Adverse childhood experiences and psychological functioning among women with schizophrenia or bipolar disorder: population-based study.

BACKGROUND: Adverse childhood experiences (ACEs) are well-known risk factors for schizophrenia and bipolar disorder. AIMS: The aim was to study the associations between specific ACEs and psychological functioning in women with schizophrenia or bipolar disorder. METHOD: Among 29 367 women (mean age 44 years) from the Icelandic Stress-And-Gene-Analysis (SAGA) study, 534 (1.8%, mean age 40) reported having been diagnosed with schizophrenia or bipolar disorder, which were combined to 'severe mental disorders'. Participants reported on 13 types of ACEs, childhood deprivation and psychological functioning (defined as coping ability and current symptoms of depression, anxiety and sleep disturbances). Adjusted Poisson regression calculated prevalence ratios (PRs) between ACEs and severe mental disorders. Linear regression assessed the association between ACEs and psychological functioning among women with a severe mental disorder. RESULTS: Women with a severe mental disorder reported more ACEs (mean 4.57, s.d. = 2.82) than women without (mean 2.51, s.d. = 2.34) in a dose-dependent manner (fully-adjusted PR = 1.23 per ACE, 95% CI 1.20-1.27). After mutual adjustment for other ACEs, emotional abuse, sexual abuse, mental illness of a household member, emotional neglect, bullying and collective violence were associated with severe mental disorders. Among women with severe mental disorders, a higher number of ACEs was associated with increased symptom burden of depression (ß = 2.79, 95% CI = 1.19-4.38) and anxiety (ß = 2.04, 95% CI = 0.99-3.09) including poorer sleep quality (ß = 0.83, 95% CI = 0.07-1.59). Findings were similar for schizophrenia and bipolar disorder separately. CONCLUSION: Women with schizophrenia or bipolar disorder show a strong history of ACEs, which may interfere with their psychological functioning and, therefore, need to be addressed as part of their treatment, for example, with trauma-focused psychotherapy.

[MDMA-assisted therapy for PTSD].

MDMA is a potential novel treatment for post-traumatic stress disorder (PTSD). Our goal is to review current knowledge on MDMA and its use in MDMA-assisted psychotherapy for PTSD. Literature searches were done on PubMed, Web of Science and Google Scholar and references reviewed in identified articles. MDMA-assisted therapy for PTSD usually consists of a few preparatory sessions before two or three sessions where one or two oral doses of MDMA are given along with supportive psychotherapy. The therapy is delivered in the presence of two therapists for about eight hours each time. In addition, the patient receives up to 9 integrative sessions in due course. This use of MDMA as a part of psychotherapy for PTSD is proposed to lessen the psychological distress that often arises in the processing of traumatic events to facilitate the treatment process and reduce the risk of drop-out. Recent studies indicate that MDMA-assisted psychotherapy reduces PTSD symptoms and is generally well tolerated. These studies are necessary if this MDMA-assisted treatment is to be approved by licensing authorities. There is an urgent need for new effective treatments for PTSD and for comparisons between this MDMA-assisted psychotherapy and currently approved psychotherapies with and without MDMA-use.

[Methylphenidate-induced psychosis in a young adult with newly diagnosed ADHD: A case report].

In view of the ongoing rise of ADHD prescriptions among adults in Iceland, it is important that doctors are aware that psychosis is a rare but at times a serious adverse reaction to such treatment. In 2022 5% of adults were prescribed medication to treat ADHD in Iceland. In this case report we present a case of methylphenidate-induced psychosis in a young man with no previous history of psychotic episodes who required admission to the psychiatric intensive care unit.

[Psychedelics and treatment of mental disorders: A survey of attitudes and knowledge among psychiatrists, general practitioners and psychologists in Iceland].

