Neuropsychological Changes Research Articles

Cognitive Impairment in Multiple Sclerosis: Clinical Manifestation, Neuroimaging Correlates, and Treatment.

Cognitive impairment is found in up to 70% of patients with multiple sclerosis (MS). Once thought of as a variant of subcortical dementia with a characteristic set of deficits, we now know that MS-related cognitive impairment can have many faces. This conceptual change in neuropsychology is embedded in a paradigm shift in the neuroscientific understanding of MS over the past 25 years: Partly based on modern neuroimaging techniques, the classical view of MS as an inflammatory demyelinating disease affecting the white matter of the central nervous system has been extended. In particular, many studies have shown that the MS pathology also includes neurodegeneration, and that gray matter structures such as the cerebral cortex can also show focal lesions, atrophy, or both. The authors present an updated summary of the clinical manifestation and neuroimaging correlates of cognitive impairment in MS, and discuss the relatively few treatment options available to date.

Decision-Making, Cognitive Distortions and Alcohol Use in Adolescent Problem and Non-problem Gamblers: An Experimental Study.

In the psychological literature, many studies have investigated the neuropsychological and behavioral changes that occur developmentally during adolescence. These studies have consistently observed a deficit in the decision-making ability of children and adolescents. This deficit has been ascribed to incomplete brain development. The same deficit has also been observed in adult problem and pathological gamblers. However, to date, no study has examined decision-making in adolescents with and without gambling problems. Furthermore, no study has ever examined associations between problem gambling, decision-making, cognitive distortions and alcohol use in youth. To address these issues, 104 male adolescents participated in this study. They were equally divided in two groups, problem gamblers and non-problem gamblers, based on South Oaks Gambling Screen Revised for Adolescents scores. All participants performed the Iowa gambling task and completed the Gambling Related Cognitions Scale and the alcohol use disorders identification test. Adolescent problem gamblers displayed impaired decision-making, reported high cognitive distortions, and had more problematic alcohol use compared to non-problem gamblers. Strong correlations between problem gambling, alcohol use, and cognitive distortions were observed. Decision-making correlated with interpretative bias. This study demonstrated that adolescent problem gamblers appear to have the same psychological profile as adult problem gamblers and that gambling involvement can negatively impact on decision-making ability that, in adolescence, is still developing. The correlations between interpretative bias and decision-making suggested that the beliefs in the ability to influence gambling outcomes may facilitate decision-making impairment.

Longitudinal Brain Changes Associated with Prophylactic Cranial Irradiation in Lung Cancer

IntroductionThe toxic effects of prophylactic cranial irradiation (PCI) and platinum-based chemotherapy on cognition in the lung cancer population have not yet been well established. In the present study we examined the longitudinal neuropsychological and brain structural changes observed in patients with lung cancer who were undergoing these treatments. MethodsTwenty-two patients with small cell lung cancer (SCLC) who underwent platinum-based chemotherapy and PCI were compared with two control groups: an age- and education-matched group of healthy controls (n = 21) and a group of patients with non-SCLC (NSCLC, n = 13) who underwent platinum-based chemotherapy. All groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging: T1-weighted and diffusion tensor imaging at baseline (before PCI for SCLC and chemotherapy for NSCLC) and at 3 months after treatment. T1 voxel-based morphometry and tract-based spatial statistics were used to analyze microstructural changes in gray matter (GM) and white matter (WM). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire—Core Questionnaire was also completed. ResultsPatients with SCLC exhibited cognitive deterioration in verbal fluency over time. Structural magnetic resonance imaging showed decreases in GM at 3 months in the right subcortical regions, bilateral insular cortex, and superior temporal gyrus in patients with SCLC compared with both control groups. Additionally, patients with SCLC showed decreases in GM over time in the aforementioned regions plus in the right parahippocampal gyrus and hippocampus, together with changes in the WM microstructure of the entire corpus callosum. These changes had a limited impact on responses to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire—Core Questionnaire, however. Patients with NSCLC showed no cognitive or brain structural differences after chemotherapy. ConclusionsThis longitudinal study documents moderate neuropsychological deficits together with notable brain-specific structural changes (in GM and WM) in patients with SCLC after chemotherapy and PCI, suggesting that chemotherapy and especially PCI are associated with the development of cognitive and structural brain toxic effects.

