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Abstract

None.
FORMAL RESPONSE TO:
January 2005 American Psychiatric Association Council on Children, Adolescents and
Their Families Resource Document
“Brain Imaging and Child and Adolescent Psychiatry with Special Emphasis on SPECT”
PREPARED BY:
Daniel G. Amen, MD, John Holttum, MD, Arthur Prezbinda, MD, and Chris Hanks, PhD
WITH SUPPORT FROM THE FOLLOWING
PSYCHIATRISTS AND NEUROSCIENTISTS

  !"#!
$%&!'(%))!
*($+! &$)
"#!!',')$
+ %,)$,
% !*##$%)*$
-.!.$%).*'!,."
$,*!$+ %$ ,!/
!'$'
, ,&&%"&'%
!"%"."&
"*!-$&*'
.##"
Summary
'#)#$
$#$$-$#)'
)#),
$" (--'0
$)1# $
2#)'###$
'#" (-#)$$)
$$/-3"'$4
$$'
$'$'$#)$
" (-$$$$,"
'$)'%)#$#
)''$,$#$
'$$)$$5$
6
'7889$ '
-+$$:$
''"($" (-;)'+'-$
 ))$# $$))#
4<<'<'=<=<<<" (-#
-#+')'##$
6>'#0#)" (-$'
-)'$'#''
)) #'
)))#'$
$$
)#$$4
The findings, opinions, and conclusions of the report do not necessarily represent the
views of the officers, trustees, or all members of the APA. The views expressed are those
of the authors of the individual sections of this document.
?)#$ #'-
##" ($
$-$'@" (-A$''#
'
'###$
$'$#$$-
)#$'#$##)$2
'$*$$#$)
#$)#)$)
#0)###
$#)$''
"$#$3$))'#'
##$))#
01#0#$'
-' )<###
'#')###)$
@"A0$'@%"A#%
" (-
#" (-#
#')$"$#$$
$'-$
#$" (-$#"0
'))#'##)
$'
-$#)')#
7
),$" (-
'$'$"#'
0$0,34
#'#)" (-
#" (-
$$#$
#
)#
')" (-## 

#)#" (-#+'
)##
#$
Safety of SPECT in Children
#$'" (-#'#0
'-,
Particular caveats are indicated with regard to brain imaging involving radioactive
nucleotides for children and adolescents because of children’s known greater sensitivity
to radiation and risk of radiation induced-cancer. The long term risks of initial and
repeated exposure to intravenous radio nucleotides are unknown.
$')#
$$
#)
#$''
''$$#2'!'$
788B3*#$C8D6$#
3*# #$D9BE3
*#$>FC8),##$'$
')$#)#0)$,
$1$$-
'''$$#$)0
/
-0#" (-8F$-$)
)-)$0G'4'#$$
$-#0
$#0
,#'#+''
)$0#'#$
0),)$@7A#"'#
#H$I4
B
The purpose of this section is to briefly describe the data regarding low-level radiation
and risk and to clarify that in fact SPECT and PET procedures have no more risk
than MRI-based procedures… Indeed, there are no data that have ever demonstrated
any harm to humans by radiation exposure at diagnostic imaging levels. In fact, current
data support the presence of radiation hormesis: that low levels of radiation exposure
induce beneficial effects of cellular repair and immune system enhancement…
Therefore it should be concluded that neither SPECT nor PET brain imaging
procedures are associated with any particular risk over activities of daily living and
certainly should not be considered to be any more “risky” than MRI or any of its
associated functional imaging derivatives.
$0#'
'$#'0$,GG)#-)##
#$#$" (-$),
-)#')##$
##+'&)$,#
#1'$,,#
##''J,###$0
'#'$,##$" (-