INTRODUCTION: Interest in the use of psychedelics has increased following reports of their possible therapeutic potential. However, little is known about the knowledge of and attitudes towards the substances among health care professional who provide treatment for mental disorders in Iceland. An online survey was therefore conducted among members of the Icelandic associations of psychiatrists, general practitioners and psychologists. METHODS: Respondents were 256 in total, including 177 psychologists, 38 psychiatrists and 41 general practitioners that provided information on their background, type of work, knowledge of and attitude towards different types of psychedelic substances and their views on optimal service delivery if psychedelics were approved by licencing authorities and used for treatment. RESULTS: Around half of psychiatrists reported having received questions about treatment with psychedelics in their clinical work, compared to only 14,6% of general practitioners and 17,5% of psychologists. The majority of respondents had little, or no knowledge of the substances targeted in the survey. A majority also expressed negative attitudes towards treatment with psilocybin mushrooms, but was positive towards ongoing scientific research and felt that such a treatment should be prescribed and provided by psychiatrists. Moreover, the majority view was that psilocybin treatment should be provided in specialised clinics or psychiatric units in a hospital setting. Scientific articles on the topic, discussions with colleagues and information in the media were identified as having had most influence on respondents´ attitudes towards psychedelics. Most respondents were interested in further education on psychedelics. CONCLUSIONS: Respondents among these three professions felt that the time has not yet come to use psychedelics in the treatment of mental disorders in Iceland but thought more education on psychedelics, their potential efficacy and adverse health effects is important given the increased interest in psychedelics.

A polygenic resilience score moderates the genetic risk for schizophrenia.

Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531-538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known "polygenic resilience score" that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.

[The use of psilocybin for treatment-resistant depression].

The hallucinogen psilocybin is a potential novel treatment for treatment-resistant depression (TRD). Our goal is to review current knowledge on psilocybin and its efficacy in TRD. Literature searches were done on PubMed, Web of Science and Google Scholar, references reviewed in identified articles and other articles found on the website of COMPASS Pathways. Psilocybin treatment consists usually of a single oral administration of 25 mg of psilocybin along with psychological support for 5-8 hours during the ensuing hallucinogenic trip. Common side-effects include headache, nausea, fatigue and insomnia. A systematic review has demonstrated significant antidepressant efficacy in certain groups and a double-blind randomized study found antidepressant efficacy of psilocybin comparable to the SSRI escitalopram. In the phase 2 study of COMPASS Pathways, the psilocybin-COMP360 treatment led to a rapid response and remission as early as three weeks following the treatment for around one third of participants. Recent studies have shown that psilocybin significantly decreases the severity of depressive symptoms and is generally well tolerated. Further research will reveal whether it will be granted a license to treat treatment-resistant depression in the near future. There remains an urgent need for novel treatments for those who do not respond to current antidepressant therapies.

CNVs conferring risk of autism or schizophrenia affect cognition in controls.

In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.

[Effectiveness of medical treatment in the adult ADHD unit of Landspitali 2015-2017].

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder among children but symptoms may persist into adulthood. At Landspitali - the National University Hospital an interdisciplinary unit is responsible for ADHD-diagnosis and for commencing treatment of adult ADHD. The aim of this study is to evaluate the effectiveness of pharmaceu-tical treatment provided by the unit and the effects of psychiatric comorbidities. METHODS: The study is retrospective and includes all individuals ≥18 years of age who received pharmaceutical treatment in the adult ADHD unit at Landspitali 2015-2017. Individuals who had previously received treatment by the unit or were already on medication for ADHD were excluded. Information on symptoms and wellbeing before and after treatment were obtained from three questionnaires, an ADHD rating scale, DASS and QOLS. RESULTS: Of 211 patients who met inclusion criteria 144 (68%) completed the treatment provided by the unit on average 143 days. Impulsivity/hyperactivity predicted treatment failure with OR=0.96 (p=0.015). There was a statistically significant difference in all key response variables before and after pharmaceutical treatment (p<0.001). The Cohen's d effect size for ADHD variables were 3.18 for attention-deficit and 1.40 for impulsivity/hyperactivity. The effect size for quality of life was 1.00 and among the DASS subscales the maximum effect size was 1.43 for stress. Increased quality of life correlated with decreased symptoms as rated by DASS and the ADHD rating scale. Treatment success rates were significantly -higher for DASS but not for attention-deficit, impulsivity/hyperactivity and quality of life among individuals with psychiatric comorbidities alongside ADHD. Gender did not affect treatment effectiveness. CONCLUSIONS: Those who complete treatment within the ADHD unit achieve good results with decreased psychiatric symptoms and improved quality of life. Treatment discontinuation is a challenge.

