Exploring Comorbid Bipolar Disorder and Autism

AimsDysregulated behaviours are prevalent amongst young people worldwide. Emotional dysregulation plays a key role in these behaviours. Several psychiatric disorders have significant elements of emotional dysregulation, making it a potentially effective transdiagnostic therapeutic target. Dialectical behaviour therapy (DBT), mentalisation-based therapy (MBT), and schema therapy (ST) can effectively manage emotional dysregulation, however access may be limited in clinical practice.We aimed to explore whether young people with emotional dysregulation engaging in dysregulated behaviours receive support for emotion regulation. We hypothesised that those with emotionally unstable personality disorder (EUPD) will have a higher prevalence of self-harm, disordered eating, and/or substance misuse and more referrals for DBT, MBT, or ST than those with bipolar disorder, autism, attention deficit/hyperactivity disorder (ADHD), schizophrenia, or schizoaffective disorder.MethodsDe-identified clinical records from the West London NHS Trust on 2,413 16- to 25-year-olds with an ICD–10 diagnosis of EUPD, bipolar disorder, autism, ADHD, schizophrenia, and/or schizoaffective disorder were obtained through Akrivia. Chi-squared tests were performed.ResultsYoung people with bipolar disorder had the highest prevalence of self-harm, disordered eating, and substance misuse (88.35%, n = 182), χ2 (4, N = 3138) = 39.14, p < 0.001, but the lowest number of references to DBT, MBT, or ST. Those with EUPD had the highest number of references to DBT, χ2 (4, N = 2585) = 886.75, p < 0.001, MBT, χ2 (4, N = 2585) = 81.63, p < 0.001, or ST, LR (4, N = 2585) = 21.03, p < 0.001.ConclusionThere could be an unmet need for psychological interventions for young people with bipolar disorder. A more transdiagnostic approach to offering psychotherapies that target emotional dysregulation should be applied in clinical practice.

BackgroundEmerging evidence suggests that fast-spiking (FS) interneurons are disrupted in multiple neuropsychiatric disorders including autism, schizophrenia, and bipolar disorder. FS cells, which are the primary source of synaptic inhibition, are critical for temporally organizing brain activity, regulating brain maturation, and modulating critical developmental periods in multiple cortical systems. Reduced expression of parvalbumin, a marker of mature FS cells, has been reported in individuals with schizophrenia and bipolar disorder and in mouse models of schizophrenia and autism. Although these results suggest that FS cells may be immature in neuropsychiatric disease, this possibility had not previously been formally assessed.MethodsThis study used time-course global expression data from developing FS cells to create a maturation index that tracked with the developmental age of purified cortical FS cells. The FS cell maturation index was then applied to global gene expression data from human cortex to estimate the maturity of the FS cell developmental program in the context of various disease states. Specificity of the index for FS cells was supported by a highly significant correlation of maturation index measurements with parvalbumin expression levels that withstood correction for multiple covariates.ConclusionsResults suggest the FS cell developmental gene expression program is immature in autism, schizophrenia, and bipolar disorder. More broadly, the current study indicates that cell-type specific maturation indices can be used to measure the maturity of developmental programs even in data from mixed cell types such as those found in brain homogenates.

Does the course of manic symptoms in pediatric bipolar disorder impact the course of conduct disorder? Findings from four prospective datasets

The onset of severe, chronic or recurrent psychiatric illnesses, such as schizophrenia-spectrum and bipolar disorders, is a dramatic clinical event often detectable during adolescence and even in childhood. At any age, pharmacotherapy, along with enhancement of social skills and family support, is the mainstay for the management of such disorders. The aim of this review is to critically analyze findings from randomized controlled trials (RCTs) that have investigated the clinical utility of second-generation antipsychotics (SGAs) for the treatment of early-onset schizophrenia and bipolar disorders. Eighteen studies were considered, all of which were unfortunately impaired by methodologic limitations, such as the paucity of long-term data and lack of a three-arm comparison (SGA vs SGA vs placebo). Nevertheless, the results of this review allow us to suggest the effectiveness of three SGAs (aripiprazole, olanzapine, and risperidone) in the short-term treatment of both early-onset schizophrenia and bipolar mania, although such agents show different safety profiles. The use of clozapine should be strictly limited to patients with non-affective, psychotic symptoms who do not respond to any of these three SGAs. In contrast, the use of quetiapine and ziprasidone in young patients with either affective or non-affective psychosis is not yet supported by evidence-based information. Given our findings, further studies are urgently required to identify the best treatment option(s) for pediatric bipolar disorder (especially the depressive phase) and the long-term management of early-onset schizophrenia.

