brain/behaviour development along adolescence … · brain/behaviour development along adolescence...

BRAIN/BEHAVIOUR DEVELOPMENT ALONG

ADOLESCENCE

Adolf Tobeña

Dept. of Psychiatry and Forensic Medicine. Institute of Neurosciences.

School of Medicine. 08193 Bellaterra Campus.

Autonomous University of Barcelona.

Dahl RE (2004), in “Adolescent Brain Development: vulnerabilities and opportunities”,

Annals NYAS, Vol. 1021, pp. 1-22

Aristotle “Youth are heated by Nature as drunken men by wine”

Shakespeare “I would that there were no age between 10 and 23,

for there’s nothing in between but getting wrenches with child,

wronging the ancientry, stealing, fighting….”. The Winter’s Tale, Act. III.

FACTORS MADURATIUS I ENTRADES AMBIENTALS

Hormones

FACTORS MADURATIUS I ENTRADES AMBIENTALS

Hyman SE (2009), Nature Neuroscience, 12, 3, 241-242.

Risky choices: blending of higher sensitivity/maturation of limbic structures with delayed prefrontal maturation

Impulsiveness: prefrontal protracted development alone

Puberty/adolescence main regulators: Hypothalamic-

Hypophysis-Gonadal interactions

Cameron JL (2004), in RE Dahl and LP Spear

(Eds.): Adolescent brain development, Annals

NYAS, Vol. 1021, 110-123.

Dahl RE (2004), in Adolescent Brain Development: vulnerabilities and opportunities,

Annals NYAS, Vol. 1021, pp. 1-22

Gonadarche (Breasts and Phallus growth); Adrenarche (Acné and pubic/

axillary hair); Growth spurt: Size, Height and muscular/fat disposition.

Mean youth values of steroid hormones in each sex

Females (N=81) Males (N=102)

Follicular Luteal

DHEAS (ng/ml) 1,32 (0,64) 1,3 (0,62) 2,07(0,93)

AD (ng/ml) 3,8 (2,56) 5,99 (2,78) 0,99 (0,6)

DHEA (ng/ml) 6,24 (6,5) 3,2 (3,4) 1,48 (1,03)

LH (miu/ml) 15,06 (6,17) 30,,57 (17,6) 10,75 (4,8)

T (ng/ml) 0,6 (0,4) 0,73 (0,4) 4,98 (2,56)

TEBG (nmol/l) 57,8 (21,7) 67,4(33,9) 46,75( (13,7)

FTI 0,04 (0,04) 0,04 (0,03) 41,8 (26,6)

P (ng/ml) 1,08 (1,23) 4,53 (5,73) -

E (ng/ml) 0,066 (0,058) 0,19 (0,10) -

DHEA= Dihidroepiandrosterone; AD: Androstenodione; LH: Luteinizing hormone; T= Testosterone; TEBG=Testosterone binding globuline; FIT= Free testosterone; P= Progesterone; E= Estradiol.

From Udry (1990).

Dahl RE (2004), in Adolescent Brain Development: vulnerabilities and opportunities, Annals NYAS, Vol. 1021, pp. 1-22

Mandela’s kids study in South Africa:

born within a week difference!!

STAGES OF HUMAN BRAIN

DEVELOPMENT

From Nelson Ch A (2004), Annals

NYAS, 1021, 105-109.

Development of synaptic density in sensory and frontal regions. The lefthand graph shows the mean synaptic density in the primary auditory cortes (red circles), in the primary visual cortex (green circles) and in the prefrontal cortex (PFC: middle frontal gyrus, crosses), in postmortem human brains at different ages. The X axis shows the conceptual age in days from 200 postconception to 10.000 days post conception (aprox. 27 years). Synaptic density increases in all three regions in early chlidhood but synaptogenesis is most prolonged in the PFC. This is further demonstrated on the right graph which shows the difference in synaptic density between the auditory cortex and the middle frontal gyrus (purple cicles) plotted against conceptual age. The line represent the best fit for the data. Although peak synaptic density in the auditory cortex occurs early (aprox. three months after birth) the peak synaptic density at PFC occurs significantly later.

Scanning adolescent’s brains

EXPLORING

BRAIN CHANGES

WITH MAGNETIC

RESONANCE

IMAGING (MRI)

SCANS

Toga AW, Thompson PM and Sowell ER (2006), Trends in

Neurosciences, 29, 3, 148-159.

