Kyoko Ohashi

The effects of childhood maltreatment on brain structure, function and connectivity

Maltreatment-related childhood adversity is the leading preventable risk factor for mental illness and substance abuse. Although the association between maltreatment and psychopathology is compelling, there is a pressing need to understand how maltreatment increases the risk of psychiatric disorders. Emerging evidence suggests that maltreatment alters trajectories of brain development to affect sensory systems, network architecture and circuits involved in threat detection, emotional regulation and reward anticipation. This Review explores whether these alterations reflect toxic effects of early-life stress or potentially adaptive modifications, the relationship between psychopathology and brain changes, and the distinction between resilience, susceptibility and compensation.

Symptom profile of multiple chemical sensitivity in actual life.

Objective: This study was conducted to confirm the definition of multiple chemical sensitivity (MCS) in actual life: that multiple symptoms are provoked in multiple organs by exposure to, and ameliorated by avoidance of, multiple chemicals at low levels. We used the Ecological Momentary Assessment to monitor everyday symptoms and the active sampling and passive sampling methods to measure environmental chemical exposure. Methods: Eighteen patients with MCS, diagnosed according to the 1999 consensus criteria, and 12 healthy controls participated in this study. Fourteen patients and 12 controls underwent 1-week measurement of physical and psychologic symptoms and of the levels of exposure to various chemicals. Linear mixed models were used to test the hypotheses regarding the symptom profile of MCS patients. Results: Some causative chemicals were detected in 11 of 14 MCS patients. Two other patients did not report any hypersensitivity episodes, whereas passive sampling showed far less exposure to chemicals than control subjects. Another subject reported episodic symptoms but was excluded from the following analyses because no possible chemical was detected. Eleven of the 17 physical symptoms and all four mood subscales examined were significantly aggravated in the interview based on “patient-initiated symptom prompts.” On the other hand, there were no differences in physical symptoms or mood subscales between MCS patients and control subjects in the interview based on “random prompts.” Conclusions: MCS patients do not have either somatic or psychologic symptoms under chemical-free conditions, and symptoms may be provoked only when exposed to chemicals. AS = active sampling; AS–PS method = active sampling and passive sampling methods; CAS = the concentration of exposure estimated by the AS method; CFS = chronic fatigue syndrome; CPS = the concentration of exposure estimated by the PS method; CS = chemical sensitivity; DAMS = Depression and Anxiety Mood Scale; DNPH = 2,4-dinitrophenyl-hydrazine; ED = electronic diary; EESI = Environmental Exposure and Sensitivity Inventory; EMA = Ecological Momentary Assessment; FM = fibromyalgia; M.I.N.I. = Mini International Neuropsychiatric Interview; MCS = multiple chemical sensitivity; PS = passive sampling; RSD = relative standard deviation; RSDAS = RSD of repeatability test in the AS method; RSDPS = RSD of repeatability test in the PS method; VOCs = volatile organic compounds.

A real-time assessment of the effect of exercise in chronic fatigue syndrome

Patients with chronic fatigue syndrome (CFS) report substantial symptom worsening after exercise. However, the time course over which this develops has not been explored. Therefore, the objective of this study was to investigate the influence of exercise on subjective symptoms and on cognitive function in CFS patients in natural settings using a computerized ecological momentary assessment method, which allowed us to track the effects of exercise within and across days. Subjects were 9 female patients with CFS and 9 healthy women. A watch-type computer was used to collect real-time data on physical and psychological symptoms and cognitive function for 1week before and 2weeks after a maximal exercise test. For each variable, we investigated temporal changes after exercise using multilevel modeling. Following exercise, physical symptoms did get worse but not until a five-day delay in CFS patients. Despite this, there was no difference in the temporal pattern of changes in psychological symptoms or in cognitive function after exercise between CFS patients and controls. In conclusion, physical symptoms worsened after several days delay in patients with CFS following exercise while psychological symptoms or cognitive function did not change after exercise.

Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome.