Back to table of contents Previous article Next article EditorialsFull AccessBipolar Disorder Treatment: An Evidence-Based Reality CheckJ. Raymond DePaulo Jr., M.D.J. Raymond DePaulo Jr.Search for more papers by this author, M.D.Published Online:1 Feb 2006https://doi.org/10.1176/appi.ajp.163.2.175AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Results from the largest treatment study of bipolar disorder ever performed, the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), are presented in this issue by Perlis et al. The authors report that just over one-half of their bipolar patients achieved full remission during the 2-year study and that almost one-half of these recovered patients relapsed at least once before the end of the study. They conclude that “these results suggest that in spite of modern evidence-based treatment, bipolar disorder remains a highly recurrent, predominantly depressive illness.” The STEP-BD data reported here are not the usual comparative assessment of treatments in a homogeneous sample of patients (i.e., an efficacy study). As a study carried out in a broadly representative sample of patients, it is an effectiveness study, and it describes a full 2 years of treatment. In addition, this study employed a “best-treatment-available” rather than a “treatment-as-usual” protocol, so I would call it an “effectiveness-plus” study. Nonetheless, the results are so similar to those observed in lithium treatment studies reported 20 to 35 years ago (1–5) that the question of whether today’s best treatments available for bipolar disorder are better than older treatment begs for an answer. Although not ideal, these outcomes are better than those reported by other large effectiveness studies of schizophrenia (the Clinical Antipsychotic Trials of Intervention Effectiveness [CATIE] [6]) and of major depression (Sequenced Treatment Alternatives to Relieve Depression [STAR*D] [7]). The three studies taken together, however, underline the suggestion that modern pharmacological treatments may be no more beneficial than older ones, despite their added cost.The authors also report that the relapses in their sample were strongly correlated with residual symptoms of depression or mania. And they suggest that if clinicians were to target residual symptoms, the overall treatment results for bipolar patients might improve. However, given the rigorous assessment and treatment protocols of the STEP-BD, which includes both psychological and pharmacological interventions, these symptoms already were the primary targets of the clinicians. It is not at all clear therefore whether clinicians could get better results with the treatments now available to them. So what should our field do today to address the needs of patients with bipolar disorder who have residual, chronic, or relapsing symptoms?Three articles in this issue (two by Perlis et al. and one by Lin et al.) point us toward logical places to look for help. Perlis et al. (in this issue), in a symptomatic comparison of depression in patients with unipolar and bipolar disorders, show, as have earlier studies, that many patients initially diagnosed and treated for depression later turn out to have bipolar disorder. Although not firmly established in the literature, if treatment of bipolar illness occurred earlier in its course, remission rates might improve. Indeed, patients might do better not only in symptomatic terms but also in social development. The diagnosis of bipolar disorder, which regularly begins in late adolescence (8; Perlis et al. in this issue), is often delayed for a decade (9). The illness is a significant hurdle on the path to normal adulthood, and delayed treatment can only make it harder to overcome.A third article in this issue, by Lin et al., on the clustering of age at onset in families as a marker of genetic heterogeneity reminds us that we still do not understand this largely genetic illness—from its origins, its molecular pathogenesis, or its pathophysiology. The sine qua non of translational research is that we must have some basic science findings in bipolar disorder to translate, i.e., to create rational treatment advances.Because we already have modestly effective, albeit empirical, treatments for bipolar disorder, we might not have to wait for decades after genes and pathways are illuminated to develop treatments, as is contemplated for Alzheimer’s and Huntington’s disease. Translatable clues to the biology of bipolar disorder could make today’s treatments much more effective by directing treatments to the patients who can best respond to them. The results of the STEP-BD study argue strongly that genetic, brain imaging, and neurobiological studies of bipolar disorder must be accelerated to help define who will respond best to which treatments in the long term. What seems clear from STEP-BD and the other major treatment studies is that we must provide clinicians and our patients with substantially better treatment options than are now available.Address correspondence and reprint requests to Dr. DePaulo, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 4-113, Baltimore, MD 21287-7413; [email protected] (e-mail).

