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Background: The nationwide shortage of mental health resources often disproportionately affects rural areas. As innovative strategies are required to address mental health resource shortages in rural areas, telepsychiatry consultation (TPC) may represent a population health-oriented approach to bridge this gap. In this case report, we examine the use of TPC from an academic consultation-liaison psychiatry service to a rural community hospital. Case Report: We describe the case of a woman with Wernicke encephalopathy seeking to leave the hospital against medical advice and the role that the TPC service played in the patient's evaluation and management, including assessing decision-making capacity. Discussion: We then examine benefits and limitations of the service, including a narrative review of the relevant, but limited, available literature as well as suggestions for how the service may be improved and incorporated into psychiatry residency and fellowship training in the future.
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Psiquiatría , Telemedicina , Femenino , Humanos , Salud Mental , Área sin Atención Médica , Derivación y ConsultaRESUMEN
BACKGROUND: Numerous studies have demonstrated that psychiatric and substance use issues in general hospital inpatients result in increased length of stay and associated costs. Additional studies have demonstrated that proactive consultation models in psychiatry can effectively address these problems. Selecting patients for proactive interventions is less well studied. OBJECTIVE: We sought to develop an automated, electronic medical record-based screening tool to select patients who might benefit from proactive psychiatric consultation. METHODS: An automated daily report was developed using information stored in electronic medical record and billing systems. Discrete data fields populating the report included diagnoses, orders, and nursing care plans. RESULTS: Over a 9-month period, the report identified 2177 patients (19% of the total nonpsychiatric adult admissions) as potentially benefitting from proactive psychiatric interventions. Of these, 367 were confirmed as likely to benefit from intervention; 139 (38%) were randomized to the proactive psychiatric consultation group. Of those patients randomized to "treatment as usual," a subset later required psychiatric consultation, which was requested an average of 4 days after the time they were flagged by the report. CONCLUSIONS: The use of an electronic medical record-based automated report is feasible to select patients for proactive psychiatric interventions on admission and throughout the hospital stay. Early identification of patients may decrease length of stay and improve patient outcomes.
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Registros Electrónicos de Salud/estadística & datos numéricos , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Derivación y Consulta/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Amputación Traumática , Trastorno de Identidad de la Integridad Corporal/psicología , Traumatismos de la Mano , Conducta Autodestructiva/psicología , Adultos Sobrevivientes del Maltrato a los Niños/psicología , Trastorno Depresivo Mayor/psicología , Mano , Humanos , Masculino , Persona de Mediana Edad , Reimplantación , Negativa del Paciente al TratamientoRESUMEN
RATIONALE: Patients with epilepsy (PWEs) and patients with nonepileptic seizures (PWNESs) constitute particularly vulnerable patient populations and have high rates of psychiatric comorbidities. This potentially decreases quality of life and increases health-care utilization and expenditures. However, lack of access to care or concern of stigma may preclude referral to outpatient psychiatric clinics. Furthermore, the optimal treatment for NESs includes longitudinal psychiatric management. No published literature has assessed the impact of colocated psychiatric services within outpatient epilepsy clinics. We, therefore, evaluated the colocation of psychiatric services within a level 4 epilepsy center. METHODS: From July 2013 to June 2014, we piloted an intervention to colocate a psychiatrist in the Dartmouth-Hitchcock Epilepsy Center outpatient clinic one afternoon a week (0.1 FTE) to provide medication management and time-limited structural psychotherapeutic interventions to all patients who scored greater than 15 on the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and who agreed to referral. Psychiatric symptom severity was assessed at baseline and follow-up visits using validated scales including NDDI-E, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and cognitive subscale items from Quality of Life in Epilepsy-31 (QOLIE-31) scores. RESULTS: Forty-three patients (18 males; 25 females) were referred to the clinic over a one-year interval; 27 (64.3%) were seen in follow-up with a median of 3 follow-up visits (range: 1 to 7). Thirty-seven percent of the patients had NESs exclusive of epilepsy, and 11% of the patients had dual diagnosis of epilepsy and NESs. Psychiatric symptom severity decreased in 84% of the patients, with PHQ-9 and GAD-7 scores improving significantly from baseline (4.6±0.4 SD improvement in PHQ-9 and 4.0±0.4 SD improvement in GAD-7, p-values<0.001). Cognitive subitem scores for NDDI-E and QOLIE-31 at their most recent visit were significantly improved compared with nadir scores (3.3±0.6 SD improvement in NDDI-E and 1.5±0.2 SD improvement in QOLIE-31, p-values<0.001). These results are, moreover, clinically significant-defined as improvement by 4-5 points on PHQ-9 and GAD-7 instruments-and are correlated with overall improvement as measured by NDDI-E and cognitive subscale QOLIE-31 items. CONCLUSION: A colocated psychiatrist demonstrated reduction in psychiatric symptoms of PWEs and PWNESs, improving psychiatric access and streamlining their care. Epileptologists were able to dedicate more time to managing epilepsy as opposed to psychiatric comorbidities. As integrated models of collaborative and colocated care are becoming more widespread, mental health-care providers located in outpatient neurology clinics may benefit both patients and providers.
