Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-6bf8c574d5-gr6zb Total loading time: 0 Render date: 2025-03-01T11:23:06.573Z Has data issue: false hasContentIssue false

Chapter 5 - Neurobiology of Mental Disorders

Published online by Cambridge University Press:  02 January 2025

By
Karen Horn ,
Anita Barrera ,
Abdul Haseeb  and
Rodrigo Machado-Vieira
Edited by
Marsal Sanches  and
Jair C. Soares
Marsal Sanches
Affiliation:
McGovern Medical School, Texas
Jair C. Soares
Affiliation:
McGovern Medical School, Texas
Get access

Summary

Psychiatric disorders are complex and multifaceted conditions that profoundly impact various aspects of an individual’s life. Although the neurobiology of these disorders is not fully understood, extensive research suggests intricate interactions between genetic factors, changes in brain structure, disruptions in neurotransmitter pathways, as well as environmental influence.

In the case of psychotic disorders, such as schizophrenia, strong genetic components have been identified as a key feature in the development of psychosis. Moreover, alterations in dopamine function and structural brain changes that result in volume loss seem to be pervasive in people affected by these disorders. Meanwhile, mood disorders, including major depressive disorder and bipolar disorder, are characterized by disruptions in neurotransmitter systems responsible for mood regulation, such as serotonin, norepinephrine, and dopamine. Anxiety and personality disorders also exhibit neurotransmitter dysfunction and neuroanatomical changes, in addition to showing a genetic overlap with mood and psychotic disorders.

Understanding the underlying mechanisms in the pathophysiology of these conditions is of paramount importance and involves integrating findings from various research areas, including at the molecular and cellular levels. This brief overview aims to highlight some of the important developments in our current understanding of psychiatric disorders. Future research should aim to incorporate a comprehensive approach to further unravel the complexity of these disorders and pave the way for targeted therapeutic strategies and effective treatments to improve the lives of individuals afflicted by them.

Keywords

moodpsychosistreatmentneurobiologymodelspharmacology
Type
Chapter
Information
Fundamentals of Clinical Psychiatry
A Practical Handbook
 , pp. 27 - 38
Publisher: Cambridge University Press
Print publication year: 2025

