Neuropsychology and Neuropsychiatric Conditions 2024 PDF

Neuropsychology and neuoropsychiatric conditions 2024 Andrew Rock Senior Clinical Neuropsychologist  Neuropsychiatric (npsic) conditions… Disorders that impact substantially on brain functioning and significantly disrupt emotions, thinking and behavi...

Neuropsychology and neuoropsychiatric conditions 2024 Andrew Rock Senior Clinical Neuropsychologist  Neuropsychiatric (npsic) conditions… Disorders that impact substantially on brain functioning and significantly disrupt emotions, thinking and behaviour “elle est fou” vs diversity; lots of them – ~300 psychiatric disorders in the DSM-5 Include … – mental illnesses (schizophrenia, mood disorders, anxiety disorders) – neurodegenerative conditions (prion disease, DLB) – Sleep disorders Kolb and Wishaw, 2022 2  Npisc conditions important to npsy because… affect lots of people National Study of Mental Health And Wellbeing, 2020-21 – ~45% of Australians aged 16-85 had a mental disorder (anxiety, depression, impulse-control, substance use) at some point in life – >20 % had a mental disorder in the last 12 months, and ~40 % aged 16-24 – 3.4 M consulted a professional for their mental health 2-way street between brain and behaviour; DLB → psychiatric features; depression → changes in brain on imaging; central to many neuropsych referrals Today’s focus: schizophrenia, depression and DLB 3  Schizophrenia “Schizophrenia remains one of the most common and disabling of all psychiatric disorders” Javitt 2016 disabling, persistent brain disorder that disrupts how a person interprets reality, and thinks, feels and behaves Probably compromises a group of disorders with heterogeneous aetiologies, and patients varying in presentations and treatment response Sadock & Sadock, 2005 Symptoms change over time A clinical diagnosis, diagnosis by exclusion; coming closer, but no sign or symptom pathognomic for schizophrenia 4  Evolution of the concept Emil Kraepelin 1856-1926 – 1887: manic depressive psychosis vs. dementia praecox – Dementia praecox a biological illness involved hallucinations and delusions, an early change in cognition, then long-term deteriorating course Eugen Bleuler: 1908 – dementia praecox as a group of diseases – “neither a question of an essential dementia, nor a necessary precociousness… I am taking the liberty of employing the word schizophrenia (to indicate) the breaking up or splitting of psychic functioning” – Not split personality; schisms between thought, emotion and behaviour resulting in difficulty relating to the world – Primary symptoms were the 4 As; associations, affect, ambivalence and autism – Move to explaining not just describing psychiatric illness 5 Approaches to diagnosis: Ernst Kretschmer – asthenic types (“thin, tall and weak”) prone to schizophrenia; – pyknic types (“squat and fleshy build”) prone to bipolar disorder – asthenic types more likely to be involved in petty theft and fraud, athletic types in violent crimes, while pyknic were involved in both 6  Kurt Schneider’s approach to diagnosis: 1 or more 1st rank symptom – Auditory halls: “thought echo;” commentary about you, your thoughts and actions, voices commenting on your actions, discussing you – Thought insertion and withdrawal – Thought broadcasting – passivity experiences (sensation, movements, thoughts) – delusional personalisation of perceptions, and primary delusions “out of a clear blue sky” 2nd rank symptoms: sudden delusional ideas, perplexity, depressive and euphoric mood changes, emotional impoverishment 7  DSM-5 criteria for diagnosis: Positive and negative symptoms A. 2 or more the following symptoms (1-4 are positive) 1. * Delusions 2.* hallucinations 3.* disorganised speech 4. grossly disorganised behaviour 5. negative symptoms, eg blunted affect, alogia or avolition. must include 1, 2, or 3, and each is present for most of a month if untreated, B. Reduced functioning for a significant period since onset in work, relationships, self-care or expected development C. Continuous disturbance for 6 months+, a month (untreated) of criterion A symptoms. Can include prodromal/attenuated periods D-F. Not due to szaffective, MDD or bipolar disorder; or drugs or medical conditions; in case of autism/communication disorder, prominent delusions/hallucinations for 1 month 8  Criterion A symptoms: Delusions 1/5 “Fixed beliefs that are not amenable to change in light of conflicting