The neural bases of obsessive-compulsive disorder in children and adults

In the paper

“Approximately 40% of cases of childhood-onset OCD continue into adulthood, and that number increases to 60% when subthreshold presentations of OCD are also considered (Stewart et al., 2004).”

What the sources say

• Not checked yetcites Stewart et al., 2004

In the paper

“The findings of this study were largely consistent with the findings in adults, including hyperactivity at rest in the caudate and ACC of treatment-naïve children, which declined following treatment.”

What the sources say

• Not checked yetcites Diler et al., 2004

In the paper

“In addition, few studies have compared the neural correlates of OCD across children and adults, severely limiting our knowledge of their similarities and differences.”

In the paper

“We are not aware of any symptom provocation studies in children with OCD.”

In the paper

“Even if compulsions are maladaptive, exaggerated habits (Graybiel & Rauch, 2000), why patients with OCD would have difficulty using the striatal habit-learning system (Packard & Knowlton, 2002) to learn other habits remains unclear.”

What the sources say

• Not checked yetcites Graybiel & Rauch, 2000
• Not checked yetcites Packard & Knowlton, 2002

In the paper

“Most brain imaging studies that include adults with OCD use mixed samples that include adults with childhood- and adult-onset OCD. Given the evidence that brain activity differs in adults with childhood- versus adult-onset OCD (Busatto et al., 2001), such heterogeneous samples may compromise statistical power and confound findings.”

What the sources say

• Not checked yetcites Busatto et al., 2001

In the paper

“Each of these loops receives inputs from multiple cortical areas and then projects back to one of its cortical areas of origin, thereby partly closing the loop (Alexander et al., 1986).”

What the sources say

• Not checked yetcites Alexander et al., 1986

In the paper

“The findings of these studies have generally been consistent with the findings of resting, symptom provocation, and pre/post-treatment studies, highlighting functional disturbances in the OFC, ACC, basal ganglia, and related areas (Menzies et al., 2008).”

What the sources say

• Not checked yetcites Menzies et al., 2008

In the paper

“On the other hand, the pathogenic relation, if any, of deficits in implicit (habit) learning and the symptoms of OCD remains unclear.”

In the paper

“The presence of deficits in inhibitory control in so many disorders with such widely varying phenotypes suggests caution in interpreting such deficits as the root cause of OCD.”

In the paper

“Several CBGTC loops exist, and they seem to run largely parallel courses through the basal ganglia (Alexander et al., 1986; Mega & Cummings, 2001; Middleton & Strick, 2001b).”

What the sources say

• Not checked yetcites Alexander et al., 1986
• Not checked yetcites Mega & Cummings, 2001
• Not checked yetcites Middleton & Strick, 2001b

In the paper

“If so, the performance of patients with OCD should suffer more than that of healthy controls when a secondary task that taxes working memory is introduced, and this was confirmed experimentally (Deckersbach et al., 2002).”

What the sources say

• Not checked yetcites Deckersbach et al., 2002

In the paper

“A more recent formulation adds two additional loops with target areas in the medial OFC and in the inferotemporal/posterior parietal cortex, and suggests that each of the loops may actually be further subdivided into multiple parallel loops (Middleton & Strick, 2001b).”

What the sources say

• Not checked yetcites Middleton & Strick, 2001b

In the paper

“but a particularly influential formulation proposes the existence of five loops, whose target areas are (a) the supplementary motor area, (b) the frontal eye fields, (c) the dorsolateral prefrontal cortex (DLPFC), (d) the lateral OFC; and (e) the ACC (Alexander et al., 1986).”

What the sources say

• Not checked yetcites Alexander et al., 1986

In the paper

“Three brain areas – the orbitofrontal cortex (OFC), the anterior cingulate cortex (ACC), and the head of the caudate nucleus – have been consistently implicated in a large number of resting, symptom provocation, and pre/post-treatment studies of adults with OCD. These areas (a) are hyperactive at rest in adults with OCD relative to healthy controls, (b) become more active with symptom provocation,”

What the sources say

• Not checked yetcites Baxter et al., 2001
• Not checked yetcites Saxena et al., 2001
• Not checked yetcites Saxena et al., 1998 source

In the paper

“However, from the idea that OCD prominently involves exaggerated habits (the compulsions), one could equally plausibly have predicted the opposite pattern of findings – that the habit learning system in OCD should be especially powerful and effective.”