Bilateral paramedian thalamic infarctions in a young woman with patent foramen ovale

Background: Simultaneous bilateral thalamic infarctions are rare and in most cases associated with typical clinical pattern which, beside other things, include neuropsychological changes. Case report: We report a case of a 37- year-old woman with acute onset ofdiplopia from skew deviation, right-sided central facial nerve palsy, left hemihypesthesia, ataxia, with normal level of consciousness and without any neuropsychological disturbances except minor memory deficit. She was diagnosed with bilateral thalamic infarction due to the cardioembolisation via patent foramen ovale. Conclusion: In cases of bilateral thalamic infarction one can presume the existence of rare anatomic variant of thalamic perfusion commonly known as the artery of Percheron, single artery trunk that branches to irrigate both paramedian territories of thalamus. The cause of infarction can be cardioembolism trough the patent foramen ovale, especially in young adults. Our case represents a combination of two specific pathological conditions - patent foramen ovale and bilateral thalamic infarction. Clinical presentation in this case was unusual for the bithalamic paramedian infarction.

Neuropsychological Correlates of Hazard Perception in Older Adults.

Hazard perception, the ability to identify and react to hazards while driving, is of growing importance in driving research, given its strong relationship to real word driving variables. Furthermore, although poor hazard perception is associated with novice drivers, recent research suggests that it declines with advanced age. In the present study, we examined the neuropsychological correlates of hazard perception in a healthy older adult sample. A total of 68 adults age 60 and older who showed no signs of dementia and were active drivers completed a battery of neuropsychological tests as well as a hazard perception task. Tests included the Repeatable Battery for the Assessment of Neuropsychological Status, Wechsler Test of Adult Reading, Trail Making Test, Block Design, Useful Field of View, and the Delis-Kaplan Executive Function System Color Word Interference Test. Hazard perception errors were related to visuospatial/constructional skills, processing speed, memory, and executive functioning skills, with a battery of tests across these domains accounting for 36.7% of the variance in hazard perception errors. Executive functioning, particularly Trail Making Test part B, emerged as a strong predictor of hazard perception ability. Consistent with prior work showing the relationship of neuropsychological performance to other measures of driving ability, neuropsychological performance was associated with hazard perception skill. Future studies should examine the relationship of neuropsychological changes in adults who are showing driving impairment and/or cognitive changes associated with Mild Cognitive Impairment or dementia.

Reporting of neuropsychological dysfunction remains discrepant between individuals with traumatic brain injury and their close others up to five years post-injury

Purpose: The degree to which individuals with traumatic brain injury (TBI) and their close others share a common understanding and experience of post-injury neuropsychological changes is currently unclear. The aim of this preliminary study was to longitudinally examine levels of agreement between self and close other reports of neuropsychological dysfunction following TBI and explore factors associated with these agreement levels. Method: Sixty-three people with TBI and their nominated close others independently completed the Structured Outcome Questionnaire at 1- and 5-years post-injury, reporting whether the person with TBI was experiencing any negative cognitive, behavioural or emotional changes compared to pre-injury. Results: Agreement levels between pair members ranged from chance to approximately 75% across neuropsychological domains and did not significantly change over 1- and 5-year time points. In the case of pair disagreement, close others were generally more likely to report difficulties. Pair disagreement was significantly associated with close other anxiety. Conclusions: Agreement between self and close others remains limited up to 5-years post-injury which questions the practice of using these reports interchangeably in research and clinical practice. Preliminary findings suggest some association between pair disagreement and close other psychological function; however, further research is warranted.Implications for RehabilitationReporting of neuropsychological dysfunction between individuals with TBI and their close others is not sufficiently reliable to warrant interchangeable use within research or clinical practice.Including both individuals with TBI and their close others in clinical assessments will facilitate a more holistic understanding of the client’s difficulties and their relationships with those close to them.Preliminary findings indicate that disagreement between individuals with TBI and their close others may be associated with close other anxiety. Clinicians should be aware of the potential for disagreement to impact on the psychological health of close others.

