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Cited by 1,609Neural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on BehaviorMemory and Neural Mechanisms

Neurocircuitry of Mood Disorders

Open access
Price, Joseph L, Drevets, Wayne C·2010·Neuropsychopharmacology
DOI 10.1038/npp.2009.104PMC PMC3055427
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Abstract

This review begins with a brief historical overview of attempts in the first half of the 20th century to discern brain systems that underlie emotion and emotional behavior. These early studies identified the amygdala, hippocampus, and other parts of what was termed the 'limbic' system as central parts of the emotional brain. Detailed connectional data on this system began to be obtained in the 1970s and 1980s, as more effective neuroanatomical techniques based on axonal transport became available. In the last 15 years these methods have been applied extensively to the limbic system and prefrontal cortex of monkeys, and much more specific circuits have been defined. In particular, a system has been described that links the medial prefrontal cortex and a few related cortical areas to the amygdala, the ventral striatum and pallidum, the medial thalamus, the hypothalamus, and the periaqueductal gray and other parts of the brainstem. A large body of human data from functional and structural imaging, as well as analysis of lesions and histological material indicates that this system is centrally involved in mood disorders.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes anatomical and clinical evidence that mood disorders arise from dysfunction in an extended medial prefrontal–limbic–striatal–pallidal–thalamic circuit. It argues that the medial prefrontal network and amygdala are central to emotional, autonomic, endocrine, and reward-related disturbances in major depression and bipolar disorder.

Key findings

  • The paper describes two main prefrontal networks: an orbital network tied to sensory integration and value assessment, and a medial network tied to limbic structures, visceral control, and mood regulation. The medial network connects with the amygdala, ventral striatum, mediodorsal thalamus, hypothalamus, periaqueductal gray, and brainstem.
  • In mood disorders, the most consistently reported structural abnormality is reduced gray matter in the left subgenual anterior cingulate cortex ventral to the corpus callosum genu. Reductions are also reported in orbitofrontal cortex, ventrolateral prefrontal cortex, frontal polar/dorsolateral prefrontal cortex, parahippocampal gyrus, and temporopolar cortex.
  • Hippocampal volume reductions in major depression are reported at 8–19% in some studies, but other studies do not replicate this. Amygdala volume findings are mixed: smaller in unmedicated bipolar disorder in one high-resolution study, but larger in bipolar subjects receiving mood-stabilizing treatments.
  • Postmortem and spectroscopy findings include reduced glia, especially oligodendrocytes, reduced synapses or synaptic proteins, reduced neuronal size, and reduced GABA and Glx levels in prefrontal regions. The review links these to stress-related dendritic atrophy and elevated glutamatergic/glucocorticoid activity.

Methods

  • Narrative review, not a primary study. It integrates historical models of the limbic system with modern axonal tracing studies in macaque monkeys, human lesion and neuroimaging data, postmortem neuropathology, magnetic resonance spectroscopy, and rodent chronic stress models.
  • The anatomical synthesis focuses on connectional networks of the orbital and medial prefrontal cortex, amygdala, striatum, pallidum, mediodorsal and midline thalamic nuclei, hypothalamus, and brainstem.
  • Clinical synthesis reviews structural MRI, functional imaging, neuropathological, and treatment studies in major depressive disorder and bipolar disorder, then proposes a circuit-based model of depression.

Limitations

  • The paper states that understanding remains at an early stage and that later generations may view current misconceptions with bemusement. It also states that translating monkey findings to humans is difficult, that the human cortex is not simply an enlarged monkey brain, and that new architectonic maps of human cortex are needed.
  • The paper states that current DSM-based nosology is insufficient for discovering disease mechanisms and that a circuit-based nosology is needed.
  • Evident from the text: as a narrative review, it does not use a systematic search or quantitative meta-analysis; it reports inconsistent findings across studies, including discrepant hippocampal and amygdala volumes and conflicting subgenual cingulate metabolism results, which the authors partly attribute to partial volume effects and clinical heterogeneity.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/npp.2009.104

Cites

374 of 374 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

36 of 262 cited sources checked · 11 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    In rats, lesions of the mPFC enhance behavioral, sympathetic, and endocrine responses to stressors or fear-conditioned stimuli.

    “Conversely, lesions of the mPFC enhance behavioral, sympathetic, and endocrine responses to stressors or fearconditioned stimuli in rats (Morgan and LeDoux, 1995;Sullivan and Gratton, 1999).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Morgan and LeDoux, 1995 source
    • cites Sullivan and Gratton, 1999 source

      The Discussion reports that right or bilateral mPFC lesions suppressed corticosterone responses and reduced stress-ulcer pathology, contrary to the claimed enhancement of endocrine and autonomic responses. Left-sided lesions increased restraint-induced defecation, but that isolated finding does not support the broad claim; this study did not test fear-conditioned stimuli. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    Lesions of the orbital cortex produce a deficit in using reward as a guide to behavior.

    “In addition, lesions of the orbital cortex produce a deficit in the ability to use reward as a guide to behavior (Rudebeck and Murray, 2008)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Rudebeck and Murray, 2008 source

      The Discussion reports that monkeys with orbitofrontal cortex lesions were impaired at using reward information to guide subsequent choices. The claim omits an important limit: this deficit was observed after a reversal, while initial discrimination learning was unaffected. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation

    fMRI studies show that medial prefrontal cortex activity correlates with visceral activation in response to emotional or non-emotional stimuli.

