Neurocircuitry of Mood Disorders

In the paper

“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).”

What the sources say

• Supported

  Haber et al. is cited for the striatal connection, not the mediodorsal thalamic connection, which has separate citations. The Discussion reports that medial prefrontal areas 25 and 32 project to the medial ventral striatum, where orbitofrontal areas 13a and 13b also project. Page numbers are unavailable in our copy. (LLM, conf=0.92)

  cites Haber et al, 1995 source
• ?Not checked — no full text of the sourcecites Ferry et al, 2000b source
• ?Not checked — no full text of the sourcecites Russchen et al, 1987 source

In the paper

“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).”

What the sources say

• Partly supported

  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)

  cites Schultz et al, 1997 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Padoa-Schioppa and Assad, 2006 source

In the paper

“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).”

What the sources say

• ?Could not verify

  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)

  cites Corbetta et al, 2002 sourceExperimental — accuracy not yet measured

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Botteron et al, 2002 source
• Partly supported

  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)

  cites Hirayasu et al, 1999 sourceExperimental — accuracy not yet measured
• ?Not matched

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

  cites Drevets et al, 2004b

In the paper

“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).”

What the sources say

• Partly supported

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

  cites Hirayasu et al, 1999 sourceExperimental — accuracy not yet measured

In the paper

“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).”

What the sources say

• Partly supported

  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)

  cites Boes et al, 2008 sourceExperimental — accuracy not yet measured

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Hastings et al, 2004 source
• Supported

  Boes et al. is cited for the male portion of the sentence, not for females or the specified diagnoses. The Results report significantly smaller rACC volume in boys with depressive symptoms than in boys without them. These were healthy children without a psychiatric diagnosis, so the finding should not be read as evidence about diagnosed depression. (LLM, conf=0.91)

  cites Boes et al, 2008 source
• ?Not checked — no full text of the sourcecites Botteron et al, 2002 source

In the paper

“The burst-firing patterns increase DA release in the accumbens, which may encode information about reward prediction in monkeys (Schultz et al, 1997).”

What the sources say

• Partly supported

  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)

  cites Schultz et al, 1997 sourceExperimental — accuracy not yet measured

In the paper

“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.”

In the paper

“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.”

In the paper

“Recently a projection from the amygdala has been identified to the posterior cingulate cortex (Buckwalter et al, 2008).”

What the sources say

• ?Not checked — no full text of the sourcecites Buckwalter et al, 2008 source

In the paper

“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)”

What the sources say

• ?Not checked — no full text of the sourcecites Zola- Morgan et al, 1991 source

In the paper

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

In the paper

“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.”

What the sources say

• ?Not matched

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

  cites James W (1884)

In the paper

“As discussed in later parts of this chapter, these circuits form the core of the neural system that has been implicated in mood disorders.”

In the paper

“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'.”

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Russchen et al, 1987 source

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites MacLean (1949) source
• ?Not checked — no full text of the sourcecites Papez (1937) source

In the paper

“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.”

In the paper

“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.”

What the sources say

• ?Not checked — no full text of the sourcecites Bard (1928) source

In the paper

“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.”

In the paper

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

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Damasio, 1994 source

In the paper

“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.”

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Ray and Price, 1993 source

In the paper

“It is possible that this region represents a multi-modal cortex that also connected to circuits responsible for emotion.”

In the paper

“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.”

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Russchen et al, 1987 source
• ?Not matched

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

  cites Carmichael et al, 1994
• ?Not matched

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

  cites Price, 2003

In the paper

“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).”

In the paper

“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.”

In the paper

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

In the paper

“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).”

What the sources say

• ?Not matched

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

  cites Miller et al, 2008

In the paper

“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.”

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Carmichael and Price, 1996 source

In the paper

“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).”

In the paper

“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”

What the sources say

• ?Not matched

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

  cites O ¨ngu ¨r et al, 1998a, b
• ?Not matched

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

  cites An et al, 1998

In the paper

“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.”

In the paper

“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.”

In the paper

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

In the paper

“They are specifically and reciprocally connected to the medial prefrontal network areas, with little connection to the orbital network.”

What the sources say

• ?Not matched

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

  cites Hsu andPrice, 2007, 2009

In the paper

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

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Coryell et al, 2005 source
• ?Not matched

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

  cites O ¨ngu ¨r et al, 1998a, b, 2003
• ?Not checked — no full text of the sourcecites Drevets et al, 1997a source

In the paper

“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.”

In the paper

“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)”

In the paper

“elevated glucocorticoid concentrations and repeated stress decrease the proliferation of oligoden-drocyte precursors (Alonso, 2000;Banasr and Duman, 2007).”

What the sources say

• Not checked yetcites Alonso, 2000
• ?Not checked — no full text of the sourcecites Banasr and Duman, 2007 source

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Caspi et al, 2003 source
• ?Not checked — no full text of the sourcecites Pezawas et al, 2005 source

In the paper

“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.”

In the paper

“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.”

In the paper

“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.”

In the paper

“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.”

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Garcia et al, 1999 source

In the paper

“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).”

What the sources say

• ?Not matched

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

  cites Drevets et al, 2004a

In the paper

“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.”

In the paper

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

In the paper

“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).”

In the paper

“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”

What the sources say

• ?Not checked — no full text of the sourcecites Gold and Chrousos, 2002 source
• ?Not matched

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

  cites Drevets et al, 2004a
• ?Not checked — no full text of the sourcecites Swaab et al, 2005 source

In the paper

“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.”

In the paper

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

In the paper

“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.”

What the sources say

• ?Not matched

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

  cites An et al, 1998
• Not checked yetcites Freedman et al, 2000

In the paper

“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).”

What the sources say

• ?Not matched

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

  cites Willner, 1995
• ?Not checked — no full text of the sourcecites Lambert et al, 2000 source
• ?Not checked — no full text of the sourcecites Meyer et al, 2001 source

In the paper

“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)”

What the sources say

• ?Not matched

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

  cites Drevets et al, 2006
• ?Not matched

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

  cites Van Laere et al, 2006

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Nestler and Carlezon, 2006 source

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Gold and Chrousos, 2002 source
• ?Not matched

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

  cites Drevets et al, 2004a
• ?Not checked — no full text of the sourcecites Swaab et al, 2005 source

In the paper

“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).”

What the sources say

• ?Not checked — no full text of the sourcecites Drevets et al, 2002a source
• ?Not checked — no full text of the sourcecites Manji et al, 2001 source