Adult Psychopathology 1

Statistical Model to define Mental Disorder

•Disorder = a statistical rarity, disorders are abnormal bc they are infrequent in the general population

Issues:

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* For where to draw cutoffs between normality and abnormality


* On which dimensions are relevant to abnormality. It treats all high scores the same (high on psychosis = high on intelligence, creativity, altruism). Why does high on anxiety matter to mental disorders and high on hair length not?
* Assumes all common conditions are normal (e.g. common cold is still a disease   despite its 100% lifetime prevalence)

Subjective Distress Model

\-•The core feature that distinguishes disorder from nondisorder is psychological pain

•However, some conditions do not cause the individual psychological pain, only those around them. E.g. antisocial personality disorder, manic episode

•Some conditions are associated with anosognosia – unaware of the fact that they are ill

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Biological Model

•Disorder is defined by a biological or evolutionary disadvantage (e.g. reduced lifespan or fitness) so that the ability to pass on genes to subsequent generations is compromised

•However, many things that affect longevity and fitness that are not disorders (e.g. celibacy, being a soldier)

•Mild conditions may still require treatment but don’t affect longevity or fitness (e.g. specific phobia) 

DSM Definition of Mental Disorder

•“A mental disorder is a syndrome characterized by clinically significant disturbance in an individual’s cognition, emotion regulation, or behavior that reflects a dysfunction in the psychological, biological, or developmental processes underlying mental functioning”.

•NOT an expected or culturally approved response to a common stressor or loss

•NOT socially deviant behaviors and conflicts between the individual and society (unless due to dysfunction)

Purpose of the DSM

•Way for variety of clinicians of all orientations to communicate the essential characteristics of mental disorders

•Reliable diagnoses  →  guide tx recommendations, id prevalence rates, id groups for research, document public health information (e.g. morbidity & mortality rates)

•Openly recognizes that mental disorders don’t always fit into the categories that the DSM creates

3 main issues of the DSM 5

1) high rates of comorbidity

2) excessive use of & need to rely on “not otherwise specified – NOS”   criteria (now Unspecified)

3) growing inability to integrate DSM disorders with genetic & other       biological studies

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•“By reordering and regrouping the existing disorders, the revised structure is meant to stimulate new clinical perspectives and to encourage researchers to identify the psychological and physiological cross-cutting factors that are not bound by strict categorical designations”.

Categorical System

•Classifies clinical presentations into types  or categories based on criteria sets with defining features

•Works best with homogeneity, clear boundaries, and mutual exclusivity

Dimensions System

•Classifies clinical presentations based on quantification of attributes rather than the assignment to categories

•Works best with continuous distributions and no clear boundaries

Dimensional Approach Support

•Taxometric analysis (can be used to determine whether categorical or dimensional models fit data best) favor dimensional approach

•No specific laboratory marker for any DSM disorders

•Lack of treatment specificity

•High rates of comorbidity/co-occurrence

•Heterogeneity of diagnostic membership

•Reliance on NOS/Unspecified

•Shifting DSM categories (one yr it’s a disorder, the next yr its not)

Categorical Approach Support (Future of Diagnoses)

•Dimensional approach vetoed by the APA board of trustees because of limited clinical utility, but included in Section III

•Problematic in that dimensional approach doesn’t define psychopathology (e.g. high sensation seeking found in both fire fighters and prison populations)

•Categorical structure has good reliability

•We’re all used to the current system (insurance structure)

Structure of the DSM

Section I: DSM-5 - TR Basics

Section II: Diagnostic Criteria and Codes

Section III: Emerging Measures and Models

Appendix

Use of the Manual

•Principal Diagnosis/Reason for Visit

•Provisional Diagnosis

•Other Specified _______ Disorder

•Communicates the specific reason that the presentation does not meet the criteria for any specific category within a diagnostic class

•Recorded by listing the name of the category followed by the specific reason

•e.g. “Other specified anxiety disorder, generalized anxiety not occurring more days than not”

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•Unspecified _________ Disorder

•Does not specify the reason that the criteria are not met for a specific disorder

Guidelines on Multicultural competency

•Clinical, research, teaching & training settings need to include multicultural competency 

•Lack specifics on how to apply multicultural knowledge

•Not a lot of research on HOW to apply cultural competency

Why the need for cultural guidelines?