Adult Neurogenic and Antidepressant Effects of Adiponectin: A Potential Replacement for Exercise?

Physical exercise has long been recognized to benefit locomotor and cardiovascular systems. Although an increasing body of evidence also suggests it to be an effective non-medicinal remedy for mental disorders such as depression, the underlying mechanisms remain elusive. A recent study has demonstrated that increases of the adipocyte-secreted hormone adiponectin in the central nervous system following exercise may be responsible for these neuropsychological changes, including enhanced generation of neurons in the adult hippocampus, as well as mitigation of depressive severity. The present review introduces the previously-reported functions of adult hippocampal neurogenesis and adiponectin, and discusses the potential relevance of adiponectin signaling in exercise-induced neural changes. Revealing these novel biological effects of adiponectin in the brain may help hunt reliable biomarkers to better guide the anti-depressive therapy with exercise intervention; meanwhile, pharmaceutical agents that raise endogenous levels of adiponectin or mimic its biological effects might serve as a replacement for physical exercise.

GABAergic Modulation in Diabetic Encephalopathy-Related Depression.

Central nervous system is not spared from the deleterious effects of diabetes, since several studies have described neuropsychological and neurobehavioral changes in diabetic subjects, suggesting that diabetic encephalopathy should be recognized as a complication of this complex metabolic disorder. In fact, psychiatric manifestations may accompany this encephalopathy, since the prevalence of depression in diabetic patients is much higher than in the general population. Furthermore, evidences from preclinical and clinical studies suggest that GABA plays a role both in the pathophysiology of the diabetic encephalopathy-related depression. So, this review addresses the GABAergic modulation in diabetic encephalopathy-related depression. Data presented from literature support the association between GABA and depressive- like behaviors in diabetic encephalopathy, being this neurotransmitter a potential target for the treatment of diabetes, depression and related comorbidities.

Importance of donor history of restless leg syndrome and pica to asses iron deficiency

Iron deficiency is associated with neuropsychological changes such as restless leg syndrome (RLS), pica, hair loss, etc. Our objective was to assess usefulness of history of RLS and pica in relation with iron stores in blood donors. During medical examination, apart from routine questionnaires specific history of RLS and pica was elicited. Along with hemoglobin markers of iron deficiency such as s. iron, s. ferritin and mean corpuscular volume were analyzed. Out of 400 blood donors 41 had h/o pica/RLS/pagophagia. Positive and negative predictive value of above history is 73.17% and 80.5% respectively. We recommend the use of a screening question for pica and/or RLS in blood donor questionnaire.

Reduced Verbal Fluency following Subthalamic Deep Brain Stimulation: A Frontal-Related Cognitive Deficit?

ObjectiveThe decrease in verbal fluency in patients with Parkinson’s disease (PD) undergoing subthalamic nucleus deep brain stimulation (STN-DBS) is usually assumed to reflect a frontal lobe-related cognitive dysfunction, although evidence for this is lacking.MethodsTo explore its underlying mechanisms, we combined neuropsychological, psychiatric and motor assessments with an examination of brain metabolism using F-18 fluorodeoxyglucose positron emission tomography, in 26 patients with PD, 3 months before and after surgery. We divided these patients into two groups, depending on whether or not they exhibited a postoperative deterioration in either phonemic (10 patients) or semantic (8 patients) fluency. We then compared the STN-DBS groups with and without verbal deterioration on changes in clinical measures and brain metabolism.ResultsWe did not find any neuropsychological change supporting the presence of an executive dysfunction in patients with a deficit in either phonemic or semantic fluency. Similarly, a comparison of patients with or without impaired fluency on brain metabolism failed to highlight any frontal areas involved in cognitive functions. However, greater changes in cognitive slowdown and apathy were observed in patients with a postoperative decrease in verbal fluency.ConclusionsThese results suggest that frontal lobe-related cognitive dysfunction could play only a minor role in the postoperative impairment of phonemic or semantic fluency, and that cognitive slowdown and apathy could have a more decisive influence. Furthermore, the phonemic and semantic impairments appeared to result from the disturbance of distinct mechanisms.

