a-b ridge count a reliable marker of developmental impairment in schizophrenia?

  2001cited by this paper
• Characterization of human cleaved N-CAM and association with schizophrenia.

  2001cited by this paper
• A review of MRI findings in schizophrenia.

  2001influential reference
• Schizophrenia as a disorder of developmentally reduced synaptic connectivity.

  2000cited by this paper
• The problem of obstetrical complications and schizophrenia.

  2000cited by this paper
• Development, disease and degeneration in schizophrenia: a unitary pathophysiological model.

  1999influential reference
• Longitudinal study of cognitive function in first-episode and recent-onset schizophrenia.

  1999cited by this paper
• The neuropathology of schizophrenia. A critical review of the data and their interpretation.

  1999cited by this paper
• Schizophrenia and complications of pregnancy and labor: an individual patient data meta-analysis.

  1999cited by this paper
• Frequency and severity of enlarged cavum septi pellucidi in childhood-onset schizophrenia.

  1998cited by this paper
• Genetic classification of primary neurodegenerative disease.

  1998cited by this paper
• A decrease of reelin expression as a putative vulnerability factor in schizophrenia.

  1998cited by this paper
• Glutamatergic Regulation of Basal and Stimulus‐Activated Dopamine Release in the Prefrontal Cortex

  1998cited by this paper
• Schizophrenia as a long-term outcome of pregnancy, delivery, and perinatal complications: a 28-year follow-up of the 1966 north Finland general population birth cohort.

  1998cited by this paper
• Delta sleep deficits in schizophrenia: evidence from automated analyses of sleep data.

  1998cited by this paper
• Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism.

  1998cited by this paper
• Cytoarchitecture of the entorhinal cortex in schizophrenia.

  1997cited by this paper
• The anthropometric assessment of dysmorphic features in schizophrenia as an index of its developmental origins

  1997cited by this paper
• Neurochemical Sensitization in the Pathophysiology of Schizophrenia: Deficits and Dysfunction in Neuronal Regulation and Plasticity

  1997cited by this paper
• The entorhinal cortex: an examination of cyto- and myeloarchitectonic organization in humans.

  1997cited by this paper
• Schizophrenia after prenatal famine. Further evidence.

  1996cited by this paper
• Increased density of microtubule associated protein 2-immunoreactive neurons in the prefrontal white matter of schizophrenic subjects.

  1996cited by this paper
• Temporal lobe morphology in childhood-onset schizophrenia.

  1996cited by this paper
• Variability in the human entorhinal region may confound neuropsychiatric diagnoses.

  1996cited by this paper
• Decreased expression of the embryonic form of the neural cell adhesion molecule in schizophrenic brains.

  1995cited by this paper
• Schizophrenia following in utero exposure to the 1957 influenza epidemics in Japan.

  1995cited by this paper
• Abnormally high neuronal density in the schizophrenic cortex. A morphometric analysis of prefrontal area 9 and occipital area 17.

  1995cited by this paper
• Glutamate receptor dysfunction and schizophrenia.

  1995cited by this paper
• Evidence Against Maternal Influenza as a Risk Factor for Schizophrenia

  1994cited by this paper
• No relation between risk of schizophrenia and prenatal exposure to influenza in Holland.

  1994cited by this paper
• Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development.

  1993cited by this paper
• Widespread cerebral gray matter volume deficits in schizophrenia.

  1992cited by this paper
• Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed tomography and the Tower of London.

  1992cited by this paper
• Prenatal Exposure to Influenza Does Not Cause Schizophrenia

  1992cited by this paper
• Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive schizophrenics. A pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy.

  1991cited by this paper
• Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients.

  1991cited by this paper
• Neuroleptics and the natural course of schizophrenia.

  1991cited by this paper
• LATE CHILDHOOD CHANGES IN BRAIN MORPHOLOGY OBSERVABLE WITH MRI

  1990cited by this paper
• Minor physical anomalies in schizophrenia.

  1989cited by this paper
• Maternal influenza in the etiology of schizophrenia.

  1989cited by this paper
• Adult schizophrenia following prenatal exposure to an influenza epidemic.

  1988cited by this paper
• Positron emission tomography study of human brain functional development

  1987cited by this paper
• Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence?

  1982cited by this paper
• Patterns of childhood social development in adult schizophrenics.

