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1.
Psychol Med ; 49(1): 75-83, 2019 01.
Article in English | MEDLINE | ID: mdl-29521610

ABSTRACT

BACKGROUND: Working memory (WM) deficits in schizophrenia (SCZ) have been linked to impairments in the encoding phase that are associated with aberrant neuronal functioning. Similar abnormalities have been observed in unaffected first-degree relatives (REL) and are thus discussed as candidate endophenotypes. The process of WM consolidation - i.e. the formation of durable WM representations - is assumed to be impaired in SCZ, but no study has investigated WM consolidation and neuronal correlates of visual WM encoding in REL before. METHOD: We examined whole-brain activation during the encoding phase with an event-related functional magnetic resonance imaging study design in 25 SCZ subjects, 22 REL subjects, and 25 healthy controls. Subjects performed a visual masked change detection task that assessed WM performance and consolidation. RESULTS: SCZ showed deficient WM performance indicating an impairment consolidation process, accompanied by broad neuronal hypoactivation, most prominently in frontal brain regions, as well as increased activity of the anterior cingulate during the encoding phase. REL showed decreased neuronal activity in the middle and medial frontal gyrus and increased activity in the precentral gyrus and insula during encoding, but no significant behavioral deficits were observed. In respect of given consolidation times, REL showed a shift from decreased frontal activity at short time intervals to increased frontal activity at longer time intervals. CONCLUSIONS: Findings suggest WM consolidation may be slowed in REL so that the deployment of compensatory neuronal resources during encoding is needed to assure proper WM performance. This supports the view of WM-related neuronal dysfunctions as a potential endophenotypic marker.


Subject(s)
Endophenotypes , Gyrus Cinguli/physiopathology , Memory Consolidation/physiology , Memory, Short-Term/physiology , Prefrontal Cortex/physiopathology , Schizophrenia/physiopathology , Visual Perception/physiology , Adult , Family , Female , Functional Neuroimaging , Gyrus Cinguli/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Prefrontal Cortex/diagnostic imaging
2.
Eur Arch Psychiatry Clin Neurosci ; 267(3): 199-212, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27549216

ABSTRACT

Proteomic analyses facilitate the interpretation of molecular biomarker probes which are very helpful in diagnosing schizophrenia (SZ). In the current study, we attempt to test whether potential differences in plasma protein expressions in SZ and bipolar disorder (BD) are associated with cognitive deficits and their underlying brain structures. Forty-two plasma proteins of 29 SZ patients, 25 BD patients and 93 non-clinical controls were quantified and analysed using multiple reaction monitoring-based triple quadrupole mass spectrometry approach. We also computed group comparisons of protein expressions between patients and controls, and between SZ and BD patients, as well. Potential associations of protein levels with cognitive functioning (psychomotor speed, executive functioning, crystallised intelligence) as well as underlying brain volume in the hippocampus were explored, using bivariate correlation analyses. The main finding of this study was that apolipoprotein expression differed between patients and controls and that these alterations in both disease groups were putatively related to cognitive impairments as well as to hippocampus volumes. However, none of the protein level differences were related to clinical symptom severity. In summary, altered apolipoprotein expression in BD and SZ was linked to cognitive decline and underlying morphological changes in both disorders. Our results suggest that the detection of molecular patterns in association with cognitive performance and its underlying brain morphology is of great importance for understanding of the pathological mechanisms of SZ and BD, as well as for supporting the diagnosis and treatment of both disorders.


Subject(s)
Apolipoproteins C/metabolism , Bipolar Disorder/complications , Bipolar Disorder/pathology , Cognition Disorders/etiology , Hippocampus/metabolism , Schizophrenia/complications , Schizophrenia/pathology , Adult , Blood Proteins/metabolism , Female , Humans , Male , Mass Spectrometry , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating Scales , Statistics as Topic
3.
BMC Med ; 13: 289, 2015 Nov 30.
Article in English | MEDLINE | ID: mdl-26621529

