The neuropsychology of hallucinations

Hallucinations are a psychopathological phenomenon with neuropsychological, neuroanatomical and pathophysiological correlates in specific brain areas. They can affect any of the senses, but auditory and visual hallucinations predominate. Verbal hallucinations reveal no gross organic lesions while visual hallucinations are connected to defined brain lesions. Functional neuroimaging shows impairments in modality specific sensory systems with the hyperactivity of the surrounding cerebral cortex. Disinhibition and expansion of the inner speech was noted with impaired internal monitoring in auditory verbal hallucinations. The subcortical areas and modal-specific associative cortex and cingulate cortex are essential for the occurrence of hallucinations

The analysis of antioxidative status in patients with major depression and bipolar disorder

Uvod. Poremećaji raspoloženja obuhvataju veliku grupu psihijatrijskih oboljenja koja se karakterišu prisustvom patološkog raspoloženja kao ključnim elementom kliničke slike. U okviru ove grupe razlikuju se unipolarna depresija ili depresivni poremećaj koji se karakteriše prisustvom isključivo depresivnih epizoda, i bipolarni afektivni poremećaj kod koga postoji smenjivanje faza povišenog rapoloženja (manija ili hipomanija) sa fazama depresivnog raspoloženja. Etiologija poremećaja raspoloženja je rezultat složenog međudelovanja brojnih bioloških, psiholoških i socijalnih faktora. Smatra se da u patogenezi značajnu ulogu imaju abnormalnosti neurotransmiterskih i neuroendokrinih funkcija sa vrlo izraženom genetskom komponentom. U skorije vreme pretpostavlja se da je oksidativni stres uključen u patogenezu poremećaja raspoloženja, kao i drugih psihijatrijskih oboljenja. Oksidativni stres predstavlja poremećaj ravnoteže između stvaranja slobodnih radikala i mehanizama antioksidativne zaštite. U toku oksidativnog stresa dolazi do oštećenja molekula lipida, proteina ili DNK, čime se narušava njihova funkcija. Mozak je posebno osetljiv na dejstvo slobodnih radikala. Uloga oksidativnog stresa u patogenezi unipolarne depresije i bipolarnog afektivnog poremećaja nije još uvek sasvim rasvetljena, iako postoje brojni dokazi o poremećenom oksidativnom statusu kod obolelih. Jedna od pretpostavki je da je redoks regulacija povezana sa regulacijom inflamatornih puteva i da povećani oksidativni stres može dovesti do inflamacije. Postoje brojni dokazi koji govore u prilog tzv. inflamatornoj hipotezi depresije. Takođe, narušena funkcija mitohondrija, koje su glavni izvor slobodnih radikala, može učestvovati u etiopatogenezi depresije. Ciljevi istraživanja. U cilju utvrđivanja promena u antioksidativnom statusu u serumu obolelih od unipolarne depresije i bipolarnog afektivnog poremećaja određuju se različiti parametri oksidativnog stresa, i to biomarkeri oksidativnog oštećenja lipida (8- izoprostan i malondialdehid – MDA) i DNK (8-hidroksi-2´-deoksiguanozin – 8-OHdG), kao i antioksidativni enzimi (superoksid dizmutaza –SOD, katalaza– CAT, glutation peroksidaza – GPx i glutation reduktaza –GR)...Introduction. Mood disorders encompass a large group of psychiatric disorders characterized by the presence of pathological mood as a key element of the clinical picture. Within this group, there is distinction between unipolar depression or major depressive disorder characterized by the presence of only depressive episodes and bipolar disorder with alternation of elevated mood (mania or hypomania) and depressive mood. The etiology of mood disorders is the result of a complex interaction between a number of biological, psychological and social factors. It is believed that abnormalities of neurotransmitter and neuroendocrine function play a significant role in their pathogenesis along with a very distinctive genetic component. Recently, it is assumed that oxidative stress is involved in the pathogenesis of mood disorders, as well as other psychiatric disorders. Oxidative stress represents an imbalance between the production of free radicals and antioxidant defense mechanisms. Oxidative stress causes damage to the molecules of lipids, proteins or DNA, and as a result disrupts their function. The brain is particularly sensitive to the effects of free radicals. The role of oxidative stress in the pathogenesis of unipolar depression and bipolar disorder is not yet completely understood, even though there is a lot of evidence of impaired oxidative status in patients. It is speculated that the redox regulation is associated with the regulation of inflammatory pathways and that increased oxidative stress can lead to inflammation. There is lots of evidence to so-called inflammatory hypothesis of depression. Also, impaired function of mitochondria, which are the main source of free radicals, may contribute to the etiopathogenesis of depression. Aims. In order to determine changes in the antioxidative status in the serum of patients with unipolar depression and bipolar disorder various parameters of oxidative stress are measured, including biomarkers of oxidative damage to lipids (8-isoprostanes and malondialdehyde – MDA) and DNA (8-hydroxy-2'-deoxyguanosine – 8-OHdG), and antioxidative enzymes (superoxide dismutase – SOD, catalase – CAT, glutathione peroxidase – GPx, and glutathione reductase – GR)..

