1. Buizer-Voskamp JE, Franke L, Staal WG, van Daalen E, Kemner C, Ophoff RA, Vorstman JA, van Engeland H, Wijmenga C. {{Systematic genotype-phenotype analysis of autism susceptibility loci implicates additional symptoms to co-occur with autism}}. {Eur J Hum Genet};2009 (Nov 25)
Many genetic studies in autism have been performed, resulting in the identification of multiple linkage regions and cytogenetic aberrations, but little unequivocal evidence for the involvement of specific genes exists. By identifying novel symptoms in these patients, enhanced phenotyping of autistic individuals not only improves understanding and diagnosis but also helps to define biologically more homogeneous groups of patients, improving the potential to detect causative genes. Supported by recent copy number variation findings in autism, we hypothesized that for some susceptibility loci, autism resembles a contiguous gene syndrome, caused by aberrations within multiple (contiguous) genes, which jointly increases autism susceptibility. This would result in various different clinical manifestations that might be rather atypical, but that also co-occur with autism. To test this hypothesis, 13 susceptibility loci, identified through genetic linkage and cytogenetic analyses, were systematically analyzed. The Online Mendelian Inheritance in Man database was used to identify syndromes caused by mutations in the genes residing in each of these loci. Subsequent analysis of the symptoms expressed within these disorders allowed us to identify 33 symptoms (significantly more than expected, P=0.037) that were over-represented in previous reports mapping to these loci. Some of these symptoms, including seizures and craniofacial abnormalities, support our hypothesis as they are already known to co-occur with autism. These symptoms, together with ones that have not previously been described to co-occur with autism, might be considered for use as inclusion or exclusion criteria toward defining etiologically more homogeneous groups for molecular genetic studies of autismEuropean Journal of Human Genetics advance online publication, 25 November 2009; doi:10.1038/ejhg.2009.206.
2. Cale SI, Carr EG, Blakeley-Smith A, Owen-Deschryver JS. {{Context-based assessment and intervention for problem behavior in children with autism spectrum disorder}}. {Behav Modif};2009 (Nov);33(6):707-742.
The present study used a context-based model of assessment and intervention to explore whether interventions that modify context result in reduction of problem behavior in ecologically valid settings (i.e., typical routines implemented by typical education personnel in neighborhood schools). The Contextual Assessment Inventory (CAI) and a postassessment interview were administered to parents and teachers of eight children with Autism Spectrum Disorder to identify problem contexts. Then, environmental modification techniques were implemented in three priority contexts: namely, transitions, termination of preferred activities, and presence of a feared stimulus. Our results demonstrated an almost complete elimination of problem behavior in the priority contexts as well as successful completion of activities and routines related to those contexts. We discuss the value of conceptualizing problem behavior as a function of context with respect to facilitating both assessment and intervention, and the need for enhancing breadth of effects to determine the larger impact of a context-based approach on promoting meaningful behavior change in the community.
3. Cashin A, Sci DA, Barker P. {{The triad of impairment in autism revisited}}. {J Child Adolesc Psychiatr Nurs};2009 (Nov);22(4):189-193.
TOPIC: The triad of impairment referred to at present in the autism-related literature is a behavioral triad. This paper extends this thinking of the triad of impairment to the triad that underlies the behavioral manifestation. The real triad of impairment. PURPOSE: This paper considers the thinking and information processing style of autism and takes the next transitional step in understanding the triad of impairment. SOURCES USED: Contemporary literature on autism and information processing. CONCLUSIONS: Exceptional pioneering work in the late 1970s gave rise to the concept of the triad of impairments as the central plank of the construct of autism: impaired communication; impaired social skills; and a restricted and repetitive way of being-in-the-world. This clear articulation of the structures of the phenomena allowed a new way for professionals and families to see and understand autism, and to relate to those with autism. Like the evolution of many concepts, this was a transitional idea. The original triad of impairments described the behavioral manifestation; the actual triad of impairments is at the level of cognitive processing. The actual triad of impairment is static and ubiquitous unlike the variable and fluctuating behavioral manifestation. The actual triad of impairment in autism is visual as opposed to linguistic processing, impaired abstraction, and lack of theory of mind. The actual triad is central to all diagnosis that together makes up the autism spectrum.