ABSTRACT

BACKGROUND: The neurotrophic hypothesis postulates that mood disorders such as bipolar disorder (BD) are associated with a lower expression of brain-derived neurotrophic factor (BDNF). However, its role in peripheral blood as a biomarker of disease activity and of stage for BD, transcending pathophysiology, is still disputed. In the last few years an increasing number of clinical studies assessing BDNF in serum and plasma have been published. Therefore, it is now possible to analyse the association between BDNF levels and the severity of affective symptoms in BD as well as the effects of acute drug treatment of mood episodes on BDNF levels. METHODS: We conducted a systematic review and meta-analysis of all studies on serum and plasma BDNF levels in bipolar disorder. RESULTS: Through a series of meta-analyses including a total of 52 studies with 6,481 participants, we show that, compared to healthy controls, peripheral BDNF levels are reduced to the same extent in manic (Hedges' g = -0.57, P = 0.010) and depressive (Hedges' g = -0.93, P = 0.001) episodes, while BDNF levels are not significantly altered in euthymia. In meta-regression analyses, BDNF levels additionally negatively correlate with the severity of both manic and depressive symptoms. We found no evidence for a significant impact of illness duration on BDNF levels. In addition, in plasma, but not serum, peripheral BDNF levels increase after the successful treatment of an acute mania episode, but not of a depressive one. CONCLUSIONS: In summary, our data suggest that peripheral BDNF levels, more clearly in plasma than in serum, is a potential biomarker of disease activity in BD, but not a biomarker of stage. We suggest that peripheral BDNF may, in future, be used as a part of a blood protein composite measure to assess disease activity in BD.


Subject(s)
Biomarkers/blood , Bipolar Disorder/blood , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Bipolar Disorder/drug therapy , Depression , Female , Humans , Male , Middle Aged
4.
Neuroimage ; 89: 81-91, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-24296331

ABSTRACT

The apolipoprotein E ε4 allele is a well established genetic risk factor for sporadic Alzheimer's disease. It is associated with structural and functional brain changes in healthy young, middle-aged and elderly subjects. In the current study, we assessed the impact of the ApoE genotype on brain macro- and microstructure, cognitive functioning and brain activity in fifty healthy young subjects (25 ApoE ε4 (ε4+) carriers and 25 non-carriers (ε4-), mean age 26.4±4.6years). We used diffusion tensor imaging (DTI) and voxel based morphometry (VBM) to assess brain structure, an extensive neuropsychological battery to test cognitive functioning and event-related functional magnetic resonance imaging (fMRI) to capture brain activity during episodic memory encoding and retrieval. ApoE ε4 carriers differed from non-carriers in fMRI activations but not in cognitive performance nor in brain micro- and macrostructure. These results suggest functional alterations in the episodic memory network that are modulated by the ε4 allele and might precede clinical or structural neurodegeneration.


Subject(s)
Apolipoprotein E4/genetics , Brain/anatomy & histology , Brain/physiology , Memory, Episodic , Adult , Brain Mapping , Diffusion Tensor Imaging , Female , Genotype , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Young Adult
5.
Eur J Neurosci ; 40(7): 3128-35, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24989884

ABSTRACT

The apolipoprotein E ε4 (ApoE ε4) allele not only represents the strongest single genetic risk factor for sporadic Alzheimer's disease, but also imposes independent effects on brain function in healthy individuals where it has been shown to promote subtle memory deficits and altered intrinsic functional brain network connectivity. Based on previous work showing a potential relevance of the default mode network (DMN) functional connectivity for episodic memory function, we hypothesized that the ApoE ε4 genotype would affect memory performance via modulation of the DMN. We assessed 63 healthy individuals (50-80 years old), of which 20 carried the ε4 allele. All participants underwent resting-state functional magnetic resonance imaging (fMRI), high-resolution 3D anatomical MRI imaging and neuropsychological assessment. Functional connectivity analysis of resting-state activity was performed with a predefined seed region located in the left posterior cingulate cortex (PCC), a core region of the DMN. ApoE ε4 carriers performed significantly poorer than non-carriers in wordlist recognition and cued recall. Furthermore, ε4 carriers showed increased connectivity relative to ε4 non-carriers between the PCC seed region and left-hemispheric middle temporal gyrus (MTG). There was a positive correlation between recognition memory scores and resting-state connectivity in the left MTG in ε4 carriers. These results can be interpreted as compensatory mechanisms strengthening the cross-links between DMN core areas and cortical areas involved in memory processing.


