Depression and Psychosis in Neurological Practice.pptx

A presentation about neuropsychiatric manifestations of neurological disorders like Stroke, CNS infections, Neurodegenerative disorders, Epilepsy, etc. and their diagnosis and management

1. Depression and Psychosis in Neurological Practice Dr Sumeet Singh Senior Resident Neurology GMC Kota

2. Introduction Emotional and cognitive processes are based on brain structure and physiology. Abnormal behavior can be attributable to the complex interplay of neural physiology, social influences, and physical environment Psychosis, mania, depression, disinhibition, obsessive compulsive behaviors, and anxiety all can occur as a result of neurological disease Dougherty DD, Rauch SL. Somatic therapies for treatment-resistant depression: new neurotherapeutic interventions. Psychiatric Clinics of North America. 2007 Mar 1;30(1):31-7.

3. Introduction……. The limbic system and the F ronto -subcortical circuits are most commonly implicated in neuropsychiatric symptoms Neurological conditions must be considered in differential diagnosis of any disorder with psychiatric symptoms Many neurological disorders like stroke, brain infections, neurodegenerative disorders, autoimmune encephalitis , etc. can present with psychiatric symptoms

4. ICD 10 classification of Psychiatric Disorders F0 – F9 : Organic, including symptomatic, mental disorders. F10 – F-19 : Mental and behavioural disorders due to use of psychoactive substances. F20 – F29 : Schizophrenia, schizotypal and delusional disorders. F30 – F39 : Mood and disorders. F40 – F49 : Neurotic, stress-related and somatoform disorders. BH P. Neurology and Psychiatry-Closing the great devide . Neurology. 2000;54:8-14

5. Primary Psychiatric Disorders Schizophrenia : A disorder lasting at least 6 months and includes at least 1 month of active symptoms (>=2 of the following: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, or negative symptoms). Schizoaffective disorder : A disorder in which a mood episode and the active symptoms of schizophrenia occur together and were preceded or are followed by at least 2 weeks of delusions or hallucinations Major depressive disorder : Characterized by one or more major depressive episodes (at least 2 weeks of depressed mood or loss of interest accompanied by at least four additional symptoms of depression). Additional symptoms -significant weight changes, sleep dysfunction, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or guilt, diminished concentration, and suicidal ideational or thoughts of death.

6. Primary Psychiatric Disorders cont ….. Manic episode : an abnormally and persistently elevated, expansive, or irritable mood persisting for at least 1 week (or less if hospitalization is required). Inflated self-esteem or grandiosity, decreased need for sleep, pressured speech, flight of ideas, distractibility, increased goal-directed activities or psychomotor agitation, and excessive involvement in pleasurable activities Bipolar I disorder : presence of both manic and major depressive episodes or manic episodes alone Bipolar II : presence of major depressive episodes alternating with episodes of hypomania

7. Psychiatric Terms of Relevance to Neurologists Abulia - state of reduced impulse to act and think associated with indifference about consequences of action Affect - examiner’s observation of the patient’s emotional state Flat - severely blunted affect in which there is no affective expression Anxiety - feeling of apprehension caused by anticipation of danger that may be internal or external Apathy - dulled emotional tone associated with detachment or indifference. Comportment - self-regulation of behavior through complex mental processes that include insight, judgment, self-awareness, empathy, and social adaptation Compulsion - uncontrollable impulse to perform an act repetitively BH P. Neurology and Psychiatry-Closing the great devide . Neurology. 2000;54:8-14 .

8. Psychiatric Terms…….. Confusion - Inability to maintain a coherent stream of thought owing to impaired attention and vigilance.. Delusion - False, unshakable conviction or judgment that is out of keeping with reality that cannot be corrected with reasoning Depression - Sustained psychopathological feeling of sadness often accompanied by anxiety, agitation, feelings of worthlessness, suicidal ideation, abulia, psychomotor retardation, that causes significant distress and impairment in social functioning.

9. Psychiatric Terms…….. Hallucination - false sensory perception not associated with real external stimuli. Mood - emotional state experienced and described by the patient and observed by others. Obsession - pathological persistence of an irresistible thought or feeling that cannot be eliminated from consciousness by logical effort and associated with anxiety and rumination Paranoia - descriptive term designating either morbid dominant ideas or delusions of self-reference concerning one or more of several themes like persecution, love, hate, envy, jealousy, honor, litigation, grandeur and the supernatural.