evidence.” Must be inconsistent with their cultural and educational background Onset may be slow or sudden mostly see them as self-evident. Usually don’t press them on others Usually hold multiple beliefs – often inconsistent, except for theme (persecutory*, referential, religious, grandiose) 9  Hallucinations in schizophrenia 2/5 Sensory experience without stimulation of the sensory organs. Auditory hallucinations most common; – Voices very characteristic, but also hear tapping, footsteps etc. – Content: single words, or phrases, or commands – Some highly suggestive of schizophrenia, e.g. repeating thoughts, commenting on what the person is doing, or arguing with each other – patients may argue with them, or try to drown them out; may or may not be able to resist commands Hallucinations occur in other modalities, but need to consider other causes 10  Disorganised speech 3/5 “formal thought disorder” –illogical, incoherent self- expression in speech or writing Examples include tangent rambling, lack of connectness of one thought to the other, neologisms (orange a tofuela), and clanging – Q: Have you been nervous or tense lately? – A: No, I got a head of lettuce. – Q: You got a head of lettuce? I don’t understand. – A: Well, it’s just a head of lettuce. – Q: Tell me about lettuce. What do you mean? – A: Well...lettuce is a transformation of a dead cougar Lack goal-directed speech; ‘word salad” 11  Grossly disorganised/ catatonic behaviour 4/5 Nb not necessarily specific for scz Too little (very slow, frozen posture, stupor) Too much (bizarre, frenzied, purposeless bvr eg repetitive rhythmic gestures, walking in circles) Bizarre affect – incongruence between the feelings they report experiencing, and what they show Tendency to dress inappropriately for the weather, untidy or unkempt 12  Negative symptoms 5/5 Affect: – Reduced emotion from blunting to flattening – Wooden lifeless face, apparent loss of emotional life – can be marked contrast between internal and external emotion; GSR vs. expressions and self-rating Alogia – Poverty of speech: the quantity said is very limited. Complain their heads are empty – Poverty of thought: amount said is ok but excessively vague, lacks useful detail Avolition – Lack impulses or inclinations; may just sit and stare doing nothing if not interrupted 13  Negative symptoms (cont) Social withdrawal Amotivation Negative symptoms harder to treat clinically, and predict poor outcome 14  Dimensions/subtypes of schizophrenia – Paranoid; delusions and hallucinations; later onset – Disorganised (hebephrenic); “childish silliness” – Catatonic: stupor and/or excited behaviours – Undifferentiated: hard to distinguish – Residual: blunting, withdrawal, psychosis mild – Simple deteriorative: early onset, negative symptoms, slow course – Dimensions: 2, 3, 4, or 5 – DSM 5: discontinued specificity, reliability, prognostic value 15  Typical course of schizophrenia 1 premorbid phase 2 prodromal period (relatively subtle symptoms, often late teens/early 20s, May follow major changes e.g. moving out, deaths etc. 2-4 year duration common, but may be weeks, and about 20 % no prodromal period 3 frank psychosis, 4 some degree of recovery but waxing and waning with enduring vulnerability to stress, lower baseline after each episode. Contrasts with mood disorders Post-psychotic depression common Psychotic symptoms tend to stabilise but negative symptoms tend to increase 16  Predicting onset Benefits: “prodromal phase provides an optimal opportunity to mitigate the profound functional disability…”Carrion et al, 2024.” “ Benefits of early detection and intervention consistently reported from many different countries.” (Coulter et al, 2019; Winkler, 2018; Cialeglio, 2018). Longer DUP ~ poorer outcome. Problem: signs often non-specific. ↓ Concentration, motivation, sleeping, mood ~ 50 % of teens show some compatible symptoms. Potential “false positive” effects – impact on life goals; side effects of medications; stigma. – False rate rising (Simon, 2014). False pos rates sometimes range from 50 -90 %. Coulter et al 2019 found of 43 patients referred with “schizophrenia,” 51 % had a different condition, and 42 % had no primary psychotic disorder. State of play – 200 with Attenuated Psychosis Syndrome tracked for 2 years. 