Subject(s)
Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Apolipoprotein E4/genetics , Gyrus Cinguli/physiology , Recognition, Psychology/physiology , Temporal Lobe/physiology , Aged , Brain/physiology , Brain Mapping , Female , Genetic Predisposition to Disease , Genotype , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Net/physiology , Neuropsychological Tests , Rest , Risk Factors
6.
Bipolar Disord ; 16(8): 830-45, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25164120

ABSTRACT

OBJECTIVES: We combined multimodal functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging to probe abnormalities in brain circuits underpinning episodic memory performance deficits in patients with bipolar disorder (BD). METHODS: We acquired whole-brain fMRI data in 21 patients with BD and a matched group of 20 healthy controls during a non-verbal episodic memory task, using abstract shapes. We also examined density of gray matter, using voxel-based morphometry (VBM), and integrity of connecting fiber tracts, using diffusion tensor imaging (DTI) and tract-based spatial statistics, for areas with significant activation differences. RESULTS: Patients with BD remembered less well than controls which shapes they had seen and had lower activation levels during the encoding stage of the task in the anterior cingulate gyrus, the precuneus/cuneus bilaterally, and the left lingual gyrus, and higher activation levels during the retrieval stage in the left temporo-parietal junction. Patients with BD showed reduced gray matter volumes in the left anterior cingulate, the precuneus/cuneus bilaterally, and the left temporo-parietal region in comparison with controls. DTI revealed increased radial, axial, and mean diffusivity in the left superior longitudinal fascicle in patients with BD compared with controls. CONCLUSIONS: Changes in task-related activation in frontal and parietal areas were associated with poorer episodic memory in patients with BD. Compared with data from single imaging modalities, integration of multimodal neuroimaging data enables the building of more complete neuropsychological models of mental disorders.


Subject(s)
Bipolar Disorder/complications , Brain/physiopathology , Memory Disorders/etiology , Memory Disorders/pathology , Memory, Episodic , Adult , Brain/blood supply , Brain/pathology , Case-Control Studies , Diffusion Tensor Imaging , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Neural Pathways/blood supply , Neural Pathways/pathology , Neuropsychological Tests , Oxygen/blood , Photic Stimulation , Psychiatric Status Rating Scales , Young Adult
7.
Eur Arch Psychiatry Clin Neurosci ; 264(7): 589-604, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24487666

ABSTRACT

Cognitive deficits are core symptoms in patients with schizophrenia (SZ) and major depressive disorder (MDD), but specific and approved treatments for cognitive deterioration are scarce. Experimental and clinical evidence suggests that aerobic exercise may help to reduce psychopathological symptoms and support cognitive performance, but this has not yet been systematically investigated. In the current study, we examined the effects of aerobic training on cognitive performance and symptom severity in psychiatric inpatients. To our knowledge, to date, no studies have been published that directly compare the effects of exercise across disease groups in order to acquire a better understanding of disease-specific versus general or overlapping effects of physical training intervention. Two disease groups (n=22 MDD patients, n=29 SZ patients) that were matched for age, gender, duration of disease and years of education received cognitive training combined either with aerobic physical exercise or with mental relaxation training. The interventions included 12 sessions (3 times a week) over a time period of 4 weeks, lasting each for 75 min (30 min of cognitive training+45 min of cardio training/mental relaxation training). Cognitive parameters and psychopathology scores of all participants were tested in pre- and post-testing sessions and were then compared with a waiting control group. In the total group of patients, the results indicate an increase in cognitive performance in the domains visual learning, working memory and speed of processing, a decrease in state anxiety and an increase in subjective quality of life between pre- and post-testing. The effects in SZ patients compared with MDD patients were stronger for cognitive performance, whereas there were stronger effects in MDD patients compared with SZ patients in individual psychopathology values. MDD patients showed a significant reduction in depressive symptoms and state anxiety values after the intervention period. SZ patients reduced their negative symptoms severity from pre- to post-testing. In sum, the effects for the combined training were superior to the other forms of treatment. Physical exercise may help to reduce psychopathological symptoms and improve cognitive skills. The intervention routines employed in this study promise to add the current psychopathological and medical treatment options and could aid the transition to a multidisciplinary approach. However, a limitation of the current study is the short time interval for interventions (6 weeks including pre- and post-testing).