The Appropriate Use of SPECT in Psychiatric Practice
-####" (-#
'+4
Brain imaging does have important clinical uses….The usefulness of SPECT to study
perfusion abnormalities in the brain as well as elsewhere (e.g., the myocardium, carotid
arteries) is well established. SPECT has a role in the diagnosis of cerebral trauma,
certain kinds of dementia, strokes, seizure disorders, and brain tumors, in which
characteristic patterns of perfusion abnormalities are detectible. In addition, brain
SPECT with neuroreceptor imaging radiopharmaceuticals is used in cerebrovascular
diseases, dementias, epilepsy, head injury, malignant brain tumors, movement
disorders, and Gilles de la Tourette's syndrome (Camargo, 2001). This imaging
modality has been used in diagnosis, prognosis assessment, evaluation of response to
therapy, risk stratification, detection of benign or malignant viable tissue, and choice of
medical or surgical therapy…The primary clinical use of SPECT in psychiatry has been
to rule out the neurological conditions listed above.
'$'#))#'$
-3'$$$#"G&'
$/$$#')#
.
#" (-##'#''J"
'##$J-
'*$'')$J#,
>
,J#$$#$)
$,)#)2#
$$/-'$'#$'
$,)',#
'
-$$$,)$4
Imaging research cannot yet be used to diagnose psychiatric illness. Specifically, no
published investigation in the field has determined that any structural or functional
brain abnormality is specific to a single psychiatric disorder. Additionally, imaging
studies examine groups of patients and groups of healthy controls; therefore, findings
may not apply to all individuals with a given disorder. Even when significant
differences are identified between groups, there is a substantial overlap among
individuals in both groups. We conclude that, at the present time, the available evidence
does not support the use of brain imaging for clinical diagnosis or treatment of
psychiatric disorders in children and adolescents.
#" (-#$'$#
$,#0'#
#" (-$,'##
',,#'#$
" (-$$$$$" (-'
#)$#$4
" (-$')0##'
)'0)#)$
'')$
+)$:0;))'#
$,$
" (-$$##$'
#)'#$#$
'#)$“yet be used to diagnose
psychiatric illness,”))'
'###'
##')'making psychiatric diagnoses is not the goal of imaging
research.)#K6888$'#$
'$$J
0)0$'
"G&''$-3
$)$#)#
#$"G&#
#$#))#$$'

-)#$#'
'"G&)//)'
"G&##$-$)
#'#")'#$
9
$#" (-#)'
'"G&)2#
'$,'"G&
#$+'',#"G&
)" (-$#$)
#$wereG#))$
$''$'$'##

$2'/,#
1$'
$'##,$#$
)4#$
'2$
*$$
$G)$-
%#$#
'/'##
$@BGEA
$$##)$
#$#''/)'###
@)2'))A#
$)####
$$#)'')#'
')'
" (-,'$#$
)'$'###'###$
" (-#'"-$)
#$/#$-#'$$
##"G&'