Improving and assessing public beliefs, knowledge and attitudes towards bipolar disorder in Pakistan

Background:Bipolar disorder (BD) is a cyclic mood disorder characterised by alternating episodes of mania/hypomania and depression interspersed with euthymic periods. Lamotrigine (LTG) demonstrated some mood improvement in patients treated for epilepsy, leading to clinical studies in patients with BD and its eventual introduction as maintenance therapy for the prevention of depressive relapse in euthymic patients. Most current clinical guidelines include LTG as a recommended treatment option for the maintenance phase in adult BD, consistent with its global licencing status.Aims:To review the evidence for the efficacy and safety of LTG in the treatment of all phases of BD.Methods:PubMed was searched for double-blind, randomised, placebo-controlled trials using the keywords: LTG, Lamictal, ‘bipolar disorder’, ‘bipolar affective disorder’, ‘bipolar I’, ‘bipolar II’, cyclothymia, mania, manic, depression, depressive, ‘randomised controlled trial’, ‘randomised trial’, RCT and ‘placebo-controlled’ and corresponding MeSH terms. Eligible articles published in English were reviewed.Results:Thirteen studies were identified. The strongest evidence supports utility in the prevention of recurrence and relapse, particularly depressive relapse, in stabilised patients. Some evidence suggests efficacy in acute bipolar depression, but findings are inconsistent. There is little or no strong evidence in support of efficacy in acute mania, unipolar depression, or rapid-cycling BD. Few controlled trials have evaluated LTG in bipolar II or in paediatric patients. Indications for safety, tolerability and patient acceptability are relatively favourable, provided there is slow dose escalation to reduce the probability of skin rash.Conclusion:On the balance of efficacy and tolerability, LTG might be considered a first-line drug for BD, except for acute manic episodes or where rapid symptom control is required. In terms of efficacy alone, however, the evidence favours other medications.

Bipolar Spectrum Disorder: Differential Diagnosis and Treatment

To the Editor: Frederick Goodwin, an influential figure in bipolar mood disorder, famously said, if you can't, or you won't use lithium, get out from the business of treating bipolar disorders! Lithium remains the gold standard treatment of bipolar mood disorder. But, sorely, it is underutilized in Child/Adolescent Psychiatry, despite Food and Drug Administration's approval for age 12 and above. Recently, Findling et al.[1] conducted the first randomized controlled trial for lithium in juvenile bipolar mood disorders ages 7–17 years where lithium was superior to placebo, well-tolerated, and, most importantly, devoid of the cardiometabolic syndrome inherent to most of the atypical antipsychotics that are currently the state-of-the-art treatment modality in most algorithms. Lithium was also shown to have a large effect size of 1.06 in an open treatment study by Kowatch et al.[2] Geller et al.[3] reported positive effects with reference to anti-manic efficacy in adolescents with bipolar and substance use disorders in a 6-week placebo-controlled double-blind study. In a meta-analysis by Liu et al.,[4] a number of open-label trials demonstrated the average efficacy of 40%. In my opinion, lithium has fallen into disfavor as a viable treatment option for juvenile bipolar disorders for a couple of reasons. Lithium is notorious to have a narrow therapeutic index, and, hence toxicity is a definitive risk, notably in hot climates in countries like this, where kids can be readily dehydrated. I'd argue that with close monitoring of serum levels every 3 months as per British National Formulary, given higher metabolic rates and renal clearance resulting in a half-life of <18 h versus 24 h in adults, and, that lithium is excreted in sweat too, all this would translate clinically into surprisingly higher dosing than in adult counterparts to achieve therapeutic effects, and, ostensibly obviates undue concerns of toxicity in pediatric population. Another major concern is the dread of mental dullness effectuated by lithium in children where anti-cognitive effects would be counterproductive regarding academic demands. Heaps of data are pouring into neuroscience literature, all converging to demonstrate rather procognitive effects of lithium. These include, inter alia, increasing of gray matter volume, promoting of hippocampal neurogenesis, increasing of N-acetyl aspartate, a putative marker of neuronal viability, increasing brain-derived neutropic factor and anti-apoptotic Bcl-2, inhibition of pro-apoptotic protein P53 and β catenin, and, inhibition of glycogen synthase kinase-3β. For these properties, lithium has been tried in major neurodegenerative disorders like amyotrophic lateral sclerosis, although it was futile. Uses of lithium in psychiatry are protean apart from bipolar mood disorders. Suffice to mention, anti-impulsivity, anti-suicidality, anti-aggressivity, dual diagnosis, schizo-affective, augmentation in unipolar depression, cyclothymia, cycloid psychosis, Klein–Levine syndrome, borderline personality, clozapine-induced neutropenia, augmentation in schizophrenia, psychogenic polydipsia, just to name few. It behoves child and adolescent psychiatrists not to deprive this population from a "real" mood-stabilizer that has withstood test of time for decades now, in the battle against the naturally more virulent juvenile bipolar disorders which take its toll relentlessly over lives of those afflicted kids and also their families, solely, for ill-founded fears in the eyes of prescribers. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

