A double‐blind, parallel, multicenter comparison of L‐acetylcarnitine with placebo on the attention deficit hyperactivity disorder in fragile X syndrome boys A prospective open-label study of aripiprazole in fragile X syndrome [L-acetylcarnitine treatment on fragile X patients hyperactive behaviour]. New clinical findings in the fragile X-associated tremor ataxia syndrome (FXTAS) Obsessive and compulsive symptoms in schizophrenia: a randomized controlled trial with fluvoxamine and neuroleptics. L-acetylcarnitine treatment of mental decline in the elderly. Developing a utility index for the Aberrant Behavior Checklist (ABC-C) for fragile X syndrome Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome A controlled trial of stimulant medication in children with the fragile X syndrome. Independent frontal-system deficits in schizophrenia: cognitive, clinical, and adaptive implications Relationship of Cognition to Clinical Response in First-Episode Schizophrenia Spectrum Disorders. [Effects of L-acetylcarnitine on mental deterioration in the aged: initial results]. Speech and school performance in children with benign partial epilepsy with centro-temporal spikes (BCECTS) The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome. Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol. Identification of clinically meaningful relationships among cognition, functionality, and symptoms in subjects with schizophrenia or schizoaffective disorder Treatment of obsessive-compulsive symptoms in schizophrenic patients with clomipramine.
Attention deficit hyperactivity disorder ( ADHD ) is a frequent behavioral problem in young boys with fragile X syndrome ( FXS ) , and its treatment is critical for improving social ability . The short‐term efficacy of stimulant medications like methylpheni date ( MPH ) is well established in children with ADHD . FXS boys treated with MPH have improved attention span and socialization skills ; however their mood becomes unstable at higher doses . Therefore , alternative pharmacological treatment of ADHD symptoms is desirable . A recent study showed that carnitine has a beneficial effect on the hyperactive – impulsive behavior in boys with ADHD without side effects . Our previous placebo‐controlled trial indicated that L‐acetylcarnitine ( LAC ) reduces hyperactivity in FXS boys . The objective of this study was to determine the efficacy of LAC in a larger sample of FXS boys with ADHD . The study design was r and omized , double blind placebo controlled , parallel , and multicenter ( with eight centers involved in Italy , France , and Spain ) . Sixty‐three FXS males with ADHD ( aged 6–13 years ) were enrolled ; 7 patients dropped out , 56 completed the one‐year treatment , and 51 were included in the statistical analysis . Both groups improved their behavior , showing that psychosocial intervention has a significant therapeutic effect . However , we observed a stronger reduction of hyperactivity and improvement of social behavior in patients treated with LAC , compared with the placebo group , as determined by the Conners ' Global Index Parents and the Vinel and Adaptive Behavior Scale . Our results show that LAC ( 20–50 mg/kg/day ) represents a safe alternative to the use of stimulant drugs for the treatment of ADHD in FXS children . © 2008 Wiley‐Liss , Rationale Fragile X syndrome ( FXS ) is the most common inherited form of developmental disability and most common single gene cause of autism . Persons with FXS frequently exhibit irritable behavior marked by aggression , self-injury , and severe tantrums . Despite frequent clinical use of atypical antipsychotic drugs to target this behavioral cluster , no systematic trials to date have assessed the efficacy and safety of these drugs in persons with FXS . Methods We conducted a prospect i ve open-label 12-week trial of aripiprazole in 12 persons aged 6–25 years ( mean age , 14.3 years ) with FXS who were free of concomitant psychoactive drugs .  Results Aripiprazole use ( mean dose , 9.8 mg/day ) was associated with treatment response ( defined by a Clinical Global Impressions-Improvement scale score of much improved or very much improved and a ≥25 % improvement on the Aberrant Behavior Checklist-Irritability subscale ) in 10 of 12 ( 87 % ) persons . Two individuals ( 13 % ) discontinued aripiprazole prior to study completion due to adverse events . One discontinuation was due to akathisia , mild drooling , and mild tiredness and the other due to moderate tiredness and moderate drooling . No significant changes in vital signs including weight or laboratory measures occurred during treatment with aripiprazole . Conclusions Aripiprazole was generally safe and well tolerated and was associated with significant improvement in irritable behavior . Given these findings , a double-blind , placebo-controlled