4. Cohen IL, Tsiouris JA, Flory MJ, Kim SY, Freedland R, Heaney G, Pettinger J, Ted Brown W. {{A Large Scale Study of the Psychometric Characteristics of the IBR Modified Overt Aggression Scale: Findings and Evidence for Increased Self-Destructive Behaviors in Adult Females with Autism Spectrum Disorder}}. {J Autism Dev Disord};2009 (Nov 26)
The psychometric characteristics of the IBR Modified Overt Aggression Scale were studied in over 2,000 people with Intellectual Disability (ID). Reliability ranged from good to excellent. Aggression toward others and objects was highest in the youngest adults, in those in the moderate to severe range of ID, and in those with an autism spectrum diagnosis. Self-injury was highest in those in the severe to profound range of ID and in those with autism, particularly the females. Females with autism were also more likely to make the most self-deprecating statements. Our data suggest that adult females with autism are a unique group and support the notion that mood and anxiety disorders play a role in self-destructive behaviors in this population.
5. Delahanty RJ, Kang JQ, Brune CW, Kistner EO, Courchesne E, Cox NJ, Cook EH, Jr., Macdonald RL, Sutcliffe JS. {{Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism}}. {Mol Psychiatry};2009 (Nov 24)
Maternal 15q11-q13 duplication is the most common copy number variant in autism, accounting for approximately 1-3% of cases. The 15q11-q13 region is subject to epigenetic regulation, and genomic copy number losses and gains cause genomic disorders in a parent-of-origin-specific manner. One 15q11-q13 locus encodes the GABA(A) receptor beta3 subunit gene (GABRB3), which has been implicated by several studies in both autism and absence epilepsy, and the co-morbidity of epilepsy in autism is well established. We report that maternal transmission of a GABRB3 signal peptide variant (P11S), previously implicated in childhood absence epilepsy, is associated with autism. An analysis of wild-type and mutant beta3 subunit-containing alpha1beta3gamma2 or alpha3beta3gamma2 GABA(A) receptors shows reduced whole-cell current and decreased beta3 subunit protein on the cell surface due to impaired intracellular beta3 subunit processing. We thus provide the first evidence of an association between a specific GABA(A) receptor defect and autism, direct evidence that this defect causes synaptic dysfunction that is autism relevant and the first maternal risk effect in the 15q11-q13 autism duplication region that is linked to a coding variant.Molecular Psychiatry advance online publication, 24 November 2009; doi:10.1038/mp.2009.118.
6. Freitag CM, Staal W, Klauck SM, Duketis E, Waltes R. {{Genetics of autistic disorders: review and clinical implications}}. {Eur Child Adolesc Psychiatry};2009 (Nov 26)
Twin and family studies in autistic disorders (AD) have elucidated a high heritability of AD. In this literature review, we will present an overview on molecular genetic studies in AD and highlight the most recent findings of an increased rate of copy number variations in AD. An extensive literature search in the PubMed database was performed to obtain English published articles on genetic findings in autism. Results of linkage, (genome wide) association and cytogenetic studies are presented, and putative aetiopathological pathways are discussed. Implications of the different genetic findings for genetic counselling and genetic testing at present will be described. The article ends with a prospectus on future directions.
7. Griffith GM, Hastings RP, Nash S, Hill C. {{Using Matched Groups to Explore Child Behavior Problems and Maternal Well-Being in Children with Down Syndrome and Autism}}. {J Autism Dev Disord};2009 (Nov 20)
Mothers of children with Down syndrome, autism, and mixed etiology intellectual disabilities, matched on child age, gender, and communication skills (n = 19 in each group) completed measures of their child’s adaptive and problem behaviors, their own parenting stress, and positive perceptions of their child. Children with autism were rated as having more problem behaviors and lower levels of social competence than children with Down syndrome and mixed etiology intellectual disabilities. Mothers of children with autism scored lower on positive perceptions of their child, and higher on stress than the other two groups. After selecting closely matched groups, we found several group differences in child behavior but little evidence of group differences in maternal outcomes.