BackgroundDisruptions in rest and activity patterns are core features of bipolar disorder (BD). However, previous methods have been limited in fully characterizing the patterns. There is still a need to capture dysfunction in daily activity as well as rest patterns in order to more holistically understand the nature of 24-h rhythms in BD. Recent developments in the standardization, processing, and analyses of wearable digital actigraphy devices are advancing longitudinal investigation of rest-activity patterns in real time. The current systematic review aimed to summarize the literature on actigraphy measures of rest-activity patterns in BD to inform the future use of this technology.MethodsA comprehensive systematic review using PRISMA guidelines was conducted through PubMed, MEDLINE, PsycINFO, and EMBASE databases, for papers published up to February 2021. Relevant articles utilizing actigraphy measures were extracted and summarized. These papers contributed to three research areas addressed, pertaining to the nature of rest-activity patterns in BD, and the effects of therapeutic interventions on these patterns.ResultsSeventy articles were included. BD was associated with longer sleep onset latency and duration, particularly during depressive episodes and with predictive value for worsening of future manic symptoms. Lower overall daily activity was also associated with BD, especially during depressive episodes, while more variable activity patterns within a day were seen in mania. A small number of studies linked these disruptions with differential patterns of brain functioning and cognitive impairments, as well as more adverse outcomes including increased suicide risk. The stabilizing effect of therapeutic options, including pharmacotherapies and chronotherapies, on activity patterns was supported.ConclusionThe use of actigraphy provides valuable information about rest-activity patterns in BD. Although results suggest that variability in rhythms over time may be a specific feature of BD, definitive conclusions are limited by the small number of studies assessing longitudinal changes over days. Thus, there is an urgent need to extend this work to examine patterns of rhythmicity and regularity in BD. Actigraphy research holds great promise to identify a much-needed specific phenotypic marker for BD that will aid in the development of improved detection, treatment, and prevention options.

There is strong evidence that genetic factors make substantial contributions to the etiology of autism, schizophrenia and bipolar disorders, with heritability estimates being at least 80% for each. These illnesses have complex inheritance, with multiple genetic and environmental factors influencing disease risk; however, in psychiatry, complex genetics is further compounded by phenotypic complexity. Autism, schizophrenia and bipolar disorder are effectively syndromic constellations of symptoms that define groups of patients with broadly similar outcomes and responses to treatment. As such the diagnostic categories are likely to be heterogeneous and the boundaries between them somewhat arbitrary. Recent applications of whole-genome technologies have discovered rare copy number variants and common single-nucleotide polymorphisms that are associated with risk of developing these disorders. Furthermore, these studies have shown an overlap between the genetic loci and even alleles that predispose to the different phenotypes. The findings have several implications. First, they show that copy number variations are likely to be important risk factors for autism and schizophrenia, whereas common single-nucleotide polymorphism alleles have a role in all disorders. Second, they imply that there are specific genetic loci and alleles that increase an individual's risk of developing any of these disorders. Finally, the findings suggest that some of the specific genetic loci implicated so far encode proteins, such as neurexins and neuroligins, that function in synaptic development and plasticity, and therefore may represent a common biological pathway for these disorders.