study of aripiprazole in FXS is warranted Hyperactivity is a significant problem for almost all young males affected by fragile X syndrome ( FXS ) , the most common inherited disease causing mental retardation . Therapeutical approaches are actually based on Central Nervous System ( CNS ) stimulants lacking a well defined rationale and efficacy while they further decrease the patient 's limited attention span . A pilot study on 17 fragile X male treated with L-acetylcarnitine ( LAC ) over one year , showed a significant reduction of their hyperactivity behaviour tested by the Conners Abbreviated Parent-Teacher Question naire . LAC use in FXS patients derives from the hypothesis that the biochemical and physiological properties this substance has may preserve brain activity . LAC is a small , hydrosoluble molecule that easily diffuses in the extracellular space and enters any cell in the nervous system through specific transporters . Different cerebral areas use this molecule differently to metabolize glucose and lipids to provide for ATP and neurotrasmitters synthesis . The acetyl group LAC carriers represents a key metabolic signaling element possibly mediating its effect in the CNS . The exogenous administration of LAC may affect brain activity in FXS by : I ) modulation of fuel partitioning for energy production , which at the mithocondrial level is associated with the Kreb 's cycle metabolic role in neurotransmitter synthesis ; II ) remodelling of lipid membrane in terms of LAC actively determining the production of polyunsaturated fatty acids ; III ) preferential effect on the attention component of the cholinergic system which relies on its peculiar modality of communication in the CNS . Based on the above premises an explorative , double-blind , placebo controlled , multicenter study is ongoing . A total population of 160 children from nine European centers will be enrolled . The objective of this study is to determine the effect of LAC on the hyperactive behaviour of FXS children as evaluated by the administration of the Conners Abbreviated Parent Question naire The objective of this paper was to assess the phenotypic variance in patients with the Fragile X-associated Tremor Ataxia Syndrome ( FXTAS ) and to further eluci date genotype – phenotype correlations in the illness . A second goal was to generate hypotheses regarding symptom progression based on careful histories in our sample that can now be tested in ongoing longitudinal studies . The variability of clinical signs and symptom progression in FXTAS complicates our underst and ing of its phenotype and presents a series of problems in clinical trial design . Similarly , pre-motor and non-motor symptoms have not been adequately explored to answer outst and ing questions regarding genotype – phenotype associations in FXTAS . This was a cross-sectional study of FMR1 premutation carriers from known fragile X syndrome pedigrees . We report on the first 50 subjects who have completed a full neurologic evaluation and a brain MRI . Subjects were selected on the basis of motor symptoms or abnormal results ( > 1 SD ) on a quantitative instrument design ed to detect mild tremor and ataxia ( CATSYS 1994 ) . A neuropsychological battery included the WAIS-III , COWA , and WCST . Statistical analysis used ANOVA and Fisher ’s exact test with p < 0.05 . All FMR1 premutation carriers were men of mean age 65 ± 7 years . According to the diagnostic criteria of Jacquemont et al. ( Am J Hum Genet 72(4):869–878 , 2003 ) , 21 subjects met criteria for definite FXTAS , 10 for probable , 9 for possible , and 10 were indeterminate . Duration of motor symptoms was significantly longer in the definitive group ( 8.6 ± 6 ) compared to the other groups ( p < 0.01 ) . The presentations in 40 subjects , excluding the indeterminate group , included : tremor 24 , ataxia 5 , memory symptoms 3 , parkinsonism 2 , and torticollis 1 . The data suggest at least two dominant phenotypic presentations : ( a ) a tremor-dominant subtype in which the onset of ataxia is delayed ; ( b ) a second in which ataxia is the dominant presentation from the outset . In both subtypes , once ataxia emerges it tends to track frontal cognitive changes ( p < 0.01 ) . The data support the view that FXTAS is a late-life neurodegenerative disorder with involvement of motor , non-motor , and cognitive systems . The results suggest at least two presentations with tremor- and ataxia-predominant phenotypes . In both , global cognitive decline appears to track ataxia . Prospect i ve longitudinal studies are needed to vali date this proposed evolution of FXTAS and its relevance to future clinical trials design Obsessive-compulsive-related disorders are frequently comorbid with schizophrenia . The existence of obsessive and compulsive symptoms in patients with schizophrenia