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Epilepsia , Trastornos Mentales/terapia , Servicios de Salud Mental/normas , Adulto , Instituciones de Atención Ambulatoria , Comorbilidad , Epilepsia/epidemiología , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Proyectos Piloto , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Guardianship may be necessary when inpatients lack medical decision-making capacity and are unwilling to go home to be cared for by interested proxy decision makers. Interventions, centered on a clinical pathway, were conducted at Dartmouth-Hitchcock Medical Center (DHMC; Lebanon, New Hampshire). Because guardianship occurs at the interface of clinical care and governmental bureaucracy, quality improvement efforts focused on "in-hospital" processes, while actions were taken to improve communication between clinical teams and the legal system. METHODS: A multidisciplinary quality improvement team mapped the DHMC guardianship process and analyzed the causes for delays before creating the clinical pathway. Specific interventions were designed and implemented to address the identified improvement areas. RESULTS: For the 26 guardianship patients during a two-year period (May 1, 2011-May 1, 2013), the charges incurred totaled approximately $4,000,000--for an average of more than $150,000 per patient. The medically unnecessary days of their length of hospital stay decreased from an average of 27.8 to 11.3, a statistically significant result as demonstrated by statistical process control analysis. The shorter hospitalizations of the last 13 patients amounted to 214.5 medically unnecessary hospital days saved and more than $1.2 million in charges reduced during the two-year period. CONCLUSIONS: Guardianship is a complex process that generates significant delays in appropriate care and increases in charges. The redesigned, standardized guardianship process, as defined in the clinical pathway, reduced associated medically unnecessary days of hospitalization.
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Vías Clínicas/organización & administración , Administración Hospitalaria/métodos , Tutores Legales , Personas con Discapacidades Mentales , Mejoramiento de la Calidad/organización & administración , Vías Clínicas/economía , Toma de Decisiones , Administración Hospitalaria/economía , Costos de Hospital , Hospitalización , Humanos , Tiempo de Internación , Evaluación de Procesos y Resultados en Atención de Salud , Mejoramiento de la Calidad/economía , Mejoramiento de la Calidad/legislación & jurisprudenciaRESUMEN
STUDY OBJECTIVE: To identify patient and clinical management factors related to emergency department (ED) length of stay for psychiatric patients. METHODS: This was a prospective study of 1,092 adults treated at one of 5 EDs between June 2008 and May 2009. Regression analyses were used to identify factors associated with ED length of stay and its 4 subcomponents. Secondary analyses considered patients discharged to home and those who were admitted or transferred separately. RESULTS: The overall mean ED length of stay was 11.5 hours (median 8.2 hours). ED length of stay varied by discharge disposition, with patients discharged to home staying 8.6 hours (95% confidence interval 7.7 to 9.5 hours) and patients transferred to a hospital outside the system of care staying 15 hours (95% confidence interval 12.7 to 17.6 hours) on average. Older age and being uninsured were associated with increased ED length of stay, whereas race, sex, and homelessness had no association. Patients with a positive toxicology screen result for alcohol stayed an average of 6.2 hours longer than patients without toxicology screens, an effect observed primarily in the periods before disposition decision. Diagnostic imaging was associated with an average 3.2-hour greater length of stay, prolonging both early and late components of the ED stay. Restraint use had a similar effect, leading to a length of stay 4.2 hours longer than that of patients not requiring restraints. CONCLUSION: Psychiatric patients spent more than 11 hours in the ED on average when seeking care. The need for hospitalization, restraint use, and the completion of diagnostic imaging had the greatest effect on postassessment boarding time, whereas the presence of alcohol on toxicology screening led to delays earlier in the ED stay. Identification and sharing of best practices associated with each of these factors would provide an opportunity for improvement in ED care for this population.