Effects of a Brief Transdiagnostic Cognitive Behavioural Group Therapy on Disorder Specific Symptoms.

BACKGROUND: In recent years, cognitive behavioural group therapies (CBGT) have been increasingly deployed as a strategy to increase the efficiency and cost-effectiveness in treatment of common mental health problems. The vast majority of these therapies are disorder specific, but in the last few years there has been growing interest in transdiagnostic CBGT. AIMS: The aim of this study was twofold: to evaluate the treatment effects of transdiagnostic CBGT on disorder specific symptoms and what (if any) differences would be observed in the treatment effects with regard to general as opposed to disorder specific symptoms measured pre- and post-treatment. METHOD: The participants were 233 adult patients diagnosed with depression and/or anxiety disorders. They underwent a 6-week transdiagnostic CBGT. To compare treatment effects on general and disorder specific symptoms, raw scores on all measures were converted to standardized scores. RESULTS: Pre-post differences were significant and there was no evidence that treatment was differentially effective for general and disorder specific symptoms. Effect sizes ranged from medium to large. CONCLUSION: The 6-week transdiagnostic CBGT is feasible for a wide range of mood and anxiety disorders. The results indicate that low-intensity transdiagnostic group therapies may have similar effects on both general and disorder specific symptoms.

Social and non-social measures of cognition for predicting self-reported and informant-reported functional outcomes in early psychosis.

The main aim of this study was to investigate the individual contributions of neurocognitive and social-cognitive domains to self-reported and informant-reported functional outcome in early psychosis. We also sought to further characterize the nature of cognitive impairments in this sample and explore the interrelationships between the social-cognitive measures and how they correlate with measures of neurocognition and clinical symptoms. In this study, 70 patients (mean age: 24.1; 87.1% males) with primary psychotic disorder diagnosed in the previous 5 years were assessed on multiple neurocognitive (processing speed, attention, working memory, immediate verbal memory, delayed recall, visual reasoning, inhibition, planning, cognitive flexibility), and social-cognitive domains (theory of mind (ToM), emotion recognition, attributional style, metacognitive overconfidence) as well as measures of clinical symptoms. Functional outcome was assessed with three self-reports and two informant-reports. On average, patients performed one or more SD below healthy controls on measures of delayed recall, ToM and metacognitive overconfidence. Emotion recognition and ToM were intercorrelated and correlated with multiple neurocognitive domains and negative symptoms. Attributional style correlated with positive symptoms. In the context of multiple variables, self-reported functional outcomes were predicted by attributional style, whereas emotion recognition and immediate verbal memory predicted variance in informant-reported community functioning. These results support the suggestion of a likely distinction between the predictive factors for self-reported and informant-reported functional outcome in early psychosis and suggest that consideration of self-assessment of functional outcome is critical when attempting to evaluate the effects attributional style has on functional disability.

[High altitude illness and related diseases - a review].

Upon reaching a height over 2500 m above seal level symptoms of altitude illness can develop over 1 - 5 days. The risk is mainly -determined by the altitude and rate of ascent and the symptoms vary. Most common are symptoms of acute mountain illness (AMS) but more dangerous high altitude cerebral edema (HACE) and high altitude pulmonary edema (HAPE) can also develop. The causes of AMS, HACE and HAPE are lack of oxygen and insufficient acclimatization, but the presenting form is determined by the responses of the body to the lack of oxygen. The most common symptoms of AMS include headache, fatique and nausea, but insomnia and nausea are also common. The most common symptoms of HAPE are breathlessness and lassitude whereas the cardinal sign of HACE is ataxia, but confusion and loss of consciousness can also develop. In this article all three main forms of altitude illness are reviewed. The emphasis is on preventive measures and treatment but new knowledge on pathogenesis is also addressed.

Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction.