represents one of the most severe types of psychotic disorders and may predict a poor prognosis in most cases . Previous pilot studies and case reports have shown that the condition of some patients with schizophrenia did not exacerbate and even improved when serotonin reuptake inhibitors ( SSRIs ) were added to their st and ard neuroleptic regimen . The aim of this study was to evaluate the efficacy of a combination treatment of an SSRI ( fluvoxamine ) and st and ard neuroleptics for the treatment of obsessive-compulsive ( OC ) symptomatology in patients with schizophrenia compared with administration of neuroleptics only . Thirty in patients who met DSM-IV criteria for schizophrenia and also had prominent OC symptoms were r and omly divided into two groups . Fourteen patients were treated with conventional neuroleptics and fluvoxamine in doses of 100 to 200 mg/day for 8 weeks . Sixteen patients comprised a control group and received only their previous therapeutic neuroleptic therapy . The patients were assessed using the Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) , the Positive and Negative Syndrome Scale ( PANSS ) , and the Clinical Global Impression Scale ( CGI ) at baseline and endpoint . Side effects were assessed weekly . The data were analyzed using an analysis of variance . A considerable reduction in PANSS ( 34.3 % ) and Y-BOCS ( 29.4 % ) scores was noted , and CGI scores decreased moderately in both groups . None of the patients showed an acute exacerbation at the end of the study . Side effects were mild and easily tolerated in most patients . This open , r and omized , controlled study reveals that coadministration of fluvoxamine , an SSRI , and neuroleptics in patients with schizophrenia and OC symptoms was associated with specific improvements of these symptoms . Thus , the use of an SSRI in treating a patient with schizophrenia and OC symptomatology may be warranted and safe . Other implication s of the findings , including general safety of the combined pharmacotherapy and the use of new antipsychotic medications , are also discussed A single-blind clinical trial was carried out on 481 subjects enrolled in 44 geriatric and neurologic units following a strict selection criteria : age , Mini Mental State Examination ( MMSE ) Global Deterioration Scale and Geriatric Depression Scale ( GDS ) . After the initial screening and enrollment , the trial was run for 150 days in four phases : phase T0 ( placebo treatment for 30 days ) , phases T1 and T2 ( L-acetylcarnitine ( LAC ) 1500 mg/day for 90 days ) , phase T3 ( further 30 days of placebo treatment ) . Drug efficacy was evaluated according to changes occurring from the beginning to the end of the tests which evaluate either whole and specific cognitive performances , or emotional-affective and relational behaviour . The outcome of phase T3 enabled the authors to estimate the possible favourable effects persisting after termination of L-acetylcarnitine therapy . The cognitive sphere evaluated by MMSE showed a significant increase in the total score at the end of LAC treatment ( p < 0.0001 ) . The R and t Memory Test also revealed that LAC treatment improved the items tested : the total score and the memory index increased significantly and the favourable effect persisted after LAC was discontinued . The emotional-affective area showed a significant improvement in the total score of the GDS after LAC therapy , and the positive results were confirmed by the Hamilton Rating Scale ( p < 0.0001 ) . The behavioural-relational aspects evaluated by the Family Stress Scale showed a significant decrease in the total score after treatment ( p < 0.0004 ) ; the same trend was observed in the scores for instability and negative feeling . No significant adverse drug reaction occurred during the trial . In conclusion , the statistical analysis of the data from this single-blind , multicentre trial of mild mental impairment in the elderly showed a significant improvement of several performances during and after LAC treatment . Other reports indicate that this drug may be effective in the treatment of dementia Purpose This study aim ed to develop a utility index ( the ABC-UI ) from the Aberrant Behavior Checklist-Community ( ABC-C ) , for use in quantifying the benefit of emerging treatments for fragile X syndrome ( FXS ) . Methods The ABC-C is a proxy-completed assessment of behaviour and is a widely used measure in FXS . A subset of ABC-C items across seven dimensions was identified to include in health state descriptions . This item reduction process was based on item performance , factor analysis and Rasch analysis performed on an observational study data set , and consultation with five clinical experts and a method ological expert . Dimensions were combined into health states using an orthogonal design and valued