8. Hayward D, Eikeseth S, Gale C, Morgan S. {{Assessing progress during treatment for young children with autism receiving intensive behavioural interventions}}. {Autism};2009 (Nov);13(6):613-633.
This study examined progress after 1 year of treatment for children with autism who received a mean of 36 hours per week one-to-one University of California at Los Angeles Applied Behavior Analysis (UCLA ABA) treatment. Two types of service provision were compared: an intensive clinic based treatment model with all treatment personnel (N = 23), and an intensive parent managed treatment model with intensive supervision only (N = 21). A non-concurrent multiple baseline design across participants (N = 13) examined whether progress was associated with ABA treatment or confounders. Between intake and follow-up, children in both groups improved significantly on IQ, visual-spatial IQ, language comprehension, expressive language, social skills, motor skills and adaptive behaviour. There were no significant differences between the two groups on any of the measures at follow-up. Mean IQ for participants in both groups increased by 16 points between intake and follow-up. These findings are consistent with previous studies demonstrating the benefits of ABA treatment.
9. Hilton CL, Fitzgerald RT, Jackson KM, Maxim RA, Bosworth CC, Shattuck PT, Geschwind DH, Constantino JN. Brief Report: {{Under-Representation of African Americans in Autism Genetic Research: A Rationale for Inclusion of Subjects Representing Diverse Family Structures}}. {J Autism Dev Disord};2009 (Nov 20)
African American children with autism are seriously under-represented in existing genetic registries and biomedical research studies of autism. We estimated the number of African American children with autism in the St. Louis region using CDC surveillance data and present the outcomes of a concerted effort to enroll approximately one-third of that population into either of two large national genetic autism registries. The results revealed that even after traditional barriers to research participation were addressed and all contacted families expressed a willingness to participate, 67% of the reachable families were disqualified from participation because of family structure alone. Comprehensive efforts-including expansion of eligibility to families of diverse structure-are warranted to facilitate the inclusion of African American children in biomedical research.
10. Hurtig T, Kuusikko S, Mattila ML, Haapsamo H, Ebeling H, Jussila K, Joskitt L, Pauls D, Moilanen I. {{Multi-informant reports of psychiatric symptoms among high-functioning adolescents with Asperger syndrome or autism}}. Autism;2009 (Nov);13(6):583-598.
The aim of the study was to examine psychiatric symptoms in high-functioning adolescents with autism spectrum disorders reported by multiple informants. Forty-three 11- to 17-year-old adolescents with Asperger syndrome (AS) or high-functioning autism (HFA) and 217 typically developed adolescents completed the Youth Self-Report (YSR), while their parents completed the Child Behavior Checklist (CBCL). Teachers of adolescents with AS/HFA completed the Teacher Report Form (TRF). The informants reported significantly more psychiatric symptoms, especially withdrawn, anxious/depressed, social and attention problems, in adolescents with AS/HFA than in controls. In contrast to findings in the general population, the psychiatric problems of adolescents with AS/HFA are well acknowledged by multiple informants, including self-reports. However, anxiety and depressive symptoms were more commonly reported by adolescents with AS/HFA and their teachers than their parents, indicating that some emotional distress may be hidden from their parents.
11. Ingersoll B. {{Broader Autism Phenotype and Nonverbal Sensitivity: Evidence for an Association in the General Population}}. {J Autism Dev Disord};2009 (Nov 20)
This study examined the relationship between characteristics of the Broader Autism Phenotype (BAP) and nonverbal sensitivity, the ability to interpret nonverbal aspects of communication, in a non-clinical sample of college students. One hundred and two participants completed a self-report measure of the BAP, the Autism Spectrum Quotient (AQ), and two tests of nonverbal sensitivity, the Test of Nonverbal Cue Knowledge (TONCK), and the Diagnostic Analysis of Nonverbal Accuracy 2 (DANVA2). AQ score was correlated with TONCK performance and number of errors on the adult faces subtest of the DANVA2, but not adult paralanguage or postures. These findings suggest that characteristics of ASD in the general population are associated with differences in both explicit and implicit knowledge of nonverbal cues.