Subject(s)
Antisocial Personality Disorder/rehabilitation , Cognition Disorders/rehabilitation , Exercise Therapy/methods , Exercise , Adult , Analysis of Variance , Antisocial Personality Disorder/etiology , Cognition Disorders/etiology , Depression/complications , Depression/psychology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating Scales , Relaxation , Schizophrenia/complications , Schizophrenic Psychology
8.
Cereb Cortex ; 23(1): 61-70, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22291030

ABSTRACT

The current study provides a complete magnetic resonance imaging (MRI) analysis of thickness throughout the cerebral cortical mantle in patients with schizophrenia (SZ) and rigorously screened and matched unaffected relatives and controls and an assessment of its relation to psychopathology and subjective cognitive function. We analyzed 3D-anatomical MRI data sets, obtained at 3 T, from 3 different subject groups: 25 SZ patients, 29 first-degree relatives, and 37 healthy control subjects. We computed whole-brain cortical thickness using the Freesurfer software and assessed group differences. We also acquired clinical and psychometric data. The results showed markedly reduced cortical thickness in SZ patients compared with controls, most notably in the frontal and temporal lobes, in the superior parietal lobe and several limbic areas, with intermediate levels of cortical thickness in relatives. In both patients and relatives, we found an association between subjective cognitive dysfunction and reduced thickness of frontal cortex, and predisposition toward hallucinations and reduced thickness of the superior temporal gyrus. Our findings suggest that changes in specific cortical areas may predispose to specific symptoms, as exemplified by the association between temporal cortex thinning and hallucinations.


Subject(s)
Cerebral Cortex/pathology , Magnetic Resonance Imaging/methods , Psychotic Disorders/complications , Psychotic Disorders/etiology , Psychotic Disorders/pathology , Adult , Atrophy/pathology , Female , Humans , Male , Organ Size , Statistics as Topic
9.
Eur Arch Psychiatry Clin Neurosci ; 263(6): 451-67, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23873090

ABSTRACT

Affective and non-affective psychoses are severe and frequent psychiatric disorders. Amongst others, they not only have a profound impact on affected individuals through their symptomatology, but also regarding cognition, brain structure and function. Cognitive impairment influences patients' quality of life as well as their ability to work and being employed. While exercise therapy has been implemented in the treatment of psychiatric conditions since the days of Kraepelin and Bleuler, the underlying mechanisms have never been systematically studied. Since the early 1990s, studies emerged examining the effect of physical exercise in animal models, revealing stimulation of neurogenesis, synaptogenesis and neurotransmission. Based on that body of work, clinical studies have been carried out in both healthy humans and in patient populations. These studies differ with regard to homogenous study samples, sample size, type and duration of exercise, outcome variables and measurement techniques. Based on their review, we draw conclusions regarding recommendations for future research strategies showing that modern therapeutic approaches should include physical exercise as part of a multimodal intervention programme to improve psychopathology and cognitive symptoms in schizophrenia and affective disorders.


Subject(s)
Brain/physiopathology , Exercise/physiology , Mood Disorders/physiopathology , Neurogenesis/physiology , Schizophrenia/physiopathology , Schizophrenia/rehabilitation , Humans , Mood Disorders/pathology , Mood Disorders/rehabilitation , Neuroimaging , Schizophrenia/pathology
10.
Neuroimage ; 59(2): 926-34, 2012 Jan 16.
Article in English | MEDLINE | ID: mdl-21964509

ABSTRACT

Changes in hemispheric asymmetry and inter-hemispheric connectivity have been reported in schizophrenia. However, the genetic contribution to these alterations is still unclear. In the current study, we applied an automatic segmentation method to structural MRI and diffusion tensor imaging (DTI) data and examined volume and fiber integrity of the corpus callosum (CC), the main interhemispheric fiber tract, in 16 chronic schizophrenia (SZ) patients, matched first degree relatives and controls. SZ patients and relatives had smaller CC volumes than controls, particularly in the posterior genu, isthmus and splenium. Fractional anisotropy (FA), an indicator of fiber integrity, was reduced in patients and relatives in the whole CC, the inferior genu, the superior genu and the isthmus. Correspondingly, the mean diffusivity (MD) values of the whole CC and the isthmus were higher in patients and their unaffected relatives, indicating decreased compactness and increased intercellular space. Relatives had intermediate values in the volumetric and fiber integrity measurements between patients and controls. Lower CC volume and fiber integrity in SZ patients were associated with more severe auditory hallucinations. These results support the connectivity hypothesis of SZ (Friston, 1998) and particularly highlight the altered interhemispheric connectivity, which appears to be a genetic feature of SZ risk.