" (-,#$#
'$,###
#$$0$)'+'
:Imaging studies examine groups of patients and groups of healthy controls; therefore, findings
may not apply to all individuals with a given disorder.”#'''
$$
'$''#)$
2$-##)#
,#$,$
+'$$/#4
We conclude that, at the present time, the available evidence does not support the use
brain imaging for clinical diagnosis or treatment of psychiatric disorders in children
and adolescents.
D
-$#$0#)$
'E#)" (-
6 (/'@)' A
7 ()@)' A
B ($@)' A
> (###$@)' A
9 "#')/')
))$00#
D (')
F $0#)$$)')
C (''
E ")'$0#0'
+',##" (-#'##
#" (-L?'" (-#' 
$'$'-0##$
))00##'2
'##$"$$$$)
$$"G&$,0#)$
)6888#)" (-
'-)))$
)'#,
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''
##)$
))#69'$$
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#"G<%<&'$)'$$
)',#$#)''
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#$#"
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+$$##
2'0$$
#$#$,)$#
Missing Studies
-:a brief summary of the research studies of psychiatric disorders in which
brain imaging tools, including SPECT, have proven fruitful.” -,#$
$)#?#'$
$'
Attention Deficit/Hyperactivity Disorder
F
#<*'')$
#)# )#$$'-'@7888A4
Findings in Attention Deficit/Hyperactivity Disorders are still provisional, but suggest
minor structural changes in frontal and caudate areas, especially on the right side.
Functional studies suggest reduced activation in these and other areas. A 2000 review
of studies in children and adults concluded, “The techniques do not yet contribute to
individual diagnosis” (Overmeyer & Taylor,2000).
#$#'
!,'')$#),#
#''#6E
" (-*@6B#$7888A$$#
#0$$@68G7CA
" (-)'!))'$@78A$*
$$G$)*!))'$
" (-$$'##
$$$
#'''
!+'4
As of this writing, no studies have been published in journals indexed by the National
Library of Medicine examining the predictive ability of neuroimaging for psychiatric
disorders in either adults or children
'$',#'0$$$
#$#)0$
#####*'$
,#$##0
,#$$
*@6C7B7CA')$'/
##@BGEA
(" (-3)*
)#$0$
Autism
M$:To date we do not have definitive answers
to questions of how the brain functions differently in this disorder (Eigsti & Shapiro, 2003;
Rumsey & Ernst, 2000).”
-)'("'$)'#
/)')#'$$$
,'$)-'
$$0,)
)'$#
C
$
Depression
-#$3" (-@7EA"
$$)'
$0$
Errors in the APA Council Report on SPECT
"#3###
)##)$
6 -“SPECTwas originally introduced in the 1980s (Goetz, 2003).”
-#" (-'6ED86ED7.
$$'-$)$)#
" (-@6EF8A# (-0'$NG
',-@B8A
7 -“SPECT makes use of radioactive tracers tagged to a molecule, which
can indicate glucose metabolism, oxygen consumption, or blood flow.”-#
" (-$)$%')
@NA)#$)
)
B $$1#)#$$
4“In addition, brain SPECT with * neuroreceptor imaging radiopharmaceuticals is
used in cerebrovascular diseases, dementias, epilepsy, head injury, malignant brain
tumors, movement disorders, and Gilles de la Tourette's syndrome (Camargo, 2001).”
O:#;$#$1
-#)$#'$#
$$)" (-)
#$#$$
" (-'*#
* ($'$'#$#
$$3$#)" (-
),'''#)
$#$
> -“Some have advocated for its use in clinical diagnosis of
psychiatric disorders (Amen, 2001).”-##" (-
$#$)'#
9 -“There is one case report of SPECT and an adolescent with OCD who
showed changes after being treated with clomipramine (Amen & Waugh, 1997).”-
'#>9'$)
E
$'
D -“There are few normative data sets on children (Hinton, 2002).
Without normative data, interpretation of findings on individual patients is meaningless.;
-$'-##"
+0$#
" (-##$$'
+0$)#
$#@00
2'A',#
Biased Representation of the Issues
#$#
$$#$#" (-##-)
,#scientific rigor and would not pass the test of any peer reviewed publication. This seems
also to indicate a level of a priori bias difficult to imagine, coming from any kind of select
Council appointed by a professional organization. It may also suggest an ulterior motive.
#," (-#
'#$'#'#
" (-"$##)$$%'
#')$) ##
 ''
#,,'#,#
$'$'$
)###)$$0'
-#$## 
$" (-,'$'
#" (- ''''$$)
" (-)'$$#$$$
##" (-," (- 3
6EEB6EED6EEE788>
Four Clinical Examples
" (-')'#)'*
)#0$" (-#'
-0$" (-)')$
6 E,))##+
'0)$')
0$)$*" (-'
###$)#$)
)'0#$)
68
'$3)$
7 ?6B#<''$2
?'$$$#'
#$'#)
/*" (-'$,##
$)##)#*
)$/@'#$))#1'
/'A$'$))

