Advance decision-making in mental health - Suggestions for legal reform in England and Wales.

This paper argues that existing English and Welsh mental health legislation (The Mental Health Act 1983 (MHA)) should be changed to make provision for advance decision-making (ADM) within statute and makes detailed recommendations as to what should constitute this statutory provision. The recommendations seek to enable a culture change in relation to written statements made with capacity such that they are developed within mental health services and involve joint working on mental health requests as well as potential refusals. In formulating our recommendations, we consider the historical background of ADM, similarities and differences between physical and mental health, a taxonomy of ADM, the evidence base for mental health ADM, the ethics of ADM, the necessity for statutory ADM and the possibility of capacity based 'fusion' law on ADM. It is argued that the introduction of mental health ADM into the MHA will provide clarity within what has become a confusing area and will enable and promote the development and realisation of ADM as a form of self-determination. The paper originated as a report commissioned by, and submitted to, the UK Government's 2018 Independent Review of the Mental Health Act 1983.

Validation of the PHQ-9 in a psychiatric sample.

BACKGROUND: The PHQ-9 was originally developed as a screener for depression in primary care and is commonly used in medical settings. However, surprisingly little is known about its psychometric properties and utility as a severity measure in psychiatric populations. We examined the full range of psychometric properties of the PHQ-9 in patients with a range of psychiatric disorders (i.e., mood, anxiety, personality, psychotic). METHODS: Patients (n=1023) completed the PHQ-9 upon admission and discharge from a partial hospital, as well as other self-report measures of depression, anxiety, well-being, and a structured diagnostic interview. RESULTS: Internal consistency was good (α=.87). The PHQ-9 demonstrated a strong correlation with a well-established measure of depression, moderate correlations with related constructs, a weak correlation with a theoretically unrelated construct (i.e., disgust sensitivity), and good sensitivity to change, with a large pre- to post-treatment effect size. Using a cut-off of ≥13, the PHQ-9 demonstrated good sensitivity (.83) and specificity (.72). A split-half exploratory factor analysis/confirmatory factor analysis suggested a two-factor solution with one factor capturing cognitive and affective symptoms and a second factor reflecting somatic symptoms. Psychometric properties did not differ between male and female participants. LIMITATIONS: No clinician-rated measure of improvement, and the sample lacked ethnoracial diversity. CONCLUSIONS: This first comprehensive validation of the PHQ-9 in a large, psychiatric sample supported its use as a severity measure and as a measure of treatment outcome. It also performed well as a screener for a current depressive episode using a higher cut-off than previously recommended for primary care samples.

Neonatal ultrasound results following very preterm birth predict adolescent behavioral and cognitive outcome.

This study investigated the association between different neonatal ultrasonographic classifications and adolescent cognitive, educational, and behavioral outcomes following very preterm birth. Participants included a group of 120 adolescents who were born very preterm (<33 weeks of gestation), subdivided into three groups according to their neonatal cerebral ultrasound (US) classifications: (a) normal (N = 69), (b) periventricular hemorrhage (PVH, N = 37), and (c) PVH with ventricular dilatation (PVH + DIL, N = 14), and 50 controls. The cognitive functions assessed were full-scale IQ, phonological and semantic verbal fluency, and visual-motor integration. Educational outcomes included reading and spelling; behavioral outcomes were assessed with the Rutter Parents' Scale and the Premorbid Adjustment Scale (PAS). Adolescent outcome scores were compared among the four groups. A main effect for group was observed for full-scale IQ, Rutter Parents' Scale total scores, and PAS total scores, after controlling for gestational age, socioeconomic status and gender, with the PVH + DIL group showing the most impaired scores compared to the other groups. The current results demonstrate that routine neonatal ultrasound classifications are associated with later cognitive and behavioral outcome. Neonatal ultrasounds could aid in the identification of subgroups of children who are at increased risk of neurodevelopmental problems. These at risk subgroups could then be referred to appropriate early intervention services.

The corpus callosum and empathy in adults with a history of preterm birth.