    “and recent fMRI studies have shown that activity in the medial prefrontal cortex correlates with visceral activation in response to emotional (Critchley et al, 2000;Williams et al, 2000) or even non-emotional (Teves et al, 2004) stimuli.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Critchley et al, 2000 source
    • cites Williams et al, 2000 source
    • cites Teves et al, 2004 source

      The paper’s opening section reports medial prefrontal cortex activation during autonomic responses to hypoglycemia, without cognitive or emotional stress, supporting the non-emotional-stimulus portion attributed to Teves et al. But it explicitly says the study used positron emission tomography (PET), not fMRI. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
  • Premisecitation

    Imaging studies show that a circuit including the medial prefrontal cortex and the periaqueductal gray area is activated by acute hypoglycemia.

    “Imaging studies show that a circuit including the medial prefrontal cortex and the periaqueductal gray area is activated by acute hypoglycemia (Teves et al, 2004)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Teves et al, 2004 source

      The Results report statistically significant activation of the medial prefrontal cortex during hypoglycemia. The Discussion reports evidence for periaqueductal gray activation, but says it did not meet the prespecified criteria for statistical significance. The claim omits that qualification for one component of the proposed circuit. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
  • Premisecitation

    The striatal projection from the LPFC as a whole is directed to the central and dorsal part of the striatum.

    “The striatal projection from the LPFC as a whole is directed to the central and dorsal part of the striatum (Calzavara et al, 2007).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Calzavara et al, 2007 source
  • May combine two claims. 46
  • Classified as probably not a substantial claim. 28

  • May combine two claims.

    Premisecitation

    The perigenual prefrontal cortex connects to the same ventromedial striatum and the same region of the mediodorsal thalamic nucleus.

    “The perigenual prefrontal cortex is also connected to both the same ventromedial part of the striatum (Haber et al, 1995;Ferry et al, 2000b), and the same region of MD (Russchen et al, 1987;Ray and Price, 1992).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Haber et al, 1995 source
    • cites Ferry et al, 2000b source
    • cites Russchen et al, 1987 source

  • May combine two claims.

    Premisecitation

    Many orbital neurons code for the presence or expectation of reward and for the relative value of stimuli.

    “In addition, many neurons appear to code for the presence or expectation of reward (Schultz et al, 1997), and for the relative value of stimuli (Padoa-Schioppa and Assad, 2006).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Schultz et al, 1997 source

      The citation to Schultz et al. is attached to the presence-or-expectation-of-reward clause, not the relative-value clause. In “Information Encoded in Dopaminergic Activity” (p. 2), the paper reports responses to unpredicted rewards and reward-predicting cues, but identifies the neurons as dopaminergic neurons of the VTA and substantia nigra, not orbital neurons. It also characterizes their signal more specifically as a reward-prediction error, rather than a general code for reward presence or expectation. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites Padoa-Schioppa and Assad, 2006 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The caudal system may be part of the dorsal attention system.

    “In addition to its role in control of saccadic eye movements, the caudal system may be part of the dorsal attention system (Corbetta et al, 2002).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Corbetta et al, 2002 source

      The Conclusions (page unavailable) identify the intraparietal and superior frontal cortex as a dorsal attention network. The section on the dorsal frontal-parietal network also discusses the frontal eye field, but our copy does not identify a ‘caudal system’ or place one in that network. Searches for ‘caudal system’ and ‘caudal’ did not resolve that link. (LLM, conf=0.72)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The extant data suggest this volumetric reduction exists early in illness and in young adults at high familial risk for MDD.

    “The extant data suggest this volumetric reduction exists early in illness and in young adults at high familial risk for MDD (Botteron et al, 2002;Hirayasu et al, 1999;Drevets et al, 2004b;Boes et al, 2008).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Botteron et al, 2002 source
    • cites Hirayasu et al, 1999 source

      The Discussion reports reduced left subgenual cingulate volume at first hospitalization, supporting the early-illness part of the claim. The Method describes a young first-episode affective-disorder group, predominantly with bipolar disorder, and the comparison is based on family history of affective disorder—not specifically young adults at high familial risk for MDD. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites Drevets et al, 2004b

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    One study showed that the mean sgACC gray matter volume was reduced significantly vs controls in subjects with psychotic affective illness who also had mood-disordered first-degree relatives but not in subjects without mood-disordered first-degree relatives.

    “One study showed that the mean sgACC gray matter volume was reduced significantly vs controls in subjects with psychotic affective illness who also had mood-disordered first-degree relatives but not in subjects without mood-disordered first-degree relatives (Hirayasu et al, 1999).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Hirayasu et al, 1999 source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The left perigenulate ACC volume was smaller in boys with subclinical depressive symptoms, and the negative correlation between left sgACC volume and depression symptoms was particularly robust in boys with a family history of depression.

    “It has also been reported that the left perigenulate ACC volume was smaller in boys with subclinical depressive symptoms, and that the negative correlation between left sgACC volume and depression symptoms was particularly robust in boys with a family history of depression (Boes et al, 2008).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Boes et al, 2008 source

      The Results (Tables 2 and 3; page unavailable) show smaller left rostral ACC (rACC) volume in boys with depressive symptoms and a stronger negative correlation in boys with a positive nuclear family history of depression. The study measured rACC, which includes the subgenual region, but did not establish these findings specifically for left subgenual ACC or an isolated perigenual region. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The volumetric deficit applies to males and females, to psychotic unipolar and bipolar depression, and to bipolar-spectrum illness.

    “The volumetric deficit applies to males (Hastings et al, 2004;Boes et al, 2008) and females (Botteron et al, 2002), to psychotic unipolar and bipolar depression (Hirayasu et al, 1999;Coryell et al, 2005;Adler et al, 2007), and to bipolar-spectrum illness (Haznedar et al, 2005).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Hastings et al, 2004 source
    • cites Boes et al, 2008 source
    • cites Botteron et al, 2002 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    This may encode information about reward prediction in monkeys.