  1978cited by this paper
• Childhood schizophrenia; clinical study on one hundred schizophrenic children.

  1947cited by this paper

• Serum High Mobility Group Box Protein-1 Levels in Schizophrenia During Acute Psychotic Episodes and Remission.

  2026cites this paper
• Retinal biomarkers in schizophrenia spectrum disorders: evidence and implications for the neurodevelopmental and neurodegenerative models

  2026cites this paper
• The role of prefrontal-hippocampal functional connectivity in schizophrenia-related cognitive dysfunction and the thalamic ventral midline involvement: in vivo and silico evidence

  2025cites this paper
• Minor immunomodulatory effects of psychotropics suggested in severe mental disorders: Associations of antipsychotics with beta defensin 2, antidepressants with C-reactive protein, and mood stabilizers with soluble interleukin 2 receptor

  2025cites this paper
• Proportion of depression in diabetes patients: A Cross-Sectional study using HAM-D scale

  2025cites this paper
• Correlation of Neuroimaging Biomarkers and Pharmacogenetic Profiles in Optimizing Personalized Therapy in Children and Adolescents with Psychotic Disorders

  2025cites this paper
• Antipsychotics Lower Peripheral Markers of Inflammation in Drug-naive Early Psychosis: A Pilot Study

  2025cites this paper
• Estimation of premorbid intelligence in schizophrenia: a systematic literature review

  2025cites this paper
• Validated RP-HPLC Method for the Quantitative Analysis of Fisetin in Pure Form and Mucoadhesive Microemulsion Formulations

  2025cites this paper
• Choroidal thickening and temporal RNFL thinning in TRD patients: no structural retinal changes following TMS treatment.

  2025cites this paper
• LSTM-Based Classification of Psychiatric Disorders Using Ultra-Short Raw ECG Signals

  2025cites this paper
• The Retinal Age Gap as a Marker of Accelerated Aging in the Early Course of Schizophrenia.

  2025cites this paper
• Measurement of Limbic System Anatomical Volumes in Patients Diagnosed with Schizophrenia Using Vol2brain and Comparison with Healthy Individuals

  2025cites this paper
• Understanding Autism as a Condition in Mental Health Clinical Practice: Clinical Perspectives from a Youth Early Psychosis Service

  2025cites this paper
• Utilization of Neuroimaging Techniques in the Differential Diagnosis of Very Late-Onset Schizophrenia and Neurodegenerative Disorders

  2025cites this paper
• Genetic insights into neurodevelopment: the critical role of copy number variations in neurodevelopmental disorders

  2025cites this paper
• Resting-state functional connectivity correlates of brain structural aging in schizophrenia

  2024cites this paper
• A novel ECG-based approach for classifying psychiatric disorders: Leveraging wavelet scattering networks.

  2024cites this paper
• Unraveling the role of the renin-angiotensin system in severe mental illnesses: An insight into psychopathology and cognitive deficits.

  2024cites this paper
• Histaminergic System Activity in the Central Nervous System: The Role in Neurodevelopmental and Neurodegenerative Disorders

  2024cites this paper
• Structural and functional connectivity in relation to executive functions in antipsychotic-naïve patients with first episode schizophrenia

  2024cites this paper
• A potential mechanism for tau protein modulating in schizophrenia with transcranial direct current stimulation intervention: A randomized controlled trial

  2024cites this paper
• Prefrontal oscillatory slowing in early-course schizophrenia is associated with worse cognitive performance and negative symptoms: a TMS-EEG study.

  2024cites this paper
• Sulcal pits of the superior temporal sulcus in schizophrenia patients with auditory verbal hallucinations

  2024cites this paper
• The effects of abnormal visual experience on neurodevelopmental disorders.