Reduced posterior corpus callosum (CC) area has been consistently observed in children and adolescents born very preterm (VPT). CC structural differences are also observed in people diagnosed with empathy disorders. This study examined empathy in relation to CC size in VPT adults and controls. CC area was manually measured for 17 VPT adults and 9 controls. Participants completed the Interpersonal Reactivity Index (Davis, 1980) and the Empathy Quotient (Baron-Cohen & Wheelwright, 2004). VPT adults had reduced posterior CC area in contrast to controls, and a positive linear trend was observed between posterior CC size and gestational age. No between-group empathy differences were observed, although self-reported personal distress in response to social situations was higher in VPT adults, and negatively associated with anterior CC area. We conclude that VPT adults have a smaller posterior CC, which is associated with gestational age, and elevated social distress, which may be mediated by anterior CC size.

Psychiatric disorder in young adults born very preterm: role of family history.

OBJECTIVE: To investigate whether young adults born very preterm (VPT) (<33 weeks) are at increased risk for psychiatric illness in adulthood and whether a family history of psychiatric disorder further increases this risk. METHODS: We assessed 169 VPT and 101 term born individuals using the Clinical Interview Schedule - Revised. RESULTS: Young adults born VPT had an increased risk for psychiatric disorder compared to controls (OR=3.1, 95% CI=1.1-8.6, p=0.03). Those born VPT who had a history of psychiatric disorder in a first-degree relative, had an increase in risk for psychiatric disorder compared to those born VPT without a family history (OR=5.2, 95% CI=1.8-14.9, p=0.002). CONCLUSION: Individuals born VPT are at increased risk of psychiatric illness in young adulthood compared to controls. In addition, a family history of psychiatric disorder in a first-degree relative may leave young adults born VPT particularly vulnerable to psychiatric illness.

Cognitive maturation in preterm and term born adolescents.

BACKGROUND: Adolescence is a critical period of brain structural reorganisation and maturation of cognitive abilities. This relatively late developmental reorganisation may be altered in individuals who were born preterm. METHODS: We carried out longitudinal neuropsychological testing in 94 very preterm individuals (VPT; before 33 weeks' gestation) and 44 term born individuals at mean ages of 15.3 years (adolescence) and 19.5 years (young adulthood). RESULTS: Full scale, verbal and performance IQ and phonological verbal fluency were significantly lower in the VPT group than the term group at both ages. Repeated measures ANOVA showed only one group by time point interaction for semantic verbal fluency (F = 10.25; df = 107; p = 0.002). Paired-sample t tests showed that semantic verbal fluency increased significantly in the term group over adolescence (t = -5.10; df = 42; p<0.001), but did not increase in the VPT group (t = 0.141; df = 69; p = 0.889). For verbal IQ, there was a significant interaction between time point and sex (F = 4.48; df = 1; p = 0.036) with paired-sample t tests showing that verbal IQ decreased in males between adolescence and adulthood (t = 3.35; df = 71; p = 0.001), but did not change significantly in females (t = 0.20; df = 52; p = 0.845). CONCLUSION: Decrements of intellectual functioning in VPT individuals persist into adulthood. Additionally, there is a deficit in the adolescent maturation of semantic verbal fluency in individuals born VPT.

Neurological abnormalities in young adults born preterm.

OBJECTIVE: Individuals born before 33 weeks' gestation (very preterm, VPT) have an increased likelihood of neurological abnormality, impaired cognitive function, and reduced academic performance in childhood. It is currently not known whether neurological signs detected in VPT children persist into adulthood or become attenuated by maturation of the CNS. METHOD: We assessed 153 VPT individuals and 71 term-born controls at 17-18 years old, using a comprehensive neurological examination. This examination divides neurological signs into primary and integrative domains, the former representing the localising signs of classical neurology, and the latter representing signs requiring integration between different neural networks or systems. Integrative signs are sub-divided into three groups: sensory integration, motor confusion, and sequencing. The VPT individuals have been followed up since birth, and neonatal information is available on them, along with the results of neurological assessment at 4 and 8 years of age and neuropsychological assessment at 18 years of age. RESULTS: The total neurology score and primary and integrative scores were significantly increased in VPT young adults compared to term-born controls. Within the integrative domain, sensory integration and motor confusion scores were significantly increased in the VPT group, but sequencing was not significantly different between the VPT and term groups. Integrative neurological abnormalities at 18 were strongly associated with reduced IQ but primary abnormalities were not. CONCLUSIONS: Neurological signs are increased in VPT adults compared to term-born controls, and are strongly associated with reduced neuropsychological function.

Diabetic keto-acidotic (DKA) coma following olanzapine initiation in a previously euglycaemic woman and successful continued therapy with olanzapine.