In the paper

“In particular, excessive relative activity in the direct pathway in OFC/ACC CBGTC loops has been suggested to result in a positive feedback loop in which obsessive thoughts become “trapped” (Baxter et al., 2001; Saxena et al., 2001; Saxena et al., 1998; Saxena & Rauch, 2000).”

What the sources say

• Not checked yetcites Baxter et al., 2001
• Not checked yetcites Saxena et al., 2001
• Not checked yetcites Saxena et al., 1998 source

In the paper

“These have, however, been criticized because they only model repetitive behaviors, whereas compulsive behaviors in OCD are intimately tied to obsessions (Shafran & Speckens, 2005) – and we have no way of assessing whether animals have obsessions.”

What the sources say

• Not checked yetcites Shafran & Speckens, 2005

In the paper

“The genetic, phenomenological, and pathophysiological similarities between TS and OCD (Fineberg, Saxena, Zohar, & Craig, 2007; Marsh, Leckman, Bloch, Yazgan, & Peterson, 2008) suggest that excessive activity in these areas in patients with OCD might reflect the inhibition of compulsions.”

What the sources say

• Not checked yetcites Fineberg et al., 2007
• Not checked yetcites Marsh et al., 2008

In the paper

“Conversely, excessive relative activity in the indirect pathway inhibits cortical motor programs, producing hypokinetic symptoms, such as the difficulty initiating movement in Parkinson’s disease.”

What the sources say

• Not checked yetcites Wichmann & DeLong, 1996

In the paper

“The problem with interpreting these activations as the cause of the symptoms is that these functional imaging findings are inherently correlational: they demonstrate only that activity in these areas correlates with a symptomatic state in OCD.”

In the paper

“A related, though slightly different idea is that hyperactivation of the OFC, ACC, and caudate nucleus simply reflects the need to inhibit compulsive behavior during the scan (Peterson, 2003).”

What the sources say

• Not checked yetcites Peterson, 2003

In the paper

“Second, the validity of the PANDAS construct remains controversial (Harris & Singer, 2006; Kurlan, 2004; Kurlan & Kaplan, 2004; Singer & Loiselle, 2003), with substantial difficulties involved in establishing a causal relation between infection with Group-A beta-hemolytic streptococcus and the development of neuropsychiatric disorders (and additional difficulties in proving that the possible”

What the sources say

• Not checked yetcites Harris & Singer, 2006
• Not checked yetcites Kurlan, 2004
• Not checked yetcites Singer & Loiselle, 2003

In the paper

“The vast majority of anatomical imaging studies of OCD have been conducted after the early functional imaging findings implicated the OFC, ACC, and caudate nucleus in the pathophysiology of OCD. Those studies were therefore strongly influenced by the theory that OFC/ACC CBGTC loops are centrally involved in the pathogenesis of OCD, and have therefore tended to look specifically at brain regions”

In the paper

“The idea is that excessive relative activity in the direct pathway disinhibits cortical motor programs, producing hyperkinetic symptoms, such as the chorea in Huntington’s disease.”

What the sources say

• Not checked yetcites Wichmann & DeLong, 1996

In the paper

“First, studies of OCD as a consequence of brain injury typically involve a small number of subjects who have diffuse lesions that vary greatly across subjects.”

In the paper

“If OFC hyperactivity played a role in causing, rather than in inhibiting symptoms, then greater activation of the OFC during symptom provocation should be associated with a greater, not a lesser, increase in symptoms.”

In the paper

“However, the OFC responds to a variety of both positive and negative emotional stimuli, as well as to neutral stimuli that have been previously paired with positive or negative outcomes (Elliott & Deakin, 2005; Elliott, Dolan, & Frith, 2000; Kringelbach & Rolls, 2004; O’Doherty, 2007; Rolls, 1996, 1999, 2004; Schultz, Tremblay, & Hollerman, 2000; Zald & Kim, 2001).”