30 % converted to psychosis, 21 % developed scz. Attenuated odd ideas and disorganised communication 17 best predictors. Brucato 2017  Prognosis and outcome “4 quarters rule:” very poor outcome; somewhat improved but requiring a lot of ongoing support; much improved, fairly independent; good prognosis, few episodes with minimal deficits More recent definitions less encouraging: Life skills: difficulties medications (86%), preparing food (85%), shopping (78%), handling finances (61%), doing laundry (52%) (Samuels 2018) Work: 9-12 % support themselves through employment. Varies from country to country “70 to 90 %..have vocational and residential challenges” Harvey, 2019 16-23 % relapse in a year (+meds) vs. 53-72 % (-meds) +meds 80 % relapse in 5 years; *5 -meds About ½ stop taking medications within two years 1/3 attempt suicide; ~10 % complete suicide Risk factors: male, paranoia, higher premorbid intelligence and social functioning, early/recent episode, longer duration untreated, * substance abuse 18  Demography of schizophrenia Lifetime prevalence about 1 percent M>F M younger; 50+ % M vs 33 % F have first psychiatric admission before 25 M: peak onset 15-25, F:25-35; F have a bimodal distribution, with 2nd, smaller peak in middle age. onset before 10 or after 60 is rare M have …more severe negative symptoms, drug use, social problems and poorer outcomes. F have…more depressive symptoms, social functioning and outcomes (Chintoh et al, 2024). 19  The genetic account adoption studies – biological not adoptive relatives Shared abnormalities bn PwS and relatives, eg prepulse inhibition 20  Limitations of the genetic explanation under the Nazis >75 % of Germans with schizophrenia were sterilised or murdered German incidence rate higher than Europe and America in 1970s, and now equivalent Reproductive rate in schizophrenia about 50 %, yet prevalence is increasing No “schizophrenia gene” identified; lots of genes all play a small contribution Hyman, 2018 21  The biochemical account Dopamine hypothesis – sz caused by too much DA activity ? Excess in release, receptors, or sensitivity Support – Drugs increasing DA activity (cocaine) mimic symptoms of psychosis – Drugs that disrupt DA activity reduce psychotic symptoms (antipsychotics) Other neurochemicals also implicated 22  The structural accounts Loss of cells: whole brain (enlarged ventricles*) and specific regions eg frontal lobes and PFC, hippocampus and limbic system, thalamus, basal ganglia and cerebellum Osimo el al, 2019; Smeland et al, 2017 Loss of connectivity: not sites, but circuits. AC-basal ganglia- thalamocortical tract → positive symptoms, PFC circuit → negative symptoms Neurodevelopmental hypothesis – 2 hit model: maldevelopment at 2 critical time points – Congenital anomalies in brain development, e.g. disrupted brain lateralisation, lead to premorbid symptoms and “soft signs” – Problems in adolescence: excessive pruning of synapses, loss of plasticity to adapt to changing environment 23  Psychosocial and psychoanalytic accounts No strong evidence for a causative role for any specific family pattern Children of sz mothers more likely to develop sz if reared in adverse circumstances than stable families Childhood abuse or trauma – in 20 studies, ½ those with psychotic symptoms reported childhood abuse Higher rates of relapse in families with high levels of negative expressed emotion 24  Influence of experience and environment Prominent variation in risk ?Male sex: 3 men for every two women 1st-2nd generation migrant, esp. if black Maternal malnutrition: *2 Dutch hongerwinter and Chinese CR Maternal viruses during gestation flu, measles, ? herpes simplex 2 Pregnancy and birth complications – pre-eclampsia, asphyxia, emergency C-section Advanced paternal age Urban birth or residence 2.4* risk Higher risk in developed nations Living at higher altitude, for males - ?vitamin D/ultraviolet light Cannabis 25  Cognitive findings in schizophrenia Cognitive impairment “a core feature of schizophrenia” independent of positive symptoms or medications European Psychiatric Assocn 2022, Green 2019 Cognition more predictive than imaging Most influential symptom re outcome and quality of life not responsive to existing treatments McCutcheon et al 2023 Very variable between individuals but frequently ~1.5 to 2 standard deviations below average Debate about specific vs global deficits (processing speed downstream effect?) but… mental speed, attention and working memory, learning and memory, reasoning and problem solving, social cognition particularly