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

Narayan, C. L., Shikha, D., Shekhar, S.. Schizophrenia in identical twins. Indian J Psychiatry. 2015;57(3):323–324.CrossRefGoogle ScholarPubMed
Uzuneser, T. C., Speidel, J., Kogias, G.. Disrupted-in-schizophrenia 1 (DISC1) overexpression and juvenile immune activation cause sex-specific schizophrenia-related psychopathology in rats. Front Psychiatry. 2019;10:222.CrossRefGoogle ScholarPubMed
Kircher, T., Wöhr, M., Nenadic, I., et al. Neurobiology of the major psychoses: a translational perspective on brain structure and function. Eur Arch Psychiatry Clin Neurosci. 2019;269:949–962.CrossRefGoogle ScholarPubMed
Craddock, N., O’Donovan, M. C., Owen, M. J.. Psychosis genetics: modeling the relationship between schizophrenia, bipolar disorder, and mixed (or “schizoaffective”) psychoses. Schizophr Bull. 2009;35(3):482–490.CrossRefGoogle ScholarPubMed
Straub, R. E., Jiang, Y., MacLean, C. J., et al. Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. Am J Hum Genet. 2002;71:337–348.CrossRefGoogle ScholarPubMed
Luvsannyam, E., Jain, M. S., Pormento, M. K. L., et al. Neurobiology of schizophrenia: a comprehensive review. Cureus. 2022;14(4):e23959.Google ScholarPubMed
Lochmann van Bennekom, M. W., Gijsman, H. J., Zitman, F. G.. Antipsychotic polypharmacy in psychotic disorders: a critical review of neurobiology, efficacy, tolerability and cost effectiveness. J Psychopharmacol. 2013;27(4):327–336.CrossRefGoogle ScholarPubMed
Kesby, J. P., Eyles, D. W., McGrath, J. J., et al. Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience. Transl Psychiatry. 2018;8(1):30.CrossRefGoogle ScholarPubMed
Howes, O. D., Kambeitz, J., Kim, E., et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry. 2012;69(8):776–786.CrossRefGoogle ScholarPubMed
Coyle, J. T.. Glutamate and schizophrenia: beyond the dopamine hypothesis. Cell Mol Neurobiol. 2006;26(4–6):365–384.CrossRefGoogle ScholarPubMed
Tsou, J. Y.. Intervention, causal reasoning, and the neurobiology of mental disorders: pharmacological drugs as experimental instruments. Stud Hist Philos Biol Biomed Sci. 2012;43(2):542–551.CrossRefGoogle ScholarPubMed
O’Connor, W. T., O’Shea, S. D.. Clozapine and GABA transmission in schizophrenia disease models: establishing principles to guide treatments. Pharmacol Therapeutics. 2015;150:47–80.CrossRefGoogle ScholarPubMed
Bain, B. K.. CT scans of first-break psychotic patients in good general health. Psychiatr Serv. 1998;49(2):234–235.CrossRefGoogle ScholarPubMed
Strahl, B., Cheung, Y. K., Stuckey, S. L.. Diagnostic yield of computed tomography of the brain in first episode psychosis. J Med Imaging Radiat Oncol. 2010;54(5):431–434.CrossRefGoogle ScholarPubMed
Forbes, M., Stefler, D., Velakoulis, D., et al. The clinical utility of structural neuroimaging in first-episode psychosis: a systematic review. Aust N Z J Psychiatry. 2019;53(11):1093–1104.CrossRefGoogle ScholarPubMed
Karlsgodt, K. H., Sun, D., Cannon, T. D.. Structural and functional brain abnormalities in schizophrenia. Curr Dir Psychol Sci. 2010;19(4):226–231.CrossRefGoogle ScholarPubMed
Dietsche, B., Kircher, T., Falkenberg, I.. Structural brain changes in schizophrenia at different stages of the illness: a selective review of longitudinal magnetic resonance imaging studies. Austral N Z J Psychiatry. 2017;51(5):500–508.CrossRefGoogle Scholar
Birur, B., Kraguljac, N. V., Shelton, R. C., et al. Brain structure, function, and neurochemistry in schizophrenia and bipolar disorder: a systematic review of the magnetic resonance neuroimaging literature. NPJ Schizophrenia. 2017;3:15.CrossRefGoogle ScholarPubMed
Pantelis, C., Yücel, M., Wood, S. J., et al. Structural brain imaging evidence for multiple pathological processes at different stages of brain development in schizophrenia. Schizophr Bull. 2005;31(3):672–696.CrossRefGoogle ScholarPubMed
Uranova, N., Orlovskaya, D., Vikhreva, O., et al. Electron microscopy of oligodendroglia in severe mental illness. Brain Res Bull. 2001;55:597–610.CrossRefGoogle ScholarPubMed
Dietz, A. G., Goldman, S. A., Nedergaard, M.. Glial cells in schizophrenia: a unified hypothesis. Lancet Psychiatry. 2020;7(3):272–281.CrossRefGoogle ScholarPubMed
Cannon, T. D., Chung, Y., He, G., et al. Progressive reduction in cortical thickness as psychosis develops: a multisite longitudinal neuroimaging study of youth at elevated clinical risk. Biol Psychiatry. 2015;77(2):147–157.CrossRefGoogle ScholarPubMed
Lawrie, S. M., McIntosh, A. M., Hall, J., et al. Brain structure and function changes during the development of schizophrenia: the evidence from studies of subjects at increased genetic risk. Schizophr Bull. 2008;34(2):330–340.CrossRefGoogle ScholarPubMed
Coleman, J. R., Gaspar, H. A., Bryois, J., et al. The genetics of the mood disorder spectrum: genome-wide association analyses of more than 185,000 cases and 439,000 controls. Biol Psychiatry. 2020;88(2):169–184.CrossRefGoogle ScholarPubMed
Howard, D. M., Adams, M. J., Shirali, M., et al. Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways. Nat Comm. 2018;9:1470.CrossRefGoogle ScholarPubMed
Sullivan, P. F., Neale, M. C., Kendler, K. S.. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry. 2000;157(10):1552–1562.CrossRefGoogle ScholarPubMed
Stahl, E. A., Breen, G., Forstner, A. J., et al. Genome-wide association study identifies 30 loci associated with bipolar disorder. Nat Genetics. 2019;51:793–803.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Drevets, W. C., Price, J. L., Furey, M. L.. Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct Funct. 2008;213(1–2):93–118.CrossRefGoogle ScholarPubMed
Bonacina, G., Carollo, A., Esposito, G.. The genetic side of the mood: a scientometric review of the genetic basis of mood disorders. Genes (Basel). 2023;14(2):352.CrossRefGoogle Scholar
Zhang, F. F., Peng, W., Sweeney, J. A., et al. Brain structure alterations in depression: psychoradiological evidence. CNS Neurosci Ther. 2018;24(11):994–1003.CrossRefGoogle ScholarPubMed
Duman, R., Aghajanian, G., Sanacora, G., et al. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med. 2016;22:238–249.CrossRefGoogle ScholarPubMed
Harrison, P. J., Geddes, J. R., Tunbridge, E. M.. The emerging neurobiology of bipolar disorder. Trends Neurosci. 2018;41(1):18–30.CrossRefGoogle ScholarPubMed
Gray, J. P., Müller, V. I., Eickhoff, S. B., et.al. Multimodal Abnormalities of Brain Structure and Function in Major Depressive Disorder: A Meta-Analysis of Neuroimaging Studies [published correction appears in Am J Psychiatry. 2022; 179(9):691]. Am J Psychiatry. 2020; 177(5):422-434.CrossRefGoogle Scholar
Iorfino, F., Hickie, I. B., Lee, R. S. C., et al. The underlying neurobiology of key functional domains in young people with mood and anxiety disorders: a systematic review. BMC Psychiatry. 2016;16:156.CrossRefGoogle Scholar
Zhang, W., Sweeney, J. A., Yao, L., et al. Brain structural correlates of familial risk for mental illness: a meta-analysis of voxel-based morphometry studies in relatives of patients with psychotic or mood disorders. Neuropsychopharmacology. 2020;45(8):1369–1379.CrossRefGoogle ScholarPubMed
Ding, J. B., Hu, K.. Structural MRI brain alterations in borderline personality disorder and bipolar disorder. Cureus. 2021;13(7):e16425.Google ScholarPubMed
Martin, E. I., Ressler, K. J., Binder, E., et al. The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. Psychiatr Clin North Am. 2009;32(3):549–575.CrossRefGoogle ScholarPubMed
Reichborn-Kjennerud, T.. Genetics of personality disorders. Clin Lab Med. 2010;30(4):893–910.CrossRefGoogle ScholarPubMed
Goodman, M., New, A., Siever, L.. Trauma, genes, and the neurobiology of personality disorders. Ann N Y Acad Sci. 2004;1032:104–116.CrossRefGoogle ScholarPubMed
Siever, L. J., Weinstein, L. N.. The neurobiology of personality disorders: implications for psychoanalysis. J Am Psychoanal Assoc. 2009;57(2):361–398.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×