This paper reviews the magnetic resonance imaging (MRI) literature on the effects of prenatal alcohol exposure on the developing human brain.

A literature search was conducted through the following databases: PubMed, PsycINFO and Google Scholar. Combinations of the following search terms and keywords were used to identify relevant studies: ‘alcohol’, ‘fetal alcohol spectrum disorders’, ‘fetal alcohol syndrome’, ‘FAS’, ‘FASD’, ‘MRI’, ‘DTI’, ‘MRS’, ‘neuroimaging’, ‘children’ and ‘infants’.

A total of 64 relevant articles were identified across all modalities. Overall, studies reported smaller total brain volume as well as smaller volume of both the white and grey matter in specific cortical regions. The most consistently reported structural MRI findings were alterations in the shape and volume of the corpus callosum, as well as smaller volume in the basal ganglia and hippocampi. The most consistent finding from diffusion tensor imaging studies was lower fractional anisotropy in the corpus callosum. Proton magnetic resonance spectroscopy studies are few to date, but showed altered neurometabolic profiles in the frontal and parietal cortex, thalamus and dentate nuclei. Resting-state functional MRI studies reported reduced functional connectivity between cortical and deep grey matter structures.

There is a critical gap in the literature of MRI studies in alcohol-exposed children under 5 years of age across all MRI modalities. The dynamic nature of brain maturation and appreciation of the effects of alcohol exposure on the developing trajectory of the structural and functional network argue for the prioritisation of studies that include a longitudinal approach to understanding this spectrum of effects and potential therapeutic time points.

Traumatic brain injury and stroke are among the leading causes of neurological disability worldwide. Although dopaminergic agents have long been associated with improvement of neuropsychiatric outcomes, to date much of the evidence to date has been in case reports and case series or open label trials.

We undertook a systematic review of double-blinded randomised controlled trials (RCT) to determine the effect of dopaminergic agents on pre-defined outcomes of (a) apathy; (b) psychomotor retardation; (c) behavioural management and (d) cognitive function. Databases searched were: Medline, EMBASE, and PsychInfo for human studies. The Cochrane Clinical Trials Database and the TRIP Medical database were also searched. All identified studies, were further hand-searched.

We identified six studies providing data on 227 participants, 150 of whom received dopaminergic therapy. Trials were compromised by cross-over design, inadequate wash out period, small numbers and heterogeneous outcome measures. However one good quality RCT demonstrates the efficacy of amantadine in behavioural management. One further RCT shows methylphenidate-levodopa is efficacious for mood post-stroke. One study shows rotigotine to improve hemi-inattention caused by prefrontal damage.

Our systematic review demonstrates an evolving evidence base to suggest some benefits in agitation and aggression, mood and attentional deficits. However, there are key limitations of the studies undertaken to date involving small numbers of participants, heterogeneous outcome measures, and variable study designs. There is a need for on-going large prospective double-blind RCTs in these medications using standardised criteria and outcomes to fully understand their effectiveness in this patient group.

The aim of this study was to evaluate the predictive validity of the apathy subsyndrome in patients with therapy-resistant depression in the dose–remission study with transcranial pulsating electromagnetic fields (T-PEMF).

The apathy subsyndrome consists of the symptoms of fatigue, concentration and memory problems, lack of interests, difficulties in making decisions, and sleep problems. We evaluated 65 patients with therapy-resistant depression. In total, 34 of these patients received placebo T-PEMF in the afternoon and active T-PEMF in the morning, that is, one daily dose. The remaining 31 patients received active T-PEMF twice daily. Duration of treatment was 8 weeks in both groups. The Hamilton Depression Scale (HAM-D17) and the Bech-Rafaelsen Melancholia Scale (MES) were used to measure remission. We also focused on the Diagnostic Apathia Scale, which is based on a mixture of items from the MINI and the HAM-D17/MES.

In patients without apathy, the remission rate after T-PEMF was 83.9% versus 58.8% in patients with apathy (p≤0.05). In patients without apathy receiving one active dose daily 94.4% remitted versus 50% for patients with apathy (p≤0.05). In patients without apathy who received two active doses 69.9% remitted versus 66.7% for patients with apathy (p≤0.05).

Taking the baseline diagnosis of the apathy syndrome into consideration, we found that in patients without apathy one daily dose of T-PEMF is sufficient, but in patients with apathy two daily doses are necessary. Including the apathy syndrome as predictor in future studies would seem to be clinically relevant.

Neuroimaging studies have indicated that prenatal alcohol exposure is associated with alterations in the structure of specific brain regions in children. However, the temporal and regional specificity of such changes and their behavioural consequences are less known. Here we explore the integrity of regional white matter microstructure in infants with in utero exposure to alcohol, shortly after birth.