impacted 26  Course of impairment By age 4, deficits in IQ and executive skills in kids at familial high risk Stephens et al, 2024 A year behind at the start of school, with some decline/slower gains by the end Deterioration with first episode mixed findings about decline vs leveling out – Zanelli et al, 2019: decline varied between people, and between domains over 10 years from diagnosis. – Verbal knowledge, memory ↓ – speed, XF, visuospatial more stable 27  Case study 1: Schizophrenia Developmental – odd interests, no friends outside family, ↑ isolated through adolescence Initially strong academically but ↓ throughout school Began studying engineering but dropped out in 2nd year Worked in family business for a while but ↑ delusions and paranoia; unable to work since early 20s. Brother arranged DoH accommodation, but wouldn’t stay. Cycles between streets, motels when Centrelink arrives, and family Believes has direct contact with Jesus, brought down the Soviet Union Testing: broadly moderate cognitive impairment. Deficits most marked in executive functioning 28  Mood disorders WHO: depression will rival heart disease as the health disorder with the highest disease burden by 2030 Main types Major depression (MDD/ clinical/ unipolar depression) - a depressed mood that lasts for at least 2 weeks. Bipolar disorder - (manic depression) – alternating periods of feeling low (depressed) and high (manic). Psychotic depression - depressed mood with psychotic symptoms, e.g. hallucinations, delusions, and paranoia Dysthymia - a less severe depression, lasts for years Mixed depression and anxiety - combined symptoms 29  Bipolar disorder A. - a distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week. Enough to impair social/occupational functioning, need hospital. May involve delusions (esp. grandiose, persecutory) or hallucinations (esp. auditory) B. - during the period of mood disturbance, 3+ of the following symptoms have been persistent and significant (4 if mood is only irritable): 1) increased self-esteem or grandiosity – the documentary man 2) decreased need for sleep (e.g., feels rested after only 3 hours of sleep) 3) more talkative than usual or pressure to keep talking 30  Manic episodes (cont.) 4. flight of ideas; sense of racing thoughts 5. distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli) 6. increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation (the CCMH patient) 7. excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., reckless buying sprees, sexual indiscretions, business investments) 31  Prevalence of BPD – ~ 2 % of Australians experience BPD at some stage – Sex ratio (F:M) 1:1 for BPD I (mania and depression), but 2:1 for BPD II (milder mania, more depression) – onset usually between childhood to 50 years. Mean age 21, most cases 15-24. Average period from 1st symptoms to diagnosis about 12 years. – onset after 50 may relate to medical triggers like CVD 32  Major depressive disorder ~ 9 % of M, 13 % of F have had a depressive episode ~ 4 % of M, 6 % of F have had one in the last 12 months » Aus. Institute of Health & Welfare, 2023 33  DSM-5 criteria A. 5+ of the following for a 2 week period; represents a change from previous functioning; must include symptom 1 or 2 1. * depressed mood nearly every day 2. * Diminished interest or pleasure in all or most activities 3. Significant unintended weight loss or gain, e.g. 5 % 4. Insomnia or sleeping too much nearly every day 5. Agitation or psychomotor retardation noticed by others 6. Fatigue or loss of energy 7. Feelings of worthlessness or excessive guilt 8. ↓ ability to think or concentrate, or indecisiveness 9. Recurrent thoughts of death B. Symptoms cause significant distress or impairment in social, occupational, other important areas C-E. Not attributable to substances, medical conditions, or psychiatric conditions 34  ABC of depression Affective component – Feelings Behavioural component – Too much or too little Cognitive component – Content – Detail, inefficiency, slowing 35  Presentation and age Prior to puberty – Weight gain; irritability; anxiety on separation; somatic complaints Adolescents – Irritability; rebelliousness; conduct problems; falls in grades; change in friends In the elderly – Agitation; more likely to deny, focus instead on hypochondriacal concerns; problems in memory and concentration 36  Course of MDD Short-term – ~ 50 % have full remission in 6-12 months