We report the case of a euglycaemic woman whose glucose control rapidly decompensated following olanzapine initiation leading to diabetic coma. Hyperglycaemia has been associated with chronic psychotic disorders and antipsychotics for many years. However, it is unusual to see such rapid and life-threatening changes associated with treatment. The case highlights that changes in antipsychotic treatment may be associated with large changes in glucose tolerance, and that it is possible to continue antipsychotic treatment with appropriate diabetic care.

The neurodevelopmental progress of infants less than 33 weeks into adolescence.

BACKGROUND: Several studies have shown an increased incidence of neurodevelopmental impairment in very preterm survivors at school age compared with controls. AIM: To compare findings in the same cohort at 8 years and 15 years. METHODS: A total of 151 of the 224 eligible infants born before 33 weeks of gestation from 1979 to 1982, and who were living in the UK, were assessed at 8 and 15 years. Items common to both assessments were compared to evaluate changes in neurodevelopmental function. The assessment included a structured neurological examination, psychometric tests using the WISC-R (in subjects born in 1981-82), a test of visuomotor integration (Beery), and a school questionnaire. RESULTS: There was a significant increase in the proportion of subjects classified as impaired with disability from 11% at 8 to 22% at 14-15 years of age. The proportion of subjects classified as impaired without disability increased from 16% at 8 to 26% at 14-15 years of age. Full scale IQ decreased from 104 to 95 from childhood to adolescence, and more adolescents (24%) were requiring extra educational provision than they had at the age of 8 years (15%). CONCLUSION: Results indicate that between the ages of 8 and 15 years in this cohort of very preterm survivors there is an apparent deterioration in neurodevelopmental outcome category, cognitive function, and extra educational support. It is not clear whether this represents a genuine deterioration in neurocognitive function or whether it represents the expression of pre-existing cerebral pathology in an increasingly complex environment.

Lateralisation of language function in young adults born very preterm.

OBJECTIVE: To explore, using functional magnetic resonance imaging (MRI), the functional organisation of phonological processing in young adults born very preterm. SUBJECTS: Six right handed male subjects with radiological evidence of thinning of the corpus callosum were selected from a cohort of very preterm subjects. Six normal right handed male volunteers acted as controls. METHOD: Blood oxygenation level dependent contrast echoplanar images were acquired over five minutes at 1.5 T while subjects performed the tasks. During the ON condition, subjects were visually presented with pairs of non-words and asked to press a key when a pair of words rhymed (phonological processing). This task alternated with the OFF condition, which required subjects to make letter case judgments of visually presented pairs of consonant letter strings (orthographic processing). Generic brain activation maps were constructed from individual images by sinusoidal regression and non-parametric testing. Between group differences in the mean power of experimental response were identified on a voxel wise basis by analysis of variance. RESULTS: Compared with controls, the subjects with thinning of the corpus callosum showed significantly reduced power of response in the left hemisphere, including the peristriate cortex and the cerebellum, as well as in the right parietal association area. Significantly increased power of response was observed in the right precentral gyrus and the right supplementary motor area. CONCLUSIONS: The data show evidence of increased frontal and decreased occipital activation in male subjects with neurodevelopmental thinning of the corpus callosum, which may be due to the operation of developmental compensatory mechanisms.

Functional imaging of the mechanisms underlying the bilateral field advantage.

Visual stimulus comparisons across the vertical meridian are faster and more accurate than those restricted to a single hemifield (the bilateral field advantage). We set out to investigate the cerebral mechanisms underlying this effect using functional magnetic resonance imaging. Seven normal volunteers were presented pairs of shape stimuli bilaterally across the vertical meridian and unilaterally within a single hemifield. We found a network of additional areas activated in the unilateral condition over the bilateral condition which have been related to working memory in previous studies. The results suggest different processing strategies with different temporal characteristics in the bilateral and unilateral conditions, providing a novel explanation for the bilateral field advantage.

The functional significance of perinatal corpus callosum damage: an fMRI study in young adults.

We used functional MRI (fMRI) to establish the functional significance of corpus callosum damage in young adults who had been born very preterm. Seven subjects from a cohort of individuals who had been born at <33 weeks gestation and who had sustained callosal damage visualized on structural MRI were compared while they carried out auditory and visual tasks requiring callosal transfer with nine very preterm subjects with corpora callosa of normal appearance on structural MRI, and with seven full-term controls. The very preterm subjects with damaged corpora callosa had significantly different activation patterns compared with the two control groups. In the visual task, additional activity was seen in the right dorsolateral prefrontal cortex of the damaged callosum group, possibly because the task was accomplished by storing information in working memory. On the auditory task, a deficit of activity was seen in the right temporal lobe of the callosum group. The findings reveal a plasticity of function compensating for early damage to the corpus callosum.