Anticonvulsants have provided major treatment advances for patients with bipolar disorder. Many of these drugs, including several with proven efficacy in bipolar mania or depression, enhance the activity of the gamma-amino butyric acid (GABA) neurotransmitter system. A new anticonvulsant, tiagabine, has selective GABAergic activity and is approved for patients with partial epilepsy. Few reports of its potential effectiveness in bipolar disorder, however, have been published. We sought to evaluate the effectiveness of tiagabine added to ongoing medication regimens in patients with bipolar disorder inadequately responsive to or intolerant of usual treatments. Seventeen treatment-refractory patients participating in the Stanley Foundation Bipolar Network (SFBN) long-term follow-up study were offered open treatment with add-on tiagabine after discussion of the risks, benefits, other treatment options and giving informed consent. Patients' clinical symptoms and somatic complaints were closely monitored with SFBN longitudinal and cross-sectional ratings. Four patients discontinued low-dose tiagabine prior to the second visit and were excluded from data analysis. Thirteen patients received a mean of 38 days of treatment at a mean dose of 8.7 mg/day of tiagabine. On the Clinical Global Impression Scale for Bipolar Disorder Overall category, three (23%) patients showed much or very much improvement and 10 (77%) patients showed no change or worsening. Three significant adverse events were noted, including two presumptive seizures. Open add-on tiagabine for treatment-refractory patients with bipolar disorder demonstrated limited efficacy with the majority of patients showing no change or worsening of clinical symptoms. In addition, patients experienced serious side-effects attributed as likely due to the medication, which resolved without lasting consequence when tiagabine was discontinued.

To review clinical trials and reports describing the efficacy and safety of atypical antipsychotics (olanzapine, ziprasidone, quetiapine, aripiprazole) in the treatment of autistic or other pervasive developmental disorders. English-language publications from the MEDLINE database (1966-February 2007) including clinical trials, case reports, and retrospective series were reviewed. Relevant data were extracted from studies of selected atypical antipsychotics in the treatment of autistic disorder in children, adolescents, and adults. Most literature found was in the form of case reports or case series; however, several open-label and double-blind trials were also identified. Autistic disorder is a chronic neurodevelopmental disorder with limited treatment options. Nonpharmacologic approaches may be the most beneficial, but pharmacologic agents are needed for some patients with significant behavioral manifestations of the disorder. The atypical antipsychotics (olanzapine, ziprasidone, quetiapine, aripiprazole) have shown some efficacy in improving certain behavioral symptoms of autistic disorder--primarily aggressiveness, hyperactivity, and self-injurious behavior. Efficacy was based on observation or changes from baseline in behavioral rating scores. Data appear to be strongest for olanzapine compared with quetiapine, with several open-label trials suggesting its efficacy. Weight gain and sedation were frequently reported adverse events with both agents. Aripiprazole has demonstrated efficacy in limited case series, with minimal adverse effects reported. Atypical antipsychotics represent a treatment option for symptoms associated with autistic disorder. However, these drugs do not affect the core symptoms of autistic disorder and are associated with potentially significant adverse effects. In addition, there is a lack of randomized controlled trials to determine the true efficacy and long-term safety of these agents in the pediatric population.

