-
[show abstract]
[hide abstract]
ABSTRACT: Patients with autism spectrum disorders (ASDs) exhibit core autistic symptoms including social impairments from early childhood and mostly show secondary disabilities such as irritability and aggressive behavior based on core symptoms. However, there are still no radical treatments of social impairments in these patients. Oxytocin has been reported to play important roles in multiple social behaviors dependent on social recognition, and has been expected as one of the effective treatments of social impairments of patients with ASDs.
We present a case of a 16-year-old girl with autistic disorder who treated by long-term administration of oxytocin nasal spray. Her autistic symptoms were successfully treated by two month administration; the girl's social interactions and social communication began to improve without adverse effects. Her irritability and aggressive behavior also improved dramatically with marked decreases in aberrant behavior checklist scores from 69 to 7.
This case is the first to illustrate long-term administration of oxytocin nasal spray in the targeted treatment of social impairments in a female with autistic disorder. This case suggests that long-term nasal oxytocin spray is promising and well-tolerated for treatment of social impairments of patients with ASDs.
BMC Psychiatry 08/2012; 12:110. · 2.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Subjects with Pervasive Developmental Disorders (PDD) often exhibit behavioral symptoms such as aggressiveness and irritability, which are targets of psychopharmacologic intervention. This retrospective study was designed to examine children and adolescents with PDD experiencing tolerability issues with risperidone treatment, and thereby assess the efficacy and tolerability of switching to aripiprazole.
This naturalistic study included 23 subjects with PDD (16 males, 7 females, age range 9-24 years, mean age 15.1±3.9 years) diagnosed according to DSM-IV criteria and followed up for 14.9±8.4 weeks after switching to aripiprazole from risperidone. Outcome measures were the Clinical Global Impression-Severity (CGI-S) and CGI Improvement (CGI-I) scales.
The mean CGI-S scores of pre-aripiprazole treatment and post-aripiprazole treatment were, respectively 4.7±1.4 and 4.6±1.3. Mean maintenance dosages of risperidone and aripiprazole were, respectively, 0.7±0.5mg/day and 2.8±1.3mg/day. The mean CGI-I score, which shows the difference induced by switching from risperidone to aripiprazole, was 3.4±0.8 for the whole sample, suggesting that the efficacy of risperidone for treating behavioral problems of PDD was maintained by aripiprazole. Some improvement of safety/tolerability issues such as increased appetite, somnolence, hyperprolactinemia, and amenorrhea occurred after switching to aripiprazole.
Results show that switching to aripiprazole might be generally well tolerated and might constitute an alternative treatment for subjects with PDD who experience tolerability issues with risperidone treatment. Additional long-term controlled studies of PDD subjects should be undertaken to evaluate the efficacy and safety of switching to aripiprazole from other antipsychotics.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2012; 37(1):128-31. · 3.25 Impact Factor
-
Hiroki C Tanabe, Hirotaka Kosaka,
Daisuke N Saito,
Takahiko Koike,
Masamichi J Hayashi,
Keise Izuma,
Hidetsugu Komeda,
Makoto Ishitobi,
Masao Omori,
Toshio Munesue,
Hidehiko Okazawa,
Yuji Wada,
Norihiro Sadato
[show abstract]
[hide abstract]
ABSTRACT: Persons with autism spectrum disorders (ASD) are known to have difficulty in eye contact (EC). This may make it difficult for their partners during face to face communication with them. To elucidate the neural substrates of live inter-subject interaction of ASD patients and normal subjects, we conducted hyper-scanning functional MRI with 21 subjects with autistic spectrum disorder (ASD) paired with typically-developed (normal) subjects, and with 19 pairs of normal subjects as a control. Baseline EC was maintained while subjects performed real-time joint-attention task. The task-related effects were modeled out, and inter-individual correlation analysis was performed on the residual time-course data. ASD-Normal pairs were less accurate at detecting gaze direction than Normal-Normal pairs. Performance was impaired both in ASD subjects and in their normal partners. The left occipital pole (OP) activation by gaze processing was reduced in ASD subjects, suggesting that deterioration of eye-cue detection in ASD is related to impairment of early visual processing of gaze. On the other hand, their normal partners showed greater activity in the bilateral occipital cortex and the right prefrontal area, indicating a compensatory workload. Inter-brain coherence in the right IFG that was observed in the Normal-Normal pairs (Saito et al., 2010) during EC diminished in ASD-Normal pairs. Intra-brain functional connectivity between the right IFG and right superior temporal sulcus (STS) in normal subjects paired with ASD subjects was reduced compared with in Normal-Normal pairs. This functional connectivity was positively correlated with performance of the normal partners on the eye-cue detection. Considering the integrative role of the right STS in gaze processing, inter-subject synchronization during EC may be a prerequisite for eye cue detection by the normal partner.