What the sources say

• Not checked yetcites Elliott & Deakin, 2005
• Not checked yetcites Kringelbach & Rolls, 2004
• Not checked yetcites O’Doherty, 2007

In the paper

“Although each of the aforementioned lines of evidence – anatomical imaging, OCD as a consequence of brain injury, PANDAS, and neurosurgery – in isolation is insufficient to establish causality, their convergence with functional imaging studies in implicating OFC/ACC CBGTC loops in OCD would provide some reassurance that those loops may indeed play a causal role in OCD.”

In the paper

“so again, hyperactivity in these areas may be a consequence of an attempt by patients with OCD to regulate their anxiety, rather than being the cause of their symptoms.”

In the paper

“One possible interpretation of these findings is that rather than being the origin of obsessional content, these regions become hyperactive as a normal consequence of the obsessional content (Shafran & Speckens, 2005).”

What the sources say

• Not checked yetcites Shafran & Speckens, 2005

In the paper

“An influential idea based on these observations is that OCD results from an imbalance between the so-called “direct” and “indirect” pathways through the basal ganglia (Figure 1; Baxter et al., 2001; Saxena et al., 2001; Saxena et al., 1998; Saxena & Rauch, 2000).”

What the sources say

• Not checked yetcites Baxter et al., 2001
• Not checked yetcites Saxena et al., 2001
• Not checked yetcites Saxena et al., 1998 source

In the paper

“Instead, we wish to emphasize that all are consistent with the findings that the OFC, ACC, and caudate nucleus are hyperactive at rest, become more active under symptom provocation, and show less activity following treatment.”

In the paper

“Why, then, “socioterritorial concerns” in particular should become locked in the OCD positive feedback loop is unclear.”

In the paper

“The evidence from functional imaging for an involvement of the OFC in response inhibition, as studied using the Go/NoGo task, also remains inconclusive, with block designs typically showing OFC activation, but event-related designs failing to show such activation (Elliott & Deakin, 2005).”

What the sources say

• Not checked yetcites Elliott & Deakin, 2005

In the paper

“OCD is, however, often diagnosed long after the onset of symptoms, making this strategy relatively impractical.”

In the paper

“Third, neurosurgical studies lack appropriate controls, and the mechanisms by which they attenuate OCD symptoms are not fully understood.”

In the paper

“To the extent that decreased levels of NAA are a more sensitive indicator of neuronal loss or dysfunction than are traditional volumetric measurements (Bartha et al., 1998; Cendes et al., 1994; Ebisu et al., 1994)”

What the sources say

• Not checked yetcites Bartha et al., 1998
• Not checked yetcites Cendes et al., 1994
• Not checked yetcites Ebisu et al., 1994

In the paper

“a study that scanned children with OCD before and after medication treatment did detect medication-induced reductions in thalamic volume that moreover correlated with symptom improvement (Gilbert et al., 2000)”

What the sources say

• Not checked yetcites Gilbert et al., 2000

In the paper

“Thus, the overall volume of the caudate could be normal (Atmaca et al., 2006; Atmaca et al., 2007; Aylward et al., 1996; Kang et al., 2004; Kellner et al., 1991; Riffkin et al., 2005) or even reduced (Luxenberg et al., 1988; D. Robinson et al., 1995) in adults with OCD, whereas the volumes of the head of the caudate (Scarone et al., 1992) and ventral striatum (Cardoner et al., 2007) could be incre”

In the paper

“Both left and right OFC volumes have been found to correlate inversely with the severity of OCD symptoms (Atmaca et al., 2007; Kang et al., 2004)”

What the sources say

• Not checked yetcites Atmaca et al., 2007
• Not checked yetcites Kang et al., 2004

In the paper

“Another study that divided the OFC into anterior and posterior regions reported a volume reduction in the left anterior OFC, but not in the left posterior or right anterior or posterior OFC (Choi et al., 2004).”

What the sources say

• Not checked yetcites Choi et al., 2004

In the paper

“In summary, considerable evidence suggests that OFC volumes are significantly reduced in adults with OCD, with greater reductions accompanying more severe symptoms.”

In the paper

“the failure of these studies to detect differences between adults with OCD and controls could conceivably be due to the effects of medication.”

In the paper

“volume reductions have been reported for both the superior temporal gyrus (Choi et al., 2006) and hippocampus (Kwon et al., 2003) in adults with OCD.”