10. Psychiatric Terms…… Prosody - melodic patterns of intonation in language that convey shades of meaning. Psychosis - inability or impaired ability to distinguish reality from hallucinations and/or delusions Flight of ideas - a rapid stream of thoughts that tend to be related to each other Magical thinking - the belief that thoughts, words, or actions have power to influence events in ways other than through reality-based mechanisms. Thought blocking - characterized by abrupt interruptions in speech during conversation before an idea or thought is finished. After a pause, the individual indicates no recall of what was being said or what was going to be said.

11. Neuropsychiatric Symptoms and Corresponding Neuroanatomy

12. Neurological Disorders and Associated Prominent Behavioral Features

13. Principles Of Neuropsychiatric Evaluation Evaluation of psychiatric symptoms must be individualized based on the patient’s history, habits, risk factors, age, gender, history and examination New neurological complaints or behavioral changes that are atypical for a coexisting primary psychiatric disorder should not be dismissed as being of psychiatric origin Symptoms such as lethargy with benzodiazepines, parkinsonism with neuroleptics, or hallucinations with dopaminergic medications must be taken into account

14. Principles…… Evaluation should include measurement of blood pressure, pulse, respirations, and temperature , SpO2 Lab- CBC, electrolyte panel, serum glucose, BUN, creatinine, calcium, total protein, and albumin, liver function assessment and thyroid function test. A toxicology screen , Serum cobalamin (B12), homocysteine, methylmalonic acid, folate, HIV serology , rapid plasma regain (RPR), ANA,ESR, CRP, ceruloplasmin, heavy metal screen, ammonia Serum and cerebrospinal fluid paraneoplastic panel Urine porphobilinogen and porphyria screen CAG repeats for Huntington disease MRI Brain, EEG Other specialized rheumatologic, metabolic, and genetic tests A careful history to rule out a primary sleep disorder such as obstructive sleep apnea should be considered for refractory depressive symptoms

15. Biology Of Psychosis Schizophrenia is a chronic disintegrative thought disorder where patients frequently experience auditory hallucinations and bizarre or paranoid delusions The neurodevelopmental model - Schizophrenia results from processes that begin long before clinical symptom onset and environmental and genetic factors has a role in it The population lifetime risk for schizophrenia is 1%, 10% for first-degree relatives, 4% for second-degree relatives, 15% for dizygotic twins and 50 % in monozygotic twins Neurotransmitters have been linked with association of Schizophrenia by dopamine and glutamate hypothesis Schizophrenia has been associated with frontal lobe dysfunction and abnormal regulation of subcortical DA and glutamate systems

16. Advancing paternal age increases risk in a linear fashion A small proportion of schizophrenia may be explained by genomic structural variations - Copy number variants (CNVs) The most common CNV disorder, 22q11.2 deletion syndrome (velocardiofacial syndrome), has an established association with schizophrenia Structural studies have identified diminished brain volume, increased ventricular size, and atrophy in hippocampal, prefrontal, superior temporal, and inferior parieta l cortices in schizophrenics Several neurologic conditions that may manifest psychosis (e.g., HD, PD, frontotemporal degenerations, stroke) are also associated with frontal and subcortical dysfunction Bassett AS, Chow EW. Schizophrenia and 22q11. 2 deletion syndrome. Current psychiatry reports. 2008 Apr;10(2):148-57 .

17. Biology Of Depression Depression is a polygenetic condition with complex gene–environment interactions Prevalence rate of depression in patients with neurological disorders ranges from 20% to 60% Depression amplifies the physiological response to pain while pain related symptoms and limitations frequently lead to the emergence of depressive symptoms Polymorphisms in the promoter region of the serotonin transporter (5-HTT) gene has been found to be associated with depression Etkin A, Egner T, Kalisch R. Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in cognitive sciences. 2011 Feb 1;15(2):85-93 .