Longer term – 90 % no longer have full form 2 years later A recurring problem – ⩾40–75% lifetime recurrence Chiu, 2017 – Average interval of ~ 5 years between episodes – Some have recurrence within a year, some stay free – With repeated episodes, common trend to shorter remissions and longer episodes 37  Risk factors Genetic findings heritability ~ 40% Corfield, 2017. Increases to ~ 70% in twins with recurrent and severe major depression may inherit a generic liability, not a specific form of depression Specific medical factors “vascular depression;” microvascular dysfunction causally linked to late-life depression van Agtmaal 2017 thyroid dysfunction, stroke, TBI, epilepsy, PD, some steroid and hormonal treatments General medical factors chronic pain 38  The monoamine hypothesis Dean, 2017 monamines (MAs, e.g. serotonin, noepinephrine, dopamine )= NTs involved in fight or flight “MDD caused by imbalance of one or more MAs” Support People and animals given drugs that reduce MAs, like reserpine, often show depression-like behaviour People with MDD have low levels of MAs; drug treatments increase levels of MAs; depression eases. depleting dietary building blocks (precursors) of serotonin associated with relapse in recovered patients People who complete suicide have lower brain stem levels of serotonin and/or its by-products 39 Limitations Reducing precursors doesn’t make heathy people depressed antidepressants don’t work for many Reserpine only induces depression in a small minority drugs increase MAs very quickly, but changes in mood take several weeks ideal/ problem levels still unknown Aspirin fixes headache, doesn’t mean headache caused by too little aspirin 40  Cognitive theories of depression depression comes from neg distortions in perception, memory, and problem solving. “the sunglasses theory” Vulnerabilities, formed thru observation or traumatic events, later triggered by parallel experiences Beck’s negative cognitive triad: dysfunctional schemas (belief systems) re the self, the world, and the future E.g. I’m unloveable; no one loves me; no one will ever love me 41  those with dysfunctional attitudes similar to Beck’s ~ 7* more likely to develop depression, and ~2 * as likely to relapse Ezawa et al 2020, Ebrahimi 2012 Chicken vs egg: maybe depression leads to depressive thoughts, not vice versa CBT remains one of the most widely used and effective methods of treating depression 42  Hypothalamic-pituitary-adrenal (HPA) axis hypothesis Under stress, the HPA axis ↑ cortisol; ↑ glucose and ↓ other production like BDNF. When the crisis is over the HPA should restore normal activity Chronic stress leads to atrophy of PFC, hippocampus and amygdala, ? possible inhibition of neurogenesis, compromised ability to “turn down” HPA axis activity Effect of damage to those areas - compromised ability to process negative emotion, display adaptive behaviour, and lose drive to engage with the environment HPA hyperactivity one of the most consistent findings in depression; it resolves with successful antidepressant treatment Dinan, 2016 ? chicken or egg? Maybe HPA axis hyperactivity not a consequence but a risk factor for depression, caused by genetic liability and early life experience 43  The gut-brain axis hypothesis Gut bacteria (microbiota)→NT→ mood Meng, 2024 Depressed and healthy controls can be distinguished by gut bacteria Jiang, 2015 Experimentally depleting rats’ gut microbiota leads to depression-like bvr Hoban, 2016; increasing gut microbiota reverses this Faecal microbiota transplantation (FMT) from an anxious mouse produces anxious behaviour, FMT from a non- anxious mouse produces non-anxious behaviour FMT from depressed humans into rats induced bvl features of depression Moodliar 2019 FMT for IBS from healthy to depressed people associated with significant gains in mood Kurokawa, 2018 44 Depression is increasingly attributed to the mix of recent events and long-term risk factors 45 beyondblue  Cognitive comparison of BPD and MDD Both characterised by cognitive dysfunction; variable findings but deficits tend to involve sustained and divided attention, speed, executive functioning, verbal learning and memory. ES generally greater in BPD than MDD MacQueen, 2017 Residual impairment in attention and EF: – Some studies find comparable severity – Some find worse verbal memory, mental flexibility and inhibitory control in BPD Most suggest BPD similar to