Although a number of studies have reported alterations in cardiac autonomic nervous system function in chronic fatigue syndrome (CFS), the results are not consistent across studies. Reasons for these discrepancies include (1) the use of a heterogeneous patient sample that included those with orthostatic postural tachycardia (POTS), a condition with an autonomic changes, and (2) the use of frequency domain techniques which require a stationary signal and averaging data across relatively long epochs. To deal with these shortcomings, we used the smoothed pseudo-Wigner-Ville transform (SPWVT) to analyze heart rate variability (HRV) and blood pressure variability (BPV) during head-up tilt (HUT) by separating CFS patients into those with and without POTS. SPWVT has the advantage of providing instantaneous information about autonomic function under nonstable physiological conditions. We studied 18 CFS patients without POTS, eight CFS patients with POTS and 25 sedentary healthy controls during supine rest and during the first 10 min after HUT. While we found significant effects of postural change in both groups for all autonomic variables, there were significant group x time interactions between CFS without POTS and controls for only instant center frequency (ICF) within the low frequency region both from HRV (p=0.02) and from BPV (p=0.01). Although the physiological meaning of ICF still remains unknown, the data suggest that even CFS patients without POTS may have a subtle underlying disturbance in autonomic function.

Tension‐type headache and physical activity: an actigraphic study

There have been some studies on the relationship between tension-type headache (TTH) and physical activity. However, most previous studies were not prospective and assessed physical activity by questionnaire. Therefore, this study was aimed to investigate the relationship between TTH intensity and physical activity prospectively utilizing computerized ecological momentary assessment and actigraphy Thirty-one TTH patients wore watch-type computers equipped with actigraphy inside for 1 week to record momentary headache intensity and physical activity. Multilevel modelling was used to investigate the effect of headache intensity on the simultaneous and subsequent activity level. There were significant negative associations between headache intensity and the simultaneous and subsequent activity level, and activity level was significantly reduced at headache exacerbations. These results provide objective and quantitative evidence suggesting that TTH negatively affects physical activity.

Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome.

Post-exertional exacerbation of symptoms is one of the major characteristics of chronic fatigue syndrome (CFS). In this study, we evaluated the hypothesis that disturbances in circadian chronobiological regulation may play a role in generating this phenomenon. We recorded physical activity for 6-day periods in 16 women (10 CFS and 6 sedentary healthy controls, CON) before and after performing a maximal treadmill test. We calculated activity rhythms by computing autocorrelation coefficients by cutting 1 day apart from the data as a template and sliding it sequentially through each of the other days; all of 6 days were used as the templates. The peak value of autocorrelation coefficient (R) and the time between peak Rs (circadian period, CP) were calculated. CFS patients had a lengthening (P < .05) of mean circadian period (MCP) that was longer than 24 h (P < .05), while MCP in CON remained unchanged. No difference was found in the standard error of each subjects MCP (circadian period variability, CPV) before and after exercise for both groups. We interpret this increase in circadian rest-activity period seen in CFS patients following exercise to indicate that exhaustive exercise interferes with normal entrainment to 24-h zeitgeber(s). This effect may be associated in part with the common patient complaint of symptom worsening following exertion.

Power-law temporal autocorrelation of activity reflects severity of parkinsonism

We aimed to obtain a reliable, objective scale representing disease severity for appropriate management of patients with Parkinsons disease (PD). Nineteen patients with PD at the Department of Neurology, Tokyo University Hospital, were classified into mild (n = 10) or severe groups (n = 9) depending on their Hoehn‐Yahr scores, and wore accelerometers on their wrists for more than 6 consecutive days. During this time we monitored their subjective assessments of symptom severity and analyzed the power‐law exponents (α) for local maxima and minima of fluctuations in the activity time series. Statistical comparisons were made between the severe and mild groups and of individual patients on “good condition” and “bad condition” days, as well as between days before and after antiparkinsonism medication. In all patients, the α for local maxima was always lower when parkinsonism was mild than when severe. Presence of tremor did not influence the α for local maxima. As the lower α value for local maxima of fluctuations in activity records reflects more frequent switching behavior from low to high physical activities or the severity of akinesia, actigraph monitoring of parkinsonism, and analysis of its power‐law correlation may provide useful objective information for controlling parkinsonism in outpatient clinics and for evaluating new antiparkinsonism drugs.