using time trade-off ( TTO ) , with lead-time TTO methods used where TTO indicated a state valued as worse than dead . Preference weights were estimated using mean , individual level , ordinary least squares and r and om-effects maximum likelihood estimation [ RE ( MLE ) ] regression models . Results A representative sample of the UK general public ( n = 349 ; mean age 35.8 years , 58.2 % female ) each valued 12 health states . Mean observed values ranged from 0.92 to 0.16 for best to worst health states . The RE ( MLE ) model performed best based on number of significant coefficients and mean absolute error of 0.018 . Mean utilities predicted by the model covered a similar range to that observed . Conclusions The ABC-UI estimates a wide range of utilities from patient-level FXS ABC-C data , allowing estimation of FXS health-related quality of life impact for economic evaluation from an established FXS clinical trial instrument Fragile X syndrome ( FXS ) is a rare inherited genetic disorder causing severe intellectual disability and autistic-like symptoms . Individuals with FXS , males in particular , often exhibit extreme eye gaze avoidance and hyperarousal when they encounter stressful social situations . We investigated whether oxytocin ( OT ) , a hormone with prosocial and anxiolytic effects , could alleviate symptoms of social anxiety in this population . A r and omized double-blind placebo-controlled single-dose trial was performed with intranasal administration of placebo , 24 IU OT and 48 IU OT . Measures of eye gaze frequency , heart rate , respiratory sinus arrhythmia ( RSA ) , heart rate variability ( HRV ) and salivary cortisol were obtained during a structured social challenge conducted 50 min following OT administration . Ten low-functioning males with FXS ( aged 13 - 28 years ) traveled to Stanford for the initial visit : 8 completed the study .  Eye gaze frequency improved significantly in response to the 24 IU OT dose and salivary cortisol levels decreased significantly in response to the 48 IU OT dose . There was no effect of OT on heart rate , RSA or HRV although individual plots of the heart rate data suggested that OT increased heart rate in some participants and decreased heart rate in others . These findings suggest that intranasal administration of OT may ameliorate some symptoms of social anxiety in patients with FXS . Further double-blind placebo-controlled studies of OT , conducted in combination with behavioral treatment programs , may be warranted Attentional deficits and hyperactivity frequently are major problems for fra(X ) boys . This study evaluated the effectiveness of 2 stimulant medications , methylpheni date and dextroamphetamine compared to placebo in 15 children ( 13 males , 2 females ) with the fra(X ) syndrome . A double-blind crossover design was used with outcome measures which included parent and teacher behavior checklists , a controlled observation period , continuous performance tasks and an actometer measure of movement . When the children were treated with methylpheni date only , improvement was seen in socialization skills and attention span according to teacher checklists .  Ten children were clinical ly considered responders and treatment was continued after the study was completed This study examined whether frontal-system impairments in schizophrenia occur independently of one another and whether they have distinct implication s for information processing , symptom severity , and adaptive functioning . We assessed 26 medication-free schizophrenic out patients and 18 normal control subjects on eight frontally mediated tasks , semantic information processing , IQ , the BPRS , and long-term psychosocial adaptation . Schizophrenic subjects showed three types of deficits , which were uncorrelated with one another : ( 1 ) Executive dysfunction ( inflexible problem solving ) was related to decreased use of expectancy during controlled semantic priming , lower intelligence , more severe negative symptoms and stereotyped mannerisms . ( 2 ) Disinhibition of responses ( to irrelevant stimuli ) was associated with increased automatic priming , a trend for more severe hallucinations , and was unrelated to intelligence . ( 3 ) Motor dyscoordination ( inaccurate , dysfluent motor sequencing ) was not related to semantic processing , intelligence , or symptoms . Furthermore , all three impairments were unrelated to generalized slowness , age , sex , illness length , or pre-washout neuroleptic dose . Two deficits accounted for aspects of long-term psychosocial adaptation , even after statistical correction for IQ : Executive dysfunction was associated with younger illness onset , poor purpose fulness and planning , impaired social relations , and lower global functioning . Motor dyscoordination was associated with poor treatment outcome