CHANGES ON CORTICAL THICKNESS (GRAY-MATTER DENSITY) IN

BOTH HEMISPHERES ACROSS LIFETIME.

Points correspond to regional measures taken on 176 individuals with

ages ranging from 7 to 87 years old.

CHANGES IN GRAY MATTER DENSITY ON

CORTICAL REGIONS ACROSS AGES

Toga AW, Thompson PM and Sowell ER (2006), Trends in

Neurosciences, 29, 3, 148-159.

Toga AW, Thompson PM and Sowell ER (2006), Trends in Neurosciences, 29, 3, 148-159.

Trajectory of cortical gray-matter density in13 children scanned logitudinally every two years. The

units used are gray-matter density defined as the proportion of tissue segmenting as gray matter

within a 15 mm–diameter sphere centered at each point on the cortical surface. This measure ranges from 0 to 1 and is highly correlated with cortical thickness.

Mechanism?: Synaptic pruning?; Myelinization?; Fine tuning?.....

BRAIN DEVELOPMENT TROUGH CHILDHOOD AND

ADOLESCENCE: MRI MEASURES

Total volume and white matter changes obtained from 145 healthy

individuals (89 males, 56 females, age range 4,2 to 21,6 years). 65 were subjected to a second scan and 30 to a third scan. The total

increase in white matter was 12,4%. From Giedd JN et al (1999)

Nature Neuroscience, 2, 861-863).

Sex differences in age-

related gray matter

changes in a range of

cortical regions:

predicted MRI volumes, with 95% confidence intervals, of cortical gray matter in frontal, parietal, temporal and occipital lobes from males and females aged 4 to 22 years. Gray matter at the frontal

cortex peaks at the aprox age

of puberty: 11 years in girls and

12 years in boys. The peak at the temporal cortex is not attained till 16 years. Puberty rather than age per se may be the trigger of these neuroanatomical changes (From Giedd JN et al (1999) Nature Neuroscience, 2, 861-863).

BRAIN DEVELOPMENT TROUGH

CHILDHOOD AND ADOLESCENCE: MRI MEASURES

From Giedd JN (2004), Annals NYAS, 1021, 77-85

Ongoing Brain Imaging Project at the Child Psychiatry Branch, the

National Institute of Mental Health, Bethesda, Washington.

Results from 329 scans from 95 males and 66 females (N Total = 161), plus neuropsychological testing, at aprox. 2 years intervals

From Giedd JN (2004), Annals NYAS, 1021, 77-85

Galvan A et al (2006), The Journal of Neuroscience, 26(25), 6885-92.

Subjects:

- 16 children (7-11 years old; seven females)

- 13 adolescents (13-17 years old; six females)

- 12 adults (23-29 years old; six females )

Payment: 50 $ for participating + 25 $ in variable earnings!!

Neural systems for reward

and addiction: from actions, to

habits to compulsions.

Everitt BJ and Robbins TW (2005) Nature

Neuroscience, 8, 1481-9.

Green arrows: Glutamate

Orange arrows: Dopamine

Pink arrows: GABA

Galvan A et al (2006), The Journal of Neuroscience, 26(25), 6885-92.

Risky choices: blending of higher sensitivity/maturation of limbic structures with delayed prefrontal maturation

Impulsiveness: prefrontal protracted development alone

Using A Go-NoGo Task with Fearful/Neutral faces

From Blakemore SJ (2008), Nature Reviews Neuroscience, 9, 267-277

Regions of the social brain: Medial prefrontal cortex (mPFC) and the temporo-

parietal junction, which are both involved inb thinking about mental states; the posterior superior temporal sulcus (pSTS), activated by observing faces and biological motions; the inferior frontal gyrus IFG) and the interparietal sulcus. Othe regions on the medial surface involved in social cognition include the amygdala, the anterior cingulate cortex (ACC) and the anterior insula (AI). From Blakemore SJ (2008) Nature Reviews Neuroscience, 9, 267-277

Animation tasks to

study mentalizing

(A): participants watch silent animations in

which two triangles move around in such a way that they seem to

have mental states. Autistic children do no

generate appropiate terms to describe the patterns of movement

of the triangles. The regions of the social

brain (B) including the PFC (top panel), the temporal poles (middle

pannel) and the superior temporal

sulcus (bottom) are activated when healthy participants observe

mentalizing animations relative to control

tasks that do no evoke mental attributions.