    “The burst-firing patterns increase DA release in the accumbens, which may encode information about reward prediction in monkeys (Schultz et al, 1997).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Schultz et al, 1997 source

      The ‘Information Encoded in Dopaminergic Activity’ section (p. 2) says dopamine-neuron output in monkeys appears to encode errors in reward prediction. It identifies the nucleus accumbens as a target of these neurons, but does not establish that burst-firing increases dopamine release there or that release there carries the prediction signal. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    The initial limbic framework included the hippocampus, amygdala, anterior and medial thalamus, cingulate gyrus, and visceral control areas in the hypothalamus and brainstem.

    “In spite of this the initial framework was adequate to indicate that the system included the hippocampus and amygdala, the anterior and medial thalamus, the cingulate gyrus, and related visceral control areas in the hypothalamus and brainstem.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Neurons in orbital network areas respond to multimodal stimuli, and their responses reflect affective as well as sensory qualities.

    “Remarkably, although recording studies have indeed indicated that neurons in the orbital network areas respond to multi-modal stimuli (eg, the sight, flavor, and texture of food stimuli) the responses reflect affective as well as sensory qualities of the stimuli.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A projection from the amygdala to the posterior cingulate cortex has been identified.

    “Recently a projection from the amygdala has been identified to the posterior cingulate cortex (Buckwalter et al, 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Buckwalter et al, 2008 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The hippocampus is more involved in memory processing, whereas the amygdala is more related to emotion.

    “Subsequently, the hippocampus has been shown to be more involved in memory processing, and the amygdala to be more related to emotion (Zola- Morgan et al, 1991)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zola- Morgan et al, 1991 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Early 20th-century studies identified the amygdala, hippocampus, and other limbic structures as central components of the emotional brain.

    “These early studies identified the amygdala, hippocampus, and other parts of what was termed the 'limbic' system as central parts of the emotional brain.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Visceral reactions provide the means of emotional expression and may even form the basis of emotions.

    “Emotions are obviously linked to visceral function, and visceral reactions provide the means of emotional expression and possibly even the basis for the emotions themselves, as James W (1884) argued.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites James W (1884)

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    These circuits form the core of the neural system implicated in mood disorders.

    “As discussed in later parts of this chapter, these circuits form the core of the neural system that has been implicated in mood disorders.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The anatomical and functional organization of the emotion-related circuits described in monkeys and other animals is sufficiently similar to that in humans to inform conclusions about human mood disorders.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The autonomic nervous system controls many visceral functions and is itself coordinated by the hypothalamus.

    “Work by Gaskell, Langley, Cannon and others in the late nineteenth and early twentieth century established that many visceral functions are controlled by the autonomic nervous system, which is itself controlled and coordinated by the hypothalamus, the so-called 'head ganglion of the autonomic nervous system'.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    These striatal areas project to the ventral and rostral pallidum, which sends GABAergic axons to the mediodorsal thalamic nucleus.

    “These striatal areas in turn project to the ventral and rostral pallidum, which itself sends GABAergic axons to the mediodorsal thalamic nucleus (MD, Russchen et al, 1987).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Russchen et al, 1987 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Papez and MacLean proposed that the limbic system, including hippocampal formation, cingulate gyrus, and anterior thalamus, elaborates emotion and, through interaction with the hypothalamus, participates in emotional expression.

    “Papez and MacLean proposed that the 'Limbic System,' including the hippocampal formation, cingulate gyrus, and anterior thalamus, elaborates emotion and, through its interaction with the hypothalamus, is involved in emotional expression (Figure 1).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites MacLean (1949) source
    • cites Papez (1937) source

  • May combine two claims.

    Interpretationreasoning

    The orbital network functions both in integrating multimodal stimuli and in assessing the value of those stimuli.

    “The orbital network therefore appears to function both as a system for integration of multi-modal stimuli, and as a system for assessment of the value of those stimuli.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Observations in decorticate cats suggested that the hypothalamus produces sham rage and is responsible for both the experience and expression of emotion.

    “Observations on decorticate cats by Bard (1928) and others suggested that the hypothalamus was involved in the production of sham rage, and was responsible for the experience as well as the expression of emotion.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bard (1928) source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisereasoning

    Cerebral hemisphere structures are responsible for generating and experiencing emotion, while the hypothalamus and other visceral control structures are responsible for many aspects of emotional expression.

    “Subsequently, however, many observations indicated that the structures in the cerebral hemispheres are responsible for the generation and experience of emotion, although the hypothalamus and other visceral control structures are responsible for many aspects of emotional expression.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    The dorsal system has outputs to the hypothalamus and periaqueductal gray, so it can modulate visceral functions.

    “As with the medial network, there are outputs from dorsal areas to the hypothalamus and PAG, so this system can also modulate visceral functions.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The somatic marker hypothesis proposes that the visceral or bodily reaction accompanying emotion serves as a subconscious warning or guide indicating disadvantageous behaviors.

    “To account for such deficits, Damasio and his colleagues have proposed the 'somatic marker hypothesis,' which supposes that the visceral or bodily reaction that normally accompanies emotion (the somatic marker) serves as a subconscious warning or guide, indicating some behaviors are disadvantageous and should be avoided (Damasio, 1994).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Damasio, 1994 source

  • May combine two claims.

    Interpretationreasoning

    Brainstem areas do not project directly to cortex, so lateral MD serves as a relay of information to cortex and may modulate thalamo-cortico-thalamic interactions.

    “In this case, however, the brainstem areas do not project directly to the cortex, so lateral MD serves as a relay of information to cortex, possibly as well as modulating thalamo-corticothalamic interactions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The OMPFC is generally related to medial MD, whereas the LPFC is related to more lateral parts of MD.