Twenty-eight alcohol-exposed and 28 healthy unexposed infants were imaged using diffusion tensor imaging sequences to evaluate white matter integrity using validated tract-based spatial statistics analysis methods. Second, diffusion values were extracted for group comparisons by regions of interest. Differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity were compared between groups and associations with measures from the Dubowitz neonatal neurobehavioural assessment were examined.

Lower AD values (p<0.05) were observed in alcohol-exposed infants in the right superior longitudinal fasciculus compared with non-exposed infants. Altered FA and MD values in alcohol-exposed neonates in the right inferior cerebellar were associated with abnormal neonatal neurobehaviour.

These exploratory data suggest that prenatal alcohol exposure is associated with reduced white matter microstructural integrity even early in the neonatal period. The association with clinical measures reinforces the likely clinical significance of this finding. The location of the findings is remarkably consistent with previously reported studies of white matter structural deficits in older children with a diagnosis of foetal alcohol spectrum disorders.

This paper aims to review the available evidence for the use of clozapine and electroconvulsive therapy (ECT) in combination.

Electronic searches were carried out to identify reports describing the combined use of clozapine and ECT.

Forty reports including 208 patients were identified. The majority of reports were in the form of case reports and case series, with few retrospective and open-label studies. The majority of patients were aged between 18 and 65 years and diagnosed with schizophrenia or schizoaffective disorder. Most of the patients refractory to clozapine were started on ECT as an augmentation therapy; however, in some reports, both ECT and clozapine were started concurrently, and in few cases clozapine was started after ECT. In terms of effectiveness, 37.5–100% patients improved in short-term, and sustained long-term improvement (3 weeks to 24 months) was described in few studies. In terms of the side-effect profile, five patients each had delirium and tachycardia and only four patients were described to have prolonged seizures. Overall, the combination was considered effective and safe.

There is evidence for the effectiveness and safety of the clozapine–ECT combination and it should be used in patients with treatment-resistant schizophrenia who do not respond to clozapine.

Brain-derived neurotrophic factor (BDNF) plays an important role in neural survival and was proposed to be related to psychiatric disorders. Val66Met (also known as rs6265 or G196A), the only known functional polymorphism of the BDNF gene, has been widely studied and considered to be associated with risk of some psychiatric disorders such as bipolar disorder and schizophrenia. However, studies evaluating its association with obsessive–compulsive disorder (OCD) obtained inconsistent results. The purpose of this study was to derive a more precise estimation of the association between BDNF Val66Met polymorphism and OCD susceptibility by a meta-analysis.

We carried a structured literature search in PubMed, Embase, PsycINFO and Chinese Biomedical Database up to December 2014; and retrieved all eligible case–control studies according to the including criteria. Meta-analysis was performed for four genetic models: allelic model: Met versus Val; additive model: Met/Met versus Val/Val; recessive model: Met/Met versus Val/Val+Val/Met; and dominant model: Val/Met+Met/Met versus Val/Val. Stratified analyses were performed by ethnicity and gender where appropriate.

A total of eight articles with nine studies including 1632 OCD cases and 2417 controls were identified. No significant association was detected in any comparison when the whole data were pooled together or stratified by ethnicity or gender in all four genetic models (p>0.05 for each comparison).

Despite some limitations, our meta-analysis suggests that no significant association exists between the BDNF Val66Met polymorphism and OCD susceptibility.

Disability is associated with increasing age and poverty, yet there are few reliable data regarding disability amongst the elderly in low-income countries. The aim of this study was to compare disability levels for three of the most common neurological, non-communicable diseases: dementia, stroke and Parkinson’s disease (PD).

We performed a community-based study of people aged 70 years and over in 12 randomly selected villages in the rural Hai district of Tanzania. Participants underwent disability assessment using the Barthel Index, and clinical assessment for dementia, stroke and PD.

In a representative cohort of 2232 people aged 70 years and over, there were 54 cases of stroke, 12 cases of PD and estimated (by extrapolation from a sub-sample of 1198 people) to be 112 cases of dementia. People with stroke were the most disabled, with 62.9% having moderate or severe disability. Levels of moderate or severe disability were 41.2% in people with dementia and 50.0% in people with PD. However, the higher prevalence of dementia meant that, at a population level, it was associated with similar levels of disability as stroke, with 18.5% of 249 people identified as having moderate or severe disability having dementia, compared to 13.7% for stroke and 2.4% for PD.

Levels of disability from these conditions is high and is likely to increase with demographic ageing. Innovative, community-based strategies to reduce disability levels should be investigated.

Although severe hoarding symptoms have been considered rare among obsessive-compulsive disorder (OCD) samples, the prevalence of animal hoarding in OCD is unknown. To help clarifying this issue, we searched for cases of animal hoarding among patients attending a university OCD clinic (n=420).