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Servicio de Urgencia en Hospital , Tiempo de Internación , Trastornos Mentales/terapia , Adulto , Factores de Edad , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Cobertura del Seguro , Masculino , Trastornos Mentales/psicología , Admisión del Paciente/estadística & datos numéricos , Estudios Prospectivos , Análisis de Regresión , Factores de TiempoRESUMEN
STUDY OBJECTIVE: We ascertain the components of emergency department (ED) length of stay for adult patients receiving psychiatric evaluation and to examine their variability across 5 hospitals within a health care system. METHODS: This was a prospective study of 1,092 adults treated between June 2008 and May 2009. Research staff abstracted length of stay and clinical information from the medical records. Clinicians completed a time log for each patient contact. Main outcomes were median times for the overall ED length of stay and its 4 components, or time from triage to request for psychiatric evaluation, request to start of psychiatric evaluation, start to completion of psychiatric evaluation with a disposition decision, and disposition decision to discharge from the ED. RESULTS: The overall median length of stay was more than 8 hours. Median times for the components were 1.8 hours from triage to request, 15 minutes from request to start of psychiatric evaluation, 75 minutes from start of psychiatric evaluation to disposition decision, and nearly 3 hours from disposition decision to ED discharge. The median disposition decision to discharge time was substantially shorter for patients who went home (40 minutes) than for patients who were admitted (2.5 hours) or transferred for psychiatric admission at other facilities (6.3 hours). When adjustments for patient and clinical factors were made, differences in ED length of stay persisted between hospitals. CONCLUSION: ED length of stay for psychiatric patients varied greatly between hospitals, highlighting differences in the organization of psychiatric services and inpatient bed availability. Findings may not generalize to other settings or populations.
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Servicio de Urgencia en Hospital/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Trastornos Mentales/diagnóstico , Centros Médicos Académicos/estadística & datos numéricos , Adulto , Femenino , Hospitales Comunitarios/estadística & datos numéricos , Humanos , Masculino , Massachusetts , Trastornos Mentales/terapia , Evaluación de Procesos y Resultados en Atención de Salud , Estudios Prospectivos , Factores de TiempoRESUMEN
BACKGROUND: Stiff-person syndrome (SPS) is a rare autoimmune neurologic disease characterized by painful rigidity and muscle spasms. Patients with SPS may present with psychiatric symptoms, and little is known about the presence of psychiatric comorbidities. OBJECTIVE: The objective of this study was to provide an overview of the association between SPS and psychiatric illnesses. METHODS: The protocol is registered in PROSPERO (Registration ID CRD42020159354). Peer-reviewed articles on adults with SPS and psychiatric comorbidities published before May 26, 2020, were selected by 2 independent reviewers. Qualitative summary data and relative risk of psychiatric disorders in patients with SPS compared with the general population and multiple sclerosis were calculated. RESULTS: After screening 909 articles, 52 full texts were assessed for eligibility and 27 were ultimately included, 5 of which were selected for quantitative analysis. Although limited by small sample sizes leading to large confidence intervals, the relative risk of any psychiatric comorbidity in SPS was higher than that of the general population, ranging from estimates of 6.09 (95% confidence interval: 4.09, 9.08) to 11.25 (95% confidence interval: 3.27, 38.66). There was no statistically significant difference in the risk of any psychiatric comorbidity between SPS and multiple sclerosis. The review also highlighted delays in SPS diagnosis, often related to misattribution of symptoms as being solely secondary to a psychiatric cause. CONCLUSIONS: The higher risk of psychiatric comorbidities emphasizes the important role of psychiatrists in recognizing the symptoms of SPS to reach timely diagnosis and treatment. The presence of psychiatric symptoms should support rather than delay the diagnosis of SPS.
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Enfermedades Autoinmunes del Sistema Nervioso , Esclerosis Múltiple , Síndrome de la Persona Rígida , Adulto , Comorbilidad , Humanos , Esclerosis Múltiple/epidemiología , Espasmo , Síndrome de la Persona Rígida/diagnósticoRESUMEN
Suicide is difficult to predict and prevent because people who consider killing themselves often are unwilling or unable to report their intentions. Advances in the measurement of implicit cognition provide an opportunity to test whether automatic associations of self with death can provide a behavioral marker for suicide risk. We measured implicit associations about death/suicide in 157 people seeking treatment at a psychiatric emergency department. Results confirmed that people who have attempted suicide hold a significantly stronger implicit association between death/suicide and self than do psychiatrically distressed individuals who have not attempted suicide. Moreover, the implicit association of death/suicide with self was associated with an approximately 6-fold increase in the odds of making a suicide attempt in the next 6 months, exceeding the predictive validity of known risk factors (e.g., depression, suicide-attempt history) and both patients' and clinicians' predictions. These results provide the first evidence of a behavioral marker for suicidal behavior and suggest that measures of implicit cognition may be useful for detecting and predicting sensitive clinical behaviors that are unlikely to be reported.
