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Striatal structure and function in mood disorders: a comprehensive review
Abstract
Marchand WR, Yurgelun‐Todd D. Striatal structure and function in mood disorders: a comprehensive review. Bipolar Disord 2010: 12: 764–785. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: A large and diverse literature has implicated abnormalities of striatal structure and function in both unipolar and bipolar disorder. Recent functional imaging studies have greatly expanded this body of research. The aim of this review is to provide a comprehensive and critical appraisal of the relevant literature. Methods: A total of 331 relevant articles were reviewed to develop an integrated overview of striatal function in mood disorders. Results: There is compelling evidence from multiple studies that functional abnormalities of the striatum and greater corticostriatal circuitry exist in at least some forms of affective illness. The literature does not yet provide data to determine whether these aberrations represent primary pathology or they contribute directly to symptom expression. Finally, there is considerable evidence that bipolar disorder may be associated with striatal hyperactivity and some suggestion that unipolar illness may be associated with hypoactivation. Conclusions: Additional research investigating striatal function in affective disorders will be critical to the development of comprehensive models of the neurobiology of these conditions.
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“Although functional MRI studies have identified prefrontal dysfunction in bipolar disorder and manic psychosis, evidence for abnormalities in reward-related neural network function in mania is scarce [271-275].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [273]
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Strakowski, S. M., Adler, C. M., Almeida, J., Altshuler, L. L., Blumberg, H. P., Chang, K., DelBello, M. P., Frangou, S., McIntosh, A. M., Phillips, M. L., et al. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.01022.x · Cited by 555
“Marchand WR, Yurgelun-Todd D. Striatal structure and function in mood disorders: a comprehensive review.”
ResultInfluentialMARCHAND, W. R. (2012) · Journal of Psychiatric Practice® · doi:10.1097/01.pra.0000416014.53215.86 · Cited by 305
Self-citationDichter, G. S., Damiano, C. A., & Allen, J. A. (2012) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-4-19 · Cited by 299
“Although functional MRI studies have identified prefrontal dysfunction in bipolar disorder and manic psychosis, evidence for abnormalities in reward-related neural network function in mania is scarce [271-275].”
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“…in the abnormal hedonic, behavioral and motivational functioning observed in both depression and substance use disorders (Chambers et al., 2003; Marchand & Yurgelun-Todd, 2010; Nestler & Carlezon, 2006), may contribute to understanding sex differences in the adolescent prevalence of both…”
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Marchand, W. R., Lee, J. N., Johnson, S., Thatcher, J. W., Gale, P. D., Wood, N., & Jeong, E. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.10.016 · Cited by 93
“There is extensive evidence that the function of the striatum and associated cortico-basal ganglia circuitry plays a role in the neuropathology of affective disorders, for recent reviews see Marchand (2010); Marchand and Yurgelun-Todd (2010).”
BackgroundSelf-citationAltinay, M. I., Hulvershorn, L. A., Karne, H. S., Beall, E. B., & Anand, A. (2015) · Brain Connectivity · doi:10.1089/brain.2015.0396 · Cited by 85
“In their comprehensive review, Marchand and Yurgelun-Todd (2010) reported that studies that investigated striatal activation in bipolar mania showed increased ventral striatum and caudate activity in response to motor (simple reaction time test) and emotional (alternating blocks of captioned…”
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“In addition to the important role of cortical midline structures, basal ganglia dysfunction has long been implicated in mood disorders (Marchand and Yurgelun-Todd, 2010), and our finding of reduced activity in the BGN in depressed patients further substantiates this.”