Neurodevelopmental status at 1 year predicts neuropsychiatric outcome at 14-15 years of age in very preterm infants.

BACKGROUND: Neurodevelopmental and behavioural problems have been repeatedly reported in very preterm survivors, often showing themselves later in childhood as poor school performance. Early identification of problems would mean that appropriate remedial therapy can be implemented. We have previously shown that neurodevelopmental status at 1 year was predictive of outcome at 8 years in a cohort of preterm infants. The aim of this paper was to see if neurodevelopmental outcome in adolescence could be predicted by assessment by 1 year in the same cohort of preterm infants. STUDY DESIGN: Prospective cohort study. SUBJECTS: 150 adolescents, born before 33 weeks gestation. OUTCOME MEASURES: Neurological examination, developmental quotient, vision and hearing by 1 year. At 14-15 years, neurological examination, school performance questionnaire, Schonnell test of reading age, a premorbid adjustment score, Rutter behavioural score and for those born from 1981, cognitive tests (WISC-R). RESULTS: A highly significant relationship existed between neurological status by 1 year and the need for extra educational provision, overall neurodevelopmental status, cognitive function in those that had their IQs measured and premorbid adjustment score of prepsychotic symptoms in adolescence. However, status at 1 year was not predictive of adolescent reading age or behavioural score. CONCLUSIONS: Neurodevelopmental assessment at 1 year is predictive of school performance and outcome in the adolescent period.

Neuropsychological outcome at adolescence of very preterm birth and its relation to brain structure.

Neuropsychological outcome at 14 to 15 years of age of a cohort of 75 participants (39 male, 36 female) born at <33 weeks' gestation was investigated. Research was conducted parallel to a recent MRI study by Stewart and colleagues which reported that 55% of this cohort had evidence of brain abnormality. One aim of the study was to compare neuropsychological function in those very preterm children with and without MRI abnormality. Compared to a control sample of term adolescents, very preterm participants had impairment only on a measure of word production. On measures of attention, memory, perceptual skill, and visuomotor and executive function, the adolescents born very preterm performed in the normal range, whether or not they had evidence of MRI abnormality. Our findings are encouraging as the neuropsychological consequences of damage to the very preterm brain, still evident on MRI at 14 to 15 years of age, appear to be minor.

Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term.

Individuals born before 33 weeks' gestation are at risk of brain lesions, which have the potential to disrupt subsequent neurodevelopment. As a result they manifest an increased incidence of neuromotor signs and cognitive deficits, which can still be detected in adolescence. The cerebellum is known to be involved in both the co-ordination of movement and in cognitive processes. We therefore set out to establish whether cognitive and motor impairments in adolescents born very pre-term are associated with abnormalities of the cerebellum as revealed by volumetric analysis of brain MRI scans. The volume of the whole cerebellum was determined manually using a PC-based Cavalieri procedure in 67 adolescents born very pre-term and 50 age-matched, full-term born controls. Cognitive and neurological assessments were performed at 1, 4, 8 and 14-15 years of age as part of the long-term follow-up of the pre-term subjects. The pre-term-born subjects had significantly reduced cerebellar volume compared with term-born controls (P<0.001). This difference was still present after controlling for potential confounders. There was no association between cerebellar volume and motor neurological signs. However, there were significant associations between cerebellar volume and several cognitive test scores, in particular the Wechsler Intelligence Scale for Children-Revised, the Kaufman Assessment Battery for Children and the Schonnel reading age. This provides further evidence implicating the cerebellum in cognition and suggests that cerebellar abnormalities may underlie some of the cognitive deficits found in individuals born very pre-term.

Brain structure and neurocognitive and behavioural function in adolescents who were born very preterm.