18. Imaging studies have demonstrated a 10% to 20% decrease in the hippocampal volume of patients with chronic depression Increased basal and stimuli-driven amygdala activity has been extensively characterized in depression Prefrontal cortex dysfunction plays an important role in the pathophysiology of depression The subgenual ACC has been implicated in the modulation of negative mood states In neurologic disorders, damage to the prefrontal cortex from stroke or tumor, or to the striatum from degenerative diseases such as PD and HD, is associated with depression Keedwell PA, Andrew C, Williams SC, Brammer MJ, Phillips ML. The neural correlates of anhedonia in major depressive disorder. Biological psychiatry. 2005 Dec 1;58(11):843-53 .

19. Historical Features Suggesting Neurological Disease in Patients with Psychiatric Symptoms Presence Of Atypical Psychiatric Features: Late or very early age of onset Acute or subacute onset Lack of significant psychosocial stressors Catatonia Cognitive decline Intractability despite adequate therapy Progressive symptoms

20. History Of Present Illness Includes: New or worsening headache Inattention Somnolence Incontinence Focal neurological complaints such as weakness, sensory changes, incoordination, or gait difficulty Neuroendocrine changes Anorexia/weight loss Patient History : Risk factors for cerebrovascular disease, or central nervous system infections Malignancy Immunocompromise Significant head trauma Seizures Movement disorder Hepatobiliary disorders Abdominal crises of unknown cause Biological relatives with similar diseases or complaints Ovsiew F, Murray ED, Price BH. Neuropsychiatric approach to the psychiatric inpatient. Principles of Inpatient Psychiatry, 1st Edition. Edited by Ovsiew F, Munich R. Baltimore, MD, Lippincott Williams & Wilkins. 2008 .

21. Causes of Depression and Psychosis

22. Psychiatric Manifestations Of Neurological Disease Stroke and Cerebral Vascular Disease : The neuropsychiatric consequences of stroke depends on location and size of the stroke, pre-existing brain pathology, baseline intellectual capacity and functioning, age, and premorbid psychiatric history Neuropsychiatric symptoms may occur in the setting of first strokes and multi-infarct dementia Interruption of bilateral frontotemporal lobe function is associated with an increased risk of depressive and psychotic symptoms Poststroke depression (PSD) is the most common neuropsychiatric syndrome, occurring in 30% to 50% of survivors at 1 year, with irritability, agitation, and apathy often present as well Perez DL, Catenaccio E, Epstein J. Confusion, hyperactive delirium, and secondary mania in right hemispheric strokes: a focused review of neuroanatomical correlates. J Neurol Neurophysiol . S. 2011;1:003.

23. Stroke……. Left prefrontal lesions are commonly associated with acute depression Mania is less common occurring in lesions of the OFC-subcortical circuit and medial temporal structures Nondominant hemispheric strokes may also result in Aprosody Vascular or late-life-depression : characterized by executive deficits, slowed processing speed, psychomotor retardation, lack of insight, and disability out of proportion to depressive symptoms White matter T2 MRI hyperintensities from diabetes, hyperlipidaemia, cardiac disease, and hypertension have been linked It has poor antidepressant response and higher relapse rates

24. Stroke…… Psychosis or psychotic features may present as a rare complication of a single stroke Paranoia and psychosis have been reported in association with left temporal strokes Right hemispheric lesions may be associated with visual hallucinations and delusions Reduplicative paramnesia may be seen with combined lesions of frontal and right temporal lobes( Right Anterior circulation stroke ) Capgras syndrome is the false belief that someone familiar, usually a family member or close friend, has been replaced by an identical-appearing imposter. It results from right temporal-limbic-frontal disconnection Politis M, Loane C. Reduplicative paramnesia: a review. Psychopathology. 2012 Jul 31;45(6):337-43 .

25. Stroke…… Fregoli syndrome : the patient believes a persecutor is able to take on a variety of faces, like an actor. Psychotic episodes can also be a manifestation of complex partial seizures secondary to stroke Patients with poststroke psychosis are more prone to have comorbid epilepsy Lesions or infarcts of the ventral midbrain can result in a syndrome characterized by well-formed and complex visual hallucinations referred to as Peduncular hallucinosis The vascular cognitive impairments include vascular dementia, mixed vascular dementia and AD pathology Treatment : Post stroke Psychosis responds to antipsychotics and treatment is gradually tapered once response is seen Risperidone, Quetiapine, Haroperidol and olanzapine is preferred Post stroke depression responds to SSRIs( preferably Sertraline and Escitalopram ) Cholinesterase inhibitors are beneficial for treatment of vascular dementia Rickards H. Depression in neurological disorders: Parkinson’s disease, multiple sclerosis, and stroke. Journal of Neurology, Neurosurgery & Psychiatry. 2005 Mar 1;76( suppl 1):i48-52 .