    “Although the organization of the thalamocortical interconnections are complex, the OMPFC is generally related to medial MD (MDm), whereas the LPFC is related to more lateral parts of MD (Ray and Price, 1993).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ray and Price, 1993 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Area 45a may represent a multimodal cortex that is also connected to circuits responsible for emotion.

    “It is possible that this region represents a multi-modal cortex that also connected to circuits responsible for emotion.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    A similar deficit in subjects with mood disorders might be difficulty letting go of a negative mood or mind-set long after traumatic events resolve.

    “A similar deficit in subjects with mood disorders might be the difficulty of 'letting go' of a negative mood or mind-set long after the resolution of any traumatic events that might have justified it.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The anatomical and functional organization of the emotion-related circuits described in monkeys and other animals is sufficiently similar to that in humans to inform conclusions about human mood disorders.

  • May combine two claims.

    Premisecitation

    In most cases the projection to cortex involves more neurons than that to MD, suggesting that non-thalamic input to cortex carries more detailed information.

    “Indeed, in most cases the projection to the cortex involves more neurons than that to MD, suggesting that the non-thalamic input to cortex carries more detailed information (Russchen et al, 1987;Carmichael et al, 1994;Price, 2003).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Russchen et al, 1987 source
    • cites Carmichael et al, 1994

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Price, 2003

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    The prefrontal cortex is reciprocally connected to the mediodorsal thalamic nucleus, with different prefrontal regions related to different portions of MD.

    “The prefrontal cortex as a whole is reciprocally connected to the mediodorsal thalamic nucleus (MD), with different prefrontal regions related to different portions of MD (Figure 6).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    The ventral system lacks olfactory or taste inputs and may function in the assessment of non-food sensory objects.

    “The major difference with the orbital network is that there do not appear to be olfactory or taste inputs to the ventral system; it is possible that it functions in the assessment of non-food sensory objects.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Convergent but antagonistic inputs modulate reciprocal thalamocortical interactions between the OMPFC and MDm.

    “It can be suggested that these convergent but antagonistic inputs would interact to modulate the reciprocal thalamocortical interactions between the OMPFC and MDm.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The medial network connects primarily with anterior and posterior cingulate cortex, whereas the orbital network connects primarily with the middle cingulate.

    “For example, the medial network is primarily connected with the anterior and posterior parts of the cingulate cortex, whereas the orbital network connects primarily to the middle portion of the cingulate (Miller et al, 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Miller et al, 2008

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    Limbic inputs are dominant, maintaining ongoing thalamo-cortical and cortico-thalamic activity, while more prominent pallidal inputs interrupt ongoing patterns and allow a switch from one behavior to another.

    “Although the limbic inputs are dominant, ongoing patterns of thalamo-cortical and cortico-thalamic activity would be maintained, allowing for consistent behavior.When pallidal inputs become more prominent, ongoing patterns would be interrupted, allowing a switch from one behavior to another.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The medial network consists of ventromedial frontal areas rostral and ventral to the genu, areas along the medial edge of the orbital cortex, and a small caudolateral orbital region.

    “It consists of areas on the ventromedial surface of the frontal cortex, rostral and ventral to the genu, areas along the medial edge of the orbital cortex, and a small caudolateral orbital region at the rostral end of the insula (Carmichael and Price, 1996; Figure 3).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Carmichael and Price, 1996 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    The ventral system consists of areas ventral to the principal sulcus, including area 46v, 12r, and 45b.

    “The ventral system of the LPFC consists of areas ventral to the principal sulcus, including area 46v, 12r, and 45b (area 45a is a special case, section 45a see below) (Figure 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The subgenual cortex provides the heaviest projection, terminating in medial and lateral hypothalamus and in dorsolateral and ventrolateral columns of the periaqueductal gray, while fibers from lateral medial network areas are restricted to lateral hypothalamus and ventrolateral periaqueductal gray.

    “There is some degree of organization within this system, such that the subgenual cortex provides the heaviest projection, which terminates in both the medial and lateral hypothalamus, and in both dorsolateral and ventrolateral columns of the PAG, while the fibers from the lateral part of the medical network (areas Iai, and 47/12s) are restricted to the lateral hypothalamus, and the ventrolateral P”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites O ¨ngu ¨r et al, 1998a, b

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites An et al, 1998

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    Large parts of the LPFC are closely related to the medial and orbital prefrontal networks and may have similar functional roles.

    “This analysis has indicated that large parts of the LPFC are closely related to the medial and orbital prefrontal networks, and may have similar functional roles.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    Medial network areas are preferentially interconnected and have outputs to visceral control areas in the hypothalamus and periaqueductal gray.

    “As with the orbital network, the areas of the medial network are preferentially interconnected with each other, and the network is also characterized by outputs to visceral control areas in the hypothalamus and periaqueductal gray.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Specific projections from the dorsal, ventral, and caudal parts of the LPFC to the striatum have not been clearly defined.

    “The specific projections from the dorsal, ventral, and caudal parts of the LPFC that were described above have not been clearly defined.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The midline nuclei are specifically and reciprocally connected to medial prefrontal network areas, with little connection to the orbital network.

    “They are specifically and reciprocally connected to the medial prefrontal network areas, with little connection to the orbital network.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Hsu andPrice, 2007, 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisenone given

    The dorsal system is interconnected with the medial prefrontal network and shares most of its other connections.

    “The dorsal system is interconnected with the medial prefrontal network, and shares most of its other connections (Figure 5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    These studies have implicated subgenual PFC regions of the infralimbic cortex (BA 25) and the adjacent sgACC corresponding to BA 24sg.