and restricted educational advancement . Furthermore , executive and motor deficits interacted significantly ; subjects who had both deficits showed the least favorable treatment outcome . These findings are neither consistent with generalized impairment nor with a unitary ' frontal syndrome ' in schizophrenia . They provide preliminary evidence for at least three frontal-system deficits ( dorsolateral , orbital , and premotor ) , which are dissociable from one another , can occur without general intellectual impairment , and have distinct implication s for long-term adaptive functioning First-episode schizophrenia ( FES ) spectrum disorders are associated with pronounced cognitive dysfunction across all domains . However , less is known about the course of cognitive functioning , following the first presentation of psychosis , and the relationship of cognition to clinical course during initial treatment . The present longitudinal study examined the magnitude of neurocognitive impairment , using the MATRICS Consensus Cognitive Battery , in patients experiencing their first episode of psychosis at baseline and after 12 weeks of r and omized antipsychotic treatment with either aripiprazole or risperidone .  At baseline , FES patients evidence d marked impairments in cognitive functioning . Notably , performance on the mazes task of planning and reasoning significantly predicted the likelihood of meeting stringent criteria for positive symptom remission during the first 12 weeks of the trial . Performance on indices of general cognitive function , working memory , and verbal learning improved over time , but these improvements were mediated by improvements in both positive and negative symptoms . We did not detect any differential effects of antipsychotic medication assignment ( aripiprazole vs risperidone ) on cognitive functioning . Our results suggest that a brief paper- and -pencil measure reflecting planning/reasoning abilities may index responsivity to antipsychotic medication . However , improvements in cognitive functioning over time were related to clinical symptom improvement , reflecting " pseudospecificity . In this paper the preliminary findings of a multicentre study on the effects of Acetyl-L-Carnitine on mildly impaired elderly are reported . Statistical analysis was carried out on 236 out of 469 subjects sample d in 42 different Italian geriatric or hospital units . Each subject was treated over 150 days , and a battery of tests ( investigating cognitive functioning , emotional-affective state and relational behavior ) was administered at the beginning on the treatment and the conclusion of each of its four phases . In the first and the last phases there was a 30 days placebo treatment ( aim ed respectively to wash-out the effects of previous drug and to assess the residual effects of the treatment ) , while in the second and the third ones ( both 45 days long ) the subjects took 1500 mg/day of Acetyl-L-carnitine . Repeated multivariate analysis of variance and of covariance ( taking as independent variables phases of treatment , age , gender , etiology and severity of mental impairment , as dependent variables the scores either of each test administered or of groups of items and as covariants the level of depression and the sensitivity to placebo effect ) showed that drug treatment significantly increased the effectiveness of performance on all the measures of cognitive functioning and of emotional-affective state and on some scores of the relational behavior . Age result ed significantly influential on cognitive functioning and relational behavior , but not on emotional-affective state . Severity of mental impairment significantly influenced also several measures of cognitive functioning and relational behavior , while less consistent results were shown for gender and etiology of mental impairment . The placebo effect , although significant for some cognitive processes , was lower than that of treatment . There findings suggest that Acetyl-L-carnitine treatment is effective against the outcomes of mental impairment in the cognitive ( in particular , for memory functioning and constructional thinking ) and emotional-affective domains , while its effects on relational behaviour are less consistent , probably because they are partly biased in the subjective evaluation of caregivers and relatives by factors such as age and levels of mental impairment and depression PURPOSE To assess prospect ively language and speech ability in children with benign partial epilepsy with centro-temporal spikes ( BCECTS ) . To evaluate academic performance and social competencies both during the active disease and after remission . METHODS Right-h and ed school children with typical BCECTS and a control group matched by age , sex , h and edness and socioeconomic status were