B  D$###$*#
P#D7#  "1&'*
#$ 3" (-'#
00-' $)0
-#$'$# #0
 $$' #
$,$$P68B)'*
/22G# ''!$*M'
 $788>" (-''
',)1
> ..,69'$#
-*""#''6D6EEC 
),$$$$
.$#$$)'#
-'$0$#$'
-*",'#.
,##96-77
2#." (-*
"M'-'##
$)#0
0#.')$'
)1'#0)#-#
)/#$)*'#
$)''$),)'3)#$
$'#$,)
APA Council Report Will Inhibit Further Research in the Clinical Application of SPECT
-)###$
'''#" (-6ECE$
$$'$)#4:+$
'#;-6D'L*$)#
0$##J
')" (-$$#$#M"
./-,' 
66
#$)
#$
Conclusion
)#''$)'
#?#$
##''J
-##$###'
$$+D8'$)
#*')$,##
$-'$',BGD##'
$$,)#)##$
-'$$'#'''#2
)'#,
$))###0#
3)''),
'#)0'
$$$'
References
1. #4! %%%788>
4<<#<<$<%<#
7 @7887A" (-+$4-"
$ : 96BG9BB
B N"#//%&! &*, &), 
)#+)+'@EE$A-G"
(0+#- -$$G
7887QBF@>A4B>FGB9>
> )$"-"2#.(*/
.'(+*. #(###"
)')%& #
0$ ''6EEEQ69D@CA466>EG9C
9 '% (*$)
* *"')+$"!%))
 #%-$'+2
788BQEE@DA46868GF
D %"!'%$(* *)
')*"!,+$)$)
67
#$'#)$
 ''78866Q98@EA4D9EGDF
F "$/')*"%..'""R%#G-
"!$)G#'$24$$'$
788>'Q77@6A4>8EG6C
C ')*"".-,!"%."), 
%$)####0$24
 ''788869Q>C@CA4CB8G>B
E ')*"".%.), ,$"-,!"
"-+0 -#4
#$6EEFBQC@>A4689FGD6
68 $$*G)" (-$*
''6EEFQE@7A4C6GD
66 $*)" (-$#$2$,
<* '6EECGQB8@7A478EG6>
67 # -%'(%)))
)G#$)'$$$'@" (-AG
$@((A)'$$#
G#''@*A 7888
QCE@FA4CB8G9
6B .' ,,%("($,*-$GEE$
* )" (-#''
7887Q6D@CA497FGB6
6> .$!""""!"%)#)$
#<''"$$'(
''7887Q797@9A476EG79
69 .$!""!"'))#
)2#<''?7886+)Q>7@6A46EG
7E
6D !) ($.,% '
%)*"*(###$'))
#))'#''
6F !).,%)*!"*
$'$$'#))#))'
#''$$7886Q77@67A46BBBG>8
6C !".$.(!".$?..!"%)
)##''4$)#
6B
#$'$*$7889Q7>@BA469FGD>
6E !))'$$),!$G"--$EE$
''$G$$$'@" (-A
$)G#
''@*A788>+)Q6E@7A4E6GD
78 !**,! *"'#
#',6ECEQ>D@6A4>CG97
76 !**,! +)'#'
<#6EC>Q>6@CA4C79GE
77 !**,! +)'#$
)!6EE8DQBB9@CDC8A4CG66
7B ", ,%))-
',$$')'$#)
$)788869Q78@DA4%D9
7>  '.,)(%))#
*47889Q7F@>A47FEG7C9
79 %!%$-"/)%*/*$$
$'))#G#<''
4'"'788B'Q>C@7A4CFGE
7D ".##'% +*" (-)$)$
#''6EE9Q78@6A499GD8
7F "  +! #)#
'*)$
-$7886Q68C@68A4678BG6D
7C "/)./% !) ./,+
%!-###$'))#)'
G#<''($788BQB8@BA4>7BG
D()788B66
7E +-*"*-" '.)*'%
)##$2
7886Q>7@FA4689EGD6
B8 4<<$<0#$J S668FT% S68
6>
This Response Was Prepared by:
$
$
*$-$
# '$
*, 
%$
 /)
$$
In Consultation with:

 ## ''*$
M'##"#

#$
 #$# ''*$
M'##"#

%'
 #$# ''*$
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 
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Article
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This is a preliminary report on the safety and efficacy of 1.5 ATA hyperbaric oxygen therapy (HBOT) in military subjects with chronic blast-induced mild to moderate traumatic brain injury (TBI)/post-concussion syndrome (PCS) and post-traumatic stress disorder (PTSD). Sixteen military subjects received 40 1.5 ATA/60 min HBOT sessions in 30 days. Symptoms, physical and neurological exams, SPECT brain imaging, and neuropsychological and psychological testing were completed before and within 1 week after treatment. Subjects experienced reversible middle ear barotrauma (5), transient deterioration in symptoms (4), and reversible bronchospasm (1); one subject withdrew. Post-treatment testing demonstrated significant improvement in: symptoms, neurological exam, full-scale IQ (+14.8 points; p<0.001), WMS IV Delayed Memory (p=0.026), WMS-IV Working Memory (p=0.003), Stroop Test (p<0.001), TOVA Impulsivity (p=0.041), TOVA Variability (p=0.045), Grooved Pegboard (p=0.028), PCS symptoms (Rivermead PCSQ: p=0.0002), PTSD symptoms (PCL-M: p<0.001), depression (PHQ-9: p<0.001), anxiety (GAD-7: p=0.007), quality of life (MPQoL: p=0.003), and self-report of percent of normal (p<0.001), SPECT coefficient of variation in all white matter and some gray matter ROIs after the first HBOT, and in half of white matter ROIs after 40 HBOT sessions, and SPECT statistical parametric mapping analysis (diffuse improvements in regional cerebral blood flow after 1 and 40 HBOT sessions). Forty 1.5 ATA HBOT sessions in 1 month was safe in a military cohort with chronic blast-induced PCS and PTSD. Significant improvements occurred in symptoms, abnormal physical exam findings, cognitive testing, and quality-of-life measurements, with concomitant significant improvements in SPECT.
Article
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Recently, much scientific attention has been focused on resting brain activity and its investigation through such methods as the analysis of functional connectivity during rest (the temporal correlation of brain activities in different regions). However, investigation of the magnitude of brain activity during rest has focused on the relative decrease of brain activity during a task, rather than on the absolute resting brain activity. It is thus necessary to investigate the association between cognitive factors and measures of absolute resting brain activity, such as cerebral blood flow (CBF), during rest (rest-CBF). In this study, we examined this association using multiple regression analyses. Rest-CBF was the dependent variable and the independent variables included two essential components of cognitive functions, psychometric general intelligence and creativity. CBF was measured using arterial spin labeling and there were three analyses for rest-CBF; namely mean gray matter rest-CBF, mean white matter rest-CBF, and regional rest-CBF. The results showed that mean gray and white matter rest-CBF were significantly and positively correlated with individual psychometric intelligence. Furthermore, mean white matter rest-CBF was significantly and positively correlated with creativity. After correcting the effect of mean gray matter rest-CBF the significant and positive correlation between regional rest-CBF in the perisylvian anatomical cluster that includes the left superior temporal gyrus and insula and individual psychometric intelligence was found. Also, regional rest-CBF in the precuneus was significantly and negatively correlated with individual creativity. Significance of these results of regional rest-CBF did not change when the effect of regional gray matter density was corrected. The findings showed mean and regional rest-CBF in healthy young subjects to be correlated with cognitive functions. The findings also suggest that, even in young cognitively intact subjects, resting brain activity (possibly underlain by default cognitive activity or metabolic demand from developed brain structures) is associated with cognitive functions.
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To examine the effectiveness of group cognitive processing therapy (CPT) relative to trauma-focused group treatment as usual (TAU) in the context of a Veterans Health Administration (VHA) posttraumatic stress disorder (PTSD) residential rehabilitation program. Participants were 2 cohorts of male patients in the same program treated with either CPT (n = 104) or TAU (n = 93; prior to the implementation of CPT). Cohorts were compared on changes from pre- to posttreatment using the PTSD Checklist (PCL; Weathers, Litz, Herman, Huska, & Keane, 1993) and other measures of symptoms and functioning. Minorities represented 41% of the sample, and the mean age was 52 years (SD = 9.22). The CPT group was significantly younger and less likely to receive disability benefits for PTSD; however, these variables were not related to outcome. Analyses of covariance controlling for intake symptom levels and cohort differences revealed that CPT participants evidenced more symptom improvement at discharge than TAU participants on the PCL, F(3, 193) = 15.32, p < .001, b = 6.25, 95% CI [3.06, 9.44], and other measures. In addition, significantly more patients treated with CPT were classified as "recovered" or "improved" at discharge, χ2(1, N = 197) = 4.93, p = .032. There is still room for improvement, as substantial numbers of veterans continue to experience significant symptoms even after treatment with CPT in a residential program. However, CPT appears to produce significantly more symptom improvement than treatment conducted before the implementation of CPT. The implementation of this empirically supported treatment in VHA settings is both feasible and sustainable and is likely to improve care for male veterans with military-related PTSD.