Subject(s)
Cerebrum/pathology , Corpus Callosum/pathology , Diffusion Tensor Imaging/methods , Genetic Predisposition to Disease/genetics , Nerve Fibers, Myelinated/pathology , Schizophrenia/genetics , Schizophrenia/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Neural Pathways/pathology , Organ Size , Risk Assessment
11.
J Nerv Ment Dis ; 200(4): 296-304, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22456582

ABSTRACT

This is the first study to combine psychometric and functional neuroimaging methods to study altered patterns of autobiographical memory in bipolar disorder (BD). All participants were interviewed with an expanded version of the Bielefelder Autobiographical Memory Inventory (Bielefelder Autobiographisches Gedächtnis Inventar 2004;Lisse: Swets and Zeitlinger). We then acquired functional magnetic resonance imaging data during a task of individually designed autobiographical recall. Compared with healthy controls, BD patients reported a stronger emotionality of autobiographical memories and more frequent recollections of autobiographical events during their everyday life. Furthermore, they failed to deactivate areas in the cuneus and lingual gyrus and showed decreased activation in the inferior frontal and precentral areas compared with the control group. More frequent intrusions from a person's past, which had a neural correlate in the lack of deactivation in some default mode network areas in BD patients, may contribute to manic or depressive symptoms.


Subject(s)
Bipolar Disorder/physiopathology , Emotions/physiology , Memory, Episodic , Nerve Net/physiopathology , Adult , Bipolar Disorder/psychology , Female , Humans , Magnetic Resonance Imaging/methods , Male , Mental Recall/physiology , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating Scales , Psychometrics/methods
12.
Front Psychiatry ; 9: 202, 2018.
Article in English | MEDLINE | ID: mdl-29896123

ABSTRACT

Even though extensively investigated, the nature of working memory (WM) deficits in patients with schizophrenia (PSZ) is not yet fully understood. In particular, the contribution of different WM sub-processes to the severe WM deficit observed in PSZ is a matter of debate. So far, most research has focused on impaired WM maintenance. By analyzing different types of errors in a spatial delayed response task (DRT), we have recently demonstrated that incorrect yet confident responses (which we labeled as false memory errors) rather than incorrect/not-confident responses reflect failures of WM encoding, which was also impaired in PSZ. In the present study, we provide further evidence for a functional dissociation between confident and not-confident errors by manipulating the demands on WM maintenance, i.e., the length over which information has to be maintained in WM. Furthermore, we investigate whether these functionally distinguishable WM processes are impaired in PSZ. Twenty-four PSZ and 24 demographically matched healthy controls (HC) performed a spatial DRT in which the length of the delay period was varied between 1, 2, 4, and 6 s. In each trial, participants also rated their level of response confidence. Across both groups, longer delays led to increased rates of incorrect/not-confident responses, while incorrect/confident responses were not affected by delay length. This functional dissociation provides additional support for our proposal that false memory errors (i.e., confident errors) reflect problems at the level of WM encoding, while not-confident errors reflect failures of WM maintenance. Schizophrenic patients showed increased numbers of both confident and not-confident errors, suggesting that both sub-processes of WM-encoding and maintenance-are impaired in schizophrenia. Combined with the delay length-dependent functional dissociation, we propose that these impairments in schizophrenic patients are functionally distinguishable.