What the sources say

• Not checked yetcites Choi et al., 2006
• Not checked yetcites Kwon et al., 2003

In the paper

“The amygdala also projects strongly to the mediodorsal nucleus of the thalamus (Amaral et al., 1992), the final relay station before the OFC/ACC CBGTC loops project back to the cortex (Alexander et al., 1986; Middleton & Strick, 2001b), and it is therefore critically positioned to influence the output of these loops.”

What the sources say

• Not checked yetcites Amaral et al., 1992
• Not checked yetcites Alexander et al., 1986
• Not checked yetcites Middleton & Strick, 2001b

In the paper

“Voxel-based morphometry is a popular whole-brain approach that gives voxel-by-voxel measurements (Ashburner & Friston, 2000).”

What the sources say

• Not checked yetcites Ashburner & Friston, 2000

In the paper

“the finding of thinning in the parahippocampal cortex may point to broader abnormalities in the tissue surrounding the hippocampus that would be consistent with the volume reductions that have been reported for the hippocampus proper (Kwon et al., 2003).”

What the sources say

• Not checked yetcites Kwon et al., 2003

In the paper

“Automated methods to delimit ROIs partly alleviate this problem, but they are significantly less accurate than manual methods.”

In the paper

“Considering each nucleus – caudate or putamen – as a whole misses both the distinctions between different loops within the nucleus and the fact that portions of one nucleus should be considered together with portions of the other.”

In the paper

“The insula is contiguous with the posterior OFC and is heavily interconnected with both the OFC and the ACC (Mesulam & Mufson, 1982; Mufson & Mesulam, 1982; Ongur & Price, 2000).”

What the sources say

• Not checked yetcites Mesulam & Mufson, 1982
• Not checked yetcites Mufson & Mesulam, 1982
• Not checked yetcites Ongur & Price, 2000

In the paper

“These results are surprising, given that these are not the striatal regions through which the OFC/ACC CBGTC loops run (Alexander et al., 1986; Haber, 2003; Lehericy et al., 2004; Middleton & Strick, 2001b).”

What the sources say

• Not checked yetcites Alexander et al., 1986
• Not checked yetcites Haber, 2003
• Not checked yetcites Lehericy et al., 2004

In the paper

“The cerebellum and frontal cortex are interconnected in parallel cortico-cerebellar loops (R. M. Kelly & Strick, 2003; Middleton & Strick, 1997, 2000, 2001a), and the cerebellum can also influence the striatum via a disynaptic connection through the thalamus (Hoshi, Tremblay, Feger, Carras, & Strick, 2005).”

What the sources say

• Not checked yetcites R. M. Kelly & Strick, 2003 source
• Not checked yetcites Middleton & Strick, 1997
• Not checked yetcites Hoshi et al., 2005

In the paper

“Surface analyses, however, still require the prior delimitation of ROIs, as it is within a previously-delimited ROI that surface analysis gives detailed, point-by-point measurements.”

In the paper

“The results of these surface analysis studies need to be interpreted with care because neither study corrected for multiple comparisons, and in both studies the majority of patients had a history of medication (although all were medication-free for at least 4 weeks prior to scanning).”

In the paper

“VBM studies have reported both increases (J. J. Kim et al., 2001) and decreases (Yoo et al., 2008) in gray matter in the superior temporal gyrus, as well as increases in gray matter in the parahippocampal gyrus, extending to the amygdala (Valente et al., 2005).”

What the sources say

• Not checked yetcites J. J. Kim et al., 2001
• Not checked yetcites Yoo et al., 2008
• Not checked yetcites Valente et al., 2005

In the paper

“Tensor-based morphometry is used to analyze local morphological changes on the surface of cortical or subcortical structures (a procedure often termed “surface analysis”) or to measure cortical thickness.”

In the paper

“The amygdala’s key role in mediating normal fear and anxiety (LeDoux, 2000, 2007; Phelps & LeDoux, 2005) and its prominent involvement in anxiety disorders (Bremner, 2004; Miller, Taber, Gabbard, & Hurley, 2005; Rauch, Shin, & Wright, 2003) highlight its potential relevance for understanding the pathophysiology of OCD, a disorder in which anxiety plays a crucial role (Foa, Steketee, & Ozarow, 1985”

What the sources say

• Not checked yetcites LeDoux, 2000
• Not checked yetcites Phelps & LeDoux, 2005
• Not checked yetcites Bremner, 2004

In the paper

“because manual delimitation of ROIs is laborious, ROI studies often analyze only a small number of regions for which there are prior suspicions of abnormality, which limits the opportunity to find abnormalities in unanticipated regions.”