•Expression of psychopathology differs across cultural groups, even within U.S. borders

•Ongoing racism & discrimination

* unclear if DSM dx criteria are valud cross-culturally

Cultural Formation Interview

•Brief, semi-structured interview (16 ?s) that assess the impact of culture on key aspects of pts clinical presentation and care

•Provides questions but follow-up

permitted/encouraged

•Person-centered approach, no right/wrong answers

•Can be used in its entirety or components

integrated into the interview as needed

•Focuses on pts experience and the social contexts of the clinical problem

Treatment - Colorblind Approach

•Colorblind Approach – different ethnoracial groups should be treated the same, without regard to cultural differences

* Well-meaning but generally Caucasian-centric

Treatment - Multicultural Approach

•Multicultural Approach – clients treated based on the norms & customs of their particular culture.

•Embrace differences, strengths & uniqueness of each cultural group

When to use the CFI?

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•Difficulty w/dx due to cultural, religious or socioeconomic differences between clinician and patient

•Uncertainty about the fit between sxs and diagnostic criteria

•Difficulty judging illness severity or impairment

•Disagreement between patient and clinician on the course of care

•Limited engagement in & adherence to tx by patient

4 domains the CFI assesses

•Cultural Definition of the Problem (?s 1-3)

•Cultural Perceptions of Cause, Context & Support (?s 4-10)

•Cultural Factors Affecting Self-Coping & Past Help Seeking (?s 11-13)

•Cultural Factors Affecting Current Help Seeing (?s 14-16)

MDD

A. 5 or more symptoms present during the same 2 week period that represents a change form previous functioning

\-at least 1 of the symptoms is either depressed mood or loss of interest in pleasure.

\-NO mania or hypomanic ep

B. symptoms causing clin sig distress/impairment

C/D/E. not attribuable to other disorders, substances, med con

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A1. Depressed mood most of the day, nearly every day, via self-  report or observation from others (can be irritability in children)

A2. Markedly diminished interest or pleasure in all, or almost all,   activities most of the day, nearly every day

A3. Significant weight loss (not due to dieting) __or__ weight gain (> 5%   of body weight in a month) __or__ decrease __or__ increase in appetite   nearly every day

A4. Insomnia or hypersomnia nearly every day

A5. Psychomotor agitation or retardation nearly every day\*

A6. Fatigue or loss of energy nearly every day

A7. Feelings of worthlessness or excessive or inappropriate guilt nearly   every day

A8. Diminished ability to think or concentrate, or indecisiveness, nearly   every day

A9. Recurrent thoughts of death, recurrent suicidal ideation without a   specific plan, or a suicide attempt or a specific plan for committing   suicide

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MDD Specifiers - with anxious distress

* anxious distress (need at least 2) -

1\. Feeling keyed up for tense

  2. Feeling unusually restless

  3. Difficulty concentrating because of worry

  4. Fear that something awful may happen

  5. Feeling that the individual might lose control of him/herself

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MDD - with mixed features

A. At least 3 of the following manic/hypomanic symptoms present the majority of days of the current MDD

  1. Elevated, expansive mood

  2. Inflated self-esteem or grandiosity

  3. More talkative than usual or pressure to keep talking

  4. Flight of ideas or subjective experience that thoughts are racing

  5. Increase in energy or goal-directed activity

  6. Increased or excessive involvement in activities that have a high potential for painful consequences

  7. Decreased need for sleep (feeling rested despite sleeping less)

PDD (dysthymia)

A. Depressed mood most of the day, for more days than not, for at least 2 years (kids – can be irritable, at least 1 year)

B. Presence, while depressed, of 2 or more:

„Poor appetite or overeating

„Insomnia or hypersomnia

„Low energy or fatigue

„Low self-esteem

„Poor concentration or difficulty making decisions

„Feelings of hopelessness

„C. During the 2-year period, patient has never been without the symptoms in A or B for more than 2 months at a time

„D. Criteria for major depressive disorder may be continuously present for 2 years\*

„E. There has never been a manic or hypomanic episode or cyclothymic disorder

„F. Not better explained by other disorders

„G. Not due to a substance or medical condition

„H. Symptoms cause clinically significant distress or impairment in social, occupational or other areas of functioning

Bereavement & MDD

\-Equally genetically influenced

\-Both most likely to occur in those with past personal & family histories of MDE

\-Show similar personality characteristics & patterns of comorbidity

\-Both respond to antidepressant medications

MDD & PDD differential

PDD - at least 2 years, no gap at any point for more than 2 months, 2 criteria instead of 5