    “These studies have implicated subgenual PFC regions of the infralimbic cortex (BA 25) (eg, Coryell et al, 2005) and the adjacent sgACC corresponding to BA 24sg (eg, O ¨ngu ¨r et al, 1998a, b, 2003;Drevets et al, 1997a) (Figure 9).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Coryell et al, 2005 source
    • cites O ¨ngu ¨r et al, 1998a, b, 2003

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Drevets et al, 1997a source

  • May combine two claims.

    Interpretationreasoning

    Because GFAP amount varies with astrocyte functional state and GFAP staining does not demonstrate all astrocytes, it is unclear whether these results indicate changes in astrocyte number or function.

    “Because the amount of GFAP varies with the functional state of astrocytes, and GFAP staining often does not demonstrate all astrocytes, it is unclear whether these results indicate changes in astrocyte number or function.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The neuroimaging abnormalities found in MDD and BD generally have corroborated hypotheses regarding the neural circuitry underlying depression that initially were based on observations from the behavioral effects of lesions experimentally placed in experimental animals.

    “The neuroimaging abnormalities found in MDD and BD generally have corroborated hypotheses regarding the neural circuitry underlying depression that initially were based on observations from the behavioral effects of lesions experimentally placed in experimental animals (see 'Cortico-Striatal-Thalamic Circuits Related to the OMPFC' above)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Elevated glucocorticoid concentrations and repeated stress decrease the proliferation of oligodendrocyte precursors.

    “elevated glucocorticoid concentrations and repeated stress decrease the proliferation of oligoden-drocyte precursors (Alonso, 2000;Banasr and Duman, 2007).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Alonso, 2000

      Not checked in the free run.

    • cites Banasr and Duman, 2007 source

  • May combine two claims.

    Premisecitation

    The short allele of the serotonin transporter promoter region length polymorphism (5HTT-PRL) has been identified as a genetic factor associated with both an increased vulnerability for developing MDD within the context of stress and a reduction in sgACC gray matter volume.

    “Notably, the short allele of the serotonin transporter promoter region length polymorphism (5HTT-PRL) has been identified as a genetic factor that is associated with both an increased vulnerability for developing MDD within the context of stress (Caspi et al, 2003) and a reduction in sgACC gray matter volume (Pezawas et al, 2005).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Caspi et al, 2003 source
    • cites Pezawas et al, 2005 source

  • May combine two claims.

    Interpretationreasoning

    The same domains are implicated in depression and mania, although the characteristic disturbance in emotional behavior within these syndromes appears opposite with respect to emotional valence.

    “Thus, the same domains are implicated in depression and mania, although the characteristic disturbance in emotional behavior within these syndromes appears opposite with respect to emotional valence.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    In bipolar disorder, episodes of depression occur alternately with manic or hypomanic episodes during which mood becomes euphoric and labile, capacity for deriving pleasure increases, behaviors aimed at deriving pleasure increase, and energy psychomotor activity, libido, and self esteem become elevated.

    “In BD, episodes of depression occur alternately with manic or hypomanic episodes during which the mood becomes euphoric and labile, the capacity for deriving pleasure increases, behaviors aimed at deriving pleasure increase, and energy psychomotor activity, libido, and self esteem become elevated.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisereasoning

    Extant neural models of depression posit that dysfunction within the medial network and related limbic structures underlies the disturbances in emotional behavior and other cognitive aspects of the major depressive syndrome.

    “Extant neural models of depression posit that dysfunction within the medial network and related limbic structures underlie the disturbances in emotional behavior and other cognitive aspects of the major depressive syndrome.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Neuropathological changes in the mPFC and amygdala in mood disorders may impair their roles in modulating visceral responses to stressors and emotional stimuli.

    “The neuropathological changes evident in the mPFC and amygdala in mood disorders may impair their roles in modulating visceral responses to stressors and emotional stimuli.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In rats exposed to fear-conditioned stimuli, mPFC neuronal firing activity is reduced, and its magnitude correlates inversely with the increase in amygdala neuron activity and fear behavior.

    “Rats exposed to fear-conditioned stimuli show reduced mPFC neuronal firing activity, the magnitude of which correlates inversely with the corresponding increase in amygdala neuron activity and fear behavior (Garcia et al, 1999).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Garcia et al, 1999 source

  • May combine two claims.

    Premisecitation

    In MDD, depression severity correlates positively with amygdala and sgACC activity, and negatively with activity in the left VLPFC/lateral OFC (approximately BA 45a and 47s).

    “Such reciprocal relationships between the medial prefrontal network and amygdala may be related to the observations that in MDD depression severity correlates positively with amygdala and sgACC activity, but negatively with activity in the left VLPFC/lateral OFC (approximately BA 45a and 47s) (Drevets et al, 2004a).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Drevets et al, 2004a

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    MRS studies of MDD show reductions in cerebral GABA levels and in the Glx peak.

    “The results from MRS studies of MDD show reductions in cerebral GABA levels and in the 'Glx' peak, which reflects the combined concentrations of glutamate plus glutamine, that appear compatible with the postmortem findings of cellular reductions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Dendritic atrophy presumably would be reflected by a decrease in the volume of the neuropil.

    “Dendritic atrophy presumably would be reflected by a decrease in the volume of the neuropil, which occupies most of the gray matter volume.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Neuropil occupies most of the gray matter volume.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    A neural model suggests that impairment of medial prefrontal network and BLA function disinhibits efferent transmission from the ACe and BNST to the hypothalamus and brainstem.

    “One neural model that could account for the neuroendocrine autonomic neurotransmitter attention and rewardseeking abnormalities associated with MDE suggests that impairment of medial prefrontal network and BLA function disinhibits the efferent transmission from the ACe and BNST to the hypothalamus and brainstem (Figure 10).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Severe depression is associated with hypersecretion of cortisol during the circadian nadir, pituitary and adrenal gland enlargement, and CSF-CRF levels that are increased inappropriately to plasma cortisol concentrations.