Basal ganglia pathology in ALS is associated with neuropsychological deficits.

To evaluate basal ganglia changes along the amyotrophic lateral sclerosis (ALS)-ALS-frontotemporal dementia (FTD) continuum using multiple, complementary imaging techniques. Sixty-seven C9orf72-negative patients with ALS and 39 healthy controls were included in a cross-sectional quantitative MRI study. Seven patients with ALS met criteria for comorbid behavioral variant FTD (ALS-FTD), 18 patients met the Strong criteria for cognitive and/or behavioral impairment (ALS-Plus), and 42 patients had no cognitive impairment (ALS-Nci). Volumetric, shape, and density analyses were performed for the thalamus, amygdala, nucleus accumbens, hippocampus, caudate nucleus, pallidum, and putamen. Significant basal ganglia volume differences were identified between the study groups. Shape analysis revealed distinct atrophy patterns in the amygdala in patients with ALS-Nci and in the hippocampus in patients with ALS-Plus in comparison with controls. Patients with ALS-FTD exhibited pathologic changes in the bilateral thalami, putamina, pallida, hippocampi, caudate, and accumbens nuclei in comparison with all other study groups. A preferential vulnerability has been identified within basal ganglia subregions, which connect directly to key cortical sites of ALS pathology. While the anatomical patterns were analogous, the degree of volumetric, shape, and density changes confirmed incremental pathology through the spectrum of ALS-Nci, ALS-Plus, to ALS-FTD. Performance on verbal memory tests correlated with hippocampal volumes, and accumbens nuclei volumes showed a negative correlation with apathy scores. We demonstrate correlations between basal ganglia measures and structure-specific neuropsychological performance and a gradient of incremental basal ganglia pathology across the ALS-ALS-FTD spectrum, suggesting that the degree of subcortical gray matter pathology in C9orf72-negative ALS is closely associated with neuropsychological changes.

O21.4 Decreased cellular energy in the brain frontal white matter is associated with past immunosuppresion in chronic hiv infection

Background Long-term brain neurochemical changes are not clearly understood in HIV-infected adults who are ageing and are otherwise clinically stable. Methods Forty men (mean age = 54 ± 7), 20 HIV-infected (70% with historical AIDS, nadir CD4 ≤350, all on antiretroviral treatment and virally suppressed), and 20 demographically comparable HIV-uninfected controls were enrolled into a prospective observational cohort study. All underwent standard neuropsychological testing to determine the level of neurocognitive performance over an 18-month period, and a proton magnetic resonance spectroscopy scan of the brain frontal white matter to assess in vivo neurochemical information. Clinically relevant neuropsychological change over the study period was determined using neurocognitive norms for change. Major brain metabolites: Creatine, N-Acetyl Aspartate, Choline, Glutamate/Glutamine and Myo-Inositol were fitted in jMRUI in reference to water. Brain metabolites’ change was determined using linear regression with a time effect, a group effect and a time*group interaction effect. Data were randomly selected from the larger baseline cohort (N = 120) for this preliminary analysis. Results Over the 18 months period, neurocognitive performance change did not differ between HIV-infected and controls. Creatine significantly decreased in the HIV-infected compared to the controls (p Conclusions Chronic HIV infection is associated with subclinical cellular energy abnormalities (Creatine) linked to past levels of immunosuppression and acceleration of neuronal integrity (N-Acetyl Aspartate). This preliminary study further reinforces the need for longer-term follow-up in chronic HIV-infected ageing persons to determine the prognostic value of these findings. Disclosures This project was supported in part by NHMRC project grant ID568746, NHMRC Career Development Fellowship APP1045400 and Abbvie research grant supporting the acquisition of the follow-up MRI (CIA Cysique). BJB has received research funding, consultancy fees, and lecture and travel sponsorships from Gilead Sciences, ViiV Healthcare, and MSD. LAC has received research support from MSD, Abbvie, Gilead Sciences, and ViiVhealthcare. LAC has received honoraria from Abbvie and ViiVHealthcare.