Hashimoto encephalopathy: Neurological and psychiatric perspective

Hashimoto encephalopathy (HE) is an autoimmune disease with neurological and neuropsychiatric manifestations and elevated titers of antithyroid antibodies in serum and cerebrospinal fluid. Patients are mostly women. Age varies from 8 to 86 years. Prevalence of HE is estimated to be 2.1/100,000. Neurological and/or psychiatric symptoms and signs constitute the clinical picture. The disease responds well to corticosteroid therapy, but sometimes other immunomodulatory therapies must be applied. Autoimmune mechanisms with antibodies against antigens in the brain cortex are suspected. The course of the disease can be acute, subacute, chronic, or relapsing/remitting. Some patients improve spontaneously, but a few died in spite of adequate therapy

Vitamin a and the nervous system

Vitamin A is essential for the early development and normal functioning of the brain throughout life. A deficiency of vitamin A is one of the leading causes of morbidity and mortality in developing countries, and subclinical deficiency is probably present worldwide. The main active molecule in vitamin A is retinoic acid, which is involved in vision, the immune system, skin health, olfaction and cognition (learning, memory, spatial functions, olfaction, etc.) through processes of neuroplasticity and neurogenesis. Vitamin A is involved in the regulation of about one-sixth of the human genome. It has non-genomic actions in protein translation and paracrine actions. Retinal vitamin A aldehyde is crucial for day and night vision. The best-known manifestation of hypovitaminosis A is night blindness but in more severe cases, it causes blindness. In the hypothalamus, vitamin A, with information from the retina, acts in circadian and seasonal regulation. Increased retinoic acid levels in the blood are associated with increased risk of depression, and lower levels have been connected with Alzheimer's disease, Parkinson's disease, cerebral ischemia, autistic spectrum disorders and schizophrenia. Higher doses and longer periods of treatment pose the threat of hypervitaminosis A. Vitamin A and its analogs are a promising new class of therapeutic agents in a wide spectrum of disorders, albeit with a narrow therapeutic window

8-Iso-prostaglandin F2α as a potential biomarker in patients with unipolar and bipolar depression

Objective: Previous studies have shown that the disturbance of redox homeostasis plays a role in the pathogenesis of mood disorders. It is currently unclear whether oxidative stress parameters can be used as biomarkers (state vs. trait). The aim of the present study was to investigate oxidative stress markers in patients with major depressive disorder (MDD) and bipolar disorder (BP) in acute depressive episodes and remission, and healthy individuals. Patients and methods: Thirty-two patients with a diagnosis of MDD, 32 patients with a diagnosis of BP and 32 matched healthy controls were included in the study. We measured the serum levels of markers of oxidative damage, including 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-Iso-prostaglandin F2α (8-iso-PGF2α; 8-isoprostane), and malondialdehyde (MDA), and also serum activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR) in both acute and remission phase, and in control group. Results: After controlling for the effects of age, sex, body mass index, and smoking status, serum 8-iso-PGF2α levels were significantly higher in both patient groups compared to controls, regardless of disease phase. The activities of GPX and GR were significantly lower in the acute phase in MDD patients compared to controls. Serum GR activity was lower in both acute and remission phase in MDD compared to BP. Conclusions: Our results suggest that both MDD and BP are associated with a disturbed redox balance with a particularly pronounced increase in serum 8-iso-PGF2α levels in both groups and the presence of glutathione metabolism disorders in MDD patients. Further research is needed to confirm the importance of oxidative stress parameters as potential biomarkers of MDD and BP