BackgroundRaison, C. L., Hale, M. W., Williams, L. E., Wager, T. D., & Lowry, C. A. (2015) · Frontiers in Psychology · doi:10.3389/fpsyg.2014.01580 · Cited by 77
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BackgroundSubacute Default Mode Network Dysfunction in the Prediction of Post-Stroke Depression Severity
Lassalle-Lagadec, S., Sibon, I., Dilharreguy, B., Renou, P., Fleury, O., & Michèle Allard, A. (2012) · Radiology · doi:10.1148/radiol.12111718 · Cited by 75
Basal ganglia and thalamic morphology in schizophrenia and bipolar disorder
Womer, F. Y., Wang, L., Alpert, K. I., Smith, M. J., Csernansky, J. G., Barch, D. M., & Mamah, D. T. (2014) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2014.05.017 · Cited by 73
“Both these regions have been increasingly implicated in emotional and cognitive processing, particularly via cortico-basal ganglia and cortico-thalamic circuits, and appear to play important roles in executive functions that are commonly impaired in psychotic conditions (Byne et al., 2009; Haber and Calzavara, 2009; M…”
BackgroundResultDandash, O., Yücel, M., Daglas, R., Pantelis, C., McGorry, P. D., Berk, M., & Fornito, A. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0108-8 · Cited by 69
Yoon, S. J., Kim, T. D., Kim, J., & Lyoo, I. K. (2020) · Brain and Behavior · doi:10.1002/brb3.1953 · Cited by 70
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Alexander, L., Clarke, H. F., & Roberts, A. (2019) · Brain Science · doi:10.3390/brainsci9060129 · Cited by 54
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“Results Functional MRI Findings Evidence from several key papers and reviews demonstrated striatal hypoactivation in unipolar depression when anticipating and consuming rewards (Barch et al., 2016; Marchand & Yurgelun-Todd, 2010).”
BackgroundAccelerated aging of the putamen in patients with major depressive disorder
Sacchet, M. D., Camacho, M. C., Livermore, E. E., Thomas, E. A. C., & Gotlib, I. H. (2017) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.160010 · Cited by 63
“7 Previously research has indicated that depressed individuals have decreased activation in the striatum, 5,6 and some investigators have hypothesized that this abnormal activity affects decision-making.”
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Social cognition in major depressive disorder: A new paradigm?
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“Nevertheless, we hope the fi ndings of this meta-analysis show promise for the ability of functional neuroimaging to identify group-level differences distinguishing BD that can be leveraged to advance therapeutics in the coming years.”
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Self-citationSize and shape of the caudate nucleus in individuals with bipolar affective disorder
Ong, D., Walterfang, M., Malhi, G. S., Styner, M. A., Velakoulis, D., & Pantelis, C. (2012) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867412440191 · Cited by 43
“…that bipolar disorder is generally associated with striatal overactivity at a functional level, whereas structural findings have been mixed and that the most likely reason for this variability is the use of antipsychotic medication, which affect striatal volume (Marchand and Yurgelun-Todd, 2010).”
BackgroundInfluentialDebom, G. N., Gazal, M., Soares, M. S. P., do Couto, C. A. T., de Mattos, B. D. S., Lencina, C. L., Kaster, M. P., Ghisleni, G., Tavares, R. G., Braganhol, E., et al. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.10.008 · Cited by 43
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“…serves as the substrate for psychomotor symptoms of depression, but can also affect the circuitry that is responsible for mood by means of its direct and indirect bidirectional connectivity with the frontal cortices and the amygdala (Marchand and Yurgelun-Todd, 2010, 2012; Marchand et al., 2012).”
BackgroundHagan, C. C., Graham, J. M., Tait, R. J., Widmer, B., van Nieuwenhuizen, A. O., Ooi, C., Whitaker, K. J., Simas, T., Bullmore, E. T., Lennox, B., et al. (2015) · NeuroImage Clinical · doi:10.1016/j.nicl.2014.12.019 · Cited by 43
“…reward system, cortico-basal ganglia circuit, orbital prefrontal and medial prefrontal (which incorporates the fronto-limbic system) networks (Wilkinson and Goodyer, 2011; Graham et al., 2013; Roiser et al., 2012; Gotlib et al., 2010; Marchand and Yurgelun-Todd, 2010; Price and Drevets, 2012).”
BackgroundDeep brain stimulation for bipolar disorder—review and outlook
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“Nevertheless, recent data point to the neurobiology of bipolar depression being very similar to unipolar major depression, mainly regarding striatal dysfunction.(19,20) Furthermore, anhedonia and lack of motivation are also prominent in bipolar patients who suffer from treatmentresistant depression.”
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Self-citationXekardaki, A., Santos, M., Hof, P. R., Kövari, E., Bouras, C., & Giannakopoulos, P. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1021-5 · Cited by 36
“Mood disorders in late life are seen as the final byproduct of complex interactions between genetic predispositions, environmental influences, and neurobiological abnormalities [7, 14, 16, 88, 97].”