Chart review.

Only two patients from our sample exhibited animal hoarding (<0.5%) and only one of them presented additional obsessive-compulsive symptoms. Both cases also collected inanimate objects, presented low insight, exhibited poor response to serotonin reuptake inhibitors and did not adhere to therapy.

There seems to be a lack of relationship between animal hoarding and OCD. However, further studies with larger numbers of patients are needed to better define their psychopathological profile and more appropriate nosological insertion.

Anxiety often co-occurs with major depressive disorder (MDD). This preliminary study sought to ascertain the extent to which anxious depression drives group neurobiological differences between patients with MDD and healthy volunteers (HVs).

Magnetoencephalography beta-band frequency was used to compare differences in brain response during the N-back working memory task between 30 medication-free patients with treatment-resistant MDD (anxious depression=18; nonanxious depression=12) and 28 HVs.

Compared to HVs, patients with anxious depression had significantly reduced desynchronisation (less activation) in the left precuneus, right cuneus, and left insula extending into the inferior and middle frontal cortex during the 2-back condition compared with the 1-back condition of the N-back working memory task – indicating less activation of these neural networks in patients with anxious depression during the condition with the highest level of task demands. No other significant group differences were found during the working memory conditions.

This preliminary study suggests that a subset of patients – those with anxious depression – may be driving observed group differences between patients with MDD and HVs. Further neurobiological studies and replication experiments are necessary to determine the extent to which this subgroup has preferentially influenced our understanding of the underlying neurobiology of depression.

We undertook a non-targeted lipidomics analysis of post-mortem cerebrospinal fluid (CSF), frontal cortex grey matter, and subjacent white matter to define potential biomarkers that distinguish cognitively intact subjects from those with incipient or established dementia. Our objective was to increase our understanding of the role of brain lipids in pathophysiology of aging and age-related cognitive impairment.

Levels of 650 individual lipids, across 26 lipid subclasses, were measured utilising a high-resolution mass spectrometric analysis platform.

Monoacylglycerols (MAG), diacylglycerols (DAG), and the very-long-chain fatty acid 26:0 were elevated in the grey matter of the mild cognitive impairment (MCI) and old dementia (OD) cohorts. Ethanolamine plasmalogens (PlsEtn) were decreased in the grey matter of the young dementia (YD) and OD cohorts while and phosphatidylethanolamines (PtdEth) were lower in the MCI, YD and OD cohorts. In the white matter, decrements in sulphatide levels were detected in the YD group, DAG levels were elevated in the MCI group, and MAG levels were increased in the YD and OD groups.

The parallel changes in grey matter MAGs and DAGs in the MCI and OD groups suggest that these two cohorts may have a similar underlying pathophysiology; consistent with this, MCI subjects were more similar in age to OD than to YD subjects. While PlsEtn and phosphatidylethanolamine were decreased in the YD and OD groups they were unaltered in the MCI group indicating that alterations in plasmalogen synthesis are unlikely to represent an initiating event in the transition from MCI to dementia.

This study investigated the ability of the Audio Recorded Cognitive Screen (ARCS) to detect cognitive deficit in individuals with schizophrenia, relative to the Mini Mental State Examination (MMSE) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and explored the associations between the ARCS and functional outcomes. We hypothesised that the ARCS would be able to better discriminate between individuals with schizophrenia and healthy controls than the MMSE, and that ARCS performance would be correlated with measures of social and vocational functioning.

The participants were 19 community-dwelling individuals with schizophrenia or schizoaffective disorder and 19 healthy controls recruited from the Australian Schizophrenia Research Bank (ASRB). Participants completed the ARCS, MMSE, and self-report measures of social and vocational functioning. Clinical and diagnostic data stored by the ASRB were also utilised.

The schizophrenia group performed worse than the control group on the ARCS, with memory, t(36)=2.49, p=0.02, 95% CI [−1.84, −18.79] and fluency, t(36)=2.40, p=0.02, 95% CI [−1.87, −22.24] domains being the main discriminating measures. The RBANS also discriminated between the two groups, and ARCS and RBANS total scores were moderately to strongly correlated. There was no difference between the two groups on the MMSE after controlling for demographic variables. ARCS performance was associated with employment status [χ2(1)=7.16, p=0.007].

The ARCS may be sensitive to the cognitive deficits in outpatients with schizophrenia and an indicator of functional outcomes in this population.

Previous studies have demonstrated inconsistent findings regarding the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) in treating motor symptoms of Parkinson’s disease (PD). Therefore, this meta-analysis was conducted to assess the efficacy of low-frequency rTMS.