Uloga krvno-moždane barijere u psihijatrijskim oboljenjima

The blood-brain barrier (BBB) is formed by continuous, closely connected endothelial cells, enveloped in the basal lamina, pericytes, and foot extensions of astrocytes. BBB has a vital role in brain metabolism and protects the brain parenchyma from harmful agents present in the systemic circulation. Damage to the BBB and an increase in its permeability have an important role in many neurodegenerative diseases. This paper aims to review the literature on the impact of the BBB damage on psychiatric illness, a largely neglected and under researched area. Links between BBB impairment and specific neuropsychiatric disorders are described including schizophrenia, affective disorders, dementias with behavioral disorders, and alcohol use disorder, with comparison to typical hereditary small vessel diseases affecting the BBB such as cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy (CADASIL) and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). The authors critically summarize possible pathogenic mechanisms linking BBB damage and these common disorders.Крвно-мождана баријера (КМБ) се састоји од континураних, тесно спојених ендотелних ћелија омотаних базалном ламином, перицитима и сто-паластим продужецима астроцита. КМБ има виталну функцију и можданом метаболизму и штити мождани паренхим од штетних фактора присутних у системској циркулацији. Показано је да оштећење КМБ и повећање њене пропустљи-вости има значајну улогу у многим неуродегене-ративним обољењима. Циљ овога рада је преглед литературе о значају оштећења КМБ код психијатријских обољења, до сада занемареној и недовољно истраженој облас-ти. Повезаност измедју поремећаја КМБ и неуро-психијатријских поремећаја је посебно анализи-рана за схизофренију, афективне поремећаје, де-менције са бихевиоралним изменама, поремећај употребе алкохола, са посебним освртом на на-следне болести малих крвних судова мозга са оштећењем КМБ као што су церебрална аутозо-мално доминантна артериопатија са супкортика-ним инфарктима и леукоенцефалопатијом (CADASIL) и митохондријска енцефаломиопатија са лактатном ацидозом и епизодама налик можда-ном удару (MELAS). Аутори критички сумирају могуће патогенетске механизме који повезују оштећења КМБ са овим честим обољењима

The analysis of antioxidative status in patients with major depression and bipolar disorder

Uvod. Poremećaji raspoloženja obuhvataju veliku grupu psihijatrijskih oboljenja koja se karakterišu prisustvom patološkog raspoloženja kao ključnim elementom kliničke slike. U okviru ove grupe razlikuju se unipolarna depresija ili depresivni poremećaj koji se karakteriše prisustvom isključivo depresivnih epizoda, i bipolarni afektivni poremećaj kod koga postoji smenjivanje faza povišenog rapoloženja (manija ili hipomanija) sa fazama depresivnog raspoloženja. Etiologija poremećaja raspoloženja je rezultat složenog međudelovanja brojnih bioloških, psiholoških i socijalnih faktora. Smatra se da u patogenezi značajnu ulogu imaju abnormalnosti neurotransmiterskih i neuroendokrinih funkcija sa vrlo izraženom genetskom komponentom. U skorije vreme pretpostavlja se da je oksidativni stres uključen u patogenezu poremećaja raspoloženja, kao i drugih psihijatrijskih oboljenja. Oksidativni stres predstavlja poremećaj ravnoteže između stvaranja slobodnih radikala i mehanizama antioksidativne zaštite. U toku oksidativnog stresa dolazi do oštećenja molekula lipida, proteina ili DNK, čime se narušava njihova funkcija. Mozak je posebno osetljiv na dejstvo slobodnih radikala. Uloga oksidativnog stresa u patogenezi unipolarne depresije i bipolarnog afektivnog poremećaja nije još uvek sasvim rasvetljena, iako postoje brojni dokazi o poremećenom oksidativnom statusu kod obolelih. Jedna od pretpostavki je da je redoks regulacija povezana sa regulacijom inflamatornih puteva i da povećani oksidativni stres može dovesti do inflamacije. Postoje brojni dokazi koji govore u prilog tzv. inflamatornoj hipotezi depresije. Takođe, narušena funkcija mitohondrija, koje su glavni izvor slobodnih radikala, može učestvovati u etiopatogenezi depresije. Ciljevi istraživanja. U cilju utvrđivanja promena u antioksidativnom statusu u serumu obolelih od unipolarne depresije i bipolarnog afektivnog poremećaja određuju se različiti parametri oksidativnog stresa, i to biomarkeri oksidativnog oštećenja lipida (8- izoprostan i malondialdehid – MDA) i DNK (8-hidroksi-2´-deoksiguanozin – 8-OHdG), kao i antioksidativni enzimi (superoksid dizmutaza –SOD, katalaza– CAT, glutation peroksidaza – GPx i glutation reduktaza –GR)...Introduction. Mood disorders encompass a large group of psychiatric disorders characterized by the presence of pathological mood as a key element of the clinical picture. Within this group, there is distinction between unipolar depression or major depressive disorder characterized by the presence of only depressive episodes and bipolar disorder with alternation of elevated mood (mania or hypomania) and depressive mood. The etiology of mood disorders is the result of a complex interaction between a number of biological, psychological and social factors. It is believed that abnormalities of neurotransmitter and neuroendocrine function play a significant role in their pathogenesis along with a very distinctive genetic component. Recently, it is assumed that oxidative stress is involved in the pathogenesis of mood disorders, as well as other psychiatric disorders. Oxidative stress represents an imbalance between the production of free radicals and antioxidant defense mechanisms. Oxidative stress causes damage to the molecules of lipids, proteins or DNA, and as a result disrupts their function. The brain is particularly sensitive to the effects of free radicals. The role of oxidative stress in the pathogenesis of unipolar depression and bipolar disorder is not yet completely understood, even though there is a lot of evidence of impaired oxidative status in patients. It is speculated that the redox regulation is associated with the regulation of inflammatory pathways and that increased oxidative stress can lead to inflammation. There is lots of evidence to so-called inflammatory hypothesis of depression. Also, impaired function of mitochondria, which are the main source of free radicals, may contribute to the etiopathogenesis of depression. Aims. In order to determine changes in the antioxidative status in the serum of patients with unipolar depression and bipolar disorder various parameters of oxidative stress are measured, including biomarkers of oxidative damage to lipids (8-isoprostanes and malondialdehyde – MDA) and DNA (8-hydroxy-2'-deoxyguanosine – 8-OHdG), and antioxidative enzymes (superoxide dismutase – SOD, catalase – CAT, glutathione peroxidase – GPx, and glutathione reductase – GR)..