26. Psychiatric Manifestations of CNS infections CNS infections with psychiatric manifestations are Human Immunodeficiency Virus Creutzfeldt–Jakob Disease Neurosyphilis Herpes Simplex Encephalitis, Lyme Disease, Whipple disease, cerebral malaria. Clinical features: These present with a spectrum of psychiatric phenomenon like depression, paranoia, delusions, hallucinations, psychosis, mania, irritability, and apathy HIV-associated dementia (HAD) : a syndrome that presents with bradyphrenia, memory decline, executive dysfunction, impaired concentration, and apathy HAD may be the AIDS-defining illness in up to 10% of patients Himelhoch S, Medoff DR. Efficacy of antidepressant medication among HIV-positive individuals with depression: a systematic review and meta-analysis. AIDS Patient Care & STDs. 2005 Dec 1;19(12):813-22.

27. CNS infections…… Minor cognitive motor disorder (MCMD) : a milder form that has become more common since the advent of highly active antiretroviral therapy (HAART) The nucleoside reverse transcriptase inhibitor zidovudine (AZT) may lead to mania, delirium, or depression CJD Manifests with a rapidly progressive cerebellar ataxia, dementia, myoclonus , exaggerated startle reflex, seizures, and psychiatric symptoms progressing to akinetic mutism and complete disability within months HSV encephalitis can present with acute psychosis and behavioural abnormality Inadequate treatment of early syphilis and coinfection with HIV predispose to early neurosyphilis Lynn WA, Lightman S. Syphilis and HIV: a dangerous combination. The Lancet infectious diseases. 2004 Jul 1;4(7):456-66.

28. T2 FLAIR image showing Pulvinar Sign(New variant CJD) DWI showing cortical ribbon sign(Sporadic CJD) Baldwin KJ, Correll CM. Prion disease. InSeminars in neurology 2019 Aug (Vol. 39, No. 04, pp. 428-439). Thieme Medical Publishers.

29. Metabolic Disorders with Psychiatric and Neurological Symptoms Breitbart W. Identifying patients at risk for, and treatment of major psychiatric complications of cancer. Supportive care in cancer. 1995 Jan;3:45-60 .

30. Thyroid Disease : Hypothyroidism - Neurological symptoms include headache, fatigue, apathy, inattention, slowness of speech and thought, sensorineural hearing loss, sleep apnea, and seizures Can refractory depression Rarely may cause polyneuropathy, cranial neuropathy, muscle weakness, psychosis ( myxoedema madness ), dementia, coma, and death Psychosis typically presents with paranoid delusions and auditory hallucinations. The symptoms usually resolve within 1 week of hormone replacement

31. Hyperthyroidism - Patients are typically anxious, irritable, emotionally labile, tachycardic, and tremulous. Apathy, depression, panic attacks, feelings of exhaustion, inability to concentrate, and memory problems can occur. When apathy and depression are present the term apathetic hyperthyroidism is often used Psychosis and paranoia frequently occur during thyroid storm Many patients experience complete remission of symptoms within 1 to 2 months of euthyroid state Rarely anxiety and cognitive symptoms persists for several months to up to 10 years after euthyroid state.

32. Hashimoto encephalopathy- Steroid-responsive encephalopathy associated with autoimmune thyroiditis ( STREAT ) Associated with antithyroid peroxidase antibodies and antithyroglobulin antibodies A progressive or relapsing and remitting course of tremor, myoclonus, transient aphasia, stroke- lik e episodes, psychosis, seizures, encephalopathy, hypersomnolence, stupor, or coma CSF most often shows an elevated protein level with almost no nucleated cells, with oligoclonal bands .