13.
Neuroimage Clin ; 15: 45-52, 2017.
Article in English | MEDLINE | ID: mdl-28480163

ABSTRACT

Sensory perceptual processing deficits, such as impaired visual object identification and perceptual closure, have been reported in schizophrenia. These perceptual impairments may be associated with neural deficits in visual association areas, including lateral occipital cortex and inferior temporal areas. However, it remains unknown if such deficits can be found in the intrinsic architecture of the visual system. In the current study, we measured perceptual closure performance and resting-state functional connectivity using functional magnetic resonance imaging (FMRI) in 16 schizophrenia patients and 16 matched healthy controls. We estimated intrinsic functional connectivity using self-organized grouping spatial ICA, which clusters component maps in the subject space according to spatial similarity. Patients performed worse than controls in the perceptual closure task. This impaired closure performance of patients was correlated with increased severity of psychotic symptoms. We also found that intrinsic connectivity of the visual processing system was diminished in patients compared to controls. Lower perceptual closure performance was correlated to lower visual cortical intrinsic connectivity overall. We suggest that schizophrenia is associated with impaired intrinsic connectivity of the visual system, and that it is a potential mechanism leading to impaired visual object perception. These findings contribute to increasing evidence for impairments of higher visual functions in schizophrenia.


Subject(s)
Nerve Net/diagnostic imaging , Perceptual Closure , Psychomotor Performance , Schizophrenia/diagnostic imaging , Schizophrenic Psychology , Visual Cortex/diagnostic imaging , Adult , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Nerve Net/physiopathology , Pattern Recognition, Visual/physiology , Perceptual Closure/physiology , Photic Stimulation/methods , Psychomotor Performance/physiology , Schizophrenia/physiopathology , Visual Cortex/physiopathology
14.
Psychiatry Res ; 253: 303-310, 2017 07.
Article in English | MEDLINE | ID: mdl-28412613

ABSTRACT

People suffering from depression perceive themselves and their surroundings as more negative than healthy ones. An explanation might be that depressed individuals experience negative information as more stressful than non-depressed subjects and, consequently, respond in an amplified manner on a subjective and physiological level. To test this proposition, we presented 41 patients with recurrent depressive episodes and 42 controls with stimuli from the International Affective Picture System split into three valence categories while different parameters of physiological arousal (e.g., heart rate variability) and subjective perceptions of valence and arousal were assessed. Furthermore, we examined social skills and emotional competence. Results regarding physiological arousal revealed an elevated skin temperature and a more accentuated respiratory frequency in depressed subjects. Furthermore, depressed subjects rated the stimuli as more negative and arousing, which was associated with reduced social and emotional competence. Variation in antidepressant medication, menstrual cycle and other factors that have an impact on HRV are a potential bias. Our findings suggest an intensified perception of negative emotion in depressed individuals as compared to controls that manifests itself in an increased physiological arousal as well as on a subjective level. This intensified emotion perception is further associated with deficits in social and emotional competence.


Subject(s)
Arousal/physiology , Depression/psychology , Depressive Disorder, Major/psychology , Emotions/physiology , Perception/physiology , Adaptation, Physiological , Adult , Case-Control Studies , Depression/physiopathology , Depressive Disorder, Major/physiopathology , Female , Heart Rate/physiology , Humans , Male , Middle Aged
15.
Curr Alzheimer Res ; 14(3): 240-254, 2017.
Article in English | MEDLINE | ID: mdl-27335040

ABSTRACT

Neurodegenerative diseases may directly affect memory performance, thus leading to functional impairments. An increasing body of evidence suggests an association between dietary intake of omega-3 fatty acids and memory functioning in animal models as well as in human studies. Recent evidence supports a potential beneficial role of omega-3 fatty acid supplementation on psychopathological and cognitive symptoms, beside their established positive effects on cardiovascular health. OBJECTIVE: We summarize relevant and recent evidence from epidemiological, interventional and experimental studies investigating dietary consumption of omega-3 fatty acids and emphazing mechanisms of memory disorders, with a focus on mild cognitive impairment (MCI) and dementia. Omega-3 fatty acid could represent an affordable and accessible adjunctive treatment option to improve cognitive and non-cognitive function with a focus on MCI or dementia. However, apart from its translational promise, which is based on mechanistic models and evidence from animal studies, evidence for clinical benefits in humans is lacking. METHOD: To follow this research question, a search through electronic databases for the following search terms to identify relevant studies was conducted: 'omega 3 fatty acids', 'cognition', 'memory', ´Alzheimer´s Disease ´, ´dementia´, ´MCI`. Studies were included if they presented original data and were published in English between 1990 and 2015. RESULTS: To our the best of our knowledge, there are only 8 interventional studies that investigated the effects of n3-PUFAs in dementia patients, while 6 studies were conducted in healthy individuals, which in combination show equivocal results. CONCLUSION: This verifies the need for larger and (more) well designed clinical trials.