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Asociación , Actitud Frente a la Muerte , Cognición , Autoimagen , Intento de Suicidio/psicología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Persona de Mediana Edad , Oportunidad Relativa , Inventario de Personalidad/estadística & datos numéricos , Psicometría , Factores de Riesgo , Estadística como Asunto , Intento de Suicidio/prevención & control , Intento de Suicidio/estadística & datos numéricosAsunto(s)
Tutores Legales , Tiempo de Internación , Competencia Mental , Alta del Paciente , Femenino , Humanos , Persona de Mediana Edad , PsiquiatríaRESUMEN
We report studies of six individuals with marked elevations of cystathionine in plasma and/or urine. Studies of CTH, the gene that encodes cystathionine gamma-lyase, revealed the presence among these individuals of either homozygous or compound heterozygous forms of a novel large deletion, p.Gly57_Gln196del, two novel missense mutations, c.589C>T (p.Arg197Cys) and c.932C>T (p.Thr311Ile), and one previously reported alteration, c.200C>T (p.Thr67Ile). Another novel missense mutation, c.185G>T (p.Arg62His), was found in heterozygous form in three mildly hypercystathioninemic members of a Taiwanese family. In one severely hypercystathioninemic individual no CTH mutation was found. Brief clinical histories of the cystathioninemic/cystathioninuric patients are presented. Most of the novel mutations were expressed and the CTH activities of the mutant proteins determined. The crystal structure of the human enzyme, hCTH, and the evidence available as to the effects of the mutations in question, as well as those of the previously reported p.Gln240Glu, on protein structure, enzymatic activity, and responsiveness to vitamin B(6) administration are discussed. Among healthy Czech controls, 9.3% were homozygous for CTH c.1208G>T (p.Ser403Ile), previously found homozygously in 7.5% of Canadians for whom plasma total homocysteine (tHcy) had been measured. Compared to wild-type homozygotes, among the 55 Czech c.1208G>T (p.Ser403Ile) homozygotes a greater level of plasma cystathionine was found only after methionine loading. Three of the four individuals homozygous or compound heterozygous for inactivating CTH mutations had mild plasma tHcy elevations, perhaps indicating a cause-and-effect relationship. The experience with the present patients provides no evidence that severe loss of CTH activity is accompanied by adverse clinical effects.
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Cistationina gamma-Liasa/genética , Adulto , Errores Innatos del Metabolismo de los Aminoácidos/genética , Dominio Catalítico , Preescolar , Cistationina/metabolismo , Cistationina gamma-Liasa/metabolismo , Femenino , Eliminación de Gen , Humanos , Lactante , Recién Nacido , Masculino , Modelos Moleculares , Mutación MissenseRESUMEN
Velocardiofacial syndrome, DiGeorge syndrome, and conotruncal anomaly face syndrome, now collectively referred to as 22q11deletion syndrome (22q11DS) are caused by microdeletions on chromosome 22q11. The great majority ( approximately 90%) of these deletions are 3 Mb in size. The remaining deleted patients have nested break-points resulting in overlapping regions of hemizygosity. Diagnostic testing for the disorder is traditionally done by fluorescent in situ hybridization (FISH) using probes located in the proximal half of the region common to all deletions. We developed a novel, high-resolution single-nucleotide polymorphism (SNP) genotyping assay to detect 22q11 deletions. We validated this assay using DNA from 110 nondeleted controls and 77 patients with 22q11DS that had previously been tested by FISH. The assay was 100% sensitive (all deletions were correctly identified). Our assay was also able to detect a case of segmental uniparental disomy at 22q11 that was not detected by the FISH assay. We used Bayesian networks to identify a set of 17 SNPs that are sufficient to ascertain unambiguously the deletion status of 22q11DS patients. Our SNP based assay is a highly accurate, sensitive, and specific method for the diagnosis of 22q11 deletion syndrome.