33. Hashimoto encephalopathy…… EEG shows generalized slowing or frontal intermittent rhythmic delta activity. Triphasic waves, focal slowing, and epileptiform abnormalities can also be seen MRI brain is often normal but may reveal hyperintensities on T2-weighted or FLAIR in subcortical white matter or at the gray/white matter junction Serum TSH is usually normal( can be high in some cases) Treatment : The neurological and psychiatric symptoms respond to high-dose steroids Inj Methylprednisolone 1g/ day for 3-5 days followed by a taper of oral Prednisone

34. Wilson Disease: Autosomal recessive disorder produced by a mutation on chromosome 13 About 1/3 rd of patients present with psychiatric symptoms and 1/3 rd with neurological features Personality and mood changes are the most common neuropsychiatric features, with depression occurring in approximately 30% of patients Bipolar spectrum symptoms occur in about 20% of patients. Suicidal ideation is recognized in about 5% to 15% WD patients can present with increased sensitivity to neuroleptics Treatment Neurological and psychiatric symptoms show partial improvement with chelation therapy with either Penicillamine (0.75-1.5g/day)or Trientine (1g/day in 3 divided doses)in combination with zinc acetate(150 mg/day) Svetel M, Potrebić A, Pekmezović T, Tomić A, Kresojević N, Ješić R, Dragašević N, Kostić VS. Neuropsychiatric aspects of treated Wilson's disease. Parkinsonism & Related Disorders. 2009 Dec 1;15(10):772-5.

35. Vitamin B12 and Folic Acid Deficiency: 12%-30 % of elderly persons Deficiency states associated with personality change, cognitive dysfunction, mania, depression, and psychosis Psychotic features include paranoid or religious delusions and auditory and visual hallucinations Reversible dementia can occur Folate deficiency tends to produce more depression as compared to psychosis Repletion of folate if comorbid vitamin B12 deficiency is not first corrected can result in an acute exacerbation of the neuropsychiatric symptoms

36. Porphyria: Porphyrias with neuropsychiatric features: acute intermittent porphyria ( AIP ), variegated porphyria ( VP ), hereditary mixed coproporphyria ( HMP ), and Plumboporphyria (extremely rare) Can present as fatal neurovisceral crisis, abdominal pain, delirium, psychosis, neuropathy, autonomic instability and seizures The episodic nature, clinical variability, and unusual features can simulate somatoform, functional (psychogenic) or other psychiatric disorders Attacks are precipitated by infection, alcohol use, pregnancy, anesthesia, and medications that include antidepressants, anticonvulsants , and oral contraceptives

37. Porphyria…… Anxiety, restlessness, insomnia, depression, mania, hallucinations, delusions, confusion, catatonia, and psychosis can occur The diagnosis can be confirmed during an acute attack by measuring urine porphobilinogens Acute attacks are treated with avoidance of precipitating factors, IV hemin, IV glucose , and pain control.

38. Drug Abuse Neuropsychiatric symptoms can develop due to effects of intoxication, side effects, and withdrawal syndromes Can range from somnolence with sedatives to psychosis from hallucinogens and stimulants. Withdrawal may be lethal as in the case of alcohol withdrawal and delirium tremens The behavioral and cognitive manifestations of substance abuse may be transient but in may be chronic MDMA “ecstasy” may promote the development of depression and impaired cognition due to changes in structural and functional neuroanatomy Cannabis use confers an increased relative risk for developing schizophrenia later in life Parrott AC. Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research. Human Psychopharmacology: Clinical and Experimental. 2013 Jul;28(4):289-307.

39. Systemic Lupus Erythematosus: Primary neurological and psychiatric manifestations are due to vascular abnormalities, autoantibodies, and the local production of inflammatory mediators Secondary manifestations occur as a result of therapies (e.g., immunosuppression with steroids) or complications of the disease Depression and anxiety each occur in approximately 25% of patients Mood disturbances in between 16% and 75% and anxiety disorders in 7% to 70%. Psychosis tends to occur in the context of confusional states with overall prevalence between 5% to 8% with increased incidence in patients receiving prednisone doses between 60 and 100 mg/day. Deficits in processing speed, attention, learning and memory, conceptual reasoning, and cognitive flexibility seen in around 11% to 54% of patients Kimura A, Kanoh Y, Sakurai T, Koumura A, Yamada M, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M, Inuzuka T. Antibodies in patients with neuropsychiatric systemic lupus erythematosus. Neurology. 2010 Apr 27;74(17):1372-9 .