12. Koegel LK, Koegel RL, Green-Hopkins I, Barnes CC. {{Brief Report: Question-Asking and Collateral Language Acquisition in Children with Autism}}. {J Autism Dev Disord};2009 (Nov 20)
The literature suggests children with autism use communication primarily for requests and protests, and almost never for information-seeking. This study investigated whether teaching « Where » questions using intrinsic reinforcement procedures would produce the generalized use of the question, and whether concomitant improvements in related language structures, provided as answers to the children’s questions, would occur. In the context of a multiple baseline across participants design, data showed that the children could rapidly acquire and generalize the query, and that there were collateral improvements in the children’s use of language structures corresponding to the answers to the questions the children asked. The results are discussed in the context of teaching child initiations to improve linguistic competence in children with autism.
13. Mann JR, McDermott S, Bao H, Hardin J, Gregg A. {{Pre-Eclampsia, Birth Weight, and Autism Spectrum Disorders}}. {J Autism Dev Disord};2009 (Nov 20)
Autism spectrum disorders (ASD) are primarily inherited, but perinatal or other environmental factors may also be important. In an analysis of 87,677 births from 1996 through 2002, insured by the South Carolina Medicaid program, birth weight was significantly inversely associated with the odds of ASD (OR = 0.78, p = .001 for each additional kilogram). Maternal pre-eclampsia/eclampsia was significantly associated with greater odds of ASD (OR = 1.85, p < .0001 without controlling for birth weight; OR = 1.69, p = .0005, when controlling for birth weight). We conclude that reduced birth weight partially mediates the association between pre-eclampsia/eclampsia and ASD. Additional research is needed to investigate the potential mechanism(s) by which pre-eclampsia/eclampsia may influence ASD risk.
14. May-Benson TA, Koomar JA, Teasdale A. {{Incidence of pre-, peri-, and post-natal birth and developmental problems of children with sensory processing disorder and children with autism spectrum disorder}}. {Front Integr Neurosci};2009;3:31.
As the diagnosis of sensory processing disorder (SPD) is advanced, it is important to investigate potential contributing factors to this disorder as well as early diagnostic signs. An exploratory descriptive study, utilizing retrospective chart review, was conducted to investigate the incidence of pre-, peri- and post-natal, birth and developmental problems in a sample of 1000 children with SPD and of 467 children with autism spectrum disorder (ASD), who also had SPD. This study revealed that although no one factor was strongly associated with SPD or ASD, an average of seven events for children with SPD and eight events for children with ASD occurred across categories. These included: one pre-natal/pregnancy problem, delivery complication, assisted delivery, gestational or birth-related injury/illness; one or more early childhood illnesses or injuries; two or more infancy/early childhood developmental problems; and one or more delayed early childhood developmental milestones. When comparing results to national studies of the typical population, most remarkable was the incidence of jaundice, three to four times higher in both the SPD and ASD groups than in typical children. In addition, rates of breech position, cord wrap/ prolapse, assisted delivery methods (particularly forceps and suction deliveries), and high birth-weight were greater in both groups. Incidence of premature birth was higher in the ASD although not significantly different from the SPD group. Also of note was a high frequency of absent or brief crawling phase, and high percentages of problems with ear infections, allergies, and maternal stresses during pregnancy.
15. Niederhofer H. {{Arbohydrate-deficient transferrin does not seem to be associated with ADHD and autism}}. {Psychiatr Danub};2009 (Dec);21(4):517.
16. O’Hare A. {{Autism spectrum disorder: diagnosis and management}}. {Arch Dis Child Educ Pract Ed};2009 (Dec);94(6):161-168.
Autism spectrum disorders are of high prevalence and have a potentially complex range of presentations within the core impaired domains of social communication, reciprocal social interaction, imaginary thought and restricted and repetitive behaviours. Paediatricians need to recognise the possibility of these conditions among the high-risk populations of children with whom they work. This includes those presenting in the preschool years to child development clinics with delayed acquisition of language or general development delay or those presenting in the school years with coordination, academic, peer interaction and behavioural difficulties. In addition, paediatricians are essential members of the multidisciplinary teams charged with specialist assessment and their clinical history and examination can direct investigations for aetiology. This is a fast moving field with a challenging range of « grey evidence » causes and interventions. The approaches to managing these areas of work are discussed with an emphasis on recognition, important features in the history and clinical examination to aid differential diagnosis and investigations, interpreting the « grey evidence » and understanding intervention and prognosis.