(Castelli F et al (2000), Neuroimage, 12, 314-325).

Madurative and Environmental Inputs: from early

maltreatment to drug/toxic insults

Pathways to individual aggressiveness

Frans De Waal (2000): Multiple sources of individual aggression, Science, 289, 586-90.

Different weights depending on interactions along vital itineraires!!!

THE HYPOTHALAMIC-PITUITARY-

GONADAL AXIS: Hormonal steps and negative feedback loop.

RELATIONSHIPS OF ANDROGENIC STEROIDS WITH REPRODUCTIVE

FUNCTION, SEXUAL BEHAVIOR

AND AGGRESSION.

Late adolescence-youth upsurge

of violent behavior in humans (males mainly!).

.

The discrete

character of

high-lethality

of youth

violence

FE Zimring (2004),

in J Devine, J Gilligan, KA Miczeck, R

Shaikh and D. Pfaff (Eds), Youth violence:

scientific

approaches to

prevention, Annals NYAS, 1036, 290-299.

ANDROGENIC STEROIDS AND AGGRESSION

NEUROHORMONES AND AGGRESSION

Aggression-enhancers: Aggression-dampening:

Androgens Serotonin

Vasopressine Corticoids

P substance Oxitocine

Dopamine Opioids

Noradrenaline Adenosine

Cholecystocinin Y neuropeptide

Insulin… Anandamides …..

Neuroregulators with differential actions:

GABA ( ; ) : Defensive attacks/fear; Offensive attacks

Progestagen/Estrogens: variations on aggressive outputs depending on ratios

Others (Glicine, Glutamate, NO, intracellular messengers…)

BUT!

But!!: Subtle variations depending on Aggression Modalities for several neuroregulators.

GENES AND AGGRESSIVENESS: links and pathways

- Mutations leading to neural malfunction (Uncommon)

(MAOA data…., but dozens of other markers!!…)

- Genetical “templates” for temperamental traits (Common)

Impulsivity

Sensation seeking

Fearfulness Threshold for aggression

Irritability

Empathy…

- Genetic “templates” for physiological traits (Common)

Corpulence

Heart rate

Cortisol Threshold for aggression

Testosterone

Serotonin function…

Heritability estimates: 0,7/0,8

(Twin/adoption studies)

Temperamental traits/ High-order personality factors.

Temperamental traits:

fearfulness, novelty-,

seeking, aggressiveness, empathy, altruism,

extraversion, persistence, conservatism, religiosity,

resilience…

Two views of the relationships between genes and personality (modified from D. Hamer (2004), Rethinking behavior genetics, Science, 298, 71-72). A. Early studies looked for linear relationships between gene markers and temperamental traits or high-order personality factors. B. Reality is likely to be far more complex with gene networks interacting with environmental inputs impacting on brain development and leaving enduring neural dispositions that, in turn, influence behavioral, cognitive and affective styles (temperamental traits).

GENES AND TEMPERAMENT

Annals NYAS (1996), 794, 224-237.

- recruitment: 1967-71 908 Ss. Versus 667 Matched Controls

- 1st. measures: 1987-88

- 2nd. measures: 1994 94% > 25 years old

A 27 years long study following maltreated infants:

Annals NYAS (1996), 794, 224-237.

Science (2002), 297, 851-53.

Caspi A et al (2002), Science, 297, 851-53.

A New Zealand cohort of 1037

children (52% male) were followed

triannually during 23 years, from 3 to

26 years-old, recording medical,

physical and psychological conditions.

8% suffered maltreatment, 28%

probable maltreatment and 64% no

maltreatment at all. At the end, 96%

of the initial sample was reached.

Caspi et al (2002), Science, 297, 851-53.

Early maltreatment

and MAO genotype:

long term results with different

violent-related

measures.

Male results, also confirmed in females

Temperamental traits/ High-order personality factors.