40. SLE Cont ….. Elevated IgG and IgA anticardiolipin antibody levels may be causative or a marker of long-term subtle deterioration in cognitive function in SLE patient Focal or generalized seizures may occur in the setting of active generalized Seizure Treatment: Treatment of NPSLE includes C orticosteroids and Immunosuppressive therapy , including pulse IV cyclophosphamide or plasmapheresis. Anticoagulation is used in patients with thrombotic disease in the setting of antiphospholipid antibody syndrome

41. Demyelinating diseases (Multiple Sclerosis): Neuropsychiatric manifestations occur in up to 60% of patients at some point The lifetime prevalence of major depression in MS is approximately 50%. The lifetime prevalence of bipolar disorder is twice the prevalence in the general population. Euphoria may be present in more advanced MS, usually in association with cognitive deficits Pseudobulbar affect- defined as outbursts of involuntary, uncontrollable, stereotypical episodes of laughing or crying occurs in approximately 10% of patients Other symptoms include anxiety, sleep disorder, emotional lability/irritability, apathy, mania, suicidality, and rarely psychosis Minden SL, Feinstein A, Kalb RC, Miller D, Mohr DC, Patten SB, Bever Jr C, Schiffer RB, Gronseth GS, Narayanaswami P. Evidence-based guideline: assessment and management of psychiatric disorders in individuals with MS: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Jan 14;82(2):174-81.

42. Multiple sclerosis Cont …. Occasionally, psychiatric symptoms may present as the major manifestation of an episode of demyelination The presence of psychiatric symptomatology does not preclude the use of steroids to abbreviate clinical attacks of MS. Treatment : Combination of Dextromethorphan and quinidine may be considered for the treatment of pseudobulbar affect Pharmacological and behavioral treatment mirrors the management of depression and psychosis in patients without MS

43. Psychiatric Manifestations of Neoplastic diseases 15% to 20% of patients with intracranial tumors may present with neuropsychiatric manifestations before the development of primary neurological problems. Meningiomas due to their slow growth over years can present solely with behavioral manifestations Neurological paraneoplastic syndromes are primarily immune-mediated disorders that results from antigens shared between the nervous system and tumor cells

44. Neoplastic diseases…….. Ovarian and small-cell lung cancer (SCLC) present as neurological paraneoplastic syndromes Limbic encephalitis , associated with SCLC, testicular cancer, and ovarian teratomas Present as amnestic syndrome and neuropsychiatric symptoms including agitation, depression, personality changes, apathy, delusions, hallucinations, psychosis and seizures Anti N-methyl-D-aspartate (NMDA) receptor encephalitis presents commonly in young women with ovarian teratomas Present with anxiety, agitation, bizarre behaviour, paranoid delusions, visual or auditory hallucinations, and/or memory loss. Often progressive and refractory to therapy, although in some cases significant improvement follows tumor resection and early immunotherapy . Significant neuropsychiatric sequelae can arise from the various chemotherapeutic and radiation therapies used for cancer treatment Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, Dessain SK, Rosenfeld MR, Balice-Gordon R, Lynch DR. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. The Lancet Neurology. 2008 Dec 1;7(12):1091-8 .

45. Psychiatric Manifestations of Neuro Degenerative disorders Alzheimer Disease and Frontotemporal Dementia : Agitation, aggression, delusions including paranoia, hallucinations, anxiety, apathy, social withdrawal, reduced speech output Apathy (50%), hallucinations (25%), delusions (20%), depressed mood (46%), verbal aggression (37%), and physical aggression (17%) ,psychosis in 30-50% Atypical antipsychotic drugs are widely used to treat psychosis, aggression, and agitation in patients with AD Klüver – Bucy syndrome in late stages due to involvement of bilateral medial temporoamygdalar regions SSRIs are effective in treating behavioral symptoms including disinhibition

46. Idiopathic Parkinson Disease and Dementia with Lewy Bodies : Depression is the most common psychiatric symptom, with a prevalence of 25% to 50%. Psychosis is also prevalent and generally related to dopaminergic agents Hallucinations, usually fleeting and nocturnal, are typically visual and occur in 30% of treated patients In DLB Fluctuating cognition, recurrent visual hallucinations, and spontaneous features of parkinsonism Impulse-control disorders including pathological gambling, binge-eating, and compulsive sexual behavior and buying are associated with dopamine agonist treatment in PD Typical neuroleptics should be avoided. Novel atypical neuroleptics such as Quetiapine(50- 300mg/day) and Clozapine(50-200 mg) are effective Kirsch-Darrow L, Fernandez HF, Marsiske M, Okun MS, Bowers D. Dissociating apathy and depression in Parkinson disease. Neurology. 2006 Jul 11;67(1):33-8 .