Frontiers in Human Neuroscience 01/2012; 6:268. · 2.34 Impact Factor
-
Kosuke Narita,
Kazuyuki Fujihara,
Yuichi Takei,
Masashi Suda,
Yoshiyuki Aoyama,
Toru Uehara,
Takehiko Majima, Hirotaka Kosaka,
Makoto Amanuma,
Masato Fukuda,
Masahiko Mikuni
[show abstract]
[hide abstract]
ABSTRACT: Recent human studies have indicated that adverse parenting experiences during childhood and adolescence are associated with adulthood hypothalamus-pituitary-adrenal (HPA) axis hypoactivity. Chronic HPA axis hypoactivity inhibits hippocampal gray matter (GM) development, as shown by animal studies. However, associations among adverse parenting experiences during childhood and adolescence, HPA axis activity, and brain development, particularly hippocampal development, are insufficiently investigated in humans. In this voxel-based structural magnetic resonance imaging study, using a cross-sectional design, we examined the associations among the scores of parental bonding instrument (PBI; a self-report scale to rate the attitudes of parents during the first 16 years), cortisol response determined by the dexamethasone/corticotropin-releasing hormone test, and regional or total hippocampal GM volume in forty healthy young adults with the following features: aged between 18 and 35 years, no cortisol hypersecretion in response to the dexamethasone test, no history of traumatic events, or no past or current conditions of significant medical illness or neuropsychiatric disorders. As a result, parental overprotection scores significantly negatively correlated with cortisol response. Additionally, a significant positive association was found between cortisol response and total or regional hippocampal GM volume. No significant association was observed between PBI scores and total or regional hippocampal GM volume. In conclusion, statistical associations were found between parental overprotection during childhood and adolescence and adulthood HPA axis hypoactivity, and between HPA axis hypoactivity and hippocampal GM volume reduction in healthy young adults, but no significant relationship was observed between any PBI scores and adulthood hippocampal GM volume.
Human Brain Mapping 12/2011; 33(9):2211-23. · 5.88 Impact Factor
-
Psychiatry and Clinical Neurosciences 10/2011; 65(6):607. · 2.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Individuals with autism spectrum disorders (ASD) show impaired emotional responses to self-face processing, but the underlying neural bases are unclear. Using functional magnetic resonance imaging, we investigated brain activity when 15 individuals with high-functioning ASD and 15 controls rated the photogenicity of self-face images and photographs of others' faces. Controls showed a strong correlation between photogenicity ratings and extent of embarrassment evoked by self-face images; this correlation was weaker among ASD individuals, indicating a decoupling between the cognitive evaluation of self-face images and emotional responses. Individuals with ASD demonstrated relatively low self-related activity in the posterior cingulate cortex (PCC), which was related to specific autistic traits. There were significant group differences in the modulation of activity by embarrassment ratings in the right insular (IC) and lateral orbitofrontal cortices. Task-related activity in the right IC was lower in the ASD group. The reduced activity in the right IC for self-face images was associated with weak coupling between cognitive evaluation and emotional responses to self-face images. The PCC is responsible for self-referential processing, and the IC plays a role in emotional experience. Dysfunction in these areas could contribute to the lack of self-conscious behaviors in response to self-reflection in ASD individuals.