Omega 3 fatty acids in psychiatry

Omega-3 long-chain polyunsaturated fatty acids (ω-3 LC-PUFAs) are thought to be important for normal dopaminergic, glutamatergic and serotonergic neurotransmission. Depression is less prevalent in societies with high fish consumption, and depressed patients have significantly lower red blood cell ω-3 levels. Studies with ω-3 supplementation have led to controversial results. A significantly longer remission of bipolar symptomatology has been confirmed from a high-dose DHA and EPA mixture. Greater seafood consumption per capita has been connected with a lower prevalence of bipolar spectrum disorders. Reduced levels of ω-6 and ω-3 PUFAs were found in patients with schizophrenia

The anterior cingulate cortex

The anterior cingulate cortex (ACC) has a role in attention, analysis of sensory information, error recognition, problem solving, detection of novelty, behavior, emotions, social relations, cognitive control, and regulation of visceral functions. This area is active whenever the individual feels some emotions, solves a problem, or analyzes the pros and cons of an action (if it is a right decision). Analogous areas are also found in higher mammals, especially whales, and they contain spindle neurons that enable complex social interactions. Disturbance of ACC activity is found in dementias, schizophrenia, depression, the obsessive-compulsive syndrome, and other neuropsychiatric diseases

Correlation of cognitive decline and behavioral changes in patients with presenile and senile onset Alzheimer's disease

Alzheimer's disease (AD), the most prevalent dementia, is characterized not only by cognitive but also behavior- al changes that pose the heaviest burden to caregivers. Differences in the clinical picture depending on the time of disease onset have been observed. We correlated cognitive and behavioral deficits in patients with presenile- and senile-onset AD to explore the differences. We tested 60 AD patients, 19 male and 41 female, mean age 65.2 years with the Dementia Behavior Disturbance Scale (DBD) and a standard neuropsychological battery. The patients were divided according to their DBD score into two groups: group I - score 0-2 (n=24; 40%), group II - score 3≥ (n=36; 60%), comparable in disease duration and neurological findings. The cognitive scores were significantly higher in the group with less behavioral changes than in the group with more behavioral changes: Mini Mental State Examination score (p=0.0015), serial subtraction (p=0.0009), block design (p=0.0049), copy of complex figure (p=0.0125), complex visual organization (p=0.0099), divided attention, visual memory and speech comprehension. A significantly higher frequency of behavioral disturbances was registered in patients with senile onset than in the presenile-onset group (p lt 0.005). There were no sex differences. Our data show a correlation between cognitive decline and behavioral changes in late onset AD patients, indicating that more behavioral disturbances were associated with a more severe degree of cognitive decline, especially in non-verbal functions and attention deficits, compared to early onset patients