Treating a GAD65 Antibody-Associated Limbic Encephalitis with Basiliximab: A Case Study.

Antibodies (ABs) against the 65-kDa isoform of the intracellular enzyme glutamate decarboxylase (GAD65) have been found in limbic encephalitis (LE) and other neurological conditions. The direct significance of anti-GAD65-ABs for epilepsy is unclear. However, in histological preparations from biopsies of resective epilepsy surgeries, predominantly cytotoxic T-lymphocytes were detected making close contacts to neurons. Activated T-lymphocytes can, in turn, be selectively controlled by therapeutic interleukin-2 receptor Abs, such as basiliximab. We report of a 25-year-old male patient with epilepsy since the age of 18 and displaying clinical signs of LE and a high titer of GAD65 ABs in cerebrospinal fluid (CSF) and serum. Monthly, repetitive, intravenous cortisone pulse therapies that were initially administered for 6 months failed to improve his condition. Subsequent flow-cytometry analysis of CSF showed especially an increased fraction of activated HLA-DR(+) CD8(+) T-lymphocytes (fCD8(+)TL) when compared to controls. Thus, a second, intravenous cortisone pulse therapy with an additional basiliximab dose of 20 mg/month was started. After 3 months, the fCD8(+)TL in the CSF normalized; after 6 months, the psychological impulse-control deficits normalized; and after 11 months the patient was seizure free. However, 7 weeks later, seizures and, later on, psychological deficits recurred and fCD8(+)TL was once again present in the CSF. Flumazenil PET, magnetic resonance imaging-volumetry, and neuropsychological changes during therapy are described. The correlation of the fCD8(+)TL in the CSF with clinical and paraclinical measures of disease activity combined with the unambiguous response to basiliximab strongly argues in favor of the putative pathogenic role fCD8(+)TL in anti-GAD65 LE. The clinical relapse at the end of the observation period might be due to the formation of human anti-drug ABs, a well-known complication of therapy with chimeric ABs.

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Long-term cognitive dysfunction in the rat following docetaxel treatment is ameliorated by the phosphodiesterase-4 inhibitor, rolipram

Clinical studies report evidence of long-term cognitive and other deficits following adjunctive chemotherapy treatment, which is often termed “chemobrain” or “chemo-fog”. The neurological bases of these impairments are poorly understood. Here, we hypothesize that systemic chemotherapy treatment causes long-term neurobehavioral deficits, and that these deficits are reversed by manipulation of cAMP by the PDE4 inhibitor, rolipram.Male han Wistar rats were treated with docetaxel (an adjunctive chemotherapeutic agent (1mg/kg i.v.)) or control solution (ethanol/Tween 20/0.9% Saline – 5/5/90) once per week for 4 weeks. They were allowed to recover for 4 weeks, administration of rolipram (0.5mg/kg po) or vehicle (maple syrup) then began and continued daily for 4 weeks. At the end of the treatment regime animals were tested for spatial and recognition memory deficits with the object exploration task and for depressive- and anxiety-like behavior in the forced swim test (FST) and open field exploration.We report docetaxel treatment impaired spatial memory but not object recognition memory, compared to control rats. Docetaxel-treated rats also spent significantly more time immobile than controls in the FST. Chronic rolipram treatment attenuated all of these docetaxel-associated changes, recovering spatial memory and reducing immobility. In conclusion, docetaxel-treated rats exhibit alterations in spatial memory and depressive-like behavior, which are reversed following chronic rolipram administration. These results detect long-term cognitive and mood changes following docetaxel treatment and identify PDE4 inhibition as a target treatment of neuropsychological changes associated with “chemobrain”.