  2023cites this paper
• Schizophrenia and Glutathione: A Challenging Story

  2023cites this paper
• Absence of the interthalamic adhesion (ITA) as a neuroanatomical association or risk factor for neuropsychiatric disorders: A systemic review and meta-analysis

  2023cites this paper
• Similarities in cognitive impairment between recent- onset and chronic schizophrenia patients: a consideration for the neurodevelopmental hypothesis

  2023cites this paper
• Emerging role of MRI to assess the Volume of Pineal Glands in Schizophrenia and Mood Disorders: Literature Review

  2023cites this paper
• Progressive trajectories of schizophrenia across symptoms, genes, and the brain

  2023cites this paper
• Neuroprotective factors in schizophrenia: BDNF, NGF, NT3, GDNF and their connection to the pathogenesis of schizophrenia. A narrative review

  2023cites this paper
• Fibre density and fibre-bundle cross-section of the corticospinal tract are distinctly linked to psychosis-specific symptoms in antipsychotic-naïve patients with first-episode schizophrenia

  2023cites this paper
• Association of circulatory Klotho levels and its expression with miRNA- 339 in patients with schizophrenia.

  2023cites this paper
• Neurodegeneration Markers in the Cerebrospinal Fluid of 100 Patients with Schizophrenia Spectrum Disorder.

  2022cites this paper
• Cannabis Use and Mental Health: Paradoxes of Medicalization

  2022cites this paper
• Biological hypotheses, risk factors, and biomarkers of schizophrenia.

  2022cites this paper
• Effect of Polymers and Permeation Enhancers in the Release of Quetiapine Fumarate Transdermal Patch through the Dialysis Membrane

  2022cites this paper
• A novel ternary pattern-based automatic psychiatric disorders classification using ECG signals

  2022cites this paper
• Shared genetic links between frontotemporal dementia and psychiatric disorders

  2022cites this paper
• Pharmaco-Magnetic Resonance as a Tool for Monitoring the Medication-Related Effects in the Brain May Provide Potential Biomarkers for Psychotic Disorders

  2021cites this paper
• The importance of non-coding RNAs in environmental stress-related developmental brain disorders: a systematic review of evidence associated with exposure to alcohol, anesthetic drugs, nicotine, and viral infections.

  2021cites this paper
• Human-specific cognition

  2021cites this paper
• Role of neurotransmitters in schizophrenia: a comprehensive study

  2021cites this paper
• Heterogeneous trajectories in schizophrenia: insights from neurodevelopment and neuroprogression models

  2021cites this paper
• Grey matter microstructural alterations in schizophrenia patients with treatment-resistant auditory verbal hallucinations.

  2021cites this paper
• Age-Specific Prevalence and Incidence of Dementia Diagnoses Among Older US Adults With Schizophrenia.

  2021cites this paper
• Changes in the Brain Extracellular Matrix Composition in schizophrenia: A Pathophysiological Dysregulation and a Potential Therapeutic Target

  2021cites this paper
• A Neurodevelopment Approach for a Transitional Model of Early Onset Schizophrenia

  2021cites this paper
• NDT_A_283395 555..565

  2021cites this paper
• Comparative Study of the Effects of Atypical Antipsychotic Drugs on Plasma and Urine Biomarkers of Oxidative Stress in Schizophrenic Patients

  2021cites this paper
• Overlapping Genetic Architecture Between Schizophrenia and Neurodegenerative Disorders

  2021cites this paper
• Onset of Schizophrenia Prior to the End of Brain Maturation Alters Grey Matter Volume Loss.

  2021cites this paper
• Schizophrenia-Mimicking Layers Outperform Conventional Neural Network Layers

  2020cites this paper
• How autophagy can restore proteostasis defects in multiple diseases?

  2020cites this paper
• Increased Risk of Dementia Among Veterans With Bipolar Disorder or Schizophrenia Receiving Care in the VA Health System.

  2020cites this paper
• Current Status of microRNA-Based Therapeutic Approaches in Neurodegenerative Disorders

  2020cites this paper
• Drosophila Glia: Models for Human Neurodevelopmental and Neurodegenerative Disorders

  2020cites this paper
• Plasma β-III tubulin, neurofilament light chain and glial fibrillary acidic protein are associated with neurodegeneration and progression in schizophrenia

  2020cites this paper
• Study of ZNF804A and DISC1 Genes in Iranian Patients with Schizophrenia

  2019cites this paper
• Evidence for an association of serum melatonin concentrations with recognition and circadian preferences in patients with schizophrenia

  2019cites this paper
• The Role of the Subplate in Schizophrenia and Autism: A Systematic Review.

  2019cites this paper
• Blonanserin versus haloperidol in Japanese patients with schizophrenia: A phase 3, 8‐week, double‐blind, multicenter, randomized controlled study

  2019cites this paper
• Analysis of Themes and Issues in Neurodevelopmental Disorders

  2019cites this paper
• Neurodevelopmental disorders with epigenetic dysregulation and Drosophila.