In the paper

“several CBGTC loops run through the caudate nucleus (Alexander et al., 1986; Middleton & Strick, 2001b) and each of those loops also partly seems to run through the putamen (Haber, 2003).”

What the sources say

• Not checked yetcites Alexander et al., 1986
• Not checked yetcites Middleton & Strick, 2001b
• Not checked yetcites Haber, 2003

In the paper

“The findings from this study should be interpreted with care because most patients were medicated.”

What the sources say

• Not checked yetcites Shin et al., 2007

In the paper

“No abnormalities were detected in the ACC or anywhere in the right hemisphere.”

What the sources say

• Not checked yetcites Shin et al., 2007

In the paper

“The few studies that have examined volumes of the amygdala in adults with OCD have, however, yielded inconsistent findings”

In the paper

“A meta-analysis of PET and SPECT studies of OCD that found reliable differences between patients with OCD and normal controls in the orbital gyrus and the head of the caudate nucleus, but not in the OFC or caudate nucleus as a whole (Whiteside et al., 2004)”

What the sources say

• Not checked yetcites Whiteside et al., 2004

In the paper

“This study found cortical thinning in several areas of the left hemisphere of adults with OCD, including not only the OFC but also the ventrolateral prefrontal, middle frontal, precentral, superior temporal, parahippocampal, and lingual cortices.”

What the sources say

• Not checked yetcites Shin et al., 2007

In the paper

“We are not aware of any volumetric studies of the OFC in pediatric OCD.”

In the paper

“The findings of increased ACC volumes in children with OCD, however, are in contrast to the findings in adults with OCD, which have generally failed to detect volumetric abnormalities in the ACC, although they are consistent with several 1H-MRS studies that have reported decreased NAA levels in the ACC of adults with OCD.”

In the paper

“Establishing a clear and definitive causal role for GAS infections in these cases has, however, proven difficult, in part because GAS infections are so common in childhood (T. K. Murphy, Sajid, & Goodman, 2006).”

What the sources say

• Not checked yetcites T. K. Murphy, Sajid, & Goodman, 2006

In the paper

“GAS infection was first observed to produce Sydenham’s chorea, an illness associated with rheumatic fever and characterized primarily by involuntary rapid, jerky movements, which are, however, often accompanied by other motor, behavioral, and emotional problems, including obsessive-compulsive symptoms and OCD (Swedo et al., 1993; Swedo et al., 1989).”

What the sources say

• Not checked yetcites Swedo et al., 1993
• Not checked yetcites Swedo et al., 1989 source

In the paper

“A possible explanation for this difference in findings across age groups is that the ACC may develop differently in patients with OCD and healthy controls.”

In the paper

“If this finding is confirmed, ideally in a longitudinal study, it could mean that ACC volumes are larger in children with OCD but then stay relatively constant with advancing age, whereas ACC volumes in healthy children might be smaller but then increase with age, resulting in similar ACC volumes in patients with OCD and healthy controls by adulthood.”

In the paper

“Abnormalities in other areas – e.g., increased NAA levels in the left but not right DLPFC of children with OCD (Russell et al., 2003) and decreased pituitary volumes in boys but not girls with OCD (MacMaster et al., 2006) – have been reported sporadically, but need to be replicated.”

What the sources say

• Not checked yetcites Russell et al., 2003
• Not checked yetcites MacMaster et al., 2006

In the paper

“two findings receive convergent support from more than one study of children with OCD: increased volumes of the ACC and abnormal metabolite concentrations in the thalamus.”

In the paper

“Other large clusters of decreased gray matter were found in the middle frontal gyrus, with the cluster in the right middle frontal gyrus remaining significant after correcting for multiple comparisons.”

What the sources say

• Not checked yetcites Carmona et al., 2007

In the paper

“Volumetric studies in adults with OCD have generally not measured the putamen, so whether reduced putamen volumes are found in adults with OCD remains unclear.”