BACKGROUND: Infants born very preterm (<33 weeks) are at increased risk of neurocognitive deficits. Their neurodevelopmental outcome up to age 8 years can be predicted by neonatal ultrasonography, but little is known of their later function. We investigated the effect of very preterm birth on brain structure and neurocognitive and behavioural functioning in adolescence. METHODS: A cohort of 105 infants born before 33 weeks of gestation in 1979-80 had ultrasonographic scans at University College Hospital, London, and were prospectively examined at 1, 4, and 8 years. At age 14-15 years, 72 of those who remained in UK (cases) and 21 age-matched full-term controls underwent brain magnetic resonance imaging (MRI), as well as neurological, cognitive, and behavioural assessment. MRI images were assessed by two neuroradiologists unaware of ultrasonographic findings or case or control status. FINDINGS: Of the 72 cases, 40 had unequivocally abnormal MRI and 15 had equivocal scans. Of the 21 controls, one had abnormal and five equivocal MRI. Abnormalities of ventricles, corpus callosum, and white matter were especially common in cases. More brain lesions were identified by MRI than by neonatal ultrasonography. The cases had significantly more reading, adjustment, and neurological impairments than controls, but their behaviour was significantly related to MRI abnormality. INTERPRETATION: Individuals born very preterm show an excess of neurocognitive and behavioural problems in adolescence, and more than half have abnormal MRI brain scans.

A pneumatic device for rapid loading of DNA sequencing gels.

This work describes the design and construction of a device that facilitates the loading of DNA samples onto polyacrylamide gels for detection in the Perkin Elmer/Applied Biosystems (PE/ABI) 373 and 377 DNA sequencing instruments. The device is mounted onto the existing gel cassettes and makes the process of loading high-density gels less cumbersome while the associated time and errors are reduced. The principle of operation includes the simultaneous transfer of the entire batch of samples, in which a spring-loaded air cylinder generates positive pressure and flexible silica capillaries transfer the samples. A retractable capillary array carrier allows the delivery ends of the capillaries to be held up clear of the gel during loader attachment on the gel plates, while enabling their insertion in the gel wells once the device is securely mounted. Gel-loading devices capable of simultaneously transferring 72 samples onto the PE/ABI 373 and 377 are currently being used in our production sequencing groups while a 96-sample transfer prototype undergoes testing.

Premorbid social functioning in schizophrenia and bipolar disorder: similarities and differences.

OBJECTIVE: This research examined social functioning in childhood and adolescence among patients with schizophrenia and patients with bipolar disorder compared with healthy subjects and investigated the relation between premorbid adjustment and risk factors for psychosis. METHOD: Maternal recall was used to assess the premorbid adjustment of patients with schizophrenia (N = 70) and patients with bipolar disorder (N = 28) recruited from a survey of consecutive hospital admissions for psychosis and of healthy comparison subjects (N = 100) drawn from the same catchment area. RESULTS: The patients with schizophrenia had significantly poorer premorbid adjustment in childhood and adolescence than the comparison subjects and were impaired in both sociability and school adjustment. The patients with bipolar disorder exhibited poorer social impairment in adolescence than the comparison subjects, though to a lesser degree than the schizophrenic subjects, but functioned well at school. There were significant linear trends in the risk of psychosis with worsening premorbid functioning, which was most marked in the schizophrenic group, and a specific linear relation between low birth weight and poor premorbid adjustment among the schizophrenic patients. CONCLUSIONS: Impaired premorbid social functioning is not specific to schizophrenia and is seen also in bipolar disorder. The data support the view that poor premorbid social adjustment is one manifestation of vulnerability to adult psychotic disorders. These results are consistent with other findings pointing to early developmental deficits in patients who subsequently develop psychosis.

Linkage analysis of manic depression (bipolar affective disorder) in Icelandic and British kindreds using markers on the short arm of chromosome 18.

Attempts were made to follow up results of a previous linkage study which suggested that a locus-modifying susceptibility to bipolar and related unipolar affective disorder might be present in the pericentromeric region of the short arm of chromosome 18. Twenty-three multiply affected pedigrees collected from Iceland and the UK were genotyped using three highly polymorphic microsatellite markers at D18S37, D18S40 and D18S44 which span the region implicated. Lod score analyses under the assumption of heterogeneity and non-parametric linkage analyses were performed. The total lod scores obtained were strongly negative, and analysis allowing for heterogeneity did not suggest that any subgroup of the families was linked. Model-free linkage analysis using extended relative pair analysis and MFLINK also failed to detect any evidence for linkage. Our study provides no support for the presence of a locus-modifying genetic susceptibility to bipolar affective disorder in the pericentromeric region of chromosome 18q11. Further analyses in independent samples should help to reveal whether our negative results are due to locus heterogeneity or whether the original results were false-positive.