Mood dysregulation and affective instability in emerging adults with childhood maltreatment: An ecological momentary assessment study

Childhood maltreatment increases risk for mood, anxiety, substance use and personality disorders and is associated with alterations in structure, function and connectivity of brain regions involved in emotional regulation. We sought to assess whether maltreatment was specifically associated with disturbances in positive or negative mood regulation. Ecological momentary ratings were collected with a wristwatch-like device with joy-stick (Seiko ecolog) approximately six times per day over a week in 60 unmedicated participants (22 control, 38 maltreated, 18-25 years old). Forty-five percent of maltreated subjects had a history of major depression but all were currently euthymic. Principal component analysis with varimax rotation was used to provide orthogonal measures of positive and negative valence, which were analyzed for indices of variability, circadian rhythmicity and persistence, using linear and non-linear hierarchical modeling and Hurst analysis. Groups did not differ in mean levels of positive or negative affect. Maltreated subjects had increased variability and circadian and hemicircadian abnormalities in ratings of positive but not negative affect. Conversely, they had higher estimated Hurst exponents for negative but not positive affect ratings indicating a greater degree of persistence. Abnormalities in variability, rhythmicity and persistence were present in both maltreated subjects with and without histories of major depression. These findings suggest that both positive and negative valence systems may be dysregulated in individuals with childhood maltreatment. However the nature of the dysregulation appears to differ fundamentally in these domains, as positive mood ratings were more variable and negative ratings more persistent.

Differential effects of childhood neglect and abuse during sensitive exposure periods on male and female hippocampus

ABSTRACT The hippocampus is a highly stress susceptible structure and hippocampal abnormalities have been reported in a host of psychiatric disorders including major depression and post‐traumatic stress disorder (PTSD). The hippocampus appears to be particularly susceptible to early life stress with a graded reduction in volume based on number of types (multiplicity) or severity of maltreatment. We assessed whether the most important predictors of adult hippocampal volume were multiplicity, severity or duration of exposure or timing of maltreatment during developmental sensitive periods. 3T MRIs were collected on 336 unmedicated, right‐handed subjects (132M/204F, 18–25 years). Exposure to broad categories of abuse and neglect during each year of childhood were assessed using the Maltreatment and Abuse Chronology of Exposure scale and evaluated using artificial intelligence and predictive analytics. Male hippocampal volume was predicted by neglect, but not abuse, up through 7 years of age. Female hippocampal volume was predicted by abuse, but not neglect, at 10, 11, 15 and 16 years. Exposure at peak age had greater predictive importance than multiplicity, severity or duration. There were also marked gender differences in subfields and portions (head, body or tail) affected by exposure. History and symptoms of major depression, PTSD or anxiety disorders were not predictive of hippocampal volume once maltreatment was accounted for. Neglect appears to foster inadequate hippocampal development in males while abuse appears to produce a stress‐related deficit in females. Studies assessing hippocampal volume in psychiatric disorders need to control for the gender‐specific effects of abuse and neglect. HighlightsHippocampal volume in males was predicted by neglect during first seven years.Hippocampal volume in females was predicted by abuse, particular at ages 10 and 11.Neglect at peak age correlated most strongly with volume of the CA1 in males.Abuse at peak age correlated most strongly with volume of CA3 in females.Abuse had greater effects on shape of female hippocampal head and tail than body.

Childhood maltreatment is associated with alteration in global network fiber-tract architecture independent of history of depression and anxiety

Abstract Childhood maltreatment is a major risk factor for psychopathology. It is also associated with alterations in the network architecture of the brain, which we hypothesized may play a significant role in the development of psychopathology. In this study, we analyzed the global network architecture of physically healthy unmedicated 18–25 year old subjects (n=262) using diffusion tensor imaging (DTI) MRI and tractography. Anatomical networks were constructed from fiber streams interconnecting 90 cortical or subcortical regions for subjects with no‐to‐low (n=122) versus moderate‐to‐high (n=140) exposure to maltreatment. Graph theory analysis revealed lower degree, strength, global efficiency, and maximum Laplacian spectra, higher pathlength, small‐worldness and Laplacian skewness, and less deviation from artificial networks in subjects with moderate‐to‐high exposure to maltreatment. On balance, local clustering was similar in both groups, but the different clusters were more strongly interconnected in the no‐to‐low exposure group. History of major depression, anxiety and attention deficit hyperactivity disorder did not have a significant impact on global network measures over and above the effect of maltreatment. Maltreatment is an important factor that needs to be taken into account in studies examining the relationship between network differences and psychopathology. HighlightsChildhood maltreatment was associated with global network architecture abnormalitiesAbnormalities included increased small‐worldness and decreased degree and efficiencyMood, anxiety and ADHD didn’t account for network differences related to maltreatmentFiber stream numbers were reduced bilaterally especially frontal to basal ganglia