Diagnosis of cognitive impairment onset in older adults based on limitations in language skills / Diagnóstico del inicio del deterioro cognitivo en mayores a partir de limitaciones en las capacidades lingüísticas

Progressive decline in language has been described in neuropsychological studies on Alzheimer’s disease and Mild Cognitive Impairment (MCI). We investigate this decline in its early stages, as well as its manifestations and the linguistic differences between participants at risk of developing MCI and without impairment. Participants were 36 older adults, all aged over 65. They were assessed using 31 subtests grouped into eight areas: fluency, comprehension, oral expression, reading, writing, memory, perceptual organization and processing speed. Our results showed significant differences between participants at risk of developing MCI and without impairment in verbal tests but not in manipulative tests. All participants at risk of developing MCI scored lowest in these eight areas. Our findings illustrate the relevance of investigating language skills in people at risk of developing MCI. Investigating these neuropsychological changes will help design appropriate intervention programmes that affect areas with higher levels of impairment.

Neuropsychological and functional outcomes in recent-onset major depression, bipolar disorder and schizophrenia-spectrum disorders: a longitudinal cohort study.

Functional disability is the lead contributor to burden of mental illness. Cognitive deficits frequently limit functional recovery, although whether changes in cognition and disability are longitudinally associated in recent-onset individuals remains unclear. Using a prospective, cohort design, 311 patients were recruited and assessed at baseline. One hundred and sixty-seven patients met eligibility criteria (M=21.5 years old, s.d.=4.8) and returned for follow-up (M=20.6 months later, s.d.=7.8). Two-hundred and thirty participants were included in the final analysis, comprising clinically stable patients with major depression (n=71), bipolar disorder (BD; n=61), schizophrenia-spectrum disorders (n=35) and 63 healthy controls. Neuropsychological functioning and self-rated functional disability were examined using mixed-design, repeated-measures analysis, across diagnoses and cognitive clusters, covarying for relevant confounds. Clinical, neuropsychological and functional changes did not differ between diagnoses (all P>0.05). Three reliable neuropsychological subgroups emerged through cluster analysis, characterized by psychomotor slowing, improved sustained attention, and improved verbal memory. Controlling for diagnosis and changes in residual symptoms, clusters with improved neuropsychological functioning observed greater reductions in functional disability than the psychomotor slowing cluster, which instead demonstrated a worsening in disability (P<0.01). Improved sustained attention was independently associated with greater likelihood of follow-up employment (P<0.01). Diagnosis of BD uniquely predicted both follow-up employment and independent living. Neuropsychological course appears to be independently predictive of subjective and objective functional outcomes. Importantly, cognitive phenotypes may reflect distinct pathophysiologies shared across major psychiatric conditions, and be ideal targets for personalized early intervention.

The neuropsychology of obsessive-compulsive personality disorder: a new analysis.