PTSD

A.Exposure to actual or threatened death, serious injury, or sexual violence in at least one of the following ways:

B. Presence of at least one of the following intrusion symptoms associated with the traumatic event, beginning after the event

* (eg. distressing mems, nightmares, dissociative reactions, physiological reaction)

C. Persistent avoidance of stimuli associated with the traumatic event, beginning after the event occurred, as evidenced by 1 or both (avoidance of distressing mem and/or avoidance of external reminders)

D. Negative alterations in cognitions & mood associated with the event, beginning or worsening after the traumatic event occurred, as evidenced by 2 or more of the following:

E. Marked alterations in arousal & reactivity associated with the traumatic events, beginning or worsening after the event, by 2 (eg. irritable behav, reckless behav, hypervig, etc)

F. Last more than a month

G/H - clin sig distress, not attrib to other stuff

PTSD - with dissociative symptoms

the individual experiences persistent or recurrent symptoms of either of the following:

  1. Depersonalization: persistent or recurrent experiences of feeling   detached from, and as if one were an outside observer of, one’s mental   processes or body (e.g. dreamlike state, sense of unreality, time moving   slowly)

  2. Derealization: persistent or recurrent experiences of unreality of   surroundings (e.g. world is unreal, dreamlike, distant, distorted)

PTSD with Delayed Expression

Full diagnostic criteria are not met until at least 6 months after the event (some symptoms may have immediate onset)

Acute Stress Disorder

A. Exposure to actual or threatened death, serious injury or sexual violation in 1 or more of the following ways:

B. Presence of 9 or more of the following symptoms from ANY of the 5 categories of intrusion, negative mood, dissociation, avoidance & arousal beginning or worsening after the traumatic event.

C. Duration of the disturbance (symptoms in criterion B) is 3 days to 1 month after trauma exposure (i.e. must last at least 3 days, not longer than 1 month)

D/E - not atrributable to anything else

Adjustment Disorders

A.Development of emotional or behavioral symptoms in response to an identifiable stressor occurring within 3 months of the onset of the stressor

B.These symptoms or behaviors are clinically significant, by 1 or both of the following:

1.Marked distress that is out of proportion to the severity or intensity of the stressor, taking into account the external context & cultural factors that might influence symptom severity & presentation

2.Significant impairment in social, occupational or other important areas of functioning

C. does not meet criteria of another disorder

D. does not represent normal bereavement

E. once stress or consequences have terminated the symps do not persist longer than 6 months

PTSD - Acute Stress Disorder - Adjustment Disorder Differentials

* Acute Stress Disorder & PTSD have similar criteria for severity of traumatic event
* Acute Stress Disorder timing 3 days – 1 month

„PTSD timing > 1 month

* Adjustment disorder, traumatic event can be of any severity

Abdallahh et al - Chronic Stress Pathology

* Acute stress response can cause measurable brain changes within 24 hours
* Chronic stress response:
* reduced synaptic connectivity in PFC & hippocampus (neural   atrophy) = behavioral change, anxiety & mood dysregulation

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* increased synaptic connectivity in NAc and basolateral   amygdala

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Chronic stress is a major component in most psychiatric disorders (not specific to PTSD)
* Anti-depressant medications work through reversal of stress-related   damage

Bipolar Disorder 1

´A. Distinct period of abnormally & persistently elevated, expansive or irritable mood & persistently increased goal-directed activity or energy, lasting at least 1 week, present most of the day, nearly every day

´ - Or any duration if hospitalized

´B. During that time, 3 or more of the following (4 if mood only irritable) are present to a significant degree & are a noticeable change from usual

* ´Inflated self-esteem or grandiosity

´ - Decreased need for sleep

-´More talkative than usual or pressured speech

´- Flight of ideas or experience of racing thoughts

´- Distractibility as reported or observed

´- ncrease in goal-directed activity or psychomotor agitation

´- Excessive involvement in activities that have a high potential for negative consequences

C. cause marked impairment to necessitate hospitalization to prevent harm to others

D/E - not better explained by ohter stuff

BP 1 - Differential

´1. Major depressive disorder

´. - Past mania? Manic symptoms that don’t meet criteria. Irritability

´Other bipolar disorders

´ -Mania vs hypomania, substance use?