47. Huntington Disease: Cognitive slowing, memory retrieval deficits, attentional difficulties, and executive dysfunction. Patients lack awareness of their chorea and their cognitive and emotional deficits. Psychiatric features such as personality changes, apathy, irritability, and depression are common. Depression may be exacerbated by tetrabenazine(dopamine-depleting agent) used for the treatment of chorea . Psychosis may occur in up to 25% of patients .

48. Epilepsy: A complex array of factors influence the neuropsychiatric effect of epilepsy Temporal lobe epilepsy may be associated with memory defects Frontal lobe epilepsy may be associated with performance deficits in executive functioning Behavioral disturbances are most common with complex partial seizures and seizures involving foci in the Temporolimbic structures. Onset of epilepsy before 5 years of age appears to be a risk factor for a lower intelligence quotient (IQ)

49. Epilepsy….. Generalized tonic- clonic seizures may have greater associated cognitive impairment Depression is the most common symptom(11% to 44%). The prevalence of psychosis is estimated at between 2% and 8%. Other psychiatric symptoms include anxiety, aggression, personality disorders, and panic disorders After a seizure, depressive symptoms have been known to last up to 2 weeks with increased suicide risk. Interictal depression is considered the most common type of depression in epileptic patients SSRIs(Sertraline and Escitalopram)) have a lower risk of associated seizures and should be considered as first-line pharmacotherapy

50. Postictal psychosis (PIP): An episode of psychosis emerging within 1 week after the return of normal mental function following a seizure Lengths between 24 hours and 3 months No evidence of EEG-supported nonconvulsive status epilepticus, anticonvulsant toxicity, previous history of interictal psychosis, recent head injury, or alcohol or drug intoxication Most commonly associated with temporal lobe epilepsy . Psychotic symptoms may include auditory, visual, or olfactory hallucinations. Responds to low-dose antipsychotics or benzodiazepines Seizure risk is particularly increased with use of clozapine and chlorpromazine

51. Depression-Related Cognitive Impairment Complex pattern of cognitive impairment seen in association with affective disorders such as major depression Patients tend to complain of memory and concentration problems Impairments in word generation, visuoconstruction , short-term memory, visual memory, executive functioning, and psychomotor and information-processing occurs Successful treatment of depression results in improvement of cognitive performance, particularly in memory and executive domains

52. Delirium Delirium or acute confusional state is a subacute- to acute onset disorder of attentional mechanisms that affect cognition Disturbance of vigilance, inability to maintain a coherent stream of thought, and difficulty or inability to carry out goal-directed movements Impaired sleep/ wake cycle is often seen and may be a presenting symptom. Advanced age, metabolic derangements, infections, medications, withdrawal syndromes, toxic exposures, major surgeries, head trauma, other CNS disease are risk factors Focal damage to unilateral or bilateral fusiform gyri and lingual gyri , nondominant posteroparietal regions

53. Delirium…… Early EEG changes show slowing of alpha rhythms, which may be succeeded by further slowing described as medium - to high-voltage generalized activity in the theta-delta range. Triphasic waves may be seen in a number of conditions that commonly include hepatic and renal encephalopathy. Treatment : Maintain ABC Resolution of delirium depends on resolution of primary cause. Antipsychotics - Olanzapine(1.25-2.5 mg OD/BD), Risperidone( 0.25- 0.5 mg OD/BD), Quetiapine(6.25-12.5mgOD/BD), Haloperidol are effective

54. Catatonia Catatonia is characterized by motor abnormalities that occur in association with changes in thought, mood, and vigilance. Mutism, stupor, stereotypies, mannerisms, diminished motor function ( including waxy flexibility or rigidity ), staring, negativism, automatic obedience, echopraxia, and echolalia Up to 20% of catatonia in psychiatric inpatients is associated with mania, and 5% to 15% with schizophrenia There are two principal forms of catatonia: a hypokinetic retarded-stuporous variety and a hyperkinetic excited-delirious variety Stroke, demyelinating disease, encephalitis, head trauma, medications, and CNS malignancy are individually associated with catatonia May progress to a malignant state marked by fever, hyperexcitability, and autonomic instability, followed by exhaustion, dehydration and coma Treatment with IV Benzodiazepines, IV Sodium amobarbital, or bilateral ECT can result in dramatic improvement Fink M, Taylor MA. The catatonia syndrome: forgotten but not gone. Archives of General Psychiatry. 2009 Nov 1;66(11):1173-7.