A comprehensive literature search (including PubMed, CCTR, Embase, Web of Science, CNKI, CBM-disc, NTIS,EAGLE, Clinical Trials, Current Controlled Trials, International Clinical Trials Registry) was conducted dating until June 2014. The key search terms (‘Parkinson’, ‘PD’, ‘transcranial magnetic stimulation’, ‘TMS’, ‘RTMS’ and ‘noninvasive brain stimulation’) produced eight high-quality randomised controlled trials (RCT) of low-frequency rTMS versus sham stimulation.

These eight studies, composed of 319 patients, were meta-analysed through assessment of the decreased Unified Parkinson’s Disease Rating Scale (UPDRS part III) score. Pooling of the results from these RCTs yielded an effect size of −0.40 (95%CI=−0.73 to −0.06, p<0.05) in UPDRS part III, which indicated that low-frequency rTMS could have 5.05 (95%CI=−1.73 to −8.37) point decrease in UPDRS part III score than sham stimulation.

Low-frequency rTMS had a significant effect on motor signs in PD. As the number of RCTs and PD patients included here was limited, further large-scale multi-center RCTs were required to validate our conclusions.

After the discovery of ‘homocystinuria syndrome’, many studies have suggested that high blood levels of homocysteine may be associated with schizophrenia. The aim of this study was to analyse the association between hyperhomocysteinaemia and schizophrenia.

In a population of inpatients suffering from exacerbated schizophrenic disorders (N=100), we evaluated homocysteine levels the day after their admission to an acute psychiatric ward and compared it with that of a non-patient control group (N=110), matched for age and gender. We statistically analysed the correlation between homocysteine levels and selected variables: gender, age, years of illness and number of previous psychiatric admissions as well as Brief Psychiatric Rating Scale, Positive Negative Syndrome Scale and Global Assessment Functioning (GAF) Scores.

We observed elevated homocysteine levels (an increase of 7.84 µM on average per patient) in 32% of the patients, but we did not find any statistically significant difference between the homocysteine levels of our patients and controls. Hyperhomocysteinaemia presented a positive statistically significant correlation with years of illness (p<0.005) and a negative statistically significant correlation with GAF score (p<0.001), but not with other clinical variables.

Hyperhomocysteinaemia, which occurred in our schizophrenia patients with poor social and relational functioning after many years of illness, could represent an effect of altered lifestyle due to psychosis, but not a specific marker for schizophrenia.

Oxidative stress has been shown to play an important role in the pathogenesis of post-traumatic stress disorder (PTSD). Although there are some studies on oxidative stress and PTSD, there is no report available on the serum total oxidant and antioxidant status in earthquake survivors with PTSD. Therefore, this study aimed to investigate the serum total oxidant and antioxidant status in earthquake survivors with chronic PTSD.

The study group included 45 earthquake survivors with PTSD and 40 earthquake survivors without PTSD. The oxidative status was determined using the total antioxidant status and total oxidant status (TOS) measurements and by calculating the oxidative stress index (OSI).

There were no statistically significant differences in the total antioxidant status, TOS, or OSI when comparing individuals with and without PTSD (all, p>0.05). There were no correlations between Clinician-Administered PTSD Scale scores and oxidant and antioxidant stress markers (all, p>0.05).

Our results suggest that the total oxidant and antioxidant status may not affect earthquake survivors with PTSD. This is the first study to evaluate the oxidative status in earthquake survivors with PTSD. Further studies are necessary to confirm these findings.

Although poor sleep accompanies depression, it is unknown which specific sleep abnormalities precede depression. This is similarly the case for depression developing during interferon-α (IFN-α) therapy. Because vulnerability becomes evident in those who slept poorly before IFN-α, we prospectively determined which specific aspect of sleep could predict subsequent depression.

Two nights of polysomnography with quantitative electroencephalogram (EEG) were obtained in 24 adult, euthymic subjects – all subsequently treated with IFN-α for hepatitis C. Every 2 weeks, a Beck Depression Inventory-II (BDI-II) score was obtained, and the maximal increase in BDI-II from pre-treatment baseline – excluding the sleep question – was determined.

The delta sleep ratio (DSR; an index of early-night restorative delta power) was inversely associated with BDI-II increases (p<0.01), as was elevated alpha power (8–12 Hz; p<0.001). Both delta (0.5–4 Hz) and alpha power exhibited high between-night correlations (r=0.83 and 0.92, respectively). In mixed-effect repeated-measure analyses, there was an interaction between alpha power and DSR (p<0.001) – subjects with low alpha power and elevated DSR were resilient to developing depression. Most other sleep parameters – including total sleep time and percentage of time in slow wave sleep – were not associated with subsequent changes in depression.

Both high DSR and low alpha power may be specific indices of resilience. As most other aspects of sleep were not associated with resilience or vulnerability, sleep interventions to prevent depression may need to specifically target these specific sleep parameters.