´PTSD

´ - Irritability, mood lability

´Borderline Personality Disorder

´. - Depression, mood lability & impulsivity

Bipolar Disorder II

**Must meet criteria for a current or past hypomanic episode** __**AND**__ **criteria for a current or past major depressive episode**

A.Distinct period of abnormally & persistently elevated, expansive or irritable mood & increased activity or energy, lasting at least 4 consecutive days & present most of the day, nearly every day

B.During mood elevation, 3 (or more) of the following symptoms have persisted (4 if mood is only irritable), represent a noticeable change from usual behavior & have been present to a significant degree:

•Inflated self-esteem or grandiosity

•Decreased need for sleep

•More talkative than usual or pressure to keep talking

•Flight of ideas or subjective experience that thoughts are racing

•Distractibility

•Increase in goal-directed activity (socially, work/school, or sexually) or psychomotor agitation

•Excessive involvement in activities that have a high potential for painful consequences

C. episode represents a change in individual

D. disturbances in mood & change are observable by other

E. NOT severe enough to cause marked impariments

F. not form substance

NO MANIC EPISODE EVER

BP II - Differentials

´Major Depressive Disorder

´. -Accompanied with subclinical manic or hypomanic symptoms

´Cyclothymic Disorder

´Anxiety Disorders

´. -75% comorbid

´Personality Disorders

-´Look for change from baseline

Cyclothymia Disorder

A.For at least 2 years (1 in kids) there have been numerous periods with hypomanic symptoms that do not meet criteria for a hypomanic episode AND numerous periods with depressive symptoms that do not meet criteria for a major depressive episode

B.During the above 2 year period (1 in kids) the hypomanic & depressive periods have been present for at least half the time & the individual has not been without the symptoms for more than 2 months at a time

C. No met crit for MD, manic or hypomania

D/E/F - sig distress, not attributable by others

Anorexia Nervosa

A.Restriction of energy intake relative to requirements, leading to a significantly low body weight in the context of age, sex, developmental trajectory & physical health.

* Significantly low body weight = weight that is less than minimally normal or, for children & adolescents, less than minimally expected

B.Intense fear of gaining weight or of becoming fat, or persistent behavior that interferes with weight gain, even though at a significantly low weight.

C.Disturbance in the way in which one’s body weight or shape is experienced, undue influence of body weight or shape on self-evaluation, or persistent lack of recognition of the seriousness of the current low body weight

AN specifiers

\-(F50.01) Restricting type: During the last 3 months, the individual has not engaged in recurrent episodes of binge eating or purging behavior. Weight loss is accomplished primarily through dieting, fasting &/or excessive exercise

\-(F50.02) Binge-eating/Purging type: During the last 3 months, the individual has engaged in recurrent episodes of binge eating or purging behavior

\-In Partial Remission: Criterion A no longer met (for a sustained period), but either Criterion B or Criterion C is still met

\-In Full Remission: None of the criteria have been met for a sustained period of time

Bulima Nervosa

A.Recurrent episodes of binge eating.  An episode of binge eating is characterized by __both__ of the following:

1.Eating, in a discrete period of time (e.g. within any 2 hour period), an amount of food that is definitely larger than what most individuals would eat in a similar period of time

2.Sense of lack of control over eating during the episode

B.Recurrent inappropriate compensatory behaviors to prevent weight gain (self-induced vomiting; laxatives, diuretics, fasting, excessive exercise)

C.Binge eating & compensatory behaviors occur, on average, at least 1 x week for 3 months

D.Self-evaluation is unduly influenced by body shape & weight

E.Does not occur exclusively during episodes of anorexia nervosa

Binge-Eating Disorders

A.Recurrent episodes of binge eating. Both of the following:

1.Eating, in a discrete period of time, an amount of food that is definitely larger than what most people would eat in a similar period of time

2.A sense of lack of control over eating during the episode

B.The binge-eating episodes are associated with 3 (or more) of:

1.Eating much more rapidly than normal

2.Eating until feeling uncomfortably full

3.Eating large amounts of food when not feeling physically hungry

4.Eating alone because of feeling embarrassed by how much one is eating

5.Feeling disgusted with oneself, depressed, or very guilty afterward

C. marked distress

D. at least 1x week for 3 months

E. not associated with recurrent use of inappropriate compensatory behavior

BN vs. BED

•Bulimia Nervosa → binge eating and compensatory behaviors, body image disturbance

•Binge Eating Disorder → binge eating only, binge-associated features

PICA

A.Persistent eating of nonnutritive, nonfood substances over a period of at least 1 month