  2019cites this paper
• Brain-Derived Neurotropic Factor Serum Level and Severity Symptom of Bataknese Male Patients with Schizophrenia in North Sumatera, Indonesia

  2019cites this paper
• Clozapine response trajectories and predictors of non-response in treatment-resistant schizophrenia: a chart review study

  2019cites this paper
• Nicotine consumption during the prodromal phase of schizophrenia – a review of the literature

  2019cites this paper
• Characteristics of the effects of genetic variation in rodent models of risk for schizophrenia and neurodevelopment disorder

  2019cites this paper
• NDT_A_210199 2943..2958

  2019cites this paper
• Antipsihotici u kliničkoj praksi

  2019influential citation
• Integrative analysis of DNA methylation and gene expression in Schizophrenia

  2019cites this paper
• Estrogen: The necessary evil for human health, and ways to tame it.

  2018cites this paper
• Stem Cells for Nerve and Muscle Repair: Harnessing Developmental Dynamics in Therapeutics

  2018cites this paper
• Big Data and Data Science Applications for Independent and Healthy Living

  2018cites this paper
• hiPSC-derived neural stem cells from patients with schizophrenia induce an impaired angiogenesis

  2018cites this paper
• Cognitive Impairment in Schizophrenia: Description and Cognitive Familiar Endophenotypes. A Review of the Literature

  2018cites this paper
• Usefulness of Optical Coherence Tomography Measures as Biomarkers in Schizophrenia

  2018cites this paper
• Sulfation of catecholamines and serotonin by SULT1A3 allozymes

  2018cites this paper
• Risk factors in early and late onset schizophrenia.

  2018cites this paper
• Evaluation of retinal nerve fiber layer, macular, and choroidal thickness in schizophrenia: spectral optic coherence tomography findings

  2018cites this paper
• Association of Dopamine Beta-Hydroxylase Polymorphisms with Alzheimer’s Disease, Parkinson’s Disease and Schizophrenia: Evidence Based on Currently Available Loci

  2018cites this paper
• Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy.

  2018cites this paper
• The evaluation of neutrophil-lymphocyte ratio in patients with first episode psychosis

  2017cites this paper
• Automated Immunohistochemical Analysis of the Orbitofrontal Cortex in Patients with Schizophrenia, Bipolar Disorder and Major Depressive Disorder

  2017cites this paper
• Dysbindin-1 Involvement in the Etiology of Schizophrenia

  2017cites this paper
• Disruption of aromatase homeostasis as the cause of a multiplicity of ailments: A comprehensive review.

  2017cites this paper
• The influence of physical activity on cognitive functions in patients suffering from schizophrenia

  2017cites this paper
• Phytochemicals Effects on Neurodegenerative Diseases

  2017cites this paper
• Schizophrenia: neuroinflammation, neurodegeneration or neurodevelopment? A genetic overview

  2017cites this paper
• Factors Moderating the Relationship Between Childhood Trauma and Premorbid Adjustment in First-Episode Schizophrenia

  2017cites this paper
• The Impact of Drug and Gene Interaction on the Antipsychotic Medication for Schizophrenia

  2017cites this paper
• Multiple retinal anomalies in schizophrenia.

  2017cites this paper
• Localized vs. Systematic Neurodegeneration: A Paradigm Shift in Understanding Neurodegenerative Diseases

  2017cites this paper
• Connectome organization is related to longitudinal changes in general functioning, symptoms and IQ in chronic schizophrenia.

  2016cites this paper
• Efectos de la terapia asistida con animales en dominios cognitivos en pacientes con esquizofrenia

  2016cites this paper
• Synthesis of Fused Triazolo-Pyridobenzodiazepine Analogs for Use as Potential Atypical Antipsychotic Treatments in Schizophrenia

  2016cites this paper
• The Importance of Social Cognition:The impact of age, gender and personality on Social Cognition

  2016cites this paper
• Oxidative and nitrative stress in schizophrenia

  2016cites this paper
• Prescribing patterns in schizophrenic patients attending a tertiary care hospital, Kerala

  2016cites this paper
• Pineal gland volume in schizophrenia and mood disorders.

  2015cites this paper