We use polygenic risk scores (PRSs) for schizophrenia (SCZ) and bipolar disorder (BPD) to predict smoking, and addiction to nicotine, alcohol or drugs in individuals not diagnosed with psychotic disorders. Using PRSs for 144 609 subjects, including 10 036 individuals admitted for in-patient addiction treatment and 35 754 smokers, we find that diagnoses of various substance use disorders and smoking associate strongly with PRSs for SCZ (P = 5.3 × 10-50 -1.4 × 10-6 ) and BPD (P = 1.7 × 10-9 -1.9 × 10-3 ), showing shared genetic etiology between psychosis and addiction. Using standardized scores for SCZ and BPD scaled to a unit increase doubling the risk of the corresponding disorder, the odds ratios for alcohol and substance use disorders range from 1.19 to 1.31 for the SCZ-PRS, and from 1.07 to 1.29 for the BPD-PRS. Furthermore, we show that as regular smoking becomes more stigmatized and less prevalent, these biological risk factors gain importance as determinants of the behavior.

Constipation, ileus and medication use during clozapine treatment in patients with schizophrenia in Iceland.

Purpose of the article: Clozapine is the only evidence based treatment for treatment-resistant schizophrenia. Constipation is a well known side effect of clozapine treatment. The aims of this study are to describe the prevalence of constipation and ileus during clozapine treatment of patients with schizophrenia in Iceland and to assess the concomitant use of medication that can cause constipation, and laxatives used to treat constipation. MATERIALS AND METHODS: We identified 188 patients treated with clozapine by searching the electronic health records of Landspitali, the National University Hospital, during the study period 1.1.1998 - 21.11.2014. Cases of constipation and ileus were identified using an electronic search with keywords related to ileus in the patients' electronic health records. Detailed medication use was available for 154 patients that used clozapine for at least one year. RESULTS: Four out of 188 patients were diagnosed with ileus that resulted in admission to hospital. Two of these required a permanent stoma as a consequence of their ileus. Laxatives were prescribed for 24 out of 154 patients (15.4%) while on clozapine. In total 40.9% of the patients either had laxatives prescribed or had constipation documented in the medical records. Apart from clozapine, other medications known to cause constipation were prescribed to 28 out of 154 patients (18.2%). CONCLUSIONS: Constipation is a common problem during clozapine treatment which can progress to full-blown ileus which can be fatal. Clinicians need to monitor signs of constipation during treatment with clozapine and respond to it with lifestyle advice and laxative treatment.

Risk of diabetes and dyslipidemia during clozapine and other antipsychotic drug treatment of schizophrenia in Iceland.

BACKGROUND: Type 2 diabetes (T2D) and raised blood lipids are associated with the use of antipsychotics, not least clozapine. AIMS: To describe the prevalence of high blood glucose levels, T2D, and dyslipidemia, in association with the use of clozapine or other antipsychotics in patients with schizophrenia in Iceland. METHOD: This study identified 188 patients treated with clozapine and 395 patients never treated with clozapine by searching the electronic health records of Landspitali, the National University Hospital. The comparison group consisted of Icelandic population controls. Data were obtained on blood glucose, HbA1c, and blood lipid levels from these health records. RESULTS: The prevalence of T2D was 14.3% in the clozapine group, where the mean age was 51.2 years, and 13.7% in the never-on-clozapine group, where the mean age was 58.6 years. Males on clozapine were 2.3-times more likely and females 4.4-times more likely to have developed T2D than controls from an age-adjusted Icelandic cohort, while males on other antipsychotics were 1.5-times more likely and females 2.3-times as likely to have T2D than controls. Only one case of ketoacidosis was identified. Triglyceride levels were significantly higher in both treatment groups compared to controls in the age-adjusted Icelandic cohort. CONCLUSIONS: Clinicians must take active steps to reduce the risk of T2D and raised triglycerides in patients with schizophrenia. Antipsychotics were associated with a greater risk of T2D developing in females compared to males.

Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland.

BACKGROUND: Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia. METHODS: The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well. RESULTS: The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500-1900 neutrophils/mm3). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500-1400 /mm3 of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine. CONCLUSIONS: Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by clozapine. These findings have implications in assessing the balance between the risk of progression from neutropenia to agranulocytosis against the morbidity resulting from the premature discontinuation of clozapine under the current monitoring regulations in the US and in most of Europe.

Intravenous Use of Prescription Psychostimulants; A Comparison of the Pattern and Subjective Experience between Different Methylphenidate Preparations, Amphetamine and Cocaine.