B.Eating of nonnutritive, nonfood substances is inappropriate to the developmental level of the individual

C.Eating behavior is not part of a culturally supported or socially normative practice

D.If eating behaviors occur in the context of another mental disorder (e.g. autism spectrum disorder) or medical condition (including pregnancy), it is sufficiently severe to warrant additional clinical attention

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Specify- In remission: Criteria have not been met for a sustained period of time

PICA differential

–Anorexia Nervosa – if intent is to control appetite

–Factitious Disorder – if deception present

OCD - Obsessions

A. Presence of obsessions, compulsions or both:

__Obsessions:__

  1. Recurrent & persistent thoughts, urges, or images that are   experienced as intrusive or unwanted, & that (in most) cause marked   anxiety or distress

 

  2. The individual attempts to ignore or suppress such thoughts, urges, or   images, or to neutralize them with some other thought or action (i.e.   performing a compulsion)

OCD - Compulsions

__Compulsions:__

  1. Repetitive behaviors (e.g. hand washing, ordering, checking) or   mental acts (e.g. praying, counting, repeating words silently) that the   individual feels driven to perform in response to an obsession or   according to rules that must be applied rigidly

 

  2. Behaviors or mental acts are aimed at preventing or reducing anxiety   or distress, or preventing some dreaded event or situation; however,   these behaviors or mental acts are not connected in a realistic way with   what they are   designed to neutralize or prevent, or are clearly excessive

OCD criteria

A. Presence of obsessions, compulsions or both:

B. The obsessions or compulsions are time-consuming (take > 1 hour per day) or cause clinically significant distress or impair social, occupational or other functioning

C. Symptoms not attributable to the effects of a substance

D. Not better explained by another mental disorder (lots of examples in DSM-5-TR)

OCD Specifiers

Specifiers:

•__With good or fair insight__: recognizes beliefs are definitely or probably not true or that they may or may not be true

•__With poor insight:__ thinks OC beliefs are probably true

•__With absent insight/delusional beliefs__: completely convinced OC beliefs are true

•__Tic-related:__ individual has a current or past history of a tic disorder (\~30%)

Park et al 2020 -

•SSRI’s are the front-line treatment for OCD

•132 patients with OCD given SSRIs & evaluated at baseline & 4 weeks

•Age & “Positive Beliefs About Worry” predicted response to SSRI at 4 weeks

•Younger more likely to respond

•Fewer “Positive Beliefs About Worry” more likely to respond

• Having positive beliefs about worry may increase psychological resistance to SSRI

OCD - Anxiety Differential

•__Anxiety Disorders:__ content of obsessions versus real-life worries, presence of rituals

OCD - Body Dysmorphic Disorder

•__Body Dysmorphic Disorder:__ obsessive thoughts related to one’s body vs varied content in OCD

OCD - Hoarding Disorder Differential

fear of giving up vs needing symmetry or a complete set

OCD - Tic Disorder Differential

•presence & chronology of obsessions

**Body dysmorphic disorder**

A.Preoccupation with one or more perceived defects or flaws in physical appearance that are not observable or appear slight to others

B.Performance of repetitive behaviors  (e.g. excessive grooming, skin picking) or mental acts (e.g. comparing appearance) in response to appearance concerns

C.Preoccupation causes clinically significant distress or impairment in social, occupational or other imp areas of functioning

D.Symptoms are not better explained by an eating disorder

BDD specifiers

•__With muscle dysmorphia__: preoccupation that body is too small or insufficiently muscular

•__With good or fair insight__: Recognizes that beliefs are definitely or probably not true or that they may not be true

•__With poor insight__: beliefs are probably true

•__With absent insight/delusional beliefs__: completely convinced that beliefs are true

Moody et al. 2021. Brain Activation & Connectivity in Anorexia Nervosa & Body Dysmorphic Disorder

•BDD tend to have lower insight & more delusional beliefs than AN

•Activation was different between BDD & AN in both the Dorsal Visual Network & the Parietal Network

* •Hypoactivation in BDD in DVN & PN : reduced holistic integration & configural processing of spatial relationships -> hone in on one body part
* •Hyper-connectivity in DVN in both BDD & AN  : share spatio-temporal phenotype when visually processing bodies

•Activation correlated with clinical symptoms in BDD & AN

BDD - Differentials

•__Eating Disorders:__ concerns about being fat vs multiple concerns about a defect

•__Other OC-related disorders:__ OCD assoc. with better insight & varied obsessions, intention behind skin picking or hair removal

•__Major Depressive Disorder:__ Often co-occur. Preoccupation with appearance & excessive repetitive behaviors vs. preoccupation with negative thoughts & low self-worth. MDD often a result of body dysmorphic disorder

•__Anxiety Disorders:__ Often co-occur. Focus of social isolation/avoidance is body focused in BDD, not so with other anxiety disorders

Hoarding Disorder

A.Persistent difficulty discarding or parting with possessions, regardless of their actual value.