17. Ploeger A, Raijmakers ME, van der Maas HL, Galis F. {{The Association Between Autism and Errors in Early Embryogenesis: What Is the Causal Mechanism?}} {Biol Psychiatry};2009 (Nov 20)
The association between embryonic errors and the development of autism has been recognized in the literature, but the mechanism underlying this association remains unknown. We propose that pleiotropic effects during a very early and specific stage of embryonic development-early organogenesis-can explain this association. In humans early organogenesis is an embryonic stage, spanning Day 20 to Day 40 after fertilization, which is characterized by intense interactivity among body parts of the embryo. This implies that a single mutation or environmental disturbance affecting development at this stage can have several phenotypic effects (i.e., pleiotropic effects). Disturbances during early organogenesis can lead to many different anomalies, including limb deformities, craniofacial malformations, brain pathology, and anomalies in other organs. We reviewed the literature and found ample evidence for the association between autism and different kinds of physical anomalies, which agrees with the hypothesis that pleiotropic effects are involved in the development of autism. The proposed mechanism integrates findings from a variety of studies on autism, including neurobiological studies and studies on physical anomalies and prenatal influences on neurodevelopmental outcomes. The implication is that the origin of autism can be much earlier in embryologic development than has been frequently reported.
18. Sokhadze E, Baruth J, Tasman A, Mansoor M, Ramaswamy R, Sears L, Mathai G, El-Baz A, Casanova MF. {{Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Affects Event-Related Potential Measures of Novelty Processing in Autism}}. {Appl Psychophysiol Biofeedback};2009 (Nov 26)
In our previous study on individuals with autism spectrum disorder (ASD) (Sokhadze et al., Appl Psychophysiol Biofeedback 34:37-51, 2009a) we reported abnormalities in the attention-orienting frontal event-related potentials (ERP) and the sustained-attention centro-parietal ERPs in a visual oddball experiment. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. In the present study we examine the effects of low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) on novelty processing as well as behavior and social functioning in 13 individuals with ASD. Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex (DLFPC) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons. We expected to find post-TMS differences in amplitude and latency of early and late ERP components. The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism. After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli. Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli. Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings. These results indicate a significant change in early, middle-latency and late ERP components at the frontal, centro-parietal, and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment. Overall, our preliminary results show that rTMS may prove to be an important research tool or treatment modality in addressing the stimulus hypersensitivity characteristic of autism spectrum disorders.
19. Stamova B, Green PG, Tian Y, Hertz-Picciotto I, Pessah IN, Hansen R, Yang X, Teng J, Gregg JP, Ashwood P, Van de Water J, Sharp FR. {{Correlations Between Gene Expression and Mercury Levels in Blood of Boys With and Without Autism}}. {Neurotox Res};2009 (Nov 24)
Gene expression in blood was correlated with mercury levels in blood of 2- to 5-year-old boys with autism (AU) compared to age-matched typically developing (TD) control boys. This was done to address the possibility that the two groups might metabolize toxicants, such as mercury, differently. RNA was isolated from blood and gene expression assessed on whole genome Affymetrix Human U133 expression microarrays. Mercury levels were measured using an inductively coupled plasma mass spectrometer. Analysis of covariance (ANCOVA) was performed and partial correlations between gene expression and mercury levels were calculated, after correcting for age and batch effects. To reduce false positives, only genes shared by the ANCOVA models were analyzed. Of the 26 genes that correlated with mercury levels in both AU and TD boys, 11 were significantly different between the groups (P(Diagnosis*Mercury) </= 0.05). The expression of a large number of genes (n = 316) correlated with mercury levels in TD but not in AU boys (P </= 0.05), the most represented biological functions being cell death and cell morphology. Expression of 189 genes correlated with mercury levels in AU but not in TD boys (P </= 0.05), the most represented biological functions being cell morphology, amino acid metabolism, and antigen presentation. These data and those in our companion study on correlation of gene expression and lead levels show that AU and TD children display different correlations between transcript levels and low levels of mercury and lead. These findings might suggest different genetic transcriptional programs associated with mercury in AU compared to TD children.