Temperamental traits:

fearfulness, novelty-,

seeking, aggressiveness, empathy, sociability,

persistence, conservatism, religiosity, altruism,

resilience…

Two views of the relationships between genes and personality (modified from D. Hamer (2004), Rethinking behavior genetics, Science, 298, 71-72). A. Early studies looked for linear relationships between gene markers and temperamental traits or high-order personality factors. B. Reality is likely to be far more complex with gene networks interacting with environmental inputs impacting on brain development and leaving enduring neural dispositions that, in turn, influence behavioral, cognitive and affective styles (temperamental traits).

GENES AND TEMPERAMENT

Chromosomes Genes RNA’s Proteins/Peptides

Humans: 20.000 genes

> 100.000 proteins/peptides (>50% active in the brain)

Burmeister M, McInnis MG and Zollner S (2008), Nature Review Genetics, 9, 527-540.

Gene-environment interactions in psychiatric diseases

GENES AND PSYCHIATRIC DISEASES

Genes code for proteins and are associated with

biological processes …, they do’nt relate directly, howewer, to psychological traits, cognitive functions

or behavioural symptomatology…,

DNA variants (genic and nongenic) can be strongly

linked to psychiatric vulnerabilities through specified

neuromolecular systems!!!.

Pathological cognition,

affect and behavior

McGowan PO et al (2009), Nature Neuroscience, 12, 3, 342-348.

Nestler EJ et al (2002), Neuron, 34, 13-25.

Cronic stress and vulnerability to disease: molecular

and cellular pathways

Developmental pathways and stress vulnerability: from early

separation distress to the “well-groomed” child

MATERNAL CARE MEDIATES

LONG-TERM TOUGHENING EFFECTS OF POSTNATAL

HANDLING

Sapolsky RM (1997), Science, 277, 1620-1621.

Separation distress

pionnering experiments:

- Harlow

- Levine

- Suomi…

Science, (1997), 277, 1659-62.

Liu et al (1997), Science, 277, 1659-62.

Hyman SE (2009), Nature Neuroscience,

12, 3, 241-242.

Moffit TE, Caspi A, Farrington T and Milne BJ (2002) Development and

Psychopathology, 14, 179-207.

The Dunedin (New Zealand) longitudinal study of a cohort of 1037 children

(477 males), from 3 to 26 years old: a minority (10%) explained for most of violent acts and offenses across maturation.

Vinding E (2004) On the nature and nurture of antisocial behavior and violence, in J Devine, J Gilligan, KA Miczeck, R Shaikh and D. Pfaff (Eds), Youth violence: scientific approaches to prevention, Annals NYAS, 1036, 267-277.

An ongoing study of antisocial behavior in more than 7000 twin children.

Heritabilities for callous/unemotional kids versus children without these traits.

Science (2002), 295, 2468-71.

Johnson JG et al (2002), Science, 295, 2468-71.

N=1517 (12-15 years old) N= 1239 (81,7%) 984 (80,3%)

Self-reports, Caregiver reports, Census data.

Bingenheimer JB, Brennan RT and Earls FG (2005), Science, 308, 1323-26.


Variables at start that

show differences between adolescents

subsequently exposed vs. nonexposed to

gun-linked violence.


Individual

“propensity”

scores established by a

regression model

fitting 48 start

variables

ADOLESCENT AND YOUTH RISK AND PROTECTIVE FACTORS

FOR SUBSEQUENT ANTISOCIAL BEHAVIOR

Risk factors Protective factors

Uncontrolled temperament, age 3 Shyness

Impulsive traits by ages 8-10 Inhibited temperament

Hyperactive traits, age 13 Intelligence

Callous traits by ages 7-12 Close relations with adults

Low IQ Good achievement at school

Poor academic achievement Sports achievements

Major depression at age 14 Non antisocial peers…

Oppositional defiant behavior by ages 7-12

Conduct disorder by ages 9-16

Substance abuse by ages 8-12

Poor parenting and supervision

Abuse under age 12

Association with a deviant peer group…

From Fonagy P (2004), Annals

NYAS, 1036,181-200.

80% of adolescents navigate through ADOLESCENCE

TRANSITIONS (from puberty to adult responsabilitIes) without

major problems

END OF ADOLESCENCE?: Stabilized sleep chronotypes closing the typical

delayed pattern: around 19,5 years old in women and 21 years old in men.

brain/behaviour development along adolescence … · brain/behaviour development along adolescence...

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