B.Difficulty due to perceived need to save items & to distress associated with discarding them.

C.Results in accumulation of possessions that congest & clutter active living areas & substantially compromises their intended use. If living areas are uncluttered, it is only because of the interventions of third parties

D.Causes clinically significant distress or impairment in social, occupational or other imp areas of functioning

E.Not due to a medical condition

F.Not better explained by another mental disorder

Hoarding Disorder Specifiers

__With excessive acquisition__: difficulty discarding items is accompanied   by excessive acquisition of items that are not needed or for which there   is no available space

  __With good or fair insight__: Recognizes that hoarding-related beliefs &   behaviors are problematic

  __With poor insight__: Mostly convinced that hoarding-related beliefs &   behaviors are not problematic despite evidence to the contrary

  __With absent/delusional beliefs__: Completely convinced beliefs &   behaviors are not problematic despite evidence to the contrary

**Nakao et al. 2019. Pathophysiology and Treatment of Hoarding Disorder**

•Hoarding disorder presents similarly across cultures (UK, Spain, Japan & Brazil)

•Hoarding disorder was originally conceptualized as an OCD subtype – when OCD was considered an Anxiety disorder

•Impairment in functioning separates Hoarding from Collecting

•Few imaging studies: small samples & inconsistent findings

•Trend for increased activation in frontal cortices

•SSRIs used to treat HD: \~70% response rate

Specialized CBT is promising

Hoarding Disorder - Differentials

•OCD: Obsessions about incompleteness associated with discarding things or avoidance of rituals associated with discarding things.

•OCD – behaviors are unwanted & highly distressing, acquisition associated with obsessive thoughts, not with the intent to accumulate/save.

•Other mood & anxiety disorders: 75% comorbidity

•Up to 50% have comorbid MDD

•Social Anxiety Disorder & GAD

**Trichotillomania**

A.Recurrent pulling out of one’s hair, resulting in hair loss

B.Repeated attempts to decrease or stop hair pulling

C.The hair pulling causes clinically significant distress or impairment in social, occupational or other important areas of functioning

D.Not due to another medical condition

E.Not better explained by another mental disorder

**Trichotillomania - Differentials**

•Other Obsessive-Compulsive & Related Disorders

•OCD – Body Dysmorphic Disorder

•Most common comorbidity with MDD & Excoriation

Excoriation Disorders

A.Recurrent skin picking resulting in skin lesions

B.Repeated attempts to decrease or stop skin picking

C.Skin picking causes clinically significant distress or impairment in social, occupational or other important areas of functioning

D.Skin picking is not attributable to the physiological effects of a substance (e.g. cocaine) or another medical condition (e.g. scabies)

E.Skin picking is not better explained by symptoms of another mental disorder (e.g. delusions or tactile hallucinations in a psychotic disorder, attempts to improve a perceived defect or flaw in appearance in body dysmorphic disorder, stereotypies in stereotypic movement disorder, or intention to harm oneself in nonsuicidal self-injury)

Scaini et al 2020 - Neurobio of BP1

´Immune-Inflammatory Imbalance

* ´Elevated levels of pro-inflammatory cytokines during mood episodes

´Hypothalamic-Pituitary-Adrenal Axis – biological response to stress

* ´Hyperactive HPA axis in manic states correlates with cognitive deficits & neurotoxic effects on hippocampus

´Greater sleep/wake/activity variability predicts mood episode

Pinto e tal 2018 - Neurobio of BP

´- Injury, illness or stress can cause astrocytes to lose control of the blood brain barrier, making it more permeable

´- Peripheral proinflammatory markers gain access to the brain, creating conditions for a chronic immune response

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´- BP associated with reduced brain volume driven by white matter loss

´. The longer someone is on lithium, greater white matter integrity

´ -Lithium, valproic acid & clozapine neuroprotection may be through inhibited astrocyte & proinflammatory cytokine production