examined . The German version of WISC-R , the " Tübinger Luria Christensen Neuropsychological Test Set for children " ( TUKI ) , the " Verbal Learning Memory Test " ( VLMT ) , the " Heidelberger Speech Development Test-second edition " ( HSET ) , and the " Salzburger reading and writing test " ( SLRT ) were applied . The Child Behavior Checklist ( CBCL ) and a semi-structured interview were performed with the children 's teachers to gain insight into school performance , behavioral and emotional problems . RESULTS During the active phase , the patient group - despite normal global intellectual abilities - showed few , but significant impairments both in expressive speech and in receptive and expressive vocabulary . A significant deficit in the ability to recognize and express interpersonal relations was also found . Patients ' teachers stated deficits concerning academic performance and complained about disturbing behavior . Parents reported significantly more psycho-pathological features in the subscales " Aggressive Behavior " , " Attention Problems " and " Anxious/Depressed " of the CBCL . Results were independent of medication and spike localization . After complete recovery from BCECTS , these problems were not found any more . CONCLUSIONS Both deficits of speech-related abilities ( in both expressive and receptive vocabulary ) and behavioral disturbances can be detected in children with typical BCECTS , but are no longer apparent after remission of the seizure disorder STUDY OBJECTIVE To determine the efficacy of melatonin on  sleep problems in children with autistic spectrum disorder ( ASD ) and fragile X syndrome ( FXS ) . METHODS A 4-week , r and omized , double blind , placebo-controlled , crossover design was conducted following a 1-week baseline period . Either melatonin , 3 mg , or placebo was given to participants for 2 weeks and then alternated for another 2 weeks . Sleep variables , including sleep duration , sleep-onset time , sleep-onset latency time , and the number of night awakenings , were recorded using an Actiwatch and from sleep diaries completed by parents . All participants had been thoroughly assessed for ASD and also had DNA testing for the diagnosis of FXS . RESULTS Data were successfully obtained from the 12 of 18 subjects who completed the study ( 11 males , age range 2 to 15.25 years , mean 5.47 , SD 3.6 ) . Five participants met diagnostic criteria for ASD , 3 for FXS alone , 3 for FXS and ASD , and 1 for fragile X premutation . Eight out of 12 had  melatonin  first . The conclusions from a nonparametric repeated- measures technique indicate that mean night sleep duration was longer on melatonin than placebo by 21 minutes ( p = .02 ) , mean sleep-onset latency was shorter by 28 minutes ( p = .0001 ) , and mean sleep-onset time was earlier by 42 minutes ( p = .02 ) . CONCLUSION The results of this study support the efficacy and tolerability of melatonin treatment for sleep problems in children with ASD and FXS OBJECTIVE To assess the efficacy of quetiapine , a recently introduced second generation antipsychotic medication , in reducing cognitive impairment in patients with schizophrenia . DESIGN Prospect i ve , r and omized , double-blind clinical trial . PATIENTS 25 patients who met the Diagnostic and Statistical Manual of Mental Disorders , fourth edition , ( DSM-IV ) criteria for schizophrenia were recruited from 3 Canadian hospitals . INTERVENTION AND OUTCOME MEASURES After a 48-hour washout period , 25 patients with schizophrenia were r and omly assigned to double-blind treatment with quetiapine or haloperidol for 6 months and evaluated with rating scales for psychotic symptoms , mood and extrapyramidal side effects , as well as st and ardized neuropsychological measures sensitive to 6 cognitive domains : fine motor skill , attention span , verbal reasoning and fluency , visuospatial construction and fluency , executive skills and visuomotor tracking , and immediate recall of verbal and nonverbal material s. The measures were repeated 8 weeks and 6 months after treatment was initiated . RESULTS Quetiapine improved psychosis and mood without inducing extrapyramidal symptoms . Quetiapine also had beneficial effects on cognitive skills , particularly verbal reasoning and fluency skills and immediate recall , with additional improvements on executive skills and visuomotor tracking and on the average of the 6 cognitive domains with sustained treatment . Patients taking haloperidol showed improvements in general clinical status , but no specific improvements on the positive syndrome , the negative syndrome , depression ratings or cognitive skills . CONCLUSIONS These preliminary results support the potential value of quetiapine for improving cognitive impairment in patients with schizophrenia and emphasize the importance of further research