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Macfarlane, M. D., Looi, J. C., Walterfang, M., Spulber, G., Velakoulis, D., Crisby, M., Örndahl, E., Erkinjuntti, T., Garde, E., Waldemar, G., et al. (2013) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2013.05.010 · Cited by 31
“The neostriatum, comprising the caudate nuclei and putamina, connects to a number of different cortical and subcortical structures (Marchland and Yurgelun-Todd, 2010).”
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Kozicky, J.-M., Ha, T. H., Torres, I. J., Bond, D. J., Honer, W. G., Lam, R. W. M., & Yatham, L. N. (2013) · Bipolar Disorders · doi:10.1111/bdi.12103 · Cited by 28
Zhang, L., Wu, H., Zhang, A., Bai, T., Ji, G., Tian, Y., & Wang, K. (2021) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-020-01219-7 · Cited by 29
“The basal ganglia have close associations with sensorimotor, associative/cognitive, and limbic systems, and alterations in this region could be associated with BP patients [1, 36, 46, 50, 54, 98].”
BackgroundMarchand, W. R. (2011) · Depression Research and Treatment · doi:10.1155/2012/246725 · Cited by 28
“A large literature documents the role of striatal and associated corticobasal ganglia circuitry dysfunction in affective disorders, see [166, 167] for recent reviews.”
BackgroundSelf-citationElevated striatal γ-aminobutyric acid in youth with major depressive disorder
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“The striatum has been shown to be inextricably linked to reward function and is known to play a role in the pathophysiology of mood disorders (Marchand and Yurgelun-Todd, 2010).”
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“…striatal activity (Blumberg et al. 2000; Marchand & Yurgelun-Todd, 2010; Delvecchio et al. 2012; Hajek et al. 2013); whereas in remitted BD, both increased (Wessa et al. 2007; Marchand & Yurgelun-Todd, 2010) and decreased (Marchand & Yurgelun-Todd, 2010; Hajek et al. 2013) activity was reported.”
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The Purinergic System as a Target for the Development of Treatments for Bipolar Disorder
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“The capability of adenosine receptors to form heterodimers with dopamine receptors becomes especially relevant in this context, as A2AR-D2R heterodimers in the basal ganglia regulate corticostriatal dopamine neurotransmission, found hyperactive in patients with BD [137, 138] (Fig.”
BackgroundCaMKK2 as an emerging treatment target for bipolar disorder
Kaiser, J., Nay, K., Horne, C. R., McAloon, L. M., Fuller, O. K., Muller, A. G., Whyte, D. G., Means, A. R., Walder, K. R., Berk, M., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02260-3 · Cited by 19
“In addition, lithium increases CaMKK2 expression in the striatum, an area of the brain that displays structural abnormalities in bipolar disorder [173, 174].”
BackgroundChoi, K. W., Han, K., Kim, H., Kim, A., Kang, W., Kang, Y., Tae, W., & Ham, B. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.01.011 · Cited by 17
Hammar, Å., Neto, E., Clemo, L., Hjetland, G. J., Hugdahl, K., & Elliott, R. (2016) · PsyCh Journal · doi:10.1002/pchj.134 · Cited by 18
“…linked to MDD in several studies and meta-analyses (Arnone, McIntosh, Ebmeier, Munafo, & Anderson, 2012; Emre Bora, Harrison, Davey, Yücel, & Pantelis, 2012; Kim, Hamilton, & Gotlib, 2008; Koolschijn et al., 2009; Macfarlane et al., 2013; Marchand & YurgelunTodd, 2010; Pizzagalli et al., 2009).”
Dennison, M., Whittle, S., Yücel, M., Byrne, M. L., Schwartz, O., Simmons, J. G., & Allen, N. B. (2014) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-014-0319-2 · Cited by 16
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Bootsman, F., Brouwer, R. M., Kemner, S. M., Schnack, H. G., van der Schot, A. C., Vonk, R., Hillegers, M. H. J., Boomsma, D. I., Pol, H. E. H., Nolen, W. A., et al. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.09.023 · Cited by 13
“In BD, particular attention has been given to abnormalities in subcortical brain regions that are part of or associated with the cortico-striatothalamic and limbic networks involved in emotion processing, including the amygdala, hippocampus, striatum and thalamus (Phillips et al., 2003, 2008; Emsell and McDonald, 2009…”
InfluentialSriram, K., Lin, G. X., Jefferson, A. M., McKinney, W., Jackson, M. C., Cumpston, J. L., Cumpston, J. B., Leonard, H. D., Kashon, M. L., & Fedan, J. S. (2022) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2022.116137 · Cited by 12
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Dou, R., Gao, W., Meng, Q., Zhang, X., Cao, W., Kuang, L., Niu, J., Guo, Y., Cui, D., Jiao, Q., et al. (2022) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2022.915477 · Cited by 10
“Additionally, functional neuroimaging findings have also demonstrated greater pallidual activity during a motor task in bipolar mania patients (Marchand and Yurgelun-Todd, 2010), and higher BOLD responses of left pallidum in BD mania groups (Caligiuri et al., 2003).”