MDD, but more severe; EF and memory stronger in depressed patients 46  Case study 2: depression 48 year-old man, married, 2 kids Healthy but 12 month history of depression: social isolation, guilt, fatigue, hopelessness and helplessness Triggered by intolerable work stress, sick leave, laid off On testing: general cognition WNL, but inefficient working memory and mild to moderate cognitive slowing. Memory deficits due to encoding: recall OK Spatial skills, language generally OK Deficits in executive functioning related to complex attention, planning, indecisive responding: difficulty sustaining effortful performance 47 Neuropsychiatric symptoms in degenerative conditions: Dementia with Lewy bodies DLB 2nd or 3rd most common form of dementia hybrid of Alzheimer’s and Parkinson’s disease Fourth Consensus report 2017: 2 or more core features : 1. Fluctuating cognition with pronounced fluctuations in concentration and attention; 2. recurrent well-formed visual hallucinations; 3. REM sleep behavioural disorder 4. One or more spontaneous motor features of parkinsonism Supportive features: – severe sens. to antipsychotics, falls, syncope… hallucinations in other modalities, systematised delusions, apathy, anxiety and depression 48  Visual hallucinations Recurrent, detailed, well formed. Not flashing lights Typically involve people or animals intruding into the home, but also involve perceptual distortions, e.g. misidentification syndromes, seeing faces emerging out of patterns on carpets, or backgrounds like trees VH more common, appear earlier in women Chiu, 2023. 82 % of women, 66 % of men and 79 % overall Choudhury, 2021 Not usually the earliest symptom but early, recent VH far more specific for diagnosis 49 Can be enjoyable or frightening  VH not unique to DLB, e.g. delirium and other dementias, but distinguished by early onset, persistence, non mood-congruent nature Hallucinations less common in other modalities VH correlate with greater visuospatial problems; Capgras delusion and delusional misidentification; better response to medications 50  Basis of VH in DLB A) Basic problem with visuoperception? But Posterior Cortical Atrophy defined by visuospatial problems due to occipito-parietal degeneration, and VH rare B) DLB patients typically have hypoperfusion or hypometabolism in occipital lobes, possibly due to loss of cholinergic input. Primary visual cortex malfunctioning with abnormal sensory experiences C) Fluctuating cognition – intrusions of dream imagery into wakefullness Still contentious 51  Pat 3: DLB or psychotic depression? 70 year-old, immigrated in late childhood. Primary level education, factory worker and seamstress depression, osteoarthritis, hypertension, repeated falls No lesions on recent CT brainscan No known psychiatric history until unexpected death of son 8 months ago; husband died about 20 years ago Since son’s death converses and interacts with him: expected him to pay for food 52  Observations Would ask for food for son because he was hungry Had 2 sons: reported there were 2 versions of each Hallucinations mainly son, husband, but included strangers wandering through house Stopped doing laundry because worried about the man in the dryer Recognised me but not the route to the assessment room Fluctuating difficulty following instructions 53  DLB or psychotic depression? timing, personal relevance of much of the hallucinations supports PMD, but wouldn’t explain: – recurrent VH of strangers; reduplicative phenomena; falls – cognitive features: disproportionate impairment in visuospatial and executive functioning, with fluctuating alertness Evidence consistent with probable DLB, with psychotic depression possibly imposed on top 54  Concluding observations Mental distress ≠ mental disorder. Consider: 1. Characteristics of the experience 2. Cultural context (the case of the cursed fridge mechanic) 3. Personal context: 1/3 to ½ of bereaved spouses report some level of hallucination involving the deceased therapy helps even when it can’t cure early intervention really helps talk to the person; don’t try doing therapy on them, but engage them and include them Talk directly about mental health problems e.g. asking if someone’s thinking about suicide doesn't make it more likely. Depressed people can struggle with motivation and organisation: consider helping organise the appointment Good resources: – beyondblue.org.au, blackdoginstitute.org.au, GPs 55