with this promising atypical antipsychotic INTRODUCTION Cognitive impairment in schizophrenia and schizoaffective disorder is a major determinant of disability . This study explored the relationships among cognitive functioning , clinical symptoms , overall functionality , and demographic characteristics . METHODS This was a post hoc analysis of a 52-week , prospect i ve , r and omized , double-blind study ( N=323 ) comparing 2 doses of risperidone long-acting injectable ( RLAI ) in stable subjects with schizophrenia or schizoaffective disorder . Cognitive evaluations were performed and st and ardized using a healthy age- and sex-matched comparison group . Simple and multiple regression models were used to identify relationships among neurocognitive composite scores ( NCS ) , clinical symptom end points ( Positive and Negative Syndrome Scale [ PANSS ] total and factor scores ) , overall functionality ( Personal and Social Performance [ PSP ] score ) , and demographics . RESULTS A simple regression model identified significant relationships between the NCS at end point and PANSS total score , PANSS disorganized thoughts factor score , functioning ( PSP ) and age . A 1-point decrease on PANSS total score and PANSS disorganized thoughts factor score corresponded to an increase in NCS of 0.126-point , and 0.81-point increases , respectively . A 1-point increase on the PSP corresponded to a 0.186-point increase in the NCS T-score . Among the demographic variables , only age correlated significantly with cognition ( 10-year increase in age corresponded to 1.1-point decrease in NCS T-score ) in a multiple regression model . CONCLUSION Improved cognition was associated with beneficial changes in functional status and clinical symptoms ( particularly disorganization symptoms ) in subjects with schizophrenia/schizoaffective disorder . Older subjects showed less overall cognitive improvement . Improved cognitive and functional outcome is correlated with symptom improvements in RLAI-treated  patients with schizophrenia Recent studies show that obsessive-compulsive symptoms may occur in many patients with schizophrenia and may predict a poor prognosis . Pilot studies have shown that some schizophrenic patients may improve if a serotonin reuptake blocker is added to their neuroleptic . We have performed a pilot , double-blind , crossover study of clomipramine ( CMI ) or placebo , added to maintenance psychotropic medication . Six schizophrenic patients with obsessive-compulsive symptoms were studied in a double-blind CMI versus placebo crossover protocol . The patients met DSM-III-R criteria for chronic schizophrenia , experienced obsessive-compulsive symptoms , and had been previously stabilized on their psychiatric medication . The patients were rated at baseline and longitudinally through the study with the Positive and Negative Symptom Scale for Schizophrenia ( PANSS ) and the Yale Brown Obsessive-Compulsive Scale ( YBOCS ) . An analysis of covariance was used to compare the drug versus placebo effect at the final visit with the baseline rating as a covariate . Ratings on both the YBOCS and the PANSS showed that patients improved significantly more on CMI than on placebo . No patients experienced an exacerbation of psychotic symptoms . Preliminary findings from this double-blind , crossover , pilot study of CMI and placebo , design ed to assess the effect of CMI in the treatment of schizophrenic patients with obsessive symptoms  , suggest that CMI is superior to placebo in the treatment of obsessions and compulsions and improves overall schizophrenic symptoms . Further studies with larger sample s and longer follow-up period are necessary to confirm these preliminary findings
Regarding the primary outcome of psychological and learning capabilities , both studies assessed the effect of interventions on  children 's verbal and non-verbal intellectual functioning using the Wechsler Intelligence Scale for Children - Revised .
AUTHORS ' CONCLUSIONS Low- quality evidence from two small trials showed that when compared to placebo , LAC may not improve intellectual functioning or hyperactive behaviour in children with FXS
BACKGROUND People with fragile X syndrome ( FXS ) have an intellectual dysfunction that can range from very mild to severe .
Symptoms can include speech and language delays and behavioural difficulties such as aggression or self injurious behaviours , emotional lability , and anxiety-related problems ( for example obsessive-compulsive symptoms and perseverative behaviours ) .
In some cases , affected people may have an additional diagnosis of attention deficit hyperactivity disorder or an autism spectrum disorder .
OBJECTIVES To review the efficacy and safety of L-acetylcarnitine in improving the psychological , intellectual , and social performance of people with FXS .