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Deleción Cromosómica , Cromosomas Humanos Par 22 , Polimorfismo de Nucleótido Simple , Secuencia de Bases , Teorema de Bayes , ADN , Humanos , Hibridación Fluorescente in Situ , Datos de Secuencia Molecular , Sensibilidad y EspecificidadRESUMEN
While psychiatrists may commonly discuss family history in clinical practice, there has been little systematic research documenting the role and effectiveness of genetic counseling for psychiatric disorders. In the coming years, the expected identification of susceptibility genes for psychiatric disorders may bring new opportunities and expectations from patients and families for the clinical translation of research findings in psychiatric genetics. We review evidence for possible increasing demand for genetic counseling, particularly if specific genes related to psychiatric disorders are identified. We then explore both the potential role of genetic counseling for psychiatric disorders and the issues involved in conveying genetic information in the clinical setting. Further research regarding the effectiveness of counseling interventions, as well as additional efforts directed at genetics education for clinicians, will be needed if emerging advances in genetic research are to be incorporated into clinical practice.
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Asesoramiento Genético , Trastornos Mentales/genética , Trastornos Mentales/prevención & control , Pruebas Genéticas , Humanos , Psiquiatría/educación , Recurrencia , Medición de RiesgoRESUMEN
OBJECTIVE: To assess nonclinical factors delaying hospital discharge of guardianship patients. DATA: Utilization review data over 3 years. DESIGN: Retrospective cohort study. ANALYSIS: Mann-Whitney test was used to compare patients' medically unnecessary days (MUD) of hospitalization with additional subcategories of delays-defined as beyond clinicians' control. FINDINGS: Overall median number of MUD was 19.5; 14 of 48 patients were additionally delayed while awaiting long-term care Medicaid approval (N = 7, 50%), pending insurance (N = 3, 21%), social or transportation difficulties (N = 3, 21%), or preadmission review (N = 1, 7%). The median number of MUD for the 14 delayed patients was 63, a difference of 53 days compared with the routine guardianship cohort (P < .0001) and $5.5M in net revenue opportunity. CONCLUSIONS: Nonclinical discharge delays for guardianship patients are costly and potentially unavoidable. Further exploration into policy change is therefore recommended.
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Tutores Legales , Tiempo de Internación , Alta del Paciente , Adulto , Anciano , Anciano de 80 o más Años , Canadá , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estadísticas no Paramétricas , Factores de Tiempo , Estados UnidosRESUMEN
BACKGROUND: Current evidence suggests an association between coronary artery disease and major depressive disorder (MDD). Data to support a similar association between peripheral arterial disease (PAD) and MDD are more limited. This study examines the prevalence and regional variation of both PAD and MDD in a large contemporary patient sample. METHODS: All Medicare claims, part A and B, from January 2009 until December 2011 were queried using diagnosis codes specific for a previously validated clinical algorithm for PAD and major depression. Codes for PAD included those specific to cerebrovascular disease, abdominal aortic aneurysm, and peripheral vascular disease. Peripheral arterial disease prevalence, major depression prevalence, and coprevalence rates were determined, respectively. Regional variation of both conditions was determined using zip code data to identify potential endemic areas of disease intensity for both diagnoses. RESULTS: Over the study interval, the percentage of Medicare beneficiaries with a diagnosis of PAD remained relatively constant (3.0%-3.7%, n = 0.85-1.06 million in part A and 17.4%-17.5%, n = 4.82-4.93 million in part B), and MDD showed a similar trend (1.6%-2.7%, n = 0.46-0.79 million in part A and 6.1%-6.7%, n = 1.69-1.90 million in part B). The observed rate of MDD in those with an established diagnosis of PAD was 5-fold higher than those without PAD in part A claims (1.8-fold in part B claims). Moreover, there was a significant linear geographic correlation among patients with PAD and MDD (r = .54, P ≤ .01). CONCLUSIONS: This study documents a correlation between PAD and MDD and may, therefore, identify an at-risk population susceptible to inferior clinical outcomes. Significant regional variation exists in the prevalence of PAD and MDD, though there appear to be specific endemic regions notable for both disorders. Accordingly, health-care resource allocation toward endemic regions may help improve population health among this at-risk cohort.