    “Severe depression is associated with hypersecretion of cortisol during the circadian nadir, pituitary and adrenal gland enlargement, and CSF-CRF levels that are increased to an extent that is inappropriate to the plasma cortisol concentrations”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Gold and Chrousos, 2002 source
    • cites Drevets et al, 2004a

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Swaab et al, 2005 source

  • May combine two claims.

    Interpretationreasoning

    If ACC neuropathological changes interfere with cortical drive on VTA-DA neuronal burst-firing activity, they may impair perception or learning of reward and potentially interfere with behavioral engagement in pleasurable or positively reinforcing activities.

    “If the neuropathological changes extant within the ACC in mood disorders interfere with the cortical drive on VTA-DA neuronal burst-firing activity, they may impair perception or learning of reward, and potentially interfere with behavioral engagement in pleasurable or positively reinforcing activities.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    The autonomic imbalance associated with depression could reflect medial network dysfunction coupled with excessive amygdala activity.

    “The autonomic imbalance associated with depression also could reflect medial network dysfunction coupled with excessive amygdala activity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    It may be expected that multisynaptic pathways would serve a similar function.

    “although this has not been found in primates (An et al, 1998;Freedman et al, 2000), it may be expected that multisynaptic pathways would serve a similar function.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites An et al, 1998

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Freedman et al, 2000

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Depressed subjects show abnormal reductions in CSF and jugular vein plasma levels of the DA metabolite homovanillic acid, striatal DA transporter binding, [11C]L-DOPA uptake across the blood-brain barrier, and striatal dopamine D1 receptor binding.

    “In addition, depressed subjects showed abnormal reductions in the CSF and jugular vein plasma levels of the DA metabolite homovanillic acid (Willner, 1995;Lambert et al, 2000), striatal DA transporter binding (Meyer et al, 2001), [ 11 C]L-DOPA uptake across the blood-brain barrier (A ˚gren et al, 1993), and striatal dopamine D 1 receptor binding (Cannon et al, 2009).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Willner, 1995

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Lambert et al, 2000 source
    • cites Meyer et al, 2001 source

  • May combine two claims.

    Premisecitation

    Preliminary reports indicate that chronic SSRI treatment or deep brain stimulation of the anterior capsule reduces the abnormally elevated metabolism in the accumbens area in depression or in depression associated with obsessive-compulsive disorder.

    “Preliminary reports indicate that chronic SSRI treatment or deep brain stimulation of the anterior capsule also reduces the abnormally elevated metabolism in the accumbens area in depression (Drevets et al, 2006) or in depression associated with obsessive-compulsive disorder (Van Laere et al, 2006)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Drevets et al, 2006

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Van Laere et al, 2006

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Mesolimbic DA projections from the VTA to the nucleus accumbens shell and the mPFC have major roles in learning associations between operant behaviors or sensory stimuli and reward, and in mediating the reinforcing properties of natural rewards.

    “The mesolimbic DA projections from the VTA to the nucleus accumbens shell and the mPFC thus have major roles in learning associations between operant behaviors, or sensory stimuli and reward, and in mediating the reinforcing properties of natural rewards such as food and sex (Nestler and Carlezon, 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nestler and Carlezon, 2006 source

  • May combine two claims.

    Premisecitation

    Both deficits in negative feedback systems and excessive central stimulation of the secretion of CRF and/or other ACTH secretagogues are implicated in mood disorders.

    “both deficits in negative feedback systems and excessive central stimulation of the secretion of CRF and/or other ACTH secretagogues are implicated in mood disorders (Gold and Chrousos, 2002;Drevets et al, 2004a;Swaab et al, 2005;Carroll et al, 2007).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Gold and Chrousos, 2002 source
    • cites Drevets et al, 2004a

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Swaab et al, 2005 source

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationcitation

    Antidepressant therapies may compensate for this dysfunction by modulating the pathological limbic activity that putatively mediates depressive symptoms, or by enhancing the expression of neurotrophic factors that protect medial network function from the effects of repeated stress.

    “Antidepressant therapies may compensate for this dysfunction by modulating the pathological limbic activity that putatively mediates depressive symptoms (Drevets et al, 2002a), or by enhancing the expression of neurotrophic factors that protect medial network function from the effects of repeated stress (Manji et al, 2001).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Drevets et al, 2002a source
    • cites Manji et al, 2001 source
64 of 64

  • The paper relies on this without support.

    The anatomical and functional organization of the emotion-related circuits described in monkeys and other animals is sufficiently similar to that in humans to inform conclusions about human mood disorders.

    “In the last 15 years these methods have been applied extensively to the limbic system and prefrontal cortex of monkeys, and much more specific circuits have been defined.”
    “A large body of human data from functional and structural imaging, as well as analysis of lesions and histological material indicates that this system is centrally involved in mood disorders.”

  • The paper relies on this without support.

    MDD and BD are not associated with gross brain pathology or with clear animal models for spontaneous recurrent mood episodes.

    “As these conditions are not associated with gross brain pathology, or with clear animal models for spontaneous recurrent mood episodes, the development of tools that allowed noninvasive assessment of human brain structure and function has proven critical to elucidating their neurobiology.”

  • The paper relies on this without support.

    Findings from animal models of stress and lesions can be generalized to humans to understand mood disorders.

    “It is likely that the role of the PVT is general across many types of stressors.”

  • The paper relies on this without support.

    Neuroimaging abnormalities in mood disorders reflect the underlying neural circuitry rather than epiphenomenal changes.