55. Treatment modalities for Depression and Psychosis Depression: 1)Drug therapy : First-generation antidepressants : Amitriptyline( 25–300 mg.), Clomipramine( 25–250 ),Desipramine( 25–300 mg), Imipramine( 25–300 mg), Protriptyline( 15–60 mg) Second-generation antidepressants : Bupropion 200–300 mg, Citalopram(10–40 mg), Escitalopram( 5–20 mg ), Duloxetine( 30–120 mg), Fluoxetine( 20–40 mg), Mirtazapine( 15–45 mg), Sertraline (25–150 mg), Venlafaxine (50–225 mg) MAOIs: Phenelzine( 45–60 mg), Tranylcypromine( 30–50 mg), Selegiline transdermal patch 6–12 mg/day Kroenke K, Krebs EE, Bair MJ. Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews. General hospital psychiatry. 2009 May 1;31(3):206-19.

56. Treatment…… For the first episode, antidepressant treatment may be taken for 1 to several months until remission is achieved Medication should be continued for another 4 to 9 months . For patients older than 70 years who respond to an SSRI, consider treating for 2 years to prevent recurrence 2) Psychotherapy : C ognitive behavioral therapy ( CBT ), Interpersonal therapy (IPT), and Problem-solving therapy (PST). CBT aims to modify distorted thoughts and problematic, reinforcing behaviors to yield more positive emotions. IPT requires the capacity for insight and targets conflicts and role transitions contributing to depression. In PST, patients learn to cope better with specific everyday problems

57. Treatment…… Light therapy, 6000 to 10,000 lux for 30 to 90 minutes each morning may be helpful Yoga, exercise , self-help books, and relaxation therapy may also be useful Combinations of MAOIs and either SSRIs or TCAs are not recommended because of an increased risk for serotonin syndrome Schizophrenia : Anti-Psychotic medications combined with psychological and social supports forms the base of the treatment The first-generation antipsychotics e.g., haloperidol, perphenazine, chlorpromazine The second-generation antipsychotics which also antagonize serotonin-2A receptors e.g., clozapine, risperidone, olanzapine, quetiapine

58. Side effects of anti psychotics Goff, D.C., Freudenreich , O., Henderson, D.C., 2008. Antipsychotic drugs. In: Stern, T.A., Rosenbaum, J.F., Fava, M., Rauch, S.L., et al. (Eds.), Comprehensive Clinical Psychiatry, first ed. Mosby, Philadelphia, pp. 577–594

59. Other treatment modalities : Electroconvulsive Therapy : effective for Major depressive disorder(MDD), bipolar disorder, drug-resistant chronic schizophrenia patients. Vagus Nerve Stimulation : for treatment-refractory depression (TRD) Repetitive Transcranial Magnetic Stimulation : for MDD ,OCD, posttraumatic stress disorder, and auditory hallucinations in schizophrenia. Psychiatric Neurosurgery or Psychosurgery : anterior cingulotomy, subcaudate tractotomy, limbic leucotomy and anterior capsulotomy for intractable mood and anxiety disorders Fox, M.D., Buckner, R.L., White, M.P., et al., 2012. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol. Psychiatry 72, 595–603

60. Conclusion Affective and psychotic disorders may occur as a result of neurological disease and can be indistinguishable from the idiopathic forms. Frontal-subcortical circuits and limbic system are heavily involved in cognitive, affective, and behavioral functioning. Many neurological disorders like stroke, brain infections, neurodegenerative disorders, autoimmune encephalitis present with psychiatric symptoms A detailed medication history, drug abuse, toxicology screen should be considered in patients presenting with new onset psychiatric symptoms Anti NMDA and Limbic Encephalitis presents with acute to subacute onset behavioral symptoms Treatments of primary psychiatric and neurological behavioral disturbances share common principles

61. Thank you