20. Tissot C. Establishing a sexual identity: {{Case studies of learners with autism and learning difficulties}}. {Autism};2009 (Nov);13(6):551-566.
The physical and emotional changes that occur in adolescence are part of the process of sexual maturity. These changes occur irrespective of ability and are often aligned with psychological and social factors. When the nature of a disability has an inherent limitation in social awareness, as is the case for individuals with autism, the achievement of personal sexual identity can become much more complex. Challenges in supporting individuals in this respect can be caused by the sensitive aspects of inappropriate behaviour, the abstract nature of teaching the topic, and the general reluctance on the part of parents and staff to discuss sexuality in individuals with disabilities. This article explores how a residential school addressed this gap. It provides details of how this need was met for seven students and the process undertaken to involve staff, parents and other stakeholders to establish ongoing support.
21. Warren SF, Gilkerson J, Richards JA, Oller DK, Xu D, Yapanel U, {{Gray S. What Automated Vocal Analysis Reveals About the Vocal Production and Language Learning Environment of Young Children with Autism}}. {J Autism Dev Disord};2009 (Nov 21)
The study compared the vocal production and language learning environments of 26 young children with autism spectrum disorder (ASD) to 78 typically developing children using measures derived from automated vocal analysis. A digital language processor and audio-processing algorithms measured the amount of adult words to children and the amount of vocalizations they produced during 12-h recording periods in their natural environments. The results indicated significant differences between typically developing children and children with ASD in the characteristics of conversations, the number of conversational turns, and in child vocalizations that correlated with parent measures of various child characteristics. Automated measurement of the language learning environment of young children with ASD reveals important differences from the environments experienced by typically developing children.
22. Wulffaert J, Van Berckelaer-Onnes IA, Scholte EM. Autistic {{disorder symptoms in Rett syndrome}}. {Autism};2009 (Nov);13(6):567-581.
According to the major classification systems it is not possible to diagnose a comorbid autistic disorder in persons with Rett syndrome. However, this is a controversial issue, and given the level of functioning of persons with Rett syndrome, the autistic disorder is expected to be present in a comparable proportion as in people with the same level of functioning. To investigate, parents of 52 females with classical and atypical Rett syndrome (2.4-49.3 years) completed the Developmental Behavior Checklist (DBC), the Diagnostic Interview for Social and Communication Disorders (DISCO) and the Dutch Vineland Screener 0-6 (VS 0-6). All participants had a severe to profound intellectual disability (ID) according to the VS 0-6. Behavior indicated an autistic disorder in 42 (DBC) to 58 percent (DISCO) of the Rett cases. Autistic behavior had decreased in 19 percent such that they no longer met the criteria for autistic disorder. Some participants were suspected of having a comorbid autistic disorder, though not more often than can be expected at their level of functioning. Clinicians should be aware of the possibility of a comorbid autistic disorder as much as they should be in other people with this level of functioning.
23. Yokoyama H, Hirose M, Nara C, Wakusawa K, Kubota Y, Haginoya K, Tsuchiya S, Iinuma K. {{[Waiting-for-Instruction behavior as depressive symptom in mentally retarded autistic children and adolescents and its treatment]}}. {No To Hattatsu};2009 (Nov);41(6):431-435.
We have seen 9 moderately to severely mentally-retarded autistic children and adolescents who waited for small-step instructions to perform previously acquired daily life activities (called « waiting-for-instruction » behavior). None of these patients were capable of expressing their depressive mood. All cases were considered to meet the criteria for major depressive episode described in DSM-IN. The « waiting-for-instruction » behavior was suggested to be a diagnostic key for depressive state in mentally retarded children and adolescents. GAF scales for depressive symptoms including the « waiting-for-instruction » behavior improved in 7 of these 9 cases with fluvoxamine. Risperidone and valproate sodium were useful for these symptoms in patients who were not responsive to fluvoxamine. Therefore, there is a possibility that they met the criteria for bipolar II disorder in DSM-IV.