The synapsins are a family of neuronal phosphoproteins consisting of SYN1 at chrXp11.3, SYN2 at chr3p25, and SYN3 at chr22q12.3 with alternative splicing leading to as many as 10 isoforms. They are involved in synaptic transmission and plasticity, as well as various stages of neurodevelopment, including axon outgrowth and synapse formation (Cesca et al, 2010). All synapsins are highly concentrated at presynaptic nerve terminals of central neurons and associated with the cytoplasmic surface of synaptic vesicles, but SYN3 has markedly distinct developmental expression and subcellular distribution, suggesting divergent function (Pieribone et al, 2002). Therefore, not surprisingly, a role for synapsins in neuropsychiatry has been suggested and, indeed, several studies have indicated that genetic variants at these genes can be associated with epilepsy, autism, schizophrenia, and bipolar disorder (BD) (Cesca et al, 2010). Furthermore, mRNA- and protein-level postmortem brain studies have suggested dysregulation of these genes in both BD and major depressive disorder (MDD) (Cesca et al, 2010; Cruceanu et al, 2012). Thus, the study of mechanisms responsible for this dysregulation in mood disorders becomes pertinent. In the last few years, evidence has emerged suggesting that epigenetics play a role in neuropsychiatric disorders (Jiang et al, 2008), thus it is plausible that the dysregulation observed in synapsin expression could be attributed in part to epigenetic mechanisms. We found evidence that enrichment of H3K4me3—an epigenetic mark associated with increased transcription—at the promoters of SYN1 and SYN2, but not SYN3 is correlated with increased expression of these genes in the prefrontal cortex of patients with BD and MDD compared with controls (Cruceanu et al, 2012, see Figure 1). These findings are encouraging, but future research should better characterize these mechanisms by exploring the role of other chromatin epigenetic marks and brain-region specificity. In addition, the role of DNA methylation, an equally important epigenetic mechanism, should be investigated. In silico analyses have detected rich CpG islands at the proximal promoters of SYN1 (845 bp) and SYN2 (975 bp), as well as at a distal promoter of SYN3 (613 bp) (Miklem and Hillier, 2012, see Figure 1). To date there is no evidence in the literature of altered DNA methylation at synapsins in mood disorders, although one study of a single schizophrenia patient suggests potentially variably methylated sites in the distal CpG island of SYN3 (Murphy et al, 2008). Interestingly, the CpG islands at SYN1 and SYN2 are immediately preceded by regions of enriched H3K4me3 in mood disorders (Cruceanu et al, 2012, see Figure 1). The same is not true for SYN3, and considering this gene's distinct expression profile and potential implication throughout neurogenesis (Pieribone et al, 2002), perhaps different mechanisms regulate SYN3. The figure illustrates our current knowledge of the synapsin genes' structure, as well as the epigenetic mechanisms that have been identified in psychiatric disorders to date. Figure 1 Potential epigenetic mechanisms at the promoter regions of synapsin genes. Upper panel: the SYN1 gene (chrX:47 431 300–47 479 256). In silico analysis predicts a CpG island 845 bp in size at the 5′end ... In conclusion, brain expression differences seen in synapsin genes in mood disorders may be explained in part by differences in H3K4me3. These results need additional and independent confirmation. Moreover, considering that promoter DNA methylation can modulate gene expression and lead to neuropsychiatric phenotypes, a study of DNA methylation patterns at the synapsin promoters is warranted. On the basis of growing evidence suggesting that epigenetic mechanisms may be involved in altered regulation of synapsins in mood disorders, it would be of interest to study these genes as potential therapeutic targets or biomarkers of treatment response. Evidence is starting to emerge pointing to epigenetic marks as potential biomarkers of treatment response. For instance, for brain-derived neurotrophic factor (BDNF), (Lopez et al, 2010) showed that promoter H3K27me3 levels could serve as a biomarker of response to citalopram in MDD, and (D'Addario et al, 2012) found distinct DNA methylation patterns at the BDNF promoter in BD patients depending on mood-stabilizer and antidepressant therapy. Although no such evidence has yet emerged for synapsins, a recent study showed that lithium, one of the most commonly prescribed drugs for BD, can modulate SYN2 expression in neuronal cell types (Cruceanu et al, 2012). Thus, an investigation of synapsin epigenetics in the brain compared with the periphery would be an interesting next step in elucidating their potential to serve as biomarkers for mood disorders or their treatment.

This thesis explores the range of discourses in which parents and professionals engage when a child is assessed and diagnosed with autism. The main focus is on the parents’ meaning-making in recognition of the investment parents have in the topic. It also takes an anti-discriminatory and emancipatory standpoint in recognition of the relative lack of voice parents are awarded in research and in the development of autism services. A team of professionals in an autism assessment centre were recruited along with parents of four families referred to them to receive an autism assessment for their child. Data were collected during routine assessment centre meetings between parents and professionals and in pre-assessment and post-diagnosis research interviews with parents. A critical discursive psychological approach was taken to analyse data. This synthetic approach, merging a macro-level and micro-level analysis, was used to explore the application of diagnostic criteria, policies and protocols as discursive resources alongside analysis of talk-in-action. The findings of the research programme produced three themes for the thesis: knowledge, power and possibilities. In relation to the first theme, parents talk and the practices of autism assessment and diagnosis, produced a distinction between expert ‘knowledge’ and parents’ ways of ‘knowing’. The two forms of knowledge were not of equal value in the assessment process, varying in the situated power and influence they could wield. In relation to the second theme, the thesis examined both how parents were subjectified by the processes and discourses of diagnosis and how professionals were subjectified as agents of policy and protocol. Analysis of exchanges between parents and professionals exposed further practices of self-subjection, but also identified some strategies of resistance. Prevalence rates of autism diagnosis and the challenges faced by parents and service providers mean this is currently an area of research of considerable applied significance. This thesis aims to contribute specifically to knowledge about how assessment and diagnostic practice might be improved, ultimately proposing a shift in the approach to autism diagnosis. As such, the third theme, possibilities, examined both the constraints on parents’, and professionals’, discourses in the diagnosis of a child and the opportunities to transcend those constraints. It highlighted the benefits of learning from approaches to diagnostic practices based around open dialogue. Future research could develop the work here to focus on professional meaning-making. It might also consider the complex situation of parents of children referred with autistic characteristics who do not receive a diagnosis.