In the paper

“Two studies detected no significant differences in caudate volumes between children with OCD and matched controls (Rosenberg et al., 1997; Szeszko, MacMillan, McMeniman, Chen et al., 2004), although one of these studies reported smaller putamen volumes in children with OCD (Rosenberg et al., 1997).”

What the sources say

• Not checked yetcites Rosenberg et al., 1997
• Not checked yetcites Szeszko, MacMillan, McMeniman, Chen et al., 2004

In the paper

“This is a major gap in the literature, given that reduced volumes in the OFC are the most consistent finding in the volumetric literature on adult OCD.”

In the paper

“This study, however, did not include a control group, so the possibility that the children with OCD in this study might not have significantly enlarged thalami prior to treatment cannot be excluded.”

In the paper

“Controversy remains, however, regarding not only this causal hypothesis but the validity of the PANDAS construct itself (Harris & Singer, 2006; Kurlan, 2004; Kurlan & Kaplan, 2004; Singer & Loiselle, 2003).”

What the sources say

• Not checked yetcites Harris & Singer, 2006
• Not checked yetcites Kurlan, 2004
• Not checked yetcites Kurlan & Kaplan, 2004

In the paper

“Although this is consistent with similar findings in VBM studies of adults with OCD, it contrasts with the findings of volumetric studies in children with OCD, which have generally found increased ACC volumes (Rosenberg & Keshavan, 1998; Szeszko, MacMillan, McMeniman, Chen et al., 2004).”

What the sources say

• Not checked yetcites Rosenberg & Keshavan, 1998
• Not checked yetcites Szeszko, MacMillan, McMeniman, Chen et al., 2004

In the paper

“Another potential line of evidence for the involvement of the basal ganglia in OCD comes from the study of PANDAS.”

In the paper

“Another study found no differences in volumes of the thalamus measured before and after successful cognitive-behavioral therapy (Rosenberg, Benazon, Gilbert, Sullivan, & Moore, 2000), suggesting that the reduction in volumes of the thalamus seen with paroxetine treatment is not necessary for symptom improvement.”

What the sources say

• Not checked yetcites Rosenberg, Benazon, Gilbert, Sullivan, & Moore, 2000

In the paper

“The finding of a putamen abnormality is somewhat surprising from the perspective of the pathophysiological model of OCD that emphasizes the OFC/ACC CBGTC loops, given that those loops run mostly (though not exclusively) through the caudate”

In the paper

“One study reported larger volumes of the ACC in treatment-naïve children with OCD than in matched controls, with larger ACC volumes accompanying more severe symptoms (Rosenberg & Keshavan, 1998).”

What the sources say

• Not checked yetcites Rosenberg & Keshavan, 1998

In the paper

“One of these (Gilbert et al., 2008) reported decreased gray matter in the left ACC and in the medial frontal gyrus bilaterally in children with OCD, consistent with similar findings in adults (Pujol et al., 2004; Valente et al., 2005; Yoo et al., 2008) and with the hypothesized involvement of the ACC in OCD.”

What the sources say

• Not checked yetcites Gilbert et al., 2008
• Not checked yetcites Pujol et al., 2004
• Not checked yetcites Valente et al., 2005

In the paper

“Indeed, subsequent studies from the same group did report increases in choline (Rosenberg, Amponsah, Sullivan, MacMillan, & Moore, 2001; Smith et al., 2003) and creatine/phosphocreatine levels (Mirza et al., 2006) in the medial thalami of children with OCD, suggesting that the earlier findings reflected elevated levels of choline and creatine/phosphocreatine rather than decreased levels of NAA.”

What the sources say

• Not checked yetcites Rosenberg et al., 2001
• Not checked yetcites Smith et al., 2003
• Not checked yetcites Mirza et al., 2006

In the paper

“Two studies failed to detect significant differences in amygdala volumes between children with OCD and healthy controls (Rosenberg & Keshavan, 1998; Szeszko, MacMillan, McMeniman, Lorch et al., 2004), although one of these studies found that children with OCD, unlike healthy controls, had significantly larger left than right amygdalae (Szeszko, MacMillan, McMeniman, Lorch et al., 2004).”