Social neuroscience 09/2011; · 3.17 Impact Factor
-
Journal of clinical psychopharmacology 06/2011; 31(3):400-1; author reply 401. · 5.09 Impact Factor
-
Journal of clinical psychopharmacology 04/2011; 31(2):243-5. · 5.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although rapid cycling (RC), a course specifier of bipolar I or II disorder, is particularly common among bipolar II patients compared with bipolar I patients, the pathophysiological lines of evidence regarding bipolar II with RC are still limited. In this preliminary study with a cross-sectional design, we examined the regional gray matter (GM) volume in 14 bipolar II patients with RC, 17 patients without RC and 84 healthy controls by whole-brain and region-of-interest (ROI) analysis methods, using magnetic resonance imaging with voxel-based morphometry. Whole-brain analysis in this study revealed that the bipolar II patients with RC showed GM volume reductions in the bilateral hemispheres of the medial orbital prefrontal cortex, ventromedial prefrontal cortex, anterior cingulate, insula and parahippocampus, in the left hemisphere of the inferior temporal cortex and cerebellum, and in the brainstem, compared with the healthy controls. Moreover, ROI analysis focusing on the ventral prefrontal cortex, i.e., Brodmann areas 10, 11 and 47, revealed that the bipolar II patients with RC showed GM volume reduction in the ventromedial prefrontal cortex, compared with the patients without RC. The findings of our pilot study suggest that the ventromedial prefrontal cortex is associated with the generation of RC in bipolar II disorder.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 11/2010; 35(2):439-45. · 3.25 Impact Factor
-
Progress in Neuro-Psychopharmacology and Biological Psychiatry 10/2010; 34(7):1361-2. · 3.25 Impact Factor
-
Hirotaka Kosaka,
Masao Omori,
Toshio Munesue,
Makoto Ishitobi,
Yukiko Matsumura,
Tetsuya Takahashi,
Kousuke Narita,
Tetsuhito Murata,
Daisuke N Saito,
Hitoshi Uchiyama,
Tomoyo Morita,
Mitsuru Kikuchi,
Kimiko Mizukami,
Hidehiko Okazawa,
Norihiro Sadato,
Yuji Wada
[show abstract]
[hide abstract]
ABSTRACT: Enlarged head circumference and increased brain weight have been reported in infants with pervasive developmental disorders (PDD), and volumetric studies suggest that children with PDD have abnormally enlarged brain volumes. However, little is known about brain volume abnormalities in young adults with PDD. We explored gray matter (GM) volume in young adults with PDD. T1-weighted volumetric images were acquired with a 3-T magnetic resonance scanner from 32 males with high-functioning PDD (23.8+/-4.2 years; Full Scale Intelligence Quotient [FSIQ]=101.6+/-15.6) and 40 age-matched normal male control subjects (22.5+/-4.3 years; FSIQ=109.7+/-7.9). Regional GM volumes were compared between the two groups using voxel-based morphometry (VBM) with the Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL). Compared with the control group, the high-functioning PDD group showed significantly less GM in the right insula, the right inferior frontal gyrus, and the right inferior parietal lobule. A conservative threshold confirmed considerably smaller volumes in the right insula and inferior frontal gyrus. In these areas, negative correlations were found between Autism Spectrum Quotient scores and GM volume, although no significant correlations were found between each subject's FSIQ and GM volume. No regions showed greater GM volumes in the high-functioning PDD group. The insular cortex, which works as a relay area for multiple neurocognitive systems, may be one of the key regions underlying the complex clinical features of PDD. These smaller GM volumes in high-functioning PDD subjects may reflect the clinical features of PDD itself, rather than FSIQ.
NeuroImage 05/2010; 50(4):1357-63. · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Previous epidemiologic studies using the parental bonding instrument (PBI), a self-report scale to rate attitudes of parents during the first 16 years, have suggested that a lower parental care score or higher parental overprotection score could lead to an increased risk of several psychiatric disorders, including schizophrenia and mood disorder. However, neuroimaging studies of an association between PBI scores and brain developmental abnormalities are still limited. In this region-of-interest analysis study using a cross-sectional design, we examined 50 normal young adults, in terms of relationships of parental bonding styles during the first 16 years measured by PBI with regional gray matter (GM) volume in the dorsolateral prefrontal cortex (DLPFC). Our study showed that paternal care score positively correlated with the GM volume in the left DLPFC, and paternal and maternal overprotection score negatively correlated with the GM volume in the left DLPFC. In conclusion, our results suggest that in normal young adults, lower paternal care and higher parental overprotection scores correlated with the GM volume reduction in the DLPFC.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 02/2010; 34(4):624-31. · 3.25 Impact Factor
-
Daisuke N Saito,
Hiroki C Tanabe,
Keise Izuma,
Masamichi J Hayashi,
Yusuke Morito,
Hidetsugu Komeda,
Hitoshi Uchiyama, Hirotaka Kosaka,
Hidehiko Okazawa,
Yasuhisa Fujibayashi,
Norihiro Sadato
[show abstract]
[hide abstract]
ABSTRACT: Eye contact provides a communicative link between humans, prompting joint attention. As spontaneous brain activity might have an important role in the coordination of neuronal processing within the brain, their inter-subject synchronization might occur during eye contact. To test this, we conducted simultaneous functional MRI in pairs of adults. Eye contact was maintained at baseline while the subjects engaged in real-time gaze exchange in a joint attention task. Averted gaze activated the bilateral occipital pole extending to the right posterior superior temporal sulcus, the dorso-medial prefrontal cortex, and the bilateral inferior frontal gyrus. Following a partner's gaze toward an object activated the left intraparietal sulcus. After all the task-related effects were modeled out, inter-individual correlation analysis of residual time-courses was performed. Paired subjects showed more prominent correlations than non-paired subjects in the right inferior frontal gyrus, suggesting that this region is involved in sharing intention during eye contact that provides the context for joint attention.