Subject(s)
Alzheimer Disease/diet therapy , Cognitive Dysfunction/diet therapy , Fatty Acids, Omega-3 , Alzheimer Disease/psychology , Animals , Cognition , Cognitive Dysfunction/psychology , Humans
16.
Curr Alzheimer Res ; 14(4): 441-452, 2017.
Article in English | MEDLINE | ID: mdl-27335045

ABSTRACT

Depression is a common neuropsychiatric manifestation among Alzheimer's disease (AD) patients. It may compromise everyday activities and lead to a faster cognitive decline as well as worse quality of life. The identification of promising biomarkers may therefore help to timely initiate and improve the treatment of preclinical and clinical states of AD, and to improve the long-term functional outcome. In this narrative review, we report studies that investigated biomarkers for AD-related depression. Genetic findings state AD-related depression as a rather complex, multifactorial trait with relevant environmental and inherited contributors. However, one specific set of genes, the brain derived neurotrophic factor (BDNF), specifically the Val66Met polymorphism, may play a crucial role in AD-related depression. Regarding neuroimaging markers, the most promising findings reveal structural impairments in the cortico-subcortical networks that are related to affect regulation and reward / aversion control. Functional imaging studies reveal abnormalities in predominantly frontal and temporal regions. Furthermore, CSF based biomarkers are seen as potentially promising for the diagnostic process showing abnormalities in metabolic pathways that contribute to AD-related depression. However, there is a need for standardization of methodological issues and for replication of current evidence with larger cohorts and prospective studies.


Subject(s)
Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Depression/diagnostic imaging , Alzheimer Disease/genetics , Animals , Biomarkers/metabolism , Brain/diagnostic imaging , Depression/complications , Depression/genetics , Humans
17.
Curr Alzheimer Res ; 14(1): 61-75, 2017.
Article in English | MEDLINE | ID: mdl-27298146

ABSTRACT

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) associated with Alzheimer's Disease (AD) have been linked to structural and functional alterations in fronto-temporal circuits and cortical abnormalities. However, little is known on how specific volumetric and functional brain changes may be associated with the frequency, severity and pattern of BPSD. METHODS: A systematic review of the literature regarding neuroimaging and BPSD changes in AD was performed through Pubmed/Medline, ISI, and EMBASE electronic databases from January 2000 to May 2015. Eligible references (n=40) included clinical studies in which structural or functional neuroimaging assessment was performed in AD subjects presenting BPSD features. RESULTS: BPSD symptoms, particularly apathy and psychosis have been associated in most of studies with either volume reductions or decreased metabolism in the prefrontal cortex (orbital and dorsolateral portions), anterior cingulate, insula and temporal lobes (middle portion). WM lacunes associated with AD progression have been associated with depressive symptoms. CONCLUSION: The sum of evidence highlights the importance of BPSD-related imaging findings for the understanding of the non-cognitive symptom spectrum in AD. Results suggest that structural and functional changes in fronto-limbic areas may lead to emotional deregulation and symptom unawareness. As these findings may be present early on the AD clinical course, they may have a relevance for the development of imaging markers that could be used in diagnosis, disease monitoring and prediction of therapeutic response.


Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Brain/diagnostic imaging , Humans , Neuroimaging
18.
PLoS One ; 12(1): e0169364, 2017.
Article in English | MEDLINE | ID: mdl-28125578

ABSTRACT

BACKGROUND: Previous magnetic resonance imaging (MRI) research suggests that, prior to the onset of psychosis, high risk youths already exhibit brain abnormalities similar to those present in patients with schizophrenia. OBJECTIVES: The goal of the present study was to describe the functional organization of endogenous activation in young adolescents who report auditory verbal hallucinations (AVH) in view of the "distributed network" hypothesis of psychosis. We recruited 20 young people aged 13-16 years who reported AVHs and 20 healthy controls matched for age, gender and handedness from local schools. METHODS: Each participant underwent a semi-structured clinical interview and a resting state (RS) neuroimaging protocol. We explored functional connectivity (FC) involving three different networks: 1) default mode network (DMN) 2) salience network (SN) and 3) central executive network (CEN). In line with previous findings on the role of the auditory cortex in AVHs as reported by young adolescents, we also investigated FC anomalies involving both the primary and secondary auditory cortices (A1 and A2, respectively). Further, we explored between-group inter-hemispheric FC differences (laterality) for both A1 and A2. Compared to the healthy control group, the AVH group exhibited FC differences in all three networks investigated. Moreover, FC anomalies were found in a neural network including both A1 and A2. The laterality analysis revealed no between-group, inter-hemispheric differences. CONCLUSIONS: The present study suggests that young adolescents with subclinical psychotic symptoms exhibit functional connectivity anomalies directly and indirectly involving the DMN, SN, CEN and also a neural network including both primary and secondary auditory cortical regions.


Subject(s)
Auditory Cortex/physiopathology , Cerebrum/physiopathology , Hallucinations/physiopathology , Nerve Net/physiopathology , Neural Pathways/physiopathology , Psychotic Disorders/physiopathology , Adolescent , Auditory Cortex/diagnostic imaging , Auditory Cortex/pathology , Brain Mapping , Case-Control Studies , Cerebrum/diagnostic imaging , Cerebrum/pathology , Child , Female , Hallucinations/diagnostic imaging , Hallucinations/pathology , Humans , Magnetic Resonance Imaging , Male , Nerve Net/diagnostic imaging , Nerve Net/pathology , Neural Pathways/diagnostic imaging , Neural Pathways/pathology , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/pathology
19.
Psychiatry Res ; 246: 341-347, 2016 Dec 30.
Article in English | MEDLINE | ID: mdl-27756025

ABSTRACT

Negative mental images are common in a range of mental disorders. So far, only inconclusive evidence has been obtained for depression specificity. We assessed the disparities and similarities of a variety of imagery characteristics in 17 patients suffering from depressive disorders and 17 healthy matched controls who all reported negative mental images. The number of intrusive images, their frequency, and the associated distress were significantly greater for the depressed individuals. Compared with non-depressed controls, negative images during depression were more frequently triggered by internal factors and led to depression-related emotions. Approximately 30% of the images in the depressed group did not consist of actual memories of real-life events. No significant differences in vividness or perceived controllability were observed, but the depressed patients experienced significantly more bodily symptoms during the intrusions than the healthy controls. The results indicate that the central characteristics of the negative mental images of depressed and non-depressed individuals are distinguishable, despite some similarities, and may contribute to depressive symptoms.


Subject(s)
Depressive Disorder/physiopathology , Imagination/physiology , Visual Perception/physiology , Adult , Female , Humans , Male , Middle Aged
20.
Emotion ; 16(6): 807-14, 2016 09.
Article in English | MEDLINE | ID: mdl-27337681

ABSTRACT

According to psychological models as well as common intuition, intense positive and negative situations evoke highly distinct emotional expressions. Nevertheless, recent work has shown that when judging isolated faces, the affective valence of winning and losing professional tennis players is hard to differentiate. However, expressions produced by professional athletes during publicly broadcasted sports events may be strategically controlled. To shed light on this matter we examined if ordinary people's spontaneous facial expressions evoked during highly intense situations are diagnostic for the situational valence. In Experiment 1 we compared reactions with highly intense positive situations (surprise soldier reunions) versus highly intense negative situations (terror attacks). In Experiment 2, we turned to children and compared facial reactions with highly positive situations (e.g., a child receiving a surprise trip to Disneyland) versus highly negative situations (e.g., a child discovering her parents ate up all her Halloween candy). The results demonstrate that facial expressions of both adults and children are often not diagnostic for the valence of the situation. These findings demonstrate the ambiguity of extreme facial expressions and highlight the importance of context in everyday emotion perception. (PsycINFO Database Record


Subject(s)
Emotions/physiology , Facial Expression , Adult , Female , Humans , Male , Young Adult
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