What the sources say

• Not checked yetcites Rosenberg & Keshavan, 1998
• Not checked yetcites Szeszko, MacMillan, McMeniman, Lorch et al., 2004

In the paper

“In fact, one of the studies (Gilbert et al., 2008) states precisely that its findings concern gray matter densities, not volumes, and that this may explain their discrepancy with prior volumetric studies.”

What the sources say

• Not checked yetcites Gilbert et al., 2008

In the paper

“The other VBM study in children with OCD (Carmona et al., 2007) also reported a large cluster of decreased gray matter in the cingulate cortex, although that finding did not remain significant after correcting for multiple comparisons.”

What the sources say

• Not checked yetcites Carmona et al., 2007

In the paper

“Additional clusters were also reported, but they were substantially smaller and none remained significant after correcting for multiple comparisons.”

What the sources say

• Not checked yetcites Carmona et al., 2007

In the paper

“In principle, simply because a lesion in a given brain region can produce OCD, that does not necessarily imply that all or even some cases of non-lesion-related OCD involve impairments in that region.”

In the paper

“The non-inclusion of a group of matched non-injured controls in the study precludes any inferences regarding the extent to which the changes in symptoms were caused by the injury.”

What the sources say

• Not checked yetcites Grados et al., 2008

In the paper

“To the extent that childhood- and adult-onset OCD may have differing etiologies, these cases may also bear mostly on adult-onset illness, as the vast majority of them involve adults”

In the paper

“This is consistent with neurosurgical treatments for OCD that disrupt the OFC or its connections, but contrasts with the case reports that have implicated lesions of the OFC in the onset of OCD”

In the paper

“Several studies have reported elevated anti-basal ganglia antibodies in the sera of patients with TS or OCD (Dale, Heyman, Giovannoni, & Church, 2005; Kiessling, Marcotte, & Culpepper, 1994; Rizzo, Gulisano, Pavone, Fogliani, & Robertson, 2006; Singer et al., 1998; Wendlandt, Grus, Hansen, & Singer, 2001), although at least one study failed to detect differences in anti-basal ganglia antibodies”

What the sources say

• Not checked yetcites Dale et al., 2005
• Not checked yetcites Kiessling et al., 1994
• Not checked yetcites Singer et al., 2004

In the paper

“A case study of an adolescent boy with exacerbation of OCD symptoms after a streptococcal pharyngitis showed precisely that, and the reduction in basal ganglia volumes was also accompanied by a reduction in symptom severity (Giedd, Rapoport, Leonard, Richter, & Swedo, 1996).”

What the sources say

• Not checked yetcites Giedd et al., 1996

In the paper

“A larger, prospective study (Grados et al., 2008) also suggests a role for the OFC in obsessive-compulsive symptoms following brain injury, although in that study lesions to the OFC were inversely related to symptom severity.”

What the sources say

• Not checked yetcites Grados et al., 2008

In the paper

“The specific CGBTC loops affected may determine the neuropsychiatric presentation, with disturbances in motor loops causing TS or Sydenham’s chorea and disturbances in OFC/ACC CBGTC loops causing OCD.”

In the paper

“To summarize, the existing evidence suggests but does not prove that a GAS infection may, in some cases, trigger an autoimmune response that attacks the basal ganglia, leading to OCD, TS, Sydenham’s chorea, or a combination of these disorders.”

In the paper

“Medial prefrontal and temporal lobe lesions were associated with new-onset obsessions, but this effect disappeared when obsessions and compulsions were considered conjointly.”

What the sources say

• Not checked yetcites Grados et al., 2008

In the paper

“One study reported that immunomodulatory treatment of PANDAS led to improvements in both OCD and TS symptoms (Perlmutter et al., 1999), although this study has been criticized on multiple grounds (Singer, 1999).”

What the sources say

• Not checked yetcites Perlmutter et al., 1999
• Not checked yetcites Singer, 1999

In the paper

“Two studies have reported that antibiotic prophylaxis and treatment was effective in reducing symptoms in PANDAS (M. L. Murphy & Pichichero, 2002; Snider, Lougee, Slattery, Grant, & Swedo, 2005), although these studies should be considered preliminary because neither of them included a placebo group.”

What the sources say

• Not checked yetcites M. L. Murphy & Pichichero, 2002
• Not checked yetcites Snider et al., 2005