BACKGROUND/AIMS: Methylphenidate (MPH) has been the most commonly used intravenous (i.v.) substance in Iceland in recent years. In Iceland, MPH is available in 3 forms: immediate-release (IR) tablets (MPH IR, short-acting), sustainable-release (SR) capsules (MPH SR, long-acting) and osmotic-release (OROS) tablets (MPH OROS, long-acting). The aims of the study were to compare the pattern and subjective effects of i.v. MPH use to other i.v. psychostimulants and examine whether the pattern of use differs among MPH preparations. METHODS: This is a nationwide descriptive study. Information was collected from 95 i.v. substance users undergoing inpatient detoxification and reporting i.v. MPH use in the last 30 days using a semi-structured interview. RESULTS: MPH SR was both the most commonly used (96%) and preferred i.v. psychostimulant (57%). The intensity and duration of 'euphoria' did not differ between cocaine and MPH SR. No participant reported MPH OROS as their preferred substance even though a third had used it in the past month. CONCLUSIONS: The pattern of i.v. MPH use is similar to other psychostimulants among treatment seeking patients. MPH OROS was the least preferred i.v. psychostimulant, despite having the largest market share in Iceland. The results indicate that MPH OROS has less abuse potential than other MPH preparations.

Clozapine treatment and discontinuation in Iceland: A national longitudinal study using electronic patient records.

BACKGROUND: Clozapine is the only drug approved for treatment-resistant schizophrenia. There is evidence that clozapine is underutilized. AIMS: To evaluate the initiation and discontinuation of clozapine at Landspitali University Hospital in Iceland and the prevalence of antipsychotic polypharmacy in clozapine-treated patients. METHODS: The study is a part of an ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients on clozapine or who have been on clozapine by using a keyword search in the electronic health records and by reviewing their medical records. RESULTS: Mean age at first treatment with clozapine was 37.8 years. Mean follow-up period on clozapine was 11 years. After 20 years of treatment 71.2% of patients were still on clozapine. After one year of treatment 84.4% of patients were still receiving clozapine treatment. We estimate that 11.4% of patients with schizophrenia in Iceland are taking clozapine and that 16% have been treated with clozapine at some point. Polypharmacy is common, since nearly 2/3, 65.6%, of patients taking clozapine use at least one other antipsychotic and 16.9% are also receiving depot injections. CONCLUSIONS: We need to increase the awareness of psychiatrists in Iceland with regard to treatment with clozapine, since only about half of the estimated population of patients with treatment-resistant schizophrenia in Iceland have ever been treated with clozapine. Nearly two thirds of patients who are prescribed clozapine in Iceland remain on it long-term.

Transdiagnostic cognitive behavioural treatment and the impact of co-morbidity: An open trial in a cohort of primary care patients.

BACKGROUND: The development of initiatives to improve access to psychological therapies has been driven by the realization that untreated anxiety and depression are both very common and costly to individuals as well as society. Effective and efficient treatments, mostly in the form of cognitive behavioural therapies (CBT), can be used in ways which enhance their acceptability and accessibility. To date, numbers of group therapies have been developed to improve cost efficiency, but in spite of growing interest in transdiagnostic approaches, group therapies have so far mostly been diagnosis specific. AIMS: This study is aimed at evaluating a brief transdiagnostic cognitive behavioural group therapy (TCBGT) designed to treat both anxiety and depression among patients in primary care. METHOD: The participants were 287 adult patients in primary care with diagnoses of depression and/or anxiety disorders. They underwent a 5-week TCBGT. A mixed design ANOVA was used to evaluate differential effects of treatment according to diagnostic groups (anxiety versus depression) and number of diagnoses (co-morbidity). RESULTS: Pre-post differences were significant and the treatment was equally effective for both anxiety disorders and depression. Number of diagnoses did not affect the outcome. CONCLUSIONS: The study indicates feasibility of the brief transdiagnostic group therapy for a wide range of mood and anxiety disorders in primary care. The results indicate that low intensity, brief transdiagnostic group therapies may be a feasible way to improve access to psychological therapies for a large number of patients.

Common variants conferring risk of schizophrenia.

Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.