Obsessive compulsive personality disorder (OCPD) is characterized by perfectionism, need for control, and cognitive rigidity. Currently, little neuropsychological data exist on this condition, though emerging evidence does suggest that disorders marked by compulsivity, including obsessive-compulsive disorder (OCD), are associated with impairment in cognitive flexibility and executive planning on neurocognitive tasks. The current study investigated the neurocognitive profile in a nonclinical community-based sample of people fulfilling diagnostic criteria for OCPD in the absence of major psychiatric comorbidity. Twenty-one nonclinical subjects who fulfilled Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for OCPD were compared with 15 healthy controls on selected clinical and neurocognitive tasks. OCPD was measured using the Compulsive Personality Assessment Scale (CPAS). Participants completed tests from the Cambridge Automated Neuropsychological Test Battery including tests of set shifting (Intra-Extra Dimensional [IED] Set Shifting) executive planning (Stockings of Cambridge [SOC]), and decision making (Cambridge Gamble Task [CGT]). The OCPD group made significantly more IED-ED shift errors and total shift errors, and also showed longer mean initial thinking time on the SOC at moderate levels of difficulty. No differences emerged on the CGT. Nonclinical cases of OCPD showed significant cognitive inflexibility coupled with executive planning deficits, whereas decision-making remained intact. This profile of impairment overlaps with that of OCD and implies that common neuropsychological changes affect individuals with these disorders.

Affective Disorders with or Without Comorbid Alcohol Dependence: a Longitudinal Neuropsychological and Neuroimaging Investigation in Young Adults

Introduction Limited research has examined the early neuropsychological and neurobiological changes associated with comorbid affective disorders and alcohol dependence. Objectives & Aims To investigate the cognitive and volumetric changes in individuals diagnosed with affective disorders with or without comorbid alcohol dependence. Methods Young adults (n = 21) who were undergoing medically-managed inpatient alcohol detoxification with comorbid affective disorders were neuropsychologically assessed 4-weeks following hospital discharge, and additionally underwent MRI brain scans during admission and 4-weeks following discharge. An affective disorders-only group (n = 21) with an equal distribution of anxiety and mood disorders was recruited through a youth mental health clinic. Results Compared to affective disorders only (M = 31.8 ± 4.4 years old), individuals with affective disorders and alcohol dependence (M = 33.9 ± 6.3 years old; M = 21.1 ± 9.2 standard drinks/day) exhibited worse sustained attention and visual memory functioning. There was a highly significant association between drinking levels since detoxification and total brain volume change, such that resumption of heavy drinking attenuated brain volume gains associated with short-term abstinence (r = -0.87, p Conclusions In young adults with affective disorders, comorbid alcohol dependence is associated with more pronounced cognitive dysfunction, suggesting that these deficits are most relevant for cognitive remediation interventions. Crucially, abstinence or reduced drinking was associated with brain volume gains, whereas resumption of heavy drinking was associated with brain volume reductions, suggesting that medically-managed alcohol detoxification may, at least, partially reverse the neurobiological changes associated with prolonged alcohol dependence in young adults.

Neuropsychological and Brain Functional Changes Across the Different Phases of Schizoaffective Disorder

Schizoaffective disorder was first described by J. Kasanin in 1933, since then its nosology remains a matter of controversy. We aim to add further neurobiological findings to this debate. Memory and executive function were tested in 22 acutely ill schizoaffective patients; they also underwent fMRI scanning during performance of the n-back working memory test. The same measures were obtained after they had been in remission for ≥2 months. 22 matched healthy individuals were also examined. Compared to controls, acute schizoaffective patients showed reduced activation in the DLPFC and also a failure of deactivation in the medial frontal cortex (1). In clinical remission, schizomanic patients showed an improvement of memory but not of executive function, while schizodepressive patients did not change in either domain. All schizoaffective patients in clinical remission showed memory and executive impairment compared to the controls. On fMRI, acutely ill schizomanic patients had reversible frontal hypo-activation when compared to clinical remission, while activation patterns in ill and remitted schizodepressive patients were similar. The whole group of schizoaffective patients in clinical remission showed a failure of de-activation in the medial frontal gyrus compared to the healthy controls. There was evidence for memory improvement and state dependent changes in activation in schizomanic patients across relapse and remission (2). The results demonstrate that schizoaffective disorder is characterized by medial frontal failure of deactivation and hence default mode network dysfunction (3), which is present during both active illness and remission suggesting that it is a trait factor for the disorder.