Article
Ten university students who had recovered from minor head injury between one and three years previously were given vigilance and memory tests at a simulated altitude of 3,800 metres. Their performance was significantly below that of a matched group of students who had never had a head injury. The finding supports the proposition that even minor head injury has persisting effects, though they may be subtle and only emerge under the effects of stress.
Article
Among the 714 head injuries which were treated between 1969–1972 there were 111 with a mid-brain syndrome. Ninety nine of them were selected for comparative clinical investigations. All patients were treated with the same intensive measures and every second patient recieved hyperbaric oxygenation in addition. The comparison between the intensive therapy group (Group A) and the group treated with intensive therapy plus hyperbaric oxygenation (Group B) showed: 1. The survival time was substantially longer in the patients in Group B. 2. The survival rate was materially larger in Group B, not only in the patients with contusion but also in those who had an intracranial haemorrhage as the cause of their mid-brain syndrome. 3. The proportion of survivors was definitely higher in Group B in the age group 1–30 years; after the age of 40 only a small difference in favour of the patients receiving hyperbaric oxygenation could be recognised. At the conclusion of treatment 74% of the patients in Group A were either dead or apallic, as compared to 53% in Group B; complete recovery occurred in only 6% in Group A, but in 33% of Group B. These results show that by the addition of hyperbaric oxygenation the traumatic mid-brain syndrome is reversible in substantially larger degree and that a definitely larger number of cases obtain a complete cure. The introduction of hyperbaric oxygenation with traumatic mid-brain syndrome has thus proved itself. Especially in the younger patients (1–30 years) the use of hyperbaric oxygenation greatly improved the prognosis, so that its use with these patients should be specially required.
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: Preliminary examination of the effectiveness of prolonged exposure (PE) therapy for the treatment of posttraumatic stress disorder (PTSD) with Operation Enduring Freedom and Operation Iraqi Freedom Veterans who have experienced traumatic brain injury (TBI). : Ten Veterans with a history of mild to moderate TBI and chronic PTSD. : Outpatient Mental Health/PTSD clinics and polytrauma centers at 2 VA medical centers. : Comprehensive evaluation that included clinical interview, neuropsychologic evaluation, and/or neuroimaging; Posttraumatic Stress Disorder Checklist and Beck Depression Inventory-Second Edition. : Standard implementation of the PE manual was used in all cases with slight adjustments to account for Veterans' residual cognitive deficits. Veterans completed between 8 and 18 sessions. : Veterans demonstrated significant reductions in total PTSD and depression symptoms from pre- to posttreatment. Within-group effect sizes were large. : These findings suggest that PE can be safely and effectively implemented with Veterans with PTSD, a history of mild to moderate TBI, and current cognitive impairment.
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A substantial body of literature supports the intuitive notion that a good night's sleep can facilitate human cognitive performance the next day. Deficits in attention, learning & memory, emotional reactivity, and higher-order cognitive processes, such as executive function and decision making, have all been documented following sleep disruption in humans. Thus, whilst numerous clinical and experimental studies link human sleep disturbance to cognitive deficits, attempts to develop valid and reliable rodent models of these phenomena are fewer, and relatively more recent. This review focuses primarily on the cognitive impairments produced by sleep disruption in rodent models of several human patterns of sleep loss/sleep disturbance. Though not an exclusive list, this review will focus on four specific types of sleep disturbance: total sleep deprivation, experimental sleep fragmentation, selective REM sleep deprivation, and chronic sleep restriction. The use of rodent models can provide greater opportunities to understand the neurobiological changes underlying sleep loss induced cognitive impairments. Thus, this review concludes with a description of recent neurobiological findings concerning the neuroplastic changes and putative brain mechanisms that may underlie the cognitive deficits produced by sleep disturbances.
Article
We conducted an uncontrolled pilot study to determine whether transcendental meditation (TM) might be helpful in treating veterans from Operation Enduring Freedom or Operation Iraqi Freedom with combat-related posttraumatic stress disorder (PTSD). Five veterans were trained in the technique and followed for 12 weeks. All subjects improved on the primary outcome measure, the Clinician Administered PTSD Scale (mean change score, 31.4; p = 0.02; df = 4). Significant improvements were also observed for 3 secondary outcome measures: Clinician's Global Inventory-Severity (mean change score, 1.60; p < 0.04; df = 4), Quality of Life Enjoyment and Satisfaction Questionnaire (mean change score, -13.00; p < 0.01; df = 4), and the PTSD Checklist-Military Version (mean change score, 24.00; p < 0.02; df = 4). TM may have helped to alleviate symptoms of PTSD and improve quality of life in this small group of veterans. Larger, placebo-controlled studies should be undertaken to further determine the efficacy of TM in this population.