Frontiers in Integrative Neuroscience 01/2010; 4:127.
-
[show abstract]
[hide abstract]
ABSTRACT: This study was intended to examine variations in electroencephalographic (EEG) complexity in response to photic stimulation (PS) during aging to test the hypothesis that the aging process reduces physiologic complexity and functional responsiveness.
Multiscale entropy (MSE), an estimate of time-series signal complexity associated with long-range temporal correlation, is used as a recently proposed method for quantifying EEG complexity with multiple coarse-grained sequences. We recorded EEG in 13 healthy elderly subjects and 12 healthy young subjects during pre-PS and post-PS conditions and estimated their respective MSE values.
For the pre-PS condition, no significant complexity difference was found between the groups. However, a significant MSE change (complexity increase) was found post-PS only in young subjects, thereby revealing a power-law scaling property, which means long-range temporal correlation.
Enhancement of long-range temporal correlation in young subjects after PS might reflect a cortical response to stimuli, which was absent in elderly subjects. These results are consistent with the general "loss of complexity/diminished functional response to stimuli" theory of aging.
Our findings demonstrate that application of MSE analysis to EEG is a powerful approach for studying age-related changes in brain function.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 03/2009; 120(3):476-83. · 3.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Multifractal analysis provides a precise quantitative description of the structural complexity of white matter (WM) on magnetic resonance imaging (MRI). To test this new technique as an aid to elucidating the pathology of schizophrenia, we examined a multifractal dimension (i.e. Deltaalpha) of WM in schizophrenia patients and their relations to clinical variables. We examined 16 patients with schizophrenia and 16 controls matched for age, sex and handedness. Delta alpha value of WM in the prefrontal and frontoparietal lobes and the corpus callosum (genu and splenium) on T2-weighted MRI was calculated. Delta alpha was not significantly different between groups in either region of interest. However, group-by-side interaction for Deltaalpha was found in the frontoparietal WM; post-hoc analysis revealed normal left dominant asymmetry in Deltaalpha for frontoparietal WM in control subjects, which was absent in schizophrenia patients. Furthermore, the patients with schizophrenia had a lower asymmetry coefficient ([R-L]/[R+L]) for Deltaalpha in frontoparietal WM. Relations to clinical symptoms from the Positive and Negative Syndrome Scale, Deltaalpha in corpus callosum, and the asymmetry coefficient in prefrontal WM were correlated with negative and general psychopathology symptom scores. Our results support the left-sided dysfunction hypothesis of schizophrenia and its relation to schizophrenic symptoms. Multifractal analysis reveals abnormal patterns of WM structures in schizophrenia that could be implicated in the disorder's etiology.
Psychiatry Research 03/2009; 171(3):177-88. · 2.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent accumulating lines of evidence reveal that leptin is associated with synaptic plasticity and neuroprotective activity in the brain.
In this preliminary study with a cross-sectional design, we examined the relationship between plasma leptin level and total or regional gray matter (GM) volume in 34 elderly subjects (mean age 64.5 years) with normal fasting glucose level and without dementia and metabolic syndrome by voxel-based morphometry of magnetic resonance imaging scans.
Plasma leptin level showed no significant correlation with total GM volume but showed a significantly positive correlation with GM volumes in the right hippocampus, left parahippocampus, and right cerebellum with adjustments for age, gender, body mass index (BMI), and waist-to-hip ratio (W/H). Also, after adjustments for age, gender, BMI, W/H, and intracranial volume, plasma leptin level significantly positively correlated with GM volumes in the right hippocampus and bilateral cerebella but not with that in the left parahippocampus.