    “The neuroimaging abnormalities found in MDD and BD generally have corroborated hypotheses regarding the neural circuitry underlying depression that initially were based on observations from the behavioral effects of lesions experimentally placed in experimental animals (see 'Cortico-Striatal-Thalamic Circuits Related to the OMPFC' above)”

  • The paper relies on this without support.

    MRS spectra reflect combined intracellular and extracellular pools of glutamate-glutamine and GABA but are dominated overwhelmingly by the intracellular pools.

    “Although these spectra reflect the combined intracellular and extracellular pools of glutamate-glutamine and GABA, they are dominated overwhelmingly by the intracellular pools.”

  • The paper relies on this without support.

    The majority of the GABA pool exists within GABAergic neurons.

    “The majority of the GABA pool exists within GABAergic neurons, so the reduction in GABA in the dorsal anterolateral PFC is compatible with the report of reduced GABAergic neurons in this region (BA9) in MDD (Rajkowska et al, 2007).”

  • The paper relies on this without support.

    The Glx measure reflects the intracellular glutamate and glutamine pools.

    “As the Glx measure reflects the intracellular glutamate and glutamine pools this abnormality appears compatible with the reductions in glial cells found postmortem in the same regions in MDD.”

  • The paper relies on this without support.

    Perineuronal oligodendroglia and astroglia play roles in glutamate-glutamine cycling.

    “Both perineuronal oligodendroglia and astroglia play roles in glutamate-glutamine cycling.”

  • The paper relies on this without support.

    Neuropil occupies most of the gray matter volume.

    “Dendritic atrophy presumably would be reflected by a decrease in the volume of the neuropil, which occupies most of the gray matter volume.”

  • The paper relies on this without support.

    The ACC receives extensive dopaminergic innervation from the VTA and sends projections to the VTA that regulate phasic dopamine release.

    “The ACC receives extensive dopaminergic innervation from the VTA and sends projections to the VTA that regulate phasic dopamine (DA) release.”

  • The paper relies on this without support.

    Stimulation of projections from the amygdala to the ventral striatum interrupts the maintenance of cortically driven response patterns.

    “Stimulation of projections from the amygdala to the ventral striatum interrupts the maintenance of these cortically driven response patterns, providing an adaptive over-ride that interrupts goal-directed thought or behavior in response to threat or novelty.”

  • The paper relies on this without support.

    Antidepressant drugs impact serotonergic, dopaminergic, noradrenergic, cholinergic, glutamatergic, GABAergic, glucocorticoid, and peptidergic systems through either primary or secondary pharmacological actions.

    “Antidepressant drugs (AD) impact these systems through either primary or secondary pharmacological actions.”

  • The paper relies on this without support.

    The medial and orbital prefrontal networks connect to separate but parallel cortico-striato-pallido-thalamic loops that use adjacent cortical, mediodorsal thalamic, striatal, and pallidal regions.

    “Note that the two networks are related to parallel but distinct loops that involve adjacent parts of the cortex MD thalamus striatum and pallidum.”

  • The paper relies on this without support.

    The amygdala and hippocampus, as limbic structures, are mainly associated with the medial network.

    “Limbic structures such as the amygdala and hippocampus are primarily related to the medial network.”

  • The paper relies on this without support.

    The dorsal midline paraventricular nucleus of the thalamus connects with frontal cortex, striatum, hypothalamus, amygdala, and dorsal midbrain regions.

    “Diagram of connections between the dorsal midline paraventricular nucleus of the thalamus (PVT) with areas of the frontal cortex striatum hypothalamus amygdala and dorsal midbrain.”

  • The paper relies on this without support.

    Within the amygdala, connections link the basal and lateral nuclei to the central and medial nuclei and to the bed nucleus of the stria terminalis.

    “Intra-amygdaloid connections link the basal and lateral amygdaloid nuclei to the central and medial nuclei of the amygdala and the bed nucleus of the stria terminalis (BNST).”

  • The paper relies on this without support.

    The amygdala and medial prefrontal network interact with a shared cortico-striatal-pallidal-thalamic loop via strong connections to the accumbens nucleus, medial caudate, and mediodorsal and paraventricular thalamic nuclei; this interaction may control and limit stress responses.

    “In addition, the amygdala and medial prefrontal network interact with the same cortico-striatal-pallidal-thalamic loop, through prominent connections both with the accumbens nucleus and medial caudate, and with the mediodorsal and paraventricular thalamic nuclei, which may function to control and limit responses to stress.”

  • The paper relies on this without support.

    The medial prefrontal network serves as a central node in the cortical default system, which seems to support self-referential functions like mood.

    “Finally, the medial prefrontal network is a central node in the cortical 'default system' that appears to support self-referential functions such as mood.”
18 of 18

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Brain-imaging studies provide strong and consistent evidence of decreased volume of cortical and limbic brain regions such as the prefrontal cortex and hippocampus in depressed patients, suggestive of neuronal atrophy related to length of illness and time of treatment.

    “Brain-imaging studies of depressed patients provide strong and consistent evidence of decreased volume of cortical and limbic brain regions— such as the prefrontal cortex (PFC) and the hippocampus—that control emotion, mood, and cognition, suggestive of neuronal atrophy that is related to length of illness and time of treatment (8, 9).”

    From Synaptic Dysfunction in Depression: Potential Therapeutic Targets (2012) · cites this paper as [9]

    The “Brain Structural Abnormalities in Mood Disorders” section (page not supplied) reports reduced gray-matter volume in prefrontal regions and reports that some studies found reduced hippocampal volume correlated with time spent depressed. But it also says other studies did not replicate the hippocampal finding, so “strong and consistent” overstates that evidence. The “Neuropathological Correlations with Neuroimaging Abnormalities” section (page not supplied) describes reduced neuronal size alongside glial changes, but does not establish that the imaging findings reflect neuronal atrophy related to time in treatment. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Two independent seed ROIs placed in the pregenual anterior cingulate cortex and the dorsal anterior cingulate cortex were chosen based on previous reports on their involvement in meditation and affective disorders such as depression.