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Trastorno Depresivo Mayor/epidemiología , Enfermedades Endémicas , Medicare , Enfermedad Arterial Periférica/epidemiología , Reclamos Administrativos en el Cuidado de la Salud , Anciano , Comorbilidad , Bases de Datos Factuales , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Humanos , Modelos Lineales , Enfermedad Arterial Periférica/diagnóstico , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: Knowledge about the genetic basis of psychiatric illness is growing rapidly, and psychiatrists may be called upon to incorporate this information into clinical practice. The goal of this study was to assess psychiatrists' familiarity with and attitudes toward genetic information. METHOD: We surveyed 844 participants, the majority of whom were psychiatrists, attending a continuing medical education course in the fall of 2002 and measured knowledge, opinions, and current practice patterns in regard to psychiatric genetics. RESULTS: Responses were received from 352 psychiatrists (54% of those surveyed). Most psychiatrists correctly answered fewer than half of survey items assessing general and psychiatric genetic knowledge. While 83% considered it their role to discuss genetic information with patients and families, fewer than 25% felt prepared or competent to do so. In response to hypothetical questions regarding genetic testing, a substantial proportion of psychiatrists indicated willingness to use such tests for diagnostic clarification, as well as presymptomatic and even prenatal risk prediction. The majority of respondents expressed interest in further genetics education. CONCLUSIONS: Our results suggest that psychiatrists view genetic information as clinically relevant, but have limitations in knowledge that may impact the incorporation of psychiatric genetics into clinical practice.
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Actitud del Personal de Salud , Competencia Clínica/normas , Genética Médica/educación , Trastornos Mentales/genética , Psiquiatría/normas , Recolección de Datos/estadística & datos numéricos , Educación Médica Continua , Femenino , Humanos , Masculino , Rol del Médico , Pautas de la Práctica en Medicina , Práctica Profesional/normas , Psiquiatría/educaciónRESUMEN
BACKGROUND: Variation in the COMT gene has been implicated in a number of psychiatric disorders, including psychotic, affective and anxiety disorders. The majority of these studies have focused on the functional Val108/158Met polymorphism and yielded conflicting results, with limited studies examining the relationship between other polymorphisms, or haplotypes, and psychiatric illness. We hypothesized that COMT variation may confer a general risk for psychiatric disorders and have genotyped four COMT variants (Val158Met, rs737865, rs165599, and a SNP in the P2 promoter [-278A/G; rs2097603]) in 394 Caucasian cases and 467 controls. Cases included patients with schizophrenia (n = 196), schizoaffective disorder (n = 62), bipolar disorder (n = 82), major depression (n = 30), and patients diagnosed with either psychotic disorder NOS or depressive disorder NOS (n = 24). RESULTS: SNP rs2097603, the Val/Met variant and SNP rs165599 were significantly associated (p = 0.004; p = 0.05; p = 0.035) with a broad "all affected" diagnosis. Haplotype analysis revealed a potentially protective G-A-A-A haplotype haplotype (-278A/G; rs737865; Val108/158Met; rs165599), which was significantly underrepresented in this group (p = 0.0033) and contained the opposite alleles of the risk haplotype previously described by Shifman et al. Analysis of diagnostic subgroups within the "all affecteds group" showed an association of COMT in patients with psychotic disorders as well as in cases with affective illness although the associated variants differed. The protective haplotype remained significantly underrepresented in most of these subgroups. CONCLUSION: Our results support the view that COMT variation provides a weak general predisposition to neuropsychiatric disease including psychotic and affective disorders.
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Patients with 22q11.2 deletion syndrome (22q11.2DS) represent a population at high risk for developing schizophrenia, as well as learning disabilities. Deficits in visuo-spatial memory are thought to underlie some of the cognitive disabilities. Neuronal substrates of visuo-spatial memory include the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal fasciculus (ILF), two tracts that comprise the ventral visual stream. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) is an established method to evaluate white matter (WM) connections in vivo. DT-MRI scans of nine 22q11.2DS young adults and nine matched healthy subjects were acquired. Tractography of the IFOF and the ILF was performed. DT-MRI indices, including Fractional anisotropy (FA, measure of WM changes), axial diffusivity (AD, measure of axonal changes) and radial diffusivity (RD, measure of myelin changes) of each of the tracts and each group were measured and compared. The 22q11.2DS group showed statistically significant reductions of FA in IFOF in the left hemisphere. Additionally, reductions of AD were found in the IFOF and the ILF in both hemispheres. These findings might be the consequence of axonal changes, which is possibly due to fewer, thinner, or less organized fibers. No changes in RD were detected in any of the tracts delineated, which is in contrast to findings in schizophrenia patients where increases in RD are believed to be indicative of demyelination. We conclude that reduced axonal changes may be key to understanding the underlying pathology of WM leading to the visuo-spatial phenotype in 22q11.2DS.