The results of this pilot study would be beneficial for our understanding of the neuroprotective effects of leptin on human brain aging.
Biological psychiatry 12/2008; 65(11):992-4. · 8.93 Impact Factor
-
Progress in Neuro-Psychopharmacology and Biological Psychiatry 09/2008; 33(1):150-2. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Anxiety has been shown to be associated with cardiovascular disease. Atherosclerosis is responsible for the vast majority of cardiovascular events. Recent evidence is accumulating to show that insulin resistance (IR) plays a central role in determining the clinical manifestations of established atherosclerotic lesions. The current preliminary study aimed to investigate the associations between trait anxiety, IR, and atherosclerotic progression in healthy elderly subjects with normal fasting glucose and without metabolic syndrome. Thirty-five healthy elderly subjects (19 males and 16 females, mean age 64.5+/-4.7 years) were enrolled in this study. Trait anxiety was measured using a questionnaire corresponding to the trait anxiety scale taken from the State and Trait Anxiety Inventory. The homeostasis model assessment (HOMA-R) and plasma leptin-to-adiponectin ratio (L/A ratio), which are convenient IR indexes calculated from fasting blood sampling, were examined. As measurements of atherosclerotic progression, we performed two ultrasound methods, namely brachial artery flow-mediated dilation (FMD), an endothelial function assessment quantitatively reflecting the endothelium-dependent vasodilation responses following hyperemia, and measurement of carotid intima-media thickness (IMT). The severity of trait anxiety was positively associated with HOMA-R and L/A ratio, and negatively associated with the percent change of brachial artery FMD (%FMD). HOMA-R and L/A ratio were positively associated with carotid IMT, and L/A ratio was negatively associated with %FMD. These data showed the associations between trait anxiety, IR indexes and endothelial dysfunction or atherosclerotic progression. This pilot study, with a cross-sectional design, supports the promising role of IR for clarifying the pathophysiological mechanism by which anxiety contributes to an increasing risk of atherosclerosis.
Psychoneuroendocrinology 05/2008; 33(3):305-12. · 5.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Adiponectin is an adipocyte-specific secretory protein that circulates in serum as three oligomeric complexes known as the high, medium and low molecular weight form (HMW, MMW and LMW). HMW adiponectin has been suggested to be a better predictor of metabolic variables, and it was recently reported that the ratio of HMW to total adiponectin or to LMW, not the absolute amount of plasma adiponectin, might be crucial in determining insulin sensitivity. Insulin resistance (IR) is considered to be a primary component of vascular risk factors. Although the association of depression with atherosclerotic vascular diseases has been well documented, the contribution of IR to the evolution and progression of depression-associated vascular morbidity and mortality remains unknown. The current preliminary study showed that the ratio of HMW to total adiponectin or to LMW, not the absolute amount of plasma adiponectin, was negatively associated with depression severity in healthy elderly subjects without metabolic syndrome. This pilot study supports a promising role of adiponectin multimer distribution for clarifying the pathophysiological mechanism by which depression is associated with increased risk for IR, leading to cardiovascular disease, metabolic syndrome or type 2 diabetes.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 02/2008; 32(1):124-7. · 3.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Endothelial function plays a key role in determining the clinical manifestations of atherosclerosis. Recent reports have shown that healthy elderly subjects with higher trait anxiety tend to have heightened risks of atherosclerotic lesions and cardiovascular disease. The present study was intended to examine whether an association exists between trait anxiety and endothelial function in healthy young and elderly subjects.
This study examined 26 young male and 30 elderly male subjects using brachial artery flow-mediated dilation (FMD) - a non-invasive ultrasound method - to evaluate endothelial function by measuring the dilation responses of vascular smooth muscle to the nitric oxide produced by endothelial cells following hyperemia.
A significant negative correlation was observed between the State and Trait Anxiety Inventory (STAI)-trait score as a parameter of anxiety and the percentage change of FMD (%FMD) in the elderly subjects, but not in the young subjects. The elderly subjects showed significantly lower %FMD than the young subjects.
These results suggest the possibility that trait anxiety is a predisposing risk factor for cardiovascular damage that might, over a long period, induce atherosclerotic lesions.
International Psychogeriatrics 11/2007; 19(5):947-54. · 2.24 Impact Factor