    “Two independent seed ROIs placed in the pregenual anterior cingulate cortex (pgACC) and the dorsal anterior cingulated cortex (dACC) were chosen based on previous reports on their involvement in meditation and affective disorders such as depression [55].”

    From State and training effects of mindfulness meditation on brain networks reflect neuronal mechanisms of its antidepressant effect (2016) · cites this paper as [55]

    The Brain Structural Abnormalities in Mood Disorders section links a region including the pgACC to bipolar-disorder risk, and the Neuropsychopharmacology REVIEWS passage describes perigenual ACC activity during emotional tasks (page numbers unavailable). The cited paper thus supports an affective-disorder rationale for a pgACC seed, but the passages found do not establish involvement of both the pgACC and dACC in meditation or specifically support the dACC seed choice. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Both accounts of depression are supported by the involvement of agranular visceromotor cortices in the pathophysiology of depression.

    “Both these accounts of depression are supported by the involvement of agranular visceromotor cortices in the pathophysiology of depression (e.g. [89]).”

    From Active interoceptive inference and the emotional brain (2016) · cites this paper as [89]

  • Depression is associated with reduced size of brain regions that regulate mood and cognition, including the prefrontal cortex and the hippocampus.

    “Basic and clinical studies demonstrate that depression is associated with reduced size of brain regions that regulate mood and cognition, including the prefrontal cortex and the hippocampus, and decreased neuronal synapses in these areas.”

    From Synaptic Dysfunction in Depression: Potential Therapeutic Targets (2012) · cites this paper as [9]

  • Research on mood disorder pathophysiology has implicated abnormalities in glutamatergic transmission, along with disrupted function and structure in neural circuits involved in mood regulation.

    “Research on mood disorder pathophysiology has implicated abnormalities in glutamatergic transmission, along with disrupted function and structure in neural circuits involved in mood regulation (4), findings that led to further investigation of glutamatergic N-methyl-D-aspartate (NMDA) receptor modulators in treating depression (5,6).”

    From Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study (2019) · cites this paper as [4]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Two 1978 references start on the same journal page

    Minor

    The two differently titled papers are both listed as beginning on page 225 of volume 178 of the same journal, although their stated ending pages differ.

  • Two 1977 references have identical journal pages

    Minor

    The bibliography assigns the same journal, volume, and complete page range to two differently titled papers by the same authors.

2 of 2

Cites

Flagged first, then by citations

5 of the 379 references couldn’t be matched to a known paper.

Research works printed but not linked: 7

  1. Drevets WC, Gautier C, Lowry T, Bogers W, Greer P, Kupfer DJ (2001). Abnormal hemodynamic responses to facially expressed emotion in major depression. Soc Neurosci Abstr 27: 785.1.
  2. Drevets WC, Ryan N, Bogers W, Birmaher B, Axelson D, Dahl R (2004b). Subgenual prefrontal cortex volume decreased in healthy humans at high familial risk for mood disorders. Soc Neurosci Abs 799: 18.
  3. Horovitz Z (1966). The amygdala and depression. In: Garattini S, Dukes M (eds). Antidepressant Drugs. Excerpta Medica: Amsterdam. pp 121–129.
  4. Krettek JE, Price JL (1977c). The connections of the amygdaloid complex and related olfactory cortical areas with the entorhinal cortex and the hippocampus. J Comp Neurol 172: 723–752. · DOI
  5. Martin-Soelch C, Szczepanik J, Fromm S, Barhaghi K, Wang H, Drevets W (2008). Catecholamine depletion Affects Amygdala Response to Reward: An fMRI-study. Program No. 520.10. Neuroscience Meeting Planner. Society for Neuroscience: Washington, DC (online).
  6. Miller B, Saleem KS, Price JL (2008). Cingulate Cortex Connections with Prefrontal Cortex Circuits in Monkeys. Program No. 465.11. Neuroscience Meeting Planner. Society for Neuroscience: Washington, DC (online).
  7. Öngür D, An X, Price JL (1998a). Prefrontal cortical projections to the hypothalamus in macaque monkeys. J Comp Neurol 401: 480–505. · DOI · Paper page

Cited by

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Related

Authors
Price, J. L., & Drevets, W. C.
Affiliations
  • Washington University in St. Louis (US)
  • National Institutes of Health (US)
Corresponding author
Price, Joseph L
ORCID
Drevets, Wayne C
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2009-08-19
Volume
35
Issue
1
Pages
192-216
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2009.104
PMC
PMC3055427
OpenAlex
W2122384242
Cited by
1,606
References
379
Citations by year
2026: 50 · 2025: 75 · 2024: 71 · 2023: 57 · 2022: 89 · 2021: 122 · 2020: 102 · 2019: 110 · 2018: 83 · 2017: 101 · 2016: 105 · 2015: 119 · 2014: 127 · 2013: 124 · 2012: 113
FWCI
6.57
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Public Health Service
  • National Institute of Mental Health (R01MH070941)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
mood disorders, neurocircuitry, limbic system, amygdala, medial prefrontal cortex, ventral striatum, globus pallidus, medial thalamus, hypothalamus, periaqueductal gray, brainstem, emotional behavior, history of emotion research, monkeys, human brain imaging
MeSH terms
Animals, Brain, Humans, Models, Neurological, Neural Pathways, Mood Disorders

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

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