BackgroundThe neural correlates of perceived energy levels in older adults with late-life depression
Lam, C. L. M., Liu, H., Huang, C., Wai, Y., Lee, S., Yiend, J., Lin, C., & Lee, T. M. C. (2018) · Brain Imaging and Behavior · doi:10.1007/s11682-018-9940-y · Cited by 8
Basal ganglia volumetric changes in psychotic spectrum disorders
Liu, C., Cao, B., Yu, R., & Sim, K. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.05.048 · Cited by 8
Mania during antidepressant withdrawal in late‐onset depression
Singh, A., & Alexopoulos, G. S. (2013) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.3894 · Cited by 7
“This observation is consistent with earlier reports (Blumberg et al., 2003; Marchand and Yurgelun-Todd, 2010).”
ResultLi, S., Liu, D., Hu, L., Zhang, J., & Zhang, P. (2014) · Neural Regeneration Research · doi:10.4103/1673-5374.133171 · Cited by 8
“Imaging studies have shown that DRD2 density is increased in the basal ganglia of depressive patients (D’Haenen H and Bossuyt, 1994; Marchand and Yurgelun-Todd, 2010).”
BackgroundShen, N., Chen, Z., Sun, H. X., Tian, S., Wang, Y., Huang, Y., Yan, R., Hua, L., Yao, Z., & Lü, Q. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.02.054 · Cited by 7
To BD or not to BD: functional neuroimaging and the boundaries of bipolarity
Kuiper, S., McLean, L., & Malhi, G. S. (2012) · Expert Review of Neurotherapeutics · doi:10.1586/ern.12.126 · Cited by 6
Adenosinergic-Dopaminergic Signaling in Mood Disorders: A Mini-Review
Gonçalves, M. C. B., Glaser, T., de Oliveira, S. L. B., & Ulrich, H. (2020) · Journal of Caffeine and Adenosine Research · doi:10.1089/caff.2020.0009 · Cited by 5
“91,92 Other works, however, found an association between the A1 allele of the polymorphism Taq1A on the DRD2 gene 93,94 and the allele 5 and genotype 5–5 of the intron 2 DRD2 microsatellite and the susceptibility to type II BPD. 95 The GG genotype of the Taq1A polymorphism has also been linked to the early onset of BP…”
The Serotonergic System and Its Role in Thermoregulation
Negoita, A., Amuzescu, B. P., Mihailescu, D. F., & Bordea, C. (2025) · Physiologia · doi:10.3390/physiologia5040037 · Cited by 4
“The activity of the ventral striatum, an area involved in pleasant sensations evoked by thermal stimuli, is decreased in depression and increased in bipolar disorders [131,132].”
Schlaepfer, T. E., & Kayser, S. (2012) · Der Nervenarzt · doi:10.1007/s00115-011-3428-y · Cited by 4
Mindfulness for the Treatment of Depression
Marchand, W. R. (2015) · Springer eBooks · doi:10.1007/978-3-319-22255-4_7 · Cited by 4
Self-citationEllenbroek, B. A., & Youn, J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801657-2.00007-0 · Cited by 4
Choi, K. W., Kwon, S., Pyun, S., & Tae, W. (2020) · Psychiatry Investigation · doi:10.30773/pi.2020.0025 · Cited by 4
Dontiboina, H. R., Yadava, S., Nakka, V. P., Dumala, N., Viswanadh, M. K., Guntupalli, C., Nalluri, B. N., Malothu, N., Yadagiri, G., Gujjari, L., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05967-w · Cited by 3
“The striatum is responsible for multiple activities such as motor control, reward processing, cognition, and emotional regulation [69].”
Kandilarova, S., Maggioni, E., Squarcina, L., Najar, D., Homadi, M. S., Tassi, E., Stoyanov, D., & Brambilla, P. (2025) · BMJ Mental Health · doi:10.1136/bmjment-2024-301511 · Cited by 3
“26 Moreover, striatal functional connectivity patterns also correlate with distinct mood symptoms.”
Schlaepfer, T. E., Coenen, V. A., & Bewernick, B. H. (2012) · Springer eBooks · doi:10.1007/978-3-642-30991-5_9 · Cited by 2
“Nonetheless, current data point to the fact that the neurobiological aspects of bipolar depression are very similar to those of unipolar major depression, especially regarding striatal dysfunction (Marchand and Yurgelun-Todd 2010; Kupferschmidt and Zakzanis 2011).”
BackgroundImpact of ClockΔ19 mutation on neural recording performance and neural inflammatory responses
Dhawan, V., Narayanan, S., Thompson, C. H., Shi, D., Patel, Y., McClung, C. A., & Cui, X. T. (2026) · Biomaterials · doi:10.1016/j.biomaterials.2026.124369 · Cited by 1
Bipolar disorder and cognitive functioning : a two-year naturalistic study
Arts, B. M. G. (2012) · Research Publications (Maastricht University) · doi:10.26481/dis.20120511ba
Behaviour and biomarkers in frontotemporal dementia: Implications for general psychiatry
Wijeratne, C. (2012) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867412439054
“Functional abnormalities of the striatum and greater corticostriatal circuitry also exist in certain mood disorder subtypes, with evidence of striatal hypoactivity in unipolar depression (Marchand and Yurgelun-Todd, 2010), and reduced caudate nucleus volume in older people with depression (Hickie et al.”
Procesamiento cortical rápido de estímulos emocionales y toma de decisiones en humanos
Petroni, A. (2012) · Repositorio Digital Institucional de la Universidad de Buenos Aires (Universidad de Buenos Aires)
Ablative procedures in psychiatric neurosurgery
Huie, D., Aronson, J. P., & Eskandar, E. N. (2015) · Wiley eBooks · doi:10.1002/9781118801086.ch22
The Ethics of Suicide in Mental Illness: Novel Neuroscientific Perspectives
Malhi, G. S. (2019) · The American Journal of Bioethics · doi:10.1080/15265161.2019.1654021
Behavioral Consequences of Disrupted Circadian Clock Function within the Mouse Striatum
Mayor, M. A. (2021) · Spectrum Research Repository (Concordia University)
乳癌抑制遺伝子BRCA1の機能解析 : CDK2-BRCA1-NPM pathway(第105回日本外科学会定期学術集会)
太田, 智., 呉, 文., 速水, 亮., 佐藤, 工., & 福田, 護. (2005) · 日本外科学会雑誌
Strakowski, S. M., & Malhi, G. S. (2022) · Oxford University Press eBooks · doi:10.1093/med/9780197574522.003.0015
Wei, S., Tseng, H., Chang, H. H., & Chen, P. S. (2025) · International Journal of Bipolar Disorders · doi:10.1186/s40345-025-00393-8
Hsu, T., Li, J.-R., Tsai, S., Bai, Y., Su, T., Chen, T., Hsu, J.-W., Chen, M., & Liang, C. (2026) · Psychiatry Research · doi:10.1016/j.psychres.2026.117195
Moriguchi, S., & Inagaki, R. (2026) · Research Square · doi:10.21203/rs.3.rs-9132997/v1
Metadata
- Authors
- Marchand, W. R., & Yurgelun‐Todd, D.
- Affiliations
- United States Department of Veterans Affairs (US)
- Corresponding author
- Marchand, William R
- ORCID
- Marchand, William R
- Venue
- Bipolar Disorders
- Publisher
- Wiley
- Published
- 2010-12
- Volume
- 12
- Issue
- 8
- Pages
- 764-785
- ISSN
- 1398-5647 (ISSN-L)
- 1399-5618
- OpenAlex
- W1608229171
- Cited by
- 91
- References
- 322
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 8 · 2021: 3 · 2020: 8 · 2019: 6 · 2018: 4 · 2017: 1 · 2016: 6 · 2015: 7 · 2014: 5 · 2013: 8 · 2012: 15
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bipolar Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- striatum, mood disorders, bipolar disorder, major depressive disorder, corticostriatal circuits, functional imaging
- MeSH terms
- Bipolar Disorder, Cerebral Cortex, Corpus Striatum